WO2017057784A1 - Dry multiple capsule type composition containing photosensitive substance for improving acne skin and method for preparing same - Google Patents

Dry multiple capsule type composition containing photosensitive substance for improving acne skin and method for preparing same Download PDF

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WO2017057784A1
WO2017057784A1 PCT/KR2015/010340 KR2015010340W WO2017057784A1 WO 2017057784 A1 WO2017057784 A1 WO 2017057784A1 KR 2015010340 W KR2015010340 W KR 2015010340W WO 2017057784 A1 WO2017057784 A1 WO 2017057784A1
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alcohol
acne skin
dry
group
composition
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PCT/KR2015/010340
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French (fr)
Korean (ko)
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이승용
이윤희
지윤택
나건
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(주)나노팜
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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these 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
    • 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
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin

Definitions

  • the present invention relates to a dry multi-capsule composition containing a photosensitive material for acne skin improvement and a method for producing the same.
  • acne is a refractory skin disease caused by fungal and bacterial infections, which requires a long-term treatment period and is not easy to treat.
  • photodynamic therapy is a kind of radical therapy such as chemotherapy which can treat lesions without surgery by using photosensitizer which is selective and photosensitive for various lesions.
  • PDT photodynamic therapy
  • the photosensitive material activates oxygen molecules to convert into singlet oxygen or create new radicals. Only lesions are selectively attacked and destroyed.
  • porphyrin-based compounds are typical photosensitive materials.
  • Porphyrin-based compounds extracted from lacrim, mulberry leaves, and green algae have spectroscopic characteristics suitable for use as photosensitive materials and have relatively high cell permeability. It is known that (700-900 nm) can efficiently generate an electron transition and its excited state.
  • the current technology is to add the active material which is a photosensitive material to the liquid or emulsion, or to stabilize it in the form of Liposome using phospholipids to maintain the stability of the active material for a long time. Because it does not fundamentally prevent the denaturation of active ingredients due to chemical reactions, and the process of making liposomes using phospholipid is also complicated and expensive, and the production yield is low. It is pointed out.
  • dry polycapsules in powder form are used to compensate for the drawbacks of liposome-type carriers.
  • conventional dry capsules are stable in powder form, but when mixed with liquids, they swell themselves and break into capsules. Due to the disadvantages that the efficacious substance was oozed out and denatured, there is a disadvantage of using a mixture of powder and liquid when used.
  • the present technology aims to provide a dry multicapsule-type composition and a method for preparing the same, which can be conveniently used without mixing with the liquid phase without being broken in the liquid phase.
  • an object of the present invention is to provide a dry multicapsule composition containing a photosensitive material for improving acne skin and a method for producing the same.
  • an object of the present invention is to provide a method for preparing acne skin improver comprising the dry multicapsule-type composition for improving acne skin.
  • the present invention relates to a dry multicapsule-type composition for acne skin improvement comprising an ionic complex comprising a copolymer in which a hydrophilic cationic polymer and a photosensitizer are combined, and an anionic substrate polymer and a quencher.
  • the present invention comprises the steps of preparing the primary particles using a polysaccharide as a dispersion medium of ethanol or purified water as a method for producing acne skin improver comprising the dry multicapsule-type composition for acne skin improvement;
  • a first alcohol, a second alcohol, a fatty acid, a polysaccharide, gum, titanium oxide and zinc oxide by heating a group consisting of a single or a combination thereof to prepare secondary particles by using ethanol or purified water as a dispersion medium; It relates to a method for producing a skin improver.
  • composition of the present invention is harmless to the human body and does not cause side effects, and can be utilized for photodynamic therapy (PDT) of acne skin, including a photosensitive material having optical properties and disease target properties.
  • PDT photodynamic therapy
  • composition of the present invention is excellent in the improvement effect of acne skin.
  • FIG. 1 relates to a schematic diagram of a dry multicapsule composition for acne skin improvement according to the present invention.
  • Figure 2 is a 200 times the dry microcapsule-type composition for acne skin improvement according to the present invention with an optical microscope.
  • Figure 3 relates to a dry multicapsule composition for acne skin improvement of (a) the diameter of the capsule of the present invention 1.0mm, (b) the diameter of the capsule of 0.1mm.
  • the present invention relates to a dry multicapsule-type composition for acne skin improvement comprising an ionic complex comprising a copolymer in which a hydrophilic cationic polymer and a photosensitizer are combined, and an anionic substrate polymer and a quencher.
  • the hydrophilic cationic polymer is glycol chitosan, chitosan, poly-L-lysine (PLL), poly-beta-amino ester polymer, polyethylenimine (PEI), poly (amidoamine) (PAMAM) Dendrimers and derivatives thereof may be selected from the group consisting of.
  • the hydrophilic cationic polymer may include polyethylene glycol and polyethyleneimine.
  • the polyethylene glycol (PEG) has a structural formula represented by HO- (CH 2 CH 2 O) nH, in this case strong due to the structural properties having ethylene oxide ((CH 2 CH 2 O)-) is connected repeatedly It shows hydrophilicity.
  • these properties have characteristics that impart biocompatibility when combined with proteins or compounds.
  • polyethylene glycol is also present in the form of methoxy polyethylene glycol (mPEG) in which one end is substituted with a methoxy group (CH 3 O-), and the structural formula is represented by CH 3 O- (CH 2 CH 2 O) nH. do.
  • mPEG methoxy polyethylene glycol
  • polyethylene glycol may be polyethylene glycol having a carboxyl group at the terminal having a molecular weight of 300 to 50,000.
  • the polyethylene glycol may be methoxy polyethylene glycol in which one end is substituted with a methoxy group.
  • polyethyleneimine is a cationic polymer electrolyte that has been utilized in the papermaking field for a long time.
  • polyethyleneimine is divided into linear and branched forms according to its structure, and the synthesis method of the two is different.
  • Polyethyleneimines generally used are branched, where the number of primary amines, secondary amines and tertiary amines is present in a ratio of 1: 2: 1.
  • Branched polyethyleneimine is known to exist in about one branch of 3-3.5 of the main chain nitrogen atom, the polyethyleneimine is dissolved in water, alcohol, glycol, dimethylformamide, tetrahydrofuran, esters, etc. It is known to be insoluble in high molecular weight hydrocarbons, oleic acid and diethyl ether.
  • the polyethyleneimine may be a non-toxic branched polyethyleneimine, and when the molecular weight of the polyethyleneimine is less than 100, the copolymer produced according to the present invention may not bind well with a useful bioactive substance, and the molecular weight is 25,000. If abnormal, there is a problem that is difficult to be discharged out of the body through the kidneys in the body.
  • polyethyleneimine may have a molecular weight of 100 to 25,000, and preferably 100 to 2000.
  • the hydrophilic cationic polymer may form ion composite particles by an anionic matrix polymer and electrostatic attraction described below.
  • the photosensitizer is a porphyrin-based (phorphyrins) compound, chlorins (chlorins) compounds, bacteriochlorins (bacteriochlorins) compounds, phthalocyanine compounds (phtalocyanine compounds, naphthalocyanines compounds and 5-amino
  • phorphyrins chlorins
  • chlorins chlorins
  • bacteriochlorins bacteriochlorins
  • phthalocyanine compounds phthalocyanine compounds
  • 5-aminoevuline esters compounds One selected from the group consisting of 5-aminoevuline esters compounds can be used.
  • the photosensitizer may be Chlorin e6, Zinc Phthalocyanine or Pheophorbide A.
  • the copolymer may be polyethylene glycol-polyethyleneimine-pheophorbide A.
  • the binder may be configured in a form in which a quencher is bonded to the anionic substrate polymer.
  • the anionic matrix polymers include chondroitin-6-sulfate (C6S), heparan sulfate (HS), heparan sulfate proteoglycan (HSPG), heparin, chondroitin-4-sulfate (C4S), chondroitin-6-sulfate ( C6S), dermatan sulfate (DS), keratan sulfate (KS), and hyaluronic acid (HA) can be used.
  • C6S chondroitin-6-sulfate
  • HS heparan sulfate
  • HSPG heparan sulfate proteoglycan
  • C4S heparin
  • C4S chondroitin-4-sulfate
  • C6S chondroitin-6-sulfate
  • DS dermatan sulfate
  • KS keratan sulfate
  • HA hyaluronic acid
  • the quencher may be selected from the group consisting of blackhole quencher (BHQ), blackberry quencher (BBQ), and derivatives thereof. Preferably it may be a black hole quencher.
