Classifications

• • 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
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
• • 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
  • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
  • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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  • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
  • A61K31/05—Phenols
• • 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
  • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
  • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• • 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
  • A61K31/16—Amides, e.g. hydroxamic acids
  • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
  • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• • 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
  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
• • 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
  • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
  • A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• • 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
  • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
  • A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
• • 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
• • 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
  • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
  • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• • 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
  • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• • 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
  • A61P23/00—Anaesthetics
• • 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
  • 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
  • A61P31/10—Antimycotics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

• the invention relates to an external preparation for athlete's foot treatment, comprising an anti- trichophton drug and at least one compound, which is selected from l-menthol, menthol analogue compounds and bactericidal compounds, as an essential ingredient.
• antifungal agents used for an external preparation for athlete's foot treatment
• various antifungal agents such as imidazole, triazole, thiocarbamic acid, benzylamine, allylamine and morpholine types have been developed and have been on the market.
• each of anti-fungal agents has a difference in its width of the antifungal spectrum and the antifungal activity, and there is no antifungal agent which shows a strong antibacterial activity over Trychophyton and other fungi, for example, Candida albicans and the like, fungi in general, whereby an external preparation and the like, in which an antifungal activity or the like are strengthened by a combination of two or more of antifungal agents, are reported (ex. see Patent documents 1-3).
• composition with a strengthened antifungal activity in which an allylamine type antifungal agent and menthol are blended, this increases the activity against so called Trychophyton and does not strengthen the antifungal activity against other fungi such as Candida albicans (ex. see Patent document 4).
• any external preparation disclosed in the above documents did not suppress the growth of skin habitual bacteria such as Staphylococus aureus and did not have effects in a case that the skin habitual bacteria such as Candida albicans and Staphylococus aureus , which accelerated the discomfort of athlete's foot (itch, bad smell, etc.), grew abnormally, therefore, it could not be said that it satisfactorily enhanced patient's compliance after applying such external preparation described above.
• Patent document 1 JP, A1, 3-38522
• Patent document 2 JP, A1, 9-176014
• Patent document 3 JP, A1, 2004-35411
• Patent document 4 JP, A1, 2004-149508
• Patent document 5 JP, A1, 7-233088
• Patent document 6 JP, A1, 8-20527
• an anti- trichophton drug such as butenafine hydrochloride has a very excellent antifungal action even in alone
• the invention provides an external preparation for athlete's foot treatment, having a more excellent effect in points such as enhancement of patient's compliance and reduction of the symptom of rube faction.
• Trichophyton but also other fungi such as Candida albicans and a skin habitual bacteria such as Staphylococus aureus are effectively reduced by an external preparation containing an anti- trichophton drug and at least one compound selected from l-menthol, menthol analogue compounds and bactericidal compounds as an essential ingredient.
• the invention relates to an external preparation for athlete's foot treatment, comprising an anti- trichophyton drug mixed with at least one compound selected from l-menthol, menthol analogue compounds and bactericidal compounds.
• the invention relates to the external preparation for athlete's foot treatment, wherein the anti- trichophton drug and at least one compound selected from l-menthol, menthol analogue compounds and bactericidal compounds are blended in 0.1-10% by mass and 0.5-5% by mass respectively.
• the invention relates to the external preparation for athlete's foot treatment, wherein the menthol analogue compound is 3-l -menthoxypropane-1,2-diol.
• the invention relates to an external preparation for athlete's foot treatment, wherein the bactericidal compound is isopropylmethylphenol.
• the invention relates to an external preparation for athlete's foot treatment, where in the anti- trichophyton drug is selected from benzylamine type, allylamine type, thiocarbamic acid type and imidazole type antifungal agents.
• the invention relates to an external preparation for athlete's foot treatment, wherein the anti- trichophyton drug is one kind selected from butenafine hydrochloride, terbinafine hydrochloride, tolnaftate, bifonazole, ketoconazole, neticonazole hydrochloride and lanoconazole.
• the anti- trichophyton drug is one kind selected from butenafine hydrochloride, terbinafine hydrochloride, tolnaftate, bifonazole, ketoconazole, neticonazole hydrochloride and lanoconazole.
