Language selection

Search

Patent 2623964 Summary

Third-party information liability

Some of the information on this Web page has been provided by external sources. The Government of Canada is not responsible for the accuracy, reliability or currency of the information supplied by external sources. Users wishing to rely upon this information should consult directly with the source of the information. Content provided by external sources is not subject to official languages, privacy and accessibility requirements.

Claims and Abstract availability

Any discrepancies in the text and image of the Claims and Abstract are due to differing posting times. Text of the Claims and Abstract are posted:

  • At the time the application is open to public inspection;
  • At the time of issue of the patent (grant).
(12) Patent: (11) CA 2623964
(54) English Title: USING METAL AQUACOMPLEXES FOR PREPARATION PURE AMINO ACID CHELATES FOR HUMAN AND VETERINARY USE
(54) French Title: HYDROCOMPLEXES METALLIQUES SERVANT A PREPARER DES CHELATES D'AMINO-ACIDES PURS A USAGES HUMAIN ET VETERINAIRE
Status: Granted
Bibliographic Data
(51) International Patent Classification (IPC):
  • C07C 227/44 (2006.01)
  • A23L 33/16 (2016.01)
  • A23L 33/175 (2016.01)
  • A61K 31/198 (2006.01)
  • C07B 43/04 (2006.01)
(72) Inventors :
  • MIROSHNYCHENKO, OLEKSANDR (Canada)
(73) Owners :
  • MIROSHNYCHENKO, OLEKSANDR (Canada)
(71) Applicants :
  • MIROSHNYCHENKO, OLEKSANDR (Canada)
(74) Agent:
(74) Associate agent:
(45) Issued: 2011-05-24
(22) Filed Date: 2008-03-14
(41) Open to Public Inspection: 2009-09-14
Examination requested: 2008-05-02
Availability of licence: Yes
(25) Language of filing: English

Patent Cooperation Treaty (PCT): No

(30) Application Priority Data: None

Abstracts

English Abstract




A one-pot method for preparing water-soluble pure metal amino acid chelates in
various
chelate compositions using metal aquacomplexes is disclosed and described. The
chelates
obtained are free from other organic and inorganic additives including acids,
salts, and ions and
have high solubility and stability in aqueous solution. The pH of aqueous
solutions of chelates is
optimized for intestinal absorption by using different combinations of amino
acids as ligands.
The present invention establishes a process for providing a recommended level
of intake of
essential metals and essential amino acids by humans and animals by using
chelates as
nutritional supplements or pharmaceutical applications.


French Abstract

Dans l'invention, on divulgue et décrit une méthode permettant de préparer des chélates hydrosolubles purs composés d'acides aminés et de métaux de composition variable à l'aide d'hydrocomplexes métalliques dans un récipient unique. Les chélates obtenus ont exempts d'autres additifs organiques et inorganiques, y compris d'acides, de sels et d'ions, et présentent une très bonne solubilité et stabilité en solution aqueuse. Le pH des solutions aqueuses de chélates a été optimalisé pour une absorption intestinale maximale à l'aide de différentes combinations d'acides aminés en tant que ligands. La présente invention établit une méthode permettant de recommander la concentration des métaux essentiels et des acides aminés essentiels aux humains et aux animaux en utilisant les chélates dans les suppléments nutritionnels ou les compositions pharmaceutiques.

Claims

Note: Claims are shown in the official language in which they were submitted.




18

What is claimed is:

1. A one-pot method for preparing pure metal amino acid chelates that are
water soluble and
stable in a range of pH of between about 3.8 and 9.7 and are free from
inorganic salts, inorganic or
organic acids, interfering ions in inner as well as in outer complex spheres,
consisting of these steps:
a) formation of non-water-soluble metal oxohydroxides, metal aquahydroxides
for di- and
trivalent metals, and carbonates or basic carbonates of divalent metals;
b) transformation of metal oxohydroxides, metal aquahydroxides of di- and
trivalent metals,
and carbonates or basic carbonates of divalent metals into aquaoxohydroxometal-
.alpha.-amino acid or
aquahydroximetal-.alpha.-amino acid by reaction in an aqueous solution with
.alpha.-amino acids with pI< 3.5,
while for copper it is also possible to use amino acids with pI >7.0;
c) subsequent exchange of molecules of water and hydroxyl groups in the inner
sphere by
amino acids wherein the metal amino acid chelate has a ligand to metal molar
ratio of about 2:1, 3:1
or 5:2;
d) evaporation of the aqueous solution of the amino acid chelate formed under
reduced
pressure and by drying of the obtained chelate.
2. A method as in claim 1 wherein the metal of the metal oxohydroxide and the
metal of the
metal aquahydroxides is selected from the group consisting of calcium,
chromium, cobalt, copper,
iron, magnesium, manganese, molybdenum, nickel, vanadium, and zinc.
3. A method as in claim 1 wherein said .alpha.-amino acid is selected from the
group consisting of
alanine, arginine, aspartic acid, asparagine, valine, glycine, histidine,
glutamic acid, glutamine,
isoleucine, leucine, lysine, proline, serine, methionine, threonine,
tryptophan, tyrosine, cysteine,
phenylalanine, and combinations thereof.
4. A method as in claim 1 wherein amino acid chelates of metals whose ions are
oxidized by
atmospheric oxygen are prepared under reduced pressure or in a nitrogen
atmosphere.
5. A method as in claim 1 wherein amino acid chelates of metals whose ions
form strong
bonds with carbonate ions are prepared under reduced pressure or in a nitrogen
atmosphere to
protect ions of the metals from contact with atmospheric carbon dioxide.
6. A method as in claim 1 wherein calcium is selected as the metal and the pH
of the final
amino acid chelate solution is less than 7.4, steps in claim 1(b) and 1(c) are
carried out in open air
conditions, while when the pH of the final amino acid chelate solution is
greater than 7.4, steps in
claim 1(b) and 1(c) are carried out under reduced pressure to protect the
reaction mixture from
contact with atmospheric carbon dioxide.



19

7. A method as in claim 1 wherein ligand exchange reactions for metals whose
aquacomplexes form hydroxo or oxo-hydroxo complexes by deprotonation of their
aquacomplexes
proceed in acidic solution to achieve pH < 5.7 by using only amino acids to
avoid formation of by-
products.
8. A method as in claim 1 wherein the desired pH of aqueous solutions of amino
acid
chelates is manipulated by using different combinations of amino acids as
ligands to create amino
acid chelates with high solubility and stability in aqueous solution in the
range of pH for optimal
intestinal absorption in humans and other warm-blooded animals.
9. A method as in claim 1 wherein the aqueous solutions of all amino acid
chelates having a
ligand to metal molar ratio of about 2:1 and 3:1, except in calcium chelate
solutions with pH > 7.4,
and calcium amino acid chelates having a ligand to metal ratio of about 5:2
are stable aqueous
solutions.
10. A method as in claim 1 wherein a rate of the subsequent exchange of water
molecules
and the hydroxyl groups in the inner sphere by amino acids increases at the
temperature range of
from about 40° C to 80° C.
11. A method as in claim 1 wherein the metal amino acid chelates are used in
the following
fields: food production, pharmaceutical and veterinary use.

