Note: Descriptions are shown in the official language in which they were submitted.
CA 02661953 2009-02-17
Description:
Title:
Method, Composition, and Device, for the Treatment of diseases, enzymes and
Saccharides disorders
Inventors:
Tarig Sayed Mustafa Arbab
13 Argyle Road,
North Finchley,
London N12 8JA
Assignee: Saccharides Science & Technology Ltd. - London - UK
CROSS REFERENCE TO RELATED APPLICATIONS
This application is a continuation of International Patent Application No.
10/930,538, filed 30.04.2004 designating the United States of America, the
entire disclosure of which is incorporated herein by reference. Priority is
claimed based on UK patent application No. 0407583.4, filed 05.04.2004
REFERENCES
1. Volkheimer G. [Persorption of microparticies] Pathologe 1993
Sep;14(5):247-52. [Article in German]
2. Freedman B1. Persorption of raw starch: a cause of senile dementia?
Med Hypotheses 1991 Jun;35(2):85-7.
3. Volkheimer G. [The Herbst- Volkheimer effect]. [Article in German]
Prokop O. Institut fur Gerichtliche Medizin des Bereichs Medizin (Charite) der
Humboldt-Universitat zu Berlin, DDR. Kitasato. Arch Exp Med 1990 Apr;63(I):I-6
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4. Ullmann D, Connor WE, Hatcher LF, Connor SL, Flavell DP. Will a high-
carbohydrate, low-fat diet lower plasma lipids and lipoproteins without
producing hypertriglyceridemia? . Department of Medicine, Oregon Health
Sciences University, Portland 97201-3098. Arterioscler Thromb 1991 Jul-Aug;l
1(4): 1059-67
5. Liu GC1 Couiston AM, Reaven GM. Effect of high-carbohydrate-low-
fat diets on plasma glucose, insulin and lipid responses in
hypertriglyceridemic
humans. Metabolism 1983 Aug;32(8):750-3 33.
6. Olefsky JM, Crapo P, Reaven GM. Postprandial plasma triglyceride and
cholesterol responses to a low-fat meal. Am J Clin Nutr.1976 May;29(5):535-9.
7. Ginsberg H, Olefsky JM, Kimmerling G, Crapo P, Reaven GM. J Clin
Induction of hypertriglyceridemia by a low-fat diet. Endocrinol Metab 1976
Apr;42(4):729-35
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BACKGROUND OF THE INVENTION
The present invention relates to the use of physiologically acceptable enzyme
complex with active amylases (The active site of the enzyme contains a
catalytic triad, including Asp197, GIu233 and Asp300, {Example of other
analogous: (1) Asp 196, Glu233, and Asp301; (2) Asp197, Glu232, Asp300; (3)
Asp197, GIu233, Asp 299;), active glucoamylases, active invertases, active
lipases, active proteases, active malt diastases, active cellulose, active
lactases,
and active pectinases and specific proteins such as Trimethylglycine
(betaine),
but especially of complex of enzymes such as active 1,4-a-D-glucan
glucanohydrolase; active Exo-1,4-a-glucosidase; active Beta-
fructofuranosidase; active Protease; active Pectinase; active Lipase; active
Cellulase; active Lactase; active Malt Diastase, for the treatment of diseases
associated with amylases activity malfunctioning, delayed activity or
inactivity
and excess of saccharides (polysaccharides, disaccharides and
monosaccharides) and persorped particles in the blood and body tissues, and
for the manufacturing of medicinal products suitable for this treatment. The
invention relates especially to the use of these enzyme complexes with active
amylases (The active site contains a catalytic triad, including Asp197, GIu233
and Asp300, {Example of other analogous: (1) Asp 196, Glu233, and Asp301; (2)
Asp197, Glu232, Asp300; (3) Asp197, Glu233, Asp 299;), active lipases and
active proteases, but especially of Trimethylglycine (Betaine HCL); 1,4-a-D-
glucan glucanohydrolase; Exo-1,4-a-glucosidase; Beta-fructofuranosidase;
Protease; Pectinase; Lipase; Cellulase; Lactase; Malt Diastase, or a
pharmaceutical complex containing Trimethylglycine (Betaine HCL); 1,4-a-D-
glucan glucanohydrolase; Exo-1,4-a-glucosidase; Beta-fructofuranosidase;
Protease; Pectinase; Lipase; Cellulase; Lactase; Malt Diastase, for the
adjuvant
therapy of diseases associated with malfunctioning or absence of amylases
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CA 02661953 2009-02-17
activity (The active enzyme contains a catalytic triad, including Asp197,
Glu233
and Asp300, (Example of other analogous: (1) Asp 196, GIu233, and Asp301; (2)
Asp197, Glu232, Asp300; (3) Asp197, GIu233, Asp 299;) with or without excess
and presence of high levels of saccharides (monosaccharides, disaccharides
and polysaccha rides) in blood and tissues.
As used herein the term "presence of high levels of saccharides
(polysaccharides, disaccharides and monosaccharides), in blood and tissues" is
understood to mean a condition in which amylases activity is altered or
impaired (inactivity of amylases enzymes for 24 hours or more) with or
without, the presence of high levels of monosaccharides disaccharides and
polysaccharides in blood and tissues in asymptomatic healthy individuals and
symptomatic unhealthy individuals for example individuals suffer from renal
failure.
Excess of polysaccharides disaccharides, and monosaccharides, here-called
"Saccharides sickness", can be associated with various diseases, in addition
to
that some diseases can develop as secondary due to excess saccharides as
sequelae of other primary diseases, and many groups of disorders of
metabolism are distinguished, I. e. Asthma, kidney failure, chronic wounds and
ulcers, severe infections such as wet gangrene (gas gangrene), peripheral
ischaemia, macro and microangiopthy, arthritis, D.V.T (deep vein thrombosis),
P.E (pulmonary embolism), type I diabetes due to insulin deficiency and type
II
diabetes due to reduced insulin effectiveness, epilepsy, Alzheimer's diseases,
arthritis, aging process and some skin disorders such as discolouration of
skin;
the course of the disease depending on the type concerned, among other
factors. Peripheral ischaemia, is furthermore a chronic disease with a variety
of
pathological manifestations and is accompanied, for example, by disorders of
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CA 02661953 2009-02-17
lipid metabolism, circulation and saccharides metabolism. Starch, proteins,
meat fibers, and fat particles get persorped into the blood and get
distributed
and deposited in lungs where they can act as foreign bodies and cause asthma,
in joints, where they can cause inflammatory reactions which triggers immune
responses usually detected in the blood, serum and arthritic joints,
polydaccharides and polysaccharides like proteins can also be found deposited
in the brain (Amyloidosis) in people who suffer from Alzheimer's diseases.
Gerhard Volkheimer found polysaccharides blocking microcirculation and
causing multiple organ failure in laboratory animals fed polysaccharides only
for three months, yet again Gerhard Volkheimer noticed that laboratory
animals who were fed only polysaccharides as diet for three months looked
very old and aged very quickly in comparison with animals who had normal or
other diet; here also the applicant previous experience during 2003 -2006
(when he was treating subjects in his private clinic in Sudan and UAE), he
noticed that subjects who received the pharmaceutical compound Amzylite,
looked younger and more energetic within weeks of treatment, and their
activity has improved significantly (see previous references attached and
previous G. Volkheimers research published in pubmed). Previous research
demonstrated that polysaccharides intake can cause elevations of cholesterol
levels in the blood, (please see references attached). Regarding developments
of systemic clots, pulmonary embolisms, deep veins thrombosis and other clots
related disorders, this has been related to the persorption of starch
particles
(uncooked, raw starch) in the blood. Previously, intravenous starch fluids
were
ban from use in medicine because they caused a condition similar to
disseminated intravascular coagulations (DIC), in which multiple clots were
formed in the blood and this has lead to serious complications. From our past
experience, we managed to treat subjects who had clots by dissolving theses
CA 02661953 2009-02-17
clots using the pharmaceutical compound called Amzylite only. Treatment with
Amzylite involves peripheral vascular diseases and peripheral ischaemia. The
typical symptoms of peripheral vascular disease and ischaemia include
elevated inflammatory markers, deposit of polysaccharides and atheroma in
blood vessels, vascular lumen and walls which could result in narrowing of
vessels, development of skin wounds and chronic ulcers, tendency to
infections and pruritus, and finally amputation of the limb. Peripheral
ischaemia tends to be a progressive disorder and in many cases is also
accompanied by various complications. Known complications include, for
example, neurologic, chronic wounds, bone infections and vascular diseases. It
is therefore necessary to adjust the therapy to meet each patient's individual
requirements in every phase of the illness and to select the suitable
medicinal
product for each individual case. It may also be desirable for this therapy to
supplement the selected primary medications with other medicinal products in
the form of an adjuvant treatment which can exert a supporting effect on the
therapy and beneficially influence the further course of the illness.
SUMMARY OF THE INVENTION
Therefore, it is an object of the invention to provide a new pharmaceutical
compound, with new diagnostic tests and tests devices for the treatment of
malfunctioning or inactivity of amylases (The active site of the enzyme
contains
a catalytic triad, including Asp197, GIu233 and Asp300, {Example of other
analogous: (1) Asp 196, GIu233, and Asp301; (2) Asp197, GIu232, Asp300; =(3)
Asp197, GIu233, Asp 299;) and other enzymes such as protease, lipase,
invertase, glucoamylase, cellulose, pectinase, lactase and malt-diastase, in
association with or without excess saccharides (monosaccharides,
disaccharides and polysaccharides) and other persorped particles in blood and
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CA 02661953 2009-02-17
tissues in asymptomatic healthy individuals (as prophylaxis) and symptomatic
unhealthy individuals (as treatment).
It is another objective of the invention to provide new pharmaceutical
preparations for the treatment of malfunctioning or inactivity of amylases
(The
active site of the enzyme contains a catalytic triad, including Asp197, GIu233
and Asp300, {Example of other analogous: (1) Asp 196, GIu233, and Asp301; (2)
Asp197, GIu232, Asp300; (3) Asp197, GIu233, Asp 299;), and other enzymes
such as glucoamylase, invertase, protease, lipase, pectinase, cellulose,
lactase
and malt-diastase, in association with or without excess saccharides
(monosaccharides, disaccharides, and polysaccharides) and other persorped
particles in blood and tissues in asymptomatic healthy individuals and
symptomatic unhealthy individuals.
It is a particular object of the invention to provide new pharmaceutical
preparations for adjuvant therapy in the treatment of malfunctioning or
inactivity of amylases (The active site of the enzyme contains a catalytic
triad,
including Asp197, GIu233 and Asp300, {Example of other analogous: (1) Asp
196, GIu233, and Asp301; (2) Asp197, Glu232, Asp300; (3) Asp197, GIu233, Asp
299;) and other enzymes such as glucoamylase, invertase, protease, lipase,
pectinase, lactase, cellulose, and malt-diastase, in association with or
without
excess saccharides (monosaccharides, disaccharides, and polysaccha rides) and
other persorped particles in blood and tissues in asymptomatic healthy
individuals and symptomatic unhealthy individuals which exert an additional
supportive effect on the treatment and beneficially influence the further
course of the malfunctioning or inactivity of enzymes and amylases enzymes
activity (The active site of the enzyme contains a catalytic triad, including
Asp197, GIu233 and Asp300, {Example of other analogous: (1) Asp 196,
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CA 02661953 2009-02-17
GIu233, and Asp301; (2) Asp197, GIu232, Asp300; (3) Asp197, GIu233, Asp
299;) and other enzymes such as glucoarnylase, invertase, protease, lipase,
lactase, pectinase, cellulose, and malt-diastase, in association with or
without
excess of saccharides (monosaccharides, disaccharides and polysaccharides) in
blood and tissues, illness, for example by reducing the incidence of late
complications.
Another objective of the invention is to provide, a method of diagnosis,
diagnostic tests, diagnostic test material and devices, method of treatment,
treatment compounds, treatment evaluation and follow up tests and devices
for enzymes malfunctioning activity or inactivity in association with or
without
excess monosaccharides, disaccharides, and polysaccha rides, lipids, proteins
in
the blood, urine, body fluids such as lymphatic fluids and body tissues. The
method of diagnosis, diagnostic tests, diagnostic testing 'devices are to be
applied for any subject, asymptomatic (not suffering from any diseases) or
symptomatic (suffering from one or multiple diseases such as diabetes with or
without complications, Alzheimer's disease, arthritis etc). It
According to the invention, physiologically acceptable enzyme mixtures with
active amylase (The active site of the enzyme contains a catalytic triad,
including Asp197, GIu233 and Asp300, {Example of other analogous: (1) Asp
196, GIu233, and Asp301; (2) Asp197, GIu232, Asp300; (3) Asp197, Glu233, Asp
299;) active lipase and active protease, active invertases, active lactases,
active
cellulases, active malt diastases, active glucoamylases and trimethylglycine,
such suitable enzyme mixtures of microbial origin and/or especially mixtures
of
enzymes and proteins of plant origin, human and animal origin such as
preferably Trimethylglycine (Betaine HCL); 1,4-a-D-glucan glucanohydrolase;
Exo-1,4-a-glucosidase; Beta-fructofuranosidase; Protease; Pectinase; Lipase;
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Cellulase; Lactase; Malt Diastase, or Trimethylglycine (Betaine HCL); 1,4-a-D-
glucan glucanohydrolase; Exo-1,4-a-glucosidase; Beta-fructofuranosidase;
Protease; Pectinase; Lipase; Cellulase; Lactase; Malt Diastase,-like mixtures
of
enzymes, are used for the treatment of diseases associated with
malfunctioning or inactivity of enzymes, amylases enzymes malfunctioning or
inactivity (The active site of the enzyme contains a catalytic triad,
including
Asp197, Glu233 and Asp300, {Example of other analogous: (1) Asp 196,
GIu233, and Asp301; (2) Asp197, GIu232, Asp300; (3) Asp197, GIu233, Asp
299;) and other enzymes malfunctioning or inactivity such as glucoamylase,
invertase, protease, lipase, lactase, pectinase, cellulose, and malt-diastase
in
association with or without excess saccharides (monosaccharides,
disaccharides, and polysaccharides) and persorped particles in blood and
tissues in asymptomatic healthy individuals and symptomatic unhealthy
individuals in larger mammals and humans, and for the manufacture of
pharmaceutical preparations for such treatment.
For the present invention, physiologically acceptable enzyme mixtures with
active amylolytic, active lipolytic, and active proteolytic, and active
saccharolytic can be used that are of any human, plant or microbiological
origin. The enzyme mixtures with active amylases, active lipases, active
proteases, active invertase, active cellulose, active glucoamylase, active
pectinase, active lactase and active malt diastase, used for the invention can
be both of purely microbial origin, purely animal origin and purley human
origin, or may also be a complex of enzymes of animal, human, plant and
microbial origin.
