WO2007145395A1 - Method of stabilization of active ingredients that have low solubility, using hollow type multi-layered microcapsule made of hydrophobic polymer/polyhydric alcohols and preparation method thereof, and cosmetic composition containing the microcapsules - Google Patents

Method of stabilization of active ingredients that have low solubility, using hollow type multi-layered microcapsule made of hydrophobic polymer/polyhydric alcohols and preparation method thereof, and cosmetic composition containing the microcapsules Download PDF

Info

Publication number
WO2007145395A1
WO2007145395A1 PCT/KR2006/003149 KR2006003149W WO2007145395A1 WO 2007145395 A1 WO2007145395 A1 WO 2007145395A1 KR 2006003149 W KR2006003149 W KR 2006003149W WO 2007145395 A1 WO2007145395 A1 WO 2007145395A1
Authority
WO
WIPO (PCT)
Prior art keywords
acrylate
acid
meta
poly
polyol
Prior art date
Application number
PCT/KR2006/003149
Other languages
English (en)
French (fr)
Inventor
Dong-Hwan Lee
Jin-Hui Kim
Bum-Chun Lee
Hyeong-Bae Pyo
Original Assignee
Han-Bul Cosmetics 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 Han-Bul Cosmetics Co., Ltd. filed Critical Han-Bul Cosmetics Co., Ltd.
Publication of WO2007145395A1 publication Critical patent/WO2007145395A1/en

Links

Classifications

    • 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
    • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A61K8/85—Polyesters
    • 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
    • A61K8/30—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
    • A61K8/34—Alcohols
    • A61K8/345—Alcohols containing more than one hydroxy group
    • 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
    • A61K8/37—Esters of carboxylic acids
    • A61K8/375—Esters of carboxylic acids the alcohol moiety containing more than one hydroxy group
    • 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
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • 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
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
    • A61K8/8152—Homopolymers or copolymers of esters, e.g. (meth)acrylic acid esters; Compositions of derivatives of such polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • 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

