KR100690318B1 - Process for preparing nano-hydrogel of hydrophilic polymer - Google Patents
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Abstract
본 발명은 수용성 고분자의 나노 하이드로겔의 제조방법에 관한 것이며, 더욱 상세하게는 고분자의 수용액을 지용성 계멸활성제를 이용하여 유기용제에 유화시키고, 에멀젼의 열역학적 평형을 조절하여 미셀의 크기를 수십 나노미터 수준으로 최소화시킨 것을 특징으로 하는 수용성 고분자의 나노 하이드로겔의 제조방법에 관한 것이다.The present invention relates to a method for preparing a nano hydrogel of a water-soluble polymer, and more particularly, to an aqueous solution of the polymer is emulsified in an organic solvent using a fat-soluble scavenger, and to control the thermodynamic equilibrium of the emulsion to reduce the size of the micelles to several tens of nanometers. It relates to a method for producing a nano hydrogel of a water-soluble polymer, characterized in that to minimize the level.
수용성, 고분자, 나노, 하이드로겔, 계면활성제Water Soluble, Polymer, Nano, Hydrogel, Surfactant
Description
도 1은, 본 발명에 따른 수용성 고분자의 나노 하이드로겔 제조과정의 각 단계를 모식적으로 표현한 도면;1 is a view schematically showing each step of the nano hydrogel manufacturing process of the water-soluble polymer according to the present invention;
도 2a 및 2b는 본 발명의 방법에 따라 실시예 1에서 제조된 알긴산 나노 하이드로겔의 주사전자현미경 사진;2a and 2b are scanning electron micrographs of the alginic acid nano hydrogel prepared in Example 1 according to the method of the present invention;
도 3은 본 발명의 방법에 따라 실시예 2에서 제조된 고화된 상태의 알긴산 나노 하이드로겔의 주사전자현미경 사진.Figure 3 is a scanning electron micrograph of the alginate nano hydrogel of the solidified state prepared in Example 2 according to the method of the present invention.
도 4는 본 발명의 방법에 따라 실시예 3에서 제조된 폴리비닐알코올 나노 하이드로겔의 주사전자현미경 사진.Figure 4 is a scanning electron micrograph of the polyvinyl alcohol nano hydrogel prepared in Example 3 according to the method of the present invention.
본 발명은 수용성 고분자의 나노 하이드로겔의 제조방법에 관한 것이며, 더욱 상세하게는 고분자의 수용액을 지용성 계멸활성제를 이용하여 유화시키고, 이렇게 얻어진 에멀젼의 열역학적 평형을 조절하여 미셀 내지 입자의 크기를 나노미터수준으로 최소화시킨 것을 특징으로 하는 수용성 고분자의 나노 하이드로겔의 제조 방법에 관한 것이다.The present invention relates to a method for preparing a nano hydrogel of a water-soluble polymer, and more particularly, to an aqueous solution of the polymer is emulsified using a fat-soluble scavenger activator, and to control the thermodynamic equilibrium of the emulsion thus obtained, the size of micelles to particles is measured in nanometers. It relates to a method for producing a nano hydrogel of a water-soluble polymer, characterized in that to minimize the level.
의약품 또는 화장품의 전달시스템으로 고분자의 겔 내지 입자가 사용된다. 즉 고분자의 초미세구립자와 같은 고분자 기질 내에 약물, 효소, 톡신, 조직, 세포, 박테리아, 바이러스 등의 화학적, 생물학적 물질을 봉입하여 생체 전달시스템으로 사용할 경우, 봉입되는 물질의 수분, 열, 산화에 의해 불활성화되거나 휘발되는 것을 방지하며, 생체적합성을 증가시키고, 지속성 혹은 서방성 제형을 제조할 수 있어 이러한 전달시스템이 의약품이나 화장품 등의 제조에 널리 이용되고 있다. 그런데 이들 전달시스템에 사용되는 고분자 겔 내지 입자는 생체 내의 각 원하는 표적위치에 침투할 수 있어야 전달하고자 하는 약물 등의 효과적인 전달이 가능하기 때문에 이들의 사이즈가 매우 중요하다. 특히, 뇌나 심장 등 나노 사이즈가 아니면 침투할 수 없는 기관에 약물을 전달하기 위해서는 고분자의 겔 내지 입자를 나노 사이즈로 얻는 것은 매우 중요하다.Polymeric gels or particles are used as delivery systems for pharmaceuticals or cosmetics. In other words, when chemical and biological substances such as drugs, enzymes, toxins, tissues, cells, bacteria, viruses, etc. are encapsulated in a polymer matrix such as ultrafine particles of the polymer and used as a biological delivery system, the moisture, heat, and oxidation of the encapsulated substances are used. To prevent inactivation or volatilization, to increase biocompatibility, and to prepare a sustained or sustained release formulation, such a delivery system is widely used in the manufacture of pharmaceuticals and cosmetics. However, since the polymer gel or particles used in these delivery systems can penetrate each desired target position in the living body, effective delivery of the drug to be delivered is possible, and their size is very important. In particular, in order to deliver drugs to organs that cannot penetrate other than nanoscale, such as the brain or heart, it is very important to obtain the gel or particles of the polymer in nanosize.