In one variant of the invention, the enzyme mixture used is of purely
microbial
origin. Especially enzymes produced by bacteria, i. e. by the Bacillus or
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Pseudomonas strains, or by fungal cultures such as moulds, for example of the
Rhizopus and Aspergillus strains, are especially suitable as microbial
enzymes.
Examples of such physiologically acceptable bacterial and/or mould fungi
enzymes are already described in the state of the art, e. g. in connection
with
their synthesis and use for the treatment of digestive disorders. Lipases may
be
derived from, for example, Bacillus or Pseudomonas strains, amylases and
lipases from mould fungi, for example of the Rhizopus strain, and proteases,
for example, also from Aspergillus.
Another preferred variant of the invention, however, involves the use of
complex of enzymes and proteins with, Trimethylglycine (Betaine HCL); 1,4-a-
D-glucan glucanohydrolase; Exo-1,4-a-glucosidase; Beta-fructofuranosidase;
Protease; Pectinase; Lipase; Cellulase; Lactase; Malt Diastase, that in their
properties closely resemble salivary, gastric, pancreatic and intestinal
enzymes.
For the present invention; complex of enzymes and proteins containing
Trimethylglycine (Betaine); 1,4-a-D-glucan glucanohydrolase; Exo-1,4-a-
glucosidase; Beta-fructofuranosidase; Protease; Pectinase; Lipase; Cellulase;
Lactase; Malt Diastase, and especially salivary, gastric, pancreatic and
intestinal
enzymes itself are preferably used, and one or more microbial enzymes, i. e.
enzymes synthesized by microorganisms, of the group of amylases lipases, and
proteases may if desired be added to the salivary, gastric, pancreatic and
intestinal enzymes or pharmaceutical complex containing Betaine HCL; 1,4-a-
D-glucan glucanohydrolase; Exo-1,4-a-glucosidase; Beta-fructofuranosidase;
Protease; Pectinase; Lipase; Cellulase; Lactase; Malt Diastase,.
Salivary like, gastric like, pancreatic like and intestinal like proteins and
enzymes are known enzymes complex with active amylases (The active site of
the enzyme contains a catalytic triad, including Asp197, Glu233 and Asp300,
CA 02661953 2009-02-17
{Example of other analogous: (1) Asp 196, GIu233, and Asp301; (2) Asp197,
GIu232, Asp300; (3) Asp197, GIu233, Asp 299;,) active lipases and active
proteases, active malt diastases, active pectinases, active invertases, active
cellulases, active lactases, and active invertases, which is available for
example,
under the trade name Amzylite , in the form of granules, pellets, lyophilized
powder for intravenous injection or capsules containing enteric coated
microspheres and is used medically for enzyme replacement. Amzylite is
generally obtained as a mixture of natural enzymes by extraction from
microbial, plant, yeast, fungi and human saliva or pancreatic juice, for
example
according to the process described in UK patent application GB0407583.4, and
is then converted into the desired galenical form in a manner known in the
art.
The salivary, gastric, pancreatic and intestinal like enzymes are usually
administered orally or intravenously, in the form of solid or solution
preparations.
Amzylite is private formulation invented to lower glucose in vitro and in
vivo,
and to correct a malfunctioning / inactivity of enzymes in blood, saliva,
pancreatic juice, urine and tissues. Amzylite recycles persorped particles in
the
blood such as saccharides, proteins, fats, and other particles. Amzylite F1.2
is
one of several formulations invented for the treatment and correction of
enzymes activity malfunctions in association with diseases such as for example
:rena.l failure, or excess Saccharides, (polysaccharides, disaccharides and
monosaccharides) in blood, urine and tissues. Amzylite helps to correct and
treat enzymes disorders. Amzylite formulae were developed by the inventor
after extensive research, they were formulated and designed to correct, and
treat, malfunctioning, delayed or inactive enzymes in individuals who are
diagnosed and or found to suffer from enzymes malfunctions or inactivity, also
helps correct and treat excess of saccharides (polysaccharides, disaccharides
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CA 02661953 2009-02-17
and monosaccharides) and or diseases associated with it. There are different
Amzylite formulae, F1.1, F1.2, F1.3, F1.4, F1.5, and F1.6 etc. Each formula,
designed for use with different type, different stage, of diseases associated
with enzymes malfunctioning / inactivity with or without excess of
polysaccharides, disaccharides and monosaccharides. For example F1.3 is
designed for certain complications of the disease such renal impairments.
Amzylite F1.1 formula is researched and designed as long maintenance doses
of the treatment. I.V Formulas are developed for use in emergencies situations
for example in severe lower limb infections and wet gangrene (gas gangrene),
etc. Amzylite must be considered as alternative treatment, adjuvant therapy
that helps correct and treat enzymes malfunctions or inactivity and excess
levels of saccharides in the body. Amxylite helps correct and improves
conditions associated with enzymes inactivity specially amylases, corrects,
treats and decreases excess and high levels of polysaccharides and
disaccharides levels in the blood and tissues; and finally it helps stimulate
the
pancreas to do its job, improves insulin secretion, increases insulin
production,
reduces and improves insulin-resistance syndrome. It will also reduce
cholesterol and triglyceride levels and improves kidneys blood perfusions,
thereby helping to avoid the need for dialysis.
Amzylite is a private formulae contains active 1,4-glucan-4-giucanohydrolase
as
principal ingredients: A compound made of Trimethylglycine and an active 1,4-
glucan-4-glucanohydrolase. Aactive 1,4-glucan-4-glucanohydrolase is a
glycoside hydrolase, and catalyzes the hydrolysis of (1,4) glycosidic linkages
of
polysaccharides starch. The enzyme has 3914 protein atoms, 496 residues of a
single polypeptide chain, one activator chloride ion, one structural calcium
ion,
and 393 water molecules. The active site of the enzyme contains a catalytic
triad, including Asp197, GIu233 and Asp300, {Example of other analogous: (1)
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CA 02661953 2009-02-17
Asp 196, GIu233, and Asp301; (2) Asp197, GIu232, Asp300; (3) Asp197, GIu233,
Asp 299; --- etc}. In mammals, 1,4-a-D-glucan glucanohydrolase is present in
salivary pancreatic and systemic secretions. Other ingredients in the formula
also help to correct other enzymes inactivity and reduce levels of persorped
particles in the blood, to be recycled by the main principle ingredients in
the
compound.
Amzylite mechanism of action is achieved by the following steps: Principal
active ingredients in the pharmaceutical compound of the Amzylite is, 1,4-a-D-
glucan glucanohydrolase and Trimethylglycine. Glycosidic hydrolysis by 1,4-a-
D-glucan glucanohydrolase is a double-displacement mechanism involving the
formation and hydrolysis of a covalent a -glycosyl enzyme intermediate.
Formation of the intermediate involves attack at the sugar anomeric center by
a nucleophilic amino acid (Asp197), assisted by general-acid catalysis
(GIu233).
The covalent glycosyl enzyme intermediate then undergoes general-base-
catalyzed (Glu233) hydrolysis via attack of water at the anomeric carbon. That
is to say, Amzylite mechanism of action is achieved by 3 stages: Stage 1-
Degradation and hydrolysis; Stage 2 - Hydrolysis of Monosaccharides (Glucose,
galactose and fructose); Stage 3 - Complex oxidation to C02 + H20 and energy
for the synthesis of ATP
In one variant of the invention, the pharmaceutical preparations manufactured
and / or used in accordance with the invention contain preferably active
amylases, active lipases and active proteases or complex of digestive enzymes
and proteins containing Trimethylglycine (Betaine HCL); 1,4-a-D-glucan
glucanohydrolase; Exo-1,4-a-glucosidase; Beta-fructofuranosidase; Protease;
Pectinase; Lipase; Cellulase; Lactase; Malt Diastase. These pharmaceutical
preparations manufactured according to the invention can contain active
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CA 02661953 2009-02-17
amylases, active lipases and active proteases or complex of enzymes and
specific proteins containing Trimethylglycine (Betaine HCL); 1,4-a-D-glucan
glucanohydrolase; Exo-1,4-a-glucosidase; Beta-fructofuranosidase; Protease;
Pectinase; Lipase; Cellulase; Lactase; Malt Diastase, and if desired in
addition
to active amylases one or more physiologically acceptable enzymes from the
group of lipases, proteases, Trimethylglycine (Betaine HCL); Beta-
fructofuranosidase; Protease; Pectinase; Lipase; Cellulase; Lactase; Malt
Diastase, of the kind that can be obtained from microorganisms. Microbial
enzymes suitable for use as this supplement include especially the bacterially
synthesized enzymes already mentioned above, for example by the Bacillus or
Pseudomonas strains, or by fungal cultures such as mould fungi, for example of
the Rhizopus or Aspergillus strains.
It has now been found that the physiologically acceptable enzyme complexes
and specific proteins with Betaine; 1,4-a-D-glucan glucanohydrolase; Exo-1,4-.
a-glucosidase; Beta-fructofuranosidase; Protease; Pectinase; Lipase;
Cellulase;
Lactase; Malt Diastase, which can be obtained from microbial and / or human
sources and described with reference to this invention, can be used not only
for the treatment of digestive enzyme deficiency states-of the kind associated
for example with pathological changes of the pancreas due to chronic
pancreatitis, digestive insufficiency after stomach operations, liver or
biliary
diseases-but surprisingly are also suitable for the treatment of Asthma,
kidney failure, chronic wounds and ulcers, severe infections such as wet
gangrene (gas gangrene), peripheral ischaemia, macro and micro angiopthy,
neuropathy, arthritis, D.V.T (deep vein thrombosis), P.E (pulmonary embolism),
type I diabetes due to insulin deficiency and type II diabetes due to reduced
insulin effectiveness, the course of the disease depending on the type
concerned, among other factors in larger mammals and humans. In particular,
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the aforementioned physiologically acceptable enzyme complexes with active
amylases, active lipases and active proteases, preferably however, for
example, Amzylite itself or complexes of digestive enzymes containing 1,4-a-D-
glucan glucanohydrolase; Exo-1,4-a-glucosidase; Beta-fructofuranosidase;
Protease; Pectinase; Lipase; Cellulase; Lactase; Malt Diastase, which also
contain microbial enzyme supplements, such as one or more microbial lipases,
proteases and / or amylases, are suitable for adjuvant therapy in the
management of saccharides based diseases, exert an additional effect
supporting the saccharides based diseases therapy and beneficially influence
the further course of the Asthma, kidney failure, chronic wounds and ulcers,
severe infections such as wet gangrene (gas gangrene), peripheral ischaemia,
macro and microangiopthy, neuropathy, arthritis, D.V.T (deep vein
thrombosis), P.E (pulmonary embolism), diabetes, the course of the disease
depending on the type concerned illness, i. e. especially by helping reduce
the
late complications of the saccharides based diseases associated with
malfunctioning or absence of amylases activity disorders. Another
embodiment of this invention is the use of active enzyme compound called
Amzylite and or trimethylglycine (betaine), in food industry for making low
glucose food and drink products or the compound can be used in sachets or as
capsules to reduce glucose in food and drinks such as juices and soft drinks.
Amzylite compound is scientifically proven to reduce glucose in food and
drink.
Another use of this invention is for use in glucose testing strip, such as
blood
glucose testing strips, urine testing strips, fluids testing strips and saliva
testing
strips. Amzylite compound or trimethylglicine can be used on the strip, for
testing glucose such as other enzymes currently used for glucose testing such
as oxidase, dehydrogenase and hexokinase.
CA 02661953 2009-02-17
The use of the physiologically acceptable enzyme complexes, preferably, for
example, Amzylite or complexes of digestive enzymes and specific proteins
containing 1,4-a-D-glucan glucanohydrolase; Exo-1,4-a-glucosidase; Beta-
fructofuranosidase; Protease; Pectinase; Lipase; Cellulase; Lactase; Malt
Diastase, where appropriate with further microbial enzyme supplements in
accordance with the invention also exhibits advantages in patients who in
addition to the saccharides based diseases associated with malfunctioning or
absence of amylases activity disorders have complications relating to
coexisting salivary glands diseases, digestive system diseases and exocrine
pancreatic insufficiency.
The pharmaceutical preparations manufactured and / or used according to the
invention can contain in addition to the described microbial enzyme mixtures
and / or mixtures of digestive enzymes of plant origin, such as especially 1,4-
a-
D-glucan glucanohydrolase; Exo-1,4-a-glucosidase; Beta-fructofuranosidase;
Protease; Pectinase; Lipase; Cellulase; Lactase; Malt Diastase, or complexes
of
digestive enzymes containing salivary, gastric, pancreatic and intestinal
enzymes, pharmaceutical excipients and/or additives and, if appropriate,
stabilizers.
For example, the enzyme mixtures may be contained in an effective quantity
(in each case determined on the basis of the active units of the active
amylases, active lipases and active proteases components) together with
conventional pharmaceutical excipients and/or vehicles in solid or liquid
pharmaceutical preparations. The active amylases per dose unit may be
generally within, the range of 50 to 500 mg amylase units, active lipase per
dose unit may be generally within a range of 10 to 50 mg lipase units, the
active protease per dose unit may be generally within a range of 5 to 70 mg
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CA 02661953 2009-02-17
protease units. Examples of typical dose units are, for example, enzyme
complex with the following activities: a) approx. 15 mg lipase/approx. 50 mg
amylase/approx. 5 mg protease; b) approx. 50 mg lipase/approx. 100 mg
amylase/approx. 25 mg protease; and c) approx. 25 mg lipase/approx. 150 mg
amylase/approx. 60 mg protease units. Examples of solid formulations are
preparations such as tablets, coated tablets, capsules, powder, granules or
pellets for oral administration or preparations for intravenous
administration.
These solid preparations may contain conventional inorganic and/or organic
pharmaceutical vehicles such as lactose, beet roots, dicalcium phosphate, and
magnesium stearate, talc or starch as well as conventional pharmaceutical
excipients such as glidants or tablet disintegrants. Liquid preparations such
as
solutions, suspensions or emulsions of the active ingredients may contain the
usual diluents such as water, oils and/or suspending agents such as
polyethylene glycols and the like. Further excipients such as preservatives,
flavouring agents, stabilizers (e. g. complex lipids) and the like may also be
added.
The enzyme complexes can be mixed and formulated with the pharmaceutical
excipients and / or vehicles in a manner known to the art. To manufacture
solid dosage forms, the enzyme complexes may, for example, be mixed with
the excipients and / or vehicles in the usual manner and wet or dry granulated
or pelleted. Granules, pellets or powder can be filled directly into capsules
or
sachets or compressed into tablet cores, or vial for intravenous
administration
in the usual manner. If desired, these cores can be coated to a dragee in the
manner known to the art. Liquid preparations can be obtained by dissolving or
dispersing the components and, if required, further excipients, in a suitable
liquid vehicle, in the form of solutions or suspensions.
