CA2257850A1 - Stabilized hinokitiol and compositions containing same - Google Patents
Stabilized hinokitiol and compositions containing same Download PDFInfo
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- CA2257850A1 CA2257850A1 CA002257850A CA2257850A CA2257850A1 CA 2257850 A1 CA2257850 A1 CA 2257850A1 CA 002257850 A CA002257850 A CA 002257850A CA 2257850 A CA2257850 A CA 2257850A CA 2257850 A1 CA2257850 A1 CA 2257850A1
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- hinokitiol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/005—Antimicrobial preparations
-
- 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
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/11—Encapsulated compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/29—Titanium; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/35—Ketones, e.g. benzophenone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
- A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
-
- 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
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/41—Particular ingredients further characterized by their size
- A61K2800/412—Microsized, i.e. having sizes between 0.1 and 100 microns
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/52—Stabilizers
- A61K2800/524—Preservatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/75—Anti-irritant
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1658—Proteins, e.g. albumin, gelatin
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5052—Proteins, e.g. albumin
Abstract
The present invention relates to cosmetic or pharmaceutical compositions containing a preservative-effective amount of hinokitiol-containing microcapsules, the microcapsules comprising a matrix containing collagen and a glycosaminoglycan.
Description
CA 022~78~0 1998-12-09 W097/47289 PCT~S97/09835 STABILIZED HINOKITIOL AND COMPOSITIONS CONTAINING SAME
Field of the Invention The present invention relates to preservatives useful in pharmaceutical and cosmetic compositions. In particular, the invention relates to a stahilized, anti-irritant preservative, hinokitiol.
Background of the Invention lo Contamination of pharmaceutical and cosmetic compositions by bacteria and/or fungi can present a serious problem to the formulator. To combat this problem, and in order to prolong shelf life of the product, such compositions frequently contain preservatives which have antimicrobial activity. Given the diverse chemical nature of the available preservatives, however, and the equally diverse nature of the compositions in which they are intended to be used, the ability to successfully use a given preservative in a particular formulation cannot be assumed.
One such preservative is the substance known as hinokitiol. [2-hydroxy-4-~1-methylethyl)-2,4,6-cycloheptatrien-1-one; isopropyltropolone]. Hinokitiol is a wood extract obtainable from pine, cedar, etc. Methods for its production are described, for example, in JP 0586396 and JP
05105898. This material is known to have potent antimicrobial effects, and,as such, has been previously used for a variety of purposes. For example, hinokitlol has been used in food preservation and prevention of discoloration (JP 78035145; JP
6277019; JP 6153788; JP 6090661; JP 5344861; JP 59085279); in combination with zinc, or with ethyl alcohol and propylene glycol for antisepsis and/or the treatment of infection(WO
9317559; JP 3133334); in detergent compositions (WO 9205240);
and as a wood preservative(JP 1038203). Hinokitiol has also SUBSTITUTE SHEET (RULE 26) CA 022~78~0 1998-12-09 W097l47289 PCT~S97/09835 been used in various types of cosmetic and pharmaceutical compositlons. For example, DE 4202964 discloses a water-phase hair and body treatment comprising hinokitiol and heliotropin or a cosmetic alcohol, wherein the heliotropin and alcohol is said to synergistically enhance the antimicrobial activity of hinokitiol. Similarly, JP 2243607 describes the use in cosmetic compositions of a preservative containing hinokitiol in combination with phenoxyethanol and phthalate ester. In addition, as shown herein, hinokitiol also possesses a heretofore unappreciated anti-irritancy effect.
Although hinokitiol has been shown to be an effective preservative under a wide variety of conditions, it is not itself completely stable under all conditions in which its use might be desired. For example, its use in compositions in polyethylene plastic containers can result in a discolored and~or unpleasant-smelling product. It also may not be stable after direct contact with light or air. These are limitations which under ordinary circumstances would not be acceptable, and which would recommend against its use in a cosmetic composition, where appearance and fragrance can be critical.
Therefore, in order to fully exploit its useful properties as a preservative, there remains a need for a means by which hinokitiol can itself be stabilized in the desired composition, and yet retain its useful biological properties, such as antimicrobial and anti-irritant activity. The present invention provides the means by which hinokitiol can be effectively used in cosmetic compositions.
SUMMARY OF THE INVENTION
The present invention provides cosmetic and pharmaceutical compositions containing hinokitiol-containing microcapsules, the microcapsules comprising a matrix containing collagen and a glycosaminoglycan. The microcapsule provides adequate S~JbS 1 1 1 UTE SHEET (RULE 26) CA 022~78~0 1998-12-09 W097/47289 PCT~S97/09835 stability to the hinokitiol, preventing it from discoloration and unpleasant odor in the composition containing same, while nonetheless permitting the hinokitiol to exert its preservative and anti-irritant effect on the composition containing it. The invention also provides a method for preserving a cosmetic or pharmaceutical composition, comprising adding to the composition a preservative-effective amount of the hinokitiol containing microcapsules, as well as a method for reducing irritation on the skin by application of a cosmetic composition containing an effective amount of hinokitiol-containing microspheres.
DETAI~ED DESCRIPTION OF TH~ INVENTION
The microcapsules used in the present invention are prepared according to the methodology disclosed in US Patent No. 5,395,620, the contents of which are incorporated herein by reference. Briefly, the microcapsules are prepared by combining a solution containing atelocollagen and a solution containing a polyholoside, preferably a glycosaminoglycan, in the presence of the hinokitiol and a crosslinking agent.
Atelocollagen is a type of collagen from which the telopeptides which crosslink typical collagen have been removed. The glycosaminoglycans are well known in the art, and for the present purposes may be selected, for example, from chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, heparan sulfate, keratan sulfate, heparin and derivatives thereof;
preferably the cosmetically or pharmaceutically acceptable salts, such as calcium or sodium salts, are employed. The amount of glycosaminoglycan present in the microcapsules will typically be about 15-50% by weight of the atelocollagen used in the formulation. In absolute terms, the amount of atelocollagen in the starting solution is approximately 0.5-2%
by weight, and the glycosaminoglycan solution contains about 0.5-4%, preferably 0.5-2% by weight of glycosaminoglycans. In SlJtsa l l l lJTE SHEET (RULE 26) , . .~ .. .. . .
