KR101925420B1 - Diynoic acid compound and derivatives thereof for uric acid excretion and composition comprising the same - Google Patents
Diynoic acid compound and derivatives thereof for uric acid excretion and composition comprising the same Download PDFInfo
- Publication number
- KR101925420B1 KR101925420B1 KR1020170059895A KR20170059895A KR101925420B1 KR 101925420 B1 KR101925420 B1 KR 101925420B1 KR 1020170059895 A KR1020170059895 A KR 1020170059895A KR 20170059895 A KR20170059895 A KR 20170059895A KR 101925420 B1 KR101925420 B1 KR 101925420B1
- Authority
- KR
- South Korea
- Prior art keywords
- acid
- acetyl
- compound
- present
- octadecadiene
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims abstract description 55
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Abstract
본 발명은 요산 배출용 디노익산 화합물 및 이의 유도체, 및 이를 포함하는 조성물에 관한 것으로, 본 발명에 따른 16-아세틸-9,17-옥타데카디엔-12,14-디노익산(16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물, 상기 화합물의 메틸레이션에 의해 얻어지는 16-아세틸-9,17-옥타데카디엔-12,14-디노익 메틸 에스테르(16-acetyl-9,17-octadecadiene-12,14-diynoic methyl ester)는 요산의 결정화를 저해할 수 있고, 요산의 배출을 촉진할 수 있다.The present invention relates to a dinnoic acid compound for uric acid release, a derivative thereof, and a composition comprising the same, wherein the 16-acetyl-9,17-octadecadien-12,14-dinnoic acid , 17-octadecadiene-12,14-diynoic acid) compound, 16-acetyl-9,17-octadecadien-12,14-dinomimethyl ester obtained by methylation of the above compound -octadecadiene-12,14-diynoic methyl ester) can inhibit the crystallization of uric acid and promote the release of uric acid.
Description
본 발명은 요산 배출용 디노익산 화합물 및 이의 유도체, 및 이를 포함하는 조성물에 관한 것으로, 보다 구체적으로 요산의 결정화를 저해하고, 요산의 배출을 촉진할 수 있는 디노익산 화합물 및 이의 유도체, 및 이를 포함하는 조성물에 관한 것이다.The present invention relates to a dinnoic acid compound for uric acid release, a derivative thereof, and a composition containing the same, more specifically, to a dinnoic acid compound and its derivative capable of inhibiting crystallization of uric acid and promoting the discharge of uric acid, ≪ / RTI >
통풍(Gout)이란 사람에게서만 발견되는 다양한 질병군을 나타내는 용어로 조직 및 혈중 요산의 농도의 증가에 의해 야기되는 것으로 보통 남성에게 나타나는 관절계 질병이다. 통풍 환자에게서는 혈청 요산 농도의 증가(hyperuricemia), 급성 관절염 재발 증상, 활액 백혈구(synovial fluid leukocyte) 내의 모노소디움 요산염 결정(monosodium urate crystal)의 존재, 관절 안과 그 주위의 모노소디움 요산염 결정 덩어리의 침착 및 이로 인한 관절의 기형 불구, 신장질환 등의 증상을 볼 수 있다. 통풍은 '질병의 왕', 그리고 '왕들의 질병'이라 불리며, 나이가 들수록 많이 발생하는 질병으로 굉장한 통증을 수반하는 질환이다.Gout is a term for various disease groups found only in humans. It is caused by an increase in the concentration of tissue and blood uric acid. It is an arthritic disease usually seen in men. In patients with gout, hyperuricemia, recurrence of acute arthritis, presence of monosodium urate crystals in synovial fluid leukocyte, presence of monosodium urate crystals in and around the joints Kidney disease, and so on. Gout is called 'King of Disease' and 'King's Disease', and it is a disease that occurs with the older age and accompanies tremendous pain.
