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.

What is claimed is:  
     
         1 . A preparation comprising a cross-linked insoluble oxidized keratin excipient, wherein said cross-linked insoluble oxidized keratin is chemically modified to contain sulfonate groups.  
     
     
         2 . The preparation of  claim 1 , wherein said keratin is derived from hair, fur, nails, feet, beaks, feathers, horns or hooves.  
     
     
         3 . The preparation of  claim 1 , wherein said keratin is derived from hair.  
     
     
         4 . The preparation of  claim 1 , wherein said hair is human hair.  
     
     
         5 . The preparation of  claim 1 , wherein said sulfonate groups are ionically associated with cations.  
     
     
         6 . The preparation of  claim 5 , wherein said cations comprise monovalent cations.  
     
     
         7 . The preparation of  claim 6 , wherein said monovalent cations comprise sodium or potassium.  
     
     
         8 . The preparation of  claim 1 , wherein said preparation comprising a cross-linked insoluble oxidized keratin excipient is prepared in a form selected from the group consisting of a powder, tablet, film, capsule, lotion, cream, gel, solution, suspension, emulsion and aerosol.  
     
     
         9 . The preparation of  claim 1 , further comprising at least one additive selected from the group consisting of diluents, fillers, lubricants, stabilizers, binders and gelants.  
     
     
         10 . The preparation of  claim 1 , wherein said cross-linked insoluble oxidized keratin excipient comprises a hydratable cross-linked insoluble oxidized keratin.  
     
     
         11 . The preparation of  claim 1 , wherein said cross-linked insoluble oxidized keratin excipient is a cross-linked insoluble oxidized keratin hydrogel.  
     
     
         12 . The preparation of  claim 1 , further comprising an active agent.  
     
     
         13 . The preparation of  claim 12 , wherein said sulfonate groups are ionically associated with cations.  
     
     
         14 . The preparation of  claim 13 , wherein said cations comprise the cationic form of an active agent.  
     
     
         15 . The preparation of  claim 12 , wherein said active agent is the free base of an active agent that may be otherwise formulated as a hydrochloride.  
     
     
         16 . The preparation of  claim 12 , wherein said active agent is a pharmaceutical agent  
     
     
         17 . The preparation of  claim 16 , wherein said pharmaceutical agent is a protein, polypeptide or peptide.  
     
     
         18 . The preparation of  claim 12 , wherein said active agent is a cosmetic agent.  
     
     
         19 . The preparation of  claim 18 , wherein said cosmetic ingredient is a water soluble peptide derived from keratin.  
     
     
         20 . The preparation of  claim 12 , wherein said preparation comprising a cross-linked insoluble oxidized keratin excipient and an active agent is prepared in a form selected from the group consisting of a powder, tablet, film, capsule, lotion, cream, gel, solution, suspension, emulsion and aerosol.  
     
     
         21 . The preparation of  claim 12 , wherein said preparation comprising a cross-linked insoluble oxidized keratin excipient is prepared in the form of a non-woven film.  
     
     
         22 . The preparation of  claim 12 , further comprising at least one additive selected from the group consisting of diluents, fillers, lubricants, stabilizers, binders and gelants.  
     
     
         23 . The preparation of  claim 12 , wherein association of said active agent with said cross-linked insoluble oxidized keratin excipient provides for the controlled release of said active agent.  
     
     
         24 . The method of  claim 23 , wherein the ionic association of said active agent with said keratin excipient provides for said controlled release of said active agent.  
     
     
         25 . The preparation of  claim 23 , wherein the hydrolysis of said keratin excipient provides for said controlled release of said active agent.  
     
     
         26 . The preparation of  claim 12 , wherein said cross-linked insoluble oxidized keratin excipient comprises a cross-linked insoluble oxidized hydratable keratin.  
     
     
         27 . The preparation of  claim 12 , wherein said cross-linked insoluble oxidized keratin excipient is a cross-linked insoluble oxidized keratin hydrogel.  
     
     
         28 . An absorbent wound dressing comprising the cross-linked insoluble oxidized keratin excipient of  claim 1 .  
     
     
         29 . The absorbent wound dressing of  claim 28 , wherein said absorbent wound dressing is the absorbent pad of an adhesive bandage.  
     
     
         30 . The absorbent wound dressing of  claim 28 , further comprising an active agent.  
     
     
         31 . A drug delivery device comprising the cross-linked insoluble oxidized keratin excipient of  claim 12 .  
     
     
         32 . The device of  claim 31 , wherein said device is a transdermal drug delivery device.  
     
     
         33 . The device of  claim 31 , wherein said device is an inhalation drug delivery device.  
     