  • the present invention is characterized in that the cationic polymer, that is, hydrophilic cationic polymer is used to impart hydrophilicity to the photosensitizer having hydrophobicity, so that the precipitate is not dissolved in the solution or water during optical treatment.
  • the cationic polymer that is, hydrophilic cationic polymer is used to impart hydrophilicity to the photosensitizer having hydrophobicity, so that the precipitate is not dissolved in the solution or water during optical treatment.
  • the conjugate may be a chondroitin sulfate-black hole quencher (BHQ).
  • the ion complex may be greater than 0 to 100 mg or less with respect to 100 g of the total composition.
  • the capsule is not limited thereto, but may be spherical, the size may be greater than 0mm to 10mm or less in diameter.
  • composition is 0.1-10% by weight of the emulsifier, 0.1-10% by weight of the first alcohol, 0.1-10% by weight of the second alcohol, 0.1-10% by weight of fatty acids, 1-40% by weight of polysaccharides, titanium oxide or zinc oxide 1 It may further comprise -40% by weight, 1-10% by weight of the gum and the remaining amount of purified water.
  • the acne improvement effect may be further improved.
  • the emulsifier may include a nonionic surfactant having a structure of a hydroxyl group (-OH), an ether group (-O-), an amide group (-CONH), and an ester group (-COO-) in a molecule;
  • Polymeric surfactants of polyoxyethylene type, polyhydric alcohol ester type, ethylene oxide and propylene oxide block copolymers and alkyl acrylate copolymers It may be at least one selected from the group consisting of: natural surfactant of lecithin, lanolin, cholesterol, saponin.
  • the first alcohol may be at least one selected from the group consisting of glycerin, propylene glycol, butylene glycol, dipropylene glycol, polyethylene glycol, sorbitol, or a combination thereof.
  • the second alcohol is lauryl alcohol, cetyl alcohol, stearyl alcohol, cetearyl alcohol, oleyl alcohol, behenyl alcohol, linoleyl alcohol, undecylenyl alcohol, palmitole alcohol, linolenyl alcohol, arachidonyl At least one selected from the group consisting of alcohols, erucyl alcohols, or a combination thereof.
  • the fatty acid may be at least one selected from the group consisting of stearic acid, lauric acid, myristic acid, behenic acid, isostearic acid, oleic acid, or a combination thereof.
  • the polysaccharide may be at least one selected from the group consisting of corn starch, potato starch, sweet potato starch, cellulose, dextrin, glucose, sucrose, mannitol, or a combination thereof.
  • the gum may be at least one selected from the group consisting of carrageenan gum, guar gum, alginic acid, sodium alginate, agar or a combination thereof as a water-soluble polymer.
  • the present invention provides a method for producing acne skin improver comprising the dry multicapsule-type composition for acne skin improvement, comprising the steps of preparing primary particles using a polysaccharide as a dispersion medium of ethanol or purified water; A first alcohol, a second alcohol, a fatty acid, a polysaccharide, gum and titanium oxide or zinc oxide by heating a group consisting of a single or a combination thereof to prepare a secondary particle by using ethanol or purified water as a dispersion medium; It relates to a method for producing a skin improver.
  • the present invention may further comprise the step of coating the secondary particles with a hydrophilic polymer or a lipophilic polymer.
  • the hydrophilic polymer may be carbomer, hydroxyethyl cellulose or carrageenan gum, and the lipophilic polymer may be shellac or silicone powder.
  • the polysaccharide to prepare the primary particles may be at least one selected from the group consisting of corn starch, potato starch, sweet potato starch, cellulose, dextrin, glucose, sucrose, mannitol or a combination thereof.
  • the first alcohol for preparing the secondary particles may be at least one selected from the group consisting of glycerin, propylene glycol, butylene glycol, dipropylene glycol, polyethylene glycol, sorbitol, or a combination thereof. have.
  • Secondary alcohols for preparing the secondary particles are lauryl alcohol, cetyl alcohol, stearyl alcohol, cetearyl alcohol, oleyl alcohol, behenyl alcohol, linoleyl alcohol, undecenyl alcohol, palmitole alcohol, linol At least one selected from the group consisting of reenyl alcohol, arachidyl alcohol, erucyl alcohol, or a combination thereof.
  • the fatty acid for preparing the secondary particles may be at least one selected from the group consisting of stearic acid, lauric acid, myristic acid, behenic acid, isostearic acid, oleic acid, or a combination thereof.
  • the polysaccharide to prepare the secondary particles may be at least one selected from the group consisting of corn starch, potato starch, sweet potato starch, cellulose, dextrin, glucose, sucrose, mannitol or a combination thereof.
  • the gum for preparing the secondary particles may be at least one selected from the group consisting of carrageenan gum, guar gum, alginic acid, sodium alginate, agar or a combination thereof as a water-soluble polymer.
  • polyethylene glycol 2 g was dissolved in 200 ml of chloroform. Thereafter, 0.5 g of polyethyleneimine (Alfa Aesar, 1800da) was dissolved in 50 ml of chloroform, and then a covalent reaction of polyethylene glycol and polyethyleneimine was performed by dropping a solution of the polyethylene glycol dissolved therein drop by drop.
  • polyethyleneimine Alfa Aesar, 1800da
  • reaction was carried out for 24 hours, after completion of the reaction was concentrated to a total volume of 30ml using a vacuum concentrator, and then precipitated in diethyl ether to obtain a covalent conjugate of polyethylene glycol and polyethyleneimine It was.
  • the dialysis membrane (Spectra / Por; mol. Wt. Cutoff size, 1,000) was dialyzed with primary distilled water for 2 days, and then the final reaction product was dried by lyophilization to obtain polyethylene glycol-polyethylenimine-piopho. A pheophorbide A copolymer was obtained.
  • chondroitin sulfate 0.1 g was dissolved in 20 ml of distilled water. After dissolving BHQ3 in dried DMSO, N- (3-dimethylaminopropyl) -N'-ethylcarbodiimine hydrochloride (EDC) and 4-dimethylaminopyridine (DMAP) were each added 1.5-fold to the molar ratio of BHQ. .
  • EDC N- (3-dimethylaminopropyl) -N'-ethylcarbodiimine hydrochloride
  • DMAP 4-dimethylaminopyridine
  • Sucrose and hydroxyethyl cellulose were prepared as primary particles by using ethanol or purified water as a dispersion medium, and an emulsifier, lecithin, mannitol, fatty acid, hydroxypropyl starch phosphate, gum and titanium oxide were heated to disperse ethanol or purified water.
  • the prepared secondary particles were prepared by tertiary coating with a hydrophilic polymer or a lipophilic polymer as needed.
  • Table 1 below relates to the composition of the acne skin improver comprising a dry multicapsules composition.
  • Dispersant is a volatilized amount, not included in the total amount.

Abstract

The present invention relates to a dry multiple capsule type composition containing a photosensitive substance for improving acne skin, and a method for preparing the same. The composition of the present invention is applicable to photodynamic therapy (PDT) because the same comprises a photosensitive substance which is harmless to a human body, does not cause side effects, and has optical properties and disease-targeting characteristics. In addition, the composition of the present invention is excellent in improving acne skin.

Description

여드름 피부개선을 위한 광민감성 물질을 함유한 건식다중캡슐형 조성물 및 그의 제조방법Dry multicapsule composition containing photosensitive material for acne skin improvement and preparation method thereof
본 발명은 여드름 피부개선을 위한 광민감성 물질을 함유한 건식다중캡슐형 조성물 및 그의 제조방법에 관한 것이다.The present invention relates to a dry multi-capsule composition containing a photosensitive material for acne skin improvement and a method for producing the same.
피부질환은 비록 생명에는 지장을 주지 않으나 그 발생빈도가 높으며 현대인의 경우 다양한 원인과 기후, 스트레스 등으로 점점 더 발생빈도가 높아지는 추세이다.Although skin disease does not affect life, its incidence is high, and in modern people, the frequency of occurrence is increasing due to various causes, climate, and stress.
특히, 여드름은 진균 및 세균의 감염에 의한 난치성 피부질환으로서, 장기적인 치료기간을 필요로 하며 치료도 쉽지 않다.In particular, acne is a refractory skin disease caused by fungal and bacterial infections, which requires a long-term treatment period and is not easy to treat.
