EP0487648A1 - Compositions inodores et stabilisees pour traiter les tissus keratineux, des etats pathologiques de la peau et favoriser la cicatrisation de blessures - Google Patents

Compositions inodores et stabilisees pour traiter les tissus keratineux, des etats pathologiques de la peau et favoriser la cicatrisation de blessures

Info

Publication number
EP0487648A1
EP0487648A1 EP90914307A EP90914307A EP0487648A1 EP 0487648 A1 EP0487648 A1 EP 0487648A1 EP 90914307 A EP90914307 A EP 90914307A EP 90914307 A EP90914307 A EP 90914307A EP 0487648 A1 EP0487648 A1 EP 0487648A1
Authority
EP
European Patent Office
Prior art keywords
composition according
agents
weight
compositions
protein
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP90914307A
Other languages
German (de)
English (en)
Other versions
EP0487648A4 (en
Inventor
John Rothman
Philip 27-65 West 5Th Street Band
Jack Oceta
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
John Morris Co Inc
Original Assignee
John Morris Co Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by John Morris Co Inc filed Critical John Morris Co Inc
Publication of EP0487648A1 publication Critical patent/EP0487648A1/fr
Publication of EP0487648A4 publication Critical patent/EP0487648A4/en
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/27—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A61K8/447—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof containing sulfur
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/645—Proteins of vegetable origin; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/731—Cellulose; Quaternized cellulose derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q3/00—Manicure or pedicure preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/54—Polymers characterized by specific structures/properties
    • A61K2800/542—Polymers characterized by specific structures/properties characterized by the charge
    • A61K2800/5426—Polymers characterized by specific structures/properties characterized by the charge cationic