따라서, 의약품 또는 화장품 등의 유효성분을 전달시스템에 사용하기 위한 고분자의 미세 겔 내지 미세 입자의 제조방법에 대한 연구가 활발히 진행되고 있지만, 아직까지 나노 사이즈의 겔 내지 입자를 제조하는 방법에 대한 연구성과는 그다지 보편적이지 않다.Therefore, although research into the preparation method of the fine gel to the fine particles of the polymer for using the active ingredient, such as pharmaceuticals or cosmetics in the delivery system is actively progressed, the research on the method of producing a gel or particles of the nano-size up to now Performance is not very universal.
이러한 연구들의 유형을 살펴보면, 먼저 중합방법을 이용한 것으로서 유화중합을 이용하여 지용성 고분자인 폴리메틸메타크릴레이트 나노 입자를 제조하는 방법이 보고된 바 있으며(Encyclopedia of Pharmacy Technology, 165, 1994), 계면중합법을 이용하여 폴리알킬시아노아크릴레이트 나노 입자를 제조하는 방법도 보고된 바 있다(Int. J. Pharm. 28, 125, 1986). 다음으로 공중합체를 이용한 방법으로서 지용성 고분자인 폴리락타이드와 글리콜라이드 및 이들의 공중합체를 유기 용제에 녹이고 물에 분산시켜 미셀을 형성한 다음, 다량의 물을 추가하여 유기 용제가 물에 용출되도록 하여 나노 및 마이크로겔을 제조하는 방법이 보고된 바 있다(Pharm. Res. 15, 1056, 1988; int. J. Pharm. 188, 155, 1999; Coll. Surf. A: Physicochem. Eng. Asp. 182, 123, 2001). 그러나 이들은 모두 지용성 고분자를 이용한 나노입자 및 나노겔 형성에 관한 것으로, 친수성 내지 수용성 고분자를 이용한 것은 아니다.Looking at the types of these studies, a method of preparing polymethyl methacrylate nanoparticles, which are fat-soluble polymers using emulsion polymerization, has been reported (Encyclopedia of Pharmacy Technology, 165, 1994). A method for preparing polyalkylcyanoacrylate nanoparticles using a method has also been reported (Int. J. Pharm. 28, 125, 1986). Next, as a method using a copolymer, polylactide, glycolide, and copolymers thereof, which are fat-soluble polymers, are dissolved in an organic solvent, dispersed in water to form a micelle, and then a large amount of water is added to dissolve the organic solvent in water. Has been reported to prepare nano and microgels (Pharm. Res. 15, 1056, 1988; int. J. Pharm. 188, 155, 1999; Coll. Surf. A: Physicochem. Eng. Asp. 182). , 123, 2001). However, these are all related to the formation of nanoparticles and nanogels using fat-soluble polymers, and not hydrophilic or water-soluble polymers.
수용성 내지 수분산성을 갖는 화장품 또는 약제의 전달시스템으로 사용하기 위해서는 친수성 내지 수용성을 갖는 고분자의 하이드로겔 내지 입자를 제조할 필요가 있는데, 수용성 고분자의 나노 하이드로겔 내지 나노 입자의 제조는 지용성 고분자의 경우보다 연구성과가 훨씬 적다.In order to be used as a delivery system for water-soluble or water-dispersible cosmetics or drugs, it is necessary to prepare hydrogels or particles of polymers having hydrophilicity or water solubility. Much less research results.