여드름을 치료하기 위한 방법으로는 피지 생성을 억제하는 호르몬제, 항생제 투여가 처방되고 있다. 이러한 방법은 여드름 예방과 치료에 어느 정도 효과가 있으나, 만족할 만한 효과적인 측면이나 피부안전성 측면에 있어 부작용이 문제시 되고 있다.As a treatment for acne, hormones and antibiotics that inhibit sebum production are prescribed. Although this method has some effects on acne prevention and treatment, side effects are problematic in terms of satisfactory effective and skin safety aspects.
특히, 호르몬제의 경우에는 피부의 홍반이나 건조증 등 장기 투여시, 부작용을 유발할 수 있으며, 항생제인 벤조일퍼록사이트(benzoyl peroxide)와 레티노익산(Retinoic acid)는 발암성 및 접촉성 피부염 유발의 문제가 있다. 그 외 여드름 치료제로 테트라싸이클린(tetracyclin), 에리스로마이신(erythromycin) 및 클린다마이신(clindamycin)를 사용하여 효과를 보고 있으나, 내성균의 출현 등의 가능성이 있는 것으로 보고되고 있어 사용에 제한이 따를 수 있다.In particular, in the case of hormones, long-term administration such as erythema or dryness of the skin may cause side effects, and antibiotics benzoyl peroxide and retinoic acid may cause carcinogenic and contact dermatitis problems. have. Tetracyclin, erythromycin, and clindamycin have been shown to be effective as acne treatments, but it is reported that there is a possibility of the emergence of resistant bacteria, and the use thereof may be restricted.
한편, 광역학 치료법(photodynamic therapy, PDT)이란 각종 병변에 대해 선택성 및 광증감성이 있는 광민감성 물질(photosensitizer)을 이용하여 수술 없이 병변을 치료할 수 있는 일종의 화학요법제와 같은 근치법이다. 예컨대, 상기 광민감성 물질을 정맥주사에 의해 대상자에 투여하고, 이에 적절한 광(light)을 조사함으로써, 광민감성 물질이 산소분자를 활성화시켜 단일항(singlet) 상태의 산소로 변환 혹은 새로운 라디칼을 만들어 병변만을 선택적으로 공격, 궤멸시키는 것이다.On the other hand, photodynamic therapy (PDT) is a kind of radical therapy such as chemotherapy which can treat lesions without surgery by using photosensitizer which is selective and photosensitive for various lesions. For example, by administering the photosensitive material to a subject by intravenous injection and irradiating with appropriate light, the photosensitive material activates oxygen molecules to convert into singlet oxygen or create new radicals. Only lesions are selectively attacked and destroyed.
이러한 광민감성 물질로는 포르피린(porphyrin)류의 화합물이 대표적인데, 잠분이나 뽕잎, 녹조류 등에서 추출되는 포르피린계 화합물은 광민감성 물질로 사용하기에 적합한 분광학적 특성을 갖고 있고, 비교적 세포투과력이 큰 적색광(700-900nm)에 의해 전자 전이를 일으키는 성질과 그에 따른 여기상태를 효율적으로 생성할 수 있는 것으로 알려져 있다.For example, porphyrin-based compounds are typical photosensitive materials. Porphyrin-based compounds extracted from lacrim, mulberry leaves, and green algae have spectroscopic characteristics suitable for use as photosensitive materials and have relatively high cell permeability. It is known that (700-900 nm) can efficiently generate an electron transition and its excited state.
현재의 기술로는 이러한 광민감성 물질인 활성물질을 액상 또는 유화물에 첨가하거나 포스포리피드류를 사용하여 Liposome형태로 안정화시켜 활성물질의 안정성을 장기간 유지하도록 하고 있으나 이러한 기술은 제품 내에 수분을 포함하고 있기 때문에 근본적으로 화학적 반응으로 인한 활성성분의 변성을 막지 못하며, 또한 포스포리피드를 이용하여 Liposome으로 만드는 과정 또한 복잡하고 고가의 비용을 요하며 생산수율 또한 낮기 때문에 효율적이지 못한 것이 현재 기술의 문제점으로 지적되고 있다.The current technology is to add the active material which is a photosensitive material to the liquid or emulsion, or to stabilize it in the form of Liposome using phospholipids to maintain the stability of the active material for a long time. Because it does not fundamentally prevent the denaturation of active ingredients due to chemical reactions, and the process of making liposomes using phospholipid is also complicated and expensive, and the production yield is low. It is pointed out.
또한 이러한 liposome형태의 carrier의 단점을 보완하고자 분말형태의 건식다중캡슐을 이용하기도 하지만 기존의 기술로는 이러한 건식다중캡슐은 분말상태에서는 안정하지만 액체와 혼합 시 스스로 팽윤되어 캡슐이 깨어져서 캡슐 안에 포함되어 있던 효능물질이 배어나와 변성이 되는 단점 때문에 사용 시 분말과 액상을 섞어서 사용하는 단점이 있다.In addition, dry polycapsules in powder form are used to compensate for the drawbacks of liposome-type carriers. However, conventional dry capsules are stable in powder form, but when mixed with liquids, they swell themselves and break into capsules. Due to the disadvantages that the efficacious substance was oozed out and denatured, there is a disadvantage of using a mixture of powder and liquid when used.
이에 본 기술은 액상 안에서도 깨지지 않고 사용시 액상과 혼합성이 용이하여 편리하게 사용할 수 있는 건식다중캡슐형 조성물 및 그의 제조방법을 제공함을 목적으로 한다.Therefore, the present technology aims to provide a dry multicapsule-type composition and a method for preparing the same, which can be conveniently used without mixing with the liquid phase without being broken in the liquid phase.
보다 자세하게 본 발명은 여드름 피부개선을 위한 광민감성 물질을 함유한 건식다중캡슐형 조성물 및 그의 제조방법을 제공함을 목적으로 한다.In more detail, an object of the present invention is to provide a dry multicapsule composition containing a photosensitive material for improving acne skin and a method for producing the same.
또한, 본 발명은 상기 여드름 피부 개선용 건식다중캡슐형 조성물을 포함하는 여드름 피부 개선제의 제조방법을 제공함을 목적으로 한다.In addition, an object of the present invention is to provide a method for preparing acne skin improver comprising the dry multicapsule-type composition for improving acne skin.
본 발명은 친수성 양이온 고분자와 광감작제가 결합된 공중합체 및 음이온성 기질 고분자와 소광제가 결합된 결합체를 포함하는 이온 복합체를 포함하는 여드름 피부개선용 건식다중캡슐형 조성물에 관한 것이다.The present invention relates to a dry multicapsule-type composition for acne skin improvement comprising an ionic complex comprising a copolymer in which a hydrophilic cationic polymer and a photosensitizer are combined, and an anionic substrate polymer and a quencher.
또한 본 발명은 상기 여드름 피부개선용 건식다중캡슐형 조성물을 포함하는 여드름 피부 개선제의 제조방법으로 다당류를 에탄올 또는 정제수를 분산매로 하여 1차 입자를 제조하는 단계; 제1 알콜, 제 2알콜, 지방산, 다당류, 검류, 티타늄옥사이드 및 징크옥사이드를 단일 또는 이들의 조합으로 이루어진 군을 가열하여 에탄올 또는 정제수를 분산매로 하여 2차 입자를 제조하는 단계;를 포함하는 여드름 피부 개선제의 제조방법에 관한 것이다.In another aspect, the present invention comprises the steps of preparing the primary particles using a polysaccharide as a dispersion medium of ethanol or purified water as a method for producing acne skin improver comprising the dry multicapsule-type composition for acne skin improvement; A first alcohol, a second alcohol, a fatty acid, a polysaccharide, gum, titanium oxide and zinc oxide by heating a group consisting of a single or a combination thereof to prepare secondary particles by using ethanol or purified water as a dispersion medium; It relates to a method for producing a skin improver.
본 발명의 조성물은 인체에 무해하며 부작용을 야기하지 않으며, 광학특성과 질병 표적특성을 갖는 광민감성 물질을 포함하여 여드름 피부의 광역학 치료(Photodynamic therapy, PDT)에 활용 가능하다.The composition of the present invention is harmless to the human body and does not cause side effects, and can be utilized for photodynamic therapy (PDT) of acne skin, including a photosensitive material having optical properties and disease target properties.
또한, 본 발명의 조성물은 여드름 피부의 개선 효과가 우수하다.In addition, the composition of the present invention is excellent in the improvement effect of acne skin.
