Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Reexamination Certificate
1999-06-11
2001-08-07
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
C424S444000, C424S445000, C424S446000, C424S447000, C424S449000
Reexamination Certificate
active
06270791
ABSTRACT:
FIELD OF THE INVENTION
The present invention is related generally to water-soluble peptides. More specifically, the present invention is related to water-soluble peptides derived from keratin. In particular, the present invention is related to water-soluble peptides formed from chemically processed hair, which can be used as wound-healing agents
BACKGROUND OF THE INVENTION
Chronic wounds can be caused by a variety of events, including surgery, prolonged bedrest and traumatic injuries. Partial thickness wounds can include second degree burns, abrasions, and skin graft donor sites. Healing of these wounds can be problematic, especially in cases of diabetes mellitus or chronic immune disorders. Full thickness wounds have no skin remaining, and can be the result of trauma, diabetes (e.g., leg ulcers) and venous stasis disease, which can cause full thickness ulcers of the lower extremities. Full thickness wounds tend to heal very slowly or not at all. Proper wound care technique including the use of wound dressings is extremely important to successful chronic wound management. Chronic wounds affect an estimated four million people a year, resulting in health care costs in the billions of dollars. T. Phillips, O. Kehinde, and H. Green, “Treatment of Skin Ulcers with Cultivated Epidermal Allografts,”
J. Am. Acad. Dennatol
, V. 21, pp. 191-199 (1989).
The wound-healing process involves a complex series of biological interactions at the cellular level which can be grouped into three phases: homeostasis and inflammation; granulation tissue formation and reepithelization; and remodeling. R. A. F. Clark, “Cutaneous Tissue Repair: Basic Biological Considerations,”
J. Am. Acad. Dermatol
, Vol. 13, pp. 701-725 (1985). Keratinocytes (epidermal cells that manufacture and contain keratin) migrate from wound edges to cover the wound. Growth factors such as transforming growth factor-&bgr;(TGF-&bgr;) play a critical role in stimulating the migration process. The migration occurs optimally under the cover of a moist layer. Keratins have also been found to be necessary for reepithelization. Specifically, keratin types K5 and K14 have been found in the lower, generating, epidermal cells, and types K1 and K10 have been found in the upper, differentiated cells. I. K. Cohen, R. F. Diegleman, and W. J. Lindblad, eds.,
Wound Healing: Biochemical and Clinical Aspects
, W. W. Saunders Company, 1992. Keratin types K6 and K10 are believed to be present in healing wounds, but not in normal skin. Keratins are major structural proteins of all epithelial cell types and appear to play a major role in wound healing.
An optimum wound dressing would protect the injured tissue, maintain a moist environment, be water permeable, maintain microbial control, deliver healing agents to the wound site, be easy to apply, not require frequent changes and be non-toxic and non-antigenic. Although not ideal for chronic wounds, several wound dressings are currently on the market, including occlusive dressings, non-adherent dressings, absorbent dressings, and dressings in the form of sheets, foams, powders and gels. S. Thomas,
Wound Management and Dressing
, The Pharmaceutical Press, London, 1990.
Attempts have been made to provide improved dressings that would assist in the wound-healing process using biological materials such as growth factors. These biologicals have proven very costly and, due to the lack of an appropriate delivery vehicle, have shown minimal clinical relevance in accelerating the chronic wound-healing process relative to their cost. In cases of severe full thickness wounds, autografts (skin grafts from the patient's body) are often used. Although the graft is non-antigenic, it must be harvested from a donor site on the patient's body, creating an additional wound. In addition, availability of autologous tissue may not be adequate. Allografts (skin grafts from donors other than the patient) are also used when donor sites are not an option. Allografts essentially provide a “wound dressing” that provides a moist, water-permeable layer, but are rejected by the patient, usually within two weeks, and do not become part of the new epidermis.
What would be advantageous is a non-toxic, non-antigenic, inexpensive wound-healing agent having the ability to accelerate the rate of wound healing and allow non-healing wounds to heal.
