KR102613981B1 - Solubilizing composition of insoluble material and solubilizing mehtod of insoluble material using the same - Google Patents
Solubilizing composition of insoluble material and solubilizing mehtod of insoluble material using the same Download PDFInfo
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- KR102613981B1 KR102613981B1 KR1020210053844A KR20210053844A KR102613981B1 KR 102613981 B1 KR102613981 B1 KR 102613981B1 KR 1020210053844 A KR1020210053844 A KR 1020210053844A KR 20210053844 A KR20210053844 A KR 20210053844A KR 102613981 B1 KR102613981 B1 KR 102613981B1
- Authority
- KR
- South Korea
- Prior art keywords
- aqueous solution
- poorly water
- mogroside
- curcumin
- soluble
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Classifications
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- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/35—Ketones, e.g. benzophenone
- A61K8/355—Quinones
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
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- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/49—Solubiliser, Solubilising system
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/57—Compounds covalently linked to a(n inert) carrier molecule, e.g. conjugates, pro-fragrances
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Abstract
본 발명은 난수용성 물질의 수용액 가용화 조성물 및 이를 이용한 난수용성 물질의 수용액 가용화 방법에 관한 것이다. 구체적으로, 본 발명의 난수용성 물질의 수용액 가용화 조성물은 이데베논, 레스베라트롤, 커큐민, 비스디메톡시커큐민, 탁솔, 퀘르세틴 및 올레오놀산과 같이 유용한 생리활성을 가지고 있으나 물에 대한 용해도가 낮은 난수용성 물질의 수용액 가용화 정도를 유의적으로 증가시킴으로써, 이들 난수용성 물질을 다양한 분야에 기능성 소재로서 적용할 수 있도록 난수용성 물질의 수용액 가용화 용도에 유용하게 사용될 수 있다.The present invention relates to a composition for solubilizing a poorly water-soluble material in an aqueous solution and a method for solubilizing a poorly water-soluble material in an aqueous solution using the same. Specifically, the aqueous solution solubilization composition of poorly water-soluble substances of the present invention is a poorly water-soluble substance that has useful physiological activity but has low water solubility, such as idebenone, resveratrol, curcumin, bisdimethoxycurcumin, taxol, quercetin, and oleonic acid. By significantly increasing the degree of aqueous solution solubilization, these poorly water-soluble materials can be usefully used for aqueous solution solubilization of poorly water-soluble materials so that they can be applied as functional materials in various fields.
Description
본 발명은 난수용성 물질의 수용액 가용화 조성물 및 이를 이용한 난수용성 물질의 수용액 가용화 방법에 관한 것이다.The present invention relates to a composition for solubilizing a poorly water-soluble material in an aqueous solution and a method for solubilizing a poorly water-soluble material in an aqueous solution using the same.
최근 화장품 및 식의약품 산업에서 생리활성소재의 발굴을 위해 그 활성뿐만 아니라 생체 적합성 및 생체 안전성이 우수한 천연성분을 개발하는 것의 중요성이 대두되고 있다. 그러나, 이들 천연성분들은 그 특징이 전반적으로 상이하여 이들 모두를 충분히 안정화시킬 수 있는 제형이 개발되지 않은 실정이다.Recently, in order to discover bioactive materials in the cosmetics and food and pharmaceutical industries, the importance of developing natural ingredients that are not only active but also have excellent biocompatibility and biosafety has emerged. However, since the characteristics of these natural ingredients are generally different, a formulation that can sufficiently stabilize all of them has not been developed.
현재 높은 효능을 나타내고 있는 천연성분은 잠재적 가치가 클 것으로 기대되는데, 이들 중 약 40%가 낮은 용해도로 인해 개발단계에조차 진입하지 못하고 있다. 이와 같은 난수용성 물질을 조작하여 용해도를 증진시키는 과정을 가용화(solubilization)라고 하며, 난수용성 물질을 물에 가용화할 수 있는 방법이 많은 연구자들에 의해 개발되고 있다. 이러한 가용화 기술은 산업에 미칠 수 있는 파급효과가 매우 크기 때문에, 향후 난수용성 물질의 가용화 기술은 그 발전이 더욱 가속화될 것으로 예상된다.Natural ingredients currently showing high efficacy are expected to have great potential value, but about 40% of them have not even entered the development stage due to low solubility. The process of manipulating poorly water-soluble substances to improve solubility is called solubilization, and many researchers are developing methods to solubilize poorly water-soluble substances in water. Because this solubilization technology has a very large impact on the industry, it is expected that the development of solubilization technology for poorly water-soluble substances will further accelerate in the future.
소수성의 난수용성 물질은 친수기가 없거나 매우 적을 경우, 또는 분자배열을 방해하는 위치에 있을 경우, 분자간 강한 소수성 상호작용으로 인하여 물에 가용화되기 어려운 분자배열을 이루는 것이 특징이다. 이러한 소수성 물질의 분자배열에 변형을 줄 수 있으면, 난수용성 물질이 분산 또는 가용화될 수 있는데, 이렇게 분자배열의 변화를 유도할 수 있는 물질이 계면활성제이다.Hydrophobic, poorly water-soluble substances have the characteristic of forming a molecular arrangement that is difficult to solubilize in water due to strong hydrophobic interactions between molecules when there are no or very few hydrophilic groups, or when they are in a position that interferes with the molecular arrangement. If the molecular arrangement of such hydrophobic substances can be modified, poorly water-soluble substances can be dispersed or solubilized. The substance that can induce this change in molecular arrangement is a surfactant.
화장품 및 식의약품 산업에서 유용하게 사용하고 있는 계면활성제는 매우 다양하다. 종래에는 합성 및 천연 계면활성제를 이용하여 초고압유화장치(ultrahomogenizer) 등에 의한 물리적 조건에서 나노입자화하는 기술이 개발되었다. 그러나, 상기 기술은 고농도로 난수용성 물질을 가용화하는 것과 그 안정성에 한계가 있어 새로운 방법의 개발이 요구되고 있다.There are a wide variety of surfactants that are usefully used in the cosmetics and food and pharmaceutical industries. Previously, technology was developed to convert nanoparticles into nanoparticles under physical conditions using an ultrahigh pressure emulsifier (ultrahomogenizer) using synthetic and natural surfactants. However, the above technology has limitations in solubilizing poorly water-soluble substances at high concentrations and its stability, so the development of new methods is required.
이와 관련하여, 대한민국 등록특허 제10-1138258호는 2종류의 친수성 천연고분자로부터 유래한 올리고머를 이용하여 소수성 동공구조를 갖는 구조체를 형성시키고, 난수용성 물질을 동공구조에 봉입시켜 가용화하는 방법을 개시하고 있다.In this regard, Republic of Korea Patent No. 10-1138258 discloses a method of forming a structure with a hydrophobic pore structure using oligomers derived from two types of hydrophilic natural polymers and solubilizing it by encapsulating a poorly water-soluble material in the pore structure. I'm doing it.
본 발명의 목적은 난수용성 물질의 수용액 가용화 조성물을 제공하는 것이다.The object of the present invention is to provide a composition for solubilizing a poorly water-soluble substance in aqueous solution.
본 발명의 다른 목적은 난수용성 물질을 포함하는 수용액 가용화 복합체 및 상기 복합체를 포함하는 조성물을 제공하는 것이다.Another object of the present invention is to provide an aqueous solution-solubilized complex containing a poorly water-soluble substance and a composition containing the complex.
본 발명의 또 다른 목적은 난수용성 물질의 수용액 가용화 방법을 제공하는 것이다.Another object of the present invention is to provide a method for solubilizing a poorly water-soluble substance in an aqueous solution.
상기 목적을 달성하기 위하여, 본 발명은 인삼류 추출물 및 모그로사이드 배당체로 구성된 군으로부터 선택되는 어느 하나 이상을 포함하는 난수용성 물질의 수용액 가용화 조성물을 제공한다.In order to achieve the above object, the present invention provides an aqueous solution-solubilizing composition of a poorly water-soluble substance containing at least one selected from the group consisting of ginseng extracts and mogroside glycosides.
또한, 본 발명은 난수용성 물질; 및 인삼류 추출물 및 모그로사이드 배당체로 구성된 군으로부터 선택되는 어느 하나 이상으로 구성된 수용액 가용화 복합체를 제공한다.In addition, the present invention is a poorly water-soluble material; and provides an aqueous solution solubilization complex composed of at least one selected from the group consisting of ginseng extracts and mogroside glycosides.
또한, 본 발명은 상기 수용액 가용화 복합체를 포함하는 조성물을 제공한다.Additionally, the present invention provides a composition comprising the aqueous solution-solubilized complex.
나아가, 본 발명은 난수용성 물질에 인삼류 추출물 및 모그로사이드 배당체로 구성된 군으로부터 선택되는 어느 하나 이상을 혼합하여 복합체를 제조하는 단계를 포함하는 난수용성 물질의 수용액 가용화 방법을 제공한다.Furthermore, the present invention provides a method for solubilizing a poorly water-soluble material in an aqueous solution, comprising preparing a complex by mixing a poorly water-soluble material with at least one selected from the group consisting of ginseng extract and mogroside glycoside.