Definitions

  • This invention relates to novel compositions using film forming protein ingredients and includes reducing agents and optionally at least one of the following: reactive zinc salts, cationic polymers and/or cationic or nonionic surfac ⁇ tants.
  • reducing agents optionally at least one of the following: reactive zinc salts, cationic polymers and/or cationic or nonionic surfac ⁇ tants.
  • oxidizing agents and/or antioxidants are optionally included.
  • compositions of the present inven ⁇ tion are particularly effective in promoting wound healing, the healing of abrasions and pressure sores, gingival erosion, sores and lesions of the oral cavity, corneal ulcers and abra ⁇ sions, and in inhibiting certain skin disorders and treating abnormal conditions of the skin, including eczema and seborrhea, dandruff, psoriasis and other rash-like indica ⁇ tions, scleroderma and acne.
  • the compositions of the present invention further may be used to reduce scarring associated with severe forms of acne or wounds and to ameliorate wrink ⁇ ling in skin due to exposure to the sun's rays or to aging.
  • the therapeutic methods of the present invention are effective as veterinary tools in reducing the debilitation associated with certain skin conditions in mammals including eczematoid dermatitis, chronic dermatitis, equine exuberant granuloma ("proud flesh") , decubitis ulcers, and canine cutaneous granulomas ("lick" granuloma) .
  • the compositions of the pres ⁇ ent invention are also useful as cosmetic agents for con ⁇ ditioning horny keratinous tissue of mammals such as human hair and nails and the hooves and fur of animals to improve their strength and appearance.
  • these composi ⁇ tions are useful for promoting hair and nail growth and for stabilizing the loss of hair in mammals, including humans.
  • compositions of the present invention which include film-forming protein composi ⁇ tions, reducing agents and optionally sufficient quantities of at least one or more of the following components: zinc salts, cationic polymers and cationic or non-ionic surfactants and also optionally include oxidizing agents and/or anti-oxidant compositions exhibit surprising activity for treating wounds, pyoderma, sebborhea, psoriasis, acne, miscellaneous rashes, itching, callouses, corns, burns, eczematoid dermatitis, chronic dermatitis, decubitis ulcers, miscellaneous rashes, non-specific dermatitis and certain veterinary conditions including equine exuberant granuloma ("proud flesh") and canine cutaneous granulomas (“lick” granuloma) .
  • the composi ⁇ tions of the present invention may also be used to strengthen and improve the appearance and promote the growth of hair, nails, skin and other keratinous substrates and stabilize the loss of hair.
  • the compositions of the present invention may also be used to prevent and promote the healing of hang nails.
  • compositions of the present invention exhibit a substantial absence of odor which usually accompanies the storage of reducing agents and in certain cases, thiol- containing film-forming protein compositions. It is a particularly surprising result that compositions of the pres ⁇ ent invention may be formulated to substantially reduce the malodor associated with thiol-containing reducing agents and maintain the efficacy associated with a combination of a reducing agent and a film-forming protein.
  • compositions of the pres ⁇ ent invention may be formulated to substantially reduce the malodor associated with thiol-containing reducing agents and maintain the efficacy associated with a combination of a reducing agent and a film-forming protein.
  • compositions of this invention are the reducing agent and the film-forming protein, optionally at least one agent selected from among the follow ⁇ ing: zinc salts, cationic polymers and a cationic or nonionic surfactant is also included.
  • the compositions of the present invention may also include an oxidizing agent and/or an antioxidant. Numerous additional components may also be included, for example water, bases, acids, buffering agents, emulsifying agents or surfactants, thickeners, pre ⁇ servatives, coloring agents and perfuming agents.
  • compositions which are useful for promoting the growth of normal dermal and epidermal tissue and described as being useful to promote wound healing in the soft keratin tissue of the epidermis.
  • the compositions of the patent are described as containing defined percentages of thioglycollic acid, ammonium hydroxide, glycerine, citric acid, hydrogen peroxide, gelatin, a lower alkanol, and a solvent such as acetone or diethyl ether.
  • wound healing are provided in the specifi ⁇ cation.
  • United States Patent 4,195,095 describes the use of certain formulations comprising thioglycollic acid for use in the treatment of fatty cysts, dandruff, scleroder a and other dermatological disorders, including acne vulgaris.
  • exemplary compositions comprise thioglycollic acid, hexachlorophene, sodium hydroxide, water and other ingredients, including bulk ⁇ ing or gelling polymers and preservatives, among others.
  • U.S. Patent 3,842,848 describes a method of bonding especially prepared hydrolyzed peptide products of keratinaceous materials to human hair. The process is effected by conducting the reducing step of permanent waving in the presence of the peptide products and, thereafter, in a second step, oxidizing.
  • U.S. Patent No. 4,711,780 describes a medication for treating surface epithelium comprising ascorbic acid, a zinc salt a sulfur amino acid and optionally a mucopolysaccharide and/or a polysaccharide.
  • Compositions of this patent are described as being useful for treating a number of infections and conditions, including wound healing.
  • G.B. Patent No. 2,160,419 describes a process for treating and improving the condition of keratinous tissue com ⁇ prising no fewer than three steps: contacting the hair, skin or nails with a reducing composition, rinsing the treated tis ⁇ sue with water, contacting the rinsed tissue with an aqueous keratin protein hydrolysate and finally contacting the tissue with a neutralising composition containing an oxidizing agent.
  • compositions which contain film-forming protein (preferably an activated thiol-containing film-forming protein) and a reducing agent in the absence of the sulfur stabilizing components of the present invention, although highly efficacious, tend to develop a pungent, malodor which in certain compositions may be quite unpleasant. In certain instances, such compositions, because of this malodor, may reduce the frequency with which an individual applies the com ⁇ position.
  • film-forming protein preferably an activated thiol-containing film-forming protein
  • a reducing agent in the absence of the sulfur stabilizing components of the present invention, although highly efficacious, tend to develop a pungent, malodor which in certain compositions may be quite unpleasant. In certain instances, such compositions, because of this malodor, may reduce the frequency with which an individual applies the com ⁇ position.
  • This approach exhibits surprising efficacy in treating the above-mentioned skin con ⁇ ditions.
  • compositions and methods of the pres ⁇ ent invention are useful for treating keratinous and related conditions, including wounds, gingival erosion, sores and lesions of the oral cavity, corneal ulcers and abrasions, seb- borhea, psoriasis, dandruff, allergic skin reactions, acne, itching, callouses, corns, burns, abrasions, wrinkles, miscel ⁇ laneous rashes, non-specific dermatitis and certain veterinary conditions including eczematoid dermatitis, chronic dermatitis, equine exuberant granuloma ("proud flesh") , decubitis ulcers, and canine cutaneous granuloma ("lick” granuloma) .
  • the compositions and methods of the present invention may also be used to improve the strength, condition and appearance of hair, skin and nails, including split and cracked hair, nails and hooves, and for promoting the growth of hair and nails
  • compositions compris ⁇ ing an activated protein, a compatible reducing agent, and optionally at least one of the following components: a reac ⁇ tive zinc salt, a cationic polymer and a surfactant selected from the group consisting of cationic and nonionic surfactants is contacted with an area of keratinous tissue affected with one of the above conditions.
  • an oxidizing agent and/or an antioxidant may be included in the formula ⁇ tions of the present invention.
  • the therapeutic compositions and methods of the present invention exhibit activity against non-healing skin conditions, especially canine cutaneous granulomas ("lick" granuloma) and equine exuberant granuloma ("proud flesh”) .
  • compositions of the present invention are active in a broad range of applications without exhibiting the malodor associated with non-stabilized compositions or a substantial reduction in activity. Furthermore, the compositions of the present invention do not exhibit substantial "puckering" of packaging caused by compositions which do not contain at least one of the following: a reactive zinc salt, cationic polymer and cationic or nonionic surfactant.
  • compositions useful in the therapeutic methods of the present invention include compositions having a pH of from about 3 to about 10, preferably a pH of about 4 to about 9.
  • the pH of the composition depends upon the specific applica- tion the composition is to be used for, and will vary within the above described pH ranges including a pH of 7.6 (physiological pH) .
  • Compositions of the present invention may comprise a reducing agent, a film-forming protein, preferably an activated film-forming protein, optionally in the presence of one or more of reactive zinc salts, cationic polymers and a surfactant selected from among cationic and nonionic surfac ⁇ tants in addition to other less essential components.
  • An oxidizing agent and/or an antioxidant may also be included in the formulations.
  • the film-forming protein should be hydrated.
  • a hydrated protein may be beneficial to certain types of skin conditions and wounds, especially burns, because the hydrated protein may be expected to provide additional moisture to the skin.
  • the protein in the compositions of the present invention may react with and form chemical bonds with the keratin of human and animal skin, thus effecting an attachment of moist hydrated proteins to skin.
  • the composi ⁇ tions are therefore useful for treating human and animal skin to chemically bond the activated protein to the skin, moisturize dry skin and provide a moisturizing vehicle to carry other agents into dehydrated skin.
  • compositions of the present invention may react with and form chemical bonds with the hard keratin of hitman and animal hair, nails and skin, thus effecting decreased hair breakage, increased hair thickness, increased nail hardness, decreased nail splitting and delamination and attachment of moist hydrated proteins to skin.
  • the compositions of the present invention may also function as topical pharmaceutical carriers and vehicles.
  • the amount of film-forming protein that binds to skin will vary greatly as a function of the type of film-forming protein that is used. Protein that does not contain suffi ⁇ cient cysteinyl thiol groups does not bind to the keratinous substrate to the same extent or for the same duration of time as does protein containing sufficient cysteinyl thiol groups. Moreover, such a protein does not intercalate to become part of the natural skin as is the case of the protein keratin.