     
         34 . The device of  claim 31 , wherein said device is an oral drug delivery device.  
     
     
         35 . The device of  claim 31 , wherein said device is an implantable drug delivery device.  
     
     
         36 . A preparation comprising a keratin excipient associated with an active agent, wherein said keratin excipient is chemically modified to contain sulfonate groups.  
     
     
         37 . The preparation of  claim 36 , wherein said keratin is derived from hair, fur, nails, feet, beaks, feathers, horns or hooves.  
     
     
         38 . The preparation of  claim 36 , wherein said keratin is derived from hair.  
     
     
         39 . The preparation of  claim 36 , wherein said hair is human hair.  
     
     
         40 . The preparation of  claim 1 , wherein said keratin excipient is a cross-linked insoluble oxidized keratin excipient.  
     
     
         41 . The preparation of  claim 36 , wherein said sulfonate groups are ionically associated with cations.  
     
     
         42 . The preparation of  claim 41 , wherein said cations comprise the cationic form of an active agent.  
     
     
         43 . The preparation of  claim 42 , wherein said cations comprise monovalent cations.  
     
     
         44 . The preparation of  claim 43 , wherein said monovalent cations comprise sodium or potassium.  
     
     
         45 . The preparation of  claim 36 , wherein said active agent is the free base of an active agent that may be otherwise formulated as a hydrochloride.  
     
     
         46 . The preparation of  claim 36 , wherein said active agent is a pharmaceutical agent  
     
     
         47 . The preparation of  claim 46 , wherein said pharmaceutical agent is a protein, polypeptide or peptide.  
     
     
         48 . The preparation of  claim 36 , wherein said active agent is a cosmetic agent.  
     
     
         49 . The preparation of  claim 48 , wherein said cosmetic ingredient is a water soluble peptide derived from keratin.  
     
     
         50 . The preparation of  claim 36 , wherein said preparation comprising a keratin excipient is prepared in a form selected from the group consisting of a powder, tablet, film, capsule, lotion, cream, gel, solution, suspension, emulsion and aerosol.  
     
     
         51 . The preparation of  claim 36 , wherein said preparation comprising a keratin excipient is prepared in the form of a non-woven film.  
     
     
         52 . The preparation of  claim 36 , further comprising at least one additive selected from the group consisting of diluents, fillers, lubricants, stabilizers, binders and gelants.  
     
     
         53 . The preparation of  claim 36 , wherein association of said active agent with said keratin excipient provides for the controlled release of said active agent.  
     
     
         54 . The method of  claim 53 , wherein the ionic association of said active agent with said keratin excipient provides for the controlled release of said active agent.  
     
     
         55 . The preparation of  claim 53 , wherein the hydrolysis of said keratin excipient provides for the controlled release of said active agent.  
     
     
         56 . The preparation of  claim 36 , wherein said keratin excipient comprises a hydratable keratin.  
     
     
         57 . The preparation of  claim 36 , wherein said keratin excipient is a keratin hydrogel  
     
     
         58 . An absorbent wound dressing comprising the keratin excipient of  claim 36 .  
     
     
         59 . The absorbent wound dressing of  claim 58 , wherein said absorbent wound dressing is the absorbent pad of an adhesive bandage.  
     
     
         60 . A drug delivery device comprising the keratin excipient of  claim 36 .  
     
     
         61 . The device of  claim 60 , wherein said device is a transdermal drug delivery device.  
     
     
         62 . The device of  claim 60 , wherein said device is an inhalation drug delivery device.  
     
     
         63 . The device of  claim 60 , wherein said device is an oral drug delivery device.  
     
     
         64 . The device of  claim 60 , wherein said device is an implantable drug delivery device.  
     
     
         65 . A preparation comprising a cross-linked insoluble oxidized keratin excipient containing sulfonate groups, wherein an active agent is ionically associated with said sulfonate groups.  
     
     
         66 . The preparation of  claim 65 , wherein said keratin is derived from hair, fur, nails, feet, beaks, feathers, horns or hooves.  
     
     
         67 . The preparation of  claim 65 , wherein said keratin is derived from hair.  
     
     
         68 . The preparation of  claim 65 , wherein said hair is human hair.  
     
     
         69 . The preparation of  claim 65 , wherein said active agent is a cation.  
     
     
         70 . The preparation of  claim 69 , wherein said cation is a pharmaceutical agent.  
     
     
         71 . The preparation of  claim 69 , wherein said cation is a cosmetic agent.  
     
     
         72 . The preparation of  claim 65 , wherein ionic association of said active agent with said cross-linked insoluble oxidized keratin excipient provides for the controlled release of said active agent.  
     
