Note: Descriptions are shown in the official language in which they were submitted.
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COMPOSITION AND METHOD FOR HEALING TISSUES
BACKGROUND OF THE INVENTION
1. FIELD OF THE INVENTION
[0001] The present invention relates to a method and
composition for growing, protecting, and healing tissues and
cells of animals or humans. The invention particularly pertains
to a method for repairing connective and other tissues, and, in
particular, wound healing and scar reduction by administering a
composition comprising a hydrolyzed collagen as the basic
ingredient, preferably in combination with at least one
therapeutic agent selected from the group consisting of a
polysulfated glycosaminoglycan, hyaluronic acid and salts
thereof, and a glucosamine salt.
2. DESCRIPTION OF THE RELATED ART
[0002] Just as nature has provided the skin as a barrier for
protection, it has also provided mechanisms for skin repair.
Depending upon the nature of the injury, this repair process may
take hours, days, months, or even years. Many factors determine
the length of times it takes for an injured skin to heal.
Pathogenic contaminants may enter the body through the wound
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until the skin's integrity is restored. For this reason, it
desirable to heal open wounds as quickly as possible.
[0003] Open wounds in the skin are a potential gateway for
infectious or contaminating material to enter the body. The
skin is a protective barrier to external contaminants. When the
skin is damaged with an open breach, these contaminants are free
to enter the body. Once inside the body, these contaminants may
have effects of varying degrees, but almost always become more
difficult to treat, and consequently slow the healing process of
the original wound.
[0004] To fight infection, wound management traditionally
involves an initial cleansing of the affected area to remove any
contaminants such as dirt, clothing particles, or other debris.
Damaged tissues and foreign materials are removed when
necessary, and antiseptic agents are applied to sterilize the
injured area. Sterile dressings are often applied, and
periodically changed, to keep the injured area as clean and
sterile as possible. Complex biological mechanisms occur during
the healing process such as chemical signals attracting
fibroblast cells to the wound site which ultimately generate
connective structures mainly of collagen. Endothelial cells
generate new blood capillaries that nurture the new growth. The
cell growth continues until the open wound is filled by forming
permanent new tissue.
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[0005] Because shortened periods of healing result in
shortened exposure time, it would be beneficial to have any open
wound heal as quickly as possible.
[0006] The related art of interest describes various tissue
repairing compositions, but none discloses the present
invention. There is an urgent need for a composition useful for
wound healing, scar reduction and repairing of damaged tissue,
e.g., connective tissue.
[0007] Applicant has obtained the following patents related
to this invention. U.S. Patent No. 5,929,050 issued on July 27,
1999, titled "Chondroitin Sulfate Composition And Method For
Wound Treatment" describes a composition and method for treating
open wounds comprising the application or injection of a
sterilized aqueous solution of 90 to 110 mg/mL chondroitin
sulfate which can contain hydrolyzed collagen, sodium
hyaluronate, and glucosamine sulfate or chloride.
[0008] U.S. Patent No. 6,136,341 issued on October 24, 2000,
titled "Collagen Containing Tissue Adhesive" describes a method
for applying a wound dressing composition comprising a
hydrolyzed Type I collagen having an average molecular weight of
1,000 to 10,000 gm. with uncleaved peptide ends in a physical
form of either a powder, gel, paste, and film. The composition
can include a cross-linking agent selected from the group
consisting of a humectant, propylene glycol, sorbitol, and
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glycerine. A preservative such as benzyl alcohol or paraben can
be added. The wound dressing method consisting essentially of
the steps of: (a) debriding and cleansing an open wound site
with a saline solution; (b) drying surrounding skin; (c)
applying the claimed composition; (d) applying a nonsticking
dressing; and (e) repeating steps (b) to (d) every 24 hours.
[0009] The use of medical hydrolysates and collagen in wound
healing has been the subject of previous patents. U.S. Patent
No. 5,498,606 issued to David B. Soil et al. on March 12, 1996,
describes the protection against exfoliation of the cells of the
coverings and linings of internal human and animal tissues by
the topical application or injection of 40 to 55 wt.% of the
three isomers A, B and C of chondroitin sulfate prior to or
during the trauma, using as (1) a surgical irrigating solution,
(2) interarticular injection into joints for protecting the
joint cells, (3) reducing aseptic inflammation, and (4) can be
used for preserving human and animal cells and tissues for later
in vivo use and stored by adding 1 to 20 wt.% of the storage
solution. Chondroitin sulfate A is derived from whale
cartilage; chondroitin sulfate B is derived from porcine skin;
and chondroitin sulfate C is derived from shark cartilage.
U.S. Patent Nos. 4,216,204 and 4,455,302 issued to Harry J.
Robertson on August 5, 1980, and June 19, 1984, respectively,
describes a medical protein hydrolysate and processes for making
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and using the protein hydrolysate. The protein hydrolysate is
made in powder or gel form from ground poultry feet for
application to traumatized areas. The composition is
distinguishable for being obtained from young poultry feet.
[0010] Other patents describe the use of collagen in various
wound dressings. U.S. Patent No. 4,759,354 issued to Alan J.
Quarfoot on July 26, 1988, describes a wound dressing including
a vapor-permeable layer and an absorbent adhesive layer
containing collagen. U.S. Patent No. 4,837,024 issued to Dov
Michaeli on June 6, 1989, describes compositions, articles and
methods for improving wound healing. The wound is contacted by
a combined suspension of collagen and a mixture of chemotactic
glycosaminoglycans (heparin, heparin sulfate and alginate) for
improved healing. U.S. Patent No. 4,950,699 issued to Daniel G.
Holman on August 21, 1990, describes a wound dressing
incorporating 0.1% to 10% collagen by weight in a water-based
acrylic adhesive layer. U.S. Patent No. 5,081,106 issued to J.
Peter Bentley et al. on January 14, 1992, describes a wound
dressing protocol utilizing collagen (atelopeptide) gelatin
formed with iodine. U.S. Patent No. 5,116,620 issued to Milos
Chvapil et al. on May 26, 1992, describes an antimicrobial wound
dressing, having a layer of collagen impregnated with
lyophilized, stabilized chlorine-containing compounds, e.g.,
sodium chlorate and sodium chlorite, to generate chlorine
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dioxide, and citric acid. U.S. Patent No. 5,759,570 issued to
Peter S. Arnold on June 2, 1998, describes a multi-layer wound
dressing comprising a wound contact layer (collagen material),
an absorbent layer and an outer protective membrane. U.S.
Patent No. 6,022,557 issued to Franz Maser on February 8, 2000,
describes a wound covering material based on partially modified
collagen fibers with amidated nitrogen, glucosamine and
galactosamine. U.S. Patent No. 4,407,787 issued to Axel
Stemberger on October 4, 1983, describes a dressing containing
collagen in combination with a resorbable biopolymer (fibrinogen
or gelatin). U.S. Patent No. 4,265,233 issued to Akio Sugitachi
et al. on May 5, 1981, describes a wound healing material
containing collagen with a blood coagulation Factor XIII fixed
thereto which promotes formation of stabilized fibrin at the
wound site. U.S. Patent No. 4,294,241 issued to Teruo Miyata on
October 13, 1981, describes a method for preparing collagen skin
dressing in gel or sheet form from enzyme-solubilized and/or
chemically modified collagen. U.S. Patent No. 5,196,185 issued
to Fred Silver et al. on March 23, 1993, describes a collagen-
based wound dressing and a method of application. The dressing
uses 1 to 50 micron size type I and/or type III collagen in an
aerosol delivery system. U.S. Patent No. 4,347,234 issued on
August 31, 1982, to Helmut Wahlig et al. describes a collagen
containing shaped mass composition comprising collagen and a
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polymer selected from hydroxyalkanoic acids, amino acids,
hydrolyzed collagen, and hydrolyzed elastin. U.S. Patent No.