CA 022~78~0 1998-12-09 a particularly preferred embodiment, both the atelocollagen and the glycosaminoglycans are of marine origin. Cross-linking reagents useful in preparing the microcapsules include, but are not limited to, an acid dichloride, an acid anhydride, or a dibasic or polybasic carboxylic acid. With respect to the hinokitiol, this material is present in an amount of between 0.01-10% by weight, preferably 0.5-4% by wei~ght, of the starting solution.
The microcapsules containing hinokitiol provide an lo unexpectedly high level of preservative efficacy, while itself remaining stable in the compositions in which it is included.
The retention of antimicrobial activity, at the levels seen herein, is particularly surprising in view of the fact that the hinokitiol itself is not expected to be in direct contact with the medium is intended to preserve. The microcapsules in which the hinokitiol is contained are essentially impermeable, i.e., there is apparently substantially no leakage of the hinokitiol into the medium in which the microcapsules are contained, as evidenced by the absence of unpleasant odor or color in the products containing them. Since the hinokitiol is used in quantities essentially the same as used in its unencapsulated form, the substantially complete retention of antimicro~ial activity by the "protected" hinokitiol is quite unexpected.
The encapsulated hinokitiol can be used in a wide variety of cosmetic and/or pharmaceutical compositions, as well as a preservative in food compositions. In particular, the hinokitiol can be used in virtually any form in which such compositions may be formulated, e.g., solutions, colloidal dispersions, emulsions, suspensions, creams, lotions, gels, foams, mousses and the like. Methods and components for preparing such compositions are well known in the art, and can be found for example, in CTFA Internationa~ Cosmetics Ingredients Dictionary, The Cosmetic, Toiletry, and Fragrance SUBSTITUTE SHEET (RULE 26) CA 022~78~0 lsss-l2-os W097/47289 PCT~S97/09835 Association, Washington, DC, 1991. The amount of the hinokitiol-containing microspheres will vary depending on the nature of the composition and the amount of hinokitiol contained in the microspheres, but a preservative-effective S amount of hinokitiol per se will generally be in the range of from about 0.1-1~ by weight of the composition as a whole, given the amount of hinokitiol in the microspheres is as stated above. It is well within the skill of the art to determine the desired microsphere concentration in the formulation, given o these parameters.
The compositions of the present invention will also comprise a pharmaceutically or cosmetically acceptable carrier, in an amount appropriate to accomodate the other components of the formulation. The term "pharmaceutically or cosmetically acceptable carrier" refers to a vehicle, for either pharmaceutical or cosmetic use, which vehicle delivers the active components to the intended target and which will not cause harm to humans or other recipient organisms. As used herein, "pharmaceutical" or "cosmetic" will be understood to encompass both human and animal pharmaceuticals or cosmetics.
The carrier may be in any form appropriate to the mode of delivery, for example, solutions, colloidal dispersions, emulsions, suspensions, creams, lotions, gels, foams, mousses and the like.
In a preferred embodiment, the carrier is a suspension, dispersion or emulsion. The emulsion may be an oil-in-water emulsion, or a water-in-oil emulsion. These emulsions contain one or more oil components, an aqueous component, and a specific emulsifier component chosen depending on the nature of the desired emulsion.
The oil component may be any pharmaceutically or cosmetically acceptable material which is substantially insoluble in water. These materials can be found for example in SlJd~111 UTE SHEET(RULE 26) CA 022~78~0 l998-l2-09 W097/47289 PCT~S97tO9835 the CTFA International Dictionary of Cosmetic Ingredients as well as the U.S. Pharmacopoeia or equivalent sources. Suitable oil components include, but are not limited to, natural oils, such as coconut oil; hydrocarbons, such as mineral oil and s hydrogenated polyisobutene; fatty alcohols, such as octyldodecanol; esters, such as C12-15 alkyl benzoate;
diesters, such as propylene glycol dipelargonate; triesters, such as glyceryl trioctanoate; sterol derivatives, such as lanolin; animal waxes, such as beeswax; plant waxes, such as carnauba; mineral waxes, such as ozokerite; petroleum waxes, such as paraffin wax; synthetic waxes, such as polyethylene;
and mixtures thereof. Suitable oil components may also be silicones including, but not limited to, volatile silicones such as cyclomethicone; polymeric silicones such as dimethicone; alkylated derivatives of polymeric silicones, such as cetyl dimethicone and lauryl trimethicone; hydroxylated derivatives of polymeric silicones, such as dimethiconol; and mixtures thereof. The aqueous component refers to any pharmaceutically or cosmetically acceptable material consisting essentially or predominantly of water.
For preparation of an oil-in water emulsion, the oil-in-water emulsifier will be an emulsifier having a hydrophilic-lipophilic balance(HLB) of at least 6, or a mixture of such emulsifiers with one or more water-in-oil emulsifiers(i.e., emulsifiers having an HLB of from about 2 to about 6), in which case the type and amount of each emulsifier present in the mixture is selected such that the effective HLB of the resultant oil-in-water emulsifier component is at least about 6. Techniques for combining and ascertaining the effective HLB
of a mixture of emulsifiers are known; see L.M.Prince, in M.G.
DeNavarre, "The Chemistry and Manufacture of Cosmetics", Volume III, Second Ed., (Continental Press, Orlando, ~975), pp. 25-37.
S~ 111 UTE SHEET (RULE 26) CA 022~78~0 lsss-l2-os W097/47289 PCT~S97/09835 Suitable oll-in-water emulsifiers include, but are not limited to, sorbitol derivatives, such as sorbitan monolaurate and polysorbate 20; ethoxylated alcohols such as laureth-23, ethoxylated fatty acids such as PEG-1000 stearate; amidoamine derivatives such as stearamidoethyl diethylamine; sulfate esters such as sodium lauryl sulfate; phosphate esters such as DEA cetyl phosphate; fatty acid amine salts such as TEA
stearate; and mixtures thereof.
The emulsion may also be a water-in-oil emulsion.
o For this purpose, a water-in-oil emulsifier is employed. This refers to any cosmetically acceptable emulsifier having an HLB
of no greater than 6, preferably from about 2 to about 4.