도 1은 본 발명에 의한 여드름 피부개선용 건식다중캡슐형 조성물의 모식도에 관한 것이다.1 relates to a schematic diagram of a dry multicapsule composition for acne skin improvement according to the present invention.
도 2는 본 발명에 의한 여드름 피부개선용 건식다중캡슐형 조성물을 광학현미경으로 200배 한 것이다.Figure 2 is a 200 times the dry microcapsule-type composition for acne skin improvement according to the present invention with an optical microscope.
도 3은 본 발명에 의한 (a) 캡슐의 지름이 1.0mm, (b) 캡슐의 지름이 0.1mm인 여드름 피부개선용 건식다중캡슐형 조성물에 관한 것이다.Figure 3 relates to a dry multicapsule composition for acne skin improvement of (a) the diameter of the capsule of the present invention 1.0mm, (b) the diameter of the capsule of 0.1mm.
본 발명은 친수성 양이온 고분자와 광감작제가 결합된 공중합체 및 음이온성 기질 고분자와 소광제가 결합된 결합체를 포함하는 이온 복합체를 포함하는 여드름 피부개선용 건식다중캡슐형 조성물에 관한 것이다.The present invention relates to a dry multicapsule-type composition for acne skin improvement comprising an ionic complex comprising a copolymer in which a hydrophilic cationic polymer and a photosensitizer are combined, and an anionic substrate polymer and a quencher.
본 발명에 있어서, 상기 친수성 양이온 고분자는 글라이콜 키토산, 키토산, 폴리-L-리신(PLL), 폴리-베타-아미노 에스터 고분자, 폴리 에틸렌이민(PEI), 폴리(아미도아민) (PAMAM)덴드리머 및 이들의 유도체로 이루어진 군 중에서 선택된 것을 사용할 수 있다.In the present invention, the hydrophilic cationic polymer is glycol chitosan, chitosan, poly-L-lysine (PLL), poly-beta-amino ester polymer, polyethylenimine (PEI), poly (amidoamine) (PAMAM) Dendrimers and derivatives thereof may be selected from the group consisting of.
예컨대, 상기 친수성 양이온 고분자는 폴리에틸렌글리콜 및 폴리에틸렌이민을 포함할 수 있다.For example, the hydrophilic cationic polymer may include polyethylene glycol and polyethyleneimine.
이때, 상기 폴리에틸렌글리콜(PEG)은 HO-(CH2CH2O)n-H로 표현되는 구조식을 가지며, 이 경우 반복 연결되는 에틸렌 옥사이드((CH2CH2O)-)를 가지는 구조적 특성으로 인해 강한 친수성을 나타낸다.In this case, the polyethylene glycol (PEG) has a structural formula represented by HO- (CH 2 CH 2 O) nH, in this case strong due to the structural properties having ethylene oxide ((CH 2 CH 2 O)-) is connected repeatedly It shows hydrophilicity.
또한, 이러한 특성이 단백질 또는 화합물과 결합하는 경우에 생체친화성을 부여하게 되는 특징을 가진다.In addition, these properties have characteristics that impart biocompatibility when combined with proteins or compounds.
또한, 폴리에틸렌글리콜은 한쪽 말단이 메톡시기(CH3O-)로 치환된 메톡시폴리에틸렌글리콜(mPEG)의 형태로도 존재하는데, 그 구조식은 CH3O-(CH2CH2O)n-H로 표현된다.In addition, polyethylene glycol is also present in the form of methoxy polyethylene glycol (mPEG) in which one end is substituted with a methoxy group (CH 3 O-), and the structural formula is represented by CH 3 O- (CH 2 CH 2 O) nH. do.
특히, 폴리에틸렌글리콜-단백질의 형태를 가지는 제제의 경우 폴리에틸렌글리콜로 대부분 메톡시폴리에틸렌글리콜 유도체들이 사용되고 있다. 이는 폴리에틸렌글리콜의 말단이 메톡시기로 보호되어 있어 구조의 안정성을 유지할 수 있기 때문이다.In particular, in the case of a preparation having a form of polyethylene glycol-protein, most methoxy polyethylene glycol derivatives are used as polyethylene glycol. This is because the terminal of the polyethylene glycol is protected with a methoxy group to maintain the stability of the structure.
본 발명의 일 구현예에서, 폴리에틸렌글리콜은 분자량이 300 내지 50,000인 말단에 카르복실기를 갖는 폴리에틸렌글리콜일 수 있다. 또한, 폴리에틸렌글리콜은 한쪽 말단이 메톡시기로 치환된 메톡시 폴리에틸렌글리콜일 수 있다.In one embodiment of the present invention, polyethylene glycol may be polyethylene glycol having a carboxyl group at the terminal having a molecular weight of 300 to 50,000. In addition, the polyethylene glycol may be methoxy polyethylene glycol in which one end is substituted with a methoxy group.
한편, 상기 폴리에틸렌이민은 이미 오래 전부터 제지분야에서 활용되고 있는 양이온성 고분자 전해질이다. 일반적으로 폴리에틸렌이민은 그 구조에 따라 선형과 가지형으로 나뉘는데, 이 둘의 합성 방법은 서로 다르다.On the other hand, the polyethyleneimine is a cationic polymer electrolyte that has been utilized in the papermaking field for a long time. Generally, polyethyleneimine is divided into linear and branched forms according to its structure, and the synthesis method of the two is different.
일반적으로 사용되고 있는 폴리에틸렌이민은 가지형으로, 여기에는 일차 아민, 이차 아민, 삼차 아민의 수가 1:2:1의 비율로 존재한다.Polyethyleneimines generally used are branched, where the number of primary amines, secondary amines and tertiary amines is present in a ratio of 1: 2: 1.
가지형 폴리에틸렌이민의 가지사슬은 주사슬 질소 원자의 3-3.5 개당 하나 정도 존재하는 것으로 알려져 있으며, 이러한 폴리에틸렌이민은 물, 알콜, 글리콜, 디메틸포름아미드, 테트라하이드로퓨란, 에스테르류 등에 용해되는 한편, 고분자량의 탄화수소류, 올릭산(oleic acid), 디에틸에테르에는 용해되지 않는 것으로 알려져 있다.Branched polyethyleneimine is known to exist in about one branch of 3-3.5 of the main chain nitrogen atom, the polyethyleneimine is dissolved in water, alcohol, glycol, dimethylformamide, tetrahydrofuran, esters, etc. It is known to be insoluble in high molecular weight hydrocarbons, oleic acid and diethyl ether.
예컨대, 상기 폴리에틸렌이민은 독성이 없는 가지형 폴리에틸렌이민을 사용할 수 있으며, 폴리에틸렌이민의 분자량이 100 미만일 경우에는 본 발명에 따라 생성된 공중합체가 유용한 생리활성물질과 잘 결합할 수 없으며, 분자량이 25,000 이상일 경우에는 체내에서 신장을 통해 몸 밖으로 배출되기 어려운 문제점이 있다.For example, the polyethyleneimine may be a non-toxic branched polyethyleneimine, and when the molecular weight of the polyethyleneimine is less than 100, the copolymer produced according to the present invention may not bind well with a useful bioactive substance, and the molecular weight is 25,000. If abnormal, there is a problem that is difficult to be discharged out of the body through the kidneys in the body.
따라서, 폴리에틸렌이민은 분자량이 100 내지 25,000 일 수 있으며, 바람직하게는 100 내지 2000 인 것을 사용할 수 있다.Therefore, polyethyleneimine may have a molecular weight of 100 to 25,000, and preferably 100 to 2000.
상기 친수성 양이온 고분자는 후술되는 음이온성 기질 고분자와 정전기적 인력에 의해 이온 복합체 입자를 형성할 수 있다. The hydrophilic cationic polymer may form ion composite particles by an anionic matrix polymer and electrostatic attraction described below.
본 발명에 있어서, 상기 광감작제는 포르피린계(phorphyrins) 화합물, 클로린계(chlorins) 화합물, 박테리오클로린계(bacteriochlorins) 화합물, 프탈로시아닌계(phtalocyanine) 화합물, 나프탈로시아닌계(naphthalocyanines) 화합물 및 5-아미노레불린 에스테르계(5-aminoevuline esters) 화합물로 이루어진 군 중 에서 선택된 것을 사용할 수 있다.In the present invention, the photosensitizer is a porphyrin-based (phorphyrins) compound, chlorins (chlorins) compounds, bacteriochlorins (bacteriochlorins) compounds, phthalocyanine compounds (phtalocyanine compounds, naphthalocyanines compounds and 5-amino One selected from the group consisting of 5-aminoevuline esters compounds can be used.