4,344,967 issued on August 17, 1982, to Ian A. Easton et al.
describes a film forming composition comprising a partially
hydrolyzed collagen protein having a molecular weight from 3,000
to 45,000, glycerol and ethanol to form a protective barrier on
a cow's teats. U.S. Patent No. 4,416,873 issued on November 22,
1983, to Eugene Puchalski et al. describes an allantoin-
hydrolyzed collagen containing cologne, after-shave lotion or
skin toner. U.S. Patent No. 4,804,745 issued on February 14,
1989, to Peter Koepff et al. describes hydrolyzed collagens
added to agents for the treatment of arthroses. U.S. Patent No.
4,906,460 issued on March 6, 1990, to Wendy W. Kim et al.
describes the addition of hydrolyzed collagen and silk amino
acids to hair treatment compositions. U.S. Patent No. 5,114,718
issued on May 19, 1992, to Nalinkant C. Damani describes
sustained release compositions for treating periodontal disease
comprising collagen, an antimicrobial, and vitamins.
[0011] Type I collagen is found in numerous medical
applications in the patent literature. U.S. Patent Nos.
6,019,971 issued on February 1, 2000, and 5,720,955 issued on
February 24, 1988, to Howard L. Weiner et al. describe the
treatment of autoimmune arthritis by orally administering Type
I, II and III whole collagen protein or collagen peptide
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fragments. U.S. Patent No. 5,171,574 issued to Thangavel
Kuberasampath et al. on December 15, 1992, describes Type I bone
collagen particles used in a matrix for implants. The collagen
is treated with collagen fibril modifying substance such as
acidified acetonitrile, chloroform or dichloromethane. U.S.
Patent No. 5,676,967 issued to Jeffrey M. Williams et al. on
October 14, 1997, describes a mesh matrix wound dressing
comprising a mixture of Types I and III collagen with and
oligosaccharide. U.S. Patent No. 5,512,291 issued to Shu-Tung
Li on April 30, 1996, describes a method of making vascular
wound dressings from Type I collagen to repair blood vessels.
U.S. Patent No. 4,841,962 issued to Richard A. Berg et al. on
June 27, 1989, describes a wound dressing which promotes
progressive healing and comprises a crosslinked Type I or II
collagen matrix, a bioabsorbable adhesive coated on one surface
thereof, a multilayer polymer film secured to an opposite
surface thereof, and an adhesive layer. U.S. Patent No.
5,531,791 issued on July 2, 1996, to Lloyd Wolfinbarger, Jr.
describes a biocompatible collagen/ demineralized human bone
composite material formulated as a fluid injectable, gel or
rehydratable freeze dried paste. U.S. Patent No. 5,631,243
issued on May 20, 1997, to Charles D. Kelman et al. describes a
collagen-based viscoelastic solution containing
mucopolysaccharides for ocular visco-surgery. U.S. Patent No.
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5,639,796 issued on June 17, 1997, to Clarence C. Lee describes
an injectable composition for replacing body lubricating fluids
comprising polymer particles having a diameter between 4 to 150
microns selected from a group including chondroitin sulfate,
hyaluronic acid, alginate, collagen, and cross-linked elastin
and hyaluronic acid. U.S. Patent No. 5,654,009 issued on August
5, 1997, to Takehisa Hata et al. describes a delayed action
composition comprising a core of a drug and a swelling agent,
and an outer membrane comprising sodium hyaluronate or collagen
for dispensing by oral, intramuscular or subcutaneous means.
U.S. Patent No. 5,948,766 issued on September 7, 1999, to Adam
Milan et al. describes a hydrolyzed collagen (Type I and III)
composition combined with calcitonin, calcium salts and/or
progesterone for treating osteoporosis. The hydrolyzed collagen
obtained from gelatin or animal collagenic connective tissue has
an average molecular weight from 1 to 40 kDaltons. The
composition can be formulated in the form of paste, syrup,
solution granules, pills or powder. The composition is
distinguishable for being cross-linked.
[0012] U.S. Patent No. 6,162,787 issued on December 19, 2000,
describes a composition for treating arthritis comprising
insoluble native collagen Type II, glucosamine sulfate,
chondroitin sulfate, ascorbate, boron, and magnesium. The
medications can be administered orally in the form of a tablet,
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capsule, powder, suspension or an aerosol spray. The collagen
is obtained from the breastbone of healthy chickens. The
composition is distinguishable for treating arthritis and
containing boron and magnesium.
[0013] Other compositions and methods for aiding wound
healing have also been the subjects of previous patents, but are
less related to the present invention. Examples of previous
patents describing wound healing are diverse: U.S. Patent No.
4,813,942, issued to Oscar M. Alvarez on March 21, 1989,
describes a three-step wound treatment method and dressing,
wherein the third phase dressing contains 0.05% to 20%
hyaluronic acid; U.S. Patent No. 4,921,691 issued to Richard F.
Stockel on May 1, 1990, "describes spray-on wound dressing
compositions containing anti-bacterial organosilicon quaternary
ammonium salt chemically bonded to a polymer such as collagen;
U.S. Patent No. 5,300,306 issued to Carlos A. Alvarado et al. on
April 5, 1994, describes a tissue-equivalent membrane for
treating burns from bovine esophageal tissue; European patent
document 0 530 982 Al published on March 10, 1993, for James V.
Cartmell et al. describes a wound dressing for deep wounds
containing polyhydric alcohol, isophoronediisocyanate terminated
prepolymer, polyethylene oxide based diamine, sodium chloride,
and water; U.S. Patent No. 4,892,736 issued on January 9, 1990,
to J. Max Goodson describes an intra-pocket delivery device for
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treatment of periodontal diseases comprising tetracycline mixed
with ethylene vinyl acetate copolymer; and European patent
document 0 450 671 Al published October 9, 1991, for Wilhelmus
E. Hennick et al. describes a wound dressing and method of
preparing the same comprising a lower layer of an antibacterial
agent added hydrogel of a cross-linked polymer added to other
elastomer layers. U.S. Patent No. 5,064,653 issued on November
12, 1991, to Robert W. Sessions et al. describes an absorbent
hydrophilic foam composition for wound dressings comprising an
in situ reaction product of an isocyanate-capped polyether
prepolymer, a hydrophilic agent, alcohol, a wetting agent, and
water. U.S. Patent No. 5,332,579 issued on July 26, 1994, to
Anthony J. Umbdenstock describes nutritional supplement
compositions for optimizing cellular health for smoking and
alcohol addicted patients comprising amino acids, minerals,
vitamins, and herbs.
[0014] Chondroitin sulfate and other GAGs used to aid healing
or skin trauma have been the subject of the following patents.
U.S. Patent No. 4,808,570 issued on February 28, 1989, to Dov
Michaeli describes compositions and method for improving wound
healing, wherein the composition contains a suspension of 7-10
mg./ml. collagen and 250-350 microgm./ml. glycosaminoglycans
such heparin, heparin sulfate, and alginate which is not
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covalently crosslinked. The compositions are distinguishable
for teaching against the use of chondroitin sulfate.
[0015] U.S. Patent No. 4,640,912 issued on February 3, 1987,
to Marvin S. Hausman describes the use of "active" chondroitin
sulfate A and "active" chondroitin sulfate C to prevent cancer
cell implantation, bacterial infestation, trauma, irritation or
damage from foreign instruments in the kidney, renal pelvis,
ureter, bladder, urethra, etc. by irrigation with a solution
containing the chondroitin sulfate.
[0016] U. S. Patent No. 4,863,907 issued on September 5, 1989,
to Katukiyo Sakurai et al. describes cross-linked
glycosaminoglycans (GAGs) and their salts, but excluding
hyaluronic acid. The GAG can be chondroitin sulfate, heparin,
heparin sulfate, keratin sulfate or keratinpolysulfate, which is
reacted with either epichlorohydrin or epibromohydrin. Cross-
linked GAGs with a cross-linking index of 0.05 or more per mole
are used for various medical and cosmetic reasons. Cross-linked
GAGs are not used in the present invention.
[0017] U.S. Patent No. 5,366,964 issued on November 22, 1994,
to Richard L. Lindstrom et al. describes a viscoelastic solution
containing 0.01-10% chondroitin sulfate, 0.01-10% hydroxypropyl-
methylcellulose, and 0.01-10% sodium hyaluronate among other
ingredients for use in ocular and surgical applications.
