WO2004011032A1 - External preparation - Google Patents

External preparation Download PDF

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Publication number
WO2004011032A1
WO2004011032A1 PCT/JP2003/009446 JP0309446W WO2004011032A1 WO 2004011032 A1 WO2004011032 A1 WO 2004011032A1 JP 0309446 W JP0309446 W JP 0309446W WO 2004011032 A1 WO2004011032 A1 WO 2004011032A1
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WO
WIPO (PCT)
Prior art keywords
external preparation
preparation according
wound healing
disinfectant
pectin
Prior art date
Application number
PCT/JP2003/009446
Other languages
French (fr)
Japanese (ja)
Inventor
Takayuki Ishii
Katsunori Morishita
Tomoaki Takigawa
Toshiaki Sato
Original Assignee
Mikasa Seiyaku Co., Ltd.
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 Mikasa Seiyaku Co., Ltd. filed Critical Mikasa Seiyaku Co., Ltd.
Priority to JP2004524148A priority Critical patent/JP4712380B2/en
Priority to AU2003252694A priority patent/AU2003252694A1/en
Publication of WO2004011032A1 publication Critical patent/WO2004011032A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/717—Celluloses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/719—Pullulans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/732—Pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/734—Alginic acid
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A61P23/02—Local anaesthetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents

Definitions

  • the present invention relates to an external preparation containing a medicinal ingredient generally known as an external preparation, which also exhibits an effective action of promoting wound healing when applied to a skin disease or the like accompanied by a wound.
  • the present invention relates to an external preparation obtained by blending a wound healing promoting component with an external preparation applied to a part, skin or mucous membrane.
  • skin moisturizing agents anti-inflammatory agents, anti-allergic agents, local anesthetics, vitamins, and other drugs are used for skin and mucosal diseases associated with wounds, but depending on the disease associated with wounds and mucosal damage. There were also many drugs that would benefit from the inclusion of a wound healing promoter.
  • Disinfectants and disinfectants are examples of negative effects on wound healing. Disinfectants and disinfectants are widely used for disinfecting and disinfecting wounds, skin and mucous membranes, or for preventing bacterial infection. When these disinfectants are applied to wounds, they show bactericidal and disinfecting effects, but delay wound healing (Kramer S A. J Vase Nurs 17, 17, 23–23, 1 999; E ffectofpovid on e-iocl in eon wo und healing: arevi ew), and disinfectants are known to have an adverse effect on wound healing.
  • wound healing promoters are used for treatment of pressure ulcers and skin ulcers, etc.If wounds are infected with bacteria, apply the wound healing promoter after disinfecting the wound with a disinfectant / disinfectant There is a need. Wound dressings are also suitable for wounds infected with bacteria. There are also problems such as inapplicability.
  • a preparation that simultaneously exerts a bactericidal / disinfecting action and a wound healing promoting action it is desirable to use a preparation that simultaneously exerts a bactericidal / disinfecting action and a wound healing promoting action. That is, the combination of a disinfectant and a wound healing promoter is considered to be very useful. However, not all combinations of disinfectants and wound healing promoters are acceptable. It goes without saying that a combination preparation of a bactericidal / disinfectant and a wound healing promoter is stable in terms of formulation, but it must be a formulation that simultaneously exerts bactericidal / disinfecting action and a wound healing promoting action.
  • Sucrose / povidonodo is used clinically as a formulation containing a disinfectant and a wound healing promoter.
  • bactericidal and disinfecting effects are observed, there are reports that healing is delayed despite the inclusion of sucrose as a component that promotes wound healing. It has not been.
  • urea preparations are an example where it is better to incorporate a wound healing promoter.
  • Urea preparations have been used as an active ingredient for external use on the skin because they have excellent effects on the skin, such as keratin water retention and keratolytic exfoliation.
  • urine is irritating to the skin and mucous membranes and cannot be applied to wounds. From these facts, there is a demand for a drug that can heal wounds quickly and accurately while having a water-retaining effect in the stratum corneum and that can be applied to sites with wounds.
  • An object of the present invention is to provide an external preparation having an excellent wound healing promoting action and an original pharmacological effect of an external preparation, and capable of efficiently treating a skin disease accompanied by a wound.
  • the present invention is an external preparation containing a medicinal component and a wound healing promoting component, wherein the wound healing promoting component comprises a wound healing promoting hydrophilic polymer.
  • the wound healing promoting effect and the original pharmacological effect of the external preparation can be sufficiently exhibited only by blending a wound healing promoting hydrophilic polymer with a conventionally used external preparation. It has the advantage of being able to be used in the original mode of use of the agent, and as a result, exhibits great effects in both production and use.
  • the wound healing-promoting hydrophilic polymer used in the present invention is preferably a polymer that exhibits a wound healing promoting effect of at least 20% in a rat defect wound test, and contains at least one or more of these.
  • the type and structure are not particularly limited as long as it is selected, but preferred wound healing promoting hydrophilic polymers include pectin, alginic acid, carboxymethylcellulose, gum arabic, and pullulan. ⁇ ⁇ ⁇ Kuching, alginic acid and carboxymethylcellulose also include their salts.
  • pectin which can be used in the present invention pectin of natural origin, its partial hydrolyzate and physiologically acceptable salts thereof are used.
  • the physiologically acceptable salt is not particularly limited as long as it is physiologically acceptable.
  • the molecular weight of these pectins is from about 30,000 to about 800,000, preferably from about 30,000 to about 750,000, more preferably about 60,000. 0 to about 600,000, particularly preferably about 200,000 to about 500,000.
  • the origin of Pectin is not particularly limited.
  • the molecular weight means the molecular weight of the main peak measured by gel filtration (TSK-ge LG 400 PW).
  • Pectin has a degree of esterification of 20% or more, preferably 30 to 80%.
  • the ester is preferably a methyl ester, but may be another ester such as a C 2 -C 6 alkyl ester.
  • the carboxymethylcellulose that can be used in the present invention is not particularly limited.
  • Carboxymethylcellulose having a degree of oxidation of 0.4 to 2.0, preferably 0.6 to 1.2, and most preferably 0.65 to 1.0, or a salt thereof is usually used.
  • the viscosity of the 1% solution is 5 to 3,000 OmPas, preferably 10 to 2, OOOmPas, most preferably 30 to 1,500 mPa's. s is usually used.
  • alginic acid that can be used in the present invention alginic acid, its derivatives and physiologically acceptable salts thereof are used.
  • the physiologically acceptable salt is not particularly limited as long as it is physiologically acceptable. Examples of the alginic acid derivative include propylene glycol alginate.
  • Pharmaceutical ingredients that can be used in the present invention are medically acceptable, and include one or more components that are expected to exhibit a medicinal effect when applied to a wound, skin or mucous membrane, and are classified into those types.
  • typical examples thereof include generally widely used bactericides, disinfectants, skin moisturizers, anti-inflammatory agents, anti-allergic agents, local anesthetics, vitamins and the like.
  • the germicidal disinfectant that can be used in the present invention is not particularly limited as long as it contains at least one bactericidal / disinfecting agent.
  • Suitable germicidal / disinfecting agents include povidone and podholm, Iodine and iodine complexes such as iodine tincture and resorcinol, benzalkonium chloride, benzethonium chloride, decalinium chloride, cetylpyridinium chloride, cresyl soap, and other disinfecting stone compounds, silver and mercury compounds, erythromycin, gentamicin, Examples include antibiotics such as kanamycin, antifungals, acrinol, chlorhexidine dalconate, and the like.
  • Examples of the skin moisturizing agent which can be used in the present invention include polyhydric alcohols such as glycerin, propylene glycol, 1,3-butylene glycol, polyethylene glycol, dipropylene glycol, xylitol, sorbitol, free amino acids, urea, Natural moisturizing factors such as lactic acid and citrate, heparin-like substances, collagen, elastin, chondroitin sulfate, dermatan sulfate, fibronectin, hyaluronic acid, ceramide, chitosan, and hydantoin (Japanese Patent Application Laid-Open No. 9-2788645) And the like, but are not limited thereto.
  • polyhydric alcohols such as glycerin, propylene glycol, 1,3-butylene glycol, polyethylene glycol, dipropylene glycol, xylitol, sorbitol, free amino acids, urea
  • Anti-inflammatory agents that can be used in the present invention include, for example, azulene, aminoethyl benzoate, ibuprofen, indomethacin, glycyrrhizic acid, glycyrrhetinic acid, 7-lantoin, copper chlorophyllin, ketoprofen, methyl salicylate, salicylate glycol ester, diclofenac, suprofen, naproxen
  • Non-steroidal anti-inflammatory drugs or their salts including coX2 selective inhibitors such as piroxicam, felbinac, bufexamac, flurbiprofen, and meloxicam, celecoxib, oral fuecoxib, or salts thereof, alclomethasone, clobesol, Vesuvone, diflucortron, difluprednate, diflorazone, dexamethasone, deprodone, triamcinolone aceton
  • anti-allergic agent examples include diphenhydramine, carpinoxamine, dimenhydrinate, diphenirubiralin, clemastine, pyrilamine, triberenamine, chlorpheniramine, triprolysin, dimethindene, promethazine, alimimazine, isothidyl.
  • Antihistamines or their salts such as hydroxyzine, meclizine, homochlorcyclidine, cyprohepdin, or salts thereof, mexidin, terfenadine, epinastine, astemizole, ebastine, cetirizine, oral ratadine, cromoglycic acid, tranilast, ketotifen, azelastine , Oxatomide, Amlexanox, Repirinast, Ibudilast, Emilo last, Tazanolast, Ozadarrell, Splatast, Seratrodast Emadasu Chin, pranlukast, antiallergics or a salt such as crotamiton, Shikurosu porins, evening Kurorimusu, but we include an immunosuppressant drug or a salt thereof is one bets like methotrexate, but not limited to. These may be used alone or as a mixture of two or more.
  • Examples of the local anesthetic which can be used in the present invention include, for example, procarin, oxybuprocaine, ethyl amino benzoate, piberidyl acetylaminoethyl benzoate, cocaine, tetracaine, lidocaine, terikin, propitin Power In, Hexochikai , Dimethisoquine, promoxine, benzocaine, benzyl alcohol, catalysin, paletoxicaine, pyro-in, pro-inamide, propara-in, oral oxyn-in, hexylcaine, metabutemin, methtaboxin, pyridoxine, jib Power in, bupipa power in, mepiva power in, oxesazein, and salts thereof, but are not limited thereto. These may be used alone or as a mixture of two or more.
  • vitamin preparations examples include vitamin A, vitamin B group, bimin (:, vitamin D, vitamin E, vitamin K, vitamin ⁇ , nicotinic acid, pantothenic acid, folic acid, and derivatives thereof, and the like. However, these are not limited thereto, and they may be used alone or in combination of two or more.
  • the mixing ratio of the two components used in the present invention is selected within a range sufficient to exhibit the respective effects, but the wound healing-promoting hydrophilic polymer is preferably 0.01 to 60% by weight, More preferably, it is used in an amount of 3 to 30% by weight.
  • the external preparation of the present invention is not particularly limited in other optional components, dosage forms, and the like as long as it contains the above-mentioned components.
  • the external preparation of the present invention exhibits an excellent wound healing promoting effect without impairing the performance as an original external preparation.
  • Examples of the dosage form of the external preparation of the present invention include semisolid preparations such as ointments, creams, and gels, powder preparations, granules, sticks, sheets (including films), and suppositories. And liquid preparations such as aqueous solutions, suspensions, lotions and emulsions. In addition, these can be used as sprays if necessary. Further, as a patch, a patch, a plaster, a patch and the like can be mentioned, and an ointment, a cream, a gel, a stick, a sheet (including a film), and a cataplasm are preferable.
  • the application site of the external preparation of the present invention is not limited by the application range of the existing external preparation such as skin and mucous membrane. That is, depending on the type of existing topical preparation, it can be used for whole body skin and mucous membrane.
  • various components acceptable in the production of pharmaceuticals that is, aqueous components, oil components, water-soluble polymers, oil-soluble polymers, and oxidized components, as long as the effects of the present invention are not impaired.
  • Inhibitor, surfactant, freshener, buffer, ⁇ A stabilizer, antibacterial and preservative, etc. can be appropriately compounded.