17
CA 02661953 2009-02-17
The anti-saccharides based diseases associated with anti-malfunctioning or
anti enzymes-inactivity specifically amylases enzymes disorders and its
complications, such as coexisting salivary glands diseases, digestive system
diseases, and peripheral vascular ischaemic diseases, effects the beneficial
influence on the course of the saccharides based diseases in associated with
or
without malfunctioning or absence of amylases activity disorders and its
complications illness, especially in adjuvant therapy as part of an
saccharides
based diseases regimen, can be demonstrated for the physiologically
acceptable enzyme mixtures with active amylases, active lipases and active
proteases ; active pectinase; active glucoamylase; active cellulase; active
lactase; active Malt Diastase and active invertase, used in accordance with
the
invention, such as, for example, the microbial enzyme mixtures and especially
Amzylite or complexes of digestive enzymes and specific proteins containing
1,4-a-D-glucan glucanohydrolase; Exo-1,4-a-glucosidase; Beta-
fructofuranosidase; Protease; Pectinase; Lipase; Cellulase; Lactase; Malt
Diastase, described above, by determining the effect on pharmacological
parameters of the kind generally used to evaluate saccharides and enzymes
deficiency diseases. Such parameters may, for example, be an improvement,
i.e. Decrease in saccharides level, improvement of enzymes activity and
levels,
improvement of kidney function tests such as urea and electrolytes,
improvement of cholesterol levels and decrease in glycosylated hemoglobin
(HbA ic)=
Another objective of the invention is by offering a new method, device and
composition to diagnosis treat and prognosis, saccharides and enzymes
deficiency diseases. Amzylite is private formulation invented to lower glucose
in vitro and in vivo, and to correct a malfunctioning / inactivity of enzymes
in
blood, saliva, pancreatic juice, urine and tissues, lowers and recycle
18
CA 02661953 2009-02-17
saccharides, lipids, proteins and fibers in blood, urine, body fluids and
tissues.
Amzylite recycles persorped particles in the blood such as saccharides,
proteins, fats, and other particles. Amzylite F1.2 is one of several
formulations
invented for the treatment and correction of enzymes activity malfunctions in
association with diseases such as for example :renal failure, or excess
Saccharides, (polysaccharides, disaccharides and monosaccharides) in blood,
urine and tissues. Amzylite helps to correct and treat enzymes disorders.
Amzylite formulae were developed by the inventor after extensive research,
they were formulated and designed to correct, and treat, malfunctioning,
delayed or inactive enzymes in individuals who are diagnosed and or found to
suffer from enzymes malfunctions or inactivity, also helps correct and treat
excess of saccharides (polysaccharides, disaccharides and monosaccharides)
and or diseases associated with it. There are different Amzylite formulae,
F1.1,
F1.2, F1.3, F1.4, F1.5, and F1.6 etc. Each formula, designed for use with
different type, different stage, of diseases associated with enzymes
malfunctioning / inactivity with or without excess of polysaccharides,
disaccharides and monosaccharides. For example F1.3 is designed for certain
complications of the disease such renal impairments. Amzylite F1.1 formula is
researched and designed as long maintenance doses of the treatment. I.V
Formulas are developed for use in emergencies situations for example in
severe lower limb infections and wet gangrene (gas gangrene), etc. Amzylite
must be considered as alternative treatment, adjuvant therapy that helps
correct and treat enzymes malfunctions or inactivity and excess levels of
saccharides in the body. Amzylite helps correct and improves conditions
associated with enzymes inactivity specially amylases, corrects, treats and
decreases excess and high levels of polysaccharides and disaccharides levels
in
the blood and tissues; and finally it helps stimulate the pancreas to do its
job,
19
CA 02661953 2009-02-17
improves insulin secretion, increases insulin production, reduces and improves
insulin-resistance syndrome. It will also reduce cholesterol and triglyceride
levels and improves kidneys blood perfusions, thereby helping to avoid the
need for dialysis.
The following steps can be followed to diagnosis, treatment, and evaluation of
treatment with follow up for asymptomatic and symptomatic subjects: - step
1- The Saliva / pancreatic amylases activity and function testes should be
determined in any subject as routine screening tests to predict, diagnosis,
prognosis, treatment and post treatment follow up. Step 2- Subjects with
positive tests for malfunctioning / inactivity of amylases should be tested
for
levels of monosaccharides, disaccharides and polysaccharides in blood, urine,
body fluids and tissues. Step 3- Polysaccharides and disaccharides levels in
the
blood, urine, body fluids such as lymphatic fluid or tissues should be
determined in any subject as routine screening tests, as diagnostic tests and
after a positive salivary / pancreatic amylases malfunctioning / inactivity
tests,
to predict, diagnosis, prognosis, treatment and post treatment follow up. Step
4- Amzylite should then be administered to correct malfunctioning of enzymes
activity or inactivity, Amylase malfunctioning activity / inactivity, and to
correct
high disaccharides and polysaccharides levels that could exist in association
with enzymes malfunctioning / inactivity, Amylases malfunctions / inactivity.
Step 5- The Saliva / pancreatic amylases activity and function testes should
be
applied in association or without association with Polysaccharides and
disaccharides levels tests in the blood, urine, body fluids such as lymphatic
fluid or tissues as post treatment follow up, to monitor treatment efficacy
and
prognosis. Step 6- Improvement, non improvement or deterioration on
amylases activity tests in association with or without the reduction or non
reduction of disaccharides and polysaccharides levels are considered for
CA 02661953 2009-02-17
evaluation of treatment, adjustment of Amzylite doses, and prognosis of the
condition.
Normal Ranges for Saliva Amylase activity on Disaccharides (Standard organic,
non GM, non resistant, Sucrose reagent) and Saliva Amylase activity on
Polysaccharides (Standard organic, non GM, non resistant, polysaccharides
starch) tests results
According to the invention, normal ranges of amylases activity are: 30 to 120
minutes for the degradation of disaccharides by the disaccharides specialised
amylases (disaccharides specialised salivary, pancreatic or systemic amylases
were not known before), and 4 to 6, up to 8 hours for the degradation of
polysaccharides by polysaccharides specialised amylases. Tests results for
amylase activity on polysaccharides, and amylase activity on disaccharides is
compared to a normal range of 30 to 120 minutes for disaccharides, and 6 to 8
hours for polysaccharides (meaning: 250 mg/dl of glucose detected in a
disaccharide test sample within 30 to 120 minutes, and 250 mg/dl of glucose to
be detected in a polysaccharides sample within 6 to 8 hours),. Normal range
for disaccharides and polysaccharides are the ranges detected in a healthy non
polysaccharides, oligosaccharides, disaccharides and monosaccharides
diseases, non diabetic, non diseased individuals in a low endemic diabetes
area
(normal range figures obtained from health subjects in western Sudan and
Darfur region where diabetes is approximately 7% of the population). Normal
ranges for the tests can also be compared from the following calculations:
Glucamylase: 1 unit of enzyme activity catalyzes the production of 1.0mg
(1.0ml) of glucose in 1 hour under the following condition: 40 C pH = 4.6,
Amylase: 1 unit of enzyme activity is the amount of enzyme that will
dextrinize
1.0mg (1.Om!) of soluble starch in 1 hour under the following condition: 60 C
21
CA 02661953 2009-02-17
pH = 6.0, High temperature amylase: 1 unit of enzyme activity is the amount of
enzyme that will dextrinize 1.0mg (1.Oml) of soluble starch in 1 hour under
the
following condition: 70 C pH = 6Ø
Another embodiment of this invention is the use of active enzyme compound
called Amzylite and or trimethylglycine (betaine), in food industry for making
low glucose food and drink products, or the compound can be used in sachets
or as capsules to reduce glucose in food and drinks such as juices and soft
drinks. Amzylite compound is scientifically proven to reduce glucose in food
and drink. Another use of this invention is for use in glucose testing strip,
such
as blood glucose testing strips, urine testing strips, fluids testing strips
and
saliva testing strips. Amzylite compound or trimethylglicine can be used on
the
strip, for testing glucose such as other enzymes currently used for glucose
testing such as oxidase, dehydrogenase and hexokinase. The applicant
discovered that Amzylite and or Trimethylglicine can lower glucose in vitro,
and in vivo, and this can be applied in food industry to lower glucose in food
and drinks.
Due to the powerful immediate effect of lowering glucose in vitro, the
invention also relates to the use of Amzylite separately or trimethylglycine
separately in glucose sensing strips. Amzylite and or trimethylglicine have
been
used in blood glucose testing strips and glucose urine dipsticks, to detect
and
sense for glucose levels in a sample (ARBAB-glucometers). The sample tested
by ARBAB-Glucometer can be blood sample, urine sample, body fluid sample
such as lymphatic fluid, glucose fluid sample, and soft drink sample that
contain glucose. Special analyzer for the strips was invented to read amzylite
and or trimethylglicine strips. Saliva, pancreatic, blood, urine, body fluids
test
and saliva, pancreatic juice, blood, urine, body fluid test strips were also
22
CA 02661953 2009-02-17
invented (see description below). The saliva, pancreatic fluid, blood, urine,
body fluids test were invented to help diagnostic and monitor enzymes
malfunctioning or inactivity for 24 hours before and after treatment with
Amzylite.
Another objective of the invention is invention of treatment, and treatment
monitoring to evaluate treatment with Amzylite, and or the progress of the
enzymes activity, in relation to the condition and symptoms, in symptomatic
subjects, or to evaluate progress of aging in a subject by monitoring changes
on appearance, skin turgur and level of activity when treating aging process.
Amzylite monitoring device is an analyzer designed to read enzymes activity
for
disaccharides and polysaccharides for 24 hours, in a blood sample, urine
sample, saliva sample, pancreatic juice sample, and body fluid sample. The
results will then be compared to standard normal range for amylases
disaccharides reaction per unit of time to obtain glucose and amylases
polysaccharides reaction per unit of time to obtain glucose (see normal ranges
attached with this discribtion).
Another embodiment of the invention is to test for levels of disaccharides and
polysaccharides, proteins and lipids in blood (whole blood), urine, body
fluid,
pancreatic juice, by using a new invented strip, which contain enzymes such as
amylases (alpha and beta amylases), glucoamylase, invertase, protease, lipase,
lactase, pectinase, cellulose, and malt-diastase. Some strips will contain
iodine
to read polysaccharides starch. Strips will be read by an analyzer. Readings
will
to be carried out before treatment, during and after treatment to evaluate and
prognosis of treatment and condition.
23
CA 02661953 2009-02-17
Another embodiment of the invention is to test for enzyme activity by using
strip contains different types of saccharides, for example glucose, mannose,
lactose, glactose, dextrin, sucrose, polysaccharides starch. Strips will be
read
with special analyzer.
The present invention also relates to the use of physiologically acceptable
enzyme complex for the treatment of diseases associated with enzymes
malfunctioning and inactivity, amylases activity malfunctioning, delayed
activity or inactivity and excess of saccharides, as adjuvant therapy of
diseases
associated with malfunctioning or absence of amylases activity (The active
enzyme contains a catalytic triad, including Asp197, GIu233 and Asp300,
{Example of other analogous: (1) Asp 196, Glu233, and Asp301; (2) Asp197,
Glu232, Asp300; (3) Asp197, Glu233, Asp 299;) with or without excess and
presence of high levels of saccharides (monosaccharides, disaccharides and
polysaccharides) in blood and tissues.
As used herein the term "presence of high levels of saccharides
(polysaccharides, disaccharides and monosaccharides), in blood and tissues" is
understopd to mean a condition in which amylases activity is altered or
impaired (inactivity of amylases enzymes for 24 hours or more) with or
without, the presence of high levels of monosaccharides disaccharides and
polysaccharides in blood and tissues in asymptomatic healthy individuals and
symptomatic unhealthy individuals for example individuals suffer from renal
failure.
Active salivary like, gastric like, pancreatic like and intestinal like
proteins and
other enzymes are known enzymes complex with active amylases (The active
site of the enzyme contains a catalytic triad, including Asp197, GIu233 and
24
CA 02661953 2009-02-17
Asp300, {Example of other analogous: (1) Asp 196, GIu233, and Asp301; (2)
Asp197, Glu232, Asp300; (3) Asp197, GIu233, Asp 299;,) active lipases and
active proteases, active malt diastases, active pectinases, active invertases,
active cellulases, active lactases, and active invertases, which is available
for
example, under the trade name Amzylite , in the form of granules, pellets,
lyophilized powder for intravenous injection or capsules containing enteric
coated microspheres and is used medically for enzyme replacement. Amzylite
is generally obtained as a mixture of natural enzymes by extraction from
microbial, plant, yeast, fungi and human saliva or pancreatic juice, for
example
according to the process described in UK patent application GB0407583.4, and
is then converted into the desired galenical form in a manner known in the
art.
The salivary, gastric, pancreatic and intestinal like' enzymes are usually
administered orally or intravenously, in the form of solid or solution
preparations.
An in-vitro and in-vivo, single centre, non placebo-controlled, parallel group
study with 1,4-a-D-glucan glucanohydrolase; Exo-1,4-a-glucosidase; Beta-
fructofuranosidase; Protease; Pectinase; Lipase; Cellulase; Lactase; Malt
Diastase, in the form of Amzylite (capsules) was conducted in saccharides
based diseases associated with malfunctioning or absence of amylases activity
disorders and its complications patients with coexisting salivary
malfunctioning
and absence of salivary alpha amylase in association with excess presence of
disaccharides and polysaccharides (saccharides) in the blood and tissues, to
demonstrate the positive effects of the described enzyme complexes on
diseases control. The patient sample (male/female) was randomly assigned to
groups each comprising 141 patients. Treatment was given over a period of
one year at an oral dosage of 3 to 6 Amzylite capsules daily. One or two
capsules were administered before each of the main meals (3 to 4 daily). One
CA 02661953 2009-02-17
capsule of Amzylite contained medicinal ingredients: Betaine 200 mg; 1,4-a-
D-glucan glucanohydrolase 100 mg; Exo-1,4-a-glucosidase 100 mg; Beta-
fructofuranosidase 20 mg; Protease (3.0), 52.62 mg; Pectinase 10 mg; Lipase
7.5 mg; Cellulase 5 mg; Lactase 5 mg; Malt Diastase 3.33 mg. Non-Medicinal
Ingredients: Microcrystalline cellulose, Magnesium stearate and maltodextrin.
Parameters of the kind generally used to evaluate saccharides and enzymes
deficiency diseases were recorded before start of treatment.
The efficacy of the enzyme complex used in terms of the salivary enzymes
activity control was determined by measuring, saliva enzymes functions for
disaccharides and polysaccharides, serum amylase levels, urea and
electrolytes, cholesterol levels, saccharides levels in blood and body
tissues,
the glycosylated hemoglobin level (HbA 1C). In this context a positive
influencing of the saliva enzymes function tests for saccharides, urea and
electrolytes, cholesterol levels, saccharides levels in the blood and tissues
and
HbA 1C level as a clinically relevant improvement in the saccharides based
diseases status is desired. Further saccharides based diseases parameters used
were blood glucose levels (insulin/glucagon), status of lipid soluble vitamins
(A,
D and E), daily insulin dose, body weight index and hyperglycaemic episodes.