SUMMARY OF THE INVENTION
A water-soluble peptide derived from a keratinous source such as hair and methods for making same are provided. One method includes providing a keratinous material having disulfide linkages and oxidizing the keratinous material with an oxidizing agent, such that some disulfide linkages are cleaved and oxidized, forming water-soluble peptides. The water-soluble peptides can be separated, collected, dried, and used as a wound-healing agent. A preferred source of keratinous material is hair, such as human hair.
In one method, hair is oxidized with a sufficient concentration of oxidizing agent for a sufficient time and temperature so as to cleave a significant portion of the hair disulfide bonds, such that some disulfide bonds are oxidized to form hydrophilic groups such as sulfonic acid and such that water-soluble peptides are produced. Examples of oxidizing agents include, but are not limited to, hydrogen peroxide, peracetic acid, percarbonates, persulfates, chlorine dioxide, sodium and calcium peroxides, perborates, and hypochlorite. The oxidized hair can be filtered, the filtrate collected, and neutralized with base. Water soluble peptides from the neutralized filtrate can be precipitated from solution by mixing the filtrate with a water-miscible organic solvent such as methanol. The precipitate can be collected using centrifugation and the collected filtrate dried. In one method, about 20 percent of the original hair mass is collected as peptide material after drying. The dried precipitate can be ground into a fine powder.
Peptides produced according to the present invention are largely water soluble and have an average molecular weight of about 850 daltons and an average chain length of about 10 amino acids. The peptide chains are believed to have attached a hydrophilic group, for example, an ionizable group such as sulfonic acid. In particular, most peptides are believed to have at least one sulfonic acid group formed from the oxidization of disulfide linkages of hair. One product made according to the present invention is a powder that is whitish to yellow in color and readily soluble in water.
In use, the peptide powder can be placed over a wound as a powder. The peptide powder can also be formulated into any water-based solution, cream, gel, or other vehicle for convenient application to a wound. In addition, a peptide solution could be incorporated into or cast onto a polymer wound dressing or a keratin wound dressing sheet for application to a wound. In in vitro trials, the peptide wound-healing agent was shown to enhance proliferation of human skin keratinocytes, human dermal fibroblasts, and microvascular endothelial cells. Applicants believe that the peptide fraction isolated according to the present invention is a highly active form of a wound-healing agent.
REFERENCES:
patent: 2993794 (1961-07-01), Moshy
patent: 3842848 (1974-10-01), Karjala
patent: 4135942 (1979-01-01), Kikkawa
patent: 4141888 (1979-02-01), Matsuda et al.
patent: 4232123 (1980-11-01), Braeumer et al.
patent: 4423032 (1983-12-01), Abe et al.
patent: 4495173 (1985-01-01), Matsunaga et al.
patent: 4530829 (1985-07-01), Abe
patent: 4570629 (1986-02-01), Widra
patent: 4711780 (1987-12-01), Fahim
patent: 4818520 (1989-04-01), Fleischner
patent: 4839168 (1989-06-01), Abe et al.
patent: 4895722 (1990-01-01), Abe et al.
patent: 4948876 (1990-08-01), Bore et al.
patent: 4959213 (1990-09-01), Brod et al.
patent: 4983580 (1991-01-01), Gibson
patent: 5047249 (1991-09-01), Rothman et al.
patent: 5258043 (1993-11-01), Stone
patent: 5276138 (1994-01-01), Yamada et al.
patent: 5358935 (1994-10-01), Smith et al.
patent: 5487889 (1996-01-01), Eckert et al.
patent: 5639448 (1997-06-01), Gallegu
Blanchard Cheryl R.
Siller-Jackson Arlene J.
Smith Robert A.
Timmons Scott F.
Van Dyke Mark E.
Corder Timothy S.
Ghali Isis
Keraplast Technologies Ltd.
Moloney Stephen J.
Page Thurman K.
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