  • the percent of activated protein that bonds to the keratinous tissue will vary with the concentration of reducing agents in the composition and the number of activated thiol or mercapto groups in the activated protein and the keratinous tissue. The time that the reducing agent is in contact with the keratinous tissue is also impor ⁇ tant; the longer the keratinous tissue is in contact with the reducing agent, the greater will be the likelihood of protein- keratinous tissue covalent bond formation.
  • compositions of the present invention are preferably utilized at ambient temperatures, i.e., about 20°C to about 35°C; however, higher temperatures may be used, espe ⁇ cially for treating the hair and nails of animals, including humans.
  • ambient temperatures i.e., about 20°C to about 35°C; however, higher temperatures may be used, espe ⁇ cially for treating the hair and nails of animals, including humans.
  • higher temperatures may be used, espe ⁇ cially for treating the hair and nails of animals, including humans.
  • a wound especially a burn
  • treatment is kept to a lower temperature to avoid exacerbating the wound condition.
  • treating the keratinous substrate at higher temperatures is recommended.
  • the keratinous tissue (hair and nails) may be treated over a period of time ranging from about 5 minutes to about 6 hours.
  • the keratinous tissue may be treated acutely or chronically, with or without a dressing as needed.
  • compositions useful in prac ⁇ ticing the therapeutic methods of the present invention may be formulated with sustained or controlled release polymers to produce formulations capable of delivering active agent for extended periods of time. Reaction is effected by bringing the compositions of the present invention into contact with the keratinous substrate to be treated and allowing the treated tissue to dry. The time of contact may be varied at will.
  • compositions of the present invention also comprise at least one reducing agent, preferably a pharmaceutically compatible reducing agent.
  • the reducing agent is preferably used in an amount sufficient to reduce the keratinous substrate to promote covalent binding of the film-forming protein.
  • preferred reducing agents include pharmaceutically compatible thiol-containing reducing agents.
  • the compositions preferably comprise at least one agent selected from among the following: reactive zinc salts, cationic polymers and surfactants selected from cationic and nonionic surfactants.
  • reactive zinc salts When reactive zinc salts are used, they comprise a concentration effective for producing an odor- masked, stable product which surprisingly maintains its broad range of activity.
  • a reactive zinc salt is any zinc salt which is soluble in the compositions of the present invention to the extent of at least about 0.05 weight percent.
  • Preferred reactive zinc salts for use in the present invention include any zinc salt which is soluble in water or other carrier used to formulate compositions of the present invention.
  • the preferred zinc salts include those that are more readily soluble in water.
  • Addi ⁇ tional reactive zinc salts which may be used in the present invention include those that are only marginally soluble in water or other carrier, but increase markedly in solubility when formulated in compositions of the present invention.
  • Such reactive zinc salts include zinc oxide (ZnO) , among others.
  • ZnO zinc oxide
  • the amount of reactive zinc salt utilized ranges from about 0.05 weight percent up to the solubility limit of the zinc salt in water or other suitable carrier used.
  • Preferably, at least about 0.19 weight percent of reac ⁇ tive zinc salt is used.
  • a particularly preferred combination of zinc salts for use in the present invention includes zinc oxide and zinc sulfocarbolatet 111 (zinc phenylsulfonate) .
  • the amount of reactive zinc salt included within the compositions of the present invention generally ranges from about 0.05% by weight up to about 4% by weight of the composi ⁇ tions; however, those of ordinary skill will recognize that varying amounts of reactive zinc salt outside of this range may also be used depending up the effectivness of the particu ⁇ lar salt chosen and the addition of cationic polymer and/or surfactant to compositions of the present invention. Those of ordinary skill will also recognize that the amount of reactive zinc salt to be used will also depend upon the type of zinc salt chosen and the amount of additional components, espe- ⁇ cially thiol-containing compounds which are present in the compositions of the present invention.
  • compositions of the present invention may also include at least one cationic polymer, either alone or in com ⁇ bination with one or more reactive zinc salts and/or a surfac ⁇ tant.
  • the particular structure of the cationic polymer while somewhat important to the overall efficacy of the cationic polymer, is only one of several factors which may determine the effectiveness of cationic polymers of the present inven ⁇ tion to stabilize the compositions of the present invention. It is also believed that the zinc and cationic polymers or cationic and nonionic surfactants may complex with the thiol containing reducing agents and/or the proteins to stabilize these components from breakdown into malodorous side products.
  • Representative cationic polymers may contain nitrogen, phosphorous and sulfur cationic groups or mixtures of these cationic groups. Virtually any polymer containing cationic groups may be used in compositions of the present invention. Cationic polymers containing nitrogen and particularly quaternary ammonium groups are especially preferred.
  • the cationic polymers of the present invention are water soluble and contain quaternary- ammonium groups.
  • Such polymers may be selected from among the quaternary nitrogen-containing cellulosic ethers, quaternary nitrogen-containing polysaccharides, graft copolymers of cel ⁇ lulose ethers and dialkyl diallyl ammonium halide polymers, copolymers of vinyl pyrrolidone and quaternized dialkylaminoalkyl methacrylate, copolymers of acrylamide and quaternized dialkyl amino dialkyl methacrylate as well as other polyquaternium polymers.
  • the cationic polymer is used in an amount effective to substantially reduce the malodor associated with the storage of thiol containing compositions, for example reducing agents and proteins which are included in the compositions of the present invention.
  • the cationic polymer used in the present invention comprises at least about 0.01 percent by weight to about 20 percent by weight, preferably about 0.025% to about 20% by weight and most preferably about 0.1% to about 5% by weight of the composition.
  • the cationic polymer may be used alone or in combination with reactive zinc salts and/or surfactants.
  • the amount of cationic polymer although generally falling within the weight ranges described hereinabove, may be reduced to accommodate the reac ⁇ tive zinc salt and/or surfactant chosen.
  • compositions of the present invention may also contain at least one surfactant selected from among cationic and non ⁇ ionic surfactants.
  • cationic a ine containing surfactants con ⁇ templated for use in the present invention include phenyl and alkyl ammonium surfactants, including benzalkonium bromide, benzethonium chloride, benzylhexadecyldimethylammonium chloride, and cetyltrimethylammonium bromide, among others, oxyethyl substituted ammonium surfactants, including oxyethylammonium phosphate, ethoxylated alkylamines and the alkylimidazolines, Quaternary amine containing surfactants are clearly preferred including quaternized alkylamines, and quaternized ethoxylated alkylamines.
  • Other cationic surfac ⁇ tants may also be used in compositions clearly contemplated by the present invention.
  • compositions of the present invention may also contain at least one nonionic surfactant.
  • Nonionic surfactants which are useful in the present invention include those surfactants which complex with mercaptides.
  • Especially preferred nonionic surfactants for use in compositions of the present invention include, for example, those nonionic surfactants having cationic character.
  • compositions of the present invention preferably contain at least one pyrrolidone containing surfac ⁇ tant.
  • pyrrolidone containing sur ⁇ factant is used to describe a chemical composition comprising a pyrrolidone ring to which is attached a hydrophobic group at the nitrogen position of the pyrrolidone ring which, together with the pyrrolidone ring, provides surfactant-like qualities.
  • hydrophobic groups include n-octyl, dodecyl and coco and tallow alkyl groups, most preferably n-octyl, attached to the nitrogen of the pyrrolidone ring.
  • coco and tallow alkyl groups these groups are represented by diver ⁇ sified alkyl substituents derived from cocoanut oil and tal ⁇ low.
  • a chelat-ing agent for example, ethylenediaminetetraacetic acid (EDTA) or one of its chemical analogs, may be added to the composi ⁇ tion in the presence of a reactive zinc salt to augment the scent-reducing capability.
  • EDTA ethylenediaminetetraacetic acid
  • Such compositions may optionally contain a cationic polymer and/or a cationic or nonionic sur ⁇ factant as described herein.
  • EDTA is used in composi ⁇ tions of the present invention, it generally comprises between about 0.05 and about 2.0% by weight, preferably about 0.2 and about 0.9% by weight and most preferably between about 0.35 and 0.7% by weight of the composition.
  • com ⁇ positions of the present invention may be formulated with an oxidizing agent, an antioxidant or mixtures of an oxidizing agent and an antioxidant.
  • other components may also be added to the compositions of the present invention with or without the incusion of zinc salts, cationic polymers or nonionic and cationic surfactants including at least one or more of the following: acids, bases, buffering agents, emul ⁇ sifying agents or additional surfactants, thickeners, preserv ⁇ atives, bulking agents, organic solvents, coloring agents and perfume agents. It is to be recognized by those of ordinary skill in the art that the choice of additives is made to avoid interactions with the active components of compositions of the present invention.
  • the reaction may be facilitated by heat.
  • the antioxidant in this man ⁇ ner, oxidation to promote covalent disulfide formation by the oxygen in ambient air may be promoted.
  • Certain embodiments of the present invention may employ non-volatile oxidizing agents which may promote oxidation after the volatile antioxidants evaporate from the formulations.
  • compositions of the present invention com ⁇ prise about 0.1% to about 25% by weight of a film-forming protein, preferably an activated protein component, about 1.0% to about 15% by weight of a compatible reducing agent, preferably at least one agent selected from among reactive zinc salts, cationic polymers and cationic and nonionic sur ⁇ factants, and at least one component selected from the group consisting of oxidizing agents, antioxidants, water, acids, bases, buffering agents, emulsifying agents or surfactants, thickeners, preservatives, organic solvents, chelating agents, film-forming polymers, coloring agents and perfuming agents.
  • a compatible reducing agent preferably at least one agent selected from among reactive zinc salts, cationic polymers and cationic and nonionic sur ⁇ factants, and at least one component selected from the group consisting of oxidizing agents, antioxidants, water, acids, bases, buffering agents, emulsifying agents or surfactants, thickeners, preservatives, organic solvents, chelating agents