Following a preliminary assessment for selection of the patient sample, the
patients completed an initial start-up phase of 1 to 2 weeks (without
administration of enzyme complexes) to establish the patients on individual
saccharides based diseases parameters before starting treatment with
Amzylite. Before commencing the parallel groups study period, a baseline
assessment was carried out. The patients underwent two interim assessments
in the first month of the study. Further assessments were carried out after
six
weeks of treatment, then every 8 to 10 weeks and at the end of the study.
26
CA 02661953 2009-02-17
Gastroenterologic parameters such as faecal fat, stool characteristics,
coefficient of fat absorption (CFA) and clinical symptoms were evaluated
separately from the saccharides based diseases and diabetic parameters.
The above study showed that saccharides based diseases in association with
enzymes malfunctioning or inactivity and amylases malfunction or absent
activity parameters are beneficially influenced by the administration of
Amzylite, both in terms of a decrease of saccharides and excess proteins
levels
in blood and tissues, and improvement of enzymes activity and mor specific
amylases enzymes activity as well as improved symptoms of the diseases
manifested, for example, by stabilization of blood saccharides enzymes
activity
and function and amylases activity curves and, for example, reduction of the
symptoms and progress of the diseases. The results of the study therefore
demonstrate that the administration of physiologically acceptable enzyme
complexes with active amylases, active lipases and active proteases in
addition
to other active enzymes such as glucoamylase, invertase, cellulose, lipase,
protease, lactase, malt diastase and other saccharides related enzymes
according to the invention can bring about an improvement in saccharides
based diseases and amylases and other enzymes malfunction or absent activity
and diabetes mellitus status. It was demonstrated independently of these
findings that in the group of patients with amylases enzymes absent activity
with coexisting complications, including diabetes, the gastroenterologic
parameters such as faecal fat, stool characteristics, CFA and clinical
symptoms
are also beneficially influenced and that the overall nutritional status of
these
patients is improved. Physiologically acceptable enzyme complexes with active
enzymes such as 1,4-a-D-glucan glucanohydrolase; Exo-1,4-a-glucosidase;
Beta-fructofuranosidase; Protease; Pectinase; Lipase; Cellulase; Lactase; Malt
Diastase -especially Amzylite or complexes of enzymes containing 1,4-a-D-
27
CA 02661953 2009-02-17
glucan glucanohydrolase; Exo-1,4-a-glucosidase; Beta-fructofuranosidase, also
with the microbial enzyme supplements described-are therefore suitable for
the manufacture of pharmaceutical preparations for the treatment of
saccharides based diseases associated with or without malfunctioning
amylases malfunctions or absent activity, especially for the adjuvant therapy
of
kidney failure, micro and macro angiopathy and diabetes mellitus; in these
cases the diabetes mellitus may also be accompanied by amylases malfunction
or absent activity in association with or without high levels of saccharides
(mainly polysaccharides starch) in blood, blood vessels walls, organ tissues,
skin and subcutaneous tissues and including brain tissues. Another
embodiment of this invention is the use of active enzyme compound called
Amzylite and or trimethylglycine (betaine), in food industry for making low
glucose food and drink products or the compound can be used in sachets or as
capsules to reduce glucose in food and drinks such as juices and soft drinks.
Amzylite compound is scientifically proven to reduce glucose in food and
drink.
Another use of this invention is for use in glucose testing strip, such as
blood
glucose testing strips, urine testing strips, fluids testing strips and saliva
testing
strips. Amzylite compound or trimethylglicine can be used on the strip, for
testing glucose such as other enzymes currently used for glucose testing such
as oxidase, dehydrogenase and hexokinase.
The pharmacological beneficial effects of the used enzyme complexes on the
enzymes malfunctioning or inactivity, amylases malfunctioning or inactivity
with or without saccharides based diseases and parameters on the
improvement of the saccharides based diseases, including diabetes mellitus
status shall be further elucidated by the clinical study described in the
following and by the results achieved therewith.
28
CA 02661953 2009-02-17
More explanation about how this invention works:
The following steps should be followed to practice the invention: - 1- The
Saliva
/ pancreatic amylases activity and function testes should be determined in any
subject as routine screening tests to predict, diagnosis, prognosis, treatment
and post treatment follow up. 2- Subjects with positive tests for
malfunctioning / inactivity of amylases should be tested for levels of
monosaccharides, disaccharides and polysaccharides in blood, urine, body
fluids and tissues. 3- Polysaccharides and disaccharides levels in the blood,
urine, body fluids such as lymphatic fluid or tissues should be determined in
any subject as routine screening tests, as diagnostic tests and after a
positive
salivary / pancreatic amylases malfunctioning / inactivity tests, to predict,
diagnosis, prognosis, treatment and post treatment follow up. 4- Amzylite
should then be administered to correct malfunctioning of enzymes activity or
inactivity, Amylase malfunctioning activity / inactivity, and to correct high
disaccharides and polysaccharides levels that could exist in association with
enzymes malfunctioning / inactivity, Amylases malfunctions / inactivity. 5-
The
Saliva / pancreatic amylases activity and function testes should be applied in
association or without association with Polysaccharides and disaccharides
levels tests in the blood, urine, body fluids such as lymphatic fluid or
tissues as
post treatment follow up, to monitor treatment efficacy and prognosis. 6-
Improvement, non improvement or deterioration on amylases activity tests in
association with or without the reduction or non reduction of disaccharides
and polysaccharides levels are considered for evaluation of treatment,
adjustment of Amzylite doses, and prognosis of the condition.
29
CA 02661953 2009-02-17
Important points :-
= A Pharmaceutical composition called Amzylite for use as medicament for
primary or secondary amylases activity malfunction or inactivity wherein
said, Amzylite is a pharmaceutical medicament preparation comprising
a physiologically acceptable enzyme and protein complex having
Trimethylglycine, active 4-a-D-glucan glucanohydrolase; active Exo-1,4-
a-glucosidase; active Beta-fructofuranosidase; active lipases, active
proteases {for example: Protease (3.0)}; active Pectinase; active Lipase;
active Cellulase; active Lactase; active Malt Diastase.
= A Pharmaceutical composition called Amzylite for use as medicament for
primary or secondary 4-a-D-glucan glucanohydrolase; Exo-1,4-a-
glucosidase; Beta-fructofuranosidase; lipases, proteases; Pectinase;
Lipase; ellulase; Lactase; Malt Diastase activity malfunction or inactivity
wherein said, Amzylite is a pharmaceutical medicament preparation
comprising a physiologically acceptable enzyme and protein complex
having Trimethylglycine, active 4-a-D-glucan glucanohydrolase; active
Exo-1,4-a-glucosidase; active Beta-fructofuranosidase; active lipases,
active proteases {for example: Protease (3.0)}; active Pectinase; active
Lipase; active Cellulase; active Lactase; active Malt Diastase.
= A Pharmaceutical composition called Amzylite for use as adjuvant
medicament to treat severe infections such as wet gangrene, and
chronic infected wounds, wherein said, Amzylite is a pharmaceutical
medicament preparation comprising a physiologically acceptable
enzyme and protein complex having Trimethylglycine, active 4-a-D-
CA 02661953 2009-02-17
glucan glucanohydrolase; active Exo-1,4-a-glucosidase; active Beta-
fructofuranosidase; active lipases, active proteases {for example:
Protease (3.0)}; active Pectinase; active Lipase; active Cellulase; active
Lactase; active Malt Diastase.
= A Pharmaceutical composition called Amzylite for use as medicament to
treat persorped particles in the blood, such as starch, proteins, meat
fibres, fats, microcrystallines, comprising administering an effective
amount of a pharmaceutical composition called Amzylite for use as
medicament preparation comprising a physiologically acceptable
enzyme and protein complex having Trimethylglycine, active 4-a-D-
glucan glucanohydrolase; active Exo-1,4-a-glucosidase; active Beta-
fructofuranosidase; active lipases, active proteases {for example:
Protease (3.0)1; active Pectinase; active Lipase; active Cellulase; active
Lactase; active Malt Diastase.Persorped particles can also be found in
urine, lymphatic fluid and tissues (for example subcutaneous tissue).
= A Pharmaceutical composition called Amzylite for use as anti-aging
medicament for cosmetics purposes, wherein said, Amzylite is a
pharmaceutical medicament preparation comprising a physiologically
acceptable enzyme and protein complex having Trimethylglycine, active
4-a-D-glucan glucanohydrolase; active Exo-1,4-a-glucosidase; active
Beta-fructofuranosidase; active lipases, active proteases {for example:
Protease (3.0)); active Pectinase; active Lipase; active Cellulase; active
Lactase; active Malt Diastase.
= A Pharmaceutical composition called Amzylite for use as medicament to
treat diabetes, wherein said, Amzylite is a pharmaceutical medicament
31
CA 02661953 2009-02-17
preparation comprising a physiologically acceptable enzyme and protein
complex having Trimethylglycine, active 4-a-D-glucan glucanohydrolase;
active Exo-1,4-a-glucosidase; active Beta-fructofuranosidase; ' active
Iipa'ses, active proteases {for example: Protease (3.0)1; active Pectinase;
active Lipase; active Cellulase; active Lactase; active Malt Diastase.
= A Pharmaceutical composition called Amzylite for use as medicament to
treat complications of diabetes, wherein said, Amzylite is a
pharmaceutical medicament preparation comprising a physiologically
acceptable enzyme and protein complex having Trimethylglycine, active
4-a-D-glucan glucanohydrolase; active Exo-1,4-a-glucosidase; active
Beta-fructofuranosidase; active lipases, active proteases {for example:
Protease (3.0)}; active Pectinase; active Lipase; active Cellulase; active
Lactase; active Malt Diastase.
= A Pharmaceutical composition called Amzylite for use as medicament to
treat asthma, wherein said, Amzylite is a pharmaceutical medicament
preparation comprising a physiologically acceptable enzyme and protein
complex having Trimethylglycine, active 4-a-D-glucan glucanohydrolase;
active Exo-1,4-a-glucosidase; active Beta-fructofuranosidase; active
lipases, active proteases {for example: Protease (3.0)}; active Pectinase;
active Lipase; active Cellulase; active Lactase; active Malt Diastase.
= A Pharmaceutical composition called Amzylite for use as medicament to
treat arthritis, wherein said, Amzylite is a pharmaceutical medicament
preparation comprising a physiologically acceptable enzyme and protein
complex having Trimethylglycine, active 4-a-D-glucan glucanohydrolase;
active Exo-1,4-a-glucosidase; active Beta-fructofuranosidase; active
32
CA 02661953 2009-02-17
lipases, active proteases {for example: Protease (3.0)}; active Pectinase;
active Lipase; active Cellulase; active Lactase; active Malt Diastase.
= A Pharmaceutical composition called Amzylite for use as medicament to
treat DVT (deep vein thrombosis), P.E (pulmonary embolism), and Brain
artery embolism (stroke), wherein said, Amzylite is a pharmaceutical
medicament preparation comprising a physiologically acceptable
enzyme and protein complex having Trimethylglycine, active 4-a-D-
glucan glucanohydrolase; active Exo-1,4-a-glucosidase; active Beta-
fructofuranosidase; active lipases, active proteases {for example:
Protease (3.0)}; active Pectinase; active Lipase; active Cellulase; active
Lactase; active Malt Diastase.
= A Pharmaceutical composition called Amzylite for use as medicament to
treat Alzheimers disease, wherein said, Amzylite is a pharmaceutical
medicament preparation comprising a physiologically acceptable
enzyme and protein complex having Trimethylglycine, active 4-a-D-
glucan glucanohydrolase; active Exo-1,4-a-glucosidase; active Beta-
fructofuranosidase; active lipases, active proteases {for example:
Protease (3.0)}; active Pectinase; active Lipase; active Cellulase; active
Lactase; active Malt Diastase.
= A Pharmaceutical composition called Amzylite for use as medicament to
treat renal failure, wherein said, Amzylite is a pharmaceutical
medicament preparation comprising a physiologically acceptable
enzyme and protein complex having Trimethylglycine, active 4-a-D-
glucan glucanohydrolase; active Exo-1,4-a-glucosidase; active' Beta-
fructofuranosidase; active lipases, active proteases {for example:
33
CA 02661953 2009-02-17
Protease (3.0)}; active Pectinase; active Lipase; active Cellulase; active
Lactase; active Malt Diastase.
= A Pharmaceutical composition called Amzylite for use as medicament to
treat hypercholesterolemia, wherein said, Amzylite is a pharmaceutical
medicament preparation comprising a physiologically acceptable
enzyme complex and proteins having Trimethylglycine, active 4-a-D-
glucan glucanohydrolase; active Exo-1,4-a-glucosidase; active Beta-
fructofuranosidase; active lipases, active proteases {for example:
Protease (3.0)}; active Pectinase; active Lipase; active Cellulase; active
Lactase; active Malt Diastase.
= A Pharmaceutical composition called Amzylite for use as medicament to
treat Angina and coronary artery disease, wherein said, Amzylite is a
pharmaceutical medicament preparation comprising a physiologically
acceptable enzyme and protein complex having Trimethylglycine, active
4-a-D-glucan glucanohydrolase; active Exo-1,4-a-glucosidase; active
Beta-fructofuranosidase; active lipases, active proteases {for example:
Protease (3.0)}; active Pectinase; active Lipase; active Cellulase; active
Lactase; active Malt Diastase.
= A Pharmaceutical composition called Amzylite for use as medicament to
treat epilepsy, wherein said, Amzylite is a pharmaceutical medicament
preparation comprising a physiologically acceptable enzyme and protein
complex having Trimethylglycine, active 4-a-D-glucan glucanohydrolase;
active Exo-1,4-a-glucosidase; active Beta-fructofuranosidase; active
lipases, active proteases {for example: Protease (3.0)}; active Pectinase;
active Lipase; active Cellulase; active Lactase; active Malt Diastase.
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CA 02661953 2009-02-17
= A Pharmaceutical composition called Amzylite for use as medicament to
treat irritable bowel syndrome caused by indigestion, wherein said,
Amzylite is a pharmaceutical medicament preparation comprising a
physiologically acceptable enzyme and, protein complex having
Trimethylglycine, active 4-a-D-glucan glucanohydrolase; active Exo-1,4-
a-glucosidase; active Beta-fructofuranosidase; active lipases, active
proteases {for example: Protease (3.0)}; active Pectinase; active Lipase;
active Cellulase; active Lactase; active Malt Diastase.
