Note: Descriptions are shown in the official language in which they were submitted.
CA 02829731 2013-10-15
USE OF STERILE INTRAVENOUS OR INTRACAVERNOUS GLYCERIN
IN DESTRUCTION OF BACTERIAL BIOFILM
BACKGROUND OF THE INVENTION
[0001] Field of Invention
This invention pertains to the use of sterile intravenous or intracavernous
glycerin solutions
to treat biofilms that infect humans and animals.
[0002] Description of Related Art
[0003] A biofilm occurs when bacteria stick to each other on a surface. These
adherent
cells are frequently embedded within a self-producing matrix of extra cellular
polymeric
substance. Biofilms are also referred to as slime. The polymeric
conglomeration is generally
composed of extra-cellular DNA, proteins and polysaccharides. Initially the
biofilm is weak
and adhesion is by van der Waals forces. Later, the bacteria form cell
adhesion structures
such as pili. Once colonization has begun the biofilm grows through a
combination of cell
division and recruitment.
[0004] The development of biofilm may allow for an aggregated cell colony to
be
increasingly antibiotic resistant. Bacteria from the biofilm can disperse
which causes the
spread and colonization of new surfaces. The matrix protects the bacteria
within it and
facilitates communication among them through biochemical signals. Biofilm has
been
implicated in such problems as urinary tract infections, endocarditis, cystic
fibrosis and
infections of prosthesis and heart valve. Invariably the only recourse for
treating prosthetics
such as mechanical heart valve is to have them replaced. Biofilms are present
on the removed
tissue of 80% of patients undergoing surgery for chronic sinusitis.
[0005] In the 1980's Danish pioneers first connected biofilms with human
disease and then
antibiotic resistant infections. They discovered that once these biofilm
infections had begun
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they are difficult to get rid of in the body. The immune system can mop up
free-floating
bacteria in the blood but reaching bacteria in biofilms is difficult.
[0006] Even if an antibiotic reaches a biofilm, a large portion of the
bacteria would be
insensitive to the specific antibiotic as bacteria in a biofilm occupied a
spectrum of
physiological state from rapid growing to dormant. The dormant bacteria are
not vulnerable
to the antibiotic. Later, these dormant bacteria can quickly renew the
biofilm. Low oxygen
concentration in the biofilm also protects the bacteria from some antibiotics.
[0007] The CDC claims that 65% of bacterial infections that are treated by
physicians
develop biofilm. Biofilm have been implicated in chronic infections. Most
notable among
them is staphylococcus aureus especially the methicillin resistant variety,
staphylococcus
epidermis and pseudomonas aeruginosa. Topical glycerin can treat biofilm in
the mouth such
as halitosis.
[0008] A 66 year old female developed cellulitis and an open ulcer on her leg.
This was
treated by oral antibiotics and was also treated at an outpatient wound care
center. When the
outpatient care was not successful she was admitted to the hospital for
intravenous
antibiotics. After 3 weeks there was no sign of improvement and the ulcer was
enlarging. At
this stage the ulcer measured 3 cm by 1 1/2 cm in size and there was
surrounding redness
suggestive of inflammation. She was then given intravenous glycerin. The
intravenous
glycerin was given as a solution of 3% glycerin and 3% amino acids. This is
currently the
only commercially available source of intravenous glycerin. She was given the
infusion at a
rate of 80 cubic centimeters (cc) per hour. At the end of 48 hours there was
evidence of
healing in the ulcer. During these 48 hours she was continued on intravenous
antibiotics.
After 72 hours the patient was discharged home on oral antibiotics. When she
was re-
examined 3 weeks later there was no evidence of the ulcer and the surrounding
inflammation
that was caused by cellulitis had totally cleared. Ulcers such as this patient
had develop
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bacterial biofilm and can have increased resistance to antibiotics that at
times cause the
antibiotics to be ineffective.
SUMMARY OF THE INVENTION
[0009] The use of intravenous normal saline solution containing glycerin and
amino acids
to prevent or inhibit internal biofilm formation by bacteria is disclosed.
[0010] In some embodiments, the concentration of glycerin in the normal saline
solution is
approximately 3%.
[0011] In some embodiments, the concentration of amino acids in the normal
saline solution
is approximately 3%.
[0012] In some embodiments, the intravenous solution is administered for 48
hours at 80
cc/hour.
[0013] In some embodiments, the normal saline solution comprising a certain
percentage
concentration by volume of glycerin and a certain percentage by volume of an
amino acid
solution is infused into an infected body cavity.
[0014] In some embodiments, the bacterial infection comprises methicillin
resistant
staphylococcus aureus.
[0015] In some embodiments, the bacterial infection comprises staphylococcus
epidermis.
[0016] In some embodiments, the bacterial infection comprises pseudomonas
aeruginosa.
[0017] In some embodiments, the infected body cavity is a pleural cavity.
[0018] In some embodiments, the infected body cavity is a peritoneal cavity.
[0019] In some embodiments, approximately 500 cc of the normal saline solution
comprising
a certain percentage concentration by volume of glycerin and a certain
percentage by volume
of an amino acid solution is infused into an infected body cavity.