Description

Note: Descriptions are shown in the official language in which they were submitted.



CA 02623964 2010-08-11

1
Using metal aquacomplexes for preparation of pure
amino acid chelates for human and veterinary use
Inventor (Country): Miroshnychenko, Oleksandr (Canada)

References Cited:
Canadian Patent document
CA 24575840 4/2003 Ashmead et al.
U.S. Patent document
U.S. Pat. 2,877,253 A 3/1959 Rummel et al.;
U.S. Pat. 2,957.806 A 10/1960 Rummel et al.;
U.S. Pat. 4,599,152 A 7/1986 Ashmead;
U.S. Pat. 4,948,594 A 8/1989 Abdel-Monem et al.;
U.S. Pat. 5,385,933 A 1/1995 Rabinovitz et al.;
U.S. Pat. 5,516,925 A 5/1996 Pedersen et al.;
U.S. Pat. 6,197,815 B1 3/2001 Hsu;
U.S. Pat. 6,407,138 B1 6/2002 Ashmead et al.;
U.S. Pat. 6,710,079 B1 3/2004 Ashmead et al.;
U.S. Pat. 2004/0097748 Al 5/2004 Abdel-Monem et al.;
U.S. Pat. 7,087,775 B2 8/2006 Lee et al.;
U.S. Pat. 7,129,375 B2 11/2006 Abdel-Monem et al.;
U.S. Pat. 7,144,737 B2 12/2006 Hartle et al.
OTHER PUBLICATIONS
Ahrland S., Chat J., Davies N.R. Quart. Rev. Chem. Soc. 1958, 12, 265-267;

Ashmead H.D. The Roles of Amino Acid Chelates in Animal Nutrition, Noyes
Publications, Park
Ridge, N.J., 1993;
Ashmead H.D. Chelated Mineral Nutrition in Plants, Animals and Man, Charles C.
Thomas
Publisher; 1982;


CA 02623964 2010-08-11

2
Ashmead H.D., Graff D.J., Ashmead H.H. Intestinal Absorption of Metal Ions and
Chelates, Charles
C. Thomas Publisher, 1985;
Banner D.W., D'Arcy A., Chene C., Winkler F.K., Guna A., Konigsberg W.H.,
Nemerson Y.,
Kirchhofer D. Nature, 1996, 380, 41-46;
Bell C.F. Principles and Applications of Metal Chelation. Oxford, Clarendon
Press, 1977, 147;
Bellamy L.J. The Infra-red Spectra of Complex Molecules, London: Methuen & Co
LTD New
York: John Wiley & Sons, Inc., 1966;

Bellamy L.J. The Infra-red Spectra of Complex Molecules, John Wiley & Son,
Inc., 1975;
Bentley F.F., Smithson L.D., Rozek A.L. Infrared Spectra and Characteristic
Frequencies -700-300
cm-1, Interscience Publishers, 1968;
Berman H.M., Westbrook J., Feng Z., Gilliland G., Bhat T.N., Weissig H.,
Shindyalov I.N.,
Bernstein F.C., Koetzle T.F., Williams G.J., Meyer E.F., Brice M.D., Rodgers
J.R., Kennard 0.,
Bioinorganic chemistry: transition metals in biology and their coordination
chemistry/ Deutsche
Forschungsgemeinschaft. Research Report Editor Trautwein A.X. Wiley-VCH Verlag
GmbH, 1997;
Bernstein F.C., Koetzle T.F., Williams G.J., Meyer E.F., Brice M.D., Rodgers
J.R., Kennard 0.,
Shimanouchi T, Tasumi M.J. J. Mol. Biol., 1977, 112, 535-542;
Bourne P.E. Nucleic Acids Res. 2000, 28, 235-242;
Bradley D.C., Gitlitz M.H. J. Chem. Soc. A, 1969, 980-984;
Brown C.E., Vidrine D.W., Julian R.L., Froncisz W. J. Chem.Soc. Dalton
Transact., 1982, 2371-
2377;
Condrate R.A., Nakamoto K. J. Chem. Phys., 1965, 42, 2590-2598;
Costisor 0., Linert W. Metal Mediated Template Synthesis of Ligands. World
Scientific Publishing
Co. Ltd, 2004;

Crans D.C., Yang L., Alfano J.A., Chi L.H., Jin W., Mahroof-Tahir M., Robbins
K., Toloue M.M.,
Chan L.K., Plante A.J., Grayson R.Z., Willsky G.R. Coordination Chemistry
Reviews, 2003, 237,
13-22;

Denisov E.T. Kinetics of Homogeneous Chemical Reactions. Vysshaya Shkola,
Moscow, 1988
(Rus.);
Fujita J., Nakamoto K., Kobayashi M. J. Am. Chem. Soc., 1956, 78, 3963-3965;
Fujita J., Martell A.E., Nakamoto K. J. Chem. Phys., 1962, 36, 324-331;
Harding M.M. Acta Cryst., 2004, D60, 849-859;
Harding M.M. Acta Cryst., 2006, D62, 678-682;
Harlle J.W., Ashmead H.D. Feedstuffs, 2006, September 11, 16-17;