수용성 고분자의 경우, 키토산과 지용성 고분자를 공중합하여 나노입자를 제조하였다는 보고가 있으나(Pharm. Res. 14, 1431, 1997; STP Pharm. Sci. 10, 77, 2000), 수용성이 극히 제한되어 하이드로겔을 형성하지는 못한다는 단점이 있다. 한편, 대한민국 특허공고 제164462호 공보에는 수용성 고분자인 알긴산염의 수용액을 계면활성제가 첨가된 유기용매에 분산, 교반시켜 에멀젼을 만든 다음, 칼슘 용액을 이 에멀젼에 첨가하여 겔화하고, 탈수 용매를 가해 탈수시키고 경화시켜 이루어지는 알긴산염 초미세구립자의 제조방법이 개시되어 있다. 그러나 이 방법에 의할 경우, 얻어지는 알긴산염의 입자의 평균이 수백 나노미터 내지 수십 마이크론 정도로 마이크로입자가 주류를 이루기 때문에 나노 사이즈를 요구하는 용도로 사용하기에는 부족하다. In the case of water-soluble polymers, it was reported that nanoparticles were prepared by copolymerizing chitosan and fat-soluble polymers (Pharm. Res. 14, 1431, 1997; STP Pharm. Sci. 10, 77, 2000). The disadvantage is that it does not form a gel. Meanwhile, Korean Patent Publication No. 164462 discloses an aqueous solution of an alginate, a water-soluble polymer, in an organic solvent added with a surfactant, followed by stirring to form an emulsion, and then a calcium solution is added to the emulsion to gel, and a dehydration solvent is added to dehydrate. A method for producing alginate ultrafine granules, which is made by curing and curing, is disclosed. However, according to this method, since the average particle size of the obtained alginate particles is in the order of several hundred nanometers to several tens of microns, it is insufficient to be used for applications requiring nano size.
본 발명은 의약품 내지 화장품 등에 사용되는 수용성 물질의 전달시스템에 사용되는 수용성 고분자를 사용하여, 평균적인 입자 사이즈가 수십 나노미터 단위를 갖는 하이드로겔을 제조하는 방법을 제공하는 것을 목적으로 한다. It is an object of the present invention to provide a method for producing a hydrogel having an average particle size of several tens of nanometers by using a water-soluble polymer used in a delivery system of a water-soluble substance used in medicine or cosmetics.
본 발명의 수용성 고분자의 나노 하이드로겔의 제조방법은,Method for producing a nano hydrogel of the water-soluble polymer of the present invention,
알긴산, 키토산, 카르복시메틸셀룰로오즈, 아크릴아미드의 단독 및 공중합체, 폴리아크릴산, 폴리에틸렌옥시드, 폴리비닐알코올, 폴리비닐알코올-폴리비닐아세테이트 공중합체, 폴리(N-비닐피롤리돈), 폴리하이드록시에틸아크릴레이트로 이루어진 군으로부터 선택되는 수용성 고분자를 물에 용해시키는 단계와;Alginic acid, chitosan, carboxymethylcellulose, homopolymers and copolymers of acrylamide, polyacrylic acid, polyethylene oxide, polyvinyl alcohol, polyvinyl alcohol-polyvinylacetate copolymers, poly (N-vinylpyrrolidone), polyhydroxy Dissolving a water-soluble polymer selected from the group consisting of ethyl acrylate in water;
중량기준으로 물과 3~50% 범위의 혼용성이 있고, 상기 수용성 고분자에 대해 용해성이 없는 유기 용제에 HLB값이 1~10의 범위에 있는 지용성 계면활성제를 혼합하고, 이를 다시 상기 수용성 고분자의 수용액과 혼합하는 단계와;A fat-soluble surfactant having a HLB value in the range of 1 to 10 is mixed with an organic solvent having a water content in the range of 3 to 50% by weight, and insoluble in the water-soluble polymer, and again Mixing with an aqueous solution;
상기 혼합용액이 열역학적 평형에 도달하도록 방치하는 단계와;Leaving the mixed solution to reach a thermodynamic equilibrium;
상기 혼합용액을 교반하여 미셀을 형성시키는 단계와;Stirring the mixed solution to form a micelle;
상기 미셀이 형성된 혼합액에 상기 유기용제를 더 첨가하고 교반하여 미셀로부터 물을 용출시키는 단계를 포함하는 과정에 의해 제조되는 것을 특징으로 한다.It is characterized in that it is prepared by the process comprising the step of eluting the water from the micelle by further adding and stirring the organic solvent to the mixed solution formed micelle.