= A Pharmaceutical composition called Amzylite for use as medicament to
treat peripheral ischaemic diseases, in an animal or human, Amzylite is a
pharmaceutical medicament preparation comprising a physiologically
acceptable enzyme and protein complex having Trimethylglycine, active
4-a-D-glucan glucanohydrolase; active Exo-1,4-a-glucosidase; active
Beta-fructofuranosidase; active lipases, active proteases {for example:
Protease (3.0)}; active Pectinase; active Lipase; active Cellulase; active
Lactase; active Malt Diastase.
= A Pharmaceutical composition called Amzylite for use as adjuvant
medicament to treat severe infections such as wet gangrene, and
chronic infected wounds, wherein said, Amzylite is a pharmaceutical
medicament preparation comprising a physiologically acceptable
enzyme and protein complex having Trimethylglycine, active 4-a-D-
glucan glucanohydrolase; active Exo-1,4-a-glucosidase; active Beta-
fructofuranosidase; active lipases, active proteases {for example:
Protease (3.0)}; active Pectinase; active Lipase; active Cellulase; active
Lactase; active Malt Diastase.
CA 02661953 2009-02-17
= A Pharmaceutical composition called Amzylite for use as medicament to
treat high levels of persorped and deposited particles such as starch,
proteins, meat fibres, fats, microcrystallines, in the blood, in vascular
walls, in urine, in lymphatic fluid and in tissues (for example
subcutaneous tissue), comprising administering to said an effective
amount of a pharmaceutical medicament preparation called Amzylite
comprising a physiologically acceptable enzyme and protein complex
having Trimethylglycine, active 4-a-D-glucan glucanohydrolase; active
Exo-1,4-a-glucosidase; active Beta-fructofuranosidase; active lipases,
active proteases {for example: Protease (3.0)}; active Pectinase; active
Lipase; active Cellulase; active Lactase; active Malt Diastase.
= A pharmaceutical compound according to claim 1 to 18, wherein said
pharmaceutical composition called Amzylite for use as medicament
preparation comprises a physiologically acceptable enzyme and protein
complex having Trimethylglycine, active 4-a-D-glucan glucanohydrolase;
active Exo-1,4-a-glucosidase; active Beta-fructofuranosidase; active
lipases, active proteases {for example: Protease (3.0)}; active Pectinase;
active Lipase; active Cellulase; active Lactase; active Malt Diastase of
plant, animal, or human origin, salivary enzymes, gastric juice enzymes,
pancreatic juice enzymes and intestine enzymes, trimethylglycine,
lipases, and proteases enzymes.
= A pharmaceutical composition called Amzylite for use as medicament
preparation according to claim 1 to 18, wherein said the pharmaceutical
medicament preparation enzyme and protein complex having
Trimethylglycine, active 4-a-D-glucan glucanohydrolase; active Exo-1,4-
36
CA 02661953 2009-02-17
a-glucosidase; active Beta-fructofuranosidase; active lipases, active
proteases {for example: Protease (3.0)}; active Pectinase; active Lipase;
active Cellulase; active Lactase; active Malt Diastase, is administered as
an adjuvant therapy in conjunction with another, primary therapy or
alone.
= New glucose test strip containing Amzylite or an organic compound
called Trimethylglycine, also called TMG.
= Saliva disaccharide test, for testing activity of saliva disaccharide
enzymes, pH, glucose and protein in a saliva sample for twenty four
hours.
= Saliva polysaccharide test, for testing activity of saliva polysaccharide
enzymes, pH, glucose and protein in a saliva sample for twenty four
hours.
= Saliva disaccharide test, for testing activity of saliva disaccharide
enzymes, leucocytes, protein, pH, blood, specific gravity, bilirubin, and
glucose in a saliva sample for twenty four hours.
= Saliva polysaccharide test, for testing activity of saliva polysaccharide
enzymes, leucocytes, protein, pH, blood, specific gravity, bilirubin, and
glucose in a saliva sample for twenty four hours.
= A method of diagnosis of enzymes activity malfunction or inactivity and
saliva test is applied as adjuvant test in conjunction with another,
primary test.
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CA 02661953 2009-02-17
= A method of diagnosis of enzymes activity malfunction or inactivity and
saliva is applied to larger mammal or human who do not suffer from
diseases and larger mammal or human who suffer from disease such as
renal failure or diabetes.
= Saliva, pancreatic, and urine strip for determination, bilirubin, specific
gravity, blood, pH, protein, leucocytes, and measuring saliva enzymes
activity for disaccharides in saliva, pancreatic juice, and urine sample.
= Saliva, pancreatic juice, and urine strip for determination, bilirubin,
specific gravity, blood, pH, protein, leucocytes, and measuring saliva
enzymes activity for polysaccharides in saliva, pancreatic juice and urine
sa m ple.
= Saliva, pancreatic juice, and urine strip Analyzer, for use with saliva,
pancreatic juice, and urine strip for determination of specific gravity,
blood, pH, protein, leucocytes, and measurement of enzymes activity in
saliva, pancreatic juice, and urine for disaccharides and polysaccharides
in saliva, pancreatic juice and urine sample.
= Saccharides / enzymes activity functions strip and strip analyzer contain,
iodine, 1,4-a-D-glucan glucanohydrolase; Exo-1,4-a-glucosidase; Beta-
fructofuranosidase; Protease; Pectinase; Lipase; Cellulase; Lactase; Malt
Diastase enzymes to determine the presence and the level of
monosaccharides, disaccharides and polysaccharides in venous blood
samples, arterial blood samples, capillary blood samples, serum blood
samples, lymphatic fluid sample.
38
CA 02661953 2009-02-17
= Saccharides strip and strip analyzer, wherein strip contain, saccharides
for reaction with enzymes in the blood, urine, lymphatic fluid and saliva
samples, containing polysaccharides starch, disaccharides (sucrose),
mannose, dextrin, proteins, pectin, lipids, cellulose, lactose and maltose
are to be added in saliva, blood, urine pancreatic juice and lymphatic
fluid samples, to determine presence and or level of activity for
saccharides enzymes contained in a sample.
= Multifunction-Urine Strip and strip Analyzer, for determination of
glucose, bilirubin, specific gravity, blood, pH, protein, leucocytes,
haemoglobin, nitrite (produced by bacteria in a urinary tract infection),
urobilinogen and ketones in urine samples, here urine strip (dipstick)
contain Amzylite or tri.methylglycine also called TMG or betaine, on the
strip to determine glucose in a urine sample.
= New Saliva, pancreatic and urine Analyzer device for use with new
laboratory test (Amylases function test), for measuring pH media in
relation to saliva, pancreatic and urine amylases enzymes activity.
= (Amzylite Monitor) also called enzyme monitor device to rrionitor the
effect of Amzylite by measuring changes of amylases and other enzymes
activity before, during and after the use of Amzylite.
= Amzylite and or an organic compound called Trimethylglycine also called
TMG, for use to make low glucose food and drink or to lower glucose
level in food and drink.
39
CA 02661953 2009-02-17
Clinical Study
Amzylite F 1.2 As In-vitro / In-vivo Glucose Reducing Agent and Treatment for
Diabetes / Diabetes Complications
Objectives:
Our objectives were to determine the efficacy of Amzylite as in-vitro / in-
vivo
hypoglycaemic agent, anti-diabetes anti-complications for both diabetes / non
diabetes. Some of the studies were carried out at Medical & Health Center,
Abu Dhabi, U.A.E (2006 - 2007) other studies were carried out at Buhaira
Private Hospital - Omdurman - Sudan.
Methods:
Our methods were: In-vitro testing to determine glucose units in a glucose
solution before and after mixing with Amzylite against other known
hypoglaycaemic agents (metformin, sulfonylurea, etc) including insulin. 10 mis
of 10% concentrated glucose solution tested for glucose concentration using
glucose oxidase and or hexokinase (glucometers can also be used). Glucose
values were more than 600 mg/dl (Glucometer readings were Hi, 600 mg/dl or
more ;). One or two capsule of Amzylite was added to the glucose solution. In-
vivo: 141 type I and type II diabetics with diabetes neuropathy, in addition
to 9
diabetics with renal incompetency, 15 diabetics with chronic wounds to
CA 02661953 2009-02-17
extremities, 2 diabetics had progressive gas- gangrene, all patients had
neuropathy with impaired sensations to distal extremities and one none
diabetic with renal failure were identified. 31 out of 141 were excluded for
incomplete records. 8 self discharged. 128 classified into 4 groups: 33 on
insulin therapy; 20 on insulin and oral hypoglycaemic agents, 58 on only oral
hypoglycaemic therapy, 16 on diet control only. 9 with high creatinine levels,
15 with chronic wounds, 2 had gas gangrene to distal extremities and one non
diabetic had renal incompetency and was on dialysis. Laboratory tests were
determined before and after starting Amzylite. No placebo was given.
Results:
Our results showed In vitro glucose readings were significantly reduced
immediately after mixing with Amzylite. Glucose values of 160 to 100 mg/dl
and lower were obtained immediately. No changes observed with all other
known hypoglycaemic agents (metformin, sulfonylurea, etc) including insulin.
In vivo: 7 had diabetes reversed following treatment with Amzylite: 9 renal
with high creatinine of up to 8 mg/dl (nr: 0.6 - 1.2 mg/di) were recovered and
condition reversed. One non diabetic dialysis patient with high cretinine of
14.5 mg/dl (nr: 0.6 - 1.2 mg/dl), reduced to 10.20 mg/di within two month. 15
chronic wounds, reversed within 8 to 14 days. 2 gas gangrene (moist, wet
gangrene), showed improvement, and disappearance of gas gangrene
(disappearance of severe infection which resulted in stopping of progression
of
gangrene) by limitation of necrotic area but no change on necrotic tissues.
One
had very severe wound pains, required wound dressing under general
anaesthesia. 128 reversed neuropathy and regained complete sensations. 89%
managed to control symptoms and glucose readings without insulin or oral
tablets. 10 - 11 % managed to reduce insulin and tablets.
Conclusion:
41
. .... .... . ....... . . . ... .. . . . . . . .. .
CA 02661953 2009-02-17
Amzylite should be considered for screening, prophylaxes and treatment of
diabetes and its complications.
Another Clinical Study
AMZYLITE F 1.2 AS GLUCOSE REDUCING AGENT WITH DIRECT EFFECT AND
TREATMENT FOR DIABETES.
Introduction:
WHO defined diabetes as a chronic condition that occurs when the pancreas
does not produce enough insulin or when the body cannot effectively use the
insulin it produces.
Objectives:
To determine the efficacy of Amzylite as in-vitro / in-vivo hypoglycaemic
agent
and anti-diabetic. To study the relationship between hypoglycaemic agents
(including insulin) and glucose. Amzylite is a registered medicinal
formulation.
Settings:
In-vitro and in-vivo prospective studies were carried out at Medical & Health
Center, Abu Dhabi, U.A.E.
Methods:
In-vitro testing to determine glucose units in a glucose solution before and
after mixing with Amzylite against other known hypoglaycaemic agents
(metformin, sulfonylurea, etc) including insulin. 10 mis of 10% concentrated
glucose solution tested for glucose concentration using glucose oxidase and or
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CA 02661953 2009-02-17
hexokinase (glucometers can also be used). Glucose values were more than
600 mg/dl (Glucometer readings were Hi, 600 mg/dl or more ;). One capsule of
Amzylite added to the glucose solution. For In-vivo study to determine the
effectiveness of Amzylite as treatment for D.M. 141 patients with type I and
type II D.M were treated with Amzylite. 31 patients were excluded for
incomplete records. 8 patients' self withdrawn. 102 Patients were classified
into 4 groups: (1) 26 patients were on insulin therapy (4 of this group were
excluded); (2) 9 were on insulin and oral hypoglycaemic agents, (2 were
excluded) (3) 51 patients were on only oral hypoglycaemic therapy (4 were
excluded from this group). (4) 16 patients were on diet control only (1
excluded from this group). Fasting and 2 hours postprandial blood glucose
levels (HbAlc checked in some but not all patients) were determined before
starting Amzylite. Clinical examinations together with clinical history were
documented for each patient. Saliva enzymes function tests were determined
for disaccharides and polysaccharides in all patients. Patients were requested
to record 2 hour postprandial blood glucose values before and after Amzylite,
3 times per day or more. Improvement in patients' symptoms, daily glucose
readings (fasting / 2 hour postprandial) and HbAlc were set up as target and
evaluation criteria. Follow up was set up every 2 to 4 weeks for daily glucose
recording charts review, medication review, symptoms review and repeat
saliva test after 4 weeks from the start of treatment. HbAlc test 2-3 months.
No placebo was given. One or two capsules were given t.d.s or q.d.s, according
to saliva enzymes function test result. Postprandial blood glucose tests were
designed to determine and compare any changes in glucose values before and
after Amzylite. Changes were also determined by 4 improvement criteria. 1-
Improvement with complete recovery, 2- Significant improvement of
symptoms and readings (range 70 - 170 mg/dl and below 200 mg/dl), 3-
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CA 02661953 2009-02-17
Improved symptoms but no change on readings, 4- Improved readings but no
improvement on symptoms, 5- No change on symptoms or readings, 6- Higher
or lower glucose readings. 7- Deterioration of symptoms.
Results:
In vitro Results showed glucose readings were significantly reduced
immediately after mixing with Amzylite. Glucose values of 180 mg/dI and lower
were obtained immediately. Lower values were also obtained after 15, minutes
and more (hours). No changes observed on glucose values when in vitro mixing
glucose solution with all other known hypoglycaemic agents (metformin,
sulfonylurea, etc) including insulin. In vivo results showed that, 7 out of
102
patients had completely recovered from diabetes within one, two and 3
months following treatment with Amzylite, (fasting and 2 hours postprandial
blood glucose values were ranging 70 -110 mg/dl). 88 patients had positive
improvement on symptoms and readings (range 70 - 170 and below 200
mg/dl) within days to weeks following treatment with Amzylite. 3 patients
improved on symptoms, without significant change on readings and 4
withdrawn. No patient had improved readings without improved symptoms.
Zero patients had no change on symptoms or readings. Zero patients had very
high or very low glucose readings. Zero patients had deterioration of
symptoms. 89% of patients on Amzylite have managed to control their
symptoms and glucose readings without insulin or oral hypoglaycaemic agents.
- 12 % have managed to significantly reduce insulin (e.g. insulin reduced
from 100 to 10 units per day) and tablets to one or half per day. Amzylite
reacts directly with glucose to reduce it. Insulin and oral hypoglaycaemic
agents react indirectly to reduce glucose by stimulating other enzymes
(glucose reducing enzymes) which reduce glucose. Two thirds of fully
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CA 02661953 2009-02-17
recovered patients were newly diagnosed diabetics (diabetes for days, weeks
and up to 6 months). Malfunction of any glucose reducing enzyme (e.g.
Amylase) could result in diabetes, diabetes complication and insulin
resistance.