Suitable water-in-oil emulsifiers include, but are not limited to, sorbitan derivatives such as sorbitan laurate and sorbitan palmitate; alkoxylated alcohols such as laureth-4;
hydroxylated derivatives of polymeric silicones, such as dimethicone copolyol; alkylated derivatives of hydroxylated polymeric silicones, such as cetyl dimethicone copolyol;
glyceryl esters such as polyglyceryl-4 isostearate; beeswax derivatives such as sodium isostearoyl-2 lactylate; lecithin;
and mixtures thereof.
The active component of the pharmaceutical or cosmetic compositions will depend on the intended purpose of the compositions. Examples of such active agents which may form part of the composition include, but are not limited to, those that improve or eradicate age spots, keratoses and wrinkles, analgesics, anesthetics, anti-acne agents, antibacterials, antiyeast agents, antifungal agents, antiviral agents, antidandruff agents, antidermatitis agents, antipruritic agents, antiemetics, antimotion sickness agents, anti-inflammatory agents, antihyperkeratolytic agents, anti-dry skin agents, antiperspirants, antipsoriatic agents, antiseborrheic agents, hair conditioners and hair treatment agents, antiaging SUBSTITUTE SHEET (RULE 26) CA 022~78~0 l998-l2-09 W097/47289 PCT~S97/09835 agents, antiwrinkle agents, antiasthmatic agents and bronchodilators, sunscreen agents, antihistamine agents, skin lightening agents, depigmenting agents, vitamins, corticosteroids, tanning agents, hormones, retinoids, topical cardiovascular agents, clotrimazole, ketoconazole, miconozole, griseofulvin, hydroxyzine, diphenhydramine, pramoxine, lidocaine, procaine, mepivacaine, monobenzone, erythromycin, tetracycline, clindamycin, meclocyline, hydroquinone, minocycline, naproxen, ibuprofen, theophylline, cromolyn, lo albuterol, retinoic acid, 13-cis retinoic acid, hydrocortisone, hydrocortisone 21-acetate, hydrocortisone 17-valerate, hydrocortisone 17-butyrate, betamethasone valerate, betamethasone diproprionate, triamcinolone acetonide, fluocinonide, clobetasol, proprionate, benzoyl peroxide, crotamiton, propranolol, promethazine, vitamin A palmitate, vitamin E acetate and mixtures thereof.
In one preferred embodiment, the composition is a sunscreen-containing composition. The term "sunscreen" as used herein refers to any material which is capable of protecting human skin from ultraviolet radiation having a wavelength of from about 280 to about 400nm, by effectively absorbing such radiation, and/or reflecting or scattering such radiation away from the surface of human skin. Suitable sunscreens for purposes of this invention include but not limited to, titanium derivatives such as titanium dioxide, especially titanium dioxide having an average particle size of from 10 to 100 nanometers, most especially titanium dioxide having an average particle size of from 10 to 100 nanometers and comprising a hydrophobic coating agent to minimize agglomeration; zinc derivatives such as zinc oxide, especially zinc oxide having an average particle size of from 10 to 100 nanometers; melanin and melanin derivatives; dioxybenzone; 2-ethylhexyl 2-cyano-3,3-diphenylacrylate; 2-ethylhexyl p-methoxycinnamate; 2-ethylhexyl SUBSTITUTE SHEET (RULE 26) CA 022~78~0 1sss-12-os W097/47289 PCT~S97/09835 salicylate; homosalate; menthyl anthranilatei oxybenzone; octyl dimethyl PABA; red petrolatum; ferulic acid ester; and mixtures thereof.
In addition to those components specifically noted above, the compositions may also comprise additional preservatives, fragrances, emollients, antiseptics, antiinflammatories, antibacter als, stabilizers, antioxidants, vitamins, pigments, dyes, humectants, and propellants, as well as other classes of materials the presence of which in the compositions may be cosmetically, medicinally, or otherwise desired. Such components can be found in the CTFA International Cosmetics Ingredients Dictionary, supra.
The present invention is further illustrated by the following non-limiting examples.
EXAMPLE I
Thalaspheres~ (30~m) containing hinokitiol are provided by Bioetica, Inc., Portland, Malne). The composition of the Thalaspheres~, in grams per lOOg, is as follows:
20 In~redient Total Support phase Capsules composition ~eionized water 81.494 77.86% 89.98%
Butylene glycol 15.0 21.43%
Hinokltiol 2.4 8.0%
25 Xanthan gum 0.5 0.7l%
atelocollagen 0.441 l.47~
chondroitin 0.l65 0.55%
lOO g 100% 100%
30 equivalent~in g/lOOg of product) 70g 30g SlJ-~ 111 UTE SHEET (RULE 26) CA 022~78~0 l998-l2-09 W097l47289 PCT~S97/09835 The encapsulated hinokitiol, as described in Example 1, is incorporated by art-recognized procedures into a sunscreen-containing dispersion, a molsturizing cream emulsion, and a skin desensitizing lotion emulsion. The components are as follows:
SUNSCREEN FORMULATION
Component Weight lo cyclomethicone/dimethicone copolyol 16.0 Titanium dioxide Dispersion 13.0 cyclomethicone 15.5 dimethicone 10.5 phenyltrimethicone 6.0 lS hydrogenated lecithin 0.5 deionized water 36.0 magnesium sulfate 1.5 encapsulated hinokitiol 1.0 MOISTURIZING FORMULATION
Component Weight Deionized water 62.0 25 oat stearate 0 9 Disodium EDTA 0.1 squalane 5.0 cetearyl alcohol/cetearyl glucoside 5.0 shea butter 6.0 35 sucrose 2.0 isostearyl neopentanoate 2.0 cyclomethicone 7-5 carbomer 0.25 SUBSTITUTE SHEET (RULE 26) CA 022~78~0 1998-12-09 W097/47289 PCT~S97/09835 glycerine USP 95% 2.5 triethanolamine 99~ 0.05 sodium hyaluronate 2.5 encapsulated hinokitiol 4.2 SKIN DESENSITIZING FORMULATION
Component Weight %
Satin Finish~ 50~
15 Disodium EDTA 0.1 Shea butter 0.5 rosemary extract 0.1 glycerine USP 95% 9.5 gorgonian extract 0.1 2s aluminum starch octenyl succinate 1.2 carbomer 0.2 sucrose 1.8 caffeine powder 0.4 triethanolamine 99% 0-05 35 magnesium aluminum sulfate 0.25 deionized water 36.6 encapsulated hinokitiol 4.2 4~
*a commercial(Collaborative Labs) emulsion comprising phenyl ~ trimethicone, cyclomethicone, phosophoglycerides, dimethiconol, phen~xyethanol, carbomer, and triethanolamine The formulations so prepared exhibit no deterioration, no discoloration and no unpleasant odor even after prolonged SUBSTITUTE SHEET (RULE 26) CA 022~78~0 l998-l2-09 W097/47289 PCT~S97/09835 storage, showing the encapsulated hinokitiol retains its preservative effect while at the same time being stabilized by the encapsulation.