• the invention relates to an external preparation for athlete's foot treatment, wherein the anti- trichophton drug and l-menthol are blended.
• the invention relates to the external preparation for athlete's foot treatment, wherein butenafine hydrochloride, l-menthol and isopropylmethylphenol are blended.
• the invention relates to the external preparation for athlete's foot treatment, also comprising at least one kind of a local anesthetic, an antihistamine and an anti-inflammatory drug.
• the invention relates to the external preparation for athlete's foot treatment, wherein the local anesthetic is dibucaine hydrochloride, or lidocaine or its salt.
• the invention relates to the external preparation for athlete's foot treatment, wherein the antihistamine is chlorpheniramine maleate, or diphenhydramine or its salt.
• the invention relates to the external preparation for athlete's foot treatment, wherein the anti-inflammatory drug is glycyrrhetinic acid or its salt, or allantoin.
• the invention relates to the external preparation for athlete's foot treatment, wherein butenafine hydrochloride, l-menthol, dibucaine hydrochloride, chlorpheniramine maleate and glycyrrhetinic acid are blended.
• the external preparation for athlete's foot treatment of the invention suppresses the growth of skin habitual fungi such as Staphylococus aureus and Candida albicans , which become a cause of a bad smell of foot due to athlete's foot, aggravation athlete's foot and the like, without combination of an antifungal agent, and not only improves a therapeutic effect for athlete's foot compared with a case simply to reduce Trichophyton but has effect to enhance patient's compliance.
• said external preparation for athlete's foot treatment contains at least one kind among a local anesthetic, an antihistamine and an anti-inflammatory drug, it suppresses rube faction which an anti- trichophyton drug rarely produces even if in a slight degree, and further favorable enhancement of compliance can be obtained.
• this effect can be obtained by blending at least one kind among the local anesthetic, the antihistamine and the anti-inflammatory drug, it is possible to get further favorable effect by combination of two or more kinds.
• an anti- trichophton drug is blended in a specific concentration, that is, 0.1-10.0% by mass, preferably 1-5% by mass, with at least one kind of compound selected from l-menthol, a menthol analogue compound and a bactericidal compound in the range of 0.5-5% by mass, preferably 1-3% by mass in total.
• the blend amount of the anti- trichophton drug not less than 0.1% by mass, the effect as an anti- trichophyton agent can easily be obtained, and even if blending not less than 10% by mass, the effect as the anti- trichophton agent is hardly improved.
• the anti- trichophton drugs used in the invention are benzylamine type, allylamine type, thiocarbamic acid type and imidazole type and triazole type antifungal agents, specifically, include butenafine hydrochloride, terbinafine hydrochloride, tolnaftate, miconazole, bifonazole, ketoconazole, clotrimazole, econazole nitrate, neticonazole hydrochloride, lanoconazole, isoconazole, oxiconazole, sulconazole, tioconazole, fluconazole and itraconazole, though butenafine hydrochloride, terbinafine hydrochloride, tolnaftate, bifonazole, ketoconazole, neticonazole hydrochloride and lanoconazole are preferable, and butenafine hydrochloride is particularly preferable.
• butenafine hydrochloride is high in activity against Trichophyton , the activity against Candida albicans and Staphylococus aureus can not be expected much, and therefore, by using it with at least one kind of compound in combination, which are selected from l-menthol, a menthol analogue compound and a bactericidal compound, preferably the activity against Trichophyton as well as Candida albicans and Staphylococus aureus can synergistically be enhanced.
• Compounds used together with the anti- trichophton drug in the invention include l-menthol, in addition, menthol analogue compounds such as dl -menthol, 3-l-menthoxypropane-1,2-diol, isopulegol, neoisopulegol, neomenthol, isomenthol, neo-isomenthol, citronellol and linallol, and bactericidal compounds such as isopropylmethylphenol, dequalinium chloride, dequalinium acetate, benzethonium chloride, benzalkonium chloride, chlorhexidine chloride, chlorhexidine gluconate, hinokitiol and resorcin, though 3-l-menthoxypropane-1,2-diol, isopropylmethylphenol and the like are preferably used.