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[0018] U.S. Patent No. 4,983,580 issued on January 8, 1991,
to David R. Gibson describes methods and materials for use in
corneal wound healing. A preferred embodiment includes
fibronectin and chondroitin sulfate in a corneal mortar
composition. Fibronectin is not used in the present invention.
[0019] U.S. Patent No. 5,399,351 issued on March 21, 1995, to
Edward Leshchiner et al. describes the preparation and use of
biocompatible viscoelastic gel slurries comprising a first phase
of GAGs cross-linked with a polysaccharide and a protein, and a
second phase comprising a polymer solution of either
polysaccharides, polyvinylpyrrolidone and polyethylene oxide. A
gel containing cross-linked GAGs controls adhesion formation
between tissues resulting from surgical intervention. Cross-
linked GAGs are not used in the present invention.
[0020] U.S. Patent No. 5,837,278 issued on November 17, 1998,
to Peter Geistlich et al. describes a resorbable collagen
membrane for wound healing comprising at least 90 wt.% collagen
which is cross-linked with formaldehyde, etc. and impregnate the
fibrous side of the membrane with a glycosaminoglycan (GAG) such
as hyaluronic acid, chondroitin sulfate, dermatin sulfate or
keratin sulfate. Cross-linked GAGS are not used in the present
invention.
[0021] U. S. Patent No. 5,871,767 issued on February 16, 1999,
to Keith E. Dionne et al. describes methods for treatment of
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neurodegenerative conditions by implanting a vehicle with a
biocompatible jacket in the form of a hollow fiber or a flat
sheet and a matrix core, wherein the matrix contains cross-
linked collagen and glycosaminoglycans (hyaluronic acid,
chondroitin sulfate, heparin, and heparin sulfate). Cross-
linked GAGS are not used in the present invention.
[0022] The following art describes various oral nutritional
products for improving various physiological functions of the
human body, and discussed according the perceived relevance to
the present invention.
[0023] U.S. Patent No. 5,141,928 issued on August 25, 1992,
to Lawrence Goldman describes ophthalmic medications containing
glycosaminoglycan polysulfates (GAGPS) or mucopolysaccharides
having a molecular weight in the range of 5,000 to 20,000
Daltons combined with antibiotics for treating eye infections
and antimicrobial agents such as pilocarpine or epinephrine for
glaucoma. GAGPS include chondroitin sulfate and hyaluronic acid
that contain hexosamines. The medicament composition is
distinguishable for its reliance on GAGPS, antibiotics, and
anti-microbial agents which is limited to human eye use.
[0024] U.S. Patent No. 1,950,100 issued on March 6, 1934, to
Lathan A. Crandall, Jr. et al. describes a chemical composition
for the treatment of migraine, urticarial eruptions, peptic
ulcers, and multiple sclerosis, inter alia. Chondroitin sulfate
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is combined with either calcium, magnesium or iron. The
composition is distinguishable for its sole ingredient
containing a sulfate which is useful only for other human
ailments than tissue and cell growth.
[0025] U.S. Patent No. 5,364,845 issued on November 15, 1994,
to Robert W. Henderson describes a therapeutic composition
administered in capsules for the protection, treatment and
repair of connective tissue in mammals. The medicament contains
250-3000 mg. glucosamine hydrochloride or sulfate, 50-1000 mg.
chondroitin sulfate and 150-950 mg. manganese ascorbate. The
dosages for human use are in the lower regions of the given
ranges. The composition is distinguishable from the present
invention for not requiring hydrolyzed or native collagen,
sodium hyaluronate, and L-malic acid.
[0026] U.S. Patent No. 5,438,043 issued on August 1, 1995, to
Olle Ljungqvist describes a hypotonic solution for ingestion by
patients undergoing surgery for suppressing insulin resistance.
The solution contains dextrin, maltose, glucose, sodium
chloride, and sodium hydroxide at a pH between 5.6 to 6.8. The
composition is distinguishable for its absence of every
ingredient in the present invention.
[0027] U.S. Patent No. 5,442,053 issued on August 15, 1995,
to Francesco della Valle et al. describes a pharmaceutical
composition and method for treating ophthalmic conditions,
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dermatological conditions, diseases of the mucous of the oral
and nasal cavities or diseases of the outer ear by administering
a salt of hyaluronic acid (alkali, alkali metal, magnesium,
aluminum or ammonium) combined with a pharmacologically active
substance such as erythromycin. The hyaluronic acid fraction
has an average molecular weight of 30,000 to 730,000 gm. . The
topical medicament can be applied as solids or in solution. The
pharmaceutical composition is distinguishable for its reliance
on only a hyaluronic acid salt and a multitude of
pharmacological substances for ophthalmic use.
[0028] U.S. Patent No. 4,006,224 issued on February 1, 1977,
to John F. Prudden describes a method and agent for treating
inflammatory disorders of the gastrointestinal tract by
administering 20 to 300 mg. per Kg. of body weight per day of D-
glucosamine hydrochloride in either solid or liquid form.
Lactose and cornstarch can be added for making tablets. The
composition is distinguishable for its limitation to only D-
glucosamine hydrochloride for treating gastrointestinal
problems.
[0029] U.S. Patent No. 5,252,339 issued on October 12, 1993,
to Manlio Cristofori et al. describes pharmaceutical
compositions for oral intake containing glucosaminoglycan
sulfate such as heparin, a thickening substance such as gum
arabic, a plasticizer such as diethylphthalate, and a surfactant
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such as sodium cholate. The compositions make possible the
absorption of the glycosaminoglycan sulfate in the intestine for
performance of their anticoagulant, fibrinolytic,
antithrombotic, antiatherosclerotic, and
antihyperlipoproteinemic properties. The compositions are
distinguishable for utilizing only one ingredient of the present
invention.
[0030] U.S. Patent No. 5,840,715 issued on November 24, 1998,
to Vito V. Florio describes a dietary regimen of a nutritional
supplement composition containing gamma-linolenic acid,
eicosapentaenoic acid and docosahexaneoic acid mixture, a
mixture of chondroitin sulfate, N-acetyl glucosamine sulfate,
glucosamine sulfate and manganese aspartate (Chondrox) for
treating arthritis. The composition is distinguishable for
requiring other organic acids with chondroitin sulfate and
glucosamine sulfate.
[0031] French Patent Application NO. 2.035.781 published on
December 24, 1970, for Jean Dumazert describes a glucosamine-
based medicament containing glucosamine chlorohydrate or acetyl
glucosamine and a lipotropic agent such as either betaine,
methionine or choline. The medicament is distinguishable for
containing only glucosamine chlorohydrate or acetyl glucosamine
and a lipotropic agent which are not included in the present
invention.
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[0032] German Patent Application No. DE 3445324 Al published
on June 12, 1986, for Erich Enghofer et al. describes a
synergistic composition for treatment of arthritis and contains
glucosamine and an anti-exudative venous agent such as aescin or
hydroxyethyl-rutoside. The composition is distinguishable for
showing only glucosamine and requiring an anti-exudative venous
agent.
(0033] U.K. Patent Application No. 896,940 published on May
26, 1962, for Chas. Pfizer & Co. describes a healing agent for
wounds of the body surface containing glucosasmine and/or N-
acetylglucosamine and glucosamine phosphate in a saline
solution. The composition is distinguishable for requiring a
phosphate salt of glucosamine.
