WO2009057847A1

WO2009057847A1 - Sustained-release nanoparticle and the cosmetic composition containing the same

Info

Publication number: WO2009057847A1
Application number: PCT/KR2007/005994
Authority: WO
Inventors: Do Hoon Kim; Jongwon Shim; Chang Man Park; Jin Woong Kim; Junch Kim; Byung-Young Kang
Original assignee: Amorepacific Corporation
Priority date: 2007-10-31
Filing date: 2007-11-26
Publication date: 2009-05-07
Also published as: KR20090044269A

Abstract

The present invention relates to a sustained-release nanoparticle and a cosmetic composition comprising the nanoparticle. Specifically, the present invention relates to a sustained-release nanoparticle that is prepared using phytantriol to inhibit an initial burst release of drugs or active ingredients and slowly release the drugs or active ingredients, and to a cosmetic composition comprising the nanoparticle.

Description

[DESCRIPTION]

[invention Title]

Sustained-release nanoparticle and the cosmetic composition containing the same

[Technical Field]

The present invention relates to a sustained-release nanoparticle and a cosmetic composition comprising the nanoparticle. Specifically, the present invention relates to a sustained-release nanoparticle that is prepared using phytantriol to inhibit an initial burst release of drugs or active ingredients and slowly release the drugs or active ingredients, and to a cosmetic composition comprising the nanoparticle .

[Background Art]

Recently, many studies of sustained-release particles that release drugs over a long period of time have been made by using Polylactic-co-glycolic acid (PLGA) as a base material, and medical preparations, cosmetics and the like utilizing the particles have been developed (Japanese

Patent Application Laid-open Nos . (Hei) 11-286403A, 2000-

239104A, and 2002-326960A) . Particularly, sustained-release particles comprising water- and oil-soluble drugs have been studied, and a system that inhibits an initial burst release of a drug and releases the drug over a long period of time, thereby reducing side effects and showing the drug efficacy for a long time, has been actively studied in the field of medicine. The current market of cosmetics needs a high functional product such as anti-wrinkling and whitening products. In accordance with said needs, products comprising various extracts and active ingredients are prepared. Since such extracts and active ingredients may be highly irritable to skin compared with other cosmetic raw materials, an initial burst release of the extracts and active ingredients to the skin should be reduced, thereby reducing irritation to skin, and the efficacy of active ingredients should be evenly exerted over a long period of time. Therefore, a technique that inhibits an initial burst release of the drugs and enables the drugs to be slowly released is needed.

Phytantriol has been used in cosmetic and hair products for over forty (40) years, and is well known as having an effect of hair moisturizing, adsorption enhancement of active ingredients, etc. (German Patent No. 3,817,623) .

[Disclosure] [Technical problem]

The present inventors have studied a sustained- release nanoparticle that can reduce skin irritation of active ingredients in cosmetics and show an even effect over a prolonged time, and have found that nanoparticles prepared using phytantriol inhibit an initial burst release of drugs or active ingredients and release the drugs or active ingredients over a long period of time, even if the drugs or active ingredients are water-soluble.

Therefore, an object of the present invention is to provide a sustained-release nanoparticle that is effective in inhibiting an initial burst release of drugs or active ingredients and releasing the drugs or active ingredients over a long period of time, and a cosmetic composition comprising the nanoparticle .

[Technical solution]

The present invention provides a sustained-release nanoparticle that is prepared using phytantriol to inhibit an initial burst release of drugs or active ingredients and slowly release the drugs or active ingredients over a long period of time, and a cosmetic composition comprising the nanoparticle.

[Advantageous Effects] The water dispersible nanoparticles of the present invention comprising phytantriol have a sustained-release behavior of drugs or active ingredients and inhibit an initial burst release. The water dispersible nanoparticles enable the active ingredients comprised in the cosmetics to show an even efficacy for a long time and inhibit an initial burst release of the active ingredients, thereby reducing a stimulus of the active ingredients to skin.

According to the present invention, phytantriol is dispersed in the form of nanoparticles into water, which contributes to the preparation of systems that are safe to skin and have a good efficacy when applied to functional cosmetic formulations.

[Description of Drawings] Further objects and advantages of the invention can be more fully understood from the following detailed description taken in conjunction with the accompanying drawings, in which:

FIG. 1 is a graph showing the change of nanoparticle size according to the ratio of surfactant;

FIG. 2 is a graph showing the releasing behavior of a drug in a water dispersible nanoparticle with the lapse of time;

FIG. 3 is a graph showing the initial releasing behavior of a drug in a water dispersible nanoparticle.

[Best Mode]

The term "sustained-release nanoparticle" used herein means a water dispersible nanoparticle that is prepared by entrapping drugs or active ingredients for cosmetics into the particle, which prevents the drugs or active ingredients from bursting at once at an early stage and slowly releases the entrapped drugs to thereby prolong the effect of the drugs, wherein the average diameter of the particle is 20 to 300 ran.