Definitions

  • the present invention relates to a preparing method of hollow-type multi-layered microcapsules containg copious amounts of low-soluble cosmetic ingredients with low solubility, and a cosmetic composition containing the microcapsules.
  • Polyphenols are one of the most important natural substances that possess anti-free radical and anti-oxidant activities ( 'Polyphenol ic Phenomena 1 , A. SCALBERT, Editor, INRA Editions, Paris, 1993).
  • Polyphenol compounds containing flavonoids have valuable biological features related to anti-free radical activity. These compounds can prevent the harmful effects of free radicals on skin, and can protect against accelerated skin aging resulting from sunlight exposure. They also are useful as antitumor agents. The compounds can prevent the onset of diseases that are caused by free radicals, such as cancer.
  • Polyphenols containing flavonoids also are used to preserve foods owing to their antioxidant properties.
  • Flavonoids one class of polyphenols, have a 2-phenyl-benzo-r-pyrone ring, namely a flavone structure, "flavonoids is a generic term for flavans, flavonones, flavones, anthocyanins, etc. At present, about 3,000 species of flavonoids are known, and they commonly have 2-phenyl-chroman linkage as their basic structure. Flavonoids can be classified into several groups according to the degree to which the central pyran ring is oxidized. In nature, flavonoids occasionally exist in free form, but more often they are present in the glycoside form, linked with rhamnose, glucose, rutinose, etc.
  • Flavonoids a group of phytochemicals renowned for their anti-candiosis properties, have additional disease-fighting properties, including antioxidant, tumor, thrombotic, inflammatory, allergic and microbial activities. Discovery of the physiological functions of flavonoids led to the development of foods, pharmaceuticals and cosmetics containing the compound. Flavonoids possess antioxidant and enzyme-inhibiting activities. Therefore, the compound is used in cosmetics, pharmaceuticals and foods. Various forms of flavonoids are used in cosmetics because of their anti-wrinkle, whitening, antioxidant and moisturizing effects.
  • ⁇ 5> the most important characteristic of a cosmetic ingredient is stability.
  • the stability of flavonoids is influenced by various physical and chemical factors in the environment, such as oxygen, light, high temperature, extreme pH, and presence of other cosmetic ingredients.
  • the stability of flavonoids may deteriorate depending on what environmental factors are present during manufacturing, circulation, consumer's use, and storage.
  • Quercetin a representative flavonoid, which has powerful antioxidant, free-radicals scavenging, liver-protective, inhibition of platelet- aggregation, anti-allergy, and anti-inflammatory effects, has solubilities of 0.0003% in water, 0.012% in myristic acid isopropyl, and 0.156% in oleyl alcohol- all common cosmetic solvents.
  • stabilization methods include the following: the physical method, which stabilizes the active ingredients by isolating them from water or solvent via encapsulation; and, the chemical method, which stabilizes the active ingredients by adding antioxidants or by transforming them into derivatives.
  • liposomes which are widely used in pharmaceuticals, cosmetics and foods. Liposomes are classified into multi lamella vesicles (MLV) and uni lamella vesicles (ULV), which are further reclassified into large (LUV) and small unilamella vesicles (SUV). Among these liposomes, LUV contains the largest number of active molecules, but are unstable; SUV are the most stable, but cannot contain many molecules. Furthermore, the stability of liposomes in cosmetics has not been sufficiently verified.
  • MUV multi lamella vesicles
  • UUV uni lamella vesicles
  • SUV small unilamella vesicles
  • microcapsulation As a stabilization method, microcapsulation has many advantages. Microcapsules protect sensitive molecules from deterioration and control delivery of active molecules.
  • a microcapsule preparation method using natural macromolecules such as albumin, gelatin and starch, ethylcellulose or polyalkylcyanoacrylate [J. of Pharm. Sci. 1970, vol.59, 1367; J. of Pharm. Pharmacol. 1988, vol.40, 754; J. of Microencapsulation 1991, vol.8, 335; J. of Microencapsulation 1989, vol. 6, 1; Polymer Eng. & Sci. 1989, vol. 29, 1746], to coat and encapsulate active molecules, thereby separating them from the external environment [Advanced Drug Delivery Reviews 1997, vol.28, 25-42; US patent 4,954,298; US patent 5,788,687; US patent 5,916,598] has been reported. Among others, multi-emulsion method [US patent 4,954,298] also has been reported.
  • microcapsules are dense. Therefore, the microcapsules have poor active molecule content. Porous microcapsules are problematic because solvent water filters into the capsule and deteriorates active molecules.
  • the base is dispersed and dissolved in water- phase to produce an emulsion"
  • the emulsion is then added to another water- phase containing counter-ionic macromolecules or salt to induce coacervation.
  • the emulsion is added to counter-ionic macromolecular or surfactant aqueous solution to induce coacervation.
  • lipophilic or hydrophilic active ingredients can be encapsulated, but active molecules with low solubility in water or oil, such as flavonoids, cannot be sufficiently encapsulated. Because an excess amount of water negatively affects the stability of flavonoids, coacervation is not effective for encapsulation and stabilization of low-soluble active ingredients.
  • lipophilic molecules generally are encapsulated in hydrophobic macromolecules, and water-soluble molecules are encapsulated in hydrophilic macromolecules.
  • Korean patent No. 537952 (2005.12.14.) describes hollow-type hydrophobic macromolecular microcapsules and a method for preparing them, but, the capsule could only encapsulate water-soluble active molecules. And, since bases of the inner water-phase and the outermost water-phase are water, this method is not appropriate for dissolving and encapsulating low-soluble active molecules, such as polyphenols. In addition to this problem, osmotic pressure causes inner active molecules to be eluted to the outermost water-phase. [Disclosure] [Technical Probleml
  • the present inventors prepared hollow-type, multi-layered microcapsules using hydrophobic macromolecules, polyhydric alcohols (hereafter synonymous with 'polyol' and hydrophilic or amphiphilic macromolecules.