한편, 필요에 따라서는 상기 제조된 수용성 고분자의 나노 하이드로겔에 상기 수용성 고분자의 가교제 또는 고화제를 첨가하여 수용성 고분자의 나노 하이드로겔의 표층을 고화시켜 수안정성이 향상된 고화된 수용성 고분자 나노 하이드로겔을 얻을 수도 있다.On the other hand, if necessary, by adding a cross-linking agent or a solidifying agent of the water-soluble polymer to the nano-hydrogel of the water-soluble polymer prepared to solidify the surface layer of the nano-hydrogel of the water-soluble polymer to improve the water stability of the water-soluble polymer nano hydrogel You can also get
도 1은 이상의 본 발명에 따른 수용성 고분자의 나노 하이드로겔 제조공정의 각 단계를 모식적으로 정리하여 나타낸 도면이다.1 is a view schematically showing each step of the nano hydrogel manufacturing process of the water-soluble polymer according to the present invention.
도 1을 참조하여 본 발명에 따른 수용성 고분자의 나노 하이드로겔 제조방법을 좀 더 상세하게 설명하면, 먼저 수용성 고분자를 물에 용해시킨 수용액과 지용성 계면활성제가 용해된 유기 용제를 각각 준비하여(A), 이들을 혼합하고 교반하면, W/O형 에멀젼이 생성되고, 수용성 고분자는 미셀 내에 용해되게 된다(B). 이때, 상기 유기 용제로 물과 다소간(중량기준으로 3~50%정도) 혼용성이 있는 클로로포름, 에틸아세테이트 및 프로필렌카보네이트 등을 사용하기 때문에 일정 시간의 정치시간을 거치면 물과 유기 용제는 부분적으로 서로 용해되어 열역학적 평형상태를 이루게 된다.Referring to Figure 1 in more detail the nano-hydrogel manufacturing method of the water-soluble polymer according to the present invention, by first preparing an aqueous solution in which a water-soluble polymer is dissolved in water and an organic solvent in which a fat-soluble surfactant is dissolved (A) When these mixtures are mixed and stirred, a W / O emulsion is formed, and the water-soluble polymer is dissolved in the micelle (B). At this time, since the chloroform, ethyl acetate, and propylene carbonate, which are mixed with water to some extent (about 3 to 50% by weight), are used as the organic solvent, the water and the organic solvent partially cross each other after a fixed time. Dissolves into thermodynamic equilibrium.
여기에 다시, 위에서 사용한 유기 용제를 다량 첨가하면, 물과 유기 용제간의 열역학적 평형을 유지하기 위해 미셀 내의 물이 유기용제 쪽으로 확산되어 나오게 되고 미셀은 축소된다(C). 이렇게 하여 일정 시간이 경과하면, 대부분의 물은 수용성 고분자로부터 분리되어 나오게 되어 미셀은 나노미터단위 수준으로 축소된다(D). Here again, when a large amount of the organic solvent used above is added, the water in the micelle diffuses out to the organic solvent to reduce the thermodynamic equilibrium between the water and the organic solvent and the micelle is reduced (C). In this way, after a certain period of time, most of the water is separated from the water-soluble polymer and the micelle is reduced to nanometer level (D).
그리고, 여기에 칼슘이온과 같은 고화제 내지 가교제를 첨가하면 수용성 고분자는 가교/고화된 상태로 된다(E). 이 상태에서 그대로 이용할 수도 있으며, 유기용제를 분리해 내어 최종적으로 수용성 고분자의 나노 하이드로겔을 얻을 수도 된다. 유기용제의 분리방법에 관한 기술은 보편화되어 있다.Then, when a solidifying agent or a crosslinking agent such as calcium ions is added thereto, the water-soluble polymer is in a crosslinked / solidified state (E). In this state, it may be used as it is, or an organic solvent may be separated to finally obtain a nano hydrogel of a water-soluble polymer. Techniques for separating organic solvents are common.