     
         73 . The preparation of  claim 65 , wherein the hydrolysis of said cross-linked insoluble oxidized keratin excipient provides for the controlled release of said active agent.  
     
     
         74 . The preparation of  claim 65 , wherein said preparation comprising a cross-linked insoluble oxidized keratin excipient is prepared in a form selected from the group consisting of a powder, tablet, film, capsule, lotion, cream, gel, solution, suspension, emulsion and aerosol.  
     
     
         75 . The preparation of  claim 65 , wherein said preparation comprising a cross-linked insoluble oxidized keratin excipient is prepared in the form of a non-woven film.  
     
     
         76 . The preparation of  claim 65 , further comprising at least one additive selected from the group consisting of diluents, fillers, lubricants, stabilizers, binders and gelants.  
     
     
         77 . An absorbent wound dressing comprising the cross-linked insoluble oxidized keratin excipient of  claim 65 .  
     
     
         78 . The absorbent wound dressing of  claim 43 , wherein said absorbent wound dressing is the absorbent pad of an adhesive bandage.  
     
     
         79 . A method for the delivery of an active agent comprising providing an active agent in a keratin excipient, wherein said keratin excipient contains sulfonate groups.  
     
     
         80 . The method of  claim 79 , wherein said keratin excipient is a cross-linked insoluble oxidized keratin excipient.  
     
     
         81 . The method of  claim 79 , wherein said active agent is a pharmaceutical agent or a cosmetic agent.  
     
     
         82 . The method of  claim 79 , wherein said keratin is obtained from hair, fur, nails, feet, beaks, feathers, horns or hooves.  
     
     
         83 . The method of  claim 79 , wherein said keratin is obtained from hair.  
     
     
         84 . The method of  claim 83 , wherein said hair is human hair.  
     
     
         85 . The method of  claim 79 , wherein said active agent is ionically associated with said sulfonate groups.  
     
     
         86 . The method of  claim 79 , wherein said keratin excipient is delivered to the lungs of an animal by inhalation of particles of said keratin excipient.  
     
     
         87 . The method of  claim 86 , wherein said keratin excipient particles are less than about 1 micron in diameter.  
     
     
         88 . The method of  claim 79 , wherein said delivery is transdermal delivery.  
     
     
         89 . The method of  claim 79 , wherein said delivery is oral delivery.  
     
     
         90 . The method of  claim 79 , wherein said keratin excipient is implanted.  
     
     
         91 . The method of  claim 79 , wherein said delivery of said active agent provides for the controlled delivery of said active agent.  
     
     
         92 . The method of  claim 79 , wherein the ionic association of said active agent with said keratin excipient provides for the controlled release of said active agent.  
     
     
         93 . The method of  claim 79 , wherein the hydrolysis of said keratin excipient provides for the controlled release of said active agent.  
     
     
         94 . The method of  claim 79 , wherein the ionic association of said active agent with said cross-linked insoluble oxidized keratin excipient and the hydrolysis of said cross-linked insoluble oxidized keratin excipient provide for the controlled release of said active agent.  
     
     
         95 . A process for the preparation of a preparation comprising an active agent bound to a keratin excipient, wherein said active agent is ionically associated with said sulfonate group, comprising the steps: 
 (a) oxidizing keratin in a first solution comprising a soluble oxidizing agent, such that a portion of the disulfide bonds of said keratin are oxidized to form sulfonic acid residues to obtain an oxidized solid fraction;    (b) separating said oxidized solid fraction from said first solution; contacting said oxidized solid fraction with a second solution comprising a cationic form of an active agent dissolved in a solvent;    (c) maintaining said second solution containing said oxidized solid fraction and said active agent for a time and at a temperature effective to cause an ionic interaction between said sulfonic acid residues and said cationic form of said active agent; and    (d) substantially removing the solvent from said salt solution to obtain a solid preparation.    
     
     
         96 . The process of  claim 95 , further comprising grinding said solid preparation to form a powder.  
     
     
         97 . The process of  claim 95 , wherein said active agent is a pharmaceutical agent or a cosmetic agent capable of forming a cation  
     
     
         98 . The process of  claim 95 , wherein said keratin is obtained from hair, fur, nails, feet, beaks, feathers, horns or hooves.  
     
     
         99 . The process of  claim 95 , wherein said keratin is obtained from hair.  
     
     
         100 . The process of  claim 99 , wherein said hair is human hair.  
     
     
         101 . A preparation made by the process of  claim 95 .  
     