예컨대, 상기 광감작제는 클로린 e6(Chlorin e6), 프탈로시아닌(Zinc Phthalocyanine) 또는 피오포바이드(pheophorbide) A 일 수 있다.For example, the photosensitizer may be Chlorin e6, Zinc Phthalocyanine or Pheophorbide A.
본 발명에 있어서, 상기 공중합체는 폴리에틸렌글리콜-폴리에틸렌이민- 피오포바이드(pheophorbide) A일 수 있다.In the present invention, the copolymer may be polyethylene glycol-polyethyleneimine-pheophorbide A.
또한, 본 발명에 있어서, 상기 결합체는 음이온성 기질 고분자에 소광제가 결합된 형태로 구성될 수 있다.In addition, in the present invention, the binder may be configured in a form in which a quencher is bonded to the anionic substrate polymer.
보다 구체적으로, 음이온성 기질 고분자는 콘드로이틴-6-설페이트(C6S), 헤파란 설페이트(HS), 헤파란 설페이트 프로테오글리칸(HSPG), 헤파린, 콘드로이틴-4-설페이트(C4S), 콘드로이틴-6-설페이트(C6S), 더마탄 설페이트(DS), 케라탄 설페이트(KS), 및 히알루론산(HA)으로 이루어진 군으로부터 선택된 것을 사용할 수 있다.More specifically, the anionic matrix polymers include chondroitin-6-sulfate (C6S), heparan sulfate (HS), heparan sulfate proteoglycan (HSPG), heparin, chondroitin-4-sulfate (C4S), chondroitin-6-sulfate ( C6S), dermatan sulfate (DS), keratan sulfate (KS), and hyaluronic acid (HA) can be used.
또한, 본 발명에 있어서, 상기 소광제로는 블랙홀 소광제(blackhole quencher, BHQ), 블랙베리 소광제(blackberry quencher, BBQ) 및 이들의 유도체로 이루어지는 군에서 선택되는 것을 사용할 수 있다. 바람직하게는 블랙홀 소광제일 수 있다.In the present invention, the quencher may be selected from the group consisting of blackhole quencher (BHQ), blackberry quencher (BBQ), and derivatives thereof. Preferably it may be a black hole quencher.
이에 따라, 본 발명에서는 양이온성 고분자, 즉, 친수성 양이온 고분자를 이용하여 소수성을 갖는 광감작제에 친수성을 부여함으로써 광학 치료 시 용액 또는 물에 잘 용해되어 침전물이 생기지 않는 특징이 있다.Accordingly, the present invention is characterized in that the cationic polymer, that is, hydrophilic cationic polymer is used to impart hydrophilicity to the photosensitizer having hydrophobicity, so that the precipitate is not dissolved in the solution or water during optical treatment.
본 발명에 있어서, 상기 결합체는 콘드로이틴설페이트-블랙홀소광제 (blackhole quencher, BHQ)일 수 있다.In the present invention, the conjugate may be a chondroitin sulfate-black hole quencher (BHQ).
본 발명에 있어서, 상기 이온 복합체는 총 조성물 100g에 대하여 0 초과~100mg 이하일 수 있다.In the present invention, the ion complex may be greater than 0 to 100 mg or less with respect to 100 g of the total composition.
또한, 본 발명에 있어서, 상기 캡슐은 이에 제한되지 않으나, 구형일 수 있고, 크기는 지름이 0mm초과 내지 10mm이하 일 수 있다.In addition, in the present invention, the capsule is not limited thereto, but may be spherical, the size may be greater than 0mm to 10mm or less in diameter.
또한, 상기 조성물은 유화제 0.1-10중량%, 제1 알콜 0.1-10중량%, 제2 알콜 0.1-10중량%, 지방산 0.1-10중량%, 다당류 1-40중량%, 티타늄옥사이드 또는 징크옥사이드 1-40중량%, 검류 1-10중량% 및 잔량의 정제수를 더 포함할 수 있다.In addition, the composition is 0.1-10% by weight of the emulsifier, 0.1-10% by weight of the first alcohol, 0.1-10% by weight of the second alcohol, 0.1-10% by weight of fatty acids, 1-40% by weight of polysaccharides, titanium oxide or zinc oxide 1 It may further comprise -40% by weight, 1-10% by weight of the gum and the remaining amount of purified water.
상기 유화제, 제1 및 제2 알콜, 지방산, 다당류, 티타늄옥사이드 또는 징크옥사이드, 검류 및 정제수의 함량이 상기 범위와 같은 경우 여드름 개선 효과가 보다 더 향상될 수 있다.When the content of the emulsifier, the first and second alcohols, fatty acids, polysaccharides, titanium oxide or zinc oxide, gum and purified water is the same as the above range, the acne improvement effect may be further improved.
상기 유화제는 분자 중에 수산기(-OH), 에테르기(-O-), 아미드기(-CONH), 에스테르기(-COO-)의 구조를 가진 비이온성계면활성제; 폴리옥시에틸렌형, 다가알콜에스테르형, 에틸렌옥사이드 및 프로필렌옥사이드블록공중합체, 아크릴산알킬공중합체의 폴리머릭계면활성제; 레시틴, 라놀린, 콜레스테롤, 사포닌의 천연계면활성제;로 이루어진 군으로부터 선택된 적어도 하나일 수 있다.The emulsifier may include a nonionic surfactant having a structure of a hydroxyl group (-OH), an ether group (-O-), an amide group (-CONH), and an ester group (-COO-) in a molecule; Polymeric surfactants of polyoxyethylene type, polyhydric alcohol ester type, ethylene oxide and propylene oxide block copolymers and alkyl acrylate copolymers; It may be at least one selected from the group consisting of: natural surfactant of lecithin, lanolin, cholesterol, saponin.
상기 제1 알콜은 다가 알콜로서, 글리세린, 프로필렌글라이콜, 부틸렌글라이콜, 디프로필렌글라이콜, 폴리에틸렌글리콜, 솔비톨 또는 이들의 조합으로 이루어진 군으로부터 선택된 적어도 하나일 수 있다.The first alcohol may be at least one selected from the group consisting of glycerin, propylene glycol, butylene glycol, dipropylene glycol, polyethylene glycol, sorbitol, or a combination thereof.
상기 제2 알콜은 라우릴알콜, 세틸알콜, 스테아릴알콜, 세테아릴알콜, 올레일알콜, 베헤닐알콜, 리놀레일알콜, 운데실레닐알콜, 팔미톨레일알콜, 리놀레닐알콜, 아라키도닐알콜, 에루실알콜 또는 이들의 조합으로 이루어진 군으로부터 선택된 적어도 하나일 수 있다.The second alcohol is lauryl alcohol, cetyl alcohol, stearyl alcohol, cetearyl alcohol, oleyl alcohol, behenyl alcohol, linoleyl alcohol, undecylenyl alcohol, palmitole alcohol, linolenyl alcohol, arachidonyl At least one selected from the group consisting of alcohols, erucyl alcohols, or a combination thereof.
상기 지방산은 스테아린산, 라우린산, 미리스틴산, 베헤닌산, 이소스테아린산, 올레인산 또는 이들의 조합으로 이루어진 군으로부터 선택된 적어도 하나일 수 있다.The fatty acid may be at least one selected from the group consisting of stearic acid, lauric acid, myristic acid, behenic acid, isostearic acid, oleic acid, or a combination thereof.
상기 다당류는 옥수수전분, 감자전분, 고구마전분, 셀룰로오스, 덱스트린, 글루코스, 수크로스, 마니톨 또는 이들의 조합으로 이루어진 군으로부터 선택된 적어도 하나일 수 있다.The polysaccharide may be at least one selected from the group consisting of corn starch, potato starch, sweet potato starch, cellulose, dextrin, glucose, sucrose, mannitol, or a combination thereof.
상기 검류는 수용성고분자중합체로서 카라기난검, 구아검, 알긴산, 알긴산나트륨, 아가 또는 이들의 조합으로 이루어진 군으로부터 선택된 적어도 하나일 수 있다.The gum may be at least one selected from the group consisting of carrageenan gum, guar gum, alginic acid, sodium alginate, agar or a combination thereof as a water-soluble polymer.