CA 02623964 2010-08-11

3
Herlinger A. W., Wenhold S. L., Long T.V. J. Am. Chem. Soc., 1970, 92, 6474-
648 1;
Hoorper R.J., Lane T.J., Walter J.L. Inorganic Chemistry, 1964, 3, 1568-1573;
Housecroft C. E. The Heavier d-Block Metals: Aspects of Inorganic and
Coordination Chemistry.
Oxford University Press, 1999;
Glemser V.O., Schwarzmann E. Z. Anorg. Allg. Chem., 1955, 278, 249-254;
Gurskaya G.V. The Molecular Structure of Amino acids. Determination by X-Ray
Diffraction
Analysis, Nauka Press, 1966;
Ippolito J.A., Steitz T.A. Proc. Nat. Acad. Sci. USA 1998, 95, 9819-9824;
Irving H., Williams R.J.P. Nature, 1948,162,746; J. Chem. Soc., 1953, 3192;
Katz A.K., Glusker J.P., Beebe S.A., Bock C.W. J. Am. Chem. Soc., 1996, 118,
5752-5763;
Kirschner S., Kiesling R. J. Am. Chem. Soc., 1960, 82, 4174-4176;
Kukushkin V. Yu., Kukushkin Yu. N. Theory and Practice of the Synthesis of
Coordination
Compounds. Vysshaya Shkola, Moscow, 1985 (Rus.);
Lane T.J., C.S.C., Durkin J.A., Hooper R.J. Spectrochim. Acta, 1964, 20, 1013-
1019;
Lekchiri A., Castellano A., Morcellet J., Morcellet M. Eur. Polym. J., 1991,
27, 1271-1278;
Lightstone F.C., Schwegler E., Allesch M., Gygi F., Galli G. ChemPhysChem,
2005, 6, 1745-1749;
Martell A. "The Relationship of Chemical Structure to Metal-Binding Action" in
Seven M.J., ed.
Metal Binding in Medicine; proceedings of a symposium. Philadelphia, J.B.
Lippincott. Co, 1960,
17;

Matsukura T., Tanaka H. Biochemistry (Moscow), 2000, 65, 817-823;
McNeill J.H., Yuen V.G., Hoveyda H.R., Orvig C. J. Med. Chem., 1992, 35,1489-
1491;
Mikami M., Nakagava I., Shimanouchi T. Spectrochim. Acta, 1967, 23A, 1037-
1053;
Mohamed G.G., Omar M.M., Hindy A.M. Turk. J. Chem., 2006, 30, 361-382;
Nakamoto K. Infrared Spectra of Inorganic Coordination Compounds, John Wiley &
Sons, Inc.,
1963;

Nagypal I., Gergely A. J. Chem. Soc. Dalton Trans., 1977, 1109-1111;
Orgel L.E. An Introduction to Transition-Metal Chemistry: Ligand-Field Theory,
Methuen and Co.,
Ltd., London, 1961;
Pearson R.G. J. Am. Chem. Soc., 1963, 85, 3533-3539;
Pidcock E., Moore G. R. J. Biol. Chem., 2001, 6, 479-489;
Rosenberg A. Acta Chem. Scand., 1956, 10, 840-85 1;
Sabaceno A.J., Nakagawa I., Mizushima S., Curran C., Quagliano J.V. J. Am.
Chem. Soc., 1958, 80,
5018- 5021;


CA 02623964 2010-08-11

4
Sartory G., Furlani C., Damiani A. J. Inorg. Nucl. Chem., 1958, 8, 119-125;
Sawyer D.T., McKinnie J.M. J. Am. Chem. Soc., 1960, 82, 4191-4196;
Sawyer D.T., Paulsen P.J. J. Am. Chem. Soc., 1959, 81, 816-820;
Shimanouchi T., Tasumi M. J. Mol. Biol., 1977, 112, 535-542;
Sigel H. Accounts. Chem. Res., 1970, 3, 201-208;

Sillen L.G., Vartell A.E. Stability Constant of Metal Ion Complexes, Special
Publication No.17, The
Chemical Society, London, 1964;

Silva J.J.R.F., Williams R.S.P. The Biological Chemistry of the Elements.
Oxford, Oxford
University Press, 2001;
Sobczak J., Ziolkowski J.J. Transition Met. Chem., 1985, 10, 319;
Socrates G. Infrared Characteristic Group Frequencies, 2-ed., John Wiley &
Sons, Inc., 1994;
Svatos G.F., Curran C., Quagliano J.V. J. Am. Chem. Soc., 1955, 77, 6159-6163;
Sweeny D.M., Curran C., Quagliano J.V. J. Am. Chem. Soc., 1955, 77, 5508;
Sen D.N., Mirzushima S., Curran C., Quagliano J.V. J. Am. Chem. Soc., 1955,
77, 211-212;
Yang W., Jones L.M., Isley L., Ye Y., Lee H.W., Lui Z., Hellinga H.W., Malchow
R., Ghazi M.,
Yang J.J. J. Am. Chem. Soc., 2003, 125, 6165-6171;

Yang W., Lee H.W., Hellinga H. Yang J.J. Proteins: Structure, Function, and
Genetics, 2002, 47,
344-356;
Walter J.L., C.S.C., Hooper R.J. Spectrochim. Acta, 1969, 25A, 647-65 1;
Williams R.J.P. Endeavor, 1967, 26, 96-100.


CA 02623964 2010-11-15

BACKGROUND OF THE INVENTION
Unbalanced consumption of amino acids and metal ions leads to serious
illnesses. Metal ions
are readily absorbed if they are bonded in complexes with organic molecules.
Recently such
complexes have been used not only as food supplements, but also for treatment
of some diseases.
For example, copper complexes have been used for cancer treatment (U.S.
Pat.5,385,933), zinc
complexes have been approved as anti-ulcer drugs (Matsukura, 2000), and
vanadium-containing
drugs may be used for treatment of diabetes (McNeill, 1992; Crans, 2003).
Selecting ligands of
desired stability is important. When metals are chelated with organic acids
like ascorbic or citric
acid, the resulting stability of the chelate is relatively low. EDTA
(Ethylenediaminetetraacetic acid)-
type ligands have very high stability, but it is hard for a biological system
to absorb chelated metals
easily. The main advantage of amino acid chelates with amino acids as ligands
is their sufficient
stability and easy absorbance into biological systems.
The actual structure of amino acid chelates depends on the metal to ligand
molar ratio. As
defined by the American Association of Feed Control Officials, a metal amino
acid chelate is the
product resulting from the reaction of a metal ion from a soluble metal salt
with amino acids having
a mole ratio of one mole of metal to one to three (preferably two) moles of
amino acids to form
coordinate covalent bonds. The average weight of the hydrolyzed amino acids
must be
approximately 150 and the resulting molecular weight of the chelate must not
exceed 800.
The structure, chemistry, and bioavailability of amino acid chelates are well
documented in
the literature, e.g. Gurskaya (1966); Sigel (1970); Williams (1967); Silva
(1991); Ashmead (1993,
1982, 1985, 1971); Bellamy (1966).
However, two serious problems are known for amino acid chelates: low
solubility (e.g. US
Pat. 2004/0097748 Al or US Pat. 7,129,375 B2) and the presence of interfering
ions (e.g. US Pat.
2,877,253 or US Pat. 2,957,806). To improve the solubility of amino acid
chelates, they are mixed
with an effective amount of an organic acid solubilizing agent (e.g. CA Pat.
24575840). The other
problem, as indicated previously, is the presence of interfering ions in the
final product. In previous
art, amino acid chelates have additional interfering ions because they are
formed by adding an
already dissolved water soluble metal salt to an aqueous solution of amino
acid (e.g. US Pat.
6,197,815 B1); adding insoluble salts or oxides (e.g. US Pat. 4,948,594) to an
acidic solution
prepared by mixing an amino acid with an organic (e.g. U.S. Pat. 5,516,925;
U.S. Pat. 6,197,815 B1)
or inorganic (e.g. US Pat. 4,948,594) acid. However, as indicated in U.S. Pat.
No. 2,877,253, if a
water soluble metal salt was used as a mineral source for chelation purposes,
the resulting complex
contain anion of this salt. Another method (U.S. Pat. 4,599,152) consists of
the preparation of metal