  • compositions for use in the method aspects of the present invention are formulated to enhance the forma ⁇ tion of free mercaptide or thiol groups in a thiol containing protein and the keratinous tissue to maximize the probability that a free thiol in the protein and a free thiol in the keratinous tissue will interact to form a covalent disulfide bond.
  • the inclusion of an oxidizing agent in the same for- mulation with or without an antioxidant may serve to promote covalent disulfide formation without having to resort to a second oxidizing solution.
  • compositions utilizing a non-thiol containing protein for example, gelatin or collagen
  • the film-forming characteristics of the protein may be the factor most responsible for enhanced activity.
  • the present invention utilizes compositions formulated as gels, creams, lotions, sprays or liquids of varying vis ⁇ cosities.
  • the present invention relates to compositions compris ⁇ ing a film-forming protein, preferably an activated protein, a reducing agent and optionally at least one component selected from among the following: reactive zinc salts, cationic polymers and surfactants, including cationic and pyrrolidone containing surfactants.
  • at least one component selected from among oxidizing agents, antioxidants, water, bases, acids, buffering agents, emulsifying agents or surfac ⁇ tants, thickeners, preservatives, organic solvents, coloring agents and perfuming agents may be included in the composi ⁇ tions of the present invention.
  • the protein used may be any film-forming protein.
  • a film-forming protein is any protein which forms a film on a keratinous substrate after being deposited. In these compositions, the film-forming protein is used in an amount effective to form a film on the keratinous substrate.
  • Film-forming proteins for use in the present invention may include, for example, proteins which do not contain sufficient numbers of cysteinyl thiol groups to be capable of covalently bonding to a keratinous substrate. Proteins which do not con ⁇ tain significant cysteine but are film-forming proteins include collagen and gelatin, among others.
  • Film-forming protein comprises about 0.1 to about 25.0% by weight of the composition, preferably about 1.0 to about 15.0% by weight for certain formulations and about 6 to about 10% by weight for other applications. -13-
  • Film-forming proteins used in compositions employed in the present invention are exemplified by a number of proteins.
  • Preferred proteins are those containing sufficient cysteine, i.e., at least about 1 cysteine amino acid for every 200 amino acids in a peptide chain (approximately, at least about 0.5% by weight cysteine, preferably, at least about 1.0% by weight cysteine, and most preferably at least about 5% by weight cysteine) to covalently bind to the keratinous tissue of hair, skin and nails to produce a durable permanent bond to keratinous tissue.
  • permanent bond we mean that the protein is not easily washed or rubbed off from the keratinous tissue and becomes as permanent as normal hair and nails.
  • a large number of exemplary film-forming proteins may be used in the present invention including gelatin, collagen, mucin, salmine, and sturine.
  • Preferred proteins include keratin, food proteins, for example, casein, alpha and beta- lactalbumin, seed proteins, for example, soybean proteins, linseed protein, cotton seed protein, corn protein and peanut protein, among others, hemoglobin, insulin, myosin, zein, ovalbumin, hemoglobin, trypsin, chymotrypsin, chymotryp- sinogen, elastases, thrombins, plasminogen, fibrinogen/ ibrin, lysozyme, papain, serum albumin, heat coagulable mucoproteins isolated from cartilage, bones and skin, gamma globulin blood proteins, and a number of the blood factor proteins, includ ⁇ ing, for example, factor VIII, XII, IXa and Xa, among others.
  • proteins which contain large numbers of cysteinyl residues are preferred, because these proteins would form the greatest number of covalent bonds with the keratinous tissue and thus, produce the greatest durability.
  • the most preferred film-forming proteins for use in the present invention are those which contain sufficient cysteine to covalently bind to the keratinous substrate being treated.
  • Particularly preferred proteins for use in the present invention include proteins containing high percentages by weight of cysteine, for example, ribonuclease Tl, human serum albumin and gamma globulins.
  • An especially preferred protein for use in the present invention is keratin, because of its particularly high cysteine content (about 12% to about 17% by weight of cysteine) and because it is found in those sub ⁇ strates which are conditioned.
  • exemplary compositions utilize keratin -1 4- either alone or in combination with fibrinogen/fibrin or modified fibrinogen.
  • Other compositions which may be used to treat wounds may comprise fibrinogen/fibrin or modified fibrinogen alone.
  • the activated proteins used in the present invention i.e. those proteins containing sufficient cysteinyl content to covalently bind to a keratinous substrate may be activated in the presence of reducing agent at a pH of about 9.0 or above for a time sufficient to produce free thiol group. This period is generally about 5 minutes up to about one hour. Activation periods of greater than one hour are less preferred because although such activation periods may marginally increase the amount of activated thiol groups in the protein, such periods may also result in hydrolysis of the protein into shorter, less advantageous peptide units.
  • a number of globular proteins contain cysteinyl residues within hydrophobic or other internal pockets of the protein structure. To activate these proteins and expose cysteinyl groups to the keratinous tissue, it may be advantageous to subject the proteins to denaturation and activation so that an activated cysteinyl residue of the dena ⁇ tured protein may be placed in proximity to the cysteinyl residues of the keratinous tissue to promote covalent binding.
  • the proteins of the present invention are preferably activated in the presence of reducing agent separately before they are formulated with the other components, because the addition of components other than a reducing agent at a pH above about 9.0 may adversely affect the rate at which cystinyl disulfide bonds in the protein are converted to cysteinyl mercaptide groups. This may lower the overall activity of the protein.
  • the activated protein is preferably a keratin, but any protein which contains sufficient cysteinyl content to promote binding to activated keratinous tissue is contemplated for use in the present invention.
  • Preferred proteins are keratins because of their high cysteinyl content (generally, greater than 10% by weight of the protein and often as high as 15-17% by weight of the protein) which may be obtained by hydrolysis of skin, feathers, wool and hair.
  • a particularly preferred keratin is Kerasol tm from Croda Chemicals International, Chesire, England.
  • the molecular weight of proteins useful in the present invention preferably varies between about 5,000 and 500,000 Daltons, and most preferably varies between about 120,000 and 130,000 Daltons.
  • Reducing agents which are useful in compositions of the present invention include sulfides, thiol-containing com ⁇ positions including dithiothreitol, trithiohexitol, glutathione, cysteine, mercaptoethanol, thioglycerol, thioalkanoic acid and mercaptocarboxylic acid analogues, for example, mercaptosuccinic acid, thiolactic acid and their pharmaceutically acceptable salts, among others, including thioglycollic acid and salts of thioglycollic acid.
  • Preferred reducing agents for activating the protein are thioglycerol, cysteine, thiolactic acid and thioglycollic acid, and their pharmaceutically acceptable salts.
  • Especially preferred reducing agents for use in the present invention include thioglycerol and salts of thioglycollic acid, especially ammonium thioglycollate.
  • the reducing agent for activating the protein should be the same as the pharmaceutically compatible reducing agent which is used in the final formulation of the invention.
  • the use of strong pharmaceutically incompatible reducing agents to activate the protein are less preferred and may make the use of the protein more difficult because the reducing agent may have to be removed from the activated protein before formulation.
  • compositions for use in the method of the present invention also contain a pharmaceutically compatible reducing agent in an amount equal to about 0.1 to about 15% by weight of the formulation.
  • a pharmaceutically compatible reducing agent in an amount equal to about 0.1 to about 15% by weight of the formulation.
  • Preferred compositions contain about 0.5% to about 10% by weight, most preferably greater than about 1% by weight of a pharmaceutically compatible reducing agent.
  • the amount of pharmaceutically compatible reducing agent varies according to the therapeutic or cosmetic use for which the compositions are intended, but generally falls within the range of about 0.1% to about 10% by weight.
  • a pharmaceutically compatible reduc ⁇ ing agent is an agent which reduces cystinyl disulfide linkages in keratinous tissue to produce free thiol or mercap- tide groups and is compatible with biological and/or pharmaceutical systems, especially for use on the skin, hair and nails of humans and/or the coats and hooves of animals.
  • Pharmaceutically compatible reducing agents which are con ⁇ templated for use in the present invention include mercap- toethanol, dithiothreitol, thioglycerol, thiolactic acid, glutathione, cysteine and thioglycollic acid and its salts.
  • An especially preferred reducing agent is ammonium thioglycol- late.
  • compositions of the present invention may additionally comprise at least one component selected from the following: reactive zinc salts, cationic polymers and cationic or non ⁇ ionic surfactants.
  • the reactive zinc salt is util ⁇ ized in an amount effective to stabilize the compositions and prevent the formation of malodorous side products.
  • the reactive zinc salt is used in an amount ranging from about 0.05 to about the solubility limit of the zinc salt in water or other suitable carrier.
  • the amount of zinc salt utilized may comprise as little as about 0.05 weight per ⁇ cent, an amount greater than 0.19 percent is preferred.
  • Preferred zinc salts for use in the compositions of the pres ⁇ ent invention include highly water soluble organic and inorganic zinc salts including, for example, zinc acetate, zinc ammonium chloride, zinc bromide, zinc butyrate, zinc chlorate, zinc chloride, zinc fluoroborate, zinc formate, zinc formaldehyde sulfoxylate, zinc iodide, zinc lactate, zinc nitrate, zinc sulfocarbolate (zinc phenylsulfonate) and zinc sulfate, among others.
  • highly water soluble organic and inorganic zinc salts including, for example, zinc acetate, zinc ammonium chloride, zinc bromide, zinc butyrate, zinc chlorate, zinc chloride, zinc fluoroborate, zinc formate, zinc formaldehyde sulfoxylate, zinc iodide, zinc lactate, zinc nitrate, zinc sulfocarbolate (zinc phenylsulfonate) and zinc