이상 설명한 본 발명에 따른 방법에 있어서, 상기 지용성 계면활성제는 HLB 값이 약 1~10범위에 있는 것 중에서 선택하여 사용하면 된다. 그리고 이러한 지용 성 계면활성제의 바람직한 예로는 L-α-포파티딜촐린, 수크로스, 아세틸화 수크로스 디에스테르, 라놀린 알코올, 올레산, 에틸렌글리콜 유도체, 아세틸화 글리세린 유도체, 폴리옥시에틸렌 옥틸페놀, 소르비탄 유도체, 소야 레시틴, 칼슘 도데실 벤젠 술포네이트, 데가글리세롤 유도체, 폴리에틸렌글리콜, 지방산 아민 등을 들 수 있지만, 반드시 이들에 한정되는 것은 아니다.In the method according to the present invention described above, the fat-soluble surfactant may be selected and used among those having an HLB value in the range of about 1 to 10. Preferred examples of such fat-soluble surfactants include L-α-phosphatidylcholine, sucrose, acetylated sucrose diester, lanolin alcohol, oleic acid, ethylene glycol derivatives, acetylated glycerin derivatives, polyoxyethylene octylphenol, sorbent Although a non-elastic derivative, soya lecithin, calcium dodecyl benzene sulfonate, a degglycerol derivative, polyethyleneglycol, fatty acid amine, etc. are mentioned, It is not necessarily limited to these.
한편, 상술한 본 발명의 방법은 알긴산, 키토산, 카르복시메틸셀룰로오즈, 아크릴아미드의 단독 및 공중합체, 폴리아크릴산, 폴리에틸렌옥시드, 폴리비닐알코올, 폴리비닐알코올-폴리비닐아세테이트 공중합체, 폴리(N-비닐피롤리돈), 폴리하이드록시에틸아크릴레이트와 같은 천연 및 합성 수용성 고분자에 대해 적용 가능하다.On the other hand, the above-described method of the present invention is a single and copolymer of alginic acid, chitosan, carboxymethyl cellulose, acrylamide, polyacrylic acid, polyethylene oxide, polyvinyl alcohol, polyvinyl alcohol-polyvinylacetate copolymer, poly (N- Vinylpyrrolidone), polyhydroxyethyl acrylate, and the like.
이때 사용되는 상기 수용성 고분자의 평균분자량은 100~1,000,000사이의 범위이며, 바람직하게는 약 700~200,000의 범위 내인 것을 선택한다. 상기 범위는 실험결과로 얻어진 경험치이지만, 상기 범위에서 다소 벗어나도 본 발명의 실시가 불가능한 것은 아니다.At this time, the average molecular weight of the water-soluble polymer used is in the range of 100 ~ 1,000,000, preferably selected in the range of about 700 ~ 200,000. The above range is an empirical value obtained as a result of the experiment, but the invention is not impossible even if somewhat out of the above range.
한편, 상술한 바와 같이 본 발명의 방법에 따라 얻어진 수용성 고분자의 나노 하이드로겔에 고화제 내지 가교제를 첨가하여 수안정성이 향상된 표층이 고화된 형태를 얻을 수 있는데, 상기 수용성 고분자가 알긴산일 경우에는 얻어진 나노 하이드로겔에 염화칼슘 수용액과 같은 칼슘이온을 첨가하여 고분자 사이에 가교를 형성하여 고화시킬 수 있다. On the other hand, by adding a solidifying agent or a crosslinking agent to the nano hydrogel of the water-soluble polymer obtained according to the method of the present invention as described above, it is possible to obtain a form in which the surface layer with improved water stability is solidified. By adding calcium ions such as calcium chloride aqueous solution to the nano hydrogel, it is possible to solidify by forming crosslinks between the polymers.
이상 설명한 본 발명의 방법에 의해 얻어진 수용성 고분자의 나노 하이드로 겔 내지 나노 입자는 제조 과정 중에 물과 유기 용제간의 열역학적 평형을 유지하기 위해 미셀 내의 물이 미셀 외부로 확산되어 가면서 미셀의 크기가 최소한으로 줄어들기 때문에 평균직경이 수십 나노미터 내지 수백 나노미터수준으로 얻어지게 된다.The nano hydrogels to nanoparticles of the water-soluble polymers obtained by the method of the present invention described above are reduced in size to a minimum as the water in the micelle diffuses out of the micelles in order to maintain the thermodynamic equilibrium between the water and the organic solvent during the manufacturing process. Therefore, the average diameter is obtained in the tens of nanometers to several hundred nanometers.