Hinokitiol alone is tested for its ability to prevent irritation. Hinokitiol (unencapsulated, 0.5% by weight)is applied to the ventral forearms of panelists. The material is allowed to absorb for twenty minutes and then Balsam of Peru, an irritant, is applied to the test sites. Skin irritation is measured in terms of increase in skin redness. Cola nitida(10%
hydro-alcohol 1:1) is used as a positive control.
The degree of redness is measured with the Minolta chromameter and compared with the positive and negative controls. The positive control is the color of skin treated with Balsam of Peru alone and the negative control is the skin treated with cola material challenged as with the hinokitiol.
Hinokitiol exhibits a 71% activity, as compared with an average of 67% for cola.
The encapsulated hinokitiol is then tested for its retained anti-irritant activity. Encapsulated hinokitiol, prepared as described above, is prepared in 4.2% and 2.8%
aqueous solution. These solutions are tested against empty microcapsules, as well as against cola nitida~10% hydro-alcohol 2~ 1:1), using the same protocol as described in the previous example. Results show that the activity of the encapsulated hinokitiol at 4.2% is approximately equivalent to that of 10%
cola ~61% vs 64%, respectively) in reducing the onset of irritation due to Balsam of Peru. The lower concentration of hinokitlol capsules shows 53% activity, while empty microcapsules show 28% activity.
SUts~ ~ JTE SHEET (RULE 26)
Field of the Invention The present invention relates to preservatives useful in pharmaceutical and cosmetic compositions. In particular, the invention relates to a stahilized, anti-irritant preservative, hinokitiol.
Background of the Invention lo Contamination of pharmaceutical and cosmetic compositions by bacteria and/or fungi can present a serious problem to the formulator. To combat this problem, and in order to prolong shelf life of the product, such compositions frequently contain preservatives which have antimicrobial activity. Given the diverse chemical nature of the available preservatives, however, and the equally diverse nature of the compositions in which they are intended to be used, the ability to successfully use a given preservative in a particular formulation cannot be assumed.
One such preservative is the substance known as hinokitiol. [2-hydroxy-4-~1-methylethyl)-2,4,6-cycloheptatrien-1-one; isopropyltropolone]. Hinokitiol is a wood extract obtainable from pine, cedar, etc. Methods for its production are described, for example, in JP 0586396 and JP
05105898. This material is known to have potent antimicrobial effects, and,as such, has been previously used for a variety of purposes. For example, hinokitlol has been used in food preservation and prevention of discoloration (JP 78035145; JP
6277019; JP 6153788; JP 6090661; JP 5344861; JP 59085279); in combination with zinc, or with ethyl alcohol and propylene glycol for antisepsis and/or the treatment of infection(WO
9317559; JP 3133334); in detergent compositions (WO 9205240);
and as a wood preservative(JP 1038203). Hinokitiol has also SUBSTITUTE SHEET (RULE 26) CA 022~78~0 1998-12-09 W097l47289 PCT~S97/09835 been used in various types of cosmetic and pharmaceutical compositlons. For example, DE 4202964 discloses a water-phase hair and body treatment comprising hinokitiol and heliotropin or a cosmetic alcohol, wherein the heliotropin and alcohol is said to synergistically enhance the antimicrobial activity of hinokitiol. Similarly, JP 2243607 describes the use in cosmetic compositions of a preservative containing hinokitiol in combination with phenoxyethanol and phthalate ester. In addition, as shown herein, hinokitiol also possesses a heretofore unappreciated anti-irritancy effect.
Although hinokitiol has been shown to be an effective preservative under a wide variety of conditions, it is not itself completely stable under all conditions in which its use might be desired. For example, its use in compositions in polyethylene plastic containers can result in a discolored and~or unpleasant-smelling product. It also may not be stable after direct contact with light or air. These are limitations which under ordinary circumstances would not be acceptable, and which would recommend against its use in a cosmetic composition, where appearance and fragrance can be critical.
Therefore, in order to fully exploit its useful properties as a preservative, there remains a need for a means by which hinokitiol can itself be stabilized in the desired composition, and yet retain its useful biological properties, such as antimicrobial and anti-irritant activity. The present invention provides the means by which hinokitiol can be effectively used in cosmetic compositions.
SUMMARY OF THE INVENTION
The present invention provides cosmetic and pharmaceutical compositions containing hinokitiol-containing microcapsules, the microcapsules comprising a matrix containing collagen and a glycosaminoglycan. The microcapsule provides adequate S~JbS 1 1 1 UTE SHEET (RULE 26) CA 022~78~0 1998-12-09 W097/47289 PCT~S97/09835 stability to the hinokitiol, preventing it from discoloration and unpleasant odor in the composition containing same, while nonetheless permitting the hinokitiol to exert its preservative and anti-irritant effect on the composition containing it. The invention also provides a method for preserving a cosmetic or pharmaceutical composition, comprising adding to the composition a preservative-effective amount of the hinokitiol containing microcapsules, as well as a method for reducing irritation on the skin by application of a cosmetic composition containing an effective amount of hinokitiol-containing microspheres.
DETAI~ED DESCRIPTION OF TH~ INVENTION
The microcapsules used in the present invention are prepared according to the methodology disclosed in US Patent No. 5,395,620, the contents of which are incorporated herein by reference. Briefly, the microcapsules are prepared by combining a solution containing atelocollagen and a solution containing a polyholoside, preferably a glycosaminoglycan, in the presence of the hinokitiol and a crosslinking agent.