  • aqueous component examples include lower alcohols such as ethanol, propyl alcohol and isopropyl alcohol; polyhydric alcohols such as glycerin and sorbitol; dalicols such as ethylene glycol, propylene glycol, butylene glycol, and polyethylene glycol; sucrose; Examples include sugars such as lactose, maltose, mannitol, erythritol, and xylitol, sugar alcohols, and purified water.
  • lower alcohols such as ethanol, propyl alcohol and isopropyl alcohol
  • polyhydric alcohols such as glycerin and sorbitol
  • dalicols such as ethylene glycol, propylene glycol, butylene glycol, and polyethylene glycol
  • sucrose examples include sugars such as lactose, maltose, mannitol, erythritol, and xylitol, sugar alcohols, and purified water.
  • oils component examples include saturated hydrocarbons such as white petrolatum and liquid paraffin, waxes such as salami beeswax and carnauba wax, oils and fats such as soybean oil and hard fat, stearyl alcohol, oleyl alcohol, and higher alcohols such as cholesterol.
  • saturated hydrocarbons such as white petrolatum and liquid paraffin
  • waxes such as salami beeswax and carnauba wax
  • oils and fats such as soybean oil and hard fat
  • fatty acids such as coals, isopropyl adipate, isopropyl sebacate, octyldodecyl myristate, and cetyl lactate
  • fatty acids such as palmitic acid, stearic acid, and oleic acid
  • silicone oils such as methylpolysiloxane.
  • water-soluble polymers examples include plant polymers such as guar gum, karaya gum, carrageenan, agar, starch, tragacanth gum, and oral cast bean gum; microbial polymers such as xansu gum, dextran, collagen, casein, and gelatin.
  • Alginic acid polymers such as methylcellulose, methylcellulose, methylhydroxypropylcellulose, nitrocellulose, sodium cellulose sulfate, cellulosic polymers such as crystal cell mouth, polyvinyl methyl ether, Polymer, polyoxyethylene-based polymer, polyacrylic acid-based polymer, polyvinyl alcohol, polyvinylpyrrolidone, and the like.
  • oil-soluble polymer examples include an acrylic acid / alkyl methacrylate copolymer.
  • surfactant examples include sorbitan monolaurate, sorbitan sesquioleate, sorbitan trioleate, polyoxyethylene sorbitan monolaurate, polyethylene glycol monoolate, polyoxyethylene alkyl ester, polyglycol ester, and lauroyl ester Evening amide, fatty acid isopropanolamide, maltitol hydroxyaliphatic ether, alkylated poly Nonionic surfactants such as sugars, alkyl darcosides, sugar esters, etc., cationic surfactants such as stearyl trimethylammonium chloride, lauryl amine oxide, sodium palmitate, sodium laurate, potassium lauryl sulfate, alkyl Examples thereof include anionic surfactants such as triethanolamine sulfate, linear dodecylbenzene sulfate, polyoxyethylene hydrogenated castor oil, maleic acid, and acylmethyltaurine, and naturally-derived surfactants such as lecithin
  • antioxidants examples include tocopherol, ascorbic acid, erythorbic acid, propyl gallate, BHT (dibutylhydroxytoluene), and BHA (butylhydroxyanisole).
  • cooling agent examples include menthol and camphor.
  • the buffer for example, disodium hydrogen phosphate-monocitrate, dihydrogen phosphate-disodium hydrogen phosphate, disodium citrate-disodium hydrogen phosphate and the like can be mentioned.
  • Examples of the pH regulator include organic acids such as citric acid, acetic acid, malic acid, lactic acid, and tartaric acid, and metal salts thereof, amine salts such as monoethanolamine, jetanolamine, and triethanolamine, phosphoric acid, Inorganic acids such as boric acid and hydrochloric acid; metal salts thereof; hydroxide salts such as sodium hydroxide and potassium hydroxide; and carbonate salts such as sodium carbonate.
  • Antibacterial and preservatives include, for example, benzoate, salicylate, sorbate, dehydroacetate, paraoxybenzoate, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, benzalkonium chloride , Ethanol and the like.
  • Table 1 shows the results of the gel (Meiji Seika Co., Ltd.). As is evident from the results, the combination of ⁇ -kutin and povidonodo (Formulation No. 4) showed a clearly stronger wound healing promoting effect than the povidone-doped formulation (Formulation No. 2) or the comparative drug.
  • the pectin used in these cases was a pectin having a molecular weight of about 300,000 and a degree of (methyl) esterification of 74%, unless otherwise specified.
  • test drug was prepared based on macrogol.
  • a negative value for the wound healing promoting effect indicates that healing is delayed compared to the control.
  • Table 2 shows the results of the test drug prepared by dissolving (suspending) in water and Isodin (trademark) liquid (Meiji Seika Co., Ltd.), which is a comparative drug.
  • the combination of Pectin and Povidonide (Formulation No. 8) showed a clearly stronger wound healing promoting effect than the Povidonold formulation (Formulation No. 6) or the comparative drug.
  • the test drug was prepared by dissolving (suspending) it in water.
  • Table 3 shows the results of the test drug prepared using white petrolatum as a base and the comparative drug Elis Mouth Shin TM Ointment (Dainippon Pharmaceutical Co., Ltd.). Erythromycin formulation (Formulation No. 10) 'and the comparative drug delayed wound healing. In contrast, a combination of Pectin and erythromycin (Formulation No. 12) clearly showed a strong wound healing promoting effect.
  • Table 3 shows the results of the test drug prepared using white petrolatum as a base and the comparative drug Elis Mouth Shin TM Ointment (Dainippon Pharmaceutical Co., Ltd.).
  • the test drug was prepared based on white petrolatum.
  • a negative value for the wound healing promoting effect indicates that healing is delayed compared to the control.
  • Table 4 shows the results of the test drug and the comparative drug Hibitene (trademark) gel (Sumitomo Pharmaceutical Co., Ltd. ⁇ AstraZeneca Co., Ltd.), which were prepared using the ⁇ / W emulsion base. Chlorhexidine gluconate (Formulation No. 14) and a comparative drug delayed wound healing. In contrast, a combination of pectin and chlorhexidine dalconate (Formulation No. 16) clearly showed a strong wound healing promoting effect.
  • test drug was prepared based on an O-type emulsion base.
  • a negative value for the wound healing promoting effect indicates that healing is delayed compared to the control.
  • Table 5 shows the results of the test drugs prepared based on white P-serine. As is evident from the results, even with the combination of sodium alginate, carboxymethylcellulose mono-Na or pullulan and povidonodo (formulation no. It showed a healing promoting effect. NNNNNN
  • test drug was prepared based on a 0 ZW type emulsion base.
  • S taphylococcusepide rm idis cell suspension (10 6 cells / mL) Add 4.5 g or 4.5 mL of each test preparation to 10 OmL, and immediately shake at 37 ° C and 100 rpm to obtain the sample solution. And After 10 minutes and 20 minutes from the start of shaking, 0.2 mL of 0.1 mo 17L thiosulfate Na solution was added to inactivate povidone, and the cells were cultured at 37 ° C for 48 hours. As a control, 4.5 mL of sterilized physiological saline was added to 10 OmL of a 10 6 cells // mL bacterial suspension, and the test was carried out in the same manner as for each preparation.
  • Isodine TM gel (Meiji Seika Co., Ltd.) and Isodine TM liquid (Meiji Seika Co., Ltd.), which are comparative drugs, exhibited antibacterial activity.
  • antibacterial activity was also observed with the combination of Pectin and Povidonol (Formulation Nos. 4 and 25). This And showed antibacterial activity even when mixed with Pectin.
  • Example 3 Examining the molecular weight of Pectin and its effect on promoting wound healing
  • the molecular weight indicates the molecular weight of the main peak measured by gel filtration.
  • a partial hydrolyzate of pectin was prepared by treating pectin (molecular weight about 300,000, esterification degree 74%) with pectinase.
  • the molecular weight is T
  • the molecular weight of the main peak was determined using a standard sample (Standard P-82, Showa Denko).
  • Wound healing promoting action was observed from a peak molecular weight of about 3,000 to about 300,000. As the peak molecular weight increased, the wound healing promoting effect became stronger, and a peak molecular weight of 200,000 or more ( Formulation Nos. 26 and 27) were found to have a strong wound healing promoting effect.
  • Example 4 Examination of the degree of esterification of pectin and the effect of promoting wound healing
  • the molecular weights of Pectin A are about 300,000, and that of Pectin B and Vectin C are about 250,000.
  • Table 8 shows the results of the wound healing promoting effect of pectins having different degrees of esterification. Vectin with a degree of esterification of 31 to 74% exhibited a wound healing promoting effect. On the other hand, no effect of promoting wound healing was observed with pectic acid having a degree of esterification of 0%.
  • Example 5 Guinea pig rough skin improvement test
  • a rough skin model was prepared according to the method of Sagi V et al. (Skin Res Tecno 6; 372000). However, for the purpose of the present invention, it was necessary to prepare a more severe rough skin model, so that the concentration of the surfactant for causing rough skin, i.e., sodium lauryl sulfate, was increased, and the Hartley guinea pig was used as a severe rough skin model. After shaving the back coat, a 2.5 cm X 2.5 cm cloth immersed in 5% aqueous sodium lauryl sulfate solution was applied once a day for 5 minutes for 3 consecutive days. Skin roughness was produced.
  • TEWL transdermal water loss
  • Skin roughness improvement promotion effect (%) X 100 Average value of control group No.
  • a skin external ointment having the composition shown in Table 9 was prepared in a mortar using white ⁇ -serine as a base, and the effects of promoting wound healing and improving skin roughness were examined. Unless otherwise specified, the blending amount is shown in% by weight.
  • the preparations containing Pectin (Formulation Nos. 35 and 36) showed an extremely high wound healing promoting effect as compared with Comparative Preparations 1 and 2 containing no Pectin.
  • a preparation containing urea (Formulation No. 35, Comparative Preparation 2) was found to have an effect of improving skin roughness. That is, it was clarified that the preparation containing urea and pectin (formulation No. 35) had an effect of promoting wound healing and an effect of improving skin roughness.
  • the preparation containing Pectin (Formulation Nos. 37 and 38) showed an extremely high wound healing promoting effect as compared with Comparative Preparations 3 and 4 containing no Pectin.
  • the preparations containing urea (Formulation No. 37, Comparative Preparation 4) were found to have an effect of improving skin roughness.
  • a preparation containing urea and pectin (Formulation No. 37) had an effect of promoting wound healing and improving skin roughness.
  • the preparations containing Pectin showed an extremely high wound healing promoting effect as compared with the comparative preparations 5 and 6 containing no Pectin.
  • Formulations containing urea were found to have an effect of improving skin roughness.
  • a preparation containing urea and pectin had an effect of promoting wound healing and an effect of improving skin roughness.

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Abstract

An external preparation comprising a drug component and a wound healing promoter component wherein a hydrophilic polymer such as pectin is employed as the wound healing promoter component to thereby enable effective treatment of a skin disease with a wound.

Description

明細書  Specification
外用剤  External preparation
〔発明の属する技術分野〕  [Technical field to which the invention belongs]
本発明は外用剤として一般的に知られた薬効成分を含む外用剤を創傷を伴った 皮膚疾患等に適用した際、 有効な創傷治癒促進作用をも示す外用剤に関し、 より 詳細には、 創傷部、 皮膚又は粘膜に適用する外用薬に創傷治癒促進成分を配合し てなる外用剤に関する。  The present invention relates to an external preparation containing a medicinal ingredient generally known as an external preparation, which also exhibits an effective action of promoting wound healing when applied to a skin disease or the like accompanied by a wound. The present invention relates to an external preparation obtained by blending a wound healing promoting component with an external preparation applied to a part, skin or mucous membrane.
