Keratin-based powders and hydrogel for pharmaceutical applications

Abstract

A hydratable, highly absorbent keratin solid fiber or powder capable of absorbing a large weight excess of water may be produced by partially oxidizing hair keratin disulfide bonds to sulfonic acid residues and reacting the sulfonic acid residues with a cation. The neutralized suspension can be filtered, washed, and dried, leaving keratin solid which can be shredded into fibers and further ground into powder. Addition of water to the solid produces a hydrogel. The powder or hydrogel may be useful as an absorbent material, as a therapeutic for skin, or as an excipient. The keratin materials can be incorporated into nonwoven films. The hydrogel can be used as a biocompatible viscoelastic filler for implant applications. Another use for the absorbent keratin and keratin hydrogel is as an excipient in pharmaceutical and cosmetic applications.

Description

I. RELATED APPLICATIONS[0001] The present application is a divisional of U.S. patent application Ser. No. 09 / 638,643 filed Aug. 13, 2000, now U.S. Pat. No. 6,544,548, which is a continuation-in-part of U.S. patent application Ser. No. 09 / 587,157 filed Jun. 5, 2000, which is a continuation-in-part of U.S. patent application Ser. No. 09 / 528,893 filed Mar. 20, 2000, which is a continuation-in-part of U.S. patent application Ser. No. 09 / 512,918, filed Feb. 25, 2000 which is a continuation-in-part of U.S. patent application Ser. No. 09 / 394,782 filed on Sep. 13, 1999.II. FIELD OF THE INVENTION[0002] 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, prosthet...

AI Technical Summary

Benefits of technology

[0012] The keratin suspension may be heated, and is preferably heated to boiling for a time sufficient to swell the keratin. The keratin suspension may be stirred without heat for a longer period of time to allow a more complete association or reaction between the sulfonic acid groups and the base cations. The continued reaction time at or near room temperature, or even below room temperature while stirring is contemplated by the inventors to allow the base cations to approach and bind to the keratin anionic sites with a lower incidence of peptide backbone degradation that could occur with continued boiling. The cations for use in the present invention, therefore, must be able to interact with the anionic cysteic groups in the keratin material. The use of the term "cations" or "monovalent cations" in the present disclosure and claims is indication of those cations that are able to do so. Salts of aspartate and glutamate may also be present in high concentration and will contribute to the absorbency of the hydratable keratin material. After a sufficient reaction time, the keratin solid may be removed from the suspension by filtration, for example, and dried, leaving a solid salt formed of the keratin sulfonic acid or cysteic acid groups and base cations. This solid may be shredded into a fibrous form and / or ground into a finely divided powder. This solid may be used in certain embodiments, or it may be hydrated by adding water, for example, and the hydrogel, or viscoelastic hydrogel thus formed may be used in certain embodiments.

[0014] The hydratable keratin solids as described herein form a hydrogel or a viscoelastic hydrogel upon application of water, and also are contemplated to contain skin healing peptides associated with the keratin, which may leach out of the keratin products when wet. The keratin products thus provide an added benefit, in addition to water absorbency, that is, healing or soothing peptides are also released that may have beneficial effects on the skin of a user of the products. This property offers certain benefits in embodiments such as wound dressings, as well as cosmetics, gels or lotions for application to the skin.

[0016] The keratin hydrogel is also believed to be suitable for use as an implant filler, for example, used to fill a breast implant, or to augment soft tissue for cosmetic, reconstructive or aesthetic reasons, or in a tissue expander application. The keratin product may also be used in cosmetics to retain moisture next to the skin. The performance of cosmetics which reduce the greasy appearance of skin can be enhanced through the use of moisture absorbent keratin material as an additive or base ingredient, for example, in a cosmetic formulation. The keratin absorbent and hydrogel can also be used for a variety of tissue engineering applications. Both materials may act as biocompatible scaffolds that provide a mitogen, the keratin peptide, to the cellular components of a tissue-engineered implant. In the case of a keratin hydrogel tissue engineered implant, the degradation of keratin to lower molecular weight peptides can be controlled through a combination of processing and formulation parameters. As with other materials known in the art, the degradation rate is directly related to the rate of resorbtion in-vivo (Agrawal, 1997). Therefore, the resorbtion rate of the keratin hydrogel can be directly controlled.

[0034] In certain embodiments the present invention may be described as a method for promoting skin healing, in particular in those embodiments in which a keratin solid or hydrogel as described herein, such as a keratin solid or hydrogel in which the keratin is obtained from human hair, for example, is contained in, or forms a portion of a cream, lotion, or gel for application to skin, hair, lips, or nails, for example. Such formulations can offer various advantages such as moisturizing the skin, or inhibiting loss of moisture from the skin, as well as providing the healing effects of peptides that may leach from the keratin containing product. Such creams, lotions and gels may be applied to damaged skin, such as dry, burned, sunburned, wrinkled, cut, scraped, chapped, irritated, ulcerated or otherwise damaged skin or other tissue.

[0046] It is an aspect of the present invention that a keratin composition as described herein, and in particular keratin obtained from human hair is also useful as an excipient for the delivery of an active agent. An embodiment of the invention maybe described, therefore, as a composition comprising a keratin having oxidized cysteic groups and an active agent or as a cross-linked insoluble oxidized keratin excipient with an active agent. In certain embodiments the active agent is physically or sterically entrapped within the keratin excipient and released over time by diffusion, or as a keratin excipient is degraded. Further, in some embodiments the active agent may be associated with the keratin excipient. The association between the active agent and the keratin excipient may be by non-covalent attraction or association, through electrostatic, hydrophilic or ionic interaction, for example, or it may be covalently attached to a keratin excipient by covalent bonding to an oxidized keratin as described herein. In one embodiment, the active agent is in a cationic form that ionically binds to the sulfonate groups of the ionized keratin. In another embodiment the active agent is associated with the keratin excipient by Van der Waal's forces. Association of the active agent with a keratin excipient allows for the sustained and / or controlled release of active agents. In some embodiments, the controlled release of the active agent is provided by the hydrolysis of the keratin excipient. Such a formulation may include a hydratable keratin solid excipient, or a keratin hydrogel depending on the particular application. In some embodiments the active agent is a pharmaceutical agent while in other embodiments the active agent is a cosmetic agent.

[0050] Keratin excipient preparations may also include other compounds such as diluents, fillers, lubricants, stabilizers, binders and gelants. Diluents and fillers are added to increase bulk formation, and lubricants to reduce friction during the tableting or other formulation process. Binders are used in tableting and provide the cohesiveness necessary for bonding together the ingredients under compression. They also increase the strength of the compressed tablet and decrease its friability, leading to an improvement in the both appearance and mechanical characteristics.

Problems solved by technology

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.