  • Zinc salts of lower solubility include zinc caproate, zinc carbonate, zinc fluoride, zinc iodate, zinc laurate, zinc oxalate, zinc oxide, zinc sulfite, zinc tartrate, zinc hydride, zinc cyanide dithiocarbamates (e.g., dimethyl) , zinc phosphate, zinc potassium chromate and zinc tetraoxide chromate, among others.
  • Especially preferred zinc salts include zinc oxide and zinc phenylsulfonate (zinc sul- focarbolate tm available from Universal Preservachem, Inc., Brooklyn, New York, USA) , used alone or in combination.
  • compositions of the present invention may also include at least one cationic polymer, either alone or preferably in combination with a reactive zinc salt and/or cationic or non ⁇ ionic surfactant.
  • a reactive zinc salt and/or cationic or non ⁇ ionic surfactant Virtually any cationic polymer which stabi ⁇ lizes the compositions of the present invention and inhibits the formation of malodorous gasses and other side products are contemplated for use in the present invention.
  • Such cationic polymers may be selected from among synthetic, semi-synthetic and natural cationic polymers.
  • the cationic polymers of the present invention may be selected from among polysaccharides, for example polycellulosic polymers, condensation polymers, polyamines, polyoxyalkylenes, polyalkyleneimines, homo and co ⁇ polymers of ethylenically unsaturated compounds, including poly(meth)acrylamides, poly(meth)a ⁇ rylates, polyvinylpyrrol- lidones, diallyl dialkyl ammonium halides, as well as grafts or copolymers of such materials, among others, each of which contains cationic groups.
  • polysaccharides for example polycellulosic polymers, condensation polymers, polyamines, polyoxyalkylenes, polyalkyleneimines, homo and co ⁇ polymers of ethylenically unsaturated compounds, including poly(meth)acrylamides, poly(meth)a ⁇ rylates, polyvinylpyrrol- lidones, diallyl dialkyl ammonium halides, as well as graft
  • the cationic polymers of the present invention are water soluble and contain quaternary- ammonium groups.
  • Exemplary preferred polymers may be selected from among the quaternary nitrogen-containing cellulosic ethers for example, JR-30M tm , JR-125 tm and JR-400 tm , available from Amerchol Corp. New Jersey, USA, LR-400, LR-30M and SR-10, available from Union Carbide Corp., USA, quaternary nitrogen- containing polysaccharides, for example the Quatrisoft ⁇ 111 polymers available from Union Carbide Corp.
  • graft copolymers of cellulose ethers and dialkyl diallyl ammonium halide polymers for example the Celquat ⁇ 1 " polymers, availabe from National Starch, New Jersey, USA, homo and copolymers of of dialkyl diallyl ammonium halide, for example the Merquat tm polymers available from Calgon Corp., USA, copolymers of vinyl pyrrolidone and quaternized dialkylaminoalkyl methacrylate, for example, the Gafquat tm polymers, available from GAF Corp.
  • copolymers of acrylamide and quaternized dialkyl amino dialkyl methacrylate for example, the Reten*- m polymers, available from Hercules, Inc. , Wilming ⁇ ton, Del. USA as well as other polyquaternium polymers.
  • the cationic polymer is used in an amount effective to substantially reduce the malodor associated with the storage of thiol containing compositions, for example reducing agents and certain proteins which are included in the compositions of the present invention.
  • the cationic polymer is used in an amount comprising at least about 0.01 percent by weight to about 20 percent by weight, preferably about 0.025% to about 20% by weight and most preferably about 0.1% to about 5% by weight of the composition.
  • Some cationic polymers may produce irritation when placed in proximity to the skin. Those of ordinary skill in the art will understand to adjust the amount and type of cationic polymer used in compositions of the present invention.
  • the cationic polymer may be used alone or preferably in combination with reactive zinc salts and/or cationic or nonionic surfactants. Where compositions are formulated using a cationic polymer in the presence of reactive zinc salts and/or cationic or nonionic surfactants, the amount of cationic polymer, although generally falling within the weight ranges described hereinabove, may be reduced to accommodate the zinc salt and/or surfactant.
  • compositions of the present invention may also contain at least one surfactant selected from among cationic and non ⁇ ionic surfactants.
  • surfactants may be added to the compositions to stabilize and prevent the formation of malodorous side products. Therefore, cationic and nonionic surfactants which tend to complex and stabilize mercaptides without reducing their activity are contemplated for use in the present invention. While any cationic surfactant which complexes and stabilizes mercaptides is contemplated for use in the present invention, it is preferred that cationic sur ⁇ factants containing amines, and in particular, quaternary amines, are used in the present invention.
  • the surfactant comprises at least about 0.05% by weight of com ⁇ positions of the present invention up to about 15% by weight of the compositions.
  • the surfactant comprises about 0.05% to about 5% by weight of the compositions of the present invention.
  • cationic amine containing surfactants con ⁇ templated for use in the present invention include phenyl and alkyl ammonium surfactants, including benzalkonium bromide, benzethonium chloride, benzylhexadecyldimethylammonium chloride, and cetyltrimethylammonium bromide, among others, oxyethyl substituted ammonium surfactants, including oxyethylammonium phosphate, ethoxylated alkylamines, for exam ⁇ ple the Dehyquat tln surfactants available from Henkel Corp., Ambler Pennsylvania and the alkylimidazolines, available from Mona Industries, Inc., West Paterson, New Jersey.
  • phenyl and alkyl ammonium surfactants including benzalkonium bromide, benzethonium chloride, benzylhexadecyldimethylammonium chloride, and cetyltrimethylammonium bromid
  • Quaternary amine containing surfactants are .clearly preferred including quaternized alkylamines, and quaternized ethoxylated alkylamines, the Monaquat tm surfactants, available from Mona Industries, Inc., West Patterson, New Jersey. Other cationic surfactants may also be used in compositions clearly con- templated by the present invention.
  • compositions of the present invention may also contain at least one nonionic surfactant.
  • Nonionic surfactants which are useful in the present invention include those surfactants which complex with mercaptides.
  • Especially preferred nonionic surfactants for use in compositions of the present invention include, for example, those nonionic surfactants having cationic character, i.e., exist as cations in certain resonance forms which may complex with mercaptides and stabi ⁇ lize the compositions of the present invention from producing malodorous side products.
  • Preferred nonionic surfactants for use in the present invention include alkanolamide surfactants, Amide 6560 tm , available from Emery Corp., Mauldin, South Carolina, USA, ethoxylated alkanolamides, for example, ethoxy ⁇ lated taloamine, Trymeen tm surfactant, available from Emery Corp., South Carolina and pyrrolidone containing surfactants.
  • alkanolamide surfactants Amide 6560 tm , available from Emery Corp., Mauldin, South Carolina, USA
  • ethoxylated alkanolamides for example, ethoxy ⁇ lated taloamine
  • Trymeen tm surfactant available from Emery Corp., South Carolina
  • certain fatty alcohol nonionic sur ⁇ factants such as for example seteth and steareth alcohols may also be included in compositions of the present invention.
  • compositions of the present invention most preferably contain at least one pyrrolidone containing surfactant in which a hydrophobic group is attached to the nitrogen of the pyrrolidone ring.
  • a number of hydrophobic groups on the nitrogen of the pyrrolidone ring may be employed, preferred hydrophobic groups include n-octyl, dodecyl and coco and tallow alkyl groups, most preferably n-octyl, attached to the nitrogen of the pyrrolidone ring in the surfactants LP- 100 tm , LP-300 tm , LP-800 tm , and LP-940 tm , available from GAF Corp., Linden, New Jersey USA.
  • the compositions of the present invention contain about 0.05 to about 5% by weight of a pyrrolidone containing surfactant.
  • compositions do not exhibit appreciable malodor, precipitation or "puckering" of containers caused by reaction of the formulations with gasses present in the container.
  • ethylenediaminetetraacetic acid for example Hampene 100 tm , available from Lowenstein, Inc. , Brooklyn, New York, USA, disodium, tetrasodium and zinc EDTA, or one of their chemical analogs, may be added to the composition in the presence of a reactive zinc salt.
  • Such compositions may optionally contain a cationic polymer and/or a pyrrolidone containing surfactant as described herein.
  • EDTA is used in compositions of the present invention, it generally com ⁇ prises between about 0.05 and about 2.0% by weight, preferably about 0.2 and about 0.9% by weight and most preferably between about 0.35 and 0.7% by weight of the composition.
  • compositions used in the present invention may addi ⁇ tionally comprise an effective amount of an oxidizing agent, generally ranging from about 0.01 to about 4.0% by weight of the compositions.
  • Preferred compositions comprise about 0.1 to about 1.5% of the oxidizing agent and most preferably about 0.5% to about 1.0% of the oxidizing agent.
  • the oxidizing agent is included in compositions of the present invention to enhance oxidation which may promote the formation of covalent disulfide bonds between activated protein and keratinous tis ⁇ sue. Additionally, the oxidizing agent may function as a dis ⁇ infecting agent to clean the keratinous tissue and enhance healing.
  • Exemplary oxidizing agents include hydrogen peroxide (which may or may not be stabilized with, for example, urea) and its salts including ammonium sulfate peroxide, urea peroxide, pyrophosphate peroxide, carbonate peroxide, organic peroxides including acetyl peroxide, benzoyl peroxide, among others, alkali metal perborates including sodium perborate, the alkali metal bromates including sodium and potassium bromate and sodium and potassium iodate.
  • hydrogen peroxide is the preferred oxidizing agent.
  • the amount of hydrogen peroxide should be included in an amount equal to about 0.01 to about 1.5% by weight of the com ⁇ position and most preferably about 0.05 to about 1.0% by weight.
  • oxidizing agents other than hydrogen peroxide are used, a higher percentage by weight is usually used com ⁇ pared to hydrogen peroxide which has a high oxidation equiv ⁇ alent per unit weight.
  • oxidizing agent may promote the polymerization of certain keratin molecules in situ, a condition which is advantageous for promoting the film-forming characteristics of certain thiol containing proteins.
  • compositions of the present invention may also include an antioxidant instead of, or in addition to, an oxidizing agent in an amount equal to about 0.01 to about 2.0% by weight of the composition.
  • an antioxidant is included to promote the storage stability of the formulations.
  • Exemplary antioxidants may include alpha-tocopherol, hydroxyquinone, unipherol, tocopherol ascorbate, lecithin, chlorophyll, ascorbylpal- mitate, linseed oil, tongue oil, other natural antioxidants such as the steam distillation extract of rosemary as dis ⁇ closed in U.S. Patent No. 4,450,097, thiazoline carboxylate, dihydroquinolines, methyl gallate, propyl gallate, alkylaryl and diarylamines.
  • Certain chelating agents for example, EDTA, may be employed to enhance the antioxidant effect of the above agents. It has also been found advantageous to add EDTA to the formulations containing a reactive zinc salt, as described hereinabove.