• menthol analogue compounds such as dl -menthol, 3-l-menthoxypropane-1
• the growth of Candida albicans and Staphylococus aureus can preferably be suppressed, and making it not more than 5% by mass is preferable because a problem of difficult drying in a liquid preparation does not occur.
• antihistamines used in the invention include cholorpheniramine or its salts, diphenhydramine or its salts, promethazine, mequitazine and the like, cholorpheniramine, diphenhydramine or its salts are preferable.
• the concentration of the antihistamine is preferably 0.05-5.0% by mass, more preferably 0.05-2.0% by mass.
• lidocaine or its salts dibucaine or its salts, tetracaine or its salts, procaine or its salts, ethyl aminobenzoate and the like, dibucaine hydrochloride, or lidocaine or is salts are preferable.
• the concentration of the local anesthetic is preferably 0.01-5.0% by mass, more preferably 0.05-2.0% by mass.
• the kinds of anti-inflammatory drugs used in the invention include glycyrrhetinic acid or its salts, non-steroidal types such as methyl salicylate, glycol salicylate, indometacin, diclofenac, felbinac, piroxicam, ketoprofen, ibuprofenpiconol, bufexamac or allantoin, and steroidal types such as amcinonide, prednisolone valerate, diflucortolone valerate, dexamethasone valerate, betamethasone valerate, dexamethasone acetate, hydrocortisone acetate, dexamethasone, triamcinolone acetonide, halcinonide, betamethasone dipropionate, fluocinonide, fluocinolone acetonide, prednisolone, deprodone propionate, clobetasol propionate or betamethasone, though glycyr
• the concentration of the anti-inflammatory drug is preferably 0.05-10.0% by mass, more preferably 0.05-2.0%by mass.
• dibucaine hydrochloride, cholorpheniramine maleate and glycyrrhetinic acid are blended for an external preparation for athlete's foot treatment consisting of butenafine hydrochloride and l-menthol is particularly preferable because it can synergistically enhance the compliance.
• the external preparation described in the invention includes a liquid preparation, a cream, a lotion, an aerosol preparation, a patch and the like.
• the external preparation of the invention may contain a usual base according to its form, and in the case of the liquid preparation or the lotion, a lower alcohol, apolyhydric alcohol, water or the like may be contained.
• an oily base a higher alcohol, a fatty acid ester, or a polyhydric alcohol or its derivative, a surfactant, a gellant, water or the like may be contained.
• a lower alcohol As the aerosol preparation, a lower alcohol, a polyhydric alcohol or the like may be contained to dissolve the drug of the invention.
• methanol, ethanol, denatured ethanol, isopropanol and the like may be illustrated.
• liquid paraffin, vaseline, paraffin-wax and the like may be illustrated, and the higher alcohol is C 10-20 alcohol, preferably cetyl alcohol, stearyl alcohol, cetostearyl alcohol and oleyl alcohol are preferable.
• the polyhydric alcohol and its derivative there are glycerol, ethylene glycol. propylene glycol, 1,3-butylene glycol, dipropylene glycol, polyethylene glycol, polypropylene glycol, and these esters or ethers.
• the fatty acid ester is a higher fatty acid ester, and esters of a higher fatty acid such as myristic acid, palmitic acid, stearic acid or oleic acid, with a lower alcohol (C 1-6 ) may be illustrated.
• the surfactant may be an anionic surfactant such as polyoxyethylenealkylether phosphate or sodium alkylsulfate, a sorbitan fatty acid ester such as sorbitan sesquioleate, sorbitan trioleate, sorbitan monostearate, sorbitan monolaurate, polyoxyethylene sorbitan stearate, a nonionic surfactant such as polyoxyethylene nonylether, monooxyethylene cetylether or monooxyethylene laurylether, in addition, a cationic surfactant such as benzethonium chloride or benzalkonium chloride, or an amphoteric surfactant.