Atelocollagen is a type of collagen from which the telopeptides which crosslink typical collagen have been removed. The glycosaminoglycans are well known in the art, and for the present purposes may be selected, for example, from chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, heparan sulfate, keratan sulfate, heparin and derivatives thereof;
preferably the cosmetically or pharmaceutically acceptable salts, such as calcium or sodium salts, are employed. The amount of glycosaminoglycan present in the microcapsules will typically be about 15-50% by weight of the atelocollagen used in the formulation. In absolute terms, the amount of atelocollagen in the starting solution is approximately 0.5-2%
by weight, and the glycosaminoglycan solution contains about 0.5-4%, preferably 0.5-2% by weight of glycosaminoglycans. In SlJtsa l l l lJTE SHEET (RULE 26) , . .~ .. .. . .
CA 022~78~0 1998-12-09 a particularly preferred embodiment, both the atelocollagen and the glycosaminoglycans are of marine origin. Cross-linking reagents useful in preparing the microcapsules include, but are not limited to, an acid dichloride, an acid anhydride, or a dibasic or polybasic carboxylic acid. With respect to the hinokitiol, this material is present in an amount of between 0.01-10% by weight, preferably 0.5-4% by wei~ght, of the starting solution.
The microcapsules containing hinokitiol provide an lo unexpectedly high level of preservative efficacy, while itself remaining stable in the compositions in which it is included.
The retention of antimicrobial activity, at the levels seen herein, is particularly surprising in view of the fact that the hinokitiol itself is not expected to be in direct contact with the medium is intended to preserve. The microcapsules in which the hinokitiol is contained are essentially impermeable, i.e., there is apparently substantially no leakage of the hinokitiol into the medium in which the microcapsules are contained, as evidenced by the absence of unpleasant odor or color in the products containing them. Since the hinokitiol is used in quantities essentially the same as used in its unencapsulated form, the substantially complete retention of antimicro~ial activity by the "protected" hinokitiol is quite unexpected.
The encapsulated hinokitiol can be used in a wide variety of cosmetic and/or pharmaceutical compositions, as well as a preservative in food compositions. In particular, the hinokitiol can be used in virtually any form in which such compositions may be formulated, e.g., solutions, colloidal dispersions, emulsions, suspensions, creams, lotions, gels, foams, mousses and the like. Methods and components for preparing such compositions are well known in the art, and can be found for example, in CTFA Internationa~ Cosmetics Ingredients Dictionary, The Cosmetic, Toiletry, and Fragrance SUBSTITUTE SHEET (RULE 26) CA 022~78~0 lsss-l2-os W097/47289 PCT~S97/09835 Association, Washington, DC, 1991. The amount of the hinokitiol-containing microspheres will vary depending on the nature of the composition and the amount of hinokitiol contained in the microspheres, but a preservative-effective S amount of hinokitiol per se will generally be in the range of from about 0.1-1~ by weight of the composition as a whole, given the amount of hinokitiol in the microspheres is as stated above. It is well within the skill of the art to determine the desired microsphere concentration in the formulation, given o these parameters.
The compositions of the present invention will also comprise a pharmaceutically or cosmetically acceptable carrier, in an amount appropriate to accomodate the other components of the formulation. The term "pharmaceutically or cosmetically acceptable carrier" refers to a vehicle, for either pharmaceutical or cosmetic use, which vehicle delivers the active components to the intended target and which will not cause harm to humans or other recipient organisms. As used herein, "pharmaceutical" or "cosmetic" will be understood to encompass both human and animal pharmaceuticals or cosmetics.
The carrier may be in any form appropriate to the mode of delivery, for example, solutions, colloidal dispersions, emulsions, suspensions, creams, lotions, gels, foams, mousses and the like.
In a preferred embodiment, the carrier is a suspension, dispersion or emulsion. The emulsion may be an oil-in-water emulsion, or a water-in-oil emulsion. These emulsions contain one or more oil components, an aqueous component, and a specific emulsifier component chosen depending on the nature of the desired emulsion.
The oil component may be any pharmaceutically or cosmetically acceptable material which is substantially insoluble in water. These materials can be found for example in SlJd~111 UTE SHEET(RULE 26) CA 022~78~0 l998-l2-09 W097/47289 PCT~S97tO9835 the CTFA International Dictionary of Cosmetic Ingredients as well as the U.S. Pharmacopoeia or equivalent sources. Suitable oil components include, but are not limited to, natural oils, such as coconut oil; hydrocarbons, such as mineral oil and s hydrogenated polyisobutene; fatty alcohols, such as octyldodecanol; esters, such as C12-15 alkyl benzoate;
diesters, such as propylene glycol dipelargonate; triesters, such as glyceryl trioctanoate; sterol derivatives, such as lanolin; animal waxes, such as beeswax; plant waxes, such as carnauba; mineral waxes, such as ozokerite; petroleum waxes, such as paraffin wax; synthetic waxes, such as polyethylene;
and mixtures thereof. Suitable oil components may also be silicones including, but not limited to, volatile silicones such as cyclomethicone; polymeric silicones such as dimethicone; alkylated derivatives of polymeric silicones, such as cetyl dimethicone and lauryl trimethicone; hydroxylated derivatives of polymeric silicones, such as dimethiconol; and mixtures thereof. The aqueous component refers to any pharmaceutically or cosmetically acceptable material consisting essentially or predominantly of water.
For preparation of an oil-in water emulsion, the oil-in-water emulsifier will be an emulsifier having a hydrophilic-lipophilic balance(HLB) of at least 6, or a mixture of such emulsifiers with one or more water-in-oil emulsifiers(i.e., emulsifiers having an HLB of from about 2 to about 6), in which case the type and amount of each emulsifier present in the mixture is selected such that the effective HLB of the resultant oil-in-water emulsifier component is at least about 6. Techniques for combining and ascertaining the effective HLB
of a mixture of emulsifiers are known; see L.M.Prince, in M.G.
DeNavarre, "The Chemistry and Manufacture of Cosmetics", Volume III, Second Ed., (Continental Press, Orlando, ~975), pp. 25-37.