[0034] Publications such as (1) Body Ammo Supplement, "Joint
Connection Capsules", Product Alert, October 27, 1997); (2)
Arthred-G (Product Alert, September 5, 1997); The Merck Index,
10th Edn., Entry No. 2297, 1983, pp. 2297 and 2298; (4) The
Merck Index, 12th Edn., Entry No.5747, 1996, p. 974; (5) Sigma
Catalog, "Biochemicals, Organic Compounds for Research and
Diagnostic Reagents"; and (6) H. Ansel et al., Ed., Pharma-
ceutical Dosage Forms and Drug Delivery, Chapter 8, "Parenteral
Medications and Sterile Fluids", 1995, pp. 286-336; describe,
respectively, (1) a capsule for nutritional support of
connective tissue comprising glucosamine sulfate, chondroitin
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sulfate and hyaluronic acid; (2) a powdered food supplement for
reconstructing bone cartilage comprising glucosamine sulfate,
chondroitin sulfate and hydrolyzed collagen; (3) citric acid as
another alpha-hydroxy di-acid; (4) use of malic acid as a
flavoring agent, flavor enhancer and acidulant in foods; (5)
glucosamine compounds; and (6) shows injection information,
electrolytes and vitamins.
[0035] These publications are distinguishable because only
parts of the present inventive composition are shown. More than
routine experimentation would be required to obtain the present
invention.
[0036] Although many wound dressings exist, there is still a
need for a wound dressing applicable in various forms, i.e.,
powder, gel, foam, paste or film, which will also reduce scars
and repair connective tissues and a method of application, i.e.,
topically or injected, using the beneficial properties of
hydrolyzed collagen as the basic ingredient for reduction of
skin injuries such as bedsores, diabetic wounds, and the like
without the addition of disinfectants such as alcohol and the
like.
[0037] None of the above inventions and patents, taken either
singularly or in combination, is seen to describe the instant
invention as claimed. Thus, a composition and method for
healing tissues solving the aforementioned problems is desired.
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SUMMARY OF THE INVENTION
[0038] The present invention is a method and composition for
healing tissues, promoting tissue and cell growth, protecting
cells and tissues, and for the reduction of scar tissue and the
repair of damaged animal tissues such as connective tissues by
administering a medicinal composition comprising hydrolyzed
collagen which serves as both the essential therapeutic
ingredient and as a pharmaceutical carrier when combined with at
least one other therapeutic agent. The medicinal composition
containing hydrolyzed collagen as a carrier is preferably
combined with hyaluronic acid or a salt thereof, or a
polysulfated glycosaminoglycan, or a glucosamine salt, or
mixtures thereof. The compositions of the present invention can
be administered in any physical form such a powder, a gel, a
paste, a foam, a film, a capsule, a tablet, a chewing gum, a
topically applied patch with adhesive and with a reservoir
system, a liquid which can be sprayed, taken orally or injected,
and a rehydratable freeze-dried paste or sponge.
[0039] The compositions according to the present invention
can be formulated as an oral or injectable nutritional
preparation. In addition to hydrolyzed collagen, the oral and
injectable nutritional preparations can include glucosamine
hydrochloride, chondroitin sulfate, sodium hyaluronate, a
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manganese salt such as manganese ascorbate (U.S.P. food grade),
and L-malic acid (U.S.P. food grade) which acts as a detoxifying
agent by ridding the body of lactic acid often found in
connective tissue.
[0040] It is believed that the underlying chemical mechanisms
involved for the compositions of the present invention are as
follows: (1) hydrolyzed collagen acts as a transport/carrier for
the larger molecules of hyaluronic acid, chondroitin sulfate,
glucosamine hydrochloride or sulfate; (2) hyaluronic acid is
rapidly hydrolyzed upon contact with the treated tissue surfaces
to the monosaccharides, i.e., glucuronic acid and N-acetyl
glucosamine, and (3) chemical binding is enhanced
chemotactically with the presence of hydrolyzed collagen.
[0041] The preferred main ingredient of the present
compositions is hydrolyzed Type I collagen. The collagen is
preferably derived from a bovine source such as any bovine bone
or skin, and preferably from calves less than one year of age.
The powder form has better hemostatic qualities than in a 60%
gel form. The hydrogel, i.e., gel, can be made from 5% to 85%
active collagen. The collagen-containing composition is
administered to the cleaned wound site where it absorbs the
exudate, provides a physical barrier to bacterial infestation,
reduces pain and expedites wound healing.
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[0042] In another aspect, the composition may be formulated
as a liquid eye drop in an aqueous solution prepared from
hydrolyzed collagen in combination with compounds selected from
hyaluronic acid or a hyaluronic acid salt, a polysulfated
glycosaminoglycan or glucosamine salt, carboxymethylcellulose, a
vasoconstrictor, such as tetrahydrozoline hydrochloride, and
hypertonicity agents, such as sodium chloride and boric acid.
[0043] Accordingly, it is a principal object of the invention
to provide a favorable environment that encourages wound healing
and scar reduction.
[0044] It is another object of the invention to protect the
wound bed and newly formed tissue including connective tissue.
[0045] It is a further object of the invention to conform to
any wound site.
[0046] It is an object of the invention to control the
evaporation of fluid, thereby acting as a barrier retaining a
moist environment.
[0047] It is a further object of the invention to reduce pain
at the wound site.
[0048] It is another object of the invention to protect the
wound from bacterial infection.
[0049] It is a further object of the invention to increase
chemotactic activity of the wound site.
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[0050] Still another object of the invention is to enhance
the body's natural healing ability by making resources readily
available.
[0051] It is also an object of the invention to provide an
oral or injectable nutritional composition for promoting the
healing of wounds and tissues in humans and animals.
[0052] It is a further object of the invention to provide an
injectable nutritional composition for tissue and cartilage
repair of either a chronic or an acute nature.
[0053] Yet another object of the invention is to provide an
oral or injectable nutritional composition for promoting the
healing of wounds in animals containing hydrolyzed collagen, a
glucosamine hydrochloride, sulfate, nitrate or iodide,
chondroitin sulfate, sodium hyaluronate, and L-malic acid.
[0054] It is an object of the invention to provide improved
elements and arrangements thereof for the purposes described
which is inexpensive, dependable and fully effective in
accomplishing its intended purposes.
[0055] These and other objects of the present invention will
become readily apparent upon further review of the following
specification.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
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[0056] The present compositions comprise hydrolyzed collagen,
which not only serves as the main therapeutic component, but
acts as a pharmaceutical carrier when preferably combined with a
medicinal agent selected from the group consisting of hyaluronic
acid and salts thereof, a polysulfated glycosaminoglycan, a
glucosamine salt, and mixtures thereof to aid tissue and cells
to grow and wounds to heal as quickly as possible.
[0057] In a preferred embodiment of the present invention,
uncleaved hydrolyzed collagen is the main active ingredient.
However, cleaved hydrolyzed collagen exhibits beneficial
activity and can also be used. In uncleaved hydrolyzed
collagen, the terminal peptide groups remain and are not lost or
chemically altered in use. In cleaved collagen the terminal
peptide groups are chemically removed during preparation or from
the uncleaved product.
[0058] Hydrolyzed collagen has an increased number of
chemically active sites as compared to native collagen. Native
collagen typically has a molecular weight within the range of
100 to 300,000 Daltons. A native collagen molecule can have
four chemically active sites. Therefore, not only is hydrolyzed
collagen chemically more active, but its chemotactic properties
are logarithmically increased versus that of native collagen.
In addition, the hydrolyzed collagen composition of the present
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invention exhibits excellent thermal stability, which is not
associated with native collagen.
[0059] Hydrolyzed collagen is defined as a collagen
hydrolysate polypeptide having a molecular weight lower than
native collagen, i.e., in the 100 to 300,000 Daltons range, and
is derived by hydrolysis. Hydrolyzed collagen is commercially
available in powdered form or an aqueous solution. Commercial
preparation is typically accomplished by one of four methods:
(1) alkaline hydrolysis; (2) enzymatic hydrolysis; (3) acid
hydrolysis; and (4) synthetically by fermentation. Any of these
methods can be used to derive the hydrolyzed collagen from
either a bovine (bone and skin preferred), porcine, fish, avian
or a synthetic source. The types of amino acid constituents
and their sequences determine the beneficial healing qualities
of hydrolyzed collagen. Hydroxylysine and hydroxyproline are
amino acids found only in collagen and in no other medical
protein hydrolysates. Hydroxylysine is typically found in
concentrations from 0.7 to 1.2 wt.% in hydrolyzed collagen.