Conclusion:
Amzylite is a trade mark for a private formulation, registered in United Arab
Emirates as dietary supplement. This study demonstrated that Amzylite F1.2 is
an effective in-vitro and in-vivo glucose lowering agent as well as anti-
diabetic
agent. Study demonstrated that patients with diabetes can be reversed back to
normal health, especially newly diagnosed. Diabetes screening programs
should be considered in association with Amzylite for prevention or treatment
of diabetes. Prophylaxes with Amzylite could help control spread of the
disease. Amzylite capsules should be considered for treatment and
prophylaxes against type 1 and type 2 diabetes mellitus. Due to its in-vitro
immediate glucose lowering action Amzylite could become one of the most
potential life saving hypoglycaemic agents.
Another Clinical Study
DIABETIC AND NON-DIABETIC SALIVA, ALPHA AMYLASE ACTIVITY INCREASED
IN ACID MEDIA
Objectives:
To study pH changes during saliva alpha amylase activity in diabetic and non
diabetic subjects in relation to glucose yielding. Explain mechanism of action
and occurrence of DKA.
Methods:
CA 02661953 2009-02-17
750 fresh saliva samples were collected from 200 diabetic and 50 non-diabetic
subjects. All subjects were fasting over night for 12 hours. Glucose oxidase
testing was used to detect amylase activity. Three identical 10 mis samples of
fresh well-prepared saliva were accepted from each patient for the study. One
sample from each subject was used as marker and tested for pH changes and
sugar hourly for 24 hours. Each second and third study samples were tested
initially for pH and sugar content; 1 ml of flour powder was added in each
second sample (250 flour sample). 1 ml of sucrose was added in each third
sample (250 sucrose samples). pH changes together with sugar readings were
tested hourly in each study sample for 24 hours.
Results:
750 (250 marker + 250 flour + 250 sucrose study sample) fresh saliva samples
of non diabetics and diabetic patients showed pH of 9 to 7 on immediate
testing. 250 marker samples showed no significant change in pH and zero sugar
reading for 24 hours. 235 flour, 223 sucrose study samples showed decrease in
pH 5>, in association with glucose detection in samples. 2 flour and 2 sucrose
samples showed decrease in pH from 9 to 7 in association with glucose yielding
within 24 hours. 8 isolated flour, 11 isolated sucrose diabetic samples, 4
same
patient flour and sucrose diabetes samples, 5 flour and 14 sucrose non
diabetic
samples showed decrease in pH 5 > without glucose yielding in 24 hours
(absent amylase activity). Zero non diabetic samples, same subject showed
absent amylase activity for both flour and sucrose. Decrease in pH in study
samples was noticed to be associated with increase in glucose yielding. 92% of
study samples showed decreased pH 5 > in association with high glucose
readings (250 - 500 mg/dl or more).
Discussion:
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CA 02661953 2009-02-17
Significant but nonspecific elevations of amylase can be seen in DKA (Diabetes
Care 26:3193-3194, 2003). Similarity between DKA and this study in terms of
increased acidity in the presence of elevated serum amylase, and in
association
with high glucose from degradation of disaccharides / polysaccharides
particles
that could exist in slightly larger amounts in the blood of diabetic compared
to
non diabetic subjects (persorption phenomenon - Gerhard Volkheimer).
Conclusion:
Saliva alpha amylase activity should be determined in relation to pH media.
Saliva alpha amylase is active in acid media. Correction of stomach pH and or
abnormal amylase activity could help treat / prevent diabetes and obesity.
Another Example of Study
Amzylite and Trimethylglycine as Glucose Sensing Agents and In-Vitro
Glucose Metabolism Indicators
Author: Dr Tarig S M Arbab, MD, MSc, DIC,
Saccharides Science & Technology
www.saccharidestech:com
Introduction: Previous and recent studies showed that Amzylite F1.2 (Amzylite
contains Trimethylglycine and Maltose) is an effective in-vitro and in-vivo
glucose reducing agent. Objectives: To study Amzylite F1.2 and
Trimetylglycine,
as in-vitro glucose metabolism indicators, and glucose sensing agents for use
in
glucose strips and ARBAB-Glucometers. Methods: 400 samples each 100
sample contains 10 mis of Amzylite F 1.2, Amzylite F1.2 (Trimethylglycine
Free),
Amzylite F1.2 (Maltase Free), trimethylglycine, 400 samples 200 containing 10
47
CA 02661953 2009-02-17
mis 10% glucose solution, and 200 containing 10 mis maltose solution were
initially tested for sugar using glucose oxidase and dehydrogenase. Amzylite
F1.2, Amzylite F1.2 (Trimethylglycine Free), Amzylite F1.2 (Maltose Free) and
Trimethylglycine, preparations were mixed and dissolved separately in 50
glucose samples and 50 maltose samples each. Then sugar content of each 200
glucose samples and 200 maltose samples were checked using oxidase and
dehydrogenase. Results: Oxidase and dehydrogenase readings were positive
for sugar in 100 samples containing 10 mis of Amzylite F 1.2 solution and in
100 samples containing 10 mis Amzylite F1.2 (Trimethylglycine Free) solution.
Both oxidase and dehydrogenase readings were negative for sugar in 100
samples containing 10 mis of Amzylite F1.2 (Maltase Free) solution, and 100
samples containing 10 mis of trimethylglycine solution. Both oxidase and
dehydrogenase readings were positive for glucose presence in 200 samples
containing 10 mis 10% glucose solution. Negative oxidase readings and positive
dehydrogenase readings for maltose sugar in 200 samples containing 10 mis
maltose solution. All glucose samples mixed with Amzylite F1.2 (Except
Amzylite Trimethylglycine free formulae), and trimethylglycine tested with
glucose oxidase, showed immediate reaction to glucose, with immediate and
significant reductions of glucose readings. All maltose samples mixed with
Amzylite F1.2 and tested with glucose oxidase showed positive sugar readings,
samples mixed with trimethylglycine showed negative readings. Amzylite had
significant advantages, with less reaction time and higher glucose reductions
compared to Trimethylglycine alone. Discussion: Many glucose meters employ
the oxidation of glucose by glucose oxidase, and glucose dehydrogenase.
Glucose dehydrogenase is more susceptible to interfering reactions with other
substances. Amzylite F1.2 and Trimethylglycyine, react with glucose for
immediate catalyze glucose oxidation of 1 to 5 seconds. Amzylite is more
48
CA 02661953 2009-02-17
specific for monosaccharide glucose. It was able to oxidize and reduce
monosaccharide glucose in the sample despite containing maltose in its
compound. Oxidase was able to read maltose contained in the Amzylite
compound, it was also able to read reduced glucose in the glucose sample
mixed with Amzylite. This has the advantage of sensitivity over glucose
oxidase
and dehydrogenase. Conclusion: Amzylite F1.2 and Trimetylglycine, are glucose
reducing compounds that catalyzes the hydrolysis / oxidation of glucose. The
reduction, hydolysis / oxidation of glucose in vitro by Amzylite F1.2 and
Trimetylglycine, introduces new scientific fact into Glucose Metabolism, that
Glucose Metabolism should be reclassified and reviewed. New classification of
glucose metabolism should consider: 1- Glucose Metabolism in-vitro, 2-
Glucose Metabolism in-vivo. Amzylite and Trimethylglycine are used as high
quality glucose sensing agents and in-vitro glucose metabolism indicator.
ARBAB-Glucometer, is new glucose sensing technology based on the reaction
between glucose and Amzylite or glucose and an organic compound called
Trimethylglycine, that catalyzes the hydrolysis / oxidation of glucose.
Overall, there is strong evidence that Amzylite is beneficial in the treatment
of
saccharides based diseases in association with malfunction or absence of
amylases activity disorders and its complications patients with or without
exocrine pancreatic insufficiency and leading to a better control of the
disease.
This means that Amzylite should be added to the treatment of those patients
in order to improve the most important factor in their treatment in addition
to
asymptomatic patients as prophylaxis from the disease.
As kidney failure, peripheral ischaemic diseases and diabetic patients have
been used as model, and it can be estimated that the same beneficial effects
will be seen in other patients who are symptomatic or asymptomatic and
49
CA 02661953 2009-02-17
suffer saccharides based diseases and its complications, as long as they would
have a malfunctioning or absent amylases activity.
Another study
Another study
AMZYLITE AND TRIMETHYLGLYCINE AS GLUCOSE SENSING AGENTS
AND IN-VITRO GLUCOSE METABOLISM INDICATORS
Introduction Recent studies showed that Amzylite f1.2 (Amzylite
contains Trimethylglycine, maltase and Maltose) is an effective in-vitro
glucose reducing agent.
Objectives: To study Amzylite F1.2 and Trimetylglycine, as in-vitro
glucose sensing agents for use in glucose strips and ARBAB-Glucometers
(There are several types of ARBAB-Glucometers with different range of
readings. The ARBAB-Glucometer used in this study had a reading range
of less than 20 mg/dI as lower range and 500 mg/dl as upper range).
Methods: 400 samples each 100 sample contains 10 mis of Amzylite F
1.2 (concentration 50mg/mi), Amzylite F1.2 (Trimethylglycine Free)
(concentration 50mg/mI), Amzylite F1.2 (Maltase Free, concentration
50mg/mI/), trimethylglycine (concentration 50mg/ml), 400 samples, 200
containing 10 mis, 10% glucose solution, and 200 containing 10 mis
maltose solution ( concentration 1mg) were initially tested using
glucose oxidase and dehydrogenase.
Amzylite F1.2 (500mg), Amzylite F1.2 (Trimethylglycine Free), Amzylite
F1.2 (Maltose Free) and Trimethylglycine, preparations were mixed and
dissolved separately in 50 glucose samples of 10 mis (concentration
10%), and 50 maltose samples each. Sugar content of each 200 glucose
CA 02661953 2009-02-17
samples and 200 maltose (concentration 1mg), 10m1s samples were
checked using oxidase and dehydrogenase enzyme reaction
Results: Oxidase and dehydrogenase readings were positive for sugar
(reading was ranging from 450 to Hi = above 500mg /dl) in 100 Amzylite
F 1.2 samples and 100 samples of Amzylite F1.2 (Trimethylglycine Free).
Oxidase and dehydrogenase readings were negative in 100 Amzylite F1.2
(Maltose free) samples, and 100 Trimethylglycine (Maltose free)
samples. Oxidase and dehydrogenase readings were positive (450 to Hi =
above 500mg/dl) for glucose in 200 samples of 10% glucose. Negative
oxidase readings and positive dehydrogenase readings for maltose sugar
in 200 maltose samples. All glucose samples mixed with Amzylite F1.2
(except Trimethylglycine free Amzylite), and trimethylglycine, showed
immediate reductions of glucose readings when tested with glucose
oxidase. All glucose oxidase tested maltose samples showed positive
sugar readings when mixed with Amzylite F1.2, samples mixed with
trimethylglycine showed negative readings. Amzylite had significant
advantages, with less reaction time and higher glucose reductions
(reading time ranged from immediate to 2 or 3 seconds) compared to
Trimethylglycine alone (reading time from 5 seconds to 30 seconds or
more) Discussion: Many glucose meters employ the oxidation of glucose
by glucose oxidase, and glucose dehydrogenase. Glucose dehydrogenase
is more susceptible to interfering reactions with other substances.
Amzylite is more specific for monosaccharide glucose, and able to
oxidize and reduce monosaccharide glucose in the sample despite
maltose content in the compound. This has the advantage of sensitivity
over glucose oxidase and dehydrogenase. Conclusion: Amzylite and
Trimethylglycine are used as high quality glucose sensing agents and
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CA 02661953 2009-02-17
ARBAB-Glucometer, is new glucose sensing technology based on the
reaction between glucose and Amzylite or glucose and Trimethylglycine
that catalyzes the hydrolysis / oxidation of glucose.
All patients involved in our studies gave informed consent.
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CA 02661953 2009-02-17
See attached tables, graphs and figures used with the invention:
Figure (1) Shows saliva amylase test results for disaccharides and
polysaccharides together with pH and saliva proteins reaction. Glucose
readings were taken every half an hour or every one hour. The glucose reading
for disaccharides amylase reaction, pH and saliva proteins reaction is
compared to glucose reading for polysaccharides amylase reaction, pH and
saliva proteins reaction.
Figure (2) Shows saliva amylase test results for disaccharides, and in the
same
time, the saliva sample is tested for leucocytes, protein, pH, blood, specific
gravity, and glucose.
Figure (3) Shows saliva amylase test results for polysaccharides, and in the
same time, the saliva sample is tested for leucocytes, protein, pH, blood,
specific gravity, and glucose.
Figure (4) Saliva alpha amylase activity in diabetic and non diabetic
subjects,
pH, disaccharides and polysaccharides studies, within 24 hours.
Figure (5) Total number of samples in relation to number of sources; samples
were taken from diabetic and non diabetic subjects.
Figure (6) 750 saliva samples studied for amylase activity, (250 saliva marker
samples, 250 saliva sample for disaccharide testing, and 250 saliva samples
for
polysaccharides testing)
Figure (7) Saliva alpha amylase activity study in diabetic and non diabetic
subjects for more than 24 hours
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CA 02661953 2009-02-17
Figure (8) Saliva strips for determination glucose (Glucose oxidase based
strips), bilirubin, specific gravity, blood, pH, protein, leucocytes,
disaccharides
and polysaccharides in saliva samples.
Figure (9) Saliva strips Analyser for determination of glucose, bilirubin,
specific
gravity, blood, pH, protein, leucocytes, disaccharides, polysaccharides in
saliva
samples. Disaccharides reagents (Standard disaccharides reagent "sucrose")
and polysaccharides reagents (standard polysaccharides reagent "starch") can
be mixed in fresh saliva samples, pancreatic juice samples, urine samples to
determine amylase activity for disaccharides and polysaccha rides.
Figure (10) AMZYLITE (Enzyme Complex): Each capsule contains: Medicinal
Ingredients: Trimethylglycine; 1,4-a-D-glucan glucanohydrolase (The active
site
of the enzyme contains a catalytic triad, including Asp197, Glu233 and Asp300,
{Example of other analogous: (1) Asp 196, Glu233, and Asp301; (2) Asp197,
GIu232, Asp300; (3) Asp197, Glu233, Asp 299;) ; Exo-1,4-a-glucosidase; Beta-
fructofuranosidase; Protease (3.0); Pectinase; Lipase; Cellulase; Lactase;
Malt
Diastase. Non-Medicinal Ingredients: Microcrystalline cellulose, Magnesium
stearate and maltodextrin.