CA 02623964 2010-11-15

6
cation in the aqueous electrolyte by electrolyzing pure metal or metal
chloride, which then reacts
with the amino acid ligand; but in this case, the hydroxyl ion and/or organic
anions are still present
in the final chelate. Other methods (U.S. Pat. 6,407,138 B1; U.S. Pat
6,710,079 B1) of preparing
amino acid chelates free of interfering ions consist of "blending an amino
acid ligand, a calcium
oxide and/or hydroxide, and a hydrated metal sulfate salt, placing the blend
in a closed environment,
heating the bland, and allowing the blend to react." Nevertheless, these
compositions contain
calcium sulfate. The authors maintain that the calcium sulfate which is inert
and may have desirable
properties if left in the final product as it reduces the electrostatic
properties of the spray dried
powder, makes the dried product less hydroscopic, and stabilizes the amino
acid chelate in an acidic
solution. However, the health effects of additional calcium sulfate may be
unpredictable, leading to
serious negative consequences, including but not limited to gastrointestinal
discomfort in patients.
According to the prior art described above, it is still highly desirable to
prepare a pure, highly
soluble and stable aqueous solution of a-amino acid chelates, with the pH of
their aqueous solution
being optimal for intestinal absorption (Ashmead, 1985), free of any inorganic
or organic anions,
inorganic salts or any admixtures to increase the solubility of the final
composition.

OBJECTS AND SUMMARY OF THE INVENTION
A method of preparation of metal amino acid chelates free from inorganic
salts, inorganic or
organic acids, and interfering ions in both inner and outer spheres, soluble
and stable in water is
described. These solutions possess the range of pH optimal for intestinal
absorption, where a metal
ion is selected from the group consisting of calcium, chromium, cobalt,
copper, iron, magnesium,
manganese, molybdenum, nickel, vanadium and zinc. These metal ions are
chelated with amino acid
ligands selected from the group consisting of alanine, arginine, aspartic
acid, asparagine, valine,
glycine, histidine, glutamic acid, glutamine, isoleucine, leucine, lysine,
proline, serine, methionine,
threonine, tryptophan, tyrosine, cysteine, phenylalanine; and wherein the
metal amino acid chelate
has a ligand to metal ratio of about 2:1, 3:1 or 5:2. Preparation of amino
acid chelates consists of:
a) formation of non-water-soluble metal oxohydroxides, metal aquahydroxides
for di- and
trivalent metals, and carbonates or basic carbonates for divalent metals;
b) transformation of metal oxohydroxides, metal aquahydroxides of di- and
trivalent metals,
and carbonates or basic carbonates of divalent metals into aquaoxohydroxymetal-
a-amino acid or
aquahydroxymetal-a-amino acid by reaction in an aqueous solution with a-amino
acids with pI< 3.5,
while for copper it is also possible to use amino acids with pI > 7.0;


CA 02623964 2010-11-15

7
c) subsequent exchange of the molecules of water and hydroxyl groups in the
inner sphere by
amino acids wherein the metal amino acid chelate has a ligand to metal molar
ratio of about 2:1, 3:1
or 5:2;
d) evaporation of the aqueous solution of the amino acid chelate formed under
reduced
pressure and by drying the obtained chelate.
The only by-products of these processes are carbonic acid and water. Carbonic
acid is easily
decomposed to water and carbon dioxide, which completely escapes from the
reaction mixture when
the reaction is carried out in vacuo or the final chelate is concentrated
under reduced pressure. As a
result, pure amino acid chelates are free from interfering ions in the inner
and outer sphere.

DETAILED DESCRIPTION OF THE INVENTION
The factors influencing the solution stability of the chelates are described
in detail in the
literature (for example, Kukushkin (1985); Costisor (2004); Bell (1977);
Ashmead (1985); Martell
(1960)). For M+2 ions, except calcium (its divalent cation prefers to
coordinate with seven water
molecules in the first solvation shell (Lightstone, 2005; Silva, 2001)),
octahedral six-coorditation
structure is found to be dominant (Silva, 2001). For metals selected in the
present invention,
coordination number (NC) Nc=6 was found for most protein molecules (Bernstein,
1977; Berman,
2000), although for copper Nc was predominantly 4 and 5 (Bioinorganic
chemistry, 1997), and for
zinc was 4 (Harding, 2004). The most common geometry for calcium-binding
proteins is that of a
pentagonal bipyramid, although distorted octahedral geometries are also known;
(Yang, 2002; Yang,
2003; Katz, 1996). In proteins, calcium ions are predominantly chelated with
oxygen atoms from
several types of groups such as carboxylates (bi- and monodentate
interactions), carbonyls (main-
chain or amid side-chain), and hydroxyls (either from protein side-chains or
solvent hydroxyls), less
often with nitrogen and never directly coordinated to sulfur (Silva, 2001;
Katz, 1996; Harding, 2004;
Bernstein, 1977; Berman, 2000; Yang, 2003; Ippolito, 1998). Side-chain
carboxylates of aspartame
and glutamate form a major class of ligands. The observed ratio of aspartame
to glutamate is 2.4:1.
Glycine is the largest contributor to the total number of backbone carbonyl
ligands, which represents
22% of all non-carboxylate, protein-derived ligands (Pidcock, 2001).
The hexaaqua ions of the M+3 are fairly acidic, and in aqueous solution they
act as acids by
donating hydrogen ions to water molecules. "Loss of proton though polarization
of O-H bonds in
coordinated water leads, in some cases, to formation of hydroxo ligands and
the concomitant
generation of dinuclear species. Such an example is [(HZO)4Cr( -OH)ZCr(H2O)4)
14+,, (Housecroft,
1999). According to Le Chatelier's Principle, the hexaaqua ion can be
stabilized in solution by


CA 02623964 2010-11-15

8
adding H+ (a-amino acids having pH< 5.7 were used as the acidic solution).
"The increase in
electron withdrawing power of the metal center associated with an increase in
oxidation state is
further reflected in the fact the hexaaqua ion of vanadium (IV) does not exist
in solution, loss of two
protons instead leading to the formation of [VO(H2O)5]2+õ (Housecroft 1999).
The reactions employed in preparation of metal amino acid chelates free of
interfering
anions with a ligand to metal molar ratio about 2:1, 3:1 or 5:2 are described
below:

1. Formation of water-insoluble metal hexaaquahydroxides, metal
oxoaquahydroxides,
and basic carbonates of divalent metals.