The present invention provides a nanoparticle composition comprising 0.1 to 50% by weight of phytantriol, 0.01 to 50% by weight of emulsifier, 0 to 90% by weight of organic solvent, 0 to 6% by weight of hydrophilic polymer, 0 to 90% by weight of drugs or active ingredients, and water.

The phytantriol used in the present invention is a derivative of vitamine B and is insoluble in water. It is known that phytantriol is useful for the treatment of hair damage by improving the penetration of active ingredient into hair and skin. If the amount of phytantriol exceeds 50% by weight, it is difficult to disperse the composition into nanoparticles . If the amount of phytantriol is less than 0.1% by weight, the effect of phytantriol is reduced. The emulsifier comprised in the present composition can be one or more materials selected from the group consisting of phospholipid, nonionic surfactant, anionic surfactant, and cationic surfactant.

The phospholipid can include phosphatidylcholine derivatives, phosphatidylethanolamine derivatives, phosphatidylserine derivatives, etc.

The nonionic surfactant can be floxamer, sorvitan ester, polyoxyethylene sorvitan, polyoxyethylene ether, etc.

The anionic surfactant can include phosphatidylserine derivatives, phosphatidinic acid derivatives, sodium dodecyl sulfate, etc.

The cationic surfactant can include 1, 2-dioleyl-3- trimethylammonium propane, dimethyl dioctadecylammonium chloride, 1, 2-dioleyl-3-ethylphosphocholine, N- [1-1 (1,2- dioleyloxy) propyl] -N-N-N-trimethylammonium chloride, 3β-

[N- [ (N' , N' -dimethylamino) ethan] carbamoyl] cholesterol, etc.

The organic solvent can be alcohol, ethylene glycol, propylene glycol, polyethylene glycol, butylene glycol, glycerin, dimethyl sulfoxide, chloroform, benzene, toluene, acetone, or mixture thereof.

The hydrophilic polymer used for the present invention is a random or block copolymer that has hydrophilic groups in a main chain of the molecule, such as a natural polymer, a modified polymer derived from the natural polymer, a synthetic polymer, etc. For example, the natural polymer includes chitisan, dextran, acacia gum, hyaluronic acid, pectin, xantan, and salts and derivatives thereof. The modified polymer includes glycol chitosan, carboxymethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, gelatin, and salts and derivatives thereof. The synthetic polymer includes polyacrylamide, polyvinylalcohol, polyacrylic acid, polyvinylpyrrolidone, and carboxyvinylpolymer . The composition can further comprise other additives such as fatty acid or alcohol derivatives of fatty acid in an amount of up to 10% by weight. The fatty acid can include myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, linoleic acid, oleic acid, etc. and the alcohol derivative of fatty acid can include myristyl alcohol, palmityl alcohol, stearyl alcohol, arachidyl alcohol, behenyl alcohol, etc.

Further, the present invention provides a method for preparing three-dimensionally stabilized nanoparticles, comprising the steps of: a) dissolving phytantriol and an emulsifier in an organic solvent completely to produce a single-phase liquid, and b) mixing the single-phase liquid obtained in step a) with water to disperse the liquid into water.

In step b) , dispersing the single-phase liquid into water can be performed by hand-shaking, voltexing, sonication, dispersion by micro-fluidizer or homo-mixer, etc. The drugs or active ingredients can be added to the organic solvent in step a) . In the case that the drugs or active ingredients are water-soluble, they can be added in step b) .

The drugs or active ingredients that can be used in the present invention include retinol, retinyl acetate, retinyl palmytate, α-tocoperol, tocoperil acetate, tocoperil rinolate, tocoperil nicotinate, coenzyme Q-IO, resveratrol, animal/plant extract, vitamine C and its derivatives, koji acid and its derivatives, size- fractionated peptides, caffeine, water- and oil-soluble functional extract, etc.

The present invention provides a cosmetic composition that comprises the sustained-release nanoparticles in an amount of 0.00001 to 99.9% by weight based on the total weight of the composition. The nanoparticles are combined with a cosmetic composition directly or indirectly after being diluted with water or solvent.

The cosmetic composition comprising the sustained- release nanoparticles can be formulated into any types of preparation without limitation. For example, the composition can be formulated into emollient toilet water, nutrition toilet water, massage cream, nourishing cream, pack, gel or skin-adhesion type preparation, and also can be a trans-dermal preparation such as lotion, ointment, gel, cream, patch or spray.

The water dispersible nanoparticle according to the present invention shows a sustained-release of the drugs or active ingredients loaded in the particle and inhibits an initial burst release, and thus is useful in delivering a drug. [Mode for Invention]

Hereinafter, the present invention will be described in further detail with reference to the following examples, but the scope of the present invention is not limited to these examples.