본 발명의 난수용성 물질의 수용액 가용화 조성물은 이데베논, 레스베라트롤, 커큐민, 비스디메톡시커큐민, 탁솔, 퀘르세틴 및 올레오놀산과 같이 유용한 생리활성을 가지고 있으나 물에 대한 용해도가 낮은 난수용성 물질의 수용액 가용화 정도를 유의적으로 증가시킴으로써, 이들 난수용성 물질을 다양한 분야에 기능성 소재로서 적용할 수 있도록 난수용성 물질의 수용액 가용화 용도에 유용하게 사용될 수 있다.The aqueous solution solubilization composition of poorly water-soluble substances of the present invention solubilizes poorly water-soluble substances such as idebenone, resveratrol, curcumin, bisdimethoxycurcumin, Taxol, quercetin, and oleonic acid, which have useful physiological activity but have low water solubility. By significantly increasing the degree, these poorly water-soluble materials can be usefully used for solubilizing aqueous solutions of poorly water-soluble materials so that they can be applied as functional materials in various fields.
도 1은 본 발명의 일 실시예에서 산양삼 잎 추출물로 레스베라트롤, 커큐민 또는 비스디메톡시커큐민을 수용액 가용화 시킨 결과를 TLC 분석으로 확인한 결과 도면이다(1: 산양삼 잎 추출물, 2: 레스베라트롤, 3: 수용액 가용화된 레스베라트롤, 4: 커큐민, 5: 수용액 가용화된 커큐민, 6: 비스디메톡시커큐민, 7: 수용액 가용화된 비스디메톡시커큐민).
도 2는 본 발명의 일 실시예에서 모그로사이드 V와 복합체를 형성한 이데베논(A), 레스베라트롤(B), 커큐민(C), 비스디메톡시커큐민(D), 탁솔(E), 퀘르세틴(F) 또는 올레오놀산(G)의 수용액 가용화 정도를 확인한 결과 그래프이다.
도 3은 본 발명의 일 실시예에서 모그로사이드 V와 복합체를 형성한 이데베논, 레스베라트롤, 커큐민, 비스디메톡시커큐민, 탁솔, 퀘르세틴 또는 올레오놀산의 수용액 가용화 정도를 비교한 결과 그래프이다.
도 4는 본 발명의 일 실시예에서 커큐민을 수용액 가용화시키는 과정에서 사용되는 에탄올의 농도를 확인한 결과 그래프이다.
도 5는 본 발명의 일 실시예에서 커큐민을 수용액 가용화시키는 과정에서 사용되는 모그로사이드 V의 농도를 확인한 결과 그래프이다.
도 6은 본 발명의 일 실시예에서 커큐민을 수용액 가용화시키는 과정에서 사용되는 커큐민의 농도를 확인한 결과 그래프이다.
도 7은 본 발명의 일 실시예에서 수용액 가용화된 커큐민의 세포독성을 B16F10 세포(A) 또는 RAW564.7 세포(B)에서 확인한 결과 그래프이다.
도 8은 본 발명의 일 실시예에서 수용액 가용화된 커큐민의 멜라닌 생성 억제를 세포 내(A) 및 세포 외(B)에서 확인한 결과 그래프이다.
도 9는 본 발명의 일 실시예에서 수용액 가용화된 커큐민의 티로시아제 활성 억제 효과를 확인한 결과 그래프이다.
도 10은 본 발명의 일 실시예에서 수용액 가용화된 커큐민의 산화질소 억제 활성을 확인한 결과 그래프이다.
도 11은 본 발명의 일 실시예에서 물(A), 모그로사이드(B) 또는 모그로사이드 V(C)로 수용액 가용화된 커큐민을 육안으로 확인한 결과 도면이다.Figure 1 is a diagram showing the results of solubilizing resveratrol, curcumin, or bisdimethoxycurcumin in aqueous solution with wild ginseng leaf extract in an embodiment of the present invention confirmed by TLC analysis (1: wild ginseng leaf extract, 2: resveratrol, 3: aqueous solution solubilization resveratrol, 4: curcumin, 5: curcumin solubilized in aqueous solution, 6: bisdimethoxycurcumin, 7: bisdimethoxycurcumin solubilized in aqueous solution).
Figure 2 shows idebenone (A), resveratrol (B), curcumin (C), bisdimethoxycurcumin (D), taxol (E), and quercetin ( F) This is a graph showing the results of confirming the degree of solubilization of aqueous solution of oleanolic acid (G).
Figure 3 is a graph comparing the degree of solubilization in aqueous solutions of idebenone, resveratrol, curcumin, bisdimethoxycurcumin, Taxol, quercetin or oleonolic acid complexed with mogroside V in an embodiment of the present invention.
Figure 4 is a graph showing the results of confirming the concentration of ethanol used in the process of solubilizing curcumin in an aqueous solution in one embodiment of the present invention.
Figure 5 is a graph showing the results of confirming the concentration of mogroside V used in the process of solubilizing curcumin in an aqueous solution in one embodiment of the present invention.
Figure 6 is a graph showing the results of confirming the concentration of curcumin used in the process of solubilizing curcumin in an aqueous solution in one embodiment of the present invention.
Figure 7 is a graph showing the cytotoxicity of curcumin solubilized in aqueous solution in B16F10 cells (A) or RAW564.7 cells (B) in an example of the present invention.
Figure 8 is a graph showing the results of confirming the inhibition of melanin production by curcumin solubilized in aqueous solution intracellularly (A) and extracellularly (B) in one embodiment of the present invention.
Figure 9 is a graph showing the results of confirming the inhibitory effect of curcumin solubilized in aqueous solution on tyrosyase activity in an example of the present invention.
Figure 10 is a graph showing the results of confirming the nitric oxide inhibitory activity of curcumin solubilized in aqueous solution in an embodiment of the present invention.
Figure 11 is a diagram showing the results of visual inspection of curcumin solubilized in an aqueous solution with water (A), mogroside (B), or mogroside V (C) in one embodiment of the present invention.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명은 인삼류 추출물 및 모그로사이드 배당체로 구성된 군으로부터 선택되는 어느 하나 이상을 포함하는 난수용성 물질의 수용액 가용화 조성물을 제공한다.The present invention provides an aqueous solution-solubilizing composition of a poorly water-soluble substance containing at least one selected from the group consisting of ginseng extracts and mogroside glycosides.
상기 인삼류는 통상의 기술분야에 알려진 모든 종류의 인삼을 포함할 수 있다. 일례로, 상기 인삼류는 산삼, 산양삼, 배양근, 수인삼, 화기삼, 전칠삼 및 홍삼으로 구성된 군으로부터 선택되는 어느 하나 이상일 수 있다. 상기 인삼류는 전초, 뿌리, 줄기, 잎, 열매 및 꽃으로 구성된 군으로부터 선택되는 어느 하나 이상일 수 있다. 본 발명의 일 실시예에서, 상기 인삼류 추출물은 인삼류의 잎 추출물일 수 있다. 더욱 구체적으로, 상기 인삼류의 잎 추출물은 산양삼의 잎 추출물일 수 있다.The ginseng species may include all types of ginseng known in the art. For example, the ginseng may be any one or more selected from the group consisting of wild ginseng, wild ginseng, cultured root, water ginseng, flowering ginseng, Jeonchi ginseng, and red ginseng. The ginseng family may be any one or more selected from the group consisting of whole plants, roots, stems, leaves, fruits, and flowers. In one embodiment of the present invention, the ginseng extract may be a ginseng leaf extract. More specifically, the leaf extract of the ginseng family may be a leaf extract of wild ginseng.
상기 인삼류 추출물은 하기의 단계를 포함하는 제조방법에 의해 제조될 수 있다:The ginseng extract can be prepared by a manufacturing method comprising the following steps:
1) 인삼류에 추출용매를 가하여 추출물을 제조하는 단계;1) Preparing an extract by adding an extraction solvent to ginseng;
2) 단계 1)의 추출물을 여과하는 단계; 및2) filtering the extract of step 1); and
3) 단계 2)의 여과된 여과물을 감압농축한 후 건조하는 단계.3) Concentrating the filtrate from step 2) under reduced pressure and drying it.
또한, 상기 추출용매는 물, 알코올 또는 이의 혼합물일 수 있다. 상기 알코올은 C1 내지 C2의 저급 알코올 수 있고, 구체적으로, 상기 알코올은 에탄올, 메탄올 또는 주정일 수 있다. 상기 추출용매는 통상의 기술자에 의해 적절한 양으로 사용될 수 있다.Additionally, the extraction solvent may be water, alcohol, or a mixture thereof. The alcohol may be a C 1 to C 2 lower alcohol, and specifically, the alcohol may be ethanol, methanol, or alcohol. The extraction solvent can be used in an appropriate amount by those skilled in the art.