〔従来の技術〕  [Conventional technology]
近年、 高齢化社会の進展やライフスタイルの変化やストレス等の原因により、 医療機関や在宅における褥瘡等の皮膚潰瘍、 老人性乾皮症、 アトピー性皮膚炎等 といった皮膚疾患が、 社会問題になるほど増加している。 また、 ひび、 あかぎれ 、 かゆみ等による肌荒れ、 創傷、 引つ搔き傷に悩まされている人も少なくない。 外用剤は従来それぞれの疾患に応じて選択 ·適用されてきた。 しかしながら、 皮膚及び粘膜の適用部に切り傷等の創傷を伴っている場合、 又は、 褥瘡等のよう な皮膚潰瘍部位に適用する場合、 薬物によっては創傷治癒に悪影響を及ぼす例が 見受けられていた。 さらに、 創傷を伴う皮膚あるいは粘膜疾患にも、 皮膚用保湿 剤、 抗炎症剤、 抗アレルギー剤、 局所麻酔剤、 ビタミン剤等の薬剤が使用されて いるが、 創傷、 粘膜損傷を伴う疾患によっては創傷治癒促進剤を配合した方が良 い薬剤も多く見受けられていた。  In recent years, skin diseases such as skin ulcers such as pressure ulcers, senile xerosis, atopic dermatitis, etc. in medical institutions and homes have become social problems due to the development of an aging society, changes in lifestyles, and stress. It has increased. In addition, many people are suffering from rough skin, wounds, and scratches due to cracks, rashes, itching, and the like. Conventionally, external preparations have been selected and applied according to each disease. However, when a wound such as a cut is applied to the skin and mucous membrane application site, or when applied to a skin ulcer site such as a pressure sore, there have been cases where some drugs adversely affect wound healing. In addition, skin moisturizing agents, anti-inflammatory agents, anti-allergic agents, local anesthetics, vitamins, and other drugs are used for skin and mucosal diseases associated with wounds, but depending on the disease associated with wounds and mucosal damage. There were also many drugs that would benefit from the inclusion of a wound healing promoter.
創傷治癒に悪影響を及ぼす例として、 殺菌，消毒薬がある。 殺菌 ·消毒薬は創 傷部、 皮膚、 粘膜の殺菌 ·消毒又は細菌感染の予防の目的で幅広く用いられてい る。 これらの殺菌 ·消毒薬を創傷部に適用した場合、 殺菌 ·消毒作用は示すが、 創傷治癒を遅延するという報告 （K r ame r S A. J Va s e Nu r s 17 , 1 7— 23、 1 999 ; E f f e c t o f p o v i d on e- i o cl i n e o n wo und h e a l i n g : a r e v i ew) もあり、 殺菌 ·消毒薬は創傷治癒に対しては悪影響を及ぼすことが知られている。  Disinfectants and disinfectants are examples of negative effects on wound healing. Disinfectants and disinfectants are widely used for disinfecting and disinfecting wounds, skin and mucous membranes, or for preventing bacterial infection. When these disinfectants are applied to wounds, they show bactericidal and disinfecting effects, but delay wound healing (Kramer S A. J Vase Nurs 17, 17, 23–23, 1 999; E ffectofpovid on e-iocl in eon wo und healing: arevi ew), and disinfectants are known to have an adverse effect on wound healing.
一方、 創傷治癒促進剤は褥瘡 ·皮膚潰瘍等の治療に用いられているが、 創傷部 が細菌感染を起こしている場合、 殺菌 ·消毒剤で創傷部を消毒した後に創傷治癒 促進剤を適用する必要がある。 また、 創傷被覆材は細菌感染している創傷部には 適用できないなどの問題もある。 On the other hand, wound healing promoters are used for treatment of pressure ulcers and skin ulcers, etc.If wounds are infected with bacteria, apply the wound healing promoter after disinfecting the wound with a disinfectant / disinfectant There is a need. Wound dressings are also suitable for wounds infected with bacteria. There are also problems such as inapplicability.
これらのことより、 創傷治療の観点からは、 殺菌 ·消毒作用と創傷部の治癒促 進作用が同時に発現する製剤が望ましい。 すなわち、 殺菌 '消毒薬と創傷治癒促 進薬の配合は非常に有用であると考えられる。 しかし、 殺菌 '消毒薬と創傷治癒 促進薬の配合はどの組み合わせでも良いわけではない。 殺菌 ·消毒薬と創傷治癒 促進薬の配合製剤が製剤的に安定であることは言うまでもないが、 殺菌 ·消毒作 用と創傷治癒促進作用を同時に発現する製剤でなくてはならない。  Based on these facts, from the viewpoint of wound treatment, it is desirable to use a preparation that simultaneously exerts a bactericidal / disinfecting action and a wound healing promoting action. That is, the combination of a disinfectant and a wound healing promoter is considered to be very useful. However, not all combinations of disinfectants and wound healing promoters are acceptable. It goes without saying that a combination preparation of a bactericidal / disinfectant and a wound healing promoter is stable in terms of formulation, but it must be a formulation that simultaneously exerts bactericidal / disinfecting action and a wound healing promoting action.
消毒薬と創傷治癒促進薬を配合した製剤として、 白糖 ·ポビドンョード製剤が 臨床で使用されている。 しかしながら、 殺菌 ·消毒効果は認められるが、 創傷治 癒を促進する成分として白糖を配合しているにもかかわらず、 治癒が遅延するな どの報告があり、 白糖の創傷治癒促進効果が十分に発現されていない。  Sucrose / povidonodo is used clinically as a formulation containing a disinfectant and a wound healing promoter. However, although bactericidal and disinfecting effects are observed, there are reports that healing is delayed despite the inclusion of sucrose as a component that promotes wound healing. It has not been.
これらのことから、 殺菌 ·消毒作用を有しながら、 早く適確に創部を治癒させ る薬剤の開発が望まれている。  From these facts, there is a demand for the development of a drug that has a bactericidal and disinfecting action and that can heal wounds quickly and accurately.
また、 ある種の創傷治癒促進薬と消毒薬を含有する製剤は既に知られている （ 特開平 7— 1 4 5 0 8 1、 特表 2 0 0 2— 5 1 6 2 6 5、 特表 2 0 0 2— 5 1 6 2 6 6等） が、 これらはリボソーム調製物または粒状担体を含有する製剤に関す るものである。  In addition, preparations containing certain types of wound healing promoters and disinfectants are already known (Japanese Patent Application Laid-Open No. 7-145,081; These are related to ribosome preparations or formulations containing particulate carriers.
一方、 創傷治癒促進薬を配合した方が良い例として、 尿素製剤がある。 尿素製 剤は角質内水分保持作用、 角質溶解剥離作用等、 皮膚に対して優れた作用を有す るため、 従来から皮膚外用の有効成分として用いられてきた。 しかしながら、 尿 素は皮膚や粘膜に対して刺激性を持っため、 創傷を伴う部位には適用できないと いう不便さが指摘されていた。 これらのことから、 角質内水分保持作用を有しな がら、 早く適確に創部を治癒させ、 創傷を伴う部位にも適用できる薬剤の開発が 望まれている。  On the other hand, urea preparations are an example where it is better to incorporate a wound healing promoter. Urea preparations have been used as an active ingredient for external use on the skin because they have excellent effects on the skin, such as keratin water retention and keratolytic exfoliation. However, it was pointed out that urine is irritating to the skin and mucous membranes and cannot be applied to wounds. From these facts, there is a demand for a drug that can heal wounds quickly and accurately while having a water-retaining effect in the stratum corneum and that can be applied to sites with wounds.
〔発明の目的〕  [Object of the invention]
本発明の目的は、 優れた創傷治癒促進作用と外用剤の本来の薬理効果を有し、 創傷を伴った皮膚疾患においても効率良く治療を施せるような外用剤を提供する ことである。  An object of the present invention is to provide an external preparation having an excellent wound healing promoting action and an original pharmacological effect of an external preparation, and capable of efficiently treating a skin disease accompanied by a wound.
〔発明の要旨〕 本発明者らは上記目的を達成すベく鋭意検討した結果、 創傷治癒促進効果のあ る親水性高分子は既存の外用剤との相性が良く、 両者を配合した製剤は、 外用剤 本来の薬効を損なわずに創傷治癒促進作用を付与できることを見出し本発明に到 達した。 [Summary of the Invention] The present inventors have conducted intensive studies to achieve the above object, and as a result, a hydrophilic polymer having a wound healing promoting effect has good compatibility with existing external preparations. The present inventors have found that a wound healing promoting action can be imparted without impairing the medicinal effect, and reached the present invention.
即ち、 本発明は薬効成分と創傷治癒促進成分とを含む外用薬であって、 創傷? i 癒促進成分が創傷治癒促進性親水性高分子からなることを特徴とする外用剤であ る。  That is, the present invention is an external preparation containing a medicinal component and a wound healing promoting component, wherein the wound healing promoting component comprises a wound healing promoting hydrophilic polymer.
本発明に従えば、 従来から慣用されている外用剤に創傷治癒促進性親水性高分 子を配合するだけで十分に創傷治癒促進効果と外用剤本来の薬理効果を発現する ことができ、 外用剤本来の使用態様で用いることができるという利点を持ち、 そ の結果、 製造及び使用の両面で大きな効果を発揮するものである。  According to the present invention, the wound healing promoting effect and the original pharmacological effect of the external preparation can be sufficiently exhibited only by blending a wound healing promoting hydrophilic polymer with a conventionally used external preparation. It has the advantage of being able to be used in the original mode of use of the agent, and as a result, exhibits great effects in both production and use.
〔発明の好ましい態様〕  (Preferred embodiment of the invention)
本発明において用いる創傷治癒促進性親水性高分子としては、 ラット欠損創試 験において、 2 0 %以上の創傷治癒促進効果を発現するものが好ましく、 それら を少なくとも 1種又は 2種以上含有していればその種類や構造は特に制限されな いが、 好適な創傷治癒促進性親水性高分子として、 ぺクチン、 アルギン酸、 カル ポキシメチルセルロース、 アラビアゴム、 プルラン等を挙げることができる。 ぺ クチン、 アルギン酸及びカルポキシメチルセルロースはそれらの塩も包含する。 本発明に用いうるぺクチンとしては、 天然起源のぺクチン、 その部分加水分解 物及び生理的に許容されるそれらの塩が用いられる。 生理的に許容される塩とし ては、 生理的に許容できれば特段の限定はない。 これらべクチンの分子量は約 3 ， 0 0 0〜約 8 0 0 , 0 0 0、 好ましくは約 3 0 , 0 0 0〜約 7 5 0 , 0 0 0、 更に好ましくは約 6 0， 0 0 0〜約 6 0 0 , 0 0 0、 特に好ましくは約 2 0 0 , 0 0 0〜約 5 0 0， 0 0 0である。 ぺクチンの起源は特に制限されない。  The wound healing-promoting hydrophilic polymer used in the present invention is preferably a polymer that exhibits a wound healing promoting effect of at least 20% in a rat defect wound test, and contains at least one or more of these. The type and structure are not particularly limited as long as it is selected, but preferred wound healing promoting hydrophilic polymers include pectin, alginic acid, carboxymethylcellulose, gum arabic, and pullulan.ク チ ン Kuching, alginic acid and carboxymethylcellulose also include their salts. As pectin which can be used in the present invention, pectin of natural origin, its partial hydrolyzate and physiologically acceptable salts thereof are used. The physiologically acceptable salt is not particularly limited as long as it is physiologically acceptable. The molecular weight of these pectins is from about 30,000 to about 800,000, preferably from about 30,000 to about 750,000, more preferably about 60,000. 0 to about 600,000, particularly preferably about 200,000 to about 500,000. The origin of Pectin is not particularly limited.
尚分子量はゲルろ過 （T S K— g e L G 4 0 0 0 P W) によって測定され たメインピークの分子量を意味する。 ぺクチンはそのエステル化度が 2 0 %以上 、 特に 3 0〜8 0 %であることが好ましい。 エステルはメチルエステルが好まし いが、 他のエステル、 たとえば C 2— C 6のアルキルエステルでもよい。 The molecular weight means the molecular weight of the main peak measured by gel filtration (TSK-ge LG 400 PW). Pectin has a degree of esterification of 20% or more, preferably 30 to 80%. The ester is preferably a methyl ester, but may be another ester such as a C 2 -C 6 alkyl ester.