1. 1. Formation of water-insoluble metal hexaaquahydroxides and metal
oxoaquahydroxides.
1.1.1. Reaction of hydroxide ions with di- and trivalent metal aqua ions.
{[Me(H2O)x]m+}aq + Off -> {[Me(H20)X_y(OH) y]m+}S + H2O

where:
Me - di- and trivalent metals;
for divalent metals y=2 and m=2;
for trivalent metals y=3 and m=3;
x=6 for most metals, except calcium (x=7).

1.1.2. Reaction of hexaaquametal ions with carbonate ions.
Due to the sufficient acidity of the M+3 hexaaqua ions, their reaction with
carbonate ions
produces metal aquahydroxide and releases gaseous carbon dioxide:

{ [Me(H2O)6]3+} aq + CO32- -> { [Me(H2O)3(OH)3] } s + CO2 T + H2O

Since M+2 hexaaqua ions are not strongly acidic enough to release carbon
dioxide from
carbonate, a precipitate of basic carbonate is formed:
{[Me(H20)X]2+}aq + C03 2- -+ k McCO3 = in Me(OH)2 = z H2O
where:
k =1-3;
m=1-3;
x=6 for most metals, except calcium (x=7);

z=0-4.


CA 02623964 2010-11-15

9
1.1.3. Formation of aquaoxohydroxides.
Vanadyl (IV) aquaoxohydroxide can be synthesized according to the method
described by
Glemser (1955), which consists of the reduction of aqueous V205 suspension by
SO2. Molybdenum
aquaoxohydroxide can be prepared employing a procedure described by Sobczak
(1985), which
consists of the reduction of ammonium molybdate with hydrazine (40% aqueous
solution) in 2N
H2SO4. Aquaoxohydroxide then precipitates when the solution is treated with
NH4OH.

2. Formation of aquahydroxymetal-a-amino acid or
aquaoxohydroxymetal-a-amino acid ([Z(H20)x-y(OH)y-1 RCH(NH2)COO].

2.1. Reaction of metal aquahydroxides, hydroxides, metal aquaoxohydroxides,
carbonates
and basic carbonates of divalent metals with amino acids with pI < 3.5.

After adding amino acids with pI < 3.5, a proton from the amino acid reacts
with the
hydroxyl from the aqua complex and one additional molecule of water is formed
in the inner sphere.
Since the water is bonded using the "outer" 4d orbital, the water molecule is
easily displaced by the
carboxyl group of the amino acid, and an ionic bond is formed (Complex I).
H2O + RCH(NH2)COOH -* H3O+ + RCH(NH2)000-

[Z (H20)x-Y(OH)Y] + H3O + -> [Z (H2O)x-y+1(OH)y-1]+ + H2O
[Z (H2O)x-y+1(OH)y-1]++ RCH(NH2)000- -f [Z(H20)x-y(OH)y-1RCH(NH2)000] + H2O
.,
Z - O' "-CH(NH2)R
z(j-, 0
Complex I
where:
Z are ions Me +2, Me+3, VO+2, and MoO+3
for divalent metals y=2 and m=2;
for trivalent metals y=3 and m=3;
x=6 for most metals, except calcium (x=7).
In the case of carbonate and basic carbonate in an acidic solution the
carboxyl group is
dislodged first.
Because the particular complex I is also not stable, the additional water
molecule from the
inner sphere might be replaced by amino or carboxy group from amino acid. It
is obvious that the


CA 02623964 2010-11-15

different metal ions prefer binding to different ligand atoms (Ahrland, 1958;
Orgel, 1961; Sillen,
1964; Irving, 1948, 1953; Pearson, 1963) and metal coordination sites in
proteins (Harding, 2006).
For Cat+, Mgt+, Mn2+ and V02+ ions, an additional coordinate bond Me..00 is
probably formed
(Complex IIa) and for ions Fee+, Fe3+, Coe+, Cr3+, MoO3+, Nit+, Cue+, Zn2+, an
additional coordinate
bond N...Me is evidently formed (Complex IIb).

(H )y,, Y=00 (HO, C
Z "-CH(NH2)R Z J/H)1 .
YY y' YY4 i
(H2O j (HO) y-, NH2
Complex IIa Complex IIb
where:
for divalent metals y=2 and m=2;
for trivalent metals y=3 and m=3;
x=6 for most metals, except calcium (x=7);
Z ions Me+2, Me+3, VO+2, and MoO+3

2.2. Reaction of metal aquahydroxides with amino acids with pI > 7Ø
In the case of copper aquahydroxide, it is also possible to use amino acids
with pl > 7.0 in
aqueous solution. The reaction product (Complex III) is identical with that
formed by the
displacement reaction for copper aquacomplexes in acidic solution described
above (Complex IIb,
where Z=Cu).
[Cu(H20)6(OH)2] + NH2CH(R)COOH -* [Cu(H20)5(NH2CH(R)COOH)(OH)] + H2O
[Cu(H20)5(NH2CH(R)COOH)(OH)] -* [Cu(H20)4(OH)NH2CH(R)000] + H2O

HO O--C=
\ /
Cu ( )R
(1120')4 l2
Complex III

3. Formation of chelates.
In the next step, previously formed complexes I, IIa, and IIb react with other
molecule(s) of
either the same a-amino acid used in the previous steps or of another a-amino
acid (depending on
the chelate composition having a ligand to metal molar ratio of about 2:1, 3:1
or 5:2), to form the


CA 02623964 2010-11-15

11
final chelate. According to Crystal Field Theory, replacement of water
molecules by amino acid
molecules in complexes reflects an increase in the stability of chelates in
solution. The ligand
exchange mainly occurs via a dissociative or interchange mechanism Id
(Denisov, 1988).
A rate of the subsequent exchange of water molecules and the hydroxyl groups
in the inner
sphere by amino acids increases at the temperature range of from about 40 C
to 80 C.
A chelate composition having an amino acid to metal molar ratio of 5:2 differs
from a
mixture of chelate with composition 2:1 (two moles of amino acid to one mole
of the metal) and 3:1
(three moles of amino acid to one mole of the metal). That accords with well
known literature results
and with the FT-IR spectral investigation performed in the present work.
Two carboxylate groups of dicarboxylic amino acids can donate one oxygen atom
of each
carboxylate group to a single divalent metal ion, while other carboxylic
oxygen atoms are able to
interact with an adjacent single divalent metal ion (Banner, 1996; Pidcock,
2001). The interaction of
the (3-carboxyl group with divalent metal ions and formation of a six-member
ring are often
observed for aspartic acid (Nagypal, 1977; Lekchiri, 1991). In addition, it
has been reported that
some dimmers do not dissociate in saturated solutions even at temperatures as
high as 80 C (Brown,
1982).
Amino acid chelates of the present invention are free of interfering ions in
the inner and
outer sphere and have many possible applications in food production,
pharmaceutical and veterinary
use.