  • the hollow-type, multi-layered microcapsules were able to encapsulate a large number of low-soluble active molecules and to improve the stability of encapsulated low-soluble active molecules by separating them from environmental factors, such as high temperature, oxygen and ultra-violet ray, and from factors in the inner cosmetic base, such as water and surfactant.
  • the cosmetic composition of the present invention encapsulated polyphenols such as flavonoids and triterphenoid, which possess low solubilities in water and oil, into hollow-type, multi-layered microcapsules.
  • the low-soluble active molecules encapsulated in hollow-type, multi-layered microcapsules of the present invention can be separated from factors in the inner cosmetic base, such as water and surfactant, and also from factors in the outer environment, such as high temperature, oxygen, UV and so on. Therefore, the cosmetics formulated in the present invention are stabilized and inhibit deterioration, change in color, and crystallization of the active molecule.
  • the aforementioned polyphenol compound is at least one or its derivative selected from a group containing flavonoids; isoflavonoids; neoflavonoids; gallotannins and ellagitannins; cathechols and their derivatives, such as caffeic acid, dihydrocaffeic acid, protocatechuic acid, chlorogenic acid, isochlorogenic acid, gentisic acid, homogentisic acid, garlic acid, hexahydroxydiphenic acid, ellagic acid, rosemaric acid or litospermic acid; phenolic acid derivatives, especially containing their esters or heterosides', curcumin.” polyhydroxylated coumarine,” monocyclic or polycyclic polyphenols, such as polyhydroxylated lignans, neolignans, or silymarin. These polyphenols may be the extracts of plants.
  • the aforementioned polyphenol may be selected from a group comprising flavones, such as apigenol or luteolol ; flavonols, such as quercetin or kaempferol; flavones or flavonol heterosides, such as rutin or its derivatives; flavanones, such as naringenin or hesperetin; flavanone heterosides, such as naringin, hesperidin or diosmin; flavanone derivatives, such as diosmoside and abiflavonoid; flavone or flavone dimmers, such as amentoflavon; calcones, such as isoliquirtigenin or hesperidin methylealcone; flavonol ignan such as silybin, silichristin or silidianin; flavan-3-ols, such as (+)-cathechol or (-)-epichathechol ; polymers consisting
  • the hollow-type, multi-layered microcapsules of the present invention are characterized to be stabilized and dissolved low-soluble active ingredient using polyol.
  • the microcapsule is characterized to contain large amounts of low-soluble active ingredients, and to have a multi-layer structure using either hydrophilic or amphiphilic macromolecules.
  • the present invention is about the hollow-type, O
  • multi-layered microcapsules of the present invention in which the outer coat is made of hydrophobic macromolecule, a hollow is formed in the outer coat, and, in the hollow, at least one microsphere encapsulating low-soluble active ingredient in hydrophilic or amphiphilic macromolecules; a method of preparing the microcapsules; and, a cosmetic composition containing the microcapsules.
  • the hollow-type, multi-layered microcapsules of the present invention were prepared using a multi-emulsion method with polyhydric alcohol and volatile organic solvent.
  • a polyol pase 1-in-oil (Pl/O) type first emulsion was prepared from polyol phase 1 (Pl), which was prepared by dissolving low- soluble active ingredients and hydrophilic or amphiphilic macromolecules, and an oil-phase (O), which consists of a volatile organic solvent containing hydrophobic macromolecules.
  • a polyol phase 1-in-oil-in polyol phase 2 (P1/0/P2) type multi-emulsion was prepared by adding the Pl/O type first emulsion to a polyol phase 2 (P2), which contained at least one emulsion stabilizer. Subsequently, the volatile organic solvent was removed by solvent evaporation-solvent extraction and the hollow-type, multi-layered microcapsules of the present invention were formed.
  • the cosmetic composition of the present invention is characterized to contain 0.001-25.0 wt% hollow-type, multi-layered microcapsules of the present invention.
  • the size of the hollow-type, multi-layered microcapsules of the present invention can be varied by changing the synthesis methods, such as stirring method, stirring instrument, rotating speed, temperature and so on, as is well-known to person skilled in the art.
  • the synthesized microcapsules of the present invention range in diameter approximately 0.01 j ⁇ n ⁇ 500 im-
  • ⁇ 37> 0.1-20 wt% of hydrophilic or amphiphilic macromolecules was added and stirred to the polyol phase 1 to form a homogeneous dispersion by heating or by mechanical method. Then, 0.01-40 wt% of the low-soluble active ingredient was added to polyol phase 1, gently stirred, and prepared poly phase 1 containing low-soluble active ingredient and hydrophilic or amphiphilic macromolecule.
  • Polyol is at least one selected from low-molecular weight alcohols'- polyethyleneglycol , polypropyleneglycol , and their copolymers, butyleneglycol , propyleneglycol , glycerin, ether containing hydric group, such as diethyleneglycol monoethyl ether.
  • the appropriate content of the polyol is 40-99.8 wt% of total polyol phase 1.
  • the appropriate glycerin content is 20-95 wt% of total polyol phase 1.
  • polyol-in-oil (P/0) type first emulsion of the present invention If less than 20 wt% is added, it is difficult to form the polyol-in-oil (P/0) type first emulsion of the present invention since the alcohol phase cannot be separated from the volatile organic solvent. If more than 95 wt% glycerin is added, low-soluble active molecules cannot be effectively dissolved or dispersed.
  • the content of the active ingredient dissolved in polyol phase 1 can be varied according to the intended purpose. But, to form a stable first emulsion, 0.01-40 wt% of the total polyol phase 1, preferably 1-10 wt% should be added.
  • the hydrophilic or amphiphilic macromolecules dispersed into the polyol phase 1 may vary between 0.1-20 wt%, preferably 0.1-10 wt% of the total polyol phase 1 to form a stable first emulsion.
  • ⁇ 42> 1.0-20 wt% of the hydrophobic macromolecules was dissolved into a volatile organic solvent to prepare oil-phase. If less than 1.0 wt% was added, the microcapsules of the present invention did not form. If more than 20 wt% was added, the P/0 first emulsion did not form because the high viscosity prevent the macromolecules from dispersing in the organic solvent. Therefore, the appropriate content of the hydrophobic macromolecules is 1.0-20 wt% of the total oil-phase, preferably 5-15 wt%.