상기 추출방법은 진탕추출, Soxhlet 추출 또는 환류추출일 수 있다. 이때, 추출 시간은 0.5 내지 50시간, 0.5 내지 40시간 또는 0.5 내지 30시간일 수 있다. 상기 추출은 1회 이상 반복 추출할 수 있다. 상기 추출 조건 및 방법은 통상의 기술자에 의해 적절히 선택될 수 있으며, 필요에 따라 변경될 수 있다.The extraction method may be shaking extraction, Soxhlet extraction, or reflux extraction. At this time, the extraction time may be 0.5 to 50 hours, 0.5 to 40 hours, or 0.5 to 30 hours. The extraction can be repeated one or more times. The extraction conditions and methods may be appropriately selected by those skilled in the art and may be changed as needed.
한편, 상기 단계 3)의 감압농축은 진공감압농축기 또는 진공회전증발기를 이용할 수 있다. 또한, 상기 건조는 감압건조, 진공건조, 비등건조, 분무건조 또는 동결건조일 수 있고, 구체적으로는 동결건조일 수 있다.Meanwhile, the vacuum concentration in step 3) can be performed using a vacuum vacuum concentrator or a vacuum rotary evaporator. Additionally, the drying may be reduced pressure drying, vacuum drying, boiling drying, spray drying, or freeze drying, and specifically may be freeze drying.
본 명세서에서 사용된 용어, "모그로사이드(mogroside)"는 나한과(Siraitia grosvenorii)에 함유된 물질 중 하나로서, 천연첨가물로 분류되는 감미료를 의미한다. 상기 모그로사이드는 나한과의 열매에 주로 존재하는데 트리테르펜 글리코시드 패밀리의 하나일 수 있다. 상기 모그로사이드는 당과 글리코시드 결합을 형성하여 모그로사이드 배당체의 형태로 존재하는 것일 수 있다.The term “mogroside” used in this specification refers to a sweetener classified as a natural additive, which is one of the substances contained in Siraitia grosvenorii . The mogroside is mainly present in the fruit of Monk fruit and may be one of the triterpene glycoside family. The mogroside may form a glycosidic bond with a sugar and exist in the form of a mogroside glycoside.
상기 모그로사이드 배당체는 통상의 기술분야에 배당체를 형성할 수 있는 것으로 알려진 모든 종류의 당과 모그로사이드가 결합한 것일 수 있다. 구체적으로, 상기 당은 단당류, 이당류, 다당류를 모두 포함할 수 있고, 일례로, 상기 당은 글루코스, 프룩토스, 갈락토스, 말토스, 자당, 엿당, 유당, 녹말, 글리코겐 등일 수 있다. 한편, 상기 모그로사이드 배당체는 통상의 기술분야에 알려진 모든 모그로사이드 배당체를 포함할 수 있고, 일례로, 상기 모그로사이드 배당체는 모그로사이드 II, 모그로사이드 III, 모그로사이드 IV, 모그로사이드 V, 모그로사이드 VI 및 시아메노사이드 I로 구성된 군으로부터 선택되는 어느 하나 이상일 수 있다.The mogroside glycoside may be a combination of mogroside and any type of sugar known in the art to form glycosides. Specifically, the sugar may include monosaccharides, disaccharides, and polysaccharides. For example, the sugar may be glucose, fructose, galactose, maltose, sucrose, maltose, lactose, starch, glycogen, etc. Meanwhile, the mogroside glycoside may include all mogroside glycosides known in the art. For example, the mogroside glycoside includes Mogroside II, Mogroside III, Mogroside IV, Mog It may be any one or more selected from the group consisting of rhoside V, mogroside VI and siamenoside I.
한편, 상기 난수용성 물질은 통상의 기술분야에 알려진 모든 종류의 난수용성 물질을 포함할 수 있다. 구체적으로, 상기 난수용성 물질은 이데베논, 레스베라트롤, 커큐민, 비스디메톡시커큐민, 탁솔, 퀘르세틴 및 올레오놀산으로 구성된 군으로부터 선택되는 어느 하나 이상일 수 있다. 본 발명의 일 실시예에서, 인삼류 추출물에 의해 수용액 가용화되는 난수용성 물질은 레스베라트롤, 커큐민 또는 비스디메톡시커큐민일 수 있고, 모그로사이드 배당체에 의해 수용액 가용화되는 난수용성 물질은 이데베논, 레스베라트롤, 커큐민, 비스디메톡시커큐민, 탁솔, 퀘르세틴 또는 올레오놀산일 수 있다.Meanwhile, the poorly water-soluble material may include all types of poorly water-soluble material known in the art. Specifically, the poorly water-soluble substance may be any one or more selected from the group consisting of idebenone, resveratrol, curcumin, bisdimethoxycurcumin, taxol, quercetin, and oleanolic acid. In one embodiment of the present invention, the poorly water-soluble substance solubilized in aqueous solution by ginseng extract may be resveratrol, curcumin, or bisdimethoxycurcumin, and the poorly water-soluble substance solubilized in aqueous solution by mogroside glycoside may be idebenone, resveratrol, and curcumin. , bisdimethoxycurcumin, Taxol, quercetin or oleonolic acid.
또한, 본 발명은 난수용성 물질; 및 인삼류 추출물 및 모그로사이드 배당체로 구성된 군으로부터 선택되는 어느 하나 이상으로 구성된 수용액 가용화 복합체를 제공한다.In addition, the present invention is a poorly water-soluble material; and provides an aqueous solution solubilization complex composed of at least one selected from the group consisting of ginseng extracts and mogroside glycosides.
상기 수용액 가용화 복합체를 구성하는 난수용성 물질, 인삼류 추출물 및 모그로사이드 배당체는 상기 서술한 바와 같은 특징을 가질 수 있다.The poorly water-soluble substances, ginseng extracts, and mogroside glycosides constituting the aqueous solution-solubilized complex may have the characteristics described above.
상기 난수용성 물질과 인삼류 추출물 또는 모그로사이드 배당체는 통상의 기술자에 의해 적절한 양으로 혼합될 수 있다. 구체적으로, 상기 인삼류 추출물 또는 모그로사이드 배당체는 난수용성 물질 100 중량부를 기준으로 5 내지 30 중량부, 5 내지 25 중량부, 5 내지 20 중량부 또는 5 내지 15 중량부의 함량으로 혼합될 수 있다. 상기 범위 외의 함량으로 난수용성 물질과 인삼류 추출물 또는 모그로사이드 배당체가 혼합되는 경우, 복합체의 형성 효율이 낮아져 난수용성 물질의 수용액 가용화 정도가 유의적으로 증가하지 않거나 감소될 수 있다.The poorly water-soluble substance and the ginseng extract or mogroside glycoside can be mixed in an appropriate amount by a person skilled in the art. Specifically, the ginseng extract or mogroside glycoside may be mixed in an amount of 5 to 30 parts by weight, 5 to 25 parts by weight, 5 to 20 parts by weight, or 5 to 15 parts by weight based on 100 parts by weight of the poorly water-soluble material. If a poorly water-soluble material is mixed with a ginseng extract or mogroside glycoside in an amount outside the above range, the formation efficiency of the complex may be lowered and the degree of solubilization of the poorly water-soluble material in aqueous solution may not be significantly increased or may be reduced.
또한, 본 발명은 상기 수용액 가용화 복합체를 포함하는 조성물을 제공한다.Additionally, the present invention provides a composition comprising the aqueous solution-solubilized complex.
본 발명에 따른 조성물에 포함되는 수용액 가용화 복합체는 상기 서술한 바와 같은 특징을 가질 수 있다. 일례로, 상기 수용액 가용화 복합체는 난수용성 물질; 및 인삼류 추출물 및 모그로사이드 배당체로 구성된 군으로부터 선택되는 어느 하나 이상으로 구성될 수 있다. 이때, 복합체를 구성하는 난수용성 물질과 인삼류 조성물 또는 모그로사이드 배당체의 함량은 상기 서술한 바와 같은 특징을 가질 수 있다.The aqueous solution-solubilized complex included in the composition according to the present invention may have the characteristics described above. In one example, the aqueous solution solubilized complex includes a poorly water-soluble material; And it may be composed of any one or more selected from the group consisting of ginseng extracts and mogroside glycosides. At this time, the content of the poorly water-soluble substance constituting the complex and the ginseng composition or mogroside glycoside may have the characteristics described above.
나아가, 본 발명은 난수용성 물질에 인삼류 추출물 및 모그로사이드 배당체로 구성된 군으로부터 선택되는 어느 하나 이상을 혼합하여 복합체를 제조하는 단계를 포함하는 난수용성 물질의 수용액 가용화 방법을 제공한다.Furthermore, the present invention provides a method for solubilizing a poorly water-soluble material in an aqueous solution, comprising preparing a complex by mixing a poorly water-soluble material with at least one selected from the group consisting of ginseng extract and mogroside glycoside.