本発明に用いうるカルポキシメチルセルロースも特に制限されないが、 ェ―テ ル化度が 0 . 4〜2 . 0、 好ましくは 0 . 6〜1 . 2、 最も好ましくは 0 . 6 5 〜1 . 0のカルポキシメチルセルロース又はその塩が通常用いられる。 また、 1 %溶液の粘度が 5〜 3， 0 0 O m P a · s、 好ましくは 1 0〜2 , O O O m P a • s、 最も好ましくは 3 0〜1， 5 0 0 m P a ' sのものが通常用いられる。 本発明に用いうるアルギン酸としては、 アルギン酸、 その誘導体及び生理的に 許容されるそれらの塩が用いられる。 生理的に許容される塩としては、 生理的に 許容できれば特段の限定はない。 また、 アルギン酸誘導体としてはアルギン酸プ ロピレングリコ一ルなどを挙げることができる。 The carboxymethylcellulose that can be used in the present invention is not particularly limited. Carboxymethylcellulose having a degree of oxidation of 0.4 to 2.0, preferably 0.6 to 1.2, and most preferably 0.65 to 1.0, or a salt thereof is usually used. In addition, the viscosity of the 1% solution is 5 to 3,000 OmPas, preferably 10 to 2, OOOmPas, most preferably 30 to 1,500 mPa's. s is usually used. As alginic acid that can be used in the present invention, alginic acid, its derivatives and physiologically acceptable salts thereof are used. The physiologically acceptable salt is not particularly limited as long as it is physiologically acceptable. Examples of the alginic acid derivative include propylene glycol alginate.
本発明において用いうる薬効成分は、 医学的に許容でき、 創傷部、 皮膚又は粘 膜に適用して薬効の発現が期待される成分を 1種又は 2種以上含有していればそ の種類には制限されないが、 その典型例としては一般的に広く用いられている殺 菌 ·消毒剤 ·皮膚用保湿剤、 抗炎症剤、 抗アレルギー剤、 局所麻酔剤、 ビタミン 剤等を挙げることができる。  Pharmaceutical ingredients that can be used in the present invention are medically acceptable, and include one or more components that are expected to exhibit a medicinal effect when applied to a wound, skin or mucous membrane, and are classified into those types. Although not limited, typical examples thereof include generally widely used bactericides, disinfectants, skin moisturizers, anti-inflammatory agents, anti-allergic agents, local anesthetics, vitamins and the like.
本発明に用いうる殺菌 ·消毒剤としては、 殺菌 ·消毒効果を発現するものを 1 種又は 2種以上含有していれば特に制限されないが、 好適な殺菌 ·消毒薬として は、 ポビドンョード、 ョードホルム、 ヨードチンキ、 レゾルシン等のヨウ素及び ヨウ素複合体、 塩化ベンザルコニゥム、 塩化べンゼトニゥム、 塩化デカリニゥム 、 塩化セチルピリジニゥム、 クレゾ一ルセッケン等の消毒用石鹼類化合物、 銀及 び水銀化合物、 エリスロマイシン、 ゲンタマイシン、 カナマイシン等の抗生物質 、 抗真菌薬、 ァクリノール、 ダルコン酸クロルへキシジン等を挙げることができ る。  The germicidal disinfectant that can be used in the present invention is not particularly limited as long as it contains at least one bactericidal / disinfecting agent. Suitable germicidal / disinfecting agents include povidone and podholm, Iodine and iodine complexes such as iodine tincture and resorcinol, benzalkonium chloride, benzethonium chloride, decalinium chloride, cetylpyridinium chloride, cresyl soap, and other disinfecting stone compounds, silver and mercury compounds, erythromycin, gentamicin, Examples include antibiotics such as kanamycin, antifungals, acrinol, chlorhexidine dalconate, and the like.
本発明に用いうる皮膚保湿剤としては、 例えばグリセリン、 プロピレングリコ ール、 1， 3—ブチレングリコール、 ポリエチレングリコール、 ジプロピレング リコ一ル、 キシリ トール、 ソルビトール等の多価アルコール類、 遊離アミノ酸、 尿素、 乳酸、 クェン酸塩等の天然保湿因子、 へパリン類似物質、 コラーゲン、 ェ ラスチン、 コンドロイチン硫酸、 デルマタン硫酸、 フイブロネクチン、 ヒアルロ ン酸、 セラミド、 キトサン、 ヒダントイン （特開平 9— 2 7 8 6 4 5 ) 等が挙げ られるが、 これらに限定されない。 また、 これらは単独で用いても、 2種以上を 混合して用いてもよい。 本発明に用いうる抗炎症剤としては、 例えばァズレン、 ァミノ安息香酸ェチル 、 イブプロフェン、 インドメタシン、 グリチルリチン酸、 グリチルレチン酸、 7 ラントイン、 銅クロロフィリン、 ケトプロフェン、 サリチル酸メチル、 サリチル 酸グリコールエステル、 ジクロフエナク、 スプロフェン、 ナプロキセン、 ピロキ シカム、 フエルビナク、 ブフエキサマク、 フルルビプロフェン、 及びメロキシカ ム、 セレコキシブ、 口フエコキシブ等の C o X 2選択阻害薬を含む非ステロイド 性抗炎症剤又はその塩、 アルクロメタゾン、 クロべ夕ゾール、 クロべ夕ゾン、 ジ フルコルトロン、 ジフルプレドナー卜、 ジフロラゾン、 デキサメタゾン、 デプロ ドン、 トリアムシノロンァセトニド、 ハルシノニド、 ヒドロコルチゾン、 ブデゾ ニド、 フルオシノニド、 フルォロシノロンァセトニド、 フルドロキシコルチド、 フルメタゾン、 プレドニゾロン、 ベクロメタゾン、 ベ夕メタゾン、 モメタゾン等 のステロイド、 及びそれらの塩等を挙げられるが、 これらに限定されない。 また 、 これらは単独で用いても、 2種以上を混合して用いてもよい。 Examples of the skin moisturizing agent which can be used in the present invention include polyhydric alcohols such as glycerin, propylene glycol, 1,3-butylene glycol, polyethylene glycol, dipropylene glycol, xylitol, sorbitol, free amino acids, urea, Natural moisturizing factors such as lactic acid and citrate, heparin-like substances, collagen, elastin, chondroitin sulfate, dermatan sulfate, fibronectin, hyaluronic acid, ceramide, chitosan, and hydantoin (Japanese Patent Application Laid-Open No. 9-2788645) And the like, but are not limited thereto. These may be used alone or in combination of two or more. Anti-inflammatory agents that can be used in the present invention include, for example, azulene, aminoethyl benzoate, ibuprofen, indomethacin, glycyrrhizic acid, glycyrrhetinic acid, 7-lantoin, copper chlorophyllin, ketoprofen, methyl salicylate, salicylate glycol ester, diclofenac, suprofen, naproxen Non-steroidal anti-inflammatory drugs or their salts, including coX2 selective inhibitors such as piroxicam, felbinac, bufexamac, flurbiprofen, and meloxicam, celecoxib, oral fuecoxib, or salts thereof, alclomethasone, clobesol, Vesuvone, diflucortron, difluprednate, diflorazone, dexamethasone, deprodone, triamcinolone acetonide, halcinonide, hydrocortisone, Zone Nido, fluocinonide, full O rosiglitazone Roh Ron § Seto acetonide, fludroxycortide, flumethasone, prednisolone, beclomethasone, Baie evening methasone, steroids such as mometasone, and the like salts thereof, and the like. These may be used alone or as a mixture of two or more.
本発明に用いうる抗アレルギ一剤としては、 例えばジフェンヒドラミン、 カル ピノキサミン、 ジメンヒドリナート、 ジフエ二ルビラリン、 クレマスチン、 ピリ ラミン、 トリべレナミン、 クロルフエ二ラミン、 卜リプロリジン、 ジメチンデン 、 プロメタジン、 ァリメマジン、 イソチペンジル、 ヒドロキシジン、 メクリジン 、 ホモクロルシクリジン、 シプロヘプ夕ジン等の抗ヒスタミン薬又はその塩、 メ キ夕ジン、 テルフエナジン、 ェピナスチン、 ァステミゾール、 ェバスチン、 セチ リジン、 口ラタジン、 クロモグリク酸、 トラニラスト、 ケトチフェン、 ァゼラス チン、 ォキサトミド、 アンレキサノクス、 レピリナスト、 イブジラスト、 ぺミロ ラスト、 タザノラスト、 ォザダレル、 スプラタスト、 セラトロダスト、 エマダス チン、 プランルカスト、 クロタミトン等の抗アレルギー薬又はその塩、 シクロス ポリン、 夕クロリムス、 メトトレキサ一ト等の免疫抑制薬又はその塩等を挙げら れるが、 これらに限定されない。 また、 これらは単独で用いても、 2種以上を混 合して用いてもよい。  Examples of the anti-allergic agent that can be used in the present invention include diphenhydramine, carpinoxamine, dimenhydrinate, diphenirubiralin, clemastine, pyrilamine, triberenamine, chlorpheniramine, triprolysin, dimethindene, promethazine, alimimazine, isothidyl. Antihistamines or their salts, such as hydroxyzine, meclizine, homochlorcyclidine, cyprohepdin, or salts thereof, mexidin, terfenadine, epinastine, astemizole, ebastine, cetirizine, oral ratadine, cromoglycic acid, tranilast, ketotifen, azelastine , Oxatomide, Amlexanox, Repirinast, Ibudilast, Emilo last, Tazanolast, Ozadarrell, Splatast, Seratrodast Emadasu Chin, pranlukast, antiallergics or a salt such as crotamiton, Shikurosu porins, evening Kurorimusu, but we include an immunosuppressant drug or a salt thereof is one bets like methotrexate, but not limited to. These may be used alone or as a mixture of two or more.
本発明に用いうる局所麻酔剤としては、 例えばプロ力イン、 ォキシブプロカイ ン、 ァミノ安息香酸ェチル、 ピベリジルァセチルァミノ安息香酸ェチル、 コカイ ン、 テトラカイン、 リドカイン、 テ一力イン、 プロピ卜力イン、 へキソチォカイ ン、 ジメチソキン、 プロモキシン、 ベンゾカイン、 ベンジルアルコール、 カタ力 イン、 パレトキシカイン、 ピロ力イン、 プロ力インアミド、 プロパラ力イン、 プ 口ポキシ力イン、 へキシルカイン、 メタブテ夕ミン、 メタブトキシカイン、 ピリ ドキシン、 ジブ力イン、 ブピパ力イン、 メピバ力イン、 ォキセサゼイン、 及びそ れらの塩等を挙げられるが、 これらに限定されない。 また、 これらは単独で用い ても、 2種以上を混合して用いてもよい。 Examples of the local anesthetic which can be used in the present invention include, for example, procarin, oxybuprocaine, ethyl amino benzoate, piberidyl acetylaminoethyl benzoate, cocaine, tetracaine, lidocaine, terikin, propitin Power In, Hexochikai , Dimethisoquine, promoxine, benzocaine, benzyl alcohol, catalysin, paletoxicaine, pyro-in, pro-inamide, propara-in, oral oxyn-in, hexylcaine, metabutemin, methtaboxin, pyridoxine, jib Power in, bupipa power in, mepiva power in, oxesazein, and salts thereof, but are not limited thereto. These may be used alone or as a mixture of two or more.
本発明に用いうるビタミン剤としては、 例えばビタミン A、 ビタミン B群、 ビ 夕ミン（：、 ビタミン D、 ビタミン E、 ビタミン K、 ビタミン Η、 ニコチン酸、 パ ントテン酸、 葉酸、 及びそれらの誘導体等を挙げられるが、 これらに限定されな い。 また、 これらは単独で用いても、 2種以上を混合して用いてもよい。  Examples of the vitamin preparations that can be used in the present invention include vitamin A, vitamin B group, bimin (:, vitamin D, vitamin E, vitamin K, vitamin Η, nicotinic acid, pantothenic acid, folic acid, and derivatives thereof, and the like. However, these are not limited thereto, and they may be used alone or in combination of two or more.
本発明に用いられる両成分の配合割合は、 それぞれの効果を発現するに足る範 囲でそれぞれ選択されるが、 創傷治癒促進性親水性高分子は好ましくは 0 . 0 1 〜6 0重量％、 より好ましくは 3〜3 0重量％用いられる。  The mixing ratio of the two components used in the present invention is selected within a range sufficient to exhibit the respective effects, but the wound healing-promoting hydrophilic polymer is preferably 0.01 to 60% by weight, More preferably, it is used in an amount of 3 to 30% by weight.
本発明の外用剤は上記の成分を含有する限り他の任意成分や剤形等は特に制限 されない。 本発明の外用剤は本来の外用剤としての性能を損なうことなく優れた 創傷治癒促進効果を示す。  The external preparation of the present invention is not particularly limited in other optional components, dosage forms, and the like as long as it contains the above-mentioned components. The external preparation of the present invention exhibits an excellent wound healing promoting effect without impairing the performance as an original external preparation.