또한, 본 발명은 상기 여드름 피부개선용 건식다중캡슐형 조성물을 포함하는 여드름 피부 개선제의 제조방법으로서, 다당류를 에탄올 또는 정제수를 분산매로 하여 1차 입자를 제조하는 단계; 제1 알콜, 제 2알콜, 지방산, 다당류, 검류 및 티타늄옥사이드 또는 징크옥사이드를 단일 또는 이들의 조합으로 이루어진 군을 가열하여 에탄올 또는 정제수를 분산매로 하여 2차 입자를 제조하는 단계;를 포함하는 여드름 피부 개선제의 제조방법에 관한 것이다.In addition, the present invention provides a method for producing acne skin improver comprising the dry multicapsule-type composition for acne skin improvement, comprising the steps of preparing primary particles using a polysaccharide as a dispersion medium of ethanol or purified water; A first alcohol, a second alcohol, a fatty acid, a polysaccharide, gum and titanium oxide or zinc oxide by heating a group consisting of a single or a combination thereof to prepare a secondary particle by using ethanol or purified water as a dispersion medium; It relates to a method for producing a skin improver.
또한, 본 발명은 상기 2차 입자에 친수성폴리머 또는 친유성폴리머로 코팅하는 단계;를 더 포함할 수 있다.In addition, the present invention may further comprise the step of coating the secondary particles with a hydrophilic polymer or a lipophilic polymer.
상기 친수성폴리머는 카보머, 하이드록시에칠셀룰로오스 또는 카라기난검일 수 있으며, 친유성폴리머는 쉘락 또는 실리콘파우더일 수 있다.The hydrophilic polymer may be carbomer, hydroxyethyl cellulose or carrageenan gum, and the lipophilic polymer may be shellac or silicone powder.
상기 1차 입자를 제조하는 다당류는 옥수수전분, 감자전분, 고구마전분, 셀룰로오스, 덱스트린, 글루코스, 수크로스, 마니톨 또는 이들의 조합으로 이루어진 군으로부터 선택된 적어도 하나일 수 있다.The polysaccharide to prepare the primary particles may be at least one selected from the group consisting of corn starch, potato starch, sweet potato starch, cellulose, dextrin, glucose, sucrose, mannitol or a combination thereof.
상기 2차 입자를 제조하는 제 1알콜은 다가 알콜로서, 글리세린, 프로필렌글라이콜, 부틸렌글라이콜, 디프로필렌글라이콜, 폴리에틸렌글리콜, 솔비톨 또는 이들의 조합으로 이루어진 군으로부터 선택된 적어도 하나일 수 있다.The first alcohol for preparing the secondary particles may be at least one selected from the group consisting of glycerin, propylene glycol, butylene glycol, dipropylene glycol, polyethylene glycol, sorbitol, or a combination thereof. have.
상기 2차 입자를 제조하는 제 2알콜은 라우릴알콜, 세틸알콜, 스테아릴알콜, 세테아릴알콜, 올레일알콜, 베헤닐알콜, 리놀레일알콜, 운데실레닐알콜, 팔미톨레일알콜, 리놀레닐알콜, 아라키도닐알콜, 에루실알콜 또는 이들의 조합으로 이루어진 군으로부터 선택된 적어도 하나일 수 있다.Secondary alcohols for preparing the secondary particles are lauryl alcohol, cetyl alcohol, stearyl alcohol, cetearyl alcohol, oleyl alcohol, behenyl alcohol, linoleyl alcohol, undecenyl alcohol, palmitole alcohol, linol At least one selected from the group consisting of reenyl alcohol, arachidyl alcohol, erucyl alcohol, or a combination thereof.
상기 2차 입자를 제조하는 지방산은 스테아린산, 라우린산, 미리스틴산, 베헤닌산, 이소스테아린산, 올레인산 또는 이들의 조합으로 이루어진 군으로부터 선택된 적어도 하나일 수 있다.The fatty acid for preparing the secondary particles may be at least one selected from the group consisting of stearic acid, lauric acid, myristic acid, behenic acid, isostearic acid, oleic acid, or a combination thereof.
상기 2차 입자를 제조하는 다당류는 옥수수전분, 감자전분, 고구마전분, 셀룰로오스, 덱스트린, 글루코스, 수크로스, 마니톨 또는 이들의 조합으로 이루어진 군으로부터 선택된 적어도 하나일 수 있다.The polysaccharide to prepare the secondary particles may be at least one selected from the group consisting of corn starch, potato starch, sweet potato starch, cellulose, dextrin, glucose, sucrose, mannitol or a combination thereof.
상기 2차 입자를 제조하는 검류는 수용성고분자중합체로서 카라기난검, 구아검, 알긴산, 알긴산나트륨, 아가 또는 이들의 조합으로 이루어진 군으로부터 선택된 적어도 하나일 수 있다.The gum for preparing the secondary particles may be at least one selected from the group consisting of carrageenan gum, guar gum, alginic acid, sodium alginate, agar or a combination thereof as a water-soluble polymer.
이하, 본 발명의 구현예를 상세히 설명하기로 한다. 다만, 이는 예시로서 제시되는 것으로, 이에 의해 본 발명이 제한되지는 않으며 본 발명은 후술할 청구항의 범주에 의해 정의될 뿐이다.Hereinafter, embodiments of the present invention will be described in detail. However, this is presented as an example, by which the present invention is not limited and the present invention is defined only by the scope of the claims to be described later.
<< 실시예Example >>
1. 이온 복합체의 제조1. Preparation of Ionic Composites
1-1. 공중합체(1-1. Copolymer ( 폴리에틸렌글리콜Polyethylene glycol -폴리에틸렌이민-Polyethyleneimine 광감각제A photosensor )의 합성) Synthesis
환류 응축기 설치 후 메톡시 폴리에틸렌 글리콜(mPEG-COOH)(시그마, 5000Da) 10g을 250ml의 플라스크를 이용하여 메틸렌클로라이드(CHCl2) 50ml에 용해시켰다.After the reflux condenser was installed, 10 g of methoxy polyethylene glycol (mPEG-COOH) (Sigma, 5000 Da) was dissolved in 50 ml of methylene chloride (CHCl 2 ) using a 250 ml flask.
이후, 0.52 g의 N-하이드록시숙시닐이미드와 0.74 g의 다이사이클로카보다이이미드를 첨가한 후 20시간 동안 상온에서 반응시켰다. 다이사이클로헥실우레아를 필터 과정을 통해서 제거한 후 디에틸에테르(diethylether)에 침전시킴으로써 활성화 형태의 폴리에틸렌글리콜 (mPEG-NHS)을 수득하였다.Thereafter, 0.52 g of N-hydroxysuccinylimide and 0.74 g of dicyclocarbodiimide were added, followed by reaction at room temperature for 20 hours. Dicyclohexyl urea was removed through a filter process and then precipitated in diethylether to obtain activated polyethylene glycol (mPEG-NHS).
상기 수득한 폴리에틸렌글리콜 2g을 200ml의 클로로포름에 녹였다. 이후, 0.5g의 폴리에틸렌이민(Alfa Aesar, 1800da)을 50ml의 클로로포름에 녹인 다음, 여기에 상기 폴리에틸렌글리콜을 녹인 용액을 한 방울씩 떨어뜨림으로써 폴리에틸렌글리콜과 폴리에틸렌이민의 공유결합 반응을 수행하였다.2 g of the obtained polyethylene glycol was dissolved in 200 ml of chloroform. Thereafter, 0.5 g of polyethyleneimine (Alfa Aesar, 1800da) was dissolved in 50 ml of chloroform, and then a covalent reaction of polyethylene glycol and polyethyleneimine was performed by dropping a solution of the polyethylene glycol dissolved therein drop by drop.
이때, 상기 반응은 24시간 동안 수행하였으며, 반응 완료 후 진공농축 장치를 이용하여 총 부피가 30ml이 되도록 농축한 다음, 디에틸에테르(diethyl ether)에 침전시킴으로써 폴리에틸렌글리콜과 폴리에틸렌이민의 공유결합체를 수득하였다.At this time, the reaction was carried out for 24 hours, after completion of the reaction was concentrated to a total volume of 30ml using a vacuum concentrator, and then precipitated in diethyl ether to obtain a covalent conjugate of polyethylene glycol and polyethyleneimine It was.