Hydrolyzed collagen is well suited for use as a tissue adhesive,
because it accelerates the healing process by functioning as a
protective barrier and covering for forming tissues and cells.
[0060] The compositions of the present invention preferably
contain hydrolyzed type I collagen as one ingredient having a
molecular weight by definition ranging from 1,000 to 10,000
CA 02708068 2010-06-22
Daltons. This composition can contain a molecular weight from
50,000 to 100,000 Daltons of hydrolyzed collagen. The source of
the collagen is preferably bovine and especially bovine bone or
skin.
[0061] The tissue adhesive properties of hydrolyzed collagen
allow for faster healing, and can, sometimes, negate the need
for sutures or other closure means. The hydrolyzed collagen can
be combined with hyaluronic acid, and/or glycosaminoglycans to
further speed the healing process, decrease scarring and
increase tissue strength.
[0062] Hyaluronic acid (HA) is rapidly hydrolyzed upon
contact with treated tissue surfaces to monosaccharides,
glucuronic acid and N-acetyl glucosamine. Chemical binding is
enhanced with the use of hydrolyzed collagen, i.e., it is
chemotactic. Hyaluronic acid can be used via injection into a
joint for its anti-inflammatory effect to relieve pain and
suffering. This curative effect is inherently terminated when
hyaluronic acid is consumed by the healing body.
[0063] Glycosaminoglycans (GAGs) are polysaccharides found in
vertebrate and invertebrate animals. Several GAGs have been
found in tissues and fluids of vertebrate animals. The known
GAGs are chondroitin sulfate, keratin sulfate, dermatic sulfate,
hyaluronic acid, heparin, and heparin sulfate. GAGs and
collagen are the major structural elements of all animal tissue.
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Their synthesis is essential for proper repair, treatment,
protection, and maintenance of all tissues.
[0064] Chondroitin sulfate, a polysulfated GAG, is a linear
polymer occurring in several isomers, named for the location of
the sulfate group. Chondroitin-4 sulfate is found in nasal and
tracheal cartilages of bovines and porcines. It is also found
in the bones, flesh, blood, skin, umbilical cord, and urine of
these animals. Chondroitin-6 sulfate has been isolated from the
skin, umbilical cord, and cardiac valves of the aforementioned
animals. Chondroitin-6 sulfate has the same composition, but
slightly different physical properties from the chondroitin-4
sulfate. These are the most common isomers used in the present
invention. The polymers are also known as polysulfated
glycosaminoglycans (PSGAGs), chondroitin polysulfate sodium,
chondrin, sodium chondroitin polysulfate, and sodium chondroitin
sulfate. For consistency, the term, "chondroitin sulfate", will
be recited for all chondroitin sulfate isomers throughout this
specification. Chondroitin sulfate is involved in the binding
of collagen, and is also directly involved in the retention of
moisture in the tissue. These are both valuable chemical
properties that aid the healing process.
[0065] Hydrolyzed collagen in combination with GAGs,
specifically a PSGAG such as chondroitin sulfate can be useful
for the prevention and treatment of wound diseases. The
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hydrolyzed collagen combines with a PSGAG to bond or adhere
selectively to tissue resulting in interference with and/or
displacement of bacterial or other infectious agents. In
addition, the combination product would exhibit anti-enzyme
activity or the ability to inhibit enzyme activity.
[0066] The compositions of the present invention containing
hydrolyzed collagen in combination HA and/or PSGAGs have been
found to significantly reduce scarring at a wound site, because
of enhanced wound healing rates. Thus, tissue strength of the
healed wound site is greatly enhanced. The wound site closure
rate and the lack of scar tissue are directly responsible for
higher tissue strength in the closure area.
[0067] The hydrolyzed collagen accelerates the healing
process by allowing an injured tissue to repair itself by
producing and remodeling more collagen and other proteoglycans
(PGs). The building blocks for collagen production are the
amino acids found in hydrolyzed collagen. The hyaluronic acid
and other proteoglycans (PGs) provide the framework for collagen
production to follow. The PGs hold water to provide an
excellent environment for healing of the tissue to begin. When
in the wound site, any unused collagen that was produced is
simply degraded to the amino acid. The rate-limiting step in
the production of collagen is the conversion of glucose to
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glucosamine for the production of hyaluronic acid and other
glycosaminoglycans (GAGS).
[0068] The medicinal compositions of the present invention
can take the physical form used in topical administration
selected from the group consisting of gel, spray, powder, paste,
foam, film, and incorporation in a dressing bandage, a topically
applied patch or in internal administration form selected from
the group consisting of an injectable liquid and an orally
ingestible liquid.
[0069] The powdered hydrolyzed collagen can be combined with
either powdered hyaluronic acid or a 1% solution of hyaluronic
acid sprayed secondarily to the primary dressing of hydrolyzed
collagen. When both the hydrolyzed collagen and the hyaluronic
acid are combined, the hydrolyzed collagen acts as carrier for
the high molecular weight hyaluronic acid to the injured cell
site. This combination forms an excellent environment by
providing occlusion, i.e., to close off, and a moisturizing
benefit.
[0070] The powder form will preferably have a moisture
content of approximately 2-10 wt.% and a pH range of 5.5 to 6.5.
The powder composition will have an ash content of less than 2.5
wt.o and an isotonic point of 5.0 to 6.5. In use, the powder
composition may be the preferred physical form for use with
irregularly shaped wounds. Tunnel wounds, flaps, and other non-
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conformative sites may be managed with the powder composition
because it easily conforms to any shape wound, and may be
applied by a poofer bottle or otherwise blown into difficult to
reach wound sites. The powder is especially useful in wounds
with a large amount of exudate, as the powder can absorb nearly
30 times its own weight. As the powder absorbs the exudate, a
gel is formed which completely fills the wound site, forming a
mechanical barrier against bacterial infection. The powder does
not exhibit the characteristic fly-away when being applied to
the wound site, and administration is perfected due to the
precise powder placement.
[0071] The gel form of the medicament composition is
especially useful in wounds with lesser amounts of exudate,
burns, and surgical sites. Application of the gel can be
dispensed through a tube, syringe or the reservoir in the
topical patch. The gel is made of approximately 1-75 wt.%
hydrolyzed Type I collagen and 1-99 vol.% water. It is
preferable to use approximately 60 wt.% collagen. The gel is
formed by adding sterile water to the powder. The gel has the
added advantage of adding moisture to the wound site, inherent
bacteriostatic properties and stays positioned where applied.
[0072] The present invention can be utilized in dental
applications, wherein the gel form was utilized as a
bacteriostatic agent for angular chelitis and resulted in
CA 02708068 2010-06-22
exceptional tissue adhesion, accelerated wound healing, and
tissue protection. The gel form can protect a high bacteria
containing dental wound site such as the aforementioned angular
chelitis, periodontal disease and other oral surgical sites.
Therefore, by adding small amounts of chlorohexadine gluconate,
parachloro-metaxylenol or other antimicrobial compounds, that
the final product would be a "smart gel" capable of effective
bacterial control and enhanced rates of healing wounds. It
should be noted that utilizing antimicrobial compounds, per se,
without the other ingredients would result in killing all the
good and bad cells. It has been found that testing with various
pain-killing materials such as benzocaine, that the hydrolyzed
collagen as the major constituent in a base composition of
glycerine, sorbitol and a cross-linking agent is an exceptional
vehicle or carrier for incorporating other entities into the
cell structure. They are effective wound healing agents when
either used alone or with other entities such as antibacterials,
microbials, zinc, alginate, aloe, vitamins C and E, native
fibril collagen, and other proteoglycans and glycosaminoglycans.
This product has been cleared by the Food and Drug
Administration for the following dental indications: dental
sore, oral ulcers, periodontal surgical wounds, suture sites,
burns, extraction sites, and traumatic wounds which includes
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orthodontic bracket irritation, angular chelitis, and dry
pockets.