본 발명에 따른 수용액 가용화 방법에 사용되는 난수용성 물질, 인삼류 추출물 또는 모그로사이드 배당체는 상기 서술한 바와 같은 특징을 가질 수 있다.The poorly water-soluble substance, ginseng extract, or mogroside glycoside used in the aqueous solution solubilization method according to the present invention may have the characteristics described above.
구체적으로, 상기 수용액 가용화 방법은 난수용성 물질을 저급 알코올에 용해시키고, 인삼류 추출물 및 모그로사이드 배당체로 구성된 군으로부터 선택되는 어느 하나 이상을 물에 용해시킨 후, 이들을 혼합함으로써 수행될 수 있다. 다른 측면에서, 상기 수용액 가용화 방법은 난수용성 물질을 인삼류 추출물 및 모그로사이드 배당체로 구성된 군으로부터 선택되는 어느 하나 이상과 혼합한 후, 여기에 물 및 저급 알코올의 혼합물을 첨가함으로써 수행될 수 있다.Specifically, the aqueous solution solubilization method can be performed by dissolving a poorly water-soluble substance in lower alcohol, dissolving one or more selected from the group consisting of ginseng extract and mogroside glycoside in water, and then mixing them. In another aspect, the aqueous solution solubilization method can be performed by mixing a poorly water-soluble material with one or more selected from the group consisting of ginseng extracts and mogroside glycosides, and then adding a mixture of water and lower alcohol thereto.
상기 혼합 시, 난수용성 물질과 인삼류 추출물 및 모그로사이드 배당체로 구성된 군으로부터 선택되는 어느 하나 이상을 균일하게 혼합하기 위해 교반이 동반될 수 있다.During the mixing, stirring may be accompanied to uniformly mix one or more selected from the group consisting of poorly water-soluble substances, ginseng extracts, and mogroside glycosides.
이때, 상기 인삼류 추출물 및 모그로사이드 배당체는 난수용성 물질 100 중량부를 기준으로 5 내지 30 중량부, 5 내지 25 중량부, 5 내지 20 중량부 또는 5 내지 15 중량부의 함량으로 혼합될 수 있다. At this time, the ginseng extract and mogroside glycoside may be mixed in an amount of 5 to 30 parts by weight, 5 to 25 parts by weight, 5 to 20 parts by weight, or 5 to 15 parts by weight based on 100 parts by weight of the poorly water-soluble material.
본 발명에 따른 수용액 가용화 방법은 에탄올을 제거하고 형성된 복합체를 수득하는 단계를 더 포함할 수 있다. 에탄올의 제거는 통상의 기술자에 의해 적절히 수행될 수 있다.The aqueous solution solubilization method according to the present invention may further include the step of removing ethanol and obtaining the formed complex. Removal of ethanol can be appropriately performed by a person skilled in the art.
이하, 본 발명을 하기 실시예에 의해 상세히 설명한다, 단, 하기 실시예는 본 발명을 예시하기 위한 것일 뿐, 이들에 의해 본 발명이 제한되는 것은 아니다. 본 발명의 청구범위에 기재된 기술적 사상과 실질적으로 동일한 구성을 갖고 동일한 작용 효과를 이루는 것은 어떠한 것이라도 본 발명의 기술적 범위에 포함된다.Hereinafter, the present invention will be described in detail through the following examples. However, the following examples are only for illustrating the present invention and are not intended to limit the present invention thereto. Anything that has substantially the same structure as the technical idea described in the claims of the present invention and achieves the same operation and effect is included in the technical scope of the present invention.
제조예Manufacturing example 1. One. 산양삼wild ginseng 추출물의 제조 Preparation of extract
300 ㎎의 산양삼 잎에 10 ㎖의 70% 에탄올을 첨가하여 1시간 동안 교반하면서 중탕추출하였다. 이후, 소니케이터 VCX130(Sonics and Materials Inc., 미국)을 사용하여, 40의 진폭으로 3분동안 초음파 처리 후, 5분 동안 유예기간을 가지면서 초음파 처리를 수행하였다. 초음파 처리한 시료를 통상적인 조건으로 원심분리하여 상층액을 산약삼 추출물로 회수하였다. 상기 과정을 3회 반복하여 회수된 추출물을 모두 모아 회전증발기 Hei-VAP 플래티늄 1(Hei-VAP platinum 1, Heidolph instruments, 독일)을 이용하여 에탄올을 제거하고, 동결건조기 FD-550(Eyela, 일본)으로 건조시켜 산양삼 추출물 분말을 수득하였다. 수득된 산양삼 추출물 내 진세노사이드의 함량을 통상적인 방법으로 확인하고, 하기 표 1에 나타내었다.10 ml of 70% ethanol was added to 300 mg of wild ginseng leaves, and extraction was performed by stirring for 1 hour. Afterwards, using a Sonicator VCX130 (Sonics and Materials Inc., USA), ultrasonic treatment was performed at an amplitude of 40 for 3 minutes, followed by a 5-minute grace period. The sonicated sample was centrifuged under conventional conditions, and the supernatant was recovered as a wild herbal ginseng extract. The above process was repeated three times, all recovered extracts were collected, ethanol was removed using a rotary evaporator Hei-VAP platinum 1 (Heidolph instruments, Germany), and freeze dryer FD-550 (Eyela, Japan) was used. It was dried to obtain wild ginseng extract powder. The content of ginsenosides in the obtained wild ginseng extract was confirmed by a conventional method and is shown in Table 1 below.
표 1에 나타난 바와 같이, 제조된 산양삼 잎 추출물에서 다양한 종류의 진세노사이드가 포함된 것을 확인하였다.As shown in Table 1, it was confirmed that the produced wild ginseng leaf extract contained various types of ginsenosides.
실시예Example 1. One. 커큐민curcumin 및 and 산양삼wild ginseng 추출물의 복합체 제조 Complex preparation of extracts
상기 제조된 산양삼 추출물 분말을 이용하여 난용성 화합물인 커큐민(curcumin)과의 복합체를 다음과 같은 방법을 제조하였다.A complex with curcumin, a poorly soluble compound, was prepared using the wild ginseng extract powder prepared above using the following method.
먼저, 5 ㎎의 제조예 1의 산양삼 잎 추출물 및 0.5 ㎎의 커큐민을 혼합하고, 여기에 에탄올을 첨가하여 20분 동안 방치시킨 후, 12,000 rpm에서 15분 동안 원심분리하여 펠렛을 수득함으로써 커큐민 및 산양삼 추출물의 복합체를 얻었다.First, 5 mg of wild ginseng leaf extract of Preparation Example 1 and 0.5 mg of curcumin were mixed, ethanol was added thereto, left for 20 minutes, and then centrifuged at 12,000 rpm for 15 minutes to obtain a pellet, thereby producing curcumin and wild ginseng. A complex of extracts was obtained.
실시예Example 2. 2. 비스디메톡시커큐민Bisdimethoxycurcumin 및 and 산양삼wild ginseng 추출물의 복합체 제조 Complex preparation of extracts
커큐민 대신, 비스디메톡시커큐민(bisdemethoxycurcumin)을 사용하여 비스디메톡시커큐민 및 산양삼 추출물의 복합체를 얻은 것을 제외하고는, 상기 실시예 1과 동일한 조건 및 방법으로 복합체를 제조하였다.A complex of bisdimethoxycurcumin and wild ginseng extract was prepared under the same conditions and methods as in Example 1, except that instead of curcumin, bisdemethoxycurcumin was used to obtain a complex of bisdemethoxycurcumin and wild ginseng extract.
실시에 3. 3. In implementation. 레스베라트롤Resveratrol 및 and 산양삼wild ginseng 추출물의 복합체 제조 Complex preparation of extracts
커큐민 대신, 레스베라트롤(resveratrol)을 사용하여 레스베라트롤 및 산양삼 추출물의 복합체를 얻은 것을 제외하고는, 상기 실시예 1과 동일한 조건 및 방법으로 복합체를 제조하였다.A complex of resveratrol and wild ginseng extract was prepared under the same conditions and methods as in Example 1, except that resveratrol was used instead of curcumin.
실시예Example 4. 4. 이데베논Idebenone 및 and 모그로사이드mogroside 배당체의 복합체 제조 Preparation of complexes of glycosides
모그로사이드 V를 이용하여 난용성 화합물인 이데베논(idebenone)과의 복합체를 다음과 같은 방법으로 제조하였다.A complex with mogroside V and idebenone, a poorly soluble compound, was prepared as follows.
먼저, 10 ㎎의 모그로사이드 V(mogroside V)를 물에 녹여 모그로사이드 V 수용액을 준비하였다. 한편, 난수용성 물질인 1 ㎎의 이데베논은 에탄올에 용해시켜 이데베논 용액을 준비하였다. 상기 모그로사이드 V 수용액과 이데베논 용액을 혼합하여 28℃에서 30분 동안 교반한 뒤, 12,000 rpm에서 5분 동안 원심분리하여 펠렛을 수득함으로써 이데베논 및 모그로사이드 V 복합체를 얻었다.First, 10 mg of mogroside V was dissolved in water to prepare a mogroside V aqueous solution. Meanwhile, 1 mg of idebenone, a poorly water-soluble substance, was dissolved in ethanol to prepare an idebenone solution. The mogroside V aqueous solution and the idebenone solution were mixed and stirred at 28°C for 30 minutes, then centrifuged at 12,000 rpm for 5 minutes to obtain a pellet, thereby obtaining the idebenone and mogroside V complex.