本発明の外用剤の剤形としては、 軟膏剤、 クリーム、 ゲル等の半固形状製剤、 散剤、 粒剤、 スチック剤、 シート剤 （フィルム状のものも含む） 、 坐剤等の固形 状製剤、 水溶液、 懸濁液、 ローション、 乳液等の液状製剤が挙げられる。 また、 必要に応じてこれらをスプレー剤とすることもできる。 更に、 貼付剤としてパッ プ剤、 プラスター剤、 パッチ剤等が挙げられるが、 好ましくは軟膏剤、 クリーム 、 ゲル、 スチック剤、 シート剤 （フィルム状のものも含む） 、 パップ剤が望まし い。  Examples of the dosage form of the external preparation of the present invention include semisolid preparations such as ointments, creams, and gels, powder preparations, granules, sticks, sheets (including films), and suppositories. And liquid preparations such as aqueous solutions, suspensions, lotions and emulsions. In addition, these can be used as sprays if necessary. Further, as a patch, a patch, a plaster, a patch and the like can be mentioned, and an ointment, a cream, a gel, a stick, a sheet (including a film), and a cataplasm are preferable.
また、 本発明の外用剤の適用部位は、 既存外用剤の皮膚及び粘膜等の適用範囲 からは制限されない。 すなわち、 既存外用剤の種類によっては全身の皮膚及び粘 膜に対しても使用できる。  In addition, the application site of the external preparation of the present invention is not limited by the application range of the existing external preparation such as skin and mucous membrane. That is, depending on the type of existing topical preparation, it can be used for whole body skin and mucous membrane.
本発明においてはさらに必要に応じて、 本発明の効果を損なわない範囲で、 医 薬品を製造するにあたり許容される各種成分、 すなわち水性成分、 油成分、 水溶 性高分子、 油溶性高分子、 酸化防止剤、 界面活性剤、 清涼化剤、 緩衝液、 ρ Η調 整剤、 抗菌 ·防腐剤等を適宜配合することができる。 In the present invention, if necessary, various components acceptable in the production of pharmaceuticals, that is, aqueous components, oil components, water-soluble polymers, oil-soluble polymers, and oxidized components, as long as the effects of the present invention are not impaired. Inhibitor, surfactant, freshener, buffer, ρΗ A stabilizer, antibacterial and preservative, etc. can be appropriately compounded.
水性成分としては、 例えばエタノール、 プロピルアルコール、 イソプロピルァ ルコール等の低級アルコール、 グリセリン、 ソルビト一ル等の多価アルコール、 エチレングリコール、 プロピレングリコール、 ブチレングリコール、 ポリエチレ ングリコール等のダリコール類、 ショ糖、 乳糖、 マル! ^一ス、 マンニトール、 ェ リスリ トール、 キシリトール等の糖類及び糖アルコール類、 精製水等が挙げられ る。  Examples of the aqueous component include lower alcohols such as ethanol, propyl alcohol and isopropyl alcohol; polyhydric alcohols such as glycerin and sorbitol; dalicols such as ethylene glycol, propylene glycol, butylene glycol, and polyethylene glycol; sucrose; Examples include sugars such as lactose, maltose, mannitol, erythritol, and xylitol, sugar alcohols, and purified water.
油成分としては、 例えば白色ワセリン、 流動パラフィン等の飽和炭化水素類、 サラシミツロウ、 カルナゥバロウ等のロウ類、 大豆油、 ハードフアット等の油脂 類、 ステアリルアルコール、 ォレイルアルコール、 コレステロール等の高級アル コール類、 アジピン酸イソプロピル、 セバシン酸イソプロピル、 ミリスチン酸ォ クチルドデシル、 乳酸セチル等の脂肪酸エステル類、 パルミチン酸、 ステアリン 酸、 ォレイン酸等の脂肪酸類、 メチルポリシロキサン等のシリコン油等が挙げら れる。  Examples of the oil component include saturated hydrocarbons such as white petrolatum and liquid paraffin, waxes such as salami beeswax and carnauba wax, oils and fats such as soybean oil and hard fat, stearyl alcohol, oleyl alcohol, and higher alcohols such as cholesterol. Examples thereof include fatty acids such as coals, isopropyl adipate, isopropyl sebacate, octyldodecyl myristate, and cetyl lactate; fatty acids such as palmitic acid, stearic acid, and oleic acid; and silicone oils such as methylpolysiloxane.
水溶性高分子としては、 グァーガム、 カラャガム、 カラギーナン、 カンテン、 デンプン、 トラガントガム、 口一カストビーンガム等の植物系高分子、 キサン夕 ンガム、 デキストラン等の微生物系高分子、 コラ一ゲン、 カゼイン、 ゼラチン等 の動物系高分子、 メチルセルロース、 ェチルセルロース、 メチルヒドロキシプロ ピルセルロース、 ニトロセルロース、 セルロース硫酸ナトリウム、 結晶セル口一 ス等のセルロース系高分子等のアルギン酸系高分子、 ポリビニルメチルエーテル 、 カルボキシピ二ルポリマー、 ポリオキシエチレン系高分子、 ポリアクリル酸系 高分子、 ポリビニルアルコール、 ポリビニルピロリドン等が挙げられる。  Examples of the water-soluble polymers include plant polymers such as guar gum, karaya gum, carrageenan, agar, starch, tragacanth gum, and oral cast bean gum; microbial polymers such as xansu gum, dextran, collagen, casein, and gelatin. Alginic acid polymers such as methylcellulose, methylcellulose, methylhydroxypropylcellulose, nitrocellulose, sodium cellulose sulfate, cellulosic polymers such as crystal cell mouth, polyvinyl methyl ether, Polymer, polyoxyethylene-based polymer, polyacrylic acid-based polymer, polyvinyl alcohol, polyvinylpyrrolidone, and the like.
油溶性高分子としては、 アクリル酸 ·メタクリル酸アルキル共重合体等が挙げ られる。  Examples of the oil-soluble polymer include an acrylic acid / alkyl methacrylate copolymer.
界面活性剤としては、 例えばモノラウリン酸ソルビタン、 セスキォレイン酸ソ ルビタン、 トリオレイン酸ソルビタン、 モノラウリン酸ポリオキシエチレンソル ビタン、 ポリエチレングリコールモノォレート、 ポリオキシエチレンアルキルェ 一テル、 ポリグリコールジェステル、 ラウロイルジェ夕ノールアミド、 脂肪酸ィ ソプロパノールアミド、 マルチトールヒドロキシ脂肪族エーテル、 アルキル化多 糖、 アルキルダルコシド、 シュガーエステル等の非イオン性界面活性剤、 ステア リルトリメチルアンモニゥムクロライド、 ラウリルアミンォキシド等のカチオン 界面活性剤、 パルミチン酸ナトリウム、 ラウリン酸ナトリウム、 ラウリル硫酸力 リウム、 アルキル硫酸トリエタノ一ルァミン、 リニアドデシルベンゼン硫酸、 ポ リオキシエチレン硬化ヒマシ油マレイン酸、 ァシルメチルタウリン等のァニオン 界面活性剤、 レシチン又はその誘導体などの天然由来の界面活性剤等が挙げられ る。 Examples of the surfactant include sorbitan monolaurate, sorbitan sesquioleate, sorbitan trioleate, polyoxyethylene sorbitan monolaurate, polyethylene glycol monoolate, polyoxyethylene alkyl ester, polyglycol ester, and lauroyl ester Evening amide, fatty acid isopropanolamide, maltitol hydroxyaliphatic ether, alkylated poly Nonionic surfactants such as sugars, alkyl darcosides, sugar esters, etc., cationic surfactants such as stearyl trimethylammonium chloride, lauryl amine oxide, sodium palmitate, sodium laurate, potassium lauryl sulfate, alkyl Examples thereof include anionic surfactants such as triethanolamine sulfate, linear dodecylbenzene sulfate, polyoxyethylene hydrogenated castor oil, maleic acid, and acylmethyltaurine, and naturally-derived surfactants such as lecithin and derivatives thereof.
酸化防止剤としては、 例えばトコフエロール、 ァスコルビン酸、 エリソルビン 酸、 没食子酸プロピル、 B H T (ジブチルヒドロキシトルエン） 、 B H A (プチ ルヒドロキシァニソール） 等が挙げられる。  Examples of the antioxidant include tocopherol, ascorbic acid, erythorbic acid, propyl gallate, BHT (dibutylhydroxytoluene), and BHA (butylhydroxyanisole).
清涼化剤として、 例えばメントール、 カンフル等が挙げられる。  Examples of the cooling agent include menthol and camphor.
緩衝液としては、 例えばリン酸水素ニナトリウム一クェン酸、 リン酸二水素力 リウムーリン酸水素ニナトリウム、 クェン酸ーリン酸水素ニナトリウム等が挙げ られる。  As the buffer, for example, disodium hydrogen phosphate-monocitrate, dihydrogen phosphate-disodium hydrogen phosphate, disodium citrate-disodium hydrogen phosphate and the like can be mentioned.
p H調整剤としては、 例えばクェン酸、 酢酸、 リンゴ酸、 乳酸、 酒石酸等の有 機酸及びこれらの金属塩、 モノエタノールァミン、 ジェタノ一ルァミン、 トリエ 夕ノールァミン等のアミン塩、 リン酸、 ホウ酸、 塩酸等の無機酸及びこれらの金 属塩、 水酸化ナトリウム、 水酸化カリウム等の水酸化物塩、 炭酸ナトリウム等の 炭酸塩等が挙げられる。  Examples of the pH regulator include organic acids such as citric acid, acetic acid, malic acid, lactic acid, and tartaric acid, and metal salts thereof, amine salts such as monoethanolamine, jetanolamine, and triethanolamine, phosphoric acid, Inorganic acids such as boric acid and hydrochloric acid; metal salts thereof; hydroxide salts such as sodium hydroxide and potassium hydroxide; and carbonate salts such as sodium carbonate.
抗菌 ·防腐剤としては、 例えば安息香酸塩、 サリチル酸塩、 ソルビン酸塩、 デ ヒドロ酢酸塩、 パラォキシ安息香酸エステル、 2 , 4 , 4 ' 一トリクロロー 2 ' 一ヒドロキシジフエ二ルェ一テル、 塩化ベンザルコニゥム、 エタノール等が挙げ られる。  Antibacterial and preservatives include, for example, benzoate, salicylate, sorbate, dehydroacetate, paraoxybenzoate, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, benzalkonium chloride , Ethanol and the like.
〔実施例〕  〔Example〕
次に本発明を例証するために実施例によって本発明を更に詳細に説明するが、 本発明は当該実施例によって何ら制限されるものではない。  Next, the present invention will be described in more detail by way of examples to illustrate the present invention, but the present invention is not limited to the examples.
実施例 1 ： ラット欠損創試験 Example 1: Rat defect wound test
5週齢の W i s t a r系雄性ラットを一週間予備飼育した後、 試験に供した。 ラッ卜の背部を電気バリカンで剪毛した後、 ペントパルビタール麻酔下で背部を 直径 1 0 mmの円形ポンチで打ち抜き、 正中線で対称の 2箇所の打ち抜き創を作 製した。 打ち抜き直後の創傷面の大きさ （長径 X短径） をノギスで測定した。 被 験製剤は欠損創作製日より試験終了日まで、 1日 1回 1 0 O m gずつ各欠損部に 塗布し、 布及びフィルムで覆った後、 粘着テープで固定した。 Five-week-old male male Wistar rats were preliminarily reared for one week before being subjected to the test. After shaving the back of the rat with an electric clipper, the back was removed under pentoparbital anesthesia. It was punched with a circular punch of 10 mm in diameter, and two punched wounds symmetrical about the median line were created. The size of the wound surface (major axis X minor axis) immediately after punching was measured with a caliper. The test preparation was applied to each defect at a dose of 100 mg once a day from the wound wound creation date to the test end date, covered with a cloth and film, and then fixed with adhesive tape.