• anionic surfactant such as polyoxyethylenealkylether phosphate or sodium alkylsulfate
• a sorbitan fatty acid ester such as sorbitan sesquioleate, sorbitan trioleate
• sorbitan monostearate such as sorbitan monostearate
• the gel-type vehicle includes carboxyvinyl polymer, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl-cellulose, ethylcellulose, carboxymethyl cellulose and the like.
• the external preparation for athlete's foot treatment of the invention may contain a percutaneous absorption promoter, and if said percutaneous absorption promoter is one or more compounds in which a percutaneous absorption promoting action of the anti- trichophton drug is recognized, any compound may be used.
• Examples include C 6 -C 20 fatty acids, fatty alcohols, fatty acid esters or fatty acid ethers, aromatic organic acids, aromatic alcohols, aromatic organic acid esters or aromatic organic acid ethers, furthermore lactic acid esters, acetic acid esters, monoterpene compounds, sesquiterpene compounds, Azone or Azone derivatives, glycerol fatty acid esters, sorbitan fatty acidesters, polysorbates, polyethylene glycol fatty acid esters, polyoxyethylene hydrogenated castor oils and sucrose fatty acid esters.
• Fatty acid esters and fatty alcohols are preferable, in particular, isopropyl miristate, isopropyl palmitate, sorbitan monooleate and oleyl alcohol are preferable.
• the external preparation for athlete's foot treatment of the invention may contain an antioxidant, an antiseptic agent, a preservative, a moisturizing agent, ache late agent and other additive which are usually blended in a skin external preparation.
• an aqueous phase and an oil phase were each heated at 80° C., mixed and emulsified under a sufficient stirring. Then, the emulsion was cooled under stirring to room temperature to obtain the creams of the examples 7-9.
• Example 10-12 and the comparative example 1 were applied to 20 patients with a skin fungus disease, showing the number of persons who got the refreshing feeling and the efficacy feeling (in particular, alleviation of itch) TABLE 5 Sensory test Comparative Example 10
• Example 11 Example 12 example 1 Refreshing 12 persons/ 14 persons/ 17 persons/ 8 persons/ feeling 20 persons 20 persons 20 persons 20 persons Efficacy 5 persons/ 7 persons/ 10 persons/ 2 persons/ feeling 20 persons 20 persons 20 persons 20 persons 20 persons (alleviation of itch)
• test bacteria Staphylococus aureus, Candida albicans
• SCD agar culture medium cooled to an appropriate temperature after a high-pressure wet sterilization, adjusting the bacterial count to about 10 6 /mL.
• test bacteria incubated in 1. were thinly applied to the SCD agar culture medium formed beforehand into a multilayer, cooled and fixed at room temperature.
• the blend amount of l-menthol was set in 7 classes in the range of 0-4%.
• Macrogol 400 20%
• Test bacteria Staphylococus aureus Candida albicans Butenafine hydrochloride: 1% Absence of Absence of L-Menthol: 0% inhibition ring inhibition ring Butenafine hydrochloride: 1% Absence of Absence of L-Menthol: 0.1% inhibition ring inhibition ring Butenafine hydrochloride: 1% Absence of Absence of L-Menthol: 0.2% inhibition ring inhibition ring Butenafine hydrochloride: 1% Absence of Presence of L-Menthol: 0.5% inhibition ring inhibition ring (10 mm) Butenafine hydrochloride: 1% Presence of Presence of L-Menthol: 1% inhibition ring inhibition ring (9 mm) (10 mm) Butenafine hydrochloride: 1% Presence of Presence of L-Menthol: 2% inhibition ring inhibition ring
• the antibacterial action was confirmed by blend of not less than 0.5% against Candida albicans and not less than 1% against Staphylococus aureus.
• the antibacterial action against Staphylococus aureus and Candida albicans was confirmed in the concentration of not less than 0.5% of 3-1-menthoxypropane-1,2-diol.
• the formula in which isopropylmethylphenol and l-menthol were blended in combination it was also confirmed to be able to carry out effectively the suppression of Staphylococus aureus and Candida albicans.

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• 2004
  • 2004-06-25 US US10/561,499 patent/US20070099932A1/en not_active Abandoned
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