DETERMINATION OF CHELATE FORMATION.
The FT-IR method is used to determine chelate formation. A relationship
between the
infrared absorption and the type of bonding as metal-nitrogen (M-N), metal-
oxygen (M-O) and
chelate ring formation is described in the literature.
For most amino-acids, NH3+ stretching frequencies have been found in the
region 3200-3000
cm -1 (Socrates G., 1994), but formation of nitrogen-to-metal bonds (N-M) is
associated with a shift
in the H-N stretching frequency at 3450-3030 cm' (usually two bands are
observed) with increasing
charge on the chelate and with an increasing covalent character of the N-M
bond (Stasov, 1955; Sen,
1955; Rosenberg, 1956; Sweeny, 1955).
Fairly strong NH3+ deformation bands for free amino acids are also observed at
1550-1485
cm 1 as well as a weaker band, which is not resolved for most amino acids, at
1660-1590 cm'. Free
amino acids have carboxylate stretching vibration in the region 1600-1560 cm-
1, and dicarboxylic
acids have an additional strong band near 1700 cm-1 and 1230 cm -1 due to the
stretching vibration of


CA 02623964 2010-11-15

12
the C-O bond (Socrates, 1994). As the bonding of the carboxylate groups
becomes more covalent
(after formation of the metal-carboxyl bond), the position of the absorption
bonds of the ionized
carboxyl group is located at 1650-1550 cm-1 for asymmetric modes and 1440-1335
cm-' for
symmetric modes (Sweeny, 1955; Socrates, 1994; Nakamoto, 1963; Sacareno, 1958;
Bellamy,
1975). Chelates with frequencies of 1610 cm -1 or less are considered to be
ionically bonded; those
with frequencies of 1630 cm -1 or greater - covalently bonded. The differences
in frequencies
between the major peak (or peaks) in the 1600 cm -1 and 1500-1350 cm -1 bands
are used as criteria
for the degree of covalent character of the metal-carboxylate bonds. The bonds
are primarily
covalent when the difference is 225 cm 1 or more, and the bonding is primarily
ionic when the
difference is less than 225 cm-1 (Sawyer, 1960). Although absorptions near
1600 cm -1 are also
characteristic of free amino acids and their salts, and absorption of water
around 1640 cm -1
(Socrates, 1994) complicated the identification, it is still possible to use
this region for chelate
determination. In addition, according to Harlle (2006), a band near 1643 cm -1
is evidence of chelate
ring formation.
The absorption band at 1150-1085 cm 1 corresponds to a C-C-N bond in
metalorganic
compounds with a M-N bond (Bradley, 1969) because metal acetates do not have a
peak in this
region (Sawyer, 1959). At the same time, the spectrum of copper (II) tartrate
trihydrate shows
double peaks at 1080 cm -1 and 1063 cm 1, because the metal ion is coordinated
to one hydroxyl
group and two carboxylate groups and a ring structure is formed, as was
explained by Kirschner
(1960). Evidently the formation of the chelate ring has a direct effect at
absorption at 1150-1050
cm 1.

The bond characteristics of the coordinated water in chelates are seen in the
region 970-790
cm -1 (Fujita, 1956; Sartory, 1958; Mohamed, 2006) only when water molecules
are linked to the
metal by fairly covalent bonds and to the ligand by strong hydrogen bonds
(Fujita, 1956).
The strong absorption characteristics of free amino acids in the region 700-
200 cm -1 are due
to COO- and C-C-N group deformation vibration or skeletal deformation
(Bentley, 1968; Walter,
1969). These absorptions reflect how bonds disappear and new bonds are formed
when a chelate is
obtained, as has been shown for zinc bisglycinate chelate in the region 700-
400 cm -1 (Pat. US
7,144,737 B2; Harlle, 2006). The stretching frequencies of the metal-nitrogen
bonds formed
correspond to 590-510 cm 1 (Condrate, 1965; Nakamoto, 1963; Mohamed, 2006).
For metal-oxygen
bonds, frequencies are assigned to 700-600 cm-' (Mikami, 1967).
Therefore, analysis of absorptions in regions 3450-3030 cm-1, 1650-1315 cm 1,
1100-790 cm -1
and 700-400 cm -1 can be used to determine the formation of M-O and M-N bonds
in chelates.


CA 02623964 2010-11-15

13
EXAMPLES
The following examples illustrate methods of preparing metal amino acid
chelates by means
of the present invention. The following examples should not be construed as
limitations of the
present invention, but merely demonstrate how to make pure amino acid chelates
based upon current
experimental data.
All starting chemicals are > 98% pure and are used without additional
purification. Yields
were 98% and higher.

1. Preparing chelate compositions that consist of
two moles of amino acid to one mole of the metal.
Example 1.1.
In 500 ml of distilled water, 3.0010 g of Cu(OH)2 was allowed to react with
4.4733 g of
lysine while the mixture was stirred for 40 min until the pH reached 11.1. To
this mixture, 4.0725 g
of aspartic acid was added and stirring continued for 20 min until the
solution cleared. After an
additional 10 min of stirring, the pH stabilized at 6.9. The resulting
solution was filtered, the water
evaporated in vacuo, and the concentrate dried.
FT-IR analysis: 3431(s), 3264 (s), 3138 (w.), 1618 (v s), 1573 (w), 1465 (m),
1386 (s), 1133
(m), 1042 (w), 919 (w), 797 (w), 676 (m), 660 (w), 578 (m) cm 1.
(Key: s = strong, in = medium, w = weak, v = very, br = broad. All spectra
were obtained using an
SPECORD-75-IR double-beam spectrophotometer. The solid chelates were pressed
into disks using
KBr as a diluent).

Example 1.2.
A mixture comprised of 2.8030 g of Co(OH)2 and 4.0060 g of aspartic acid was
added to 500
ml of distilled water. After 2 hours of stirring at room temperature, the pH
reached 5.3. At this
moment, 3.5848 g of threonine was added to this mixture. After 2 days of
stirring at room
temperature, the solution cleared. The resulting solution was filtered
(pH=5.9), the water evaporated
in vacuo, and the concentrate dried.
FT-IR analysis: 3423 (s), 3284 (w), 1618 (v s), 1406 (s), 1091 (m), 1042 (w),
903 (w), 669
(w), 560 (m) cm 1.