상기 수득한 폴리에틸렌글리콜-폴리에틸렌이민(mPEG-PEI) 1g을 피오포바이드(pheophorbide) A (e.q., 0.07 mmol), 디사이클로 헥실카보디미드(dicyclohexyl carbodiimide, DCC) (1.2*pheophorbide A in moles) 그리고 N-하이드록시석시닐이미드(HOSu; 1.2*pheophorbide A in moles)을 20ml 인 디메틸 설폭사이드(dimethyl sulfoxide, DMSO)에 각각 녹인 후 3시간 동안 교반시켰다. 이후, 각각 두 용액을 섞은 후에 상온에서 24시간 반응시켰다.1 g of the polyethyleneglycol-polyethylenimine (mPEG-PEI) obtained above was treated with pheophorbide A (eq, 0.07 mmol), dicyclohexyl carbodiimide (DCC) (1.2 * pheophorbide A in moles) and N-hydroxysuccinylimide (HOSu; 1.2 * pheophorbide A in moles) was dissolved in 20 ml of dimethyl sulfoxide (DMSO) and stirred for 3 hours. Thereafter, the two solutions were mixed and reacted at room temperature for 24 hours.
또한, 투석막 (Spectra/Por; mol. wt. cutoff size, 1,000)을 이용하여 2일 동안 1차 증류수를 이용하여 투석한 다음, 최종 반응물을 동결건조를 통해 건조하여 폴리에틸렌글리콜-폴리에틸렌이민-피오포바이드(pheophorbide) A 공중합체를 수득하였다.In addition, the dialysis membrane (Spectra / Por; mol. Wt. Cutoff size, 1,000) was dialyzed with primary distilled water for 2 days, and then the final reaction product was dried by lyophilization to obtain polyethylene glycol-polyethylenimine-piopho. A pheophorbide A copolymer was obtained.
1-2. 결합체(1-2. concrete( 소광제Matting agent 접합 콘드로이틴  Junction Chondroitin 설페이트Sulfate )의 합성) Synthesis
콘드로이친 설페이트 0.1g을 20ml의 증류수에 녹였다. 건조된 DMSO에 BHQ3를 녹인 후 N-(3-디메틸아미노프로필)-N′-에틸카르보디이민 하이드로클로라이드(EDC), 4-디메틸아미노피리딘(DMAP)을 각각 BHQ의 몰비에 대해 1.5배로 첨가하였다.0.1 g of chondroitin sulfate was dissolved in 20 ml of distilled water. After dissolving BHQ3 in dried DMSO, N- (3-dimethylaminopropyl) -N'-ethylcarbodiimine hydrochloride (EDC) and 4-dimethylaminopyridine (DMAP) were each added 1.5-fold to the molar ratio of BHQ. .
이후, 두 용액을 각각 상온에서 3시간 동안 교반한 후 섞고 24시간 동안 반응시켰다. 미반응된 소광제(BHQ3)의 제거는 투석막(Spectra/Por; mol. wt. cutoff size, 1,000)을 이용하여 2일 동안 1차 증류수를 이용하여 투석함으로써 제거하였고, 투석 후 최종 반응물을 동결건조를 통해 건조시켜 소광제 접합 콘드로이틴 설페이트 결합체를 수득하였다.Then, the two solutions were each stirred at room temperature for 3 hours, then mixed and reacted for 24 hours. Removal of unreacted quencher (BHQ3) was removed by dialysis using primary distilled water for 2 days using a dialysis membrane (Spectra / Por; mol. Wt. Cutoff size, 1,000), and the final reaction product was freeze-dried after dialysis. Drying through gave a quencher conjugated chondroitin sulfate conjugate.
1-3. 공중합체 및 결합체의 합성1-3. Synthesis of Copolymers and Binders
전술한 1-1. 1-2.에서 제조된 폴리에틸렌글리콜-폴리에틸렌이민-피오포바이드(pheophorbide) A 공중합체와, 소광제 접합 콘드로이틴 설페이트 결합체를 3차 증류수에 각각 녹인 후, 질량비를 기준으로 각각 1.0:0.0, 1.0:0.3, 1.0:0.6, 1.0:1.2, 1.0:2.5, 및 1.0:5.0의 비율로 혼합하였다. 2시간 후, 상기 혼합물을 0.8㎛ 주사기 필터를 이용하여 필터링하여 이온 복합체를 제조하였다.1-1. The polyethyleneglycol-polyethylenimine-pheophorbide A copolymer prepared in 1-2 and the quencher conjugated chondroitin sulfate conjugate were dissolved in tertiary distilled water, respectively, and then 1.0: 0.0 and 1.0: 0.3, 1.0: 0.6, 1.0: 1.2, 1.0: 2.5, and 1.0: 5.0 in proportions. After 2 hours, the mixture was filtered using a 0.8 μm syringe filter to prepare an ionic complex.
2. 2. 건식다중캡슐형Dry Multiple Capsule 조성물을 포함하는 여드름 피부 개선제의 제조 Preparation of Acne Skin Enhancers Comprising Compositions
슈크로스 및 하이드록시에칠셀룰로오스를 에탄올 또는 정제수를 분산매로 하여 1차 입자를 제조하였고, 유화제, 레시틴, 만니톨, 지방산, 하이드록시프로필스타치포스페이트, 검류 및 티타늄옥사이드를 가열하여 에탄올 또는 정제수를 분산매로 하여 2차 입자를 제조한 후 제조된 2차 입자를 필요에 따라 친수성폴리머 또는 친유성폴리머로 3차 코팅하여 제조하였다.Sucrose and hydroxyethyl cellulose were prepared as primary particles by using ethanol or purified water as a dispersion medium, and an emulsifier, lecithin, mannitol, fatty acid, hydroxypropyl starch phosphate, gum and titanium oxide were heated to disperse ethanol or purified water. After preparing the secondary particles, the prepared secondary particles were prepared by tertiary coating with a hydrophilic polymer or a lipophilic polymer as needed.
하기 표 1은 건식다중캡슐형 조성물을 포함하는 여드름 피부 개선제의 조성에 관한 것이다.Table 1 below relates to the composition of the acne skin improver comprising a dry multicapsules composition.
성분ingredient 함량(wt%)Content (wt%)
1차 코팅Primary coating 슈크로스Sucrose 2020
하이드록시에칠셀룰로오스Hydroxyethyl Cellulose 0.10.1
에탄올(분산제)Ethanol (dispersant) 적량Quantity
2차 코팅Secondary coating 하이드록시프로필스타치포스페이트Hydroxypropyl starch phosphate 1010
유화제Emulsifier 22
레시틴lecithin 55
티타늄옥사이드 또는 징크옥사이드Titanium oxide or zinc oxide 2020
만니톨Mannitol 1One
옥수수전분Corn starch 1One
이온 복합체Ionic complex 100mg/100gr이하100mg / 100gr or less
정제수(분산제)Purified water (dispersant) 적량Quantity
3차 코팅3rd coating 쉘락Shellac 55
방부제antiseptic 미량a very small amount
에탄올(분산제)Ethanol (dispersant) 적량Quantity
※분산제는 휘발되는 분량으로 전체 분량에는 포함시키지 않는다.※ Dispersant is a volatilized amount, not included in the total amount.
본 발명은 상기 실시예에 한정되는 것이 아니라 서로 다른 다양한 크기로 제조될 수 있으며, 본 발명이 속하는 기술분야에서 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 실시될 수 있다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다.The present invention is not limited to the above embodiments, but can be manufactured in a variety of different sizes, those skilled in the art to which the present invention pertains to other specific forms without changing the technical spirit or essential features of the present invention It will be appreciated that it may be practiced. Therefore, it should be understood that the embodiments described above are exemplary in all respects and not restrictive.

Claims (14)

  1. 친수성 양이온 고분자와 광감작제가 결합된 공중합체 및 음이온성 기질 고분자와 소광제가 결합된 결합체를 포함하는 이온 복합체를 포함하는 여드름 피부개선용 건식다중캡슐형 조성물. A dry multicapsule type composition for acne skin improvement comprising an ionic complex comprising a copolymer in which a hydrophilic cationic polymer and a photosensitizer are combined, and an anionic substrate polymer and a quencher.
  2. 제 1 항에 있어서,The method of claim 1,
    상기 공중합체는 폴리에틸렌글리콜-폴리에틸렌이민-피오포바이드 (pheophorbide) A이며, 상기 결합체는 콘드로이틴설페이트-블랙홀 소광제(blackhole quencher, BHQ)인 것을 특징으로 하는 여드름 피부개선용 건식다중캡슐형 조성물. The copolymer is polyethylene glycol-polyethylenimine-pheophorbide (pheophorbide) A, and the combination is chondroitin sulfate-black hole quencher (BHQ), dry multicapsule-type composition for acne skin improvement.