  • the P/O-type first emulsion was prepared by adding and homogenizing the oil-phase with the polyol phase 1.
  • the content of the oil-phase may vary according to the species of hydrophobic macromolecule.
  • the oil-phase should contain l ⁇ 15-fold polyol phase 1, preferably 2 ⁇ 10-fold. If less than 1-fold is added, the P/O-type emulsion cannot form efficiently, and the encapsulation rate of the low-soluble active ingredient is lowered. If more than 15-fold is added, the inner capacity of the hollow-type, multi-layered microcapsules and the content of the active ingredient are reduced.
  • Polyol phase 2 was prepared by adding 0.05-10 wt% of the emulsion stabilizer to the mixture of polyol and water.
  • the polyol contained 20-99.95 wt% glycerin and 60-99.95 wt% of at least one selected from polyethyleneglycol , polypropyleneglycol , their copolymer and their derivatives; low molecular weight alcohol compounds, such as butyleneglycol and propyleneglycol ; and, ether containing hydric group, such as diethyleneglycol monoethyl ether.
  • the proper content of the emulsion stabilizer is 0.05-10 wt%. If less than 0.05 wt% is added, the P/0/P-type multi-emulsion cannot form effectively and coagulation of the hollow-type, multi-layered microcapsules occur. If more than 10 wt% is added, it is difficult to handle.
  • the P/0/P-type multi-layered emulsion was prepared by adding 2 ⁇ 15-fold of polyol phase 2, prepared according to step (4), to the P/O-type first emulsion, prepared according to step (3), and mixing with a homogenizer etc.
  • the proper mixing ratio of the P/O-type first emulsion to polyol phase 2 is 1:2-15. If the ratio is less than 1:2, the P/O/P-type mult i-emulsion cannot form effectively. If the ratio is more than 1:15, the content of the active ingredient is low and ineffective.
  • the hollow-type, multi-layered microcapsules of the present invention were prepared by removing the volatile organic solvent from the P/O/P-type multi-emulsion, prepared according to step (4).
  • the volatile organic solvent was removed using the solvent extraction-solvent evaporation method. Briefly, the solvent was diffused slowly due to the concentration disparity of volatile solvent between capsule membrane and polyol phase 2 in extraction process.
  • the solvent in polyol phase 2 diffuses into the boundary layer between polyol phase 2 and the outer air, where it then evaporates, removing solvent which had dissolved the hydrophobic macromolecules in evaporation process. Heating slowly or reducing the pressure of polyol phase 2 increased the rate of extraction and evaporation, thereby, increasing the rate at which hollow-type multi layered microcapsules were produced.
  • the microcapsules of the present invention can be directly applied to cosmetic composition without other collecting processes such as centrifugation, filtration or drying.
  • microcapsules produced using former multi-emulsion methods contain copious amounts of water after solvent removal, the active ingredient encapsulated in the microcapsules is not stable and is eluted into the outermost continuous phase by osmotic pressure. So, the active ingredient content decreases, crystals form, and coagulation occurs. Therefore, microcapsules produced using the former multi-emulsion method should be collected by other means.
  • the microcapsules of the present invention contains polyol after evaporating the volatile solvent, the microcapsules can be directly applied to cosmetic composition without other collecting processes. If needed, the microcapsules of the present invention can be collected using centrifugation, filtration or drying and applied to cosmetic composition.
  • the present invention is about a method of preparing hollow-type, multi layered microcapsules using polyol, a stabilizing method of low-soluble active ingredients, and a cosmetic composition containing the microcapsules.
  • polyol used polyol to increase the solubility of the low-soluble active ingredient and hydrophilic or amphiphilic macromolecules to stabilize the active ingredient in the multilayered structures.
  • the hollow-type, multilayered microcapsules of the present invention using polyol separates the low-soluble active ingredients from external environmental factors, such as high temperature, oxygen or ultra violet and internal environment such as water and surfactant, thereby stabilizing the low-soluble active ingredients and preventing deterioration, discoloration and crystallization.
  • the low-soluble active ingredient which could be encapsulated in the microcapsule of the present invention, contain molecules generally used in cosmetics, such as at least one selected from a group containing, but not limited to, linoleic acid, coenzyme Q-IO, lipoic acid and so on.
  • the low-soluble active ingredient which can be encapsulated in the microcapsule, may be seledted from a group of polyphenol or its derivative as follows"- flavonoids; isoflavonoids; neoflavonoids! gallotannins and ellagitannins," cathechol and their derivatives, such as caffeic acid, dihydrocaffeic acid, protocatechuic acid, chlorogenic acid, isochlorogenic acid, gentisic acid, homogentisic acid, garlic acid, hexahydroxydiphenic acid, ellagic acid, rosemaric acid or litospermic acid; phenolic acid derivatives, especially containing their esters or heterosides; curcumin; polyhydroxylated coumarine; and, monocyclic or polycyclic polyphenols, such as polyhydroxylated lignans, neolignans, or silymarin.
  • the aforementioned polyphenols may be the extracts of plants.
  • Polyol of the present invention is used to encapsulate and stabilize copious amounts of low-soluble active ingredients.
  • the alcohol is at least one selected from low-molecular weight alcohol compounds: polyethyleneglycol , polypropyleneglycol, and their copolymers; butyleneglycol, propyleneglycol and glycerin; ether containing at least one hydric group, such as diethyleneglycol monoethyl ether.
  • the appropriate content is 20-95 wt% of total polyol phase 1. If less than 20 wtfo is added, it is difficult to form the P/O-type first emulsion of the present invention because the alcohol- phase cannot be separated from the volatile organic solvent. If more than 95 wt% is added, the low-soluble active molecule cannot be effectively dissolved or dispersed.