CA 02623964 2010-11-15

14
Example 1.3.
A reaction mixture composed of 1.5667 g of Ca(OH)2, 1.5888 g of glycine and
2.8148 g of
aspartic acid in 500 ml of distilled degassed water was placed in a rotary
evaporator flask and stirred
under vacuum at a water bath temperature of about 45 C. The vacuum pressure
was adjusted to
avoid strong boiling because of constant release of CO2. After approximately 2
hours of stirring, the
solution cleared (pH=9.7). The resulting solution was filtered, the water
evaporated in vacuo, and
the concentrate dried.
FT-IR analysis: 3422 (s), 3067 (w), 1577 (v s), 1411 (m), 1099 (m), 1038 (m),
905 (m), 670
(m), 592 (m), 526 (m) cm 1.

Example 1.4.
In 500 ml of distilled water, 1.5667 g of Mg(OH)2 was allowed to react with
4.0032 g of
aspartic acid while being stirred for 30 min. To this reaction mixture, 2.2583
g glycine was added.
After being stirred for 24 hours at room temperature, a clear solution was
obtained (pH=8.7). The
resulting solution was filtered, water evaporated in vacuo, and the
concentrate dried.
FT-IR analysis: 3423 (s), 3069 (w br), 1632 (v s), 1411 (m), 1096 (m br), 907
(w), 670 (w),
551 (m) cm 1.

2. Preparing chelate compositions that consist of
three moles of amino acid to one mole of the metal.
Example 2.1.
A reaction mixture composed of 3.1011 g CuCO3=Cu(OH)2, 3.7085 g of aspartic
acid in 500
ml of distilled water was placed in a rotary evaporator flask and stirred
under vacuum at a water bath
temperature of about 45 T. The vacuum pressure was adjusted to avoid strong
boiling because of
constant release of CO2. After CO2 was stripped (approximately 30 min.),
4.0779 g of lysine and
3.3272 g of threonine was added to this reaction mixture. To release residual
CO2 the reaction was
continued under reduced pressure, although this step is not necessary in this
case. After the solution
cleared, it was filtered (pH=6.6), water evaporated in vacuo, and the
concentrate dried.
FT-IR analysis: 3422 (s), 3254 (w), 3137 (w), 1624 (v s), 1394 (m), 1099 (m),
1048 (m), 904
(w), 659 (w), 559 (m) cm-1.


CA 02623964 2010-11-15

Example 2.2.
A reaction mixture composed of 2.8329 g CaCO3, 2.1269 g of glycine and 7.5356
g of
aspartic acid in 500 ml of distilled degassed water was placed in a rotary
evaporator flask and stirred
under vacuum at a water bath temperature of about 45 C. The vacuum pressure
was adjusted to
avoid strong boiling because of constant release of CO2. After the CO2 was
stripped (approximately
min.), the solution was additionally stirred under reduced pressure for 30
min. The resulting
solution was filtered (pH=5.4), water evaporated in vacuo, and the concentrate
dried.
FT-IR analysis: 3431 (m), 3057 (m br), 1630 (v s), 1411 (m), 1096 (m br.), 903
(m), 663 (w),
584 (w), 529 (w) cm 1.

Example 2.3.
In 500 ml of distilled water, 2.7706 g of Co(OH)2 was allowed to react with
3.9635 g of
aspartic acid for 2.5 hours at room temperature until the pH of the mixture
stabilized (pH=6.4). To
this mixture 4.3874 g of lysine was added and stirring continued for 1.5 hours
until the solution
almost cleared and the pH reached 8.6. At this moment, 4.3835 g of glutamic
acid was added to this
mixture. After one hour of stirring the solution cleared. The resulting
solution was filtered (pH=6.2),
water evaporated in vacuo, and the concentrate dried.
FT-IR analysis: 3435 (s), 3067 (w), 1625 (v s), 1404 (m), 1087 (m br), 902
(w), 635 (w), 551
(m) cm" 1.

Example 2.4.
A mixture comprised of 3.0851 g of [Zn(OH)2]3=[ZnCO3]2 and 7.5026 g of
aspartic acid was
added to 500 ml distilled water. After being stirred for 1.5 hours at room
temperature, the solution
cleared (pH=5.0). To this mixture, 4.1123 g of lysine was added and was
stirred until the pH of the
solution stabilized (approximately one hour). The resulting solution was
filtered (pH=6.5), water
evaporated in vacuo, and the concentrate dried.
FT-IR analysis: 3432 (s), 3152 (w), 1618 (v s), 1419 (m), 1129 (w), 1091 (m),
1040 (w), 669
(w), 559 (w) cm 1.

Example 2.5.
In 500 ml of distilled water, 2.2394 g of Mg(OH)2 was allowed to react with
5.1356 g of
aspartic acid at room temperature for about 20 min while being stirred. To
this reaction mixture,


CA 02623964 2010-11-15

16
5.7982 g of glycine was added. After one day of stirring at room temperature,
the solution cleared.
The resulting solution was filtered (pH=8.5), water evaporated in vacuo, and
the concentrate dried.
FT-IR analysis: 34221 (s), 3081 (w br), 1634 (v s), 1409 (m), 1096 (m), 1045
(m), 904 (w),
670 (m), 586 (w), 516 (m) cm 1.

Example 2.6.
A reaction mixture comprised of 3.5050 g of MnCO3 and 8.1058 g of aspartic
acid in 800 ml
of distilled water was refluxed under reduced pressure or in open-air
condition for approximately
2-3 hours until the pH reached 4.6 (the total volume of the solution decreased
to 500 ml). To this
mixture, 4.4509 g of lysine was added, and after 40 min stirring under reduced
pressure, the solution
almost cleared. The resulting solution was filtered (pH=7.8). The black
precipitate on the filter was
not analyzed since it weighs less than 1% of the initial quantity of MnCO3.
Water from the filtrate
solution was evaporated in vacuo, and concentrate dried.
FT-IR analysis: 3434 (s), 3057 (w br), 1525 (v s), 1406 (m), 1077 (m br), 901
(w), 656 (w),
544 (w) cm 1.