실시예Example 5. 5. 레스베라트롤Resveratrol 및 and 모그로사이드mogroside 배당체의 복합체 제조 Preparation of complexes of glycosides
이데베논 대신, 레스베라트롤을 사용하여 레스베라트롤 및 모그로사이드 V 복합체를 얻은 것을 제외하고는, 상기 실시예 4와 동일한 조건 및 방법으로 복합체를 제조하였다.A complex was prepared under the same conditions and methods as in Example 4, except that resveratrol was used instead of idebenone to obtain a resveratrol and mogroside V complex.
실시예Example 6. 6. 커큐민curcumin 및 and 모그로사이드mogroside 배당체의 복합체 제조 Preparation of complexes of glycosides
이데베논 대신, 커큐민을 사용하여 커큐민 및 모그로사이드 V 복합체를 얻은 것을 제외하고는, 상기 실시예 4와 동일한 조건 및 방법으로 복합체를 제조하였다.A complex was prepared under the same conditions and methods as in Example 4, except that curcumin and mogroside V complex were obtained using curcumin instead of idebenone.
실시예Example 7. 7. 비스디메톡시커큐민Bisdimethoxycurcumin 및 and 모그로사이드mogroside 배당체의 복합체 제조 Preparation of complexes of glycosides
이데베논 대신, 비스디메톡시커큐민을 사용하여 비스디메톡시커큐민 및 모그로사이드 V 복합체를 얻은 것을 제외하고는, 상기 실시예 4와 동일한 조건 및 방법으로 복합체를 제조하였다.The complex was prepared under the same conditions and methods as in Example 4, except that bisdimethoxycurcumin and mogroside V complex were obtained using bisdimethoxycurcumin instead of idebenone.
실시예Example 8. 8. 탁솔taxol 및 and 모그로사이드mogroside 배당체의 복합체 제조 Preparation of complexes of glycosides
이데베논 대신, 탁솔(taxol)을 사용하여 탁솔 및 모그로사이드 V 복합체를 얻은 것을 제외하고는, 상기 실시예 1과 동일한 조건 및 방법으로 복합체를 제조하였다.A complex was prepared under the same conditions and methods as in Example 1, except that Taxol and Mogroside V complex was obtained using taxol instead of idebenone.
실시예Example 9. 9. 퀘르세틴Quercetin 및 and 모그로사이드mogroside 배당체의 복합체 제조 Preparation of complexes of glycosides
이데베논 대신, 퀘르세틴(quercetin)을 사용하여 퀘르세틴 및 모그로사이드 V 복합체를 얻은 것을 제외하고는, 상기 실시예 4와 동일한 조건 및 방법으로 복합체를 제조하였다.The complex was prepared under the same conditions and methods as in Example 4, except that the quercetin and mogroside V complex was obtained using quercetin instead of idebenone.
실시예Example 10. 10. 올레오놀산Oleonolic acid 및 and 모그로사이드mogroside 배당체의 복합체 제조 Preparation of complexes of glycosides
이데베논 대신, 올레오놀산(oleanolic acid)을 사용하여 올레오놀산 및 모그로사이드 V 복합체를 얻은 것을 제외하고는, 상기 실시예 4와 동일한 조건 및 방법으로 복합체를 제조하였다.The complex was prepared under the same conditions and methods as in Example 4, except that oleanolic acid was used instead of idebenone to obtain the oleanolic acid and mogroside V complex.
실험예Experiment example 1. One. 난수용성poorly water soluble 물질의 수용액 aqueous solution of a substance 가용화Solubilization 정도 확인-(1) Check the degree - (1)
상기에서 난수용성 물질 및 산양삼 추출물의 복합체를 물에 용해시켰을 때 수용액 가용화 정도를 다음과 같이 확인하였다.When the complex of the poorly water-soluble substance and wild ginseng extract above was dissolved in water, the degree of aqueous solution solubilization was confirmed as follows.
구체적으로, 실시예 1 내지 3에서 제조된 복합체에 50 ㎕의 증류수를 첨가하고 잘 현탁시킨 후, 12,000 rpm에서 15분 동안 원심분리한 상등액만 취해 시료로서 사용하였다. 상기 시료를 실리카겔 TLC 플레이트에 점적한 후, 아세토니트릴 및 물을 85:15의 부피비로 혼합한 전개용매를 사용하여 전개시켰다. 난용성 물질의 수용화 정도는 TLC 플레이트를 UV 254 ㎚의 파장 하에서 확인하거나, 5% 황산을 포함하는 메탄올 발색 시약을 처리하고, 120℃에서 5분 동안 건조시켜 확인하였다. 그 결과, 수용화된 정도를 정량적으로 계산한 결과를 표 2에, TCL 플레이트를 확인한 결과를 도 1에 나타내었다.Specifically, 50 ㎕ of distilled water was added to the complexes prepared in Examples 1 to 3, suspended well, and then centrifuged at 12,000 rpm for 15 minutes, and only the supernatant was taken and used as a sample. The sample was spotted on a silica gel TLC plate and developed using a developing solvent mixed with acetonitrile and water in a volume ratio of 85:15. The degree of water solubility of poorly soluble substances was confirmed by using a TLC plate under a UV wavelength of 254 nm, or by treating them with a methanol coloring reagent containing 5% sulfuric acid and drying them at 120°C for 5 minutes. As a result, the results of quantitatively calculating the degree of water solubilization are shown in Table 2, and the results of checking the TCL plate are shown in Figure 1.
(㎍/㎖)Degree of water solubility of the substance alone
(㎍/㎖)
수용성 정도(㎍/㎖)Wild ginseng extract complex
Degree of water solubility (㎍/㎖)
표 2에 나타난 바와 같이, 커큐민, 비스디메톡시커큐민 또는 레스베라트롤의 수용액 가용화 정도가 산양삼 추출물과의 복합체를 형성함으로써 유의적으로 증가하였다. 이는 TLC 플레이트를 확인한 도 2에서도 확인할 수 있었다.As shown in Table 2, the degree of solubilization of curcumin, bisdimethoxycurcumin or resveratrol in aqueous solution was significantly increased by forming a complex with wild ginseng extract. This could also be confirmed in Figure 2, where the TLC plate was checked.
실험예Experiment example 2. 2. 난수용성poorly water soluble 물질의 수용액 aqueous solution of a substance 가용화Solubilization 정도 확인-(2) Check the degree - (2)
상기에서 난수용성 물질 및 모그로사이드 배당체 복합체를 물에 용해시켰을 때 수용액 가용화 정도를 다음과 같이 확인하였다.When the poorly water-soluble substance and the mogroside glycoside complex above were dissolved in water, the degree of aqueous solution solubilization was confirmed as follows.
구체적으로, 실시예 3 내지 10에서 제조된 복합체에 50 ㎕의 증류수를 첨가하고 잘 현탁시킨 후, 12,000 rpm에서 15분 동안 원심분리한 상등액만 취해 시료로서 사용하였다. 상기 시료의 수용액 가용화 정도를, U3000 UHPLC/CAD(ultra high performance liquid chromatography-charged aerosol detection) 기기 및 YMC Triart C18 250×4.6 ㎜, S-5 μM, 12 ㎚ 컬럼을 사용하여 분석을 수행하였다. 이때, 이동상은 하기 표 3에 기재된 바와 같은 조건으로, UV 227, 425, 279 또는 306 ㎚에서 수행하고, 대조군으로는 모그로사이드 V와 복합체를 형성하지 않은 난수용성 물질을 사용하였다. 그 결과는 하기 표 4, 도 2 및 3에 나타내었다.Specifically, 50 μl of distilled water was added to the complexes prepared in Examples 3 to 10, the mixture was well suspended, and then centrifuged at 12,000 rpm for 15 minutes, and only the supernatant was taken and used as a sample. The degree of aqueous solubilization of the sample was analyzed using a U3000 UHPLC/CAD (ultra high performance liquid chromatography-charged aerosol detection) instrument and a YMC Triart C18 250×4.6 mm, S-5 μM, 12 nm column. At this time, the mobile phase was performed at UV 227, 425, 279 or 306 nm under the conditions shown in Table 3 below, and a poorly water-soluble material that did not form a complex with mogroside V was used as a control. The results are shown in Table 4 and Figures 2 and 3 below.