[0073] A film form of the medicament composition may be made
by mixing under heat at 155-175 F. the powdered form with
deionized water. Cross-linking and other agents such as
humectant, propylene glycol, sorbitol, and glycerine are added
to the mixture. A preservative such as benzyl alcohol or
paraben can be added. The mixture is cast on a belt liner by
knife on a roll coating machine to form a liquid film which is
oven-dried. The film form can also be formed by a cooling the
liquid solution. These films can be used for drug or other
chemical delivery, and especially in dental applications.
Antimicrobial and other medicinal agents can also be added to
the film as needed for specific applications.
[0074] It is known that hyaluronic acid can be injected into
an injured joint for its anti-inflammatory effect. Further
benefits are the relief of pain and swelling. These effects
disappear when the hyaluronic acid is consumed by the injured
body portion. The hyaluronic acid is believed to accelerate the
initiation of the healing process by allowing the injured
tissues to repair by manufacturing and remodeling more collagen
and other proteoglycans. The building blocks for collagen
production are the amino acids found in the hydrolyzed collagen.
The hyaluronic acid and other proteoglycans provide the
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framework for collagen production to follow. The proteoglycans
hold water to provide for an excellent environment for the
healing process to begin. Any unused collagen that was produced
is simply degraded back to the amino acids. The proteoglycans
have an inherent rate-limiting production. The rate limiting
step is the conversion of glucose to glucosamine for the
production of hyaluronic acid and other glycosaminoglycans.
[0075] The hydrolyzed collagen acting as a carrier of
hyaluronic acid which enhances the absorption of large
molecules, provides for healing effects and an environment
conducive to healing. The present invention provides for the
body's ability to continue to convert the hydrolyzed collagen
into proteoglycans for aiding the repair of both connective
tissue and other tissues in humans and animals.
[0076] In another embodiment of the present invention,
hydrolyzed collagen and hyaluronic acid are further combined
with polysulfated glycosaminoglycans, glucosamine hydrochloride
or sulfate to provide an oral or injectable nutritional
composition for repair of wounds and tissue. Glycosaminoglycans
and collagen are the chief structural elements of all tissues.
Their synthesis is essential for proper repair, treatment,
protection, and maintenance of all tissues. The oral and
injectable nutritional compositions of present invention
preferably include in addition to hydrolyzed collagen,
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glucosamine hydrochloride, chondroitin sulfate, sodium
hyaluronate, a manganese salt, and L-malic acid (U.S.P. food
grade). A major advantage of the present invention is the
perfecting of a vehicle which allows for the formulations of
excellent preparations free from concentration gradients of the
active substances, and which, therefore, are perfectly adhesive,
somewhat transparent and homogeneous without potential
sensitization effects. The inventive compositions can include
salts such as sodium, potassium, calcium, barium, magnesium,
aluminum, and the like and various antimicrobials and
antibiotics. Therefore, these salts can be added to produce
gels, ointments, creams, and inserts.
[0077] The hydrolyzed collagen can be used as an excellent
drug vehicle system containing acidic, neutral or complexed drug
medications.
[0078] Testing of a composition of hydrolyzed collagen and a
1% solution of hyaluronic acid was performed on full thickness
wounds in mice. The applied composition on wounds and scars
resulted in reduced scar formation and faster healing rates. In
combination with a polysulfated glycosaminoglycans alone and
with 1% hyaluronic acid, exceptional tissue granulation was
observed. With the use of the polysulfated glycosaminoglycans,
a novel method of dressing a wound site was used by injecting
the composition directly into and under the thin film wound
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dressing without ever exposing the wound site to further
environmental contamination. The hydrolyzed collagen can be
used for the first few days of treatment, followed by the
injection of the polysulfated glycosaminoglycans to the wound
closure. Thus, hydrolyzed collagen was shown to be an efficient
vehicle capable of enhancing the bioavailability of hydrolyzed
collagen and other glycosaminoglycans, and strengthening their
activity.
[0079] In other applications, hydrolyzed collagen in
combination with hyaluronic acid and polysulfated
glycosaminoglycans can be used as a protective agent prior to
and after surgery to minimize cell damage and to expedite wound
healing. This combination can be used during surgery to foster
separation of tissue to prevent adhesion formation. It is noted
that when hydrolyzed collagen is used alone, it becomes an
excellent tissue adhesive, but when combined with other
proteoglycans, it assumes a chemotactic position for use in
accelerated wound healing.
[0080] The delivery systems for providing the inventive
composition to a wound are manifold. In powder form, various
delivery systems are packets, bottles, unit dosages, and
aerosols. In paste form, the hydrolyzed collagen in water
composition is delivered in either jars, open containers, tubes,
reservoir island dressings or filmed reservoirs. In spray form,
CA 02708068 2010-06-22
the hydrolyzed collagen composition is delivered in liposome
carriers with a pump container containing aerosol or in water.
A liposome carrier is defined as an artificial vesicle composed
of one or more concentric phospholipid bilayers. In foam form,
conventional foams are impregnated with either the gel or powder
form of the hydrolyzed collagen compositions. In sponge or
paste form, the composition can be supplied as a rehydratable
freeze-dried form. In injectable form, the hydrolyzed collagen
compositions are water-based.
[0081] It has been found that the compositions containing
hydrolyzed collagen combined with hyaluronic acid and/or
glycosaminoglycans act as tissue cell protectorants. Therefore,
these compositions can also be used for preserving tissue or
organ implants such as donor organs. A preservative composition
in solution form can comprise 5% hydrolyzed collagen, 3% of a 1%
solution of hyaluronic acid, and 3% polysulfated
glycosaminoglycans in wt./wt. in water.
[0082] It has been also found that compositions of a
hydrolyzed collagen and/or polysulfated glycosaminoglycans can
be utilized in film form to avoid undesired adhesions between
injured surfaces. An added advantage that the film form is
biodegradable and can be utilized by natural means in in vivo
degradation in the living body.
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[0083] In the situation of diabetic patients with open sores
and wounds, oral treatment with compositions containing
hydrolyzed collagen, glucosamine hydrochloride or sulfate,
chondroitin sulfate, and L-malic acid has been found to be very
effective. In addition, vitamins A, C and E with magnesium
oxide, chelated manganese, grape seed extract, zinc, chromium
picolinate, selenium, and glycosaminoglycans can be added to
produce a nutrient composition for oral intake.
[0084] It has been established that the hydrolyzed collagen
used as a carrier in powder form, paste or a lyophilized foam
has hemostatic qualities when combined with thrombin to improve
healing of wounds. Antimicrobials can be combined with the
hydrolyzed collagen to further enhance its bacteriostatic
quality, as can antibiotics, such as tetracycline, streptomycin,
cephalosporin and antibacterials, such as iodine,
parachlorometaxylenol, and chlorhexidine gluconate or acetate.
[0085] Hydrolyzed collagen combined with a polysulfated
glycosaminoglycans such as chondroitin sulfate will also prevent
wound diseases. The hydrolyzed collagen combines with a
polysulfated glycosaminoglycans to bond or adhere selectively to
tissue resulting in interference with and/or displacement of
bacterial or other infectious agents. In addition, the
combination product would inhibit anti-enzyme activity.
37
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[0086] It has been found that the following composition has
provided the above-mentioned beneficial results in both animals
and humans. The unit dose will be described for a human in
terms of dosage per bodyweight. Animals may require larger
doses due to larger weights.
[0087] (1) Glucosamine hydrochloride or other salts of
glucosamine such as the sulfate, nitrate or iodide, which are
obtained from either synthetic, bovine or porcine sources having
a molecular weight range from 5,000 to 30,000 Daltons.
[0088] (2) Chondroitin sulfate, Type A (chondroitin-4-
sulfate). Type B (chondroitin-5-sulfate), and/or Type C
(chondroitin-6-sulfate, obtained through fermentation or
extraction of bovine trachea, other bovine or porcine sources.
A molecular weight range of 5,000-50,000 Daltons can be used,
with a preferred range of 25,000-35,000 Daltons.
[0089] (3) Hydrolyzed Type I collagen, preferably natural
hydrolyzed collagen powder having a pH of 5.0-6.5, and obtained
from the bone, skin and tissue of a bovine calf less than a year
old. Preferably, the hydrolyzed Type I collagen has a molecular
weight range no greater than about 1,000 to about 1,500 Daltons.