     
         102 . A process for the preparation of a hydratable keratin excipient comprising the steps: 
 (a) oxidizing keratin in a first solution comprising a soluble oxidizing agent, such that a portion of the disulfide bonds of said keratin are oxidized to form sulfonic acid residues to obtain an oxidized solid fraction;    (b) separating said oxidized solid fraction from said first solution; contacting said oxidized solid fraction with a second solution comprising monovalent cations dissolved in a solvent;    (c) maintaining said second solution containing said oxidized solid fraction and said monovalent cations for a time and at a temperature effective to cause an interaction between said sulfonic acid residues and said monovalent cations to obtain a salt solution of said keratin and said monovalent cations; and    (d) substantially removing the solvent from said salt solution to obtain a hydratable keratin solid.    
     
     
         103 . The process of  claim 102 , further comprising grinding said hydratable keratin solid to form a powder.  
     
     
         104 . The process of  claim 102 , further comprising contacting said hydratable keratin with an aqueous solution to form a hydrogel.  
     
     
         105 . The process of  claim 104 , further comprising adding an active agent to said aqueous solution before contacting said hydratable keratin to form said hydrogel.  
     
     
         106 . The process of  claim 104 , further comprising admixing an active agent with said hydratable keratin solid.  
     
     
         107 . The process of  claim 106 , further comprising contacting said admixture of said hydratable keratin and said active agent with an aqueous solution to form a hydrogel.  
     
     
         108 . The process of  claim 104 , wherein said keratin is obtained from hair, fur, nails, feet, beaks, feathers, horns or hooves.  
     
     
         109 . The process of  claim 104 , wherein said keratin is obtained from hair.  
     
     
         110 . The process of  claim 109 , wherein said hair is human hair.  
     
     
         111 . A preparation made by the process of  claim 105 .  
     
     
         112 . A preparation made by the process of  claim 106 .  
     
     
         113 . A process for the preparation of a preparation comprising a cross-linked insoluble oxidized keratin excipient comprising the steps: 
 (a) oxidizing keratin in a first solution comprising a soluble oxidizing agent, such that a portion of the disulfide bonds of said keratin are oxidized to form sulfonic acid residues to obtain an oxidized cross-linked insoluble solid fraction;    (b) separating said oxidized cross-linked insoluble solid fraction from said first solution; and    (c) substantially removing the solvent from said oxidized cross-linked insoluble solid fraction.    
     
     
         114 . The process of  claim 113 , further comprising grinding said oxidized cross-linked insoluble solid fraction to form a powder.  
     
     
         115 . The process of  claim 113 , wherein said keratin is obtained from hair, fur, nails, feet, beaks, feathers, horns or hooves.  
     
     
         116 . The process of  claim 113 , wherein said keratin is obtained from hair.  
     
     
         117 . The process of  claim 116 , wherein said hair is human hair.  
     
     
         118 . A preparation made by the process of  claim 113 .  
     
     
         119 . A liposome preparation comprising a keratin excipient associated with an active agent, wherein said keratin is chemically modified to contain sulfonate groups.  
     
     
         120 . The preparation of  claim 119 , wherein said keratin is derived from hair, fur, nails, feet, beaks, feathers, horns or hooves.  
     
     
         121 . The preparation of  claim 119 , wherein said keratin is derived from hair.  
     
     
         122 . The preparation of  claim 121 , wherein said hair is human hair.  
     
     
         123 . The preparation of  claim 119 , wherein said sulfonate groups are ionically associated with cations.  
     
     
         124 . The preparation of  claim 123 , wherein said cations comprise the cationic form of an active agent.  
     
     
         125 . The preparation of  claim 123  wherein said cations comprise monovalent cations.  
     
     
         126 . The preparation of  claim 125 , wherein said monovalent cations comprise sodium or potassium.  
     
     
         127 . The preparation of  claim 119 , wherein said active agent is the free base of an active agent that may be otherwise formulated as a hydrochloride.  
     
     
         128 . The preparation of  claim 119 , wherein said active agent is a pharmaceutical agent  
     
     
         129 . The preparation of  claim 128 , wherein said pharmaceutical agent is a protein, polypeptide or peptide.  
     
     
         130 . The preparation of  claim 119 , wherein said active agent is a cosmetic agent.  
     
     
         131 . The preparation of  claim 130 , wherein said cosmetic ingredient is a water soluble peptide derived from keratin.  
     
     
         132 . The preparation of  claim 119 , wherein association of said active agent with said keratin excipient provides for the controlled release of said active agent.  
     
     
         133 . The preparation of  claim 119 , wherein said keratin excipient comprises a hydratable keratin.  
     
     
         134 . The preparation of  claim 119 , wherein said keratin excipient is a keratin hydrogel.