S~ 111 UTE SHEET (RULE 26) CA 022~78~0 lsss-l2-os W097/47289 PCT~S97/09835 Suitable oll-in-water emulsifiers include, but are not limited to, sorbitol derivatives, such as sorbitan monolaurate and polysorbate 20; ethoxylated alcohols such as laureth-23, ethoxylated fatty acids such as PEG-1000 stearate; amidoamine derivatives such as stearamidoethyl diethylamine; sulfate esters such as sodium lauryl sulfate; phosphate esters such as DEA cetyl phosphate; fatty acid amine salts such as TEA
stearate; and mixtures thereof.
The emulsion may also be a water-in-oil emulsion.
o For this purpose, a water-in-oil emulsifier is employed. This refers to any cosmetically acceptable emulsifier having an HLB
of no greater than 6, preferably from about 2 to about 4.
Suitable water-in-oil emulsifiers include, but are not limited to, sorbitan derivatives such as sorbitan laurate and sorbitan palmitate; alkoxylated alcohols such as laureth-4;
hydroxylated derivatives of polymeric silicones, such as dimethicone copolyol; alkylated derivatives of hydroxylated polymeric silicones, such as cetyl dimethicone copolyol;
glyceryl esters such as polyglyceryl-4 isostearate; beeswax derivatives such as sodium isostearoyl-2 lactylate; lecithin;
and mixtures thereof.
The active component of the pharmaceutical or cosmetic compositions will depend on the intended purpose of the compositions. Examples of such active agents which may form part of the composition include, but are not limited to, those that improve or eradicate age spots, keratoses and wrinkles, analgesics, anesthetics, anti-acne agents, antibacterials, antiyeast agents, antifungal agents, antiviral agents, antidandruff agents, antidermatitis agents, antipruritic agents, antiemetics, antimotion sickness agents, anti-inflammatory agents, antihyperkeratolytic agents, anti-dry skin agents, antiperspirants, antipsoriatic agents, antiseborrheic agents, hair conditioners and hair treatment agents, antiaging SUBSTITUTE SHEET (RULE 26) CA 022~78~0 l998-l2-09 W097/47289 PCT~S97/09835 agents, antiwrinkle agents, antiasthmatic agents and bronchodilators, sunscreen agents, antihistamine agents, skin lightening agents, depigmenting agents, vitamins, corticosteroids, tanning agents, hormones, retinoids, topical cardiovascular agents, clotrimazole, ketoconazole, miconozole, griseofulvin, hydroxyzine, diphenhydramine, pramoxine, lidocaine, procaine, mepivacaine, monobenzone, erythromycin, tetracycline, clindamycin, meclocyline, hydroquinone, minocycline, naproxen, ibuprofen, theophylline, cromolyn, lo albuterol, retinoic acid, 13-cis retinoic acid, hydrocortisone, hydrocortisone 21-acetate, hydrocortisone 17-valerate, hydrocortisone 17-butyrate, betamethasone valerate, betamethasone diproprionate, triamcinolone acetonide, fluocinonide, clobetasol, proprionate, benzoyl peroxide, crotamiton, propranolol, promethazine, vitamin A palmitate, vitamin E acetate and mixtures thereof.
In one preferred embodiment, the composition is a sunscreen-containing composition. The term "sunscreen" as used herein refers to any material which is capable of protecting human skin from ultraviolet radiation having a wavelength of from about 280 to about 400nm, by effectively absorbing such radiation, and/or reflecting or scattering such radiation away from the surface of human skin. Suitable sunscreens for purposes of this invention include but not limited to, titanium derivatives such as titanium dioxide, especially titanium dioxide having an average particle size of from 10 to 100 nanometers, most especially titanium dioxide having an average particle size of from 10 to 100 nanometers and comprising a hydrophobic coating agent to minimize agglomeration; zinc derivatives such as zinc oxide, especially zinc oxide having an average particle size of from 10 to 100 nanometers; melanin and melanin derivatives; dioxybenzone; 2-ethylhexyl 2-cyano-3,3-diphenylacrylate; 2-ethylhexyl p-methoxycinnamate; 2-ethylhexyl SUBSTITUTE SHEET (RULE 26) CA 022~78~0 1sss-12-os W097/47289 PCT~S97/09835 salicylate; homosalate; menthyl anthranilatei oxybenzone; octyl dimethyl PABA; red petrolatum; ferulic acid ester; and mixtures thereof.
In addition to those components specifically noted above, the compositions may also comprise additional preservatives, fragrances, emollients, antiseptics, antiinflammatories, antibacter als, stabilizers, antioxidants, vitamins, pigments, dyes, humectants, and propellants, as well as other classes of materials the presence of which in the compositions may be cosmetically, medicinally, or otherwise desired. Such components can be found in the CTFA International Cosmetics Ingredients Dictionary, supra.
The present invention is further illustrated by the following non-limiting examples.
EXAMPLE I
Thalaspheres~ (30~m) containing hinokitiol are provided by Bioetica, Inc., Portland, Malne). The composition of the Thalaspheres~, in grams per lOOg, is as follows:
20 In~redient Total Support phase Capsules composition ~eionized water 81.494 77.86% 89.98%
Butylene glycol 15.0 21.43%
Hinokltiol 2.4 8.0%
25 Xanthan gum 0.5 0.7l%
atelocollagen 0.441 l.47~
chondroitin 0.l65 0.55%
lOO g 100% 100%
30 equivalent~in g/lOOg of product) 70g 30g SlJ-~ 111 UTE SHEET (RULE 26) CA 022~78~0 l998-l2-09 W097l47289 PCT~S97/09835 The encapsulated hinokitiol, as described in Example 1, is incorporated by art-recognized procedures into a sunscreen-containing dispersion, a molsturizing cream emulsion, and a skin desensitizing lotion emulsion. The components are as follows:
SUNSCREEN FORMULATION
Component Weight lo cyclomethicone/dimethicone copolyol 16.0 Titanium dioxide Dispersion 13.0 cyclomethicone 15.5 dimethicone 10.5 phenyltrimethicone 6.0 lS hydrogenated lecithin 0.5 deionized water 36.0 magnesium sulfate 1.5 encapsulated hinokitiol 1.0 MOISTURIZING FORMULATION
Component Weight Deionized water 62.0 25 oat stearate 0 9 Disodium EDTA 0.1 squalane 5.0 cetearyl alcohol/cetearyl glucoside 5.0 shea butter 6.0 35 sucrose 2.0 isostearyl neopentanoate 2.0 cyclomethicone 7-5 carbomer 0.25 SUBSTITUTE SHEET (RULE 26) CA 022~78~0 1998-12-09 W097/47289 PCT~S97/09835 glycerine USP 95% 2.5 triethanolamine 99~ 0.05 sodium hyaluronate 2.5 encapsulated hinokitiol 4.2 SKIN DESENSITIZING FORMULATION
Component Weight %
Satin Finish~ 50~
15 Disodium EDTA 0.1 Shea butter 0.5 rosemary extract 0.1 glycerine USP 95% 9.5 gorgonian extract 0.1 2s aluminum starch octenyl succinate 1.2 carbomer 0.2 sucrose 1.8 caffeine powder 0.4 triethanolamine 99% 0-05 35 magnesium aluminum sulfate 0.25 deionized water 36.6 encapsulated hinokitiol 4.2 4~
*a commercial(Collaborative Labs) emulsion comprising phenyl ~ trimethicone, cyclomethicone, phosophoglycerides, dimethiconol, phen~xyethanol, carbomer, and triethanolamine The formulations so prepared exhibit no deterioration, no discoloration and no unpleasant odor even after prolonged SUBSTITUTE SHEET (RULE 26) CA 022~78~0 l998-l2-09 W097/47289 PCT~S97/09835 storage, showing the encapsulated hinokitiol retains its preservative effect while at the same time being stabilized by the encapsulation.