[0090] (4) Sodium hyaluronate obtained from either synthetic,
bovine or avian sources with a molecular weight range from about
50,000 to about 3,500,000 Daltons.
[0091] (5) Manganese ascorbate, U.S.P. food grade.
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[0092] (6) L-malic acid, U.S.P. food grade, acts as a
detoxifying agent by ridding the body of lactic acid often found
in connective tissue.
[0093] For injectable use, the above substances will be
dissolved in sterilized water and buffered with citric acid or
sodium chloride to improve shelf life. The pH can be adjusted
with conventional agents. Also, preservatives such as ethylene-
diaminetetraacetic acid (EDTA), benzyl alcohol, and benzalkonium
chloride can be added. Powdered, encapsulated or pilled
compositions to be taken orally by either humans or animals are
base on mg/kg bodyweight and described in the following order of
(a) a preferred concentration, (b) an optional range, and (c) a
broad range in terms of the aforementioned numbered ingredients
(1) to (6).
(1): (a) 5 mg.; (b) 3-8 mg.; (c) 2-10 mg.
(2): (a) 3.5 mg.; (b) 1-6 mg.; (c) 1-8 mg.
(3): (a) 4 mg.; (b) 3-15 mg.; (c) 2-20 mg.
(4) : (a) 5 mg.; (b) 2-6 mg.; (c) 1-7 mg.
(5): (a) 1 mg.; (b) 0.5 mg.; (c) 0.5-3 mg.
(6) : (a) 5 mg.; (b) 0.2 mg.; (c) 0.2-6 mg.
[0094] For injectable use in humans, the following
compositions are recommended as a first preference, a second
preference and a third preference. First: (1), (2), (4);
second: (1) to (4); and third: (1) to (6).
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[0095] For injectable use in animals, the following
compositions are recommended as first, second and third
preferences. First: (1), (2), (4); second: (1), (2), (4), (6);
third: (2) to (6); fourth: (1) to (4); and fifth: (1) to (6).
[0096] In terms of injectable solutions in weight of
ingredient per volume of a sterilized aqueous solution for human
and animal, the following preferred concentrations and ranges
are: (1) 150 mg./ml., 10-1,000 mg./ml.; (2) 150 mg./ml., 5-1,500
mg./ml.; (3) 2-100 mg./ml.; and (4) 5 mg./ml., 1-30 mg./ml.
However, ingredients (5) and (6) can be added, i.e., manganese
ascorbate and L-malic acid.
[0097] Unlike the compositions described in the prior art, it
is believed that the present composition provides an enhanced
chondroprotective effect by providing foundational support for
the creation of new body tissue and cartilage growth in mammals
because it comprises hydrolyzed Type I collagen having a
preferred molecular weight average no greater than 2,000
Daltons. More preferably, the hydrolyzed Type I collagen has a
molecular weight average of about 1,000 to 1,500 Daltons. It is
believed that the hydrolyzed Type I collagen having a preferred
weight average no greater than about 2,000 Daltons, acts as a
transporter or carrier for the larger molecules of sodium
hyaluronate and/or chondroitin sulfate by aiding in the
CA 02708068 2010-06-22
absorption process of these large molecules, thereby increasing
the bio-availability of each.
[0098] The following case studies illustrate the benefits of
hydrolyzed collagen applied to various tissue damage situations.
[0099] Case study 1: A diabetic patient had an advanced
wound of a 14 year old graft site 5.4 by 1.8 cm. in area from
amputation of 15% of one infected foot. The patient received
weekly applications of biodegradable hydrolyzed collagen in
powder and gel form absent preservatives or alcohols. The wound
healed in 27 days.
[0100] Case study 2: A patient having pressure ulcers or
bedsores and post-surgical wounds from first and second degree
burns. A gel and powder barrier of hydrolyzed collagen and
debridement therapy for two days removed the eschar and
minimized scarring.
[0101] Case study 3: An open wound was treated with Type I
collagen hydrolysate containing 19 amino acids with the powder
and gel forms which were never removed. The powder form was
blown into the cavity and the gel form was topically added.
When Type I collagen, being stronger, was added to infants and
small children having wounds, scarring was minimal and
superficial cuts and burns healed rapidly.
[0102] Case study 4: A foot wound of a diabetic patient
showed signs of infection, reddened, painful, foul smell of the
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drainage, gangrene, and a large ulcer. The wound was washed
with saline solution, collagen hydrolysate powder was added
topically. Saran wrap covered the wound and was secured by
tape. The dressing was changed daily for a successful cure.
[0103] Case study 5: An ankle ulcer of a diabetic patient
showed dysfunction (loss of feeling), and a yellowish exudate
which was cleaned with a saline solution. Debridement was
performed with a soft brush wet with saline solution.
Hydrolyzed collagen powder was applied and a non-stick pad was
secured with adhesive tape. The dressing was changed daily for
a successful recovery.
[0104] Case study 6: For an advanced wound, Type I
hydrolyzed collagen in the gel form was applied and noticeably
reduced scarring and blocked nerve pain.
[0105] Case study 7: A female patient had 1,000 sutures
resulting from an liposuction operation. Application of
hydrolyzed collagen was added in gel form and the wounds healed
in six days.
[0106] Case study 8: A 54 year old paraplegic male patient
having a Stage 3 pressure ulcer on the heel of his deformed
atrophic foot was treated with hydrolyzed collagen and cured in
weeks.
[0107] Case study 9: A 69 year old male patient having a
history of venous stasis ulcers and a bacterial infection on
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dorsum of foot was previously treated with calcium alginate for
over a year. Hydrolyzed collagen was administered with
antibiotics and the wound was completely healed in 3 months.
[0108] Case study 10: A 46 year old female patient developed
an infection in her jaw in the area of her enioglossus pull
through. Hydrolyzed collagen was applied twice a day until she
was cured in one month.
[0109] Case study 11: Three patients having at least a two
year history of pilonidal cysts on their buttocks were treated
with a bacteriostatic hydrogel sheet and hydrolyzed collagen
powder to be cured in 3 to 6 months.
[0110] Case study 12: A 77 year old patient had a
penetrating gastric ulcer and periesophageal hernia -which
required surgical repair. After 10 days, the patient had a
surgical abscess which was treated with calcium alginate for a
month without any wound healing. Then hydrolyzed collagen
powder treatment was initiated with wound closure in 30 days,
and a full recovery in 36 days.
[0111] Case study 13: A 5.4 cm. by 1.8 cm. wound on a 14
year old graft site on a lower left leg of a patient was
initially treated with an enzymatic debrider and a hydrocolloid
cover. Calcium alginate was added a week later, but there was
minimal closure. Hydrolyzed collagen was applied and covered
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with calcium alginate and a hydrocolloid. In three months,
there was wound closure.
[0112] Case study 14: A 30 year old male patient suffering
from a deep chronic ulcer on the right medial malleolus due to a
vehicular accident was treated with hydrolyzed collagen daily
and the 3 cm. long, 0.8 cm. wide and 0.5 cm. deep wound healed
in 7 months.
[0113] Case study 15: A female at-home patient having a
pressure wound on one heel was treated antibiotics but resisted
wound healing for a month. Hydrolyzed collagen was administered
for 3.5 months with a complete recovery and wound closure.
[0114] Case study 16: A 56 year old overweight female
patient had a traumatic left heel injury with resulting surgical
repair of the Achilles tendon. The wound measured 2.0 cm. x 0.8
cm. x 0.1 cm. with a yellow slough and considered a Stage III
wound. For almost two months, other medications were utilized
without any improvement. Then hydrolyzed collagen gel treatment
was initiated when the wound measured 4.2 cm. x 0.7 cm. with
peri-wound redness and edema. The gel treatment provided wound
healing and decreased the wound size within the first week of
treatment and no sign of infection throughout the treatment.