  • Biocompatible macromolecules available for external application can be used as hydrophobic macromolecules for the synthesis of the multi-layered microcapsules of the present invention.
  • polystyrene poly p- or m-methylstyrene, poly p- or m- ethylstyrene, poly p- or m-chlorostyrene, poly p- or m-chloromethylstyrene, polystyrene sulfonic acid, poly p- or m- or t-butoxystyrene, polymethyl(meta)acrylate, polyethyl(meta)acrylate, polypropyl(meta)acrylate, poly n-butyl(meta)acrylate, polyisobutyl(meta)acrylate, poly t- butyl(meta)acrylate, poly 2-ethylhexyl(meta)acrylate, poly n- octyl(mata)acrylate, poly1auryl(meta)acrylate, polystearyl(meta)acrylate, poly 2-hydroxyethyl(meta)acrylate,
  • Biodegradable hydrophobic aliphatic polyester available for the present invention contains poly-L-latate, poly-D,L-glycolate, poly-L-lactate-co- glycolate, poly-D,L-lactate-co-glycolate, polycaprolactone, polyvalerolactone, polyhydroxybutyrate, polyhydroxyvalerate, polyorthoester and copolymers produced from the monomers. Mixtures of polymethyl(meta)acrylate, polyethyl(meta)acrylate, poly-L-lactate, poIy-L- lactate-co-glycolate or polycaprolactone are desirable.
  • the appropriate hydrophobic macromolecule content is 1.0-20 wt% of the total oil-phase. If less than 1.0 wt% is added, it is difficult to form microcapsules. If more than 20 wt% is added, the content of active molecules is inadequate.
  • surfactants can be added.
  • Available surfactants are sorbitansesquioleate, sorbitanmonooleate, sorbitanmonostearate and so on.
  • the volatile organic solvent used in producing the hollow-type, multi- layered microcapsules of the present invention should have a solubility similar to that of the selected macromolecule.
  • appropriate solvents are as follows: linear alkanes, such as hexane, heptane, octane, nonane and decane; alkyl ester not less than 7 carbons, such as n- hexylacetate, 2-ethylhexyl acetate, methyl oleate, dibutyl sebacate, dibutyl adibate or ebutyl carbamate; aliphatic ketones, such as methyl isobutylketone, and isobutylketone; aromatic carbohydrates, such as benzene, toluene, o ⁇ and p-xylene!
  • chlorine-containing compounds such as methylene chloride, chloroform, carbon tetrachloride, etc.
  • Methylenechloride, chloroform or acetone are well-suited to this method due to their low boiling points, high volatility, and propensity to form capsules.
  • the emulsion stabilizer used in the present invention may be selected from one of the following types of compounds: natural gums, such as gum arabic, irish moss, karaya gum, gum tragacanth, gum guaiac, xanthan gum, locust bean gum,' casein; gelatin; collagen; albumin (ex, human serum albumin); globulin", fibrin; cellulose; cellulose derivatives, such as dextrin, pectin, starch, agar and mannan; polyvinyl compounds, such as polyvinylpyrrolidone, polyvinylalcohol , polyvinylmethylether , polyvinylether ; polycarboxylic acids, such as polyacrylater or carbopol; polysaccharides, such as polysucrose, polyglucose, polylactose, and their salts.
  • natural gums such as gum arabic, irish moss, karaya gum, gum tragacanth,
  • the appropriate emulsion stabilizer content is 0.05-10 wt% of the total polyhydric alcohol phase 2. If less than 0.05 wt% is added, P/0/P-type multi- emulsion cannot form effectively and coagulation of hollow-type, multi- layered microcapsules occurs. If more than 10 wt% is added, it is difficult to handle.
  • hydrophilic or amphiphatic macromolecules used in the present invention should dissolve and disperse homogeneously in the polyol phase 1, which consists of glycerin and polyol.
  • Possible hydrophilic or amphiphatic macromolecules are as follows: natural gums, such as gum arabic, irish moss, karaya gum, gum tragacanth, gum guaiac, xanthan gum, locust bean gum; gelatin; collagen; albumin (ex, human serum albumin); globulin!
  • cellulose cellulose derivatives, such as dextrin, pectin, starch, agar or mannan
  • polyvinyl compounds such as polyvinylpyrrolidone, polyvinylalcohol , polyvinylmethylether, polyvinylether
  • polycarboxylic acids such as polyacrylater and carbopol
  • polysaccharides such as polysucrose, polyglucose, polylactose, and their salts
  • polyoxyethylene polyoxypropylene block polymers ex, poloxamer series
  • acrylate/alkylacrylate crosspolymer ACRYLATES/C10-30 ALKYL ACRYLATE CROSSPOLYMER, Pemulen series
  • the appropriate hydrophilic or amphiphatic macromolecule content for stable formation of the P/O-type first emulsion is 0.05-20 wt%, desirably 0.1-10 wt% of the total polyol phase 1.
  • the hollow-type mult i layered macromolecule microcapsules of the present invention constituted 0.001-25.0 wt%, desirably 0.01-10.0 wt% of total cosmetic composition. If more than 25 wt% is added, the stability of the emulsion cannot be guaranteed and the texture of the formulation is not so good.
  • the hollow-type multi layered macromolecule microcapsules of the present invention can be varied in formulation.
  • Formulation of the cosmetics can be water-phase, water phase-alcohol or oily solution, oil-in-water, water-in-oil or mult i layered emulsion, aqueous or oily gel, liquid, paste, solid anhydride, or oil dispersion in water-phase using microspheres, or more desirably, an ionic and/or nonionic lipid reticulum.
  • the cosmetic formulation of the present invention may be fluid, a white or ivory cream, ointment, milk lotion, serum, essence, paste or mousse.
  • the cosmetic of the present invention can be applied as an aerosol spray, solid form e.g. stick, and so on.
  • the cosmetic of the present invention can be formulated as skin care and/or make-up products.
  • composition of the present invention may contain general adjuvants known to skilled person in the art, such as hydrophilic or lipophilic gelation agents, hydrophilic or lipophilic active agents, preservatives, antioxidants, solvents, fragrances, fillers, blockers, pigments, deodorants and dyes.
  • the adjuvant content is known to skilled person in the art, generally, 0.01 -20 wt%.
  • adjuvants may be present in the oil-, water-, or polyol-phases. In any case, the content of the adjuvant should be such that it does not to deteriorate the beneficial properties of the cosmetic composition.
  • Composition of the present invention may also contain general cosmetic carriers, such as water, saline, glycerol and so on.
  • the cosmetic composition of the present invention can be formulated as basic cosmetics, such as skin lotion, milk lotion, nourishing cream, massage cream, essence, cleansing form, cleansing water, pack or body oil, and color cosmetics, such as foundation, lipstick, mascara or make-up base.
