Hyaluronic acid and chondroitin sulfate based hydrolyzed...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

Reexamination Certificate

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C514S021800, C530S356000, C435S212000, C435S273000

Reexamination Certificate

active

06780841

ABSTRACT:

CROSS-REFERENCE TO RELATED APPLICATIONS
(Not Applicable)
STATEMENT RE: FEDERALLY SPONSORED RESEARCH/DEVELOPMENT
(Not Applicable)
BACKGROUND OF THE INVENTION
The present invention relates to hydrolyzed collagen type II powder compositions for inducing cartilage formation in an individual, a method of preparing the compositions and the use of the compositions in treating connective tissue disorder and replenishing skin viscoelasticity.
Studies have shown that collagen is a complex structural protein which provides strength and flexibility to skin, hair and nails. Collagen is an essential and major component of muscles, tendons, cartilage, ligaments, joints and blood vessels in the human body. There are three main types of collagen: I, II and III. Types I and III are primarily found in skin, tendon and bone. In contrast, type II is found predominantly in articular cartilage. Collagen is an unusual protein, in that the proportion of glycine residues is nearly one-third, which is unusually high in comparison to other typical proteins. Proline is also present to a much greater extent in collagen than in most other proteins. Moreover, collagen contains two amino acids, 4-hydroxyproline and 5-hydroxylysine, that are found in very few other proteins. The amino acid sequence of collagen is remarkably regular, nearly every third amino acid being glycine. In addition, the sequence glycine-proline-hydroxyproline recurs frequently. In contrast, globular proteins rarely exhibit regularities in their amino acid sequences (Stryer, L.,
Biochemistry
, Third Edition, W. H. Freeman and Co., New York, 1988, pp. 262).
In 1986, collagen was sold for the first time in the United States for use as a food supplement. Collagen (a mixture of Types I and III) was extracted from calf skin tissue, hydrolyzed and prepared in powdered form for use as a dietary supplement. The composition was sold under the name “Hydrolyzed Collagen Beauty Supplement™” (Smarter Nails & Hair, Inc., Newport Beach, Calif.). In 1987, “Hydrolyzed Collagen Beauty Supplement Tablet™” (Smarter Nails & Hair, Inc., Newport Beach, Calif.) was sold which comprised collagen powder and 10 mg vitamin C compressed into 1,000 mg tablets.
U.S. Pat. No. 4,804,745 to Koepff et al. discloses agents containing collagen peptides produced by enzymatic hydrolysis for the treatment of degenerative joint diseases. These peptides can be obtained from animal skin, animal bones and other sufficiently purified connective tissue and have average molecular weights of between 30 and 45 kilodaltons.
U.S. Pat. No. 5,399,347 to Trentham et al. and Trentham et al. (
Science
261:1727-1729, 1993) disclose the effective treatment of rheumatoid arthritis (RA) with water-soluble whole chick collagen type II or biologically active peptides derived therefrom. The mechanism by which the effect is believed to occur is via oral tolerization to autoantigens.
U.S. Pat. No. 5,364,845 to Henderson discloses a therapeutic composition and method for the protection, treatment and repair of connective tissue in mammals. This composition comprises glucosamine, chondroitin sulfate and manganese ascorbate. U.S. Pat. No. 5,587,363 to Henderson discloses a therapeutic composition and method for the protection, treatment and repair of connective tissue in mammals which includes aminosugars and glycosaminoglycans.
Another well known substance which aids in the rejuvenation and treatment of such ailments as connective tissue disorder is a substance known as Hyaluronic Acid (also known as “Hyaluronan” or “HA”). It is well known that the human body naturally contains such HA, as it is found in several parts of the body such as the soft connective tissue, the vitreous body of the eye, hyaline cartilage, synovial joint fluid, the dermis, and the epidermis. Within these parts of the body, HA acts as a lubricant between connective tissues of the skin, protects the joints by providing shock-absorption, and helps the body retain skin moisture. Over time however, as the body ages, the amount of HA present in the body deteriorates and the body may eventually develop one of several health problems, in part due to a decreased presence of HA. This effect is particularly apparent for those who are over the age of 50. Generally, the skin loses viscoelasticity, and wrinkles form ultimately as a result of this deficiency.
Due to the fact that HA is found in several different parts of the body, such a decrease in HA levels is associated with a great variety of disorders and ailments. For example, osteoarthritis patients experience decreased levels of HA in their synovial fluid. This has a detrimental effect on the joints because HA is primarily responsible for the lubricating and shock-absorbing effects of the synovial fluid. For this reason, researchers have theorized that the replacement of such lost HA may help osteoarthritis sufferers to rebuild damaged cartilage and to regain joint movement.
However, HA is not found exclusively in the human body. As a matter of fact, HA is found in most animals. For this reason, there has been substantial research conducted to extract HA from other sources so that humans may replenish the levels of HA that are lost over time. HA may be extracted from several sources such as from micro-organisms (Streptococcal cultures) through a fermentation process or from the isolation HA from rooster combs. Of these major sources, rooster combs produce HA having higher molecular weights. HA having a high molecular weight is too large to penetrate into the skin and the bloodstream and is therefore limited in its application. Generally, high molecular weight HA is used for eye surgery and cosmetics, specifically for creating a viscoelastic film to retain skin moisture and to block foreign substances.
For Osteoarthritis (“OA”) patients, one method of relieving joint pain is via a therapy known as viscosupplementation. Viscosupplementation requires an intra-articular injection of HA to alleviate the pain associated with OA and allows the patient to regain function of the affected joints. The end result of such treatment is that the HA has an anti-inflammatory effect. Alternatively, the patient may use intra-articular glucocorticoid injections. The benefit of both injections are somewhat comparable but the common disadvantage to both therapies is the invasive nature of the injections.
Another constituent which alleviates pain in the joints and helps rebuild connective tissue is an endogenous Glycosaminoglycan (“GAG”) called Chondroitin Sulfate (“CSA”) which is composed of Glucuronic Acid +N-acetyl-D-galactosamine+Glucosamine Sulfate. Generally, CSA is a biological polymer derived from connective tissue. There are three types of Chondroitin Sulfate: Chondroitin Sulfate A (“CSA-A”) (shown in
FIG. 2
) which is also known as chondroitin 6-sulphate, Chondroitin Sulfate B (“CSA-B”) (shown in
FIG. 3
) which is also known as dermatan sulphate, and Chondroitin Sulfate C (“CSA-C”) (shown in
FIG. 4
) which is also known as chondroitin 4-sulphate. The ratio of CSA-A to CSA-C declines in tandem with the progression of the aging process as does the content of CSA-B in the Dermis of the skin. In this respect, CSA levels are gradually depleted and such a decrease in CSA levels has a similar effect to a decrease in HA levels in that the shock-absorption and lubrication qualities are reduced. Thus, like HA, CSA is generally an important GAG for the maintenance of connective tissue.
Specifically, CSA-A has proven to be an effective anti-inflammatory that improves blood circulation, prevents Ischemic Heart Disease, reduces incidences of heart attacks, reduces incidences of strokes, and is also effective in supporting connective joint tissue. Insofar as Chondroitin Sulfate helps prevent heart disease, this phenomenon is due to the inherent antithrombogenic or anticoagulant properties which prevent abnormal blood clots and reduce the incidence of strokes. CSA-B is found in the dermis of the skin and is also one of the constituents responsible for maintaining viscoelasticity of the skin. CSA-C i

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