이하, 바람직한 실시예를 참조하여 본 발명을 더욱 상세하게 설명한다. 이하의 실시예들은 본 발명을 설명하기 위한 것으로, 이들 실시예에 의해 본 발명의 범위가 제한되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to preferred embodiments. The following examples are provided to illustrate the present invention, and the scope of the present invention is not limited by these examples.
실시예Example
실시예Example 1 : 알긴산 1: alginic acid 나노 하이드로겔의Of nano hydrogel 제조 Produce
알긴산 0.1g을 물 10㎖와 함께 둥근바닥 플라스크에 넣고, 상온에서 용해하여 알긴산 수용액을 제조하였다. 또, 별도의 둥근바닥 플라스크에 L-α-포파티딜촐린 0.02g과 클로로포름 10㎖를 넣고 잘 흔들어 용해시켰다.0.1 g of alginic acid was added to a round bottom flask with 10 ml of water, and dissolved at room temperature to prepare an aqueous alginic acid solution. In addition, 0.02 g of L-α-phosphatidylcurin and 10 ml of chloroform were added to another round bottom flask, and the mixture was shaken well to dissolve.
위에서 얻은 알긴산 수용액과 클로로포름 용액을 상온에서 혼합하고, 10분간 방치하여 두 용액이 열역학적 평형에 도달하도록 한 다음, 균질화기를 이용하여 13,000rpm으로 10분간 교반하여 미셀을 형성하였다. 다음으로, 미셀이 형성된 상기 혼합액에 클로로포름 100㎖를 첨가하고 하룻동안 상온에서 약하게 교반하여, 미셀로부터 물이 용출되도록 하여 알긴산 나노 하이드로겔을 얻었다.The aqueous alginic acid solution and the chloroform solution obtained above were mixed at room temperature, left for 10 minutes to reach thermodynamic equilibrium, and then stirred at 13,000 rpm for 10 minutes using a homogenizer to form micelles. Next, 100 ml of chloroform was added to the mixed solution in which the micelles were formed, and stirred gently at room temperature for one day. Thus, water was eluted from the micelles to obtain an alginate nano hydrogel.
이렇게 하여 얻어진 알긴산 나노 하이드로겔을 주사전자현미경을 사용하여 50,000배와 250,000배로 확대하여 얻은 사진을 도 2a 및 2b에 나타내었다. 도 2a 내지 도 2b에서 보는 바와 같이, 본 실시예에서 얻은 알긴산의 나노 하이드로겔은 입자 직경이 50㎚ 정도로 균일하게 얻어졌다.The alginate nano hydrogel obtained in this way was magnified 50,000 times and 250,000 times using a scanning electron microscope is shown in Figures 2a and 2b. As shown in Figures 2a to 2b, the nano hydrogel of the alginic acid obtained in this example was obtained uniformly with a particle diameter of about 50nm.
실시예Example 2 : 알긴산 2: alginic acid 나노 하이드로겔의Of nano hydrogel 분리 detach
실시예 1과 동일한 방법으로 알긴산 나노 하이드로겔 분산액을 제조한 후, 서서히 교반하면서 염화칼슘용액(100㎖, 5중량%)을 첨가하였다. 혼합액은 하룻동안 상온에서 서서히 교반하여 고화된 알긴산 나노 하이드로겔을 얻었다. 수율은 95% 이상이었다. Alginate nano hydrogel dispersion was prepared in the same manner as in Example 1, and then calcium chloride solution (100 ml, 5 wt%) was added with gentle stirring. The mixture was stirred slowly at room temperature for one day to obtain a solidified alginate nano hydrogel. The yield was 95% or more.
이렇게 얻어진 고화된 알긴산 나노 하이드로겔을 주사전자현미경을 사용하여 50,000배 확대하여 촬영한 사진을 도 3에 나타내었다. 도 3에서 보는 바와 같이 본 실시예에서 얻어진 고환된 알긴산 나노 하이드로겔의 직경은 평균 100㎚ 정도로 균일하게 얻어졌다.The solidified alginic acid nano hydrogel thus obtained was photographed at 50,000 times magnification using a scanning electron microscope. As shown in FIG. 3, the diameters of the testicular alginic acid nano hydrogels obtained in this example were uniformly obtained at an average of about 100 nm.