[Experimental Example 1] Measurement of the size of nanoparticles A mixture was prepared by mixing 1.0% by weight of phytantriol, and Floxamer 407 in an amount of 20% by weight, 30% by weight, 40% by weight, 50% by weight, 60% by weight, and 70% by weight of phytantriol, in 10.0% by weight of ethanol, allowing the mixture to the completely dissolved to form a single-phase liquid, and then mixing and dispersing the single-phase liquid into water. The nanoparticles can be re-dispersed by a high-pressure micro fluidizer. Organic solvent was removed by a rotary evaporator and replaced with water. At this time, even if the organic solvent is not removed, the preparation of nanoparticle is not influenced by the solvent.

The size of nanoparticle was measured by Malberon autosizer and the result is shown in FIG. 1. FIG. 1 depicts the reduction of size of nanoparticle according to the increase of the surfactant concentration.

[Example 1] Preparation of water dispersible nanoparticles

0.1% by weight of caffeine, 3% by weight of phytantriol, and 1.2% by weight of Floxamer 407 were completely dissolved in 10% by weight of alcohol to produce a single-phase liquid. The single-phase liquid was mixed with water and dispersed into water. The nanoparticles can be re-dispersed by a high-pressure micro fluidizer. Organic solvent was removed by a rotary evaporator and replaced with water to obtain a water dispersible nanoparticle .

[Experimental Example 2] Drug release test

The water dispersible nanoparticles prepared in Example 1 were put into a dialysis bag (MW 10000, Spectra/por, spectrum labs) . The bag was fastened by a closure at both ends and submerged into distilled water to perform the release test. While agitating the bag in a water bath at 37° C, a sample of the aqueous solution outside the dialysis bag was taken at regular intervals of time and the released amount of caffeine was determined by a high performance liquid chromatography (Hewlett Packard) . In a Comparative Example, an aqueous solution wherein 0.1% by weight of caffeine was dissolved in 99.9% by weight of water was used in the release test. The results are shown in FIGS. 2 and 3.

As shown in FIG. 2, the caffeine in the Comparative Example was almost released within 100 hours. In contrast, the water dispersible nanoparticle in Example 1 according to the present invention showed a sustained-release effect and continuously released the caffeine over 250 hours. Further, as depicted in FIG. 3, in the Comparative Example almost all caffeine was released within 20 minutes, but the water dispersible nanoparticles in Example 1 according to the present invention inhibited an initial burst release of caffeine.

Claims

[CLAIMS]

[Claim l]

A nanoparticle composition comprising phytantriol, an emulsifier, an organic solvent, a hydrophilic polymer, and water.

[Claim 2]

The nanoparticle composition of claim 1, characterized in that the emulsifier is one or more selected from the group consisting of phospholipid, nonionic surfactant, anionic surfactant, and cationic surfactant.

[Claim 3]

The nanoparticle composition of claim 2, characterized in that the phospholipid is selected from the group consisting of phosphatidylcholine derivatives, phosphatidylethanolamine derivatives, and phosphatidylserine derivatives.

[Claim 4]

The nanoparticle composition of claim 2, characterized in that the nonionic surfactant is selected from the group consisting of floxamer, sorvitan ester, polyoxyethylene sorvitan, and polyoxyethylene ether.

[Claim 5]

The nanoparticle composition of claim 2, characterized in that the cationic surfactant is selected from the group consisting of 1, 2-dioleyl-3- trimethylammonium propane, dimethyl dioctadecylammonium chloride, 1, 2-dioleyl~3-ethylphosphocholine, N- [1-1 (1,2- dioleyloxy) propyl] -N-N-N-trimethylammonium chloride, and 3β- [N- [ (N' ,N' -dimethylamino) ethan] carbamoyl] cholesterol.

[Claim 6]

The nanoparticle composition of claim 1, characterized in that the organic solvent is selected from the group consisting of alcohol, ethylene glycol, propylene glycol, polyethylene glycol, butylene glycol, glycerin, dimethyl sulfoxide, chloroform, benzene, toluene, acetone, and a mixture thereof.

[Claim 7] The nanoparticle composition of claim 1, characterized in that the hydrophilic polymer is one or more selected from the group consisting of natural polymers including chitisan, dextran, acacia gum, hyaluronic acid, pectin, xantan, and salts and derivatives thereof; modified polymers including glycol chitosan, carboxymethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, gelatin, and salts and derivatives thereof; and synthetic polymers including polyacrylamide, polyvinylalcohol, polyacrylic acid, polyvinylpyrrolidone, and carboxyvinylpolymer .

[Claim 8]

A method for preparing nanoparticles comprising the steps of: a) dissolving phytantriol and an emulsifier in an organic solvent completely to produce a single-phase liquid, and b) mixing the single-phase liquid obtained in step a) with water to disperse the liquid into water.

[Claim 9] A cosmetic composition comprising the water dispersible nanoparticles of any one of claims 1 to 7 in an amount of 0.00001 to 99.9% by weight based on the total weight of the composition. [Claim 10]

A method of inhibiting an initial burst release of drugs or active ingredients by using phytantriol. [Claim 11]

Use of nanoparticles as a sustained-release carrier wherein the nanoparticles comprise phytantriol, an emulsifier, an organic solvent, a hydrophilic polymer, and water, and slowly release drugs or active ingredients entrapped therein.