  • the chelating agent may function to chelate any dissolved metals which may be responsible for the in situ gen ⁇ eration of oxygen.
  • the chelating agent comprises between about 0.05 to about 2.0% by weight of the formulation, preferably about 0.2 and about 0.9% by weight and most preferably about 0.35 to about 0.7% by weight of the composi ⁇ tion.
  • an oxidizing agent when an oxidizing agent is not included in the formulations utilized, about 0.01% to about 2.0% of antioxidant is included in the formulations. Without the additional oxidizing agent, the antioxidant is included in compositions of the present invention to prevent atmospheric oxygen or oxygen dissolved in the solution from deactivating the protein or the reducing agent during storage.
  • the oxidizing agent comprises about 0.01% to about 4.0% by weight of an oxidizing agent and the antioxidant comprises about 0.01% to about 4.0% of the formulation.
  • compositions comprising an antioxidant and optionally, an oxidizing agent may additionally comprise acids, bases, buffering agents,.emulsifying agents or surfac ⁇ tants, thickeners, chelating agents, film-forming polymers, preservatives, organic solvents, coloring agents and perfume agents as described for other embodiments of the present invention. It is to be recognized by one of ordinary skill in the art that the choice of additives is made to avoid any interaction that may affect the activity of the film- forming protein, reducing agent, and in certain cases, reac ⁇ tive zinc salt, cationic polymer, pyrrolidone containing sur ⁇ factant, oxidizing agent or antioxidant.
  • film-forming polymer it is often preferred to add a film-forming polymer to the compositions of the present invention to promote the film- forming effects of the proteins used in compositions of the present invention.
  • Preferred film-forming polymers for use in the present invention include polyvinyl pyrrolidone, for example PVP K30 (GAF Charlotte, N.C.), carbomers, for example the Carbapolt 111 polymers such as Carbapol 940* :n ⁇ , polyacrylates, gums, for example, methylcellulose, hydroxymethylcellulose, carboxymethylcellulose, propylcellulose and hydroxypropylcel- lulose, among other film-forming polymers.
  • Exemplary acids and bases are added to adjust the pH of the formulation to desired levels.
  • Preferred acids include organic acids for example acetic acid, citric acid and tartaric acid, among others, and inorganic phosphoric acid including its salts such as the salts of mono- and di- hydrogen phosphoric acid.
  • the inorganic phosphoric acid salts may also be included in the formulations as buffering agents.
  • Preferred bases include organic amines, for example, monoethanolamine, triethanolamine, trimethylamine and triethylamine. Most preferred bases include ammonium hydroxide.
  • Buffering agents for example the inorganic phosphoric acid salts indicated above, as well as other buffering agents, for example the salts of organic acids such as acetic acid and citric acid may be included in the formulations of the present invention in amounts effective to maintain the pH of the for ⁇ mulation over time.
  • the amount of buffering agent is included in an amount no greater than about 1.5% by weight of the formulation and most preferably is less than about 0.75% by weight.
  • the pH of the formulation may be a factor in determining its stability and in maintaining the activity of certain components in the formulation, especially the activated protein and the compatible reducing agent.
  • a buffering agent may be included within the formulation to maintain the pH at a relatively constant level over time.
  • organic solvents may be included.
  • solvents that may be useful in certain embodiments of the present formulation are water soluble polar organic solvents, for example alkanols such as methanol, ethanol, propanol, butanol and carbonyl containing solvents for example acetone, butanone and the like, among others.
  • Additional sol ⁇ vents include ethers and amines, for example diethyl or dipropyl ether and trimethyl or triethyl amine. Trimethylamine and triethylamine may also be added as bases.
  • the solvent added to the formulation may enhance the solubility of certain components. Where liquid formulations are contemplated, it is sometimes advisable to add an organic solvent to promote the solubility of certain less polar com ⁇ ponents, without which the compositions may separate into more than one phase. The addition of the organic solvent may pro ⁇ cute a uniform, homogeneous single phase.
  • Emollients may also be included, especially in lotions to produce a uniform, homogeneous single phase and provide other favorable characteristics.
  • An especially preferred emollient for use in formulations of the present invention is PPG 15-sterol ether which also may be added to the formula ⁇ tions of the present invention for its emulsifying character ⁇ istics.
  • An emulsifying agent or surfactant other than those surfactants, i.e., cationic and nonionic surfactants described hereinabove which are added in certain embodiemtns to stabi ⁇ lize the compositions and reduce the formation of malodorous side products, is often added to embodiments of the present invention to enhance the characteristics of the formulation, to promote the solubility of the protein and other components and the phase stability of the formulation. Such agents also provide detergent-like qualities to the formulations.
  • Suitable surfactants or emulsifying agents may be nonionic, anionic or amphoteric.
  • Nonionic emulsifying compositions include, for example the lower alkylene oxide condensation products of hydrophobic compounds, for example ethylene oxide condensation products with higher fatty acids, higher fatty alcohols or alkylated aromatic hydrocarbons and higher molecular weight polypropylene glycols.
  • Preferred nonionic emulsifying compositions include polyoxyethylene ethers including polyoxyethyleneisohexadecyl ether, for example Arlasolve 200 tln (available from ICI Americas, Wilmin-gton Delaware) , polyoxyethylenelauryl ether, for example Brij 35 tm (ICI) , polyoxyethylenestearyl ether, for example Brij 72 tm , and Brij 78 tm (ICI) and polyoxypropylenestearyl ether, for example PPG-15 stearyl ether (Arlamol E, ICI) .
  • polyoxyethylene ethers including polyoxyethyleneisohexadecyl ether, for example Arlasolve 200 tln (available from ICI Americas, Wilmin-gton Delaware) , polyoxyethylenelauryl ether, for example Brij 35 tm (ICI) , polyoxyethylenestearyl ether, for example Brij 72 tm , and Brij 78 tm (
  • exemplary emulsifiers include ethoxylated lanolin, for example, Lanogel 41 tm (Amerchol, Inc., Edison, N.J.).
  • exemplary anionic surfactants include sulfuric acid esters of polyhydric alcohols, e.g. lauryl sul- fate, cetyl sulfate, etc.
  • higher fatty alcohol sulfates derived from coconut oil hydroxy sulfonated higher fatty acid esters such as, e.g., higher fatty acid esters of 2,3- dihydroxy-propane sulfonic acid, higher fatty acid esters of low molecular weight alkylol sulfonic acids, e.g., oleic acid ester of isethionic acid, sulfated higher fatty acid alkylola ides such as e.g., ethanolamide sulfates, higher fatty acid amides of amine alkyl sulfonic acids, e.g., lauric amide of taurine, among others, and aromatic containing anionic synthetic surfactants.
  • Exemplary amphoteric surfac ⁇ tants include the salts of N-alkyl compounds of betaamino propionic acid wherein the alkyl group is derived from a fatty acid such as a mixture of coconut oil fatty acids, among others.
  • an anti-foaming agent to certain com ⁇ positions to promote homogeneity and prevent foaming from sur ⁇ factant action.
  • a preferred anti-foaming agent for use in embodiments of the present invention includes, for example, Dimethiconet 111 , available from Dow Chemical Corp., Midland, Michigan.
  • Thickeners or gelling agents may be added to provide additional weight and a more viscous feel to the formulations or, in certain cases, to provide additional film-forming char- acteristics to the compositions of the present invention.
  • Suitable thickening agents include polyvinyl pyrollidone, for example PVP K30 (GAF Charlotte, N.C.) polyacrylates, car- bomers, for example carboxyvinyl polymer such as Carbapol 940
  • polyoxyethylene stearyl ethers for example, polyoxyethylene-2 stearyl ether such as Steareth 2 tm (ICI) and polyoxyethylene-
  • stearyl ether such as Steareth 20 tm (ICI) , sodium alginate, carageenan, agar, ethoxylated polyvinyl alcohol, gums, for example methylcellulose, hydroxymethylcellulose, car- boxymethylcellulose, propylcellulose and hydroxypropylcel- lulose, acacia, tragacanth, guar, and quince, among others.
  • ICI Steareth 20 tm
  • sodium alginate sodium alginate
  • carageenan agar
  • ethoxylated polyvinyl alcohol ethoxylated polyvinyl alcohol
  • gums for example methylcellulose, hydroxymethylcellulose, car- boxymethylcellulose, propylcellulose and hydroxypropylcel- lulose, acacia, tragacanth, guar, and quince, among others.
  • compositions which are contemplated to be formulated as a gel or lotion Isoseteth 20 tm (polyoxyethyleneisohexadecyl ether, ICI) , and Steareth 2 tm and 20 tm are preferred for use as thickening agents.
  • preferred thickeners include
  • Steareth 2 tm and Steareth 20 tm and the carbomer polymers for example Carbapol 940 " ⁇ .
  • Preservatives are added for preventing microbial growth in the presence of protein nutrients.
  • exemplary pre ⁇ servatives include benzoic acid analogs including, among others, sodium benzoate.
  • Other presevatives include propyl and methyl paraben, Dowiciltm (Dow Chemical Corp., Midland, Mi.) and formaldehyde solution.
  • An especially preferred pre ⁇ servative is Germaben II ⁇ 111 , available from Sutton Laboratories, New Jersey.
  • agents may also be added to certain embodiments of the present invention which are intended to treat wounds for the purpose of disinfecting the wounds and surrounding tissue and for providing antimicrobial protection.
  • agents for this use include the topical disinfec ⁇ tants and antiseptics, for example, Benzalkonium chloride, cetrimide, chloramine, chlorhexidine, among others.
  • Antimicrobial agents which may be used in the present, inven ⁇ tion include neomycin, bacitracin, spectinomycin, sulfa con ⁇ taining preparations, and polymixin, among others, and antifugal agents such as griseofulvin, amphotericin, chlor- dantoin, clotrimazole, dimethizole, miconazole and nystatin, among others.
  • compositions of the present invention may be used to treat acne.
  • Compositions for treating acne may include the compositions of the present invention in combina ⁇ tion with pharmaceutically effective amounts of benzoyl peroxide, tetracycline and other anti-acne agents.
  • the com ⁇ positions of the present invention may also be used to resolve pock marks and acne scars in individuals who have not had acne for years.
  • Compositions of the present invention may also be used to ameliorate wrinkling of skin that occurs with age or with overexposure to the sun and to grow hair and nails and prevent hair loss.
  • compositions of the present invention may also be used to treat dandruff.
  • Certain compositions for treating dandruff may include the compositions of the present invention in com ⁇ bination with an effective amount of a traditional anti- dandruff agent, for example, zinc pyrithione.