  3. 제 1 항에 있어서,The method of claim 1,
    상기 이온 복합체는 총 조성물 100g에 대하여 0 초과~100mg 이하인 것을 특징으로 하는 여드름 피부개선용 건식다중캡슐형 조성물. The ion complex is a dry multicapsule-type composition for acne skin improvement, characterized in that more than 0 ~ 100mg per 100g total composition.
  4. 제 1 항에 있어서,The method of claim 1,
    상기 캡슐은 구형이고, 크기는 지름이 0mm초과 내지 10mm이하인 것을 특징으로 하는 여드름 피부개선용 건식다중캡슐형 조성물. The capsule is spherical, the size of the dry multicapsule composition for acne skin improvement, characterized in that the diameter is more than 0mm to less than 10mm.
  5. 제 1 항에 있어서,The method of claim 1,
    상기 조성물은 유화제 0.1-10중량%, 제1 알콜 0.1-10중량%, 제2 알콜 0.1-10중량%, 지방산 0.1-10중량%, 다당류 1-40중량%, 티타늄옥사이드 또는 징크옥사이드 1-40중량%, 검류 1-10중량% 및 잔량의 정제수를 더 포함하는 것을 특징으로 하는 여드름 피부개선용 건식다중캡슐형 조성물. The composition is 0.1-10% by weight emulsifier, 0.1-10% by weight of the first alcohol, 0.1-10% by weight of the second alcohol, 0.1-10% by weight of fatty acids, 1-40% by weight of polysaccharides, titanium oxide or zinc oxide 1-40 Dry multicapsule type composition for acne skin improvement, characterized in that it further comprises a weight%, gum 1-10% by weight and the remaining amount of purified water.
  6. 제 5 항에 있어서,The method of claim 5,
    상기 유화제는 분자 중에 수산기(-OH), 에테르기(-O-), 아미드기(-CONH), 에스테르기(-COO-)의 구조를 가진 비이온성계면활성제; 폴리옥시에틸렌형, 다가알콜에스테르형, 에틸렌옥사이드 및 프로필렌옥사이드블록공중합체, 아크릴산알킬공중합체의 폴리머릭계면활성제; 레시틴, 라놀린, 콜레스테롤, 사포닌의 천연계면활성제;로 이루어진 군으로부터 선택된 적어도 하나인 것을 특징으로 하는 여드름 피부개선용 건식다중캡슐형 조성물.The emulsifier may include a nonionic surfactant having a structure of a hydroxyl group (-OH), an ether group (-O-), an amide group (-CONH), and an ester group (-COO-) in a molecule; Polymeric surfactants of polyoxyethylene type, polyhydric alcohol ester type, ethylene oxide and propylene oxide block copolymers and alkyl acrylate copolymers; Lecithin, lanolin, cholesterol, saponin natural surfactant; Dry multicapsule composition for acne skin improvement, characterized in that at least one selected from the group consisting of.
  7. 제 5 항에 있어서,The method of claim 5,
    상기 제1 알콜은 다가 알콜로서, 글리세린, 프로필렌글라이콜, 부틸렌글라이콜, 디프로필렌글라이콜, 폴리에틸렌글리콜, 솔비톨 또는 이들의 조합으로 이루어진 군으로부터 선택된 적어도 하나인 것을 특징으로 하는 여드름 피부개선용 건식다중캡슐형 조성물.The first alcohol is a polyhydric alcohol, acne skin improvement, characterized in that at least one selected from the group consisting of glycerin, propylene glycol, butylene glycol, dipropylene glycol, polyethylene glycol, sorbitol or a combination thereof Dry multicapsules composition.
  8. 제 5 항에 있어서,The method of claim 5,
    상기 제2 알콜은 라우릴알콜, 세틸알콜, 스테아릴알콜, 세테아릴알콜, 올레일알콜, 베헤닐알콜, 리놀레일알콜, 운데실레닐알콜, 팔미톨레일알콜, 리놀레닐알콜, 아라키도닐알콜, 에루실알콜 또는 이들의 조합으로 이루어진 군으로부터 선택된 적어도 하나인 것을 특징으로 하는 여드름 피부개선용 건식다중캡슐형 조성물.The second alcohol is lauryl alcohol, cetyl alcohol, stearyl alcohol, cetearyl alcohol, oleyl alcohol, behenyl alcohol, linoleyl alcohol, undecylenyl alcohol, palmitole alcohol, linolenyl alcohol, arachidonyl Dry polycapsule composition for acne skin improvement, characterized in that at least one selected from the group consisting of alcohol, erucyl alcohol or a combination thereof.
  9. 제 5 항에 있어서,The method of claim 5,
    상기 지방산은 스테아린산, 라우린산, 미리스틴산, 베헤닌산, 이소스테아린산, 올레인산 또는 이들의 조합으로 이루어진 군으로부터 선택된 적어도 하나인 것을 특징으로 하는 여드름 피부개선용 건식다중캡슐형 조성물.The fatty acid may be at least one selected from the group consisting of stearic acid, lauric acid, myristic acid, behenic acid, isostearic acid, oleic acid, or a combination thereof.
  10. 제 5 항에 있어서,The method of claim 5,
    상기 다당류는 옥수수전분, 감자전분, 고구마전분, 셀룰로오스, 덱스트린, 글루코스, 수크로스, 마니톨 또는 이들의 조합으로 이루어진 군으로부터 선택된 적어도 하나인 것을 특징으로 하는 여드름 피부개선용 건식다중캡슐형 조성물.The polysaccharide is dry starch capsule composition for acne skin improvement, characterized in that at least one selected from the group consisting of corn starch, potato starch, sweet potato starch, cellulose, dextrin, glucose, sucrose, mannitol or a combination thereof.
  11. 제 5 항에 있어서,The method of claim 5,
    상기 검류는 수용성고분자중합체로서 카라기난검, 구아검, 알긴산, 알긴산나트륨, 아가 또는 이들의 조합으로 이루어진 군으로부터 선택된 적어도 하나인 것을 특징으로 하는 여드름 피부개선용 건식다중캡슐형 조성물.The gum is a water-soluble polymer, carrageenan gum, guar gum, alginic acid, sodium alginate, agar or a combination of at least one selected from the group consisting of a combination of the dry multicapsule-type composition for acne skin improvement.
  12. 제 1항 내지 제11항 중 어느 한 항의 여드름 피부개선용 건식다중캡슐형 조성물을 포함하는 여드름 피부 개선제의 제조방법으로서,Claims 1 to 11 of the acne skin improving method comprising a dry multicapsule-type composition for improving acne skin,
    다당류를 에탄올 또는 정제수를 분산매로 하여 1차 입자를 제조하는 단계;Preparing primary particles using a polysaccharide as a dispersion medium of ethanol or purified water;
    제1 알콜, 제 2알콜, 지방산, 다당류, 검류 및 티타늄옥사이드 또는 징크옥사이드를 단일 또는 이들의 조합으로 이루어진 군을 가열하여 에탄올 또는 정제수를 분산매로 하여 2차 입자를 제조하는 단계;를 포함하는 여드름 피부 개선제의 제조방법.A first alcohol, a second alcohol, a fatty acid, a polysaccharide, gum and titanium oxide or zinc oxide by heating a group consisting of a single or a combination thereof to prepare a secondary particle by using ethanol or purified water as a dispersion medium; Method for preparing a skin improver.
  13. 제 12항에 있어서,The method of claim 12,
    상기 2차 입자에 친수성폴리머 또는 친유성폴리머로 코팅하는 단계;를 더 포함하는 여드름 피부 개선제의 제조방법.Coating the secondary particles with a hydrophilic polymer or a lipophilic polymer.
  14. 제 13항에 있어서,The method of claim 13,
    상기 친수성폴리머는 카보머, 하이드록시에칠셀룰로오스 또는 카라기난검 이며, 친유성폴리머는 쉘락 또는 실리콘파우더인을 특징으로 하는 여드름 피부 개선제의 제조방법.The hydrophilic polymer is carbomer, hydroxyethyl cellulose or carrageenan gum, the lipophilic polymer is a method for producing acne skin improver, characterized in that the shellac or silicone powder.
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