The following example illustrates the manufacture of a pharmaceutical
preparation containing Trimethylglycine; 1,4-a-D-glucan glucanohydrolase (The
active site of the enzyme contains a catalytic triad, including Asp197, GIu233
and Asp300, {Example of other analogous: (1) Asp 196, GIu233, and Asp301; (2)
Asp197, GIu232, Asp300; (3) Asp197, GIu233, Asp 299;); Exo-1,4-a-glucosidase;
Beta-fructofuranosidase; Protease; Pectinase; Lipase; Cellulase; Lactase; Malt
Diastase, which is suitable for the treatment of malfunctioning or absence of
amylase activity in association with saccharides based diseases, and
especially
54
CA 02661953 2009-02-17
for adjuvant therapy of kidney failure, and diabetes, without, however,
restricting the scope of the invention.
EXAMPLES OF PHARMACEUTICAL FORMULATION
1.One example of a pharmaceutical formulation includes a capsule containing:
Trimethylglycine 400 mg; 1,4-a-D-glucan glucanohydrolase 100 mg (The active
site of the enzyme contains a catalytic triad, including Asp197, GIu233 and
Asp300, {Example of other analogous: (1) Asp 196, Glu233, and Asp301; (2)
Asp197, Glu232, Asp300; (3) Asp197, GIu233, Asp 299;); Exo-1,4-a-glucosidase
100 mg; Beta-fructofuranosidase 10 mg; Maltase 10 mg;; Lactase 10 mg; and
Cellulase 10 mg. Non-Medicinal Ingredients: Beet roots, Dicalcium phosphate,
magnesium stearate.
2.Another example of a pharmaceutical formulation includes a capsule
containing: 1,4-a-D-glucan glucanohydrolase 50mg (The active site of the
enzyme contains a catalytic triad, including Asp197, Glu233 and Asp300,
{Example of other analogous: (1) Asp 196, Glu233, and Asp301; (2) Asp197,
Glu232, Asp300; (3) Asp197, GIu233, Asp 299;); Trimethylglycine 200 mg;
Lipase 80 mg; Protease 100 mg; Maltase 20 mg; Lactase 20 mg; Cellulase 20
mg; and Sodium bicarbonate 0.5 mg. Non-Medicinal Ingredients: Beet roots,
Dicalcium phosphate, magnesium stearate.
3. Another example of a pharmaceutical formulation includes a capsule
containing: Ttimethylglycine HCL 300 mg; 1,4-a-D-glucan glucanohydrolase
50 mg (The active site of the enzyme contains a catalytic triad, including
Asp197, GIu233 and Asp300, {Example of other analogous: (1) Asp 196,
Glu233, and Asp301; (2) Asp197, Glu232, Asp300; (3) Asp197, Glu233, Asp
299;); Exo-1,4-a-glucosidase 50 mg; Beta-fructofuranosidase 10.0 mg;
CA 02661953 2009-02-17
Maltase 10 mg; Lactase 10 mg; Cellulase 10 mg; Protease 40 mg; and Lipase
26 mg. Encapsulated with these ingredients: Beet roots, Dicalcium
phosphate, magnesium stearate.
4. Another example of a pharmaceutical formulation includes a capsule
containing: Trimethylglycine HCL 200 mg; 1,4-a-D-glucan glucanohydrolase 150
mg (The active site of the enzyme contains a catalytic triad, including
Asp197,
Glu233 and Asp300, {Example of other analogous: (1) Asp 196, GIu233, and
Asp301; (2) Asp197, Glu232, Asp300; (3) Asp197, GIu233, Asp 299;); Exo-1,4-a-
glucosidase 150 mg; Beta-fructofuranosidase 20.0 mg; Maltase 10 mg;
Lactase 10 mg; Cellulase 10 mg; Non-Medicinal Ingredients: Beet root,
Magnesium stearate and maltodextrin.
5. Another example of a pharmaceutical formulation includes a capsule
containing: 1,4-a-D-glucan glucanohydrolase 100 mg (The active site of the
enzyme contains a catalytic triad, including Asp197, Glu233 and Asp300,
{Example of other analogous: (1) Asp 196, GIu233, and Asp301; (2) Asp197,
Glu232, Asp300; (3) Asp197, GIu233, Asp 299;); Exo-1,4-a-glucosidase
100mg; beta-fructofuranosidase 20 mg, Trimethylglycine 100 mg; Non-
Medicinal Ingredients: Microcrystalline cellulose, Magnesium stearate and
maltodextrin.
1. Another of example of pharmaceutical formulation: Betaine HCL 300
mg; 1,4-a-D-glucan glucanohydrolase 100 mg (The active site of the enzyme
contains a catalytic triad, including Asp197, Glu233 and Asp300, {Example
of other analogous: (1) Asp 196, GIu233, and Asp301; (2) Asp197, GIu232,
Asp300; (3) Asp197, Glu233, Asp 299;); Exo-1,4-a-glucosidase 100 mg;
Beta-fructofuranosidase 12.0 mg; Protease 40 mg; Lipase 26 mg; and
56
CA 02661953 2009-02-17
Sodium bicarbonate 1.25 g. Encapsulated with these natural ingredients:
Dicalcium phosphate, magnesium stearate.
2. Another of example,of pharmaceutical formulation under the trade
name of AMZYLITE (Enzyme Complex): Each capsule contains: Medicinal
Ingredients: Trimethylglycine 200 mg; 1,4-a-D-glucan glucanohydrolase 100
mg (The active site of the enzyme contains a catalytic triad, including
Asp197, GIu233 and Asp300, {Example of other analogous: (1) Asp 196,
GIu233, and Asp301; (2) Asp197, GIu232, Asp300; (3) Asp197, Glu233, Asp
299;); Exo-1,4-a-glucosidase 100 mg; Beta-fructofuranosidase 20 mg;
Protease (3.0), 62 mg; Pectinase 10 mg; Lipase 7.5 mg; Cellulase 5 mg;
Lactase 5 mg; Malt Diastase 30 mg. Non-Medicinal Ingredients:
Microcrystalline cellulose, Magnesium stearate and maltodextrin.
3. Another example of a pharmaceutical formulation includes a capsule
containing: Trimethylglycine 400 mg; 1,4-a-D-glucan glucanohydrolase 25
mg (The active site of the enzyme contains a catalytic triad, including
Asp197, Glu233 and Asp300, {Example of other analogous: (1) Asp 196,
Glu233, and Asp301; (2) Asp197, Glu232, Asp300; (3) Asp197, Glu233, Asp
299;); Exo-1,4-a-glucosidase 100mg; Beta-fructofuranosidase 10.0 mg;
Maltase 10 mg; Lactase 10 mg; Cellulase 10 mg; Lipase 26 mg; Encapsulated
with these ingredients: beet root, magnesium stearate.
4. Another example of a pharmaceutical formulation includes a capsule
containing: 1,4-a-D-glucan glucanohydrolase 100 mg (The active site of the
enzyme contains a catalytic triad, including Asp197, GIu233 and Asp300,
{Example of other analogous: (1) Asp 196, GIu233, and Asp301; (2) Asp197,
Glu232, Asp300; (3) Asp197, GIu233, Asp 299;); Exo-1,4-a-glucosidase 100
57
CA 02661953 2009-02-17
mg; Beta-fructofuranosidase 15.0 mg; Betaine HCL 400 mg; Maltase 10 mg;
Malt diastase 270 DP; Lactase 10 mg; Cellulase 10 mg; Protease 40 mg;;
Pectinase (with phytase) 75 ENDC!/PGU; Lipase 26 mg; Encapsulated with
these ingredients: beet root, Dicalcium phosphate, magnesium stearate.
5. Another example of a pharmaceutical formulation includes a capsule
containing: Trimethylglycine HCL 400 mg; 1,4-a-D-glucan glucanohydrolase
100 mg (The active site of the enzyme contains a catalytic triad, including
Asp197, GIu233 and Asp300, {Example of other analogous: (1) Asp 196,
GIu233, and Asp301; (2) Asp197, GIu232, Asp300; (3) Asp197, Glu233, Asp
299;); Exo-1,4-a-glucosidase 100 mg; Beta-fructofuranosidase 10.0 mg;
Encapsulated with these ingredients: beet root, magnesium stearate.
6. Another example of a pharmaceutical formulation includes a capsule
containing: Trimethylglycine HCL 300 mg; 1,4-a-D-glucan glucanohydrolase
200 mg (The active site of the enzyme contains a catalytic triad, including
Asp197, Glu233 and Asp300, {Example of other analogous: (1) Asp 196,
GIu233, and Asp301; (2) Asp197, Glu232, Asp300; (3) Asp197, GIu233, Asp
299;); Exo-1,4-a-glucosidase 100 mg; Beta-fructofuranosidase 20.0 mg;
Encapsulated with these ingredients: beet root, magnesium stearate.
7. Another example of a pharmaceutical formulation includes a capsule
containing: Trimethylglycine HCL 100 mg; 1,4-a-D-glucan glucanohydrolase
100 mg (The active site of the enzyme contains a catalytic triad, including
Asp197, Glu233 and Asp300, {Example of other analogous: (1) Asp 196,
Glu233, and Asp301; (2) Asp197, GIu232, Asp300; (3) Asp197, Glu233, Asp
299;); Exo-1,4-a-glucosidase 100 mg; Beta-fructofuranosidase 15.0 mg;
Encapsulated with these ingredients: beet root, magnesium stearate.
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CA 02661953 2009-02-17
Saliva, Urine, Blood, Lymphatic fluid, Testing Strips and Testing Meters for
use
with the invention
1. New Glucose blood testing strips, and new glucometer (ARBAB): All
modern hand-held "finger-stick" blood-glucose meters are based on the
reaction between glucose and an enzyme that catalyzes the oxidation of
glucose (usually the enzyme called, logically enough, "glucose oxidase"). In
this reaction, glucose is oxidized to hydrogen peroxide plus gluconic acid. A
newer generation of glucose meters incorporates an electrochemical cell
within the device, and measures the integrated current produced by the
glucose oxidation reaction, a quantity that is proportional to the amount of
glucose present. Our new glucose meter (ARBAB-Glucometer), is using new
technology based on the reaction between glucose and Amzylite or glucose
and an organic compound called Trimethylglycine, also called TMG (Betaine
HCL which is a chloride salt from TMG) that catalyzes the hydrolysis /
oxidation of glucose. In this reaction, glucose is hydrolysed and oxidized to
carbon dioxide and water, or to hydrogen and peroxide plus gluconic acid. A
newer generation of glucose meters incorporates an electrochemical cell
within the device, and measures the integrated current produced by the
glucose oxidation reaction, a quantity that is proportional to the amount of
glucose present. There are several key characteristics of "ARBAB-
Glucometer", glucose meters that may differ from model to model:
- Size: There are different sizes, and the average size is now
approximately the size of the palm of the hand, though some are
smaller or larger. They are battery-powered.
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CA 02661953 2009-02-17
- Test strips: ARBAB-Glucometer tests strips are a consumable
element containing enzymes and chemicals (Amzylite or Betaine HCL
{Trimethylglycine, TMG}) that react with glucose in the drop of blood
is used for each measurement. For some models this element is a
plastic test strip with a small spot impregnated with Amzylite or
Betaine HCL {Trimethylglycine, TMG} and other components. Each
strip can only be used once and is then discarded. Instead of strips,
some models use discs that may be used for several readings.
- Volume of blood sample: The size of the drop of blood needed by
different models varies from 0.3 to 10 l. (Older models required
larger blood samples, usually defined as a "hanging drop" from the
fingertip.) Smaller volume requirements reduce the frequency of
unproductive pricks.
Testing times: The times it takes to read a test strip may range from 3
to 30 seconds for different models.
- Display: The glucose value in mg/dl or mmol/I is displayed in a small
window. The preferred measurement unit varies by country: mg/dl is
preferred in the US, mmol/I in Canada and Europe. To convert
mmol/I of glucose to mg/dI, multiply by 18. To convert mg/dl of
glucose to mmol/l, divide by 18 or multiply by 0.055.
CA 02661953 2009-02-17
- Clock/memory: All ARBAB-Glucometers now include a clock that is
set for date and time, and a memory for past test results. The
memory is an important aspect of diabetes care, as it enables the
person with diabetes to keep a record of management and look for
trends and patterns in blood glucose levels over days. Most memory
chips can display an average of recent glucose readings.
- Data transfer: Some of ARBAB-Glucometers have more
sophisticated data handling capabilities. Many can be downloaded by
a cable or infrared to a computer that has diabetes management
software to display the test results. Some meters allow entry of
additional data throughout the day, such as insulin dose, Amzylite
dose, amounts of carbohydrates eaten, or exercise.
Hospital glucose meters: Special glucose meters (ARBAB-Glucometer)
for multi-patient hospital use will be available soon. These will
provide more elaborate quality control records, and the data
handling capabilities are designed to transfer glucoses into electronic
medical records and the laboratory computer systems for billing
purposes.
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CA 02661953 2009-02-17
1. New urine glucose testing strips and new glucometer (ARBAB-Uro-
Glucometer): Technique is similar to blood testing strips. Our new glucose
meter (ARBAB-Uro-Glucometer), is using new technology based on the
reaction between glucose and Amzylite or glucose and an organic
compound called Trimethylglycine, also called TMG (Betaine HCL which is a
chloride salt from TMG) that catalyzes the hydrolysis / oxidation of glucose.
In this reaction, glucose is hydrolysed and oxidized to carbon dioxide and
water, or to hydrogen and peroxide plus gluconic acid. A newer generation
of glucose meters incorporates an electrochemical cell within the device,
and measures the integrated current produced by the glucose oxidation
reaction, a quantity that is proportional to the amount of glucose present.
There are several key characteristics of "ARBAB-Uro-Glucometer", glucose
meters that may differ from model to model:
- Size: There are different sizes, and the average size is now
approximately the size of the palm of the hand, though some are
smaller or larger. They are battery-powered.
- Test strips: ARBAB-Uro-Glucometer tests strips are a consumable
element containing enzymes and chemicals (Amzylite or Betaine HCL
{Trimethylglycine, TMG}) that react with glucose in the drop of urine
is used for each measurement. For some models this element is a
plastic test strip with a small spot impregnated with Amzylite or
Betaine {Trimethylglycine, TMG} and other components. Each strip
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CA 02661953 2009-02-17
can only be used once and is then discarded. Instead of strips, some
models use discs that may be used for several readings.
- Volume of blood sample: The size of the drop of urine needed by
different models varies from 0.3 to 10 l. Smaller volume
requirements reduce the frequency of unproductive repeat samples.
- Testing times: The times it takes to read a test strip may range from
3 to 30 seconds for different models.
- Display: The glucose value in mg/dl or mmol/I is displayed in a small
window. The preferred measurement unit varies by country: mg/dl is
preferred in the US, mmol/I in Canada and Europe. To convert
mmol/I of glucose to mg/dI, multiply by 18. To convert mg/dl of
glucose to mmol/I, divide by 18 or multiply by 0.055.