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[0020] In some embodiments, greater than 500 cc of the normal saline solution
comprising a
certain percentage concentration by volume of glycerin and a certain
percentage by volume
of an amino acid solution is infused into an infected body cavity.
[0021] Also disclosed is the use of a normal saline solution comprising a
certain percentage
concentration by volume of glycerin and a certain percentage by volume of an
amino acid
solution for optimizing therapeutic efficacy for treatment of a bacterial
infection within a
body cavity.
DETAILED DESCRIPTION OF THE INVENTION
[0022] Glycerin is a simple polyol compound. Tons of it is produced annually
in the United
States and Europe. It is made from animal fats and vegetable oils. Only one
company in the
United States makes a product that is sterile and used for intravenous
administration. It has
been used since 1976 as a non-glycemic source of carbohydrates as a source of
nutrition in
patients who are unable to process food via the gastrointestinal tract. It is
remarkable for its
safety profile and is free of allergic reactions. It is generally infused at a
3% concentration at
a rate of 80-100 milliliters per hour. Those with heart failure and kidney
failure may need a
slower rate of infusion. As in the case outlined here it can diffuse a
bacterial biofilm.
[0023] Glycerin can assist antibiotics and the immune system in conquering
bacteria biofilm.
In this capacity it can reduce the ever-occurring resistance of bacteria to
antibiotics. Cavity
spaces such as the pleural cavity and the peritoneal cavity can develop
infections with
biofilms. Infusing these cavities with the 3% solution of Glycerin would help
breakdown
these biofilms. For example, half a liter of the solution would be infused
into a pleural cavity.
A greater amount could be infused into the peritoneal cavity.
[0024] Embodiments are directed to use of an intravenous normal saline
solution comprising
a certain percentage concentration by volume of glycerin and a certain
percentage by volume
of an amino acid solution for treating a biofilm-associated infection in a
subject.
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[0025] In some embodiments, the concentration of glycerin in the normal saline
solution is
approximately 3%.
[0026] In some embodiments, the concentration of amino acids in the normal
saline solution
is approximately 3%.
[0027] In some embodiments, the intravenous solution is administered for 48
hours at 80
cc/hour.
[0028] In some embodiments, the normal saline solution comprising a certain
percentage
concentration by volume of glycerin and a certain percentage by volume of an
amino acid
solution is infused into an infected body cavity.
[0029] In some embodiments, the infusion occurs via intracavernous
administration.
[0030] In some embodiments, the bacterial infection comprises methicillin
resistant
staphylococcus aureus.
[0031] In some embodiments, the bacterial infection comprises staphylococcus
epidermis.
[0032] In some embodiments, the bacterial infection comprises pseudomonas
aeruginosa.
[0033] In some embodiments, the infected body cavity is a pleural cavity.
[0034] In some embodiments, the infected body cavity is a peritoneal cavity.
[0035] A concentration higher than 3% of glycerin may be more effective.
[0036] Brand names include Procalamine from B. Braun Medical Inc.
[0037] ProcalAminee (3% Amino Acid and 3% Glycerin Injection with
Electrolytes) is a
sterile, nonpyrogenic, moderately hypertonic intravenous injection containing
crystalline
amino acids, a nonprotein energy substrate and maintenance electrolytes.
[0038] A 1000 mL unit provides a total of 29 g of protein equivalent (4.6 g N)
and 130
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nonprotein calories.
[0039] All amino acids designated USP are the "U-isomer with the exception of
Glycine
USP which does not have an isomer.
[0040] Table 1 provides the component weights per 100 mL.
TABLE 1
Nonprotein energy source:
Glycerin USP (glycerol) 3.0 g
Essential amino acids
Isoleucine USP 0.21 g
Leucine USP 0.27 g
Lysine (as Lysine Acetate USP 0.31g) 0.22 g
Methionine USP 0.16 g
Phenylalanine USP 0.17 g
Threonine USP 0.12 g
Tryptophan USP 0.046 g
Valine USP 0.20 g
Nonessential amino acids
Alanine USP 0.21 g
Glycine USP 0.42 g
Arginine USP 0.29 g
Histidine USP 0.085 g
Proline USP 0.34 g
Serine USP 0.18 g
Cysteine (as Cysteine HC1=H20 USP <0.020) <0.014 g
Sodium Acetate=3H20 USP 0.20 g
Magnesium Acetate=4H20 0.054 g
Calcium Acetate=H20 0.026 g
Sodium Chloride USP 0.12 g
Potassium Chloride USP 0.15 g
Phosphoric Acid NF 0.041 g
Potassium Metabisulfite NF (as an antioxidant) <0.05 g
Water for Injection USP QS
pH adjusted with Glacial Acetic Acid USP pH 6.8 (6.5-7.0)
Calculated Osmolarity 735 mOsmol/liter
[0041] These descriptions and drawings are embodiments and teachings of the
present
invention. All variations are within the spirit and scope of the present
invention. This
disclosure is not to be considered as limiting the present invention to only
the embodiments
illustrated.
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