  • compositions of the present invention are applied as a liquid, cream, gel or lotion by rubbing an effective amount of the compositions into the keratinous tissue to be treated.
  • the composition is used in an amount effective to produce a thin film over the treated area.
  • Fol ⁇ lowing application the compounds are allowed to dry. In certain cases, drying may be accelerated by the use of heat or circulating air. Subsequent to drying, formulations may be washed off, although this is not preferred when the composi ⁇ tions are used to treat wounds. When treating dandruff or sebborhea, the compositions may be washed before drying.
  • the method aspects of the present invention comprise exposing the area of keratinous tissue to be treated to any one of the compositions previously described hereinabove.
  • the composi ⁇ tions of the present invention may be applied to the affected area at least once a day and as many times a day as is neces ⁇ sary to produce an improved condition.
  • the therapeutic compositions are applied to the affected area between one and four times a day. Applications of fewer than one per day may be performed depending upon the use, indica ⁇ tion and severity, especially in the cosmetic area.
  • the formulation need only be applied after or during shampooing, which may only be once or twice a week.
  • the duration of therapy will depend on the condition treated and on the response of the condition to the therapy. Thus, when chronic conditions that do no respond to tradi ⁇ tional therapy are being treated, it is to be expected that the duration of therapy will be longer than when less severe conditions are treated.
  • compositions of the present inven ⁇ tion a number of methods may be employed. However, a preferred method of producing the compositions involves first activating proteins containing sufficient cysteinyl groups and then stabilizing the activated proteins in the presence of one or more of a reactive zinc salt, a cationic polymer or a sur ⁇ factant selected from cationic and nonionic surfactants effec ⁇ tive to substantially reduce the formation of malodorous side products.
  • the method involves activating a protein containing cysteinyl groups in the presence of a reducing agent, as described herein, preferably, at a pH above about 9.0 to pro ⁇ quiz a protein wherein a number of the thiol groups are reduced, i.e., the thiols exist as mercaptides (cysteinyl groups) , not dithiols (cystinyl groups) .
  • an effective amount of one or more of the reactive zinc salts, cationic polymers and surfactants selected from among cationic and nonion surfactants is combined with the reducing agent, the activated protein and other
  • the composi ⁇ tions of the present invention by simply mixing the components without regard to timing or activation of the protein com ⁇ ponent.
  • This method may be useful for producing the composi ⁇ tions of the present invention when the protein is a film- forming protein which contains insufficient cysteinyl groups, i.e., too few cysteinyl groups to covalently bind to the keratinous substrate to produce covalent bonding of protein to substrate, for example edible gelatin or collagen.
  • the protein is a film- forming protein which contains insufficient cysteinyl groups, i.e., too few cysteinyl groups to covalently bind to the keratinous substrate to produce covalent bonding of protein to substrate, for example edible gelatin or collagen.
  • a reducing agent at a pH above about 9.0 to facilitate the amount of reactive zinc salt which can be dissolved into the compositions.
  • the surprising therapeutic activity exhibited by composi ⁇ tions useful in the present invention may be the result of a combination of pharmacological effects which have been main ⁇ tained through the use of the stabilized products of the pres ⁇ ent invention.
  • the possibility for the formation of biologically reactive prod ⁇ ucts must be considered.
  • compositions of the present invention maintain substantially the same activity as the compositions described, in, for example, U.S.
  • Patent Application Serial Number 319,402 entitled “Compositions and Methods for Treating Skin Conditions and Promoting Wound Heal ⁇ ing", filed March 3, 1989 and U.S. Patent Application Serial Number 319,147, entitled “Storage Stable Compositions and Methods for Treating Keratinous Tissue", filed March 3, 1989, relevant portions of which are incorporated by reference herein, without evidencing instability and the production of malodorous side products.
  • phase B ingredients separately heating at about 125"F until B.3 is melted. Mix thoroughly, then add to phase A at 100° for 10 minutes.
  • phase C Premix the ingredients in phase C in the order listed while mixing continuously. Add phase C to phases A & B, still at 100A and mix for 10 minutes.
  • phase D additive phase D to phases ABC while mixing, and mix for another 10 minutes.
  • the batch may become cloudy at this point, but this is normal.
  • phase E Combine the ingredients in phase E in the order listed, and mix for 10 minutes. This step is designed to activate the Kerasol. Add phase E to phases ABCD while mixing and con- tinue to mix for 10 minutes. The batch becomes a clear liq ⁇ uid.
  • phase F While continuing to mix, add phase F to the batch and mix for 10 minutes.
  • the final pH of this formulation ranges between about 8.0 and 8.2.
  • phase A Combine ingredients in phase A, then place phase B in a separate container and heat to 145"-150° F. , and maintain at that temperature.
  • phase A Places phase A in a high speed mixer, create a vortex, sprinkle phase B into vortex, and mix until completely and thoroughly blended.
  • phase C additive to phases AB while mixing, and mix until uniform.
  • phase D Add phase D to phases ABC, and mix until completely uniform.
  • phase E additive phase E to phases ABCD. This causes the batch to gel. Mix until completely uniform.
  • phase F Premix phase F, and add to a separate container sufficient to hold phases F and G.
  • phase G Premix phase G, mix well and allow to stand for 5 minutes. Add phase G to phase F and mix mechanically for 10 minutes. Keep mixing and add phases FG to phases ABCD while mixing. Continue mixing until smooth and uniform.
  • phase A After phase A has been prepared, place phase B in a sepa ⁇ rate container and heat to 145°-150" F. , and maintain at that temperature.
  • phase A Places phase A in a high speed mixer, create a vortex, sprinkle phase B into vortex, and mix until completely and thoroughly blended.
  • phase C additive to phases AB while mixing, and mix until uniform.
  • phase D Add phase D to phases ABC, and mix until completely uniform.
  • phase E additive phase E to phases ABCD. This causes the batch to gel. Mix until completely uniform.
  • phase F Premix phase F, and add to a separate container sufficient to hold phases F and G.
  • phase G Premix phase G, mix well and allow to stand for 5 minutes. Add phase G to phase F and mix mechanically for 10 minutes.
  • phase A Combine ingredients in phase A, then place phase B in a separate container and heat to 145 ⁇ -150"F., and maintain at that temperature.
  • phase A Places phase A in a high speed mixer, create a vortex, sprinkle phase B into vortex, and mix until completely and thoroughly blended.
  • phase C additive to phases AB while mixing, and mix until uniform.
  • phase D Add phase D to phases ABC, and mix until completely uniform.
  • phase E additive phase E to phases ABCD. This causes the batch to gel.
  • Premix phase F and add to a separate container suffi ⁇ cient to hold phases F and G.
  • Premix phase G mix well and allow to stand for 5 minutes.
  • cationic polymer JR-400 To the concentrated liquid of example 11 is added 0.5, 1, 2, 3, 4, 5 and 6% by weight of cationic polymer JR-400. All samples proved to be active; there was a dose related decrease in malodorous thiol or sulfide scents across the range tested.
  • Example 1 To Concentrated Stock Solution (Example 1) was added 0.45% Surfidone LP-100 until the mixture was thoroughly homogenized. This produced a composition which produced a further reduction in scent but maintained efficacy (See similar example 2) . To this zinc/surfidone mixture was added JR-400 up to about 4% by weight of the composition. This pro ⁇ depictd a composition which provided a further reduction in scent and a useful, efficacious composition. An excessive surfactant effect became manifest as an inhomogeneity in the formulations such that thinner and thicker areas of the for ⁇ mulation were observed. Results of this composition indicated that scent was reduced and the composition was useful.
  • Formulations which did not contain a reactive zinc salt, a cationic polymer or a cationic or nonionic surfactant evidenced a malodor which necessitated considerable scenting with heavy, cloying fragrances.
  • the scents used to cover the malodor were not ideal, because of the heavy fragrance and the need to use high concentrations. Although an improvement over unscented compositions, they were not extremely pleasing and evidenced some instability.
  • Compositions utilizing a reactive zinc salt, a cationic polymer or a cationic or nonionic sur ⁇ factant reduced the malodor of the formulations sufficiently so that only one half of the previous concentration of fragrance was required, and lighter, cleaner smelling fragrances could be utilized to enhance the smell of the for ⁇ mulations.
  • the result has been formulations which are con ⁇ siderably more pleasant to the smell and which increase com ⁇ pliance.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Birds (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Cosmetics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention concerne des compositions inodores et de conservation stable, comprenant des protéines filmogènes contenant des agents de réduction et éventuellement au moins un composant sélectionné parmi les éléments suivants: des sels de zinc réactif, des polymères cationiques et des agents tensio-actifs cationiques ou non ioniques. La présente invention concerne également ces compositions qui contiennent des agents d'oxydation et/ou des anti-oxydants, et les procédés d'utilisation. Les compositions thérapeutiques et les procédés de la présente invention sont particulièrement efficaces pour favoriser la cicatrisation des blessures, et empêcher certains problèmes de peau, y compris l'eczéma et la séborrhée, la sclérodermie, les ongles pendants, les rides et l'acné, y compris les cicatrices dues à l'acné. Les compositions thérapeutiques et les procédés de la présente invention se sont également révélés efficaces comme outil vétérinaire pour réduire la débilitation associée à certains problèmes de la peau chez des mammifères y compris la dermatite eczématiforme, la dermatite chronique, le granulome équin exubérant (''chaire exubérante''), des escarres et, des granulomes cutanés canins (granulome ''de léchage''). Les compositions de la présente invention sont également utiles pour le conditionnement de tissus cornés et kératineux de mammifères tels que les cheveux et les ongles, et les pattes et le pelage d'animaux pour améliorer leur résistance et leur aspect. De plus, ces compositions sont utiles pour favoriser la croissance des cheveux et des ongles.
EP19900914307 1989-08-18 1990-08-17 Odor-masked and stabilized compositions for treating keratinous tissue, skin conditions, and promoting wound healing Withdrawn EP0487648A4 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US39647489A 1989-08-18 1989-08-18
US396474 1989-08-18