- Clock/memory: All ARBAB-Uro-Glucometers now include a clock that
is set for date and time, and a memory for past test results. The
memory is an important aspect of diabetes care, as it enables the
person with diabetes to keep a record of management and look for
trends and patterns in blood glucose levels over days. Most memory
chips can display an average of recent glucose readings.
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CA 02661953 2009-02-17
- Data transfer: Some of ARBAB-Uro-Glucometers have more
sophisticated data handling capabilities. Many can be downloaded by
a cable or infrared to a computer that has diabetes management
software to display the test results. Some meters allow entry of
additional data throughout the day, such as insulin dose, Amzylite
dose, amounts of carbohydrates eaten, or exercise.
- Hospital glucose meters: Special glucose meters (ARBAB-Uro-
Glucometer) for multi-patient hospital use will be available soon.
These will provide more elaborate quality control records, and the
data handling capabilities are designed to transfer glucoses into
electronic medical records and the laboratory computer systems for
billing purposes.
2. Urine strips (dip sticks): A testing dipstick is usually made of paper or
cardboard and is impregnated with reagents that indicate some feature of
the liquid by changing colour. For example, medical dipsticks are used to
test urine samples for haemoglobin, nitrite (produced by bacteria in a
urinary tract infection), protein, glucose and occasionally urobilinogen or
ketones. It is used for determination glucose (using Amzylite or betaine as
reagents on the strips), bilirubin, specific gravity, blood, pH, protein,
leucocytes, in urine samples.
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CA 02661953 2009-02-17
3. Saliva strips for determination, bilirubin, specific gravity, blood, pH,
protein, leucocytes, and measuring saliva enzymes activity for disaccharides
in saliva samples. Strips comprise of multi small paper or cardboard and
each is impregnated with reagents that indicate some feature of the liquid
by changing colour. For example, strip used are similar to medical dipsticks
are used to test urine samples for haemoglobin, nitrite (produced by
bacteria in a urinary tract infection), protein, glucose and occasionally
urobilinogen or ketones. To measure Amylase activity for disaccharides in a
saliva sample, you will need 1 ml of organic disaccharide (sachets containing
standard amount of disaccharides for the reaction together with manual of
use and instructions will be supplied) to be mixed in 10 mis of fresh saliva,
collected in a sterile specimen pot with lid. Readings will be taken
immediately before adding disaccharides from sachets, then continuous
reading to be obtained every half an hour or every hour for 24 hours.
Results will be noted in a specially designed note book or graphs and or
printed analysis paper from the strips analyzer machine. (See examples of
test results note book used before in our Medical clinic in UAE and Sudan).
You can use this test to measure saliva amylase activity for 1- Genetically
Modified disaccharides, 2- Resistant disaccharides (sucrose from resistant
plant source).
4. Saliva strips for determination, bilirubin, specific gravity, blood, pH,
protein, leucocytes, and measuring saliva enzymes activity for
polysaccharides in saliva samples. Strips comprise of multi small paper or
cardboard and each is impregnated with reagents that indicate some
feature of the liquid by changing colour. For example, strips used are similar
CA 02661953 2009-02-17
to medical dipsticks are used to test urine samples for haemoglobin, nitrite
(produced by bacteria in a urinary tract infection), protein, glucose and
occasionally urobilinogen or ketones. To measure Amylase activity for
polysaccharides in a saliva sample, you will need 1 ml of organic
polysaccharide starch (sachets containing standard amount of
polysaccharides starch for the reaction together with manual of use and
instructions will be supplied) to be mixed in 10 mis of fresh saliva,
collected
in a sterile specimen pot with lid. Readings will be taken immediately before
adding polysaccharide starch, then continuous reading to be obtained every
half an hour or every hour for 24 hours. Results will be noted in a specially
designed note book or graphs and or printed analysis paper from the strips
analyzer machine. (See examples of test results note book used before in
our Medical clinic in UAE and Sudan). You can use this test to measure
saliva amylase activity for 1- Genetically Modified polysaccharides starch, 2-
Resistant polysaccharides from resistant plant source).
5. Saccharides Enzymes activity functions strips, to determine both the
presence and the level of activity of 1,4-a-D-glucan glucanohydrolase; Exo-
1,4-a-glucosidase; Beta-fructofuranosidase; Protease; Pectinase; Lipase;
Cellulase; Lactase; Malt Diastase enzymes in venous blood samples, arterial
blood samples, capillary blood samples, serum blood samples, lymphatic
fluid samples. Strips contain, (1,4-a-D-glucan glucanohydrolase; Exo-1,4-a-
glucosidase; Beta-fructofuranosidase; Protease; Pectinase; Lipase; Cellulase;
Lactase; Malt Diastase). Strips will be read by special strip analyzer.
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CA 02661953 2009-02-17
6. Saccharides strips, to determine both the presence and the level of
activity of 1,4-a-D-glucan glucanohydrolase; Exo-1,4-a-glucosidase; Beta-
fructofuranosidase; Protease; Pectinase; Lipase; Cellulase; Lactase; Malt
Diastase enzymes in venous blood samples, arterial blood samples, capillary
blood samples, serum blood samples, lymphatic fluid samples, and urine
samples. Strips contain, saccharides reagents (sachets with different types
of saccharides in powder or liquid form for reaction with enzymes in the
blood, urine, lymphatic fluid and saliva samples) containing polysaccharides
starch, disaccharides (sucrose), dextrin, proteins, pectin, lipids, cellulose,
lactose and maltose are to be added in saliva samples and urine samples, to
determine presence and or level of activity for saccharides enzymes
contained in a sample. Strips will be read by special strip analyzer.
Strips Analyzer for Saliva, and Urine Strips
1. Urine strips Analyzer for determination glucose, bilirubin, specific
gravity,
blood, pH, protein, leucocytes, haemoglobin, nitrite (produced by bacteria
in a urinary tract infection), urobilinogen and ketones in urine samples. An
analyzer for testing dipsticks impregnated with reagents that indicate some
feature of the liquid by changing colour. For example, it is similar to
medical
dipsticks are used to test urine samples for haemoglobin, nitrite (produced
by bacteria in a urinary tract infection), protein, glucose and occasionally
urobilinogen or ketones. Here dipstick uses Amzylite or betaine as reagents
instead of glucose oxidase or dehydrogenase enzymes, on the strip to
determine glucose in a urine sample.
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CA 02661953 2009-02-17
2. Saliva strips Analyzer for determination, of specific gravity, blood, pH,
protein, leucocytes, and measuring saliva enzymes activity for
polysaccharides in saliva samples. Strips comprise of multi small paper or
cardboard and each is impregnated with reagents that indicate some
feature of the liquid by changing colour. For example, strips used are similar
to medical dipsticks are used to test urine samples for haemoglobin, nitrite
(produced by bacteria in a urinary tract infection), protein, glucose and
occasionally urobilinogen or ketones. To measure Amylase activity for
polysaccharides in a saliva sample, you will need 1 ml of organic
polysaccharide starch (sachets containing standard amount of
polysaccharides starch for the reaction together with manual of use and
instructions will be supplied) to be mixed in 10. mis of fresh saliva,
collected
in a sterile specimen pot with lid. Readings will be taken immediately before
adding polysaccharide starch, then continuous reading to be obtained every
half an hour or every hour for 24 hours. Results will be noted in a specially
designed note book or graphs and or printed analysis paper from the strips
analyzer machine. (See examples of test results note book used before in
our Medical clinic in UAE and Sudan). You can use this test to measure
saliva amylase activity for 1- Genetically Modified polysaccharides starch, 2-
Resistant polysaccharides from resistant plant source). Disaccharides
reagents (Standard disaccharides reagent "sucrose") and polysaccharides
reagents (standard polysaccharides reagent "organic starch") can be mixed
in separate samples of fresh saliva samples, pancreatic juice samples, urine
samples to determine amylase activity for disaccharides and
polysaccharides.
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CA 02661953 2009-02-17
Multifunction-Urine Strips Analyzer
Detailed Product Description
Specifications:
10, Items to be tested: Leukocytes, Occult Blood, Nitrite, Urobilinogen,
Protein,
pH, Specific Gravity, Ketone, Bilirubin, Glucose.
11, Items to be tested: Leukocytes, Occult Blood, Nitrite, Urobilinogen,
Protein,
pH, Specific Gravity, Ketone, Bilirubin, Glucose, Calcium.
Strips are using new technology based on the reaction between glucose and
Amzylite or glucose and an organic compound called Trimethylglycine, also
called TMG (Betaine which is a chloride salt from TMG) that catalyzes the
hydrolysis / oxidation of glucose. In this reaction, glucose is hydrolysed and
oxidized to carbon dioxide and water, or to hydrogen and peroxide plus
gluconic acid. Test theory: Test by cold light; Wavelength: Measurement
wavelengths: 420nm, 550nm, 650nm; Print: Built in speedy thermal printer
outlet to pin printer; Methods: Test strip colour change by three wavelength;
Test speed: 60 specimens per hour; Data output: USB Port to PC; Display:
Liquid crystal; Operating environment: Temperature 10^'35 humidity :995%;
Power: AC220 22V, 50 1HZ, or DC9V, 1.5A 12VA.
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CA 02661953 2009-02-17
Examples of Test notes used with invention: (Example no 1)
* Dip Sticks Name Sa I i va Test Start test result
Date: / / Starttime: Name: File NO:
No Time S.D.T S.D.T S.P.T S.P.T
unit hour Protein pH. Protein pH.
1 1/2
2 1
3 1 1/2
4 2
2 1/2
6 3
7 3 1/2
8 4
9 41/2
5
11 5 1/2
12 6
13 6 1/2
14 7
7 1/2
16 8
17 8 1/2
18 9
19 9 1/2
10
21 10 1/2
22 11
23 11 1/2
24 12
12 1/2
26 13
27 13 1/2
28 14
29 14 1/2
15
31 15 1/2
32 16
33 16 1/2
34 17
17 1/2
36 18
37 18 1/2
38 19
39 19 1/2
20
41 20 1/2
42 21
43 21 1/2
44 22
22 1/2
46 23
47 23 1/2
48 24
SDT = Saliva Disaccharides Test, SPT= Saliva Polysaccharides Test
CA 02661953 2009-02-17
(Example no 2) Saliva Disaccharides Test
Date: 00/00/00 Time: 00:00 Name: xxxxxxxxxxx File No:
(Start) (00) (++) (++) ( 7 ) (+++) (1.010) ( - )
Hours No Leu. Pro. pH Bld. S.G Glucose
20:00 1 ++ ++ 7 +++ 1.010 -
21:00 2 ++ ++ 7 +++ 1.010 -
22:00 3 ++ ++ 7 +++ 1.010 -
23:00 4 ++ ++ 6 +++ 1.010 -
24:00 5 ++ ++ 6 +++ 1.010 -
01:00 6 ++ ++ 6 +++ 1.010 -
02:00 7 ++ ++ 6 +++ 1.010 -
03:00 8 ++ ++ 6.5 +++ 1.010 -
04:00 9 ++ ++ 6.5 +++ 1.010 -
05:00 10 ++ ++ 5.5 +++ 1.010 -
06:00 11 ++ ++ 5.5 +++ 1.010 -
07:00 12 ++ ++ 5.5 +++ 1.010 -
08:00 13 ++ ++ 5 +++ 1.010 -
09:00 14 ++ ++ 5 +++ 1.010 -
10:00 15 ++ ++ 5 +++ 1.010 Trace
11:00 16 ++ ++ 5 +++ 1.010
12:00 17 ++ ++ 5 +++ 1.010 +
13:00 18
14:00 19
15:00 20
16:00 21
17:00 22
18:00 23
19:00 24
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CA 02661953 2009-02-17
(Example no 3) Saliva Polysaccharides Test
Date: 00/00/00 Time: 00:00 Name: xxxxxxxxxxxxxxxxxx File No:
(Start) ( 00 ) ( ++ ) ( ++ ) ( 7 ) (+++) (1.010) ( - )
Hours No Leu. Pro. pH Bld. S.G Glucose
20:00 1 ++ +++ 7 +++ 1.010 -
21:00 2 ++ +++ 7 +++ 1.010 -
22:00 3 ++ +++ 6 +++ 1.010 -
23:00 4 ++ +++ 6 +++ 1.010 -
24:00 5 ++ +++ 6.5 +++ 1.020 Trace
01:00 6 ++ +++ 5.5 +++ 1.030
02:00 7 ++ +++ 5.5 +++ 1.030 +
03:00 8
04:00 9
05:00 10
06:00 11
07:00 12
08:00 13
09:00 14
10:00 15
11:00 16
12:00 17
13:00 18
14:00 19
15:00 20
16:00 21
17:00 22
18:00 23
19:00 24
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CA 02661953 2009-02-17
Normal Ranges for Saliva Amylase activity on Disaccharides (Standard organic,
non GM, non resistant, Sucrose reagent) and Saliva Amylase activity on
Polysaccharides (Standard organic, non GM, non resistant, polysaccharides
starch) tests results
According to the invention, normal ranges of amylases activity are: 30 to 120
minutes for the degradation of disaccharides by the disaccharides specialised
amylases (disaccharides specialised salivary, pancreatic or systemic amylases
were not known before), and 4 to 6, up to 8 hours for the degradation of
polysaccharides by polysaccharides specialised amylases. Tests results for
amylase activity on polysaccharides, and amylase activity on disaccharides is
compared to a normal range of 30 to 120 minutes for disaccharides, and 6 to 8
hours for polysaccharides (meaning: 250 mg/dl of glucose detected in a
disaccharide test sample within 30 to 120 minutes, and 250 mg/dl of glucose to
be detected in a polysaccharides sample within 6 to 8 hours),. Normal range
for disaccharides and polysaccharides are the ranges detected in a healthy non
polysaccharides, oligosaccharides, disaccharides and monosaccharides
diseases, non diabetic, non diseased individuals in a low endemic diabetes
area
(normal range figures obtained from health subjects in western Sudan and
Darfur region where diabetes is approximately 7% of the population). Normal
ranges for the tests can also be compared from the following calculations:
Glucamylase: 1 unit of enzyme activity catalyzes the production of 1.0mg
(1.0ml) of glucose in 1 hour under the following condition: 40 C pH = 4.6,
Amylase: 1 unit of enzyme activity is the amount of enzyme that will
dextrinize
1.0mg (1.0ml) of soluble starch in 1 hour under the following condition: 60 C
pH = 6.0, High temperature amylase: 1 unit of enzyme activity is the amount of
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CA 02661953 2009-02-17
enzyme that will dextrinize 1.0mg (1.0mI) of soluble starch in 1 hour under
the
following condition: 70 C pH = 6Ø
The foregoing description and examples have been set forth merely to
illustrate the invention and are not intended to be limiting. Since
modifications
of the described embodiments incorporating the spirit and substance of the
invention may occur to persons skilled in the art, the invention should be
construed broadly to include all variations falling within the scope of the
appended claims and equivalents thereof.
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