欠損創作製 4日後より 1 5日目まで、 再上皮化していない創傷部の長径及び短 径を測定して面積を求め、 創部の面積変化を下記の式より算出して面積変化曲線 を作成した。 各測定日の創部面積  From 4 days after the creation of the defective wound to the 15th day, the major axis and minor axis of the non-epithelialized wound area were measured to determine the area, and the area change curve of the wound area was calculated by the following formula to create an area change curve. . Wound area on each measurement day
面積変化 = = X 1 0 0  Area change = = X 1 0 0
欠損創作製日の創部面積 この面積変化曲線の曲線下面積を算出し、 創傷治癒促進効果を以下の式により 算出し、 創傷治癒促進効果の指標とした。 （値が大きいほど創傷治癒促進効果が 強い） 各被験製剤投与動物の曲線下面積  Wound area on the day of defect wound creation The area under the area change curve was calculated, and the effect of promoting wound healing was calculated by the following formula, and used as an index of the effect of promoting wound healing. (The larger the value, the stronger the wound healing promoting effect.) The area under the curve of each test preparation-administered animal
創傷治癒促進効果 （％) X 1 0 0
Figure imgf000010_0001
対照群の曲線下面積の平均値 マクロゴールを基剤として作製した被験薬剤と比較薬剤であるイソジン （商標Wound healing promoting effect (%) X 100
Figure imgf000010_0001
Average value of the area under the curve in the control group The test drug prepared using Macrogol as a base and the isodine (comparison drug)
) ゲル （明治製菓 （株） ） の結果を表 1に示した。 結果から明らかなように、 ぺ クチンとポビドンョード配合剤 （製剤番号 4 ) がポビドンョ一ド製剤 （製剤番号 2 ) 又は比較薬剤よりも明らかに強い創傷治癒促進効果を示した。 これらで用い たぺクチンは、 特に断りのない限り、 分子量約 3 0 0 , 0 0 0、 （メチル） エス テル化度 7 4 %のぺクチンである。 N N N Table 1 shows the results of the gel (Meiji Seika Co., Ltd.). As is evident from the results, the combination of ぺ -kutin and povidonodo (Formulation No. 4) showed a clearly stronger wound healing promoting effect than the povidone-doped formulation (Formulation No. 2) or the comparative drug. The pectin used in these cases was a pectin having a molecular weight of about 300,000 and a degree of (methyl) esterification of 74%, unless otherwise specified. NNN
o〇 o 10  o〇 o 10
表 1  table 1
創傷治癒促進効果  Wound healing promotion effect
製剤名  Formulation name
(%)  (%)
比較薬剤 イソジン （商標） ゲル 1 1. 1 ±4. 1 Comparative drug Isodine ™ gel 1 1.1 ± 4.1
No. 1 基剤 （マクロゴ一ル） 0. 7 ± 1. 7  No. 1 base (macrogol) 0.7 ± 1.7
No. 2 ポビドンョード （1 0重量％) 一 9. 1 ± 7. 6 No. 2 Povidone (10% by weight) 9.1 ± 7.6
No. 3 ぺクチン （ 10重量％) 60. 2 ± 1. 2 No. 3 Pectin (10% by weight) 60.2 ± 1.2
No. 4 ぺクチン （1 0重量％) +ポビドン 54. 4 ± 2. 4 No. 4 Pectin (10% by weight) + povidone 54.4 ± 2.4
ョード （1 0重量％)  Eodo (10% by weight)
被験薬剤はマクロゴールを基剤として作製した。 The test drug was prepared based on macrogol.
創傷治癒促進効果が負の値の場合は、 コントロールより治癒が遅延していること を表す。 A negative value for the wound healing promoting effect indicates that healing is delayed compared to the control.
水に溶解 （懸濁） して作製した被験薬剤と比較薬剤であるイソジン （商標） 液 (明治製菓 （株） ） の結果を表 2に示した。 結果から明らかなように、 ぺクチン とポビドンョ一ド配合剤 （製剤番号 8) がポビドンョード製剤 （製剤番号 6) 又 は比較薬剤よりも明らかに強い創傷治癒促進効果を示した。  Table 2 shows the results of the test drug prepared by dissolving (suspending) in water and Isodin (trademark) liquid (Meiji Seika Co., Ltd.), which is a comparative drug. As is evident from the results, the combination of Pectin and Povidonide (Formulation No. 8) showed a clearly stronger wound healing promoting effect than the Povidonold formulation (Formulation No. 6) or the comparative drug.
表 2  Table 2
創傷治癒促進効果  Wound healing promotion effect
製剤名  Formulation name
(%)  (%)
比較薬剤 (商標） 液 4 4 ± 1 4 Comparative agent (trademark) liquid
No. 5 水 1 7 ± 3 4 No. 5 Water 1 7 ± 3 4
6 ポビドンョ一ド （ 1 0重： ;%) 9 7 ± 4 3  6 Povidondo (10 weight:;%) 9 7 ± 4 3
7 ぺクチン （ 10重量％) 46 7 ± 5 0  7 Pectin (10% by weight) 46 7 ± 50
8 ぺクチン （10重量％) +ポビドン 43 1 ± 4 5  8 Pectin (10% by weight) + povidone 43 1 ± 4 5
ョ一ド （1 0重量％)  (10% by weight)
被験薬剤は水に溶解 （懸濁） して作製した。 The test drug was prepared by dissolving (suspending) it in water.
白色ワセリンを基剤として作製した被験薬剤と比較薬剤であるエリス口シン （ 商標） 軟膏 （大日本製薬 （株） ） の結果を表 3に示した。 エリスロマイシン製剤 (製剤番号 10)'及び比較薬剤は創傷治癒を遅延した。 それに対し、 ぺクチンと エリスロマイシン配合剤 （製剤番号 12) は明らかに強い創傷治癒促進効果を示 した。 表 3 Table 3 shows the results of the test drug prepared using white petrolatum as a base and the comparative drug Elis Mouth Shin ™ Ointment (Dainippon Pharmaceutical Co., Ltd.). Erythromycin formulation (Formulation No. 10) 'and the comparative drug delayed wound healing. In contrast, a combination of Pectin and erythromycin (Formulation No. 12) clearly showed a strong wound healing promoting effect. Table 3
創傷治癒促進効果  Wound healing promotion effect
製剤番号 製剤名 Formulation number Formulation name
(%)  (%)
比較薬剤 エリス口シン （商標） 軟膏 29. 8 ± 12. 7 No. 9 基剤 （白色ワセリン） 4. 8 ± 3. 3 Comparative drug Elis Mouth Shin ™ Ointment 29.8 ± 12.7 No. 9 base (white petrolatum) 4.8 ± 3.3
No. 10 エリスロマイシン （1重量％) 37. 7 ± 5. 0 No. 10 Erythromycin (1% by weight) 37.7 ± 5.0
No. 11 ぺクチン （ 10重量％) 58. 3 ± 5. 5 No. 11 Pectin (10% by weight) 58.3 ± 5.5
No. 12 ぺクチン （ 1 0重量％) +エリス 37. 9 ± 1. 9 No. 12 Pectin (10% by weight) + Ellis 37.9 ± 1.9
ロマイシン （1重量％)  Lomycin (1% by weight)
被験薬剤は白色ワセリンを基剤として作製した。 The test drug was prepared based on white petrolatum.
創傷治癒促進効果が負の値の場合は、 コントロールより治癒が遅延していること を表す。 A negative value for the wound healing promoting effect indicates that healing is delayed compared to the control.
〇/W型乳剤性基剤を用いて作製した被験薬剤と比較薬剤であるヒビテン （商 標） ゲル （住友製薬 （株） ·ァストラゼネカ (株） ） の結果を表 4に示した。 グ ルコン酸クロルへキシジン製剤 （製剤番号 14) 及び比較薬剤は創傷治癒を遅延 した。 それに対し、 ぺクチンとダルコン酸クロルへキシジン配合剤 （製剤番号 1 6) は明らかに強い創傷治癒促進効果を示した。  Table 4 shows the results of the test drug and the comparative drug Hibitene (trademark) gel (Sumitomo Pharmaceutical Co., Ltd. · AstraZeneca Co., Ltd.), which were prepared using the 〇 / W emulsion base. Chlorhexidine gluconate (Formulation No. 14) and a comparative drug delayed wound healing. In contrast, a combination of pectin and chlorhexidine dalconate (Formulation No. 16) clearly showed a strong wound healing promoting effect.
表 4  Table 4
創傷治癒促進効果  Wound healing promotion effect
製剤名  Formulation name
( )  ()
比較薬剤 ヒビテン （商標） ゲル - 55. 9土 2. 9 Comparative drug Hibiten ™ gel-55.9 Sat 2.9
No. 13 基剤 （〇ノ\¥型乳剤性基剤） 10. 1 ±4. 2  No. 13 base (〇 \\ type emulsion base) 10.1 ± 4.2
No. 1 ダルコン酸クロルへキシジン （1重 - 14. 2 ± 8. 5  No. 1 Chlorhexidine dalconate (single-14.2 ± 8.5
No. 15 ぺクチン （ 1 0重量％) 59 0 ± 4. 8 No. 15 Pectin (10% by weight) 590 ± 4.8
No. 16 ぺクチン （1 0重量％) +ダルコン 26 0 ± 2. 4 No. 16 Pectin (10% by weight) + Dalcon 260 ± 2.4
(1重量％)  (1% by weight)
被験薬剤は O 型乳剤性基剤を基剤として作製した。 The test drug was prepared based on an O-type emulsion base.
創傷治癒促進効果が負の値の場合は、 コントロールより治癒が遅延していること を表す。 A negative value for the wound healing promoting effect indicates that healing is delayed compared to the control.
白色ヮセリンを基剤として作製した被験薬剤の結果を表 5に示した。 結果から 明らかなように、 アルギン酸 Na、 カルボキシメチルセルロース一 N a又はプル ランとポビドンョード配合剤 （製剤番号 20、 22、 24) においても、 ポビド ンョード製剤 （製剤番号 1 8)'よりも明らかに強い創傷治癒促進効果を示した。 N N N N N N Table 5 shows the results of the test drugs prepared based on white P-serine. As is evident from the results, even with the combination of sodium alginate, carboxymethylcellulose mono-Na or pullulan and povidonodo (formulation no. It showed a healing promoting effect. NNNNNN
o o o o o o 12 表 5  o o o o o o 12 Table 5
創傷治癒促進効果  Wound healing promotion effect
製剤番号 製剤名 Formulation number Formulation name
(%)  (%)
17 (白色ヮセリン） 4. 9 ± 1 9  17 (white serine) 4. 9 ± 19
18 ポビドンョード （ 1 0重 ;%) 5. 8 ± 5 5  18 Povidon (10 times;%) 5.8 ± 5 5
19 '酸 N a (10重 :%) 35. 3 ± 8 1  19 'Acid Na (10 fold:%) 35.3 ± 8 1
20 '酸 N a ( 10重 j ;%) + 33. 4 ± 6 3  20 'acid Na (10-fold j;%) + 33.4 ± 6 3
ポビドンョード （ 10重 j ; )  Povidonold (10th j;)
No. 21 -ス N a 43. 5 ± 2  No. 21-S Na 43.5 ± 2
(10重量％)  (10% by weight)
No. 22 ース N a 41. 0 ± 3  No. 22 source Na 41.0 ± 3
( 1 0重量％) +ポビドンョード  (10% by weight) + Povidone
( 10重量％)  (10% by weight)
23 ( 10重量％) 22 5 ± 1 9  23 (10% by weight) 22 5 ± 1 9
24 (10重量％) +ポビド 28 0 ± 4 6  24 (10% by weight) + povid 28 0 ± 4 6
ンョード （ 10重量％)  Nyodo (10% by weight)
被験薬剤は 0 ZW型乳剤性基剤を基剤として作製した。 The test drug was prepared based on a 0 ZW type emulsion base.
以上の結果より、 創傷治癒促進性親水性高分子と殺菌 ·消毒薬を配合した製剤 は、 創傷治癒促進効果を発現することが明らかとなつた。  From the above results, it was clarified that a preparation comprising a wound healing-promoting hydrophilic polymer and a bactericidal / disinfectant exhibited a wound healing promoting effect.
実施例 2 ：殺菌力試験 Example 2: Bactericidal test
S t a p h y l o c o c c u s e p i d e rm i d i s菌浮遊液（ 106個 /mL) 1 0 OmLに各被験製剤 4. 5 g又は 4. 5 mLを添加し、 直ちに 37 °C、 1 00 r pmで振とうし、 試料溶液とする。 振とう開始後、 10分及び 20 分後に 0. 1 mo 17Lチォ硫酸 N a溶液 0. 2 mLを加えポビドンョードを失 活させた後、 37 °Cで 48時間培養した。 また、 コント口一ルとして 106個// mLの菌浮遊液 10 OmLに滅菌した生理食塩水 4. 5mLを添加し、 各製剤と 同様に試験した。 S taphylococcusepide rm idis cell suspension (10 6 cells / mL) Add 4.5 g or 4.5 mL of each test preparation to 10 OmL, and immediately shake at 37 ° C and 100 rpm to obtain the sample solution. And After 10 minutes and 20 minutes from the start of shaking, 0.2 mL of 0.1 mo 17L thiosulfate Na solution was added to inactivate povidone, and the cells were cultured at 37 ° C for 48 hours. As a control, 4.5 mL of sterilized physiological saline was added to 10 OmL of a 10 6 cells // mL bacterial suspension, and the test was carried out in the same manner as for each preparation.