  • the formulation may be applied as a cleanser for either the face or the body.
  • the hollow-type, mult i layered microcapsules using polyol have enhanced solubility and stability from their low-soluble active ingredients.
  • the low- soluble active ingredients are captured in the hollow structure by an outer membrane made of hydrophobic macromolecules.
  • Fig. 1 is an optical microscopic image of the hollow-type, multi layered microcapsules of the present invention.
  • Fig. 2 and Fig. 3 show the surface morphology of the hollow-type, multi layered microcapsules of the present invention obtained using scanning electron microscopy.
  • Fig. 4 is a cross-sectional image of the hollow-type, multilayered microcapsules of the present invention obtained using scanning electron microscopy.
  • FIG. 5 shows cross-sectional images of the hollow-type, multilayered microcapsules of the present invention obtained using scanning electron microscopy.
  • FIG. 6 shows surface images of the hollow-type, multilayered microcapsules of the present invention obtained using scanning electron microscopy. [Best Mode]
  • Quercetin a flavonoid
  • Polymethyl metacrylate was used as the hydrophobic macromolecule.
  • a P/O-type first emulsion was produced.
  • Glycerin, butyleneglycol , and diethyleneglycol monoethylether were mixed in a 5:4:1 weight ration to prepare the polyol mixture.
  • Quercetin a flavonoid
  • Polymethyl metacrylate was used as the hydrophobic macromolecule.
  • a P/O-type first emulsion was produced, and its features were evaluated according to the composition of the polyol phase.
  • the molecular weight of polymethyl methacrylate ranged from 3-100 kd, more properly 3-20 kd.
  • Example 1 which used less than 20 wt% glycerin in the polyol phase, stable P/0 emulsion did not form because the polyol mixture could not be separated from the oil-phase (Table 2).
  • Example 5 in which 20 wt% pure water was added to the polyol phase, needle-shaped crystals, rather than a stable P/O-type emulsion, formed because of the low solubility of quercetin.
  • Glycerin, butyleneglycol , and diethyleneglycol monoethylether were mixed in 5"-4:l weight ratio to prepare a polyol mixture.
  • 0.5 wt% of pemulen, an acrylate/alkylacrylate crosspolymer was added to the polyol mixture and stirred to prepare homogeneous polyol phase 1.
  • Example 8 Microscopic examination of Examples 6 and 7 revealed mult i layered microcapsules (Fig. 1). In Example 8, with a water content of more than 40 wt%, multi layered microcapsules formed. The capsules coagulated, however, and after a short time needle-shaped quercetin crystals were observed external to the capsules. If the water content is high in polyol phase 2, the hydrophobic macromolecular membrane will not harden completely and quercetin elutes from the inner polyol phase 1 due to osmotic pressure between the inner and outer polyol phases.
  • Example 10 in which in the polyol phase 2 contained 20 wt% glycerin, only a few multi layered microcapsules formed and a small number of needle-shaped quercetin crystals were observed. These results indicate that the polyol phase 2 cannot separate from the polyol-in-oil (P/0) emulsion and form a P/0/P-type, multi layered emulsion, and that the quercetin in the inner polyol phase 1 was eluted to the outer polyol phase 2.
  • P/0 polyol-in-oil
  • ⁇ io5> 0.5 wt% pemulen, an acrylate/alkylacrylate crosspolymer, and 5 wt% quercetin were added and dispersed homogeneously into a 5:4:1 (w/w/w) mixture of glycerin, butyleneglycol , diethyleneglycol monoethylether to produce a polyol phase 1.
  • Sorbitan sesquioleate (Arlacel 83) and polymethylmetacrylate were dispersed in methylenechloride, as shown in Table 5, to produce an oil-phase.
  • 5-fold (w/w) polyol phase 1 was added little very gradually to the oil-phase, then emulsified using a homogenizer at 10,000 rpm for 5min at room temperature to produce a polyol-in-oil (P/0)-type first emulsion.
  • polyvinylalcohol (average degree of saponification 80-90%) was dispersed in a mixture of 90 wt% glycerin and 10 wt% pure water to produce polyol phase 2.
  • Samples produced according to Table 5 were observed by scanning electrone microscopy (SEM). Samples of Examples 11 - 14 were homogeneous and continuous microcapsules; the size of microcapsules was reduced when the amount of sorbitan sesquioleate was increased (Fig. 2, 3).
  • Example 14 When a section of Example 14 was ground and then observed by SEM, a mult i layered structure was evident in hollow microcapsules (Fig. 4).
  • Hollow-type, multilayered microcapsules were produced as described for Example 14, with the exception of the hydrophobic macromolecules and surfactant that were dispersed in methylenechloride, as shown in Table 7, to produce a polyol-in-oil (P/O)-ty ⁇ e first emulsion.
  • the other steps in the process were the same as those used in Example 14, yielding hollow-type, mult i layered microcapsules, polycaprolactone hollow, multi layered microcapsules, and poly-D,L-lactate-co-glycolate hollow, mult i layered microcapsules.
  • CD Analytical instrument Waters 2695 alliance separation module, Waters 996 PDA detector ⁇ 128> (D Sample preparation: 9 mi of methanol was added to 1 g of sample, The mixture was ultrasonicated for 30 min, and filtered using 0.2 ⁇ m filter paper. The filtered solution was diluted properly and quantified.
  • a milk lotion containing hollow-type, multilayered microcapsules of the present invention were prepared as shown in Table 9.
  • the A) phase of Table 9 was heated and kept at 70°C .
  • the B) phase was added, pre-emulsified and emulsified with the A) phase using a homomixer.
  • the C) phase was added and cooled slowly.
  • hollow-type, multi layered microcapsules encapsulating quercetin, as prepared in Example 14, or free quercetin was added and to the mixture to prepare homogeneous milk lotion (Example 21 and comparative Example 1).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • Dermatology (AREA)
  • Cosmetics (AREA)
PCT/KR2006/003149 2006-06-13 2006-08-11 Method of stabilization of active ingredients that have low solubility, using hollow type multi-layered microcapsule made of hydrophobic polymer/polyhydric alcohols and preparation method thereof, and cosmetic composition containing the microcapsules WO2007145395A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2006-0053025 2006-06-13
KR1020060053025A KR100781604B1 (ko) 2006-06-13 2006-06-13 다가 알코올을 이용한 난용성 활성 성분 함유 중공형 다중마이크로캡슐의 제조 방법 및 이를 함유하는 화장료 조성물