[0115] Case study 17: The hydrolyzed collagen gel
composition was found superior to other hydrogels. The honey-
like consistency of the invention was advantageous in keeping
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the medication where it is applied and did not add to the
exudate load, especially in the tunneling wound. This feature
makes it more feasible to apply transparent film dressings over
the gel rather than a gauze or even a non-stick pad, thus
increasing the visibility of the wound bed between dressing
changes.
[0116] Case study 18: The gel form of hydrolyzed collagen
was used on a degloving injury on a small dog with very good
results.
[0117] Case study 19: The gel form of hydrolyzed collagen
was used on a cat having a chronic corneal ulcer for at least
two months, which would have needed enucleation of the eye. The
eye healed in less than three weeks and did not leave a
noticeable scar.
[0118] Case study 20: A dog's elbow with a chronic skin
ulcer healed in three weeks by adding the hydrolyzed collagen
composition. Foot pad lacerations with or without a bandage
also healed dramatically within two weeks.
[0119] Case study 21: A dog's foot pad lacerations also
healed dramatically within two weeks with treatment of the
hydrolyzed collagen composition.
[0120] Case study 22: A dog suffered from an inguinal wound
cm. by 1 cm. which extended through the fascia to the muscle
sheath and became infected. Hydrolyzed collagen powder was
CA 02708068 2010-06-22
added topically to the wound and interacted with the wound
exudate to form a gel which dried to a protective coating. By
the fourth day of treatment, the wound was covered with a newly
formed granulation tissue bed. On the tenth day, a healthy bed
of granulation tissue had formed. On the fifteen day, skin
contraction was evident, and the wound was left uncovered to
heal without a bandage. On the twenty-first day, the wound was
completely healed.
[0121] Case study 23: A stray poodle was found with an
injury of the lateral aspect of the left tarsus, starting at the
hock and extending distally. The wound measured 8 cm. by 3 cm.
and covered 25-50% of the circumference of the leg. The wound
was treated for three days with hydrolyzed collagen powder,
wherein a gel with the exudate was formed which provided a moist
healing environment conducive to healing. A newly formed
granulation tissue bed had formed. After the sixth day after
application every 2 to 3 days, a betadine soak was used to
debride necrotic tissue. The wound site was reduced to 5.5 cm.
by 1.2 cm. at the hock. After 16 days of treatment, there was
increased skin contracture and good epithelialization of the
wound bed, with the wound measuring 5 cm. by 0.4 cm. at the
tarsus and at the hock. Three days later, the wound was left to
heal without a bandage. In three weeks and four days, the wound
had healed completely.
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[0122] In these case studies, neither preservatives nor
alcohols were used.
[0123] In yet another embodiment the composition containing
hydrolyzed collagen can be formulated as a liquid eye drop. The
liquid eye drop formulation of the present invention is an
aqueous solution prepared from hydrolyzed collagen in
combination with compounds selected from hyaluronic acid or a
hyaluronic acid salt, a polysulfated glycosaminoglycan or
glucosamine salt, carboxymethylcellulose, tetrahydrozoline
hydrochloride, and hypertonicity agents, such as sodium chloride
and boric acid.
[0124] Hydrolyzed collagen serves as a pharmaceutical carrier
for active and inactive ingredients in the solution. The
collagen may be derived from any source, including porcine
sources, fish, chicken (poultry), bovine sources, and
synthetic/fermentation procedures. Hydrolyzed collagen
functions to provide healing and lubricity to the eye tissue and
surrounding membrane, as well as providing a soothing and
calming effect on the eye. It is highly chemotactic in that it
attracts other chemical compounds selectively to aid in the
healing process.
[0125] Hyaluronic acid, often provided as the sodium salt,
sodium hyaluronate, has been used in previous work with the eye,
but in such applications hyaluronic acid has not been used in
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conjunction with hydrolyzed collagen and other actives, such as
carboxymethylcellulose, tetrahydrozoline hydrochloride, and
polysulfated glycosaminoglycans. Hyaluronic acid is native to
the eye and is an anti-inflammatory. Hyaluronic acid provides
lubricity to the eye tissues thus healing and comforting the eye
tissues. Hyaluronic acid may be used as a carrier to provide an
environment in the eye for tissue repair.
[0126] In the present composition, the polysulfated
glycosaminoglycan primarily provides tissue healing, but also is
an anti-inflammatory, acts as a lubricant, and serves as a
carrier for other active ingredients. Polysulfated
glycosaminoglycan is native to the body and has synergistic
effects when combined with hyaluronic acid and hydrolyzed
collagen. The type of polysulfated glycosaminoglycan used in the
composition are isomers of chondroitin sulfate, such as
chondroitin sulfate A, B and C.
[0127] The composition may contain carboxymethylcellulose,
which provides lubricity and is a demulcent. The composition
may also contain a vasoconstrictor, such as tetrahydrozoline
HC1, ephedrine HC1, or naphazoline HC1, and hypertonicity
agents, such as sodium chloride and boric acid.
[0128] Preservatives such as benzalkonium chloride and
edetate disodium may be used in the composition. Adjustments to
the pH are made by using hydrochloric acid and sodium
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bicarbonate, as needed. The pH is adjusted to a range between
7.1 to 7.3.
[0129] The ranges of the active ingredients in the aqueous
eye drop composition are as follows:
Range (% wt.)
Hyaluronic acid 0.01-25
Hydrolyzed collagen 0.01-15
Polysulfated glycosaminoglycan 0.01-20
Carboxymethylcellulose up to 5.0
Tetrahydrozoline hydrochloride up to 5.0
Sodium chloride/Boric acid up to 8.0
[0130] Variations of the composition may be had utilizing
hydrolyzed collagen as a common ingredient. The composition may
include:
sodium hyaluronate
hydrolyzed collagen
Chondroitin sulfate/PSGAG
CMC
Tetrahydrozoline HCL
Sodium chloride
Boric acid
Hydrochloric acid (pH 7.1-7.3)
Sodium bicarbonate (pH 7.1-7.3)
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Purified water
Benzalkonium chloride
Edetate disodium
[0131] The aforementioned twelve ingredients may be combined
in any variation, the following being formula examples denoted
in %wt. by wt. In a first variation, the composition includes:
Sodium hyaluronate 0%
Hydrolyzed collagen 0.01%
Chondroitin sulfate/PSGAG 0%
CMC 2.5%
Tetrahydrozoline HC1 0.05%
Sodium chloride 1.0%
Boric acid 1.0%
Hydrochloric acid As needed
Sodium bicarbonate As needed
Purified water As needed
Benzalkonium chloride 0.01%
Edetate disodium 0.5%
[0132] In a second variation, the composition includes:
Sodium hyaluronate 0.5%
Hydrolyzed collagen 0.1%
Chondroitin sulfate/PSGAG 0.5%
CMC 1.0%
Tetrahydrozoline HC1 0.05%
CA 02708068 2010-06-22
Sodium chloride 1.0%
Boric acid 1.0%
Hydrochloric acid As needed
Sodium bicarbonate As needed
Purified water As needed
Benzalkonium chloride 0.01%
Edetate disodium 0.5%
[0133] In a third variation, the composition includes:
Sodium hyaluronate 1.0%
Hydrolyzed collagen 0.5%
Chondroitin sulfate/PSGAG 1.0%
CMC 0%
Tetrahydrozoline HCL 0%
Sodium chloride 1.0%
Boric acid 1.0%%
Hydrochloric acid As needed
Sodium bicarbonate As needed
Purified water As needed
Benzalkonium chloride 0.01%
Edetate disodium 0.5%
[0134] In a fourth variation, the composition includes:
Sodium hyaluronate 5.0%
Hydrolyzed collagen 3.0%
Chondroitin sulfate/PSGAG 5.0%
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CMC 0.01%
Tetrahydrozoline HCL 0.01%
Sodium chloride 1.0%
Boric acid 1.0%
Hydrochloric acid As needed
Sodium bicarbonate As needed
Purified water As needed
Benzalkonium chloride 0.01%
Edetate disodium 0.5%
[0135] It is to be understood that the present invention is
not limited to the embodiments described above, but encompasses
any and all embodiments within the scope of the following
claims.
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