48時間後の培地が混濁した場合は S t a phy l o c o c c u s e p i d e r m i d i sの増殖が認められ 「殺菌効果なし」 と判定した。 また、 培地が混 濁せずに透明な場合は、 S t a phy l o c o c c u s e p i d e rm i d i sの増殖を認めず 「殺菌効果あり」 と判定した。  When the medium became turbid after 48 hours, the growth of Staphylococ c cusep epidermidis was recognized, and it was determined that there was no bactericidal effect. In addition, when the medium was transparent without turbidity, the growth of Staphylococ cucepidermidis was not recognized, and it was determined to have "bactericidal effect".
比較薬剤であるイソジン （商標） ゲル （明治製菓 （株） ） 及びイソジン （商標 ) 液 （明治製菓 （株） ） は抗菌力活性を示した。 一方、 ぺクチンとポビドンョー ド配合剤 （製剤番号 4、 25) においても抗菌力活性が認められた。 このことよ り、 ぺクチンを配合しても抗菌力活性を示すことが明らかとなった Isodine ™ gel (Meiji Seika Co., Ltd.) and Isodine ™ liquid (Meiji Seika Co., Ltd.), which are comparative drugs, exhibited antibacterial activity. On the other hand, antibacterial activity was also observed with the combination of Pectin and Povidonol (Formulation Nos. 4 and 25). This And showed antibacterial activity even when mixed with Pectin.
表 6  Table 6
製剤番号 製剤名 抗菌力活性  Formulation number Formulation name Antibacterial activity
コント口一ル 生理食塩水 Control mouth saline
比較薬剤 (商標) ゲル + Comparative Drug ™ gel +
比較薬剤 (商標） 液 + Comparative drug (trademark) liquid +
No. 3 ぺクチン 1 0重』 %軟膏 (マクロゴ No. 3 Pectin 10 weight ”% ointment (Macrogo
ール基剤）  Base)
No. 4 ぺクチン 1 0重』 %+ポビドンョ一 +  No. 4 Pectin 10 weight ”% + Povidoncho +
ド 1 0重 :%軟膏 （マクロゴール基  De 10th layer:% ointment (Macrogol group
剤）  Agent)
No. 15 ぺクチン 0重量％ (OZW乳剤性  No. 15 Pectin 0% by weight (OZW emulsion
基剤）  Base)
No. 25 ぺクチン 0重量％ +ポビドンョー +  No. 25 Pectin 0% by weight + Povidon +
ド、 1 (OZW乳剤性基剤）  C, 1 (OZW emulsion base)
一 ；抗菌力活性なし +抗菌力活性あり 1. No antibacterial activity + antibacterial activity
以上の結果より、 創傷治癒促進性親水性高分子と殺菌 ·消毒薬を配合した製剤 は殺菌 ·消毒作用を示し、 殺菌消毒作用と創傷治癒促進作用の両者を有すること が明らかとなった。  From the above results, it was clarified that a preparation comprising a wound healing promoting hydrophilic polymer and a disinfectant / disinfectant exhibited a disinfecting / disinfecting action, and had both a disinfecting action and a wound healing promoting action.
実施例 3 ：ぺクチンの分子量と創傷治癒促進効果の検討 Example 3: Examining the molecular weight of Pectin and its effect on promoting wound healing
表 7  Table 7
創傷治癒促進効果 製剤名 分子 j  Wound healing promoting effect Formulation name molecule j
( )  ()
No. 26 ぺクチン （10重量％) 約 300,000 52. 8 ± 3. 2 No. 26 Pectin (10% by weight) About 300,000 52. 8 ± 3.2
No. 27 ぺクチン部分加水分解物 A (10 約 200,000 37. 2 ± 4. 7 重量％) No. 27 Pectin partial hydrolyzate A (10 about 200,000 37.2 ± 4.7% by weight)
No. 28 ぺクチン部分加水分解物 B (1 0 約 60, 000 27. 1 ± 7. 7 重量％)  No. 28 Pectin partial hydrolyzate B (10 about 60,000 27.1 ± 7.7% by weight)
No. 29 ぺクチン部分加水分解物 C (1 0 約 30,000 22. 0 ± 5. 8 重量％)  No. 29 Pectin partial hydrolyzate C (10 about 30,000 22.0 ± 5.8% by weight)
No. 30 ぺクチン部分加水分解物 D (10 約 3, 000 20. 1 ± 3. 8 重量％) _ _ _ 被験薬剤はプラスチベースを基剤として作製した。  No. 30 Pectin partial hydrolyzate D (10 about 3,000 20.1 ± 3.8% by weight) ____ The test drug was prepared based on plastibase.
分子量は、 ゲルろ過によって測定されたメインピークの分子量を表す。 The molecular weight indicates the molecular weight of the main peak measured by gel filtration.
ぺクチンの部分加水分解物はべクチン （分子量約 300, 000、 エステル化 度 74%) をべクチナ一ゼ処理することにより作製した。 また、 その分子量は T A partial hydrolyzate of pectin was prepared by treating pectin (molecular weight about 300,000, esterification degree 74%) with pectinase. The molecular weight is T
SK— g e l G4000 PWによるゲルろ過でメインピークを測定し、 プルラ 4 Measure the main peak by gel filtration with SK-gel G4000 PW. Four
ン （S t a n d a r d P— 82、 昭和電工） を標準試料として、 メインピーク の分子量を求めた。 The molecular weight of the main peak was determined using a standard sample (Standard P-82, Showa Denko).
ピーク分子量が約 3, 000のものから約 300， 000のものまで創傷治癒 促進作用が認められ、 ピーク分子量が大きくなるに従って、 創傷治癒促進効果が 強くなり、 ピーク分子量が 200， 000以上のもの （製剤番号 26、 27) が 創傷治癒促進効果が強いことが明らかになった。  Wound healing promoting action was observed from a peak molecular weight of about 3,000 to about 300,000. As the peak molecular weight increased, the wound healing promoting effect became stronger, and a peak molecular weight of 200,000 or more ( Formulation Nos. 26 and 27) were found to have a strong wound healing promoting effect.
実施例 4 ：ぺクチンのエステル化度と創傷治癒促進効果の検討 Example 4: Examination of the degree of esterification of pectin and the effect of promoting wound healing
表 8  Table 8
創傷治癒促進効果 製剤名 エステル化度  Wound healing promoting effect Formulation name Esterification degree
(%)  (%)
No. 31 ぺクチン A ( 1 0重量％) 74 % 52. 8 ± 3. 2 No. 31 Pectin A (10% by weight) 74% 52.8 ± 3.2
No. 32 ぺクチン B ( 10重量％) 36 % 5 1. 1 ± 3. 1No. 32 Pectin B (10% by weight) 36% 5 1.1 ± 3.1
No. 33 ぺクチン C ( 1 0重量％) 3 1 % 49. 0 ± 3. 1No. 33 Pectin C (10% by weight) 3 1% 49.0 ± 3.1
No. 34 ぺクチン酸 ( 10重量％) 0 % 7. 0 ± 3. 5 被験薬剤はプラスチベースを基剤として作製した。 No. 34 Pectic acid (10% by weight) 0% 7.0 ± 3.5 Test drugs were prepared based on plastibase.
分子量はぺクチン Aが約 300， 000、 ぺクチン B及びべクチン Cが約 25 0， 000である。 エステル化度の異なるぺクチンの創傷治癒促進作用の結果を 表 8に示した。 エステル化度 3 1〜74%のべクチンは創傷治癒促進作用を示し た。 一方、 エステル化度 0 %のぺクチン酸では創傷治癒促進作用は認められなか つた。  The molecular weights of Pectin A are about 300,000, and that of Pectin B and Vectin C are about 250,000. Table 8 shows the results of the wound healing promoting effect of pectins having different degrees of esterification. Vectin with a degree of esterification of 31 to 74% exhibited a wound healing promoting effect. On the other hand, no effect of promoting wound healing was observed with pectic acid having a degree of esterification of 0%.
実施例 5 ：モルモット肌荒れ改善試験 Example 5: Guinea pig rough skin improvement test
S a g i Vらの方法 （S k i n Re s Te c n o 6 ; 37 200 0) に準じて肌荒れモデルを作製した。 しかし、 本発明の目的から、 より重度の 肌荒れモデルを作製する必要があつたため、 肌荒れを惹起するための界面活性剤 、 すなわちラウリル硫酸ナトリウムの濃度を多くし、 重度の肌荒れモデルとした ハートレー系モルモットの背部被毛を刈毛後、 5 %ラウリル硫酸ナトリゥム水 溶液に浸漬した 2. 5 cmX 2. 5 cmの布を 1日 1回 5分間、 3日間連続して 塗布し、 正中線で対称の肌荒れを作製した。 最終塗布 2日後、 肌荒れ皮膚の経皮 水分蒸散量 （TEWL) を測定した後、 片側に被験薬剤を 10 Omgずつ塗布し 、 24時間後に再度 TEWLを測定し、 下記の式により肌荒れ改善促進効果を算 出した （値が大きいほど肌荒れ改善促進効果が強い） なお、 無塗布部位を対照 部位とした。 ヽ A rough skin model was prepared according to the method of Sagi V et al. (Skin Res Tecno 6; 372000). However, for the purpose of the present invention, it was necessary to prepare a more severe rough skin model, so that the concentration of the surfactant for causing rough skin, i.e., sodium lauryl sulfate, was increased, and the Hartley guinea pig was used as a severe rough skin model. After shaving the back coat, a 2.5 cm X 2.5 cm cloth immersed in 5% aqueous sodium lauryl sulfate solution was applied once a day for 5 minutes for 3 consecutive days. Skin roughness was produced. Two days after the final application, the transdermal water loss (TEWL) of the rough skin was measured, and then the test drug was applied on each side at 10 Omg. After 24 hours, the TEWL was measured again. Arithmetic (The larger the value, the stronger the effect of promoting the improvement of skin roughness.) The uncoated area was taken as the control area.ヽ
各被験製剤投与群の平均値  Average value of each test drug administration group
肌荒れ改善促進効果 （％) X 1 0 0
Figure imgf000016_0001
対照群の平均値 ノ 表 9に示す配合組成の皮膚外用軟膏を、 基剤に白色ヮセリンを用いて乳鉢にて 調製し、 創傷治癒促進効果及び肌荒れ改善促進効果を調べた。 配合量は、 他に指 定の無い限り重量％を示す。 その結果、 ぺクチンを含む製剤 （製剤番号 3 5及び 3 6 ) は、 ぺクチンを含まない比較製剤 1及び 2と比べて極めて高い創傷治癒促 進効果が認められた。 また、 尿素含む製剤 （製剤番号 3 5、 比較製剤 2 ) は肌荒 れ改善促進効果が認められた。 すなわち、 尿素とぺクチンを配合した製剤 （製剤 番号 3 5 ) は、 創傷治癒促進効果と肌荒れ改善促進効果を有することが明らかに なった。 Skin roughness improvement promotion effect (%) X 100
Figure imgf000016_0001
Average value of control group No. A skin external ointment having the composition shown in Table 9 was prepared in a mortar using white ヮ -serine as a base, and the effects of promoting wound healing and improving skin roughness were examined. Unless otherwise specified, the blending amount is shown in% by weight. As a result, the preparations containing Pectin (Formulation Nos. 35 and 36) showed an extremely high wound healing promoting effect as compared with Comparative Preparations 1 and 2 containing no Pectin. A preparation containing urea (Formulation No. 35, Comparative Preparation 2) was found to have an effect of improving skin roughness. That is, it was clarified that the preparation containing urea and pectin (formulation No. 35) had an effect of promoting wound healing and an effect of improving skin roughness.