실시예Example 3 : 폴리비닐알코올 3: polyvinyl alcohol 나노 하이드로겔의Of nano hydrogel 제조 Produce
폴리비닐알코올 0.2g을 물 10㎖와 함께 둥근바닥 플라스크에 넣고, 상온에서 용해하여 폴리비닐알코올 수용액을 제조하였다. 또, 별도의 둥근바닥 플라스크에 L-α-포파티딜촐린 0.02g과 클로로포름 10㎖를 넣고 잘 흔들어 용해시켰다.0.2 g of polyvinyl alcohol was added to a round bottom flask with 10 ml of water and dissolved at room temperature to prepare an aqueous polyvinyl alcohol solution. In addition, 0.02 g of L-α-phosphatidylcurin and 10 ml of chloroform were added to another round bottom flask, and the mixture was shaken well to dissolve.
위에서 얻은 폴리비닐알코올 수용액과 클로로포름 용액을 상온에서 혼합하고, 10분간 방치하여 두 용액이 열역학적 평형에 도달하도록 한 다음, 균질화기를 이용하여 13,000rpm으로 10분간 교반하여 미셀을 형성하였다. 다음으로, 미셀이 형성된 상기 혼합액에 클로로포름 100㎖를 첨가하고 하룻동안 상온에서 약하게 교반하여, 미셀로부터 물이 용출되도록 하여 폴리비닐알코올 나노 하이드로겔을 얻었다.The aqueous polyvinyl alcohol solution and the chloroform solution obtained above were mixed at room temperature, allowed to stand for 10 minutes to reach the thermodynamic equilibrium, and then stirred at 13,000 rpm for 10 minutes using a homogenizer to form micelles. Next, 100 ml of chloroform was added to the mixed solution in which the micelles were formed, and stirred gently at room temperature for one day. Thus, water was eluted from the micelles to obtain a polyvinyl alcohol nano hydrogel.
이렇게 하여 얻어진 폴리비닐알코올 나노 하이드로겔을 주사전자현미경을 이용하여 60,000배 확대하여 촬영한 사진을 도 4에 나타내었다. 도 4에서 보는 바와 같이 본 실시예에서 얻어진 폴리비닐알코올 나노 하이드로겔의 평균입자직경은 100㎚정도로 균일하였다.The photograph obtained by enlarging the polyvinyl alcohol nano hydrogel thus obtained using a scanning electron microscope at 60,000 times is shown in FIG. 4. As shown in FIG. 4, the average particle diameter of the polyvinyl alcohol nano hydrogel obtained in this example was uniform at about 100 nm.
상기한 바와 같이, 본 발명의 방법에 따르면 입자 직경이 수십 내지 수백 나노미터수준이고 평균 입경이 수십나노미터인 수용성 고분자의 나노 하이드로겔이 얻어지기 때문에, 특히 나노 수준의 입자 크기를 필요로 하는 수용성 및 수분산성을 갖는 기능성 화장품 및 약제분야의 전달시스템의 구축에 유용하게 이용될 수 있다.As described above, according to the method of the present invention, since a nano hydrogel of a water-soluble polymer having a particle diameter of several tens to hundreds of nanometers and an average particle diameter of several tens of nanometers is obtained, in particular, a water-soluble solution requiring a nano-level particle size is required. And it can be usefully used in the construction of a delivery system in the field of functional cosmetics and pharmaceuticals having water dispersibility.
또한, 본 발명에 따른 방법은 모든 친수성 고분자에 대해 적용할 수 있기 때문에, 필요로 하는 수용성 고분자 물질을 선택하여 다양하게 응용할 수 있는 이점이 있다.In addition, since the method according to the present invention can be applied to all hydrophilic polymers, there is an advantage in that a variety of applications can be selected by selecting the required water-soluble polymer material.
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| US8703904B2 (en) * | 2007-09-19 | 2014-04-22 | The Regents Of The University Of Colorado | Hydrogels and methods for producing and using the same |
| CN103167868B (en) * | 2010-10-14 | 2016-08-03 | 株式会社爱茉莉太平洋 | Hydrogel particle being coated with lipid and preparation method thereof |
| KR101428145B1 (en) * | 2011-11-24 | 2014-08-08 | (주)아모레퍼시픽 | Water-insoluble gel composition and manufacturing method of the same |
| KR102078334B1 (en) * | 2013-02-28 | 2020-02-18 | 아이큐어 주식회사 | Sheetless hydrogel film and Preparing method ofthere |
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