Example 2.7.
The freshly prepared precipitate of chromium (III) hexaaquahydroxide formed by
the
reaction of 2.8092 g CrC13.6H20 with 1.2657 g NaOH, was separated using an OS-
6M centrifuge
(5500 rpm, 15 min.), washed with distilled water, and stirred in 500 ml of
distilled water. To this
mixture, 2.8066 g of aspartic acid was added. After stirring for approximately
40 min, a clear green
solution (pH = 4.6) was formed. To this solution, 1.2564 g of threonine was
added. After 2 hours of
stirring, a clear solution with raspberry colour and stable pH (pH=3.8) was
formed. The resulting
solution was filtered, water evaporated in vacuo, and the concentrate dried.
FT-IR analysis: 3431 (s), 3246 (w), 3109 (w), 1630 (v s), 1395 (m), 1099 (m
br), 906 (w),
631 (w), 571 (m), 527 (m) cm 1.

3. Preparing chelate compositions that consist of
five moles of amino acid to two moles of the metal.
Example 3.1.
A reaction mixture made up of 2.3715 g of Ca(OH)2, 6.3869 g of aspartic acid
and 2.4007 g
of glycine in 500 ml of distilled degassed water was placed in a rotary
evaporator flask and allowed


CA 02623964 2010-11-15

17
to react under reduced pressure while being stirred at a water bath
temperature of about 45 C. The
pressure was reduced to about 300 mm Hg to protect the reaction mixture from
contact with
atmospheric CO2. The resulting solution was filtered (pH=8.8), water
evaporated in vacuo, and the
concentrate was dried.
FT-IR analysis: 3422 (s), 3049 (m), 1634 (v s), 1412 (m), 1099 (m br), 904
(m), 663 (m),
587 (w), 527 (m) cm 1.

Representative Drawing

Sorry, the representative drawing for patent document number 2623964 was not found.

Administrative Status

For a clearer understanding of the status of the application/patent presented on this page, the site Disclaimer , as well as the definitions for Patent , Administrative Status , Maintenance Fee  and Payment History  should be consulted.

Administrative Status

Title Date
Forecasted Issue Date 2011-05-24
(22) Filed 2008-03-14
Examination Requested 2008-05-02
(41) Open to Public Inspection 2009-09-14
(45) Issued 2011-05-24

Abandonment History

There is no abandonment history.

Maintenance Fee

Last Payment of $125.00 was received on 2021-12-15


 Upcoming maintenance fee amounts

Description Date Amount
Next Payment if small entity fee 2023-03-14 $253.00
Next Payment if standard fee 2023-03-14 $624.00

Note : If the full payment has not been received on or before the date indicated, a further fee may be required which may be one of the following

  • the reinstatement fee;
  • the late payment fee; or
  • additional fee to reverse deemed expiry.

Patent fees are adjusted on the 1st of January every year. The amounts above are the current amounts if received by December 31 of the current year.
Please refer to the CIPO Patent Fees web page to see all current fee amounts.

Payment History

Fee Type Anniversary Year Due Date Amount Paid Paid Date
Application Fee $200.00 2008-03-14
Request for Examination $400.00 2008-05-02
Maintenance Fee - Application - New Act 2 2010-03-15 $50.00 2010-02-05
Maintenance Fee - Application - New Act 3 2011-03-14 $50.00 2011-01-04
Final Fee $150.00 2011-03-04
Maintenance Fee - Patent - New Act 4 2012-03-14 $50.00 2012-01-13
Maintenance Fee - Patent - New Act 5 2013-03-14 $100.00 2013-03-05
Maintenance Fee - Patent - New Act 6 2014-03-14 $100.00 2014-02-27
Maintenance Fee - Patent - New Act 7 2015-03-16 $100.00 2015-02-09
Maintenance Fee - Patent - New Act 8 2016-03-14 $100.00 2016-02-11
Maintenance Fee - Patent - New Act 9 2017-03-14 $100.00 2017-02-09
Maintenance Fee - Patent - New Act 10 2018-03-14 $125.00 2018-01-31
Maintenance Fee - Patent - New Act 11 2019-03-14 $125.00 2019-02-04
Maintenance Fee - Patent - New Act 12 2020-03-16 $125.00 2020-02-21
Maintenance Fee - Patent - New Act 13 2021-03-15 $125.00 2021-01-26
Maintenance Fee - Patent - New Act 14 2022-03-14 $125.00 2021-12-15
Owners on Record

Note: Records showing the ownership history in alphabetical order.

Current Owners on Record
MIROSHNYCHENKO, OLEKSANDR
Past Owners on Record
None
Past Owners that do not appear in the "Owners on Record" listing will appear in other documentation within the application.
Documents

To view selected files, please enter reCAPTCHA code :



To view images, click a link in the Document Description column. To download the documents, select one or more checkboxes in the first column and then click the "Download Selected in PDF format (Zip Archive)" or the "Download Selected as Single PDF" button.

List of published and non-published patent-specific documents on the CPD .

If you have any difficulty accessing content, you can call the Client Service Centre at 1-866-997-1936 or send them an e-mail at CIPO Client Service Centre.


Document
Description 
Date
(yyyy-mm-dd) 
Number of pages   Size of Image (KB) 
Maintenance Fee Payment 2020-02-21 1 33
Maintenance Fee Payment 2021-01-26 1 33
Maintenance Fee Payment 2021-12-15 1 33
Abstract 2008-03-14 1 15
Description 2008-03-14 17 836
Claims 2008-03-14 2 93
Cover Page 2009-09-09 1 31
Claims 2010-04-06 2 92
Abstract 2010-04-06 1 46
Description 2010-04-06 17 849
Claims 2010-08-11 2 94
Description 2010-08-11 17 843
Abstract 2010-11-15 1 22
Claims 2010-11-15 2 97
Description 2010-11-15 17 870
Cover Page 2011-05-02 1 33
Prosecution-Amendment 2010-07-15 5 249
Correspondence 2008-04-15 1 15
Maintenance Fee Payment 2018-01-31 1 33
Assignment 2008-03-14 3 283
Prosecution-Amendment 2008-05-02 1 21
Correspondence 2008-05-02 2 100
Prosecution-Amendment 2009-12-11 6 305
Fees 2010-02-05 1 64
Prosecution-Amendment 2010-04-06 22 814
Prosecution-Amendment 2010-04-06 18 909
Prosecution-Amendment 2010-08-11 21 1,040
Prosecution-Amendment 2010-11-03 4 178
Prosecution-Amendment 2010-11-15 18 905
Fees 2011-01-04 1 50
Maintenance Fee Payment 2019-02-04 1 33
Prosecution-Amendment 2011-03-04 1 31
Correspondence 2011-03-04 1 31
Fees 2012-01-13 1 242
Fees 2013-03-05 2 179
Fees 2014-02-27 1 131
Fees 2015-02-09 1 132
Fees 2016-02-11 1 33
Maintenance Fee Payment 2017-02-09 1 33