Keratin-based powders and hydrogel for pharmaceutical...

Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...

Reexamination Certificate

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C424S400000, C424S070100, C424S070110, C424S070120, C424S070210, C424S070220, C424S070240, C424S070270, C424S401000, C424S402000, C424S443000, C514S002600, C514S021800

Reexamination Certificate

active

06544548

ABSTRACT:

FIELD OF THE INVENTION
The present invention is related generally to a keratin composition and method for making same. Specifically, the present invention relates to an absorbent keratin powder or fiber. More specifically, the present invention includes a hydratable keratin solid which forms a hydrogel upon addition of water for use in various applications including nonwoven films, diapers, skin treatments, prosthetic devices, excipients, tissue engineering scaffolds and the like. Active agents can be bound to the keratin excipient for controlled drug delivery.
BACKGROUND OF THE INVENTION
Absorbent materials are currently used to absorb body fluids such as urine, menses, and wound exudate. The absorbent materials are placed near the skin to serve this purpose. One class of products includes diapers, where the absorbent material can be derived from wood pulp, cellulosic fibers, or super absorbent, synthetically produced material. Diapers commonly have an inner core designed to absorb urine and water. The core is typically formed from a superabsorbent polymer dispersed in a larger amount of less absorbent material. The absorbent materials typically contained in the core are separated from the skin by at least one layer of material. The absorbent materials absorb urine and can become saturated. It is believed that some material from the absorbent core leaches from the wet absorbent and travels back to the skin. In the case of chemically treated absorbent materials and films, depending on the chemicals, the leachate may be irritating and is not believed to be beneficial. Skin contact with urine can also occur and result in irritation. This type of irritation may exacerbate diaper rash problems.
Other products which contain absorbent materials for use next to the skin include feminine hygiene products such as tampons and pads. These products serve to absorb menses. Another class of products using absorbent materials includes wound dressings, both those designed for humans, and dressings for veterinary use for application to wounds or skin irritations or disorders in animals. For specific applications, wound dressings preferably absorb exudate from wounds while keeping the wounds relatively moist to promote healing. In some applications, a gel may be desirable as a wound dressing, where the gel can maintain a moist wound environment, while absorbing excess exudate.
What would be desirable is an absorbent material formed from a natural product. What would be beneficial is a non-toxic product derived from natural sources that would cause no concern when leachate from the material contacts the body or the material itself contacts the body. What would be advantageous is a material that can absorb urine and, when wet, leach out a natural product that is beneficial with respect to diaper rash. What would be desirable is a material that can return a skin healing leachate to the skin. What would be desirable is a material that aids wound healing. What would be desirable is a hydrogel made of natural products formable by adding water to a powder or fiber. What would be desirable is a biocompatible carrier or excipient that could be used in the delivery of drug actives to various organs of the body. What would be desirable is a biocompatible carrier to which active agents can be bound and later released.
Tissue engineering is a rapidly growing field encompassing a number of technologies aimed at replacing or restoring tissue and organ function. The success of tissue-engineered implants rest on the invention of biocompatible materials that can act as cell-scaffolds and support cell growth. Of benefit are tissue-engineering scaffolds materials that are mitogenic or contain mitogenic factors. Such scaffolding materials can be used for in a wide array of tissue engineering implants containing cellular components, such as, for example, osteoblasts, chondrocytes, keratinocytes, and hepatocytes, to restore or replace bone cartilage, skin and liver tissue respectively.
SUMMARY OF THE INVENTION
The present disclosure addresses at least some of the deficiencies in the art by providing a hydratable, hydrogel-forming solid derived from a keratinous source such as hair, fur, human hair and the like. In the context of the present invention, the term “hydratable keratin” and “hydratable keratin material” is a keratin or keratin material that when hydrated can form a hydrogel. In the context of the present invention, the term “cross-linked insoluble oxidized keratin” means a network of cross-linked keratin containing sulfonic acid residues that is effectively of infinite molecular weight in that the molecular weight is approximated by the weight of the sample. Such networks may be viewed as being effectively one molecule. The status of a sample as being a “cross linked insoluble oxidized keratin” can be verified by the addition of a solvent in which an oxidized keratin monomer (prepared by breaking all cross-links) is soluble. A “cross-linked insoluble oxidized keratin” will swell upon addition of such a solvent, but will not enter solution despite agitation, heat and prolonged incubation unless and until the cross-linked insoluble oxidized keratin undergoes degradation to form lower molecular molecules. The cross-linked insoluble oxidized keratin preparation of the current invention may contain up to about 90 percent by weight of lower molecular weight polypeptides which may be soluble, but the insoluble character and gel forming are dependent upon network structure of the cross-linked insoluble oxidized keratin. The term “insoluble” refers to the properties of the of cross-linked oxidized keratin while it exists as a network of effectively infinite molecular weight. Upon hydrolysis, the cross-linked insoluble oxidized keratin network will enter into solution to the extent of degradation to lower molecular weight polypeptides. As this process ensues, molecules of finite molecular weight are generated which continue to hydrolyze and degrade to molecules of decreasing molecular weight. The solubility of these lower molecular weight polypeptides is enhanced by the fact that hydrolysis results in the generation of molecules that are more soluble by virtue of their low molecular weight (Flory, 1953). Solubility is further enhanced by the increasing relative molar percentage of amine and acid functional groups that are being generated as a result of the continued hydrolytic degradation. The rate of such degradation can be controlled by varying preparation parameters of the “cross-linked insoluble oxidized keratin” such as extent of oxidation and the solids content. When the solvent is water, a cross-linked insoluble oxidized keratin that has undergone the ion exchange process of the current invention will form a hydrogel.
In certain embodiments, a hydrogel-forming solid as disclosed herein may absorb up to 5 to 20 times its weight in water to form a hydrogel. Such a solid, as well as the hydrogel formed from the solid will be useful in various applications such as use as an absorbent with skin healing properties when incorporated into diapers, feminine hygiene products, wound dressings, including both human and veterinary uses, as a soft tissue augmentation medium when used in subdermal implants, tissue engineering cell scaffolds, as a moisture containing agent in cosmetics, oils, lotions, or gels for use on the skin, in applications related to the healing of damaged skin, and as a pharmaceutical excipient for sustained and/or controlled release pharmaceutical applications.
A hydratable keratin solid may be made by methods that include providing a keratinous material, or keratin, having disulfide linkages and partially or substantially oxidizing the keratinous material with an oxidizing agent, for example, such that some disulfide linkages are cleaved and oxidized, forming hydrophilic sulfonic acid or cysteic acid residues. A preferred source of keratinous material is human hair, although the keratin may be obtained from hair or fur of animals including any mammal, or from finger or toenail material or from hoov

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