(㎍/㎖)Degree of water solubility of the substance alone
(㎍/㎖)
수용성 정도(㎍/㎖)Mogroside V complex
Degree of water solubility (㎍/㎖)
표 4, 도 2 및 3에 나타난 바와 같이, 이데베논, 레스베라트롤, 커큐민, 비스디메톡시커큐민, 탁솔, 퀘르세틴 및 올레오놀산 모두 물에 수용액 가용화되지 않았으나, 이들을 모그로사이드 V와 복합체로 형성하면 수용액 가용화 정도가 현저히 증가하였다.As shown in Table 4 and Figures 2 and 3, idebenone, resveratrol, curcumin, bisdimethoxycurcumin, taxol, quercetin, and oleonic acid were all not solubilized in water, but when they were complexed with mogroside V, they were dissolved in aqueous solution. The degree of solubilization increased significantly.
실험예Experiment example 3. 3. 난수용성poorly water soluble 물질 및 substance and 모그로사이드mogroside 배당체의 복합체 제조 조건 확인 Confirmation of manufacturing conditions for glycoside complex
3-1. 용매농도 확인3-1. Check solvent concentration
난수용성 물질과 모그로사이드 배당체의 복합체 제조과정에서 사용되는 에탄올의 농도에 따른 수용액 가용화 정도를 확인하여, 최적의 에탄올 농도 조건을 확인하였다. 실험은 커큐민을 10, 20, 30, 40, 50, 60, 70, 80, 90 또는 100%(v/v)에 용해시킨 것을 제외하고는, 상기 실시예 4와 동일한 조건 및 방법으로 복합체를 제조하고, 커큐민의 수용화 정도는 실험예 2에 기재된 바와 같은 방법으로 확인하였다. 그 결과, 에탄올 농도에 따른 커큐민의 수용화 정도를 도 4에 나타내었다.The degree of aqueous solution solubilization according to the concentration of ethanol used in the production process of the complex of poorly water-soluble substances and mogroside glycosides was confirmed, and the optimal ethanol concentration conditions were confirmed. In the experiment, a complex was prepared under the same conditions and methods as in Example 4, except that curcumin was dissolved in 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100% (v/v). And the degree of water solubility of curcumin was confirmed by the same method as described in Experimental Example 2. As a result, the degree of water solubility of curcumin according to ethanol concentration is shown in Figure 4.
도 4에 나타난 바와 같이, 에탄올의 농도에 의존적으로 커큐민의 수용화 정도가 유의적으로 증가하였다. 특히, 80%(v/v) 이상의 에탄올을 사용한 경우에 약 7,000 ㎍/㎖의 커큐민을 수용액상에 용해시킴으로써, 난수용성 물질의 수용화에 사용되는 에탄올은 80%(v/v) 이상의 농도로 사용하는 것이 효과적임을 알 수 있었다.As shown in Figure 4, the degree of water solubility of curcumin significantly increased depending on the concentration of ethanol. In particular, when 80% (v/v) or more of ethanol is used, about 7,000 ㎍/㎖ of curcumin is dissolved in the aqueous solution, so that the ethanol used to dissolve poorly water-soluble substances in water is at a concentration of 80% (v/v) or more. It was found to be effective to use.
3-2. 3-2. 모그로사이드mogroside 배당체의 농도 확인 Check the concentration of glycosides
난수용성 물질과 모그로사이드 배당체의 복합체 제조과정에서 사용되는 모그로사이드 배당체의 농도에 따른 수용액 가용화 정도를 확인하여, 최적의 모그로사이드 배당체 농도 조건을 확인하였다. 실험은 10 ㎎의 커큐민을 1.0, 3.0, 5.0, 7.5, 10.0, 12.5, 15 또는 20%(w/v)의 모그로사이드 V와 혼합한 것을 제외하고는, 상기 실시예 4와 동일한 조건 및 방법으로 복합체를 제조하고, 커큐민의 수용화 정도는 실험예 2에 기재된 바와 같은 방법으로 확인하였다. 그 결과, 모그로사이드 배당체 농도에 따른 커큐민의 수용화 정도를 도 5에 나타내었다.By confirming the degree of solubilization in aqueous solution according to the concentration of mogroside glycoside used in the production process of a complex of poorly water-soluble substances and mogroside glycoside, the optimal concentration conditions of mogroside glycoside were confirmed. The experiment was conducted under the same conditions and methods as in Example 4, except that 10 mg of curcumin was mixed with 1.0, 3.0, 5.0, 7.5, 10.0, 12.5, 15, or 20% (w/v) of mogroside V. A complex was prepared, and the degree of water solubility of curcumin was confirmed by the same method as described in Experimental Example 2. As a result, the degree of water solubility of curcumin according to mogroside glycoside concentration is shown in Figure 5.
도 5에 나타난 바와 같이, 모그로사이드 V의 농도에 의존적으로 커큐민의 수용화 정도가 유의적으로 증가하였다. 특히, 모그로사이드가 5.0%(w/v) 이상으로 첨가된 경우에 약 5,500 ㎍/㎖의 커큐민을 수용액상에 용해시킴으로써, 난수용성 물질의 수용화에 사용되는 모그로사이드 배당체는 5.0%(w/v) 이상의 농도로 사용하는 것이 효과적임을 알 수 있었다.As shown in Figure 5, the degree of water solubility of curcumin significantly increased depending on the concentration of mogroside V. In particular, when mogroside is added in an amount of 5.0% (w/v) or more, by dissolving about 5,500 ㎍/㎖ of curcumin in an aqueous solution, the mogroside glycoside used for water solubilization of poorly water-soluble substances is reduced to 5.0% ( It was found that it was effective to use it at a concentration of w/v) or higher.
3-3. 3-3. 난수용성poorly water soluble 물질의 농도 확인 Check the concentration of the substance
난수용성 물질과 모그로사이드 배당체의 복합체 제조과정에서 사용되는 난수용성 물질의 농도에 따른 수용액 가용화 정도를 확인하여, 최적의 난수용성 물질 농도 조건을 확인하였다. 실험은 10.0%(w/v) 농도의 모그로사이드 V와 1,000, 3,000, 5,000, 7,000, 10,000, 12,000, 15,000, 17,000, 20,000, 25,000, 30,000 또는 40,000 ㎍/㎖의 커큐민을 혼합한 것을 제외하고는, 상기 실시예 4와 동일한 조건 및 방법으로 복합체를 제조하고, 커큐민의 수용화 정도는 실험예 2에 기재된 바와 같은 방법으로 확인하였다. 그 결과, 커큐민의 농도에 따른 수용화 정도를 도 6에 나타내었다.By confirming the degree of aqueous solution solubilization depending on the concentration of the poorly water-soluble material used in the production process of the complex of poorly water-soluble material and mogroside glycoside, the optimal concentration conditions of the poorly water-soluble material were confirmed. The experiment was conducted using 10.0% (w/v) concentration of mogroside V and 1,000, 3,000, 5,000, 7,000, 10,000, 12,000, 15,000, 17,000, 20,000, 25,000, 30,000 or 40,000 ㎍/㎖. Except for the addition of cumin. A complex was prepared under the same conditions and methods as in Example 4, and the degree of water solubilization of curcumin was confirmed by the same method as described in Experimental Example 2. As a result, the degree of water solubility according to the concentration of curcumin is shown in Figure 6.
도 6에 나타난 바와 같이, 커큐민의 농도에 의존적으로 수용화 정도가 증가하였다. 특히, 커큐민이 7,000 ㎍/㎖ 이상의 농도로 사용되는 경우에 6,000 ㎍/㎖의 수용성 정도를 나타냄으로써, 난수용성 물질을 7.0 ㎎/㎖ 이상의 농도로 사용하는 것이 효과적임을 알 수 있었다.As shown in Figure 6, the degree of water solubility increased depending on the concentration of curcumin. In particular, when curcumin was used at a concentration of 7,000 ㎍/㎖ or more, it showed a water solubility of 6,000 ㎍/㎖, showing that it is effective to use a poorly water-soluble substance at a concentration of 7.0 ㎎/㎖ or more.
실험예Experiment example 5. 수용액 5. Aqueous solution 가용화된solubilized 난수용성poorly water soluble 물질의 세포독성 확인 Confirmation of cytotoxicity of the substance
상기에서 모그로사이드 V에 의해 수용화된 커큐민의 세포독성을 다음과 같은 방법으로 확인하였다.The cytotoxicity of curcumin solubilized by mogroside V was confirmed by the following method.