Publications (2)

Publication Number Publication Date
EP0487648A1 true EP0487648A1 (fr) 1992-06-03
EP0487648A4 EP0487648A4 (en) 1993-03-31

Family

ID=23567320

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19900914307 Withdrawn EP0487648A4 (en) 1989-08-18 1990-08-17 Odor-masked and stabilized compositions for treating keratinous tissue, skin conditions, and promoting wound healing

Country Status (6)

Country Link
EP (1) EP0487648A4 (fr)
JP (1) JPH05503071A (fr)
AU (1) AU6425590A (fr)
CA (1) CA2065044A1 (fr)
IL (1) IL95393A0 (fr)
WO (1) WO1991002538A1 (fr)

Families Citing this family (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW222591B (fr) * 1991-08-30 1994-04-21 Procter & Gamble
IT1252061B (it) * 1991-11-22 1995-05-29 Gentili Ist Spa Composizioni per uso dermatologico e cosmetico
AU3328693A (en) * 1991-12-18 1993-07-19 Advanced Oxygen Technologies, Inc. Treatment of fungal infections
DE4142319A1 (de) * 1991-12-20 1993-06-24 Henkel Kgaa Wundantiseptikum
US5358706A (en) * 1992-09-30 1994-10-25 Union Carbide Chemicals & Plastics Technology Corporation Muco-adhesive polymers
US5645827A (en) * 1992-09-30 1997-07-08 Union Carbide Chemicals & Plastics Technology Corporation Muco-adhesive polymers
FR2704394B1 (fr) * 1993-04-27 1995-06-02 Boiron Complément nutritionnel absorbable pour le traitement des cheveux et des ongles.
FR2705564B1 (fr) * 1993-05-25 1995-07-13 Oreal Nouveau procédé de déformation permanente des cheveux et composition pour sa mise en Óoeuvre contenant en association un amino ou amidothiol et au moins un bromure minéral.
US6113893A (en) * 1993-07-28 2000-09-05 Pfizer Inc. Psoriasis treatment
KR100200447B1 (ko) * 1993-07-28 1999-06-15 디. 제이. 우드, 스피겔 알렌 제이 건선의 치료를 위한 조성물
GB9515373D0 (en) * 1995-07-21 1995-09-20 Unilever Plc Hair styling method
FR2740341B1 (fr) * 1995-10-26 1997-12-19 Oreal Utilisation de sel de lanthanide, d'etain, de zinc, de manganese, d'yttrium, de cobalt, de baryum, de strontium dans une composition pour la peau
FR2740340B1 (fr) * 1995-10-30 1997-12-05 Oreal Utilisation d'acides carboxyliques porteurs d'une fonction soufree pour favoriser la desquamation de la peau ou stimuler le renouvellement epidermique
GB2320431B (en) * 1996-12-20 2000-08-30 Johnson & Johnson Medical Compositions for the treatment of chronic wounds
JP3949176B2 (ja) 1997-03-03 2007-07-25 クエスト・インターナショナル・ビー・ブイ 還元硫黄種及び亜鉛化合物を含有する毛処理組成物
EP0973488B1 (fr) * 1997-03-03 2002-10-23 Quest International B.V. Compositions de traitement des cheveux et des poils contenant une espece sulfureuse reductrice et un compose de zinc
GB9711447D0 (fr) * 1997-04-09 1997-07-30 Reckitt & Colman France
IT1291622B1 (it) * 1997-04-18 1999-01-11 Marcello Izzo Uso dell'acido tioglicolico come agente depigmentante
CN1110298C (zh) * 1997-09-26 2003-06-04 株式会社资生堂 皮肤外用剂
JP4111546B2 (ja) * 1997-12-15 2008-07-02 ウルトラデント プロダクツ インコーポレイテッド 重合可能な隔離バリア、およびかかるバリアを形成しかつ使用する方法
DE19831043A1 (de) * 1998-07-13 2000-01-27 Deutsches Krebsforsch Hemmung von Alopezie
US6497893B1 (en) * 1999-06-30 2002-12-24 Kimberly-Clark Worldwide, Inc. Silk protein treatment composition and treated substrate for transfer to skin
EP1145707A4 (fr) * 1999-01-28 2005-08-31 Shiseido Co Ltd Compositions destinees a un usage externe
US6500443B1 (en) 1999-06-30 2002-12-31 Kimberly-Clark Worldwide, Inc. Delivery of a sacrificial substrate to inhibit protease permeation into skin
US6506394B1 (en) 1999-06-30 2003-01-14 Kimberly-Clark Worldwide, Inc. Delivery of a botanical extract to a treated substrate for transfer to skin
AU5901600A (en) * 1999-06-30 2001-01-31 Kimberly-Clark Worldwide, Inc. Delivery of a skin health benefit agent to a treated substrate for transfer to skin
US6371984B1 (en) 1999-09-13 2002-04-16 Keraplast Technologies, Ltd. Implantable prosthetic or tissue expanding device
US6503524B1 (en) 2000-06-16 2003-01-07 Kimberly-Clark Worldwide, Inc. Delivery of a skin health benefit agent to a treated substrate for transfer to skin
AU2002223679A1 (en) * 2000-12-19 2002-07-01 Unilever Plc Hair treatment composition
WO2003064449A2 (fr) 2002-01-28 2003-08-07 Keraplast Technologies, Ltd. Peptides bioactifs de keratine
US20030219465A1 (en) * 2002-05-23 2003-11-27 Suresh Kumar Gidwani Composition for delivery of dithranol
WO2004024176A1 (fr) * 2002-08-30 2004-03-25 Henkel Kommanditgesellschaft Auf Aktien Combinaison synergique de proteines de soie
AT502435B1 (de) * 2002-11-19 2008-01-15 Oekopharm Forschungs Und Entwi Pharmazeutische zusammensetzung umfassend ein wasserstoffübertragendes coenzym und chlorophyll
US7439012B2 (en) 2004-08-17 2008-10-21 Wake Forest University Health Sciences Ambient stored blood plasma expanders containing keratose
DE102004046063A1 (de) * 2004-09-22 2006-03-23 Henkel Kgaa Geruchsreduzierendes Haarbehandlungsmittel
GB0511499D0 (en) * 2005-06-06 2005-07-13 Medpharm Ltd Topical ungual formulations
US8920827B2 (en) 2005-10-21 2014-12-30 Wake Forest University Health Sciences Keratin bioceramic compositions
EP1991253B1 (fr) 2006-02-10 2013-07-31 Wake Forest University Health Sciences Régénération nerveuse utilisant des bio-matériaux de kératine
JP2009527274A (ja) 2006-02-17 2009-07-30 ウェイク・フォレスト・ユニヴァーシティ・ヘルス・サイエンシズ ケラチン医用生体材料から形成されるコーティングおよび生体用インプラント
US8273702B2 (en) 2006-02-17 2012-09-25 Wake Forest University Health Sciences Wound healing compositions containing keratin biomaterials
JP2008063334A (ja) * 2006-08-10 2008-03-21 Lion Corp 水溶性有効成分の付着化組成物及び水溶性有効成分の付着方法
GB2458531A (en) * 2008-03-26 2009-09-30 Boots Co Plc Strengthening hair care composition comprising mild reducing agent
WO2010093882A1 (fr) 2009-02-13 2010-08-19 Wake Forest University Health Sciences Biomatériaux de kératine pour culture de cellules et procédés d'utilisation
EP2542564B1 (fr) 2010-03-05 2018-05-09 Wake Forest University Health Sciences Système d'administration contrôlée
US8545893B2 (en) 2010-03-08 2013-10-01 Wake Forest University Health Sciences Keratin biomaterials for treatment of ischemia
CA2818166C (fr) 2010-11-17 2019-04-30 Wake Forest University Health Sciences Compositions keratiniques pour le traitement d'une deficience ou lesion osseuse
EP2934695B1 (fr) * 2012-12-19 2016-11-30 Colgate-Palmolive Company Produits antitranspirants contenant une protéine et des sels antitranspirants
GB2549015B (en) * 2014-12-12 2022-01-12 Valentine Kasowski Robert Flame Retardant and Flame Retardant Uses
CN109310630A (zh) * 2016-04-13 2019-02-05 诺万公司 用于治疗感染的组合物、系统、试剂盒和方法
EP3544573A1 (fr) * 2016-11-25 2019-10-02 Urgo Recherche Innovation et Développement Composition filmogène
CN113134028B (zh) * 2021-04-28 2022-04-12 维尼健康（深圳）股份有限公司 一种伤口消毒液及其制备方法
JP2024011766A (ja) * 2022-07-15 2024-01-25 株式会社ナチュラルフィールドサプライ マニキュア用ベースコート剤
JP7806385B2 (ja) * 2022-12-28 2026-01-27 ハウスウェルネスフーズ株式会社 有効成分の滞留剤

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3842848A (en) * 1971-05-27 1974-10-22 Wilson Sinclair Co Keratin polypeptide hydrolyzates as hair treating agents
US4438102A (en) * 1982-08-10 1984-03-20 Ciro's Touch, Ltd. Method of promoting tissue growth
GB2160419B (en) * 1984-06-08 1990-02-14 Crestol Ltd Treatment of hair, skin and nails
CA1278750C (fr) * 1985-07-23 1991-01-08 Nobuo Kobayashi Agents aqueux desodorisants, et methodes de desodorisation
CA1324764C (fr) * 1988-07-13 1993-11-30 Aikoh Co., Ltd. Composition a reaction pour desodorisant pouvant inhiber la corrosion
KR900701303A (ko) * 1988-07-22 1990-12-01 원본미기재 피부질환치료 및 상처 치유 촉진용 조성물 및 방법

Also Published As

Publication number Publication date
EP0487648A4 (en) 1993-03-31
JPH05503071A (ja) 1993-05-27
IL95393A0 (en) 1991-06-30
AU6425590A (en) 1991-04-03
WO1991002538A1 (fr) 1991-03-07
CA2065044A1 (fr) 1991-02-19

Similar Documents

Publication Publication Date Title
EP0487648A1 (fr) Compositions inodores et stabilisees pour traiter les tissus keratineux, des etats pathologiques de la peau et favoriser la cicatrisation de blessures
US5047249A (en) Compositions and methods for treating skin conditions and promoting wound healing
JP3157823B2 (ja) 含水ペースト型製薬組成物
US4946870A (en) Delivery systems for pharmaceutical or therapeutic actives
KR102043855B1 (ko) 표면 개질용 기능성 조성물
US3252866A (en) 2-hydrocarbon substituted-amido mercaptopropionamides in hair waving compositions and processes
EP0273952B1 (fr) Shampoing nettoyant, tonifiant et de traitement medicinal en deux phases
AU600736B2 (en) Compositions used in permanent structure altering of hair
CZ252598A3 (cs) Přípravky obsahující antifungální sloučeninu a sloučeninu síry
JP2002080401A (ja) ゲル状外用剤組成物
EP0425507B1 (fr) Compositions et procedes pour traiter des infections dermiques et activer la cicatrisation
JP2884428B2 (ja) 洗浄組成物
AU614832B2 (en) Storage-stable compositions and methods for treating keratinous tissue
HU193289B (en) Cosmetical composition for treating hair and nail containing blood plasma concentrate as active agent
EP0344708B1 (fr) Composition pour l'application externe sur la peau
JPH05170625A (ja) 養毛化粧料
WO1993024102A1 (fr) Shampoing a base de sulfure de selenium presentant des proprietes traitantes
JPS63277608A (ja) 皮膚および毛髪用組成物
JPH04305517A (ja) 養毛化粧料
JP3434635B2 (ja) 含水化粧料の変臭・変色防止方法
JPH0578223A (ja) シヤンプー
JPH069348A (ja) 養毛化粧料
JP2002241257A (ja) 皮膚化粧料
JPS6330404A (ja) 皮膚外用剤
KR20190126033A (ko) 표면 개질용 기능성 조성물

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19920302

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB IT LI LU NL SE

A4 Supplementary search report drawn up and despatched

Effective date: 19930209

AK Designated contracting states

Kind code of ref document: A4

Designated state(s): AT BE CH DE DK ES FR GB IT LI LU NL SE

17Q First examination report despatched

Effective date: 19950925

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 19960410