Publications (1)

Publication Number Publication Date
WO2007145395A1 true WO2007145395A1 (en) 2007-12-21

Family

ID=38831890

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2006/003149 WO2007145395A1 (en) 2006-06-13 2006-08-11 Method of stabilization of active ingredients that have low solubility, using hollow type multi-layered microcapsule made of hydrophobic polymer/polyhydric alcohols and preparation method thereof, and cosmetic composition containing the microcapsules

Country Status (2)

Country Link
KR (1) KR100781604B1 (ko)
WO (1) WO2007145395A1 (ko)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104398489A (zh) * 2014-11-04 2015-03-11 安徽省农业科学院农产品加工研究所 一种纳米化水飞蓟宾羟基磷灰石复合微胶囊的制备方法
US10842729B2 (en) 2017-09-13 2020-11-24 Living Proof, Inc. Color protectant compositions
US10987300B2 (en) 2017-09-13 2021-04-27 Living Proof, Inc. Long lasting cosmetic compositions
US11622929B2 (en) 2016-03-08 2023-04-11 Living Proof, Inc. Long lasting cosmetic compositions

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101293926B1 (ko) 2010-12-30 2013-08-07 조선대학교산학협력단 쿠르쿠민-함유 고체 분산체 및 이를 포함하는 조성물
KR101265955B1 (ko) 2011-09-07 2013-05-22 한불화장품주식회사 혼합 생약 추출발효물을 배합시킨 마이크로캡슐을 포함하는 화장료 조성물
KR102552770B1 (ko) * 2017-03-31 2023-07-10 (주)아모레퍼시픽 아멘토플라본의 안정도가 향상된 투명 또는 반투명 화장료 조성물
CN110559352B (zh) * 2019-10-23 2021-08-20 河北科技大学 一种山楂黄酮微胶囊及其制备方法和应用
CN112717841B (zh) * 2019-10-28 2022-10-11 中国石油化工股份有限公司 一种复合壁材的相变微胶囊及其制备方法
CN113019272B (zh) * 2021-03-12 2022-12-20 东莞波顿香料有限公司 香精胶囊及其制备方法和洗护用品