먼저, B16F10 또는 RAW264.7 세포주를 5% CO2 및 37℃의 조건하에서 10%(v/v) FBS(fetal bovine serum), 100 U/㎖의 페니실린 및 100 ㎍/㎖의 스트렙토마이신이 포함된 DMEM 배지를 이용하여 배양하였다. 배양된 세포를 96웰 플레이트의 웰당 2×104개가 되도록 분주하고, 24시간 동안 배양하였다. 배양 후, 세포를 PBS로 세척하고, 12,5, 25, 50, 100, 200, 400, 800 또는 1,600 ㎍/㎖의 농도로 모그로사이드 V로 수용화된 커큐민을 첨가하였다. 이때, 커큐민은 2%(v/v) FBS(fetal bovine serum), 100 U/㎖의 페니실린 및 100 ㎍/㎖의 스트렙토마이신이 포함된 DMEM 배지를 이용하여 처리하였다. 세포를 72시간 동안 배양한 후, 90 ㎕의 배양액을 취하여 10 ㎕의 Ez-CyTox 용액과 혼합하고, 이를 37℃에서 1시간 동안 반응시킨 후, 450 ㎚의 파장에서 스펙트라맥스 M3(SpectraMax M3)를 사용하여 흡광도를 측정하였다. 측정된 흡광도 값으로 계산된 세포사멸율을 도 7에 나타내었다.First, the B16F10 or RAW264.7 cell line was grown in a cell containing 10% (v/v) FBS (fetal bovine serum), 100 U/ml penicillin, and 100 μg/ml streptomycin under conditions of 5% CO 2 and 37°C. Cultured using DMEM medium. The cultured cells were distributed at 2×10 4 cells per well of a 96-well plate and cultured for 24 hours. After incubation, cells were washed with PBS, and curcumin solubilized with mogroside V was added at a concentration of 12,5, 25, 50, 100, 200, 400, 800, or 1,600 μg/ml. At this time, curcumin was treated using DMEM medium containing 2% (v/v) FBS (fetal bovine serum), 100 U/ml penicillin, and 100 μg/ml streptomycin. After culturing the cells for 72 hours, 90 ㎕ of culture medium was taken and mixed with 10 ㎕ of Ez-CyTox solution, reacted at 37°C for 1 hour, and then incubated with SpectraMax M3 at a wavelength of 450 ㎚. The absorbance was measured using The apoptosis rate calculated from the measured absorbance value is shown in Figure 7.
도 7에 나타낸 바와 같이, 커큐민은 50 ㎍/㎖ 이상의 농도에서 세포독성을 나타낸 반면, 모그로사이드 V로 수용액 가용화된 커큐민은 400 ㎍/㎖ 이상의 농도에서 세포독성을 나타내었다.As shown in Figure 7, curcumin showed cytotoxicity at a concentration of 50 ㎍/㎖ or more, while curcumin solubilized in aqueous solution with mogroside V showed cytotoxicity at a concentration of 400 ㎍/㎖ or more.
실험예Experiment example 6. 수용액 6. Aqueous solution 가용화된solubilized 난수용성poorly water soluble 물질의 of substance 미백활성whitening activity
상기에서 모그로사이드 V에 의해 수용화된 커큐민의 미백 활성을 다음과 같은 방법으로 확인하였다.The whitening activity of curcumin solubilized with mogroside V was confirmed in the following manner.
6-1. 멜라닌 생성 억제 활성6-1. Melanin production inhibitory activity
먼저, 상기 서술한 바와 같이 배양된 B16F10 세포주를 96웰 플레이트에 웰당 2×104개가 되도록 분주하고, 24시간 동안 배양하였다. 배양 후, 세포를 PBS로 세척하고, 10, 50, 100 또는 200 ㎍/㎖의 농도로 모그로사이드 V로 수용화된 커큐민을 첨가하였다. 이때, 커큐민은 2%(v/v) FBS(fetal bovine serum), 100 U/㎖의 페니실린 및 100 ㎍/㎖의 스트렙토마이신이 포함된 DMEM 배지를 이용하여 처리하였고, 0.5 ㎍/㎖의 α-MSH를 함께 처리하여 멜라닌의 생성을 촉진하였다. 또한, 대조군으로서 DMSO에 용해시킨 10 ㎍/㎖의 커큐민을 사용하였다. 세포를 72시간 동안 배양한 후, 200 ㎕의 배양액을 취하여 450 ㎚의 파장에서 스펙트라맥스 M3를 사용하여 흡광도를 측정함으로써, 세포외로 분비된 멜라닌의 함량을 확인하였다. 한편, 배양된 세포를 수확한 후, 수확된 세포에 10% DMSO가 포함된 1M의 NaOH 용액을 첨가하고, 85℃에서 1시간 동안 반응시켜 세포를 용해시켰다. 세포 용해물을 취하여 상기와 같이 흡광도를 측정함으로써 세포 내 존재하는 멜라닌의 함량을 확인하였다. 그 결과, 측정된 멜라닌 함량을 도 8에 나타내었다.First, the B16F10 cell line cultured as described above was dispensed into a 96-well plate at 2×10 4 cells per well and cultured for 24 hours. After incubation, cells were washed with PBS, and curcumin solubilized with mogroside V was added at a concentration of 10, 50, 100, or 200 μg/ml. At this time, curcumin was treated using DMEM medium containing 2% (v/v) FBS (fetal bovine serum), 100 U/ml of penicillin, and 100 μg/ml of streptomycin, and 0.5 μg/ml of α- Treatment with MSH promoted melanin production. Additionally, as a control, 10 μg/ml of curcumin dissolved in DMSO was used. After culturing the cells for 72 hours, 200 μl of the culture medium was taken and the absorbance was measured using Spectramax M3 at a wavelength of 450 nm to confirm the content of extracellularly secreted melanin. Meanwhile, after harvesting the cultured cells, 1M NaOH solution containing 10% DMSO was added to the harvested cells and reacted at 85°C for 1 hour to lyse the cells. The cell lysate was taken and the absorbance was measured as above to confirm the content of melanin present in the cells. As a result, the measured melanin content is shown in Figure 8.
도 8에 나타난 바와 같이, 모그로사이드 V로 수용액 가용화된 커큐민의 농도 의존적으로 멜라닌의 생성이 억제되었다. 10 ㎍/㎖의 모그로사이드 V에 수용화된 커큐민에 약 6.8 ㎎의 커큐민이 포함된 것을 고려하였을 때, 10 ㎎/㎖의 커큐민을 처리한 경우보다 모그로사이드 V에 수용화된 커큐민이 더욱 우수한 멜라닌 생성 억제 활성을 나타냄을 알 수 있었다. As shown in Figure 8, melanin production was suppressed in a concentration-dependent manner of curcumin solubilized in aqueous solution with mogroside V. Considering that curcumin solubilized in 10 ㎍/ml Mogroside V contains about 6.8 mg of curcumin, the curcumin solubilized in Mogroside V is more effective than when treated with 10 mg/ml curcumin. It was found to exhibit excellent melanin production inhibitory activity.
6-2. 6-2. 티로시나제tyrosinase 활성 억제 active inhibition
먼저, 상기 서술한 바와 같이 B16F10 세포주에 모그로사이드 V로 수용화된 커큐민을 첨가하고, 72시간 동안 배양하였다. 배양된 세포를 PBS로 세척하고, 1,000×g에서 5분 동안 원심분리하여 세포를 수득하였다. 수득된 세포에 RIPA(radioimmunoprecipitation assay) 완충액을 첨가하여 세포를 현탁하고, 이를 12,000×g에서 20분 동안 원심분리하여 상등액만을 취하였다. 100 ㎍의 수득된 상등액에 50 mM의 Na-P 완충액(pH 6.8) 및 1 mM의 L-Dopa를 혼합하고, 37℃에서 2시간 동안 반응시켰다. 상기 반응이 끝난 후, 475 ㎚의 파장에서 스펙트라맥스 M3(SpectraMax M3)를 사용하여 흡광도를 측정하였다. 측정된 흡광도 값으로부터 티로시나제 활성 억제율을 계산하여 도 9에 나타내었다.First, curcumin solubilized with mogroside V was added to the B16F10 cell line as described above, and cultured for 72 hours. Cultured cells were washed with PBS and centrifuged at 1,000 × g for 5 minutes to obtain cells. RIPA (radioimmunoprecipitation assay) buffer was added to the obtained cells to suspend the cells, which were centrifuged at 12,000 × g for 20 minutes to collect only the supernatant. 100 μg of the obtained supernatant was mixed with 50 mM Na-P buffer (pH 6.8) and 1 mM L-Dopa, and reacted at 37°C for 2 hours. After the reaction was completed, the absorbance was measured using SpectraMax M3 at a wavelength of 475 nm. The tyrosinase activity inhibition rate was calculated from the measured absorbance value and is shown in Figure 9.
도 9에 나타난 바와 같이, 모그로사이드 V로 수용액 가용화된 커큐민의 농도 의존적으로 티로시나제의 활성이 억제되었다. 10 ㎍/㎖의 모그로사이드 V에 수용화된 커큐민에 약 6.8 ㎎의 커큐민이 포함된 것을 고려하였을 때, 10 ㎎/㎖의 커큐민을 처리한 경우보다 모그로사이드 V에 수용화된 커큐민이 더욱 우수한 티로시나제 활성 억제를 나타냄을 알 수 있었다. As shown in Figure 9, the activity of tyrosinase was inhibited in a concentration-dependent manner by curcumin solubilized in aqueous solution with mogroside V. Considering that curcumin dissolved in 10 ㎍/㎖ Mogroside V contains about 6.8 mg of curcumin, the curcumin dissolved in Mogroside V is more effective than when treated with 10 mg/mL curcumin. It was found that it exhibited excellent inhibition of tyrosinase activity.