表 9  Table 9
Figure imgf000016_0002
Figure imgf000016_0002
表 1 0に示す配合組成の皮膚外用軟膏を調製し、 創傷治癒促進効果及び肌荒れ 改善促進効果を調べた。 配合量は、 他に指定の無い限り重量％を示す。 その結果 Skin external ointments having the composition shown in Table 10 were prepared, and the effects of promoting wound healing and improving skin roughness were examined. The amounts are by weight unless otherwise specified. as a result
、 ぺクチンを含む製剤 （製剤番号 3 7及び 3 8 ) は、 ぺクチンを含まない比較製 剤 3及び 4と比べて極めて高い創傷治癒促進効果が認められた。 また、 尿素含む 製剤 （製剤番号 3 7、 比較製剤 4 ) は肌荒れ改善促進効果が認められた。 すなわ ち、 尿素とぺクチンを配合した製剤 （製剤番号 3 7 ) は、 創傷治癒促進効果と肌 荒れ改善促進効果を有することが明らかになった。 表 1 0 On the other hand, the preparation containing Pectin (Formulation Nos. 37 and 38) showed an extremely high wound healing promoting effect as compared with Comparative Preparations 3 and 4 containing no Pectin. In addition, the preparations containing urea (Formulation No. 37, Comparative Preparation 4) were found to have an effect of improving skin roughness. In other words, it was revealed that a preparation containing urea and pectin (Formulation No. 37) had an effect of promoting wound healing and improving skin roughness. Table 10
Figure imgf000017_0001
Figure imgf000017_0001
表 1 1に示す配合組成の皮膚外用軟膏を調製し、 創傷治癒促進効果及び肌荒れ 改善促進効果を調べた。 配合量は、 他に指定の無い限り重量％を示す。 その結果 Skin external ointments having the composition shown in Table 11 were prepared, and the effects of promoting wound healing and improving skin roughness were examined. The amounts are by weight unless otherwise specified. as a result
、 ぺクチンを含む製剤 （製剤番号 3 9及び 4 0 ) は、 ぺクチンを含まない比較製 剤 5及び 6と比べて極めて高い創傷治癒促進効果が認められた。 また、 尿素含む 製剤 （製剤番号 3 9、 比較製剤 6 ) は肌荒れ改善促進効果が認められた。 すなわ ち、 尿素とぺクチンを配合した製剤 （製剤番号 3 9 ) は、 創傷治癒促進効果と肌 荒れ改善促進効果を有することが明らかになった。 On the other hand, the preparations containing Pectin (Formulation Nos. 39 and 40) showed an extremely high wound healing promoting effect as compared with the comparative preparations 5 and 6 containing no Pectin. Formulations containing urea (Formulation No. 39, Comparative Formulation 6) were found to have an effect of improving skin roughness. In other words, it was revealed that a preparation containing urea and pectin (formulation No. 39) had an effect of promoting wound healing and an effect of improving skin roughness.
表 1 1 Table 11
Figure imgf000018_0001
Figure imgf000018_0001
以上の結果より、 創傷治癒促進性親水性高分子であるべクチンと皮膚保湿作用 を持つ尿素を配合した製剤は、 あらゆる基剤を用いても、 尿素の皮膚保湿作用及 び創傷治癒促進性親水性高分子の創傷治癒促進効果を発現し、 本発明が非常に有 用であることが示唆された。  From the above results, it is clear that a formulation containing Vectin, a hydrophilic polymer that promotes wound healing, and urea, which has a skin moisturizing effect, can be used with any base, even if urea has a skin moisturizing effect and a wound healing promoting hydrophilicity. Since the effect of promoting the wound healing was exhibited by the conductive polymer, it was suggested that the present invention was very useful.

Claims

請求の範囲 The scope of the claims
1. 薬効成分に創傷治癒促進性親水性高分子を有効成分として配合してなること を特徴とする外用剤。  1. An external preparation characterized by compounding a medicinal ingredient with a wound healing promoting hydrophilic polymer as an active ingredient.
2. 創傷治癒促進性親水性高分子が、 ラット欠損創試験で 20 %以上の創傷治癒 促進効果を発現する親水性高分子である請求項 1記載の外用剤。  2. The external preparation according to claim 1, wherein the wound healing-promoting hydrophilic polymer is a hydrophilic polymer that exhibits a wound healing promoting effect of 20% or more in a rat defect wound test.
3. 創傷治癒促進性親水性高分子がぺクチン、 アルギン酸、 カルポキシメチルセ ルロース、 アラビアゴム及びプルランからなる群から選ばれる少なくとも 1種又 は 2種以上である請求項 1又は 2記載の外用剤。  3. The external use according to claim 1 or 2, wherein the wound healing promoting hydrophilic polymer is at least one kind or two or more kinds selected from the group consisting of pectin, alginic acid, carboxymethyl cellulose, gum arabic and pullulan. Agent.
4. 薬効成分が、 創傷部、 皮膚、 粘膜及びノ又は損傷粘膜に適用して効果を発現 する薬効成分である請求項 1〜 3のいずれか 1項記載の外用剤。  4. The external preparation according to any one of claims 1 to 3, wherein the medicinal component is a medicinal component that exerts an effect when applied to a wound site, skin, mucous membrane, or damaged mucosa.
5. 薬効成分が、 殺菌 ·消毒剤、 皮膚用保湿剤、 抗炎症剤、 抗アレルギー剤、 局 所麻酔剤及びピ夕ミン剤からなる群から選ばれる少なくとも 1種又は 2種以上で ある請求項 1〜 4のいずれか 1項記載の外用剤。  5. The medicinal component is at least one or more selected from the group consisting of a bactericidal / disinfectant, a skin moisturizer, an anti-inflammatory agent, an anti-allergic agent, a local anesthetic and a pinumin agent. An external preparation according to any one of claims 1 to 4.
6. 薬効成分が、 殺菌 '消毒剤である請求項 1〜 5のいずれか 1項記載の外用剤  6. The external preparation according to any one of claims 1 to 5, wherein the medicinal component is a disinfectant.
7. 殺菌 ·消毒剤がヨウ素及びヨウ素複合体である請求項 6記載の外用剤。7. The external preparation according to claim 6, wherein the disinfectant / disinfectant is iodine and an iodine complex.
8. ョゥ素及びヨウ素複合体がポビドンョードである請求項 7記載の外用剤。8. The external preparation according to claim 7, wherein the iodine and iodine complex is povidone oxide.
9. 殺菌 ·消毒剤が抗生物質である請求項 6記載の殺菌 ·消毒剤。 9. The disinfectant according to claim 6, wherein the disinfectant is an antibiotic.
1 0. 殺菌 ·消毒剤が抗真菌剤である請求項 6記載の外用剤。  10. The external preparation according to claim 6, wherein the disinfectant is a fungicide.
1 1. 殺菌 ·消毒剤が消毒用石鹼類化合物である請求項 6記載の外用剤。  7. The external preparation according to claim 6, wherein the disinfectant is a disinfecting stone compound.
12. 殺菌 ·消毒剤がフエノール系化合物である請求項 6記載の外用剤。  12. The external preparation according to claim 6, wherein the disinfectant / disinfectant is a phenolic compound.
1 3. 殺菌 ·消毒剤がダルコン酸クロルへキシジンである請求項 6記載の外用剤  1 3. The external preparation according to claim 6, wherein the disinfectant is chlorhexidine dalconate.
14. 殺菌 ·消毒剤がァクリノールである請求項 6記載の外用剤。 14. The external preparation according to claim 6, wherein the sterilizing / disinfecting agent is acrinol.
1 5. 薬効成分が、 皮膚用保湿剤である請求項 1〜5のいずれか 1項に記載の外 用剤。  1 5. The external preparation according to any one of claims 1 to 5, wherein the medicinal component is a skin moisturizer.
1 6. 皮膚用保湿剤が、 天然保湿因子である請求項 1 5記載の外用剤。  16. The external preparation according to claim 15, wherein the skin moisturizing agent is a natural moisturizing factor.
1 7. 薬効成分が、 抗炎症剤である請求項 1〜 5のいずれか 1項に記載の外用剤 1 7. The external preparation according to any one of claims 1 to 5, wherein the medicinal component is an anti-inflammatory agent.
1 8. 薬効成分が、 抗アレルギー剤である請求項 1〜5のいずれか 1項に記載の 外用剤。 1 8. The external preparation according to any one of claims 1 to 5, wherein the medicinal component is an antiallergic agent.
1 9. 薬効成分が、 局所麻酔剤である請求項 1〜 5のいずれか 1項に記載の外用 剤。  1 9. The external preparation according to any one of claims 1 to 5, wherein the pharmaceutically active ingredient is a local anesthetic.
20. 薬効成分が、 ビタミン剤である請求項 1〜 5のいずれか 1項に記載の外用 剤。  20. The external preparation according to any one of claims 1 to 5, wherein the medicinal ingredient is a vitamin preparation.
2 1. 創傷治癒促進性親水性高分子が、 ぺクチンである請求項 1〜20のいずれ か 1項に記載の外用剤。  21. The external preparation according to any one of claims 1 to 20, wherein the wound healing promoting hydrophilic polymer is pectin.
22. ぺクチンの分子量が約 3, 000〜約 800, 000である請求項 21記 載の外用剤。  22. The external preparation according to claim 21, wherein the molecular weight of Pectin is about 3,000 to about 800,000.
23. ぺクチンの分子量が約 200, 000〜約 500， 000である請求項 2 1又は 22記載の外用剤。  23. The external preparation according to claim 21 or 22, wherein the molecular weight of Pectin is about 200,000 to about 500,000.
24. ぺクチンのエステル化度が 20 %以上である請求項 2 1〜 23のいずれか 1項に記載の外用剤。  24. The external preparation according to any one of claims 21 to 23, wherein the degree of esterification of pectin is 20% or more.
25. ぺクチンのエステル化度が 30〜80 %である請求項 21-24のいずれ か 1項に記載の外用剤。  25. The external preparation according to any one of claims 21 to 24, wherein the degree of esterification of pectin is 30 to 80%.
26. 創傷治癒促進性親水性高分子が、 アルギン酸である請求項 1〜20のいず れか 1項に記載の外用剤。  26. The external preparation according to any one of claims 1 to 20, wherein the wound healing-promoting hydrophilic polymer is alginic acid.
27. 創傷治癒促進性親水性高分子が、 カルポキシメチルセルロースである請求 項 1〜 20のいずれか 1項に記載の外用剤。  27. The external preparation according to any one of claims 1 to 20, wherein the wound healing-promoting hydrophilic polymer is carboxymethylcellulose.
28. 創傷治癒促進性親水性高分子が、 アラビアゴムである請求項 1〜20のい ずれか 1項に記載の外用剤。  28. The external preparation according to any one of claims 1 to 20, wherein the wound healing promoting hydrophilic polymer is gum arabic.
29. 創傷治癒促進性親水性高分子が、 プルランである請求項 1〜20のいずれ か 1項に記載の外用剤。  29. The external preparation according to any one of claims 1 to 20, wherein the wound healing promoting hydrophilic polymer is pullulan.
30. 剤形が固形状製剤である請求項 1〜 29のいずれか 1項に記載の外用剤。  30. The external preparation according to any one of claims 1 to 29, wherein the dosage form is a solid preparation.
3 1. 剤形が半固形状製剤である請求項 1〜29のいずれか 1項に記載の外用剤 3 1. The external preparation according to any one of claims 1 to 29, wherein the dosage form is a semi-solid preparation.
32 · 剤形が液剤又はエアゾール剤である請求項 1〜 29のいずれか 1項に記載 の外用剤。 32. The external preparation according to any one of claims 1 to 29, wherein the dosage form is a liquid preparation or an aerosol preparation.
3 3 . 剤形が貼付剤である請求項 1〜 2 9のいずれか 1項に記載の外用剤。33. The external preparation according to any one of claims 1 to 29, wherein the dosage form is a patch.
3 4 . 創傷治癒促進性親水性高分子の含量が 0 . 0 1〜6 0重量％であることを 特徴とする請求項 1〜 3 3のいずれか 1項に記載の外用剤。 34. The external preparation according to any one of claims 1 to 33, wherein the content of the wound healing-promoting hydrophilic polymer is 0.01 to 60% by weight.
3 5 . 創傷治癒促進性親水性高分子の含量が 3〜 3 0重量％であることを特徴と する請求項 1〜 3 4のいずれか 1項に記載の外用剤。  35. The external preparation according to any one of claims 1 to 34, wherein the content of the wound healing promoting hydrophilic polymer is 3 to 30% by weight.
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