Hinokitiol alone is tested for its ability to prevent irritation. Hinokitiol (unencapsulated, 0.5% by weight)is applied to the ventral forearms of panelists. The material is allowed to absorb for twenty minutes and then Balsam of Peru, an irritant, is applied to the test sites. Skin irritation is measured in terms of increase in skin redness. Cola nitida(10%
hydro-alcohol 1:1) is used as a positive control.
The degree of redness is measured with the Minolta chromameter and compared with the positive and negative controls. The positive control is the color of skin treated with Balsam of Peru alone and the negative control is the skin treated with cola material challenged as with the hinokitiol.
Hinokitiol exhibits a 71% activity, as compared with an average of 67% for cola.
The encapsulated hinokitiol is then tested for its retained anti-irritant activity. Encapsulated hinokitiol, prepared as described above, is prepared in 4.2% and 2.8%
aqueous solution. These solutions are tested against empty microcapsules, as well as against cola nitida~10% hydro-alcohol 2~ 1:1), using the same protocol as described in the previous example. Results show that the activity of the encapsulated hinokitiol at 4.2% is approximately equivalent to that of 10%
cola ~61% vs 64%, respectively) in reducing the onset of irritation due to Balsam of Peru. The lower concentration of hinokitlol capsules shows 53% activity, while empty microcapsules show 28% activity.
SUts~ ~ JTE SHEET (RULE 26)
Claims (14)
1. A cosmetic or pharmaceutical composition containing a preservative-effective amount of hinokitiol-containing microcapsules, the microcapsules comprising a matrix containing collagen and a glycosaminoglycan.
2. The composition of claim 1, in which the matrix comprises atelocollagen and chondroitin sulfate.
3. The composition of claim 1 in which the hinokitiol is present in the microcapsules in an amount of from 0.1-10% by weight.
4. The composition of claim 1 in which the microcapsules are present in an amount of from about 1-10%.
5. The composition of claim 1 which is in the form of a solution, colloidal dispersion, emulsion, suspension, cream, lotion, gel, foam, or mousse.
6. The composition of claim 5 which is a dispersion.
7. The composition of claim 5 which is an emulsion.
8. The composition of claim 7 which is a water in-oil emulsion.
9. The composition of claim 6 which also contains a sunscreen.
10. The composition of claim 9 in which the sunscreen is titanium dioxide.
11. The composition of claim 10 in which the microcapsules are present in an amount of about 1-5%.
12. A food composition containing a preservative-effective amount of hinokitiol-containing microcapsules, the microcapsules comprising a matrix containing collagen and a glycosaminoglycan.
13. A method for preserving a pharmaceutical, food or cosmetic composition comprising adding to the composition a preservative effective amount of hinokitiol-containing microcapsules.
14. A method for reducing the irritating effects of a cosmetic or pharmaceutical composition on the skin comprising adding to the composition an anti-irritant effective amount of hinokitiol-containing microcapsules.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US08/662,870 | 1996-06-12 | ||
US08/662,870 US5811114A (en) | 1996-06-12 | 1996-06-12 | Stabilized hinokitiol and compositions containing same |
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CA2257850A1 true CA2257850A1 (en) | 1997-12-18 |
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ID=24659581
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CA002257850A Abandoned CA2257850A1 (en) | 1996-06-12 | 1997-06-09 | Stabilized hinokitiol and compositions containing same |
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US (1) | US5811114A (en) |
EP (1) | EP0952852A1 (en) |
JP (1) | JP2000512294A (en) |
AU (1) | AU3379497A (en) |
CA (1) | CA2257850A1 (en) |
WO (1) | WO1997047289A1 (en) |
ZA (1) | ZA975204B (en) |
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US6017549A (en) * | 1997-09-30 | 2000-01-25 | E-L Management Corp. | Non-irritating cosmetic and pharmaceutical compositions |
US6685965B1 (en) * | 1997-10-22 | 2004-02-03 | Industria E Comercio De Cosmeticos Natura Ltda. | Process for stabilizing levogyre ascorbic acid (laa), a stable aqueous laa composition, a process for preparing a stable topical solution, an emulsion, a vitamin product, and a method for cosmetic, pharmaceutical or nutritional treatment |
JP4087938B2 (en) * | 1998-02-04 | 2008-05-21 | 高砂香料工業株式会社 | Antibacterial agent comprising branched cyclodextrin inclusion compound of hinokitiols and composition containing the same |
JP3134068B2 (en) * | 1999-02-03 | 2001-02-13 | 株式会社トピックス | Method for producing hinokitiol-containing aromatic antibacterial agent |
US6217913B1 (en) * | 1999-07-15 | 2001-04-17 | Fatemeh Mohammadi | Cosmetic compositions with gorgonian extract |
JP2002179549A (en) * | 2000-12-12 | 2002-06-26 | Kishohin Kagaku Kaiho Kenkyusho:Kk | Skin care preparation |