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5837290A (en) * 1993-02-09 1998-11-17 Ciba-Geigy Corporation Process for the preparation of microcapsules
US5916598A (en) * 1996-05-07 1999-06-29 Alkermes Controlled Therapeutics Inc. Ii Preparation of biodegradable, biocompatible microparticles containing a biologically active agent

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5591932A (en) * 1994-05-09 1997-01-07 Fmc Corp. Break action cannon

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5837290A (en) * 1993-02-09 1998-11-17 Ciba-Geigy Corporation Process for the preparation of microcapsules
US5916598A (en) * 1996-05-07 1999-06-29 Alkermes Controlled Therapeutics Inc. Ii Preparation of biodegradable, biocompatible microparticles containing a biologically active agent

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104398489A (zh) * 2014-11-04 2015-03-11 安徽省农业科学院农产品加工研究所 一种纳米化水飞蓟宾羟基磷灰石复合微胶囊的制备方法
US11622929B2 (en) 2016-03-08 2023-04-11 Living Proof, Inc. Long lasting cosmetic compositions
US10842729B2 (en) 2017-09-13 2020-11-24 Living Proof, Inc. Color protectant compositions
US10987300B2 (en) 2017-09-13 2021-04-27 Living Proof, Inc. Long lasting cosmetic compositions
US11707426B2 (en) 2017-09-13 2023-07-25 Living Proof, Inc. Color protectant compositions

Also Published As

Publication number Publication date
KR100781604B1 (ko) 2007-12-03

Similar Documents

Publication Publication Date Title
WO2007145395A1 (en) Method of stabilization of active ingredients that have low solubility, using hollow type multi-layered microcapsule made of hydrophobic polymer/polyhydric alcohols and preparation method thereof, and cosmetic composition containing the microcapsules
Yang et al. Encapsulating plant ingredients for dermocosmetic application: An updated review of delivery systems and characterization techniques
EP1928594B1 (en) Method for production of multi-layer microcapsules
JP3583133B2 (ja) 架橋した植物ポリフェノールの壁を有するマイクロカプセルおよびそれを含有する組成物
DK175307B1 (da) Kosmetisk eller farmaceutisk komposition indeholdende mikrosfærer af polymere eller af fedtstoffer forsynet med mindst et aktivt produkt
US6379683B1 (en) Nanocapsules based on dendritic polymers
CN104379175A (zh) 高度支化的α-D-葡聚糖
CN102341166A (zh) 分散组合物及分散组合物的制造方法
Mosaddik et al. Development and use of polymeric nanoparticles for the encapsulation and administration of plant extracts
CN113194907A (zh) 包含着色剂的颗粒及其使用方法
KR101114659B1 (ko) 생분해성 고분자를 이용하여 유용성 활성성분을 안정화한나노입자 및 이의 제조방법
JP2004250450A (ja) 有効成分をマイクロカプセル内に含有する化粧料
CN107405313A (zh) 难溶性药物传递用的可溶性微针
Dos Santos et al. Vasorelaxant effect of standardized extract of Cecropia glaziovii Snethl encapsulated in PLGA microparticles: In vitro activity, formulation development and release studies
KR20100123007A (ko) 다중 지질 마이크로캡슐 및 이를 함유하는 화장료 조성물
KR101827611B1 (ko) 피코시아닌을 포함하는 유중수 마이크로 또는 나노에멀젼
FR3031669A1 (fr) Systeme de delivrance avancee
KR20100120731A (ko) 유용성 활성물질 함유 미세캡슐 입자, 이의 제조방법 및 이를 포함하는 화장료 조성물
KR101346844B1 (ko) 다중 에멀션에 의한 수용성 활성물질과 지용성 활성물질이 함께 함유된 마이크로스피어 및 이를 함유하는 화장료 조성물
Tran et al. Lipid-Based Vesicles Containing Rutin: Phytosome and Niosome
Suruthelaya et al. An Effective Liposomal Gel Preparation for the Long-lasting Herbal Mosquito Repellent
Kumar et al. Design and Development of Nanoemulsions and Hydrogel Based Systems for Enhanced Intestinal Permeability and Controlled Release of Phytochemicals
CN118121502A (zh) 麦角硫因组合物包埋递送制剂及其制备方法和应用
IL189633A (en) Method for production of double-layer and triple-layer microcapsules
Shanmugarathinam et al. Formulation and In vitro Evaluation of Simvastatin Microspheres Using Ethyl Cellulose as the Release Retarding Polymer

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 06783571

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC EPO FORM 1205A MAILED 04.03.09

122 Ep: pct application non-entry in european phase

Ref document number: 06783571

Country of ref document: EP

Kind code of ref document: A1