실험예Experiment example 7. 수용액 7. Aqueous solution 가용화된solubilized 난수용성poorly water soluble 물질의 항염증 활성 Anti-inflammatory activity of the substance
상기에서 모그로사이드 V에 의해 수용화된 커큐민의 항염증 활성을 다음과 같은 방법으로 확인하였다.The anti-inflammatory activity of curcumin solubilized by mogroside V was confirmed by the following method.
먼저, RAW264.7 세포주를 실험예 5에 기재된 바와 같이 96웰 플레이트에 분주 및 배양하였다. 배양 후, 세포를 PBS로 세척하고, 25, 50, 100 또는 200 ㎍/㎖의 농도로 모그로사이드 V로 수용화된 커큐민, 또는 1.6, 3.2, 6.3, 12.5 또는 25 ㎍/㎖의 커큐민을 1 ㎍/㎖의 LPS와 함께 첨가하였다. 이때, 양성 대조군으로 100 μM의 인도메타신을 사용하였다. 세포를 72시간 동안 배양한 후, 80 ㎕의 배양액을 취하여 동량의 그리스(griess) 시약과 혼합하여 20분 동안 반응시킨 후, 540 ㎚의 파장에서 스펙트라맥스 M3를 사용하여 흡광도를 측정하였다. 측정된 흡광도 값으로 계산된 산화질소 억제 활성을 도 10에 나타내었다.First, the RAW264.7 cell line was distributed and cultured in a 96-well plate as described in Experimental Example 5. After incubation, cells were washed with PBS and incubated with curcumin solubilized with mogroside V at concentrations of 25, 50, 100, or 200 μg/ml, or curcumin at 1.6, 3.2, 6.3, 12.5, or 25 μg/ml. It was added along with ㎍/㎖ LPS. At this time, 100 μM indomethacin was used as a positive control. After culturing the cells for 72 hours, 80 μl of the culture medium was mixed with an equal amount of Griess reagent and reacted for 20 minutes, and then the absorbance was measured using Spectramax M3 at a wavelength of 540 nm. The nitric oxide inhibitory activity calculated from the measured absorbance values is shown in Figure 10.
도 10에 나타난 바와 같이, 모그로사이드 V로 수용액 가용화된 커큐민의 농도에 의존적으로 산화질소의 활성이 억제되었다. 구체적으로, 약 50%의 산화질소 억제 활성을 보이는 100 ㎍/㎖의 모그로사이드 V로 수용화된 커큐민에는 실제로 6.8 ㎎의 커큐민이 포함되어 있는데, 커큐민만을 처리한 경우에 산화질소 억제 IC50값이 8.01±0.04 ㎍/㎖인 것으로 확인되었다. 즉, 실제로 활성을 나타내는 커큐민의 함량을 비교하였을 때, 모그로사이드 V로 수용화된 커큐민이 약 33% 우수한 산화질소 억제능을 나타냄을 알 수 있었다.As shown in Figure 10, the activity of nitric oxide was inhibited depending on the concentration of curcumin solubilized in aqueous solution with mogroside V. Specifically, curcumin solubilized with 100 ㎍/㎖ Mogroside V, which shows about 50% nitric oxide inhibition activity, actually contains 6.8 mg of curcumin, and when treated with curcumin alone, the nitric oxide inhibition IC 50 value It was confirmed to be 8.01±0.04 ㎍/㎖. That is, when comparing the content of curcumin that is actually active, it was found that curcumin solubilized with mogroside V exhibited an excellent nitric oxide inhibitory ability of about 33%.
실험예Experiment example 8. 8. 모그로사이드mogroside 배당체를 이용한 using glycosides 커큐미노이드의of curcuminoids 추출 extraction
모그로사이드 배당체를 이용하여 강황분말에서 커큐미노사이드를 수용액 가용화시켜 다음과 같이 추출하였다.Curcuminoside was solubilized in aqueous solution from turmeric powder using mogroside glycoside and extracted as follows.
구체적으로, 7.5%(w/v)의 모그로사이드 또는 모그로사이드 V를 2.5%(w/v)의 강황 분말과 혼합하고, 여기에 70%(v/v) 에탄올을 첨가하였다. 상기 혼합물을 80℃에서 30분 동안 반응시킨 후, 8,000 rpm으로 원심분리하였다. 원심분리 후, 상층액의 에탄올을 회전증발기를 이용하여 증발시키고, 펠렛을 동결건조시켰다. 동결건조된 펠렛을 물에 현탁한 후, 추출된 수용성 커큐미노이드의 함량을 425 ㎚의 파장에서 스펙트라맥스 M3를 사용하여 흡광도를 측정함으로써 확인하였다. 이때, 커큐미노이드의 함량은 커큐민의 표준곡선을 이용하여 계산하였다. 그 결과, 모그로사이드 또는 모그로사이드 V를 이용하여 강황분말에서 추출된 커큐미노이드를 육안으로 관찰한 결과를 도 11에 나타내었다.Specifically, 7.5% (w/v) of mogroside or mogroside V was mixed with 2.5% (w/v) of turmeric powder, and 70% (v/v) ethanol was added thereto. The mixture was reacted at 80°C for 30 minutes and then centrifuged at 8,000 rpm. After centrifugation, the ethanol in the supernatant was evaporated using a rotary evaporator, and the pellet was freeze-dried. After suspending the freeze-dried pellet in water, the content of the extracted water-soluble curcuminoid was confirmed by measuring the absorbance using Spectramax M3 at a wavelength of 425 nm. At this time, the content of curcuminoids was calculated using the standard curve of curcumin. As a result, the results of visual observation of curcuminoids extracted from turmeric powder using mogroside or mogroside V are shown in Figure 11.
도 11에 나타난 바와 같이, 모그로사이드 또는 모그로사이드 V의 첨가로 강황 분말에서 커큐미노사이드가 높은 함량으로 추출되었다. 구체적으로, 모그로사이드의 첨가로 1.1±0.0 ㎎/g의 커큐미노이드가, 모그로사이드 V에 의해 0.6±0.0 ㎎/g의 커큐미노이드가 추출되었다. 한편, 모그로사이드 배당체 대신 물을 첨가한 대조군의 경우 커큐미노이드가 추출되지 않았다.As shown in Figure 11, curcuminosides were extracted at a high content from turmeric powder by the addition of mogroside or mogroside V. Specifically, 1.1 ± 0.0 mg/g of curcuminoids were extracted with the addition of mogroside, and 0.6 ± 0.0 mg/g of curcuminoids were extracted with Mogroside V. Meanwhile, in the control group where water was added instead of mogroside glycoside, curcuminoids were not extracted.
Claims (9)
상기 난수용성 물질은 이데베논, 레스베라트롤, 커큐민, 비스디메톡시커큐민, 탁솔, 퀘르세틴 및 올레오놀산으로 구성된 군으로부터 선택되는 어느 하나 이상인 난수용성 물질의 수용액 가용화 조성물.
A composition for solubilizing an aqueous solution of a poorly water-soluble substance containing a ginseng extract,
A composition for solubilizing an aqueous solution of a poorly water-soluble material, wherein the poorly water-soluble material is at least one selected from the group consisting of idebenone, resveratrol, curcumin, bisdimethoxycurcumin, taxol, quercetin, and oleonolic acid.
The composition for solubilizing an aqueous solution of a poorly water-soluble substance according to claim 1, wherein the ginseng extract is a wild ginseng extract.
The composition for solubilizing an aqueous solution of a poorly water-soluble substance according to claim 2, wherein the wild ginseng is a wild ginseng leaf.
The composition according to claim 1, wherein the extract is extracted with water, a C 1 to C 2 lower alcohol, or a mixture thereof.
인삼류 추출물로 구성된 수용액 가용화 복합체로서,
상기 난수용성 물질은 이데베논, 레스베라트롤, 커큐민, 비스디메톡시커큐민, 탁솔, 퀘르세틴 및 올레오놀산으로 구성된 군으로부터 선택되는 어느 하나 이상인 수용액 가용화 복합체.
poorly water-soluble substances; and
An aqueous solution-solubilized complex composed of ginseng extract,
An aqueous solution solubilization complex wherein the poorly water-soluble substance is at least one selected from the group consisting of idebenone, resveratrol, curcumin, bisdimethoxycurcumin, taxol, quercetin, and oleonolic acid.
A composition comprising the aqueous solution solubilized complex of claim 7.
상기 난수용성 물질은 이데베논, 레스베라트롤, 커큐민, 비스디메톡시커큐민, 탁솔, 퀘르세틴 및 올레오놀산으로 구성된 군으로부터 선택되는 어느 하나 이상인 난수용성 물질의 수용액 가용화 방법.A method of solubilizing a poorly water-soluble material in an aqueous solution comprising preparing a complex by mixing a poorly water-soluble material with a ginseng extract,
A method of solubilizing an aqueous solution of a poorly water-soluble material, wherein the poorly water-soluble material is at least one selected from the group consisting of idebenone, resveratrol, curcumin, bisdimethoxycurcumin, Taxol, quercetin, and oleonolic acid.
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