US6680062B2 (en) * | 2001-10-05 | 2004-01-20 | Color Access, Inc. | Anti-irritating rosacea treatment |
US20040120915A1 (en) * | 2002-12-19 | 2004-06-24 | Kaiyuan Yang | Multifunctional compositions for surface applications |
US7211249B2 (en) * | 2003-03-17 | 2007-05-01 | Color Access, Inc. | Heat-generating composition for topical application to skin |
US20070104809A1 (en) | 2003-08-22 | 2007-05-10 | Danisco A/S | Composition comprising a bacteriocin and an extract from a plant of the labiatae family |
WO2005018333A1 (en) * | 2003-08-22 | 2005-03-03 | Danisco A/S | Composition comprising a bacteriocin and an extract from a plant of the labiatae family |
GB2388581A (en) | 2003-08-22 | 2003-11-19 | Danisco | Coated aqueous beads |
US20070027152A1 (en) * | 2005-07-27 | 2007-02-01 | Clark Kathleen L | Topical anti-pruritic compositions and methods of action of same |
JP2010534675A (en) * | 2007-07-24 | 2010-11-11 | マローネ バイオ イノベーションズ,インコーポレイテッド | Hinokitiol as a plant herbicide |
US9717818B2 (en) * | 2009-05-08 | 2017-08-01 | Medline Industries, Inc. | Absorbent articles having antimicrobial properties and methods of manufacturing the same |
US9180112B2 (en) * | 2010-03-23 | 2015-11-10 | Ermis Labs, LLC | Dermal compositions containing gorgonian extract |
JP5642002B2 (en) * | 2011-03-28 | 2014-12-17 | 株式会社コーセー | Vesicle-containing composition, cosmetic or external preparation containing the same |
JP2018522051A (en) * | 2015-08-06 | 2018-08-09 | ラボラトリ デリバティ オルガニチ スパ | Compositions containing dermatan sulfate and chondroitin sulfate and their use in cosmetic compositions |
FR3064179B1 (en) * | 2017-03-24 | 2021-07-16 | Greenpharma Sas | PRESERVATIVE AGENT CONTAINING HINOKITIOL WITH AT LEAST ONE ACID AND COMPOSITIONS PRESERVED BY LEDIT AGENT |
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JPS5335145B2 (en) * | 1973-02-09 | 1978-09-26 | ||
JPS5985279A (en) * | 1982-11-08 | 1984-05-17 | Seiwa Kasei Kk | Preventing animal or plant from blackening or browning |
JPS6438203A (en) * | 1987-08-05 | 1989-02-08 | Aomori Prefecture | Natural wood protective colorant |
US5268174A (en) * | 1988-09-29 | 1993-12-07 | Kabushiki Kaisha Sangi | Antimicrobial hydroxyapatite powders containing hinokitiol, protamine or sorbic acid |
US5395620A (en) * | 1989-01-31 | 1995-03-07 | Coletica | Biodegradable microcapsules having walls composed of crosslinked atelocollagen and polyholoside |
JP2795879B2 (en) * | 1989-03-16 | 1998-09-10 | 株式会社アルソア央粧 | Preservatives for cosmetics |
JPH03133334A (en) * | 1989-10-19 | 1991-06-06 | Takara Nenryo Kogyo Kk | Antiseptic composition and antiseptic water containing the same |
ATE175433T1 (en) * | 1990-08-17 | 1999-01-15 | Yoshihide Hagiwara | ACTIVE ANTIOXIDANT SUBSTANCE AND USE THEREOF |
WO1992005240A1 (en) * | 1990-09-14 | 1992-04-02 | Otsuka Pharmaceutical Co., Ltd. | Detergent composition |
JP2777680B2 (en) * | 1991-08-22 | 1998-07-23 | 富田製薬株式会社 | Salty seasoning having antimicrobial and insect repellent effects and method for producing the same |
JPH05105898A (en) * | 1991-09-25 | 1993-04-27 | Sumitomo Seika Chem Co Ltd | Method for separating acid oil from essential plant oil |
JPH0586396A (en) * | 1991-09-25 | 1993-04-06 | Jiyumoku Chiyuushiyutsu Seibun Riyou Gijutsu Kenkyu Kumiai | Refining of hinokitiol |
DE4202964A1 (en) * | 1992-02-01 | 1993-08-05 | Wella Ag | HAIR AND BODY TREATMENT |
EP0589047B1 (en) * | 1992-03-13 | 1999-06-09 | Otsuka Pharmaceutical Co., Ltd. | Method of treating infectious disease, method of preventing putrefaction of cosmetic, and antibacterial/antifungal agent and cosmetic |
JPH0690661A (en) * | 1992-09-09 | 1994-04-05 | Sumitomo Seika Chem Co Ltd | Freshness-keeping material containing hinokitiol |
JP2640899B2 (en) * | 1992-11-20 | 1997-08-13 | 耕平 森 | Preservative method of moromi pickles and moromi pickles |
JP3424930B2 (en) * | 1992-12-09 | 2003-07-07 | 協和醗酵工業株式会社 | N-acylglutamine derivatives |
JPH06277019A (en) * | 1993-03-31 | 1994-10-04 | Gunze Ltd | Preservative containing red koji and production of food and feed utilizing the same |
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1996
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-
1997
- 1997-06-09 EP EP97929825A patent/EP0952852A1/en not_active Withdrawn
- 1997-06-09 CA CA002257850A patent/CA2257850A1/en not_active Abandoned
- 1997-06-09 WO PCT/US1997/009835 patent/WO1997047289A1/en not_active Application Discontinuation
- 1997-06-09 JP JP10501709A patent/JP2000512294A/en active Pending
- 1997-06-09 AU AU33794/97A patent/AU3379497A/en not_active Abandoned
- 1997-06-12 ZA ZA9705204A patent/ZA975204B/en unknown
Also Published As
Publication number | Publication date |
---|---|
EP0952852A4 (en) | 1999-11-03 |
US5811114A (en) | 1998-09-22 |
EP0952852A1 (en) | 1999-11-03 |
AU3379497A (en) | 1998-01-07 |
WO1997047289A1 (en) | 1997-12-18 |
ZA975204B (en) | 1997-12-31 |
JP2000512294A (en) | 2000-09-19 |
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