통풍의 원인이 되는 고요산증(Hyperuricemia)이란 혈액에 요산의 농도가 증가 된 상태를 말하는 것으로, 이는 혈청에서 모노소디움 요산염의 농도가 제한된 용해도의 한계를 넘을 때 발생한다. 37℃에서 인간 혈장의 요산 포화도는 약 7mg/dl이며, 이 농도를 넘으면 물리화학적으로 과포화 상태가 된다. 정상인의 평균 혈청 요산 농도보다 +2 SD를 초과한 경우 혈청 요산 농도는 높은 것으로 보며, 대부분의 역학 조사에서 남자의 상위한계는 7mg/dl, 여자는 6mg/dl이다. 이에 고요산증으로 보는 실질적인 상위 한계수준은 7.0mg/dl 이상인 경우로 정의되고 있다.Hyperuricemia, a cause of gout, refers to an increase in the concentration of uric acid in the blood, which occurs when the concentration of monosodium iodate in serum exceeds the limited solubility limit. The degree of uric acid saturation of human plasma is about 7 mg / dl at 37 ° C, and when it exceeds this concentration, it becomes physically and chemically supersaturated. Serum uric acid concentration is higher when the mean serum uric acid concentration is higher than normal serum uric acid concentration of normal people. In most epidemiological studies, the upper limit of men is 7 mg / dl, and that of women is 6 mg / dl. Therefore, the upper limit of the actual upper limit is defined as 7.0mg / dl or more.
통풍의 치료제로서는 크산틴 산화효소(xathine oxidase)의 저해제로서 하이포크산틴(hypoxanthine)과 구조가 유사한 알로퓨리놀(allopurinol)과 같은 약물이 사용되고 있으나 이는 피부발진, 위장장애, 골수억제, 가려움증, 구역질, 근육통 등과 같은 심각한 부작용이 있는바, 안전하고 부작용이 없으면서 통풍을 예방하고 치료할 수 있는 통풍의 예방 및 치료용 조성물 발명이 요구되고 있다.Drugs such as allopurinol, which is structurally similar to hypoxanthine, have been used as inhibitors of xanthine oxidase as a treatment for gout. However, they have been used for skin rash, gastrointestinal disorders, bone marrow suppression, itching, nausea, There is a need for a composition for the prevention and treatment of gout which can be prevented and treated with gentle side effects without serious side effects.
한국등록특허 제10-1677944호는 포유동물에서 요산을 감소시키거나 요산 배출을 증가시킬 수 있는 2-(3-(2,6-디메틸벤질옥시)-4-메틸페닐)아세트산, 또는 그의 제약학적으로 허용 가능한 염 및 이를 포함하는 약제학적 조성물을 개시하고 있다.Korean Patent No. 10-1677944 discloses 2- (3- (2,6-dimethylbenzyloxy) -4-methylphenyl) acetic acid, which can reduce uric acid or increase uric acid emissions in mammals, Acceptable salts and pharmaceutical compositions containing them.
본 발명의 일 실시형태의 목적은 요산의 결정화를 저해하고, 요산의 배출을 촉진할 수 있는 디노익산 화합물 및 이의 유도체, 및 이를 포함하는 조성물을 제공하는 것이다.It is an object of one embodiment of the present invention to provide a dinoic acid compound and a derivative thereof capable of inhibiting crystallization of uric acid and promoting the discharge of uric acid, and a composition containing the same.
본 발명의 일 실시형태는 요산 배출용 16-아세틸-9,17-옥타데카디엔-12,14-디노익산 (16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물 또는 이의 에스테르 유도체를 제공한다.One embodiment of the present invention relates to a method for the production of uric acid by removing 16-acetyl-9,17-octadecadiene-12,14-diynoic acid or its ester Lt; / RTI >
본 발명의 일 실시형태에 따르면, 상기 화합물은 하기 화학식 1로 표시될 수 있다.According to one embodiment of the present invention, the compound may be represented by the following general formula (1).
[화학식 1][Chemical Formula 1]
본 발명의 일 실시형태에 따르면, 상기 에스테르 유도체는 하기 화학식 2로 표시될 수 있다.According to one embodiment of the present invention, the ester derivative may be represented by the following general formula (2).
[화학식 2](2)
상기 에스테르 유도체는 상기 화학식 1의 화합물의 메틸레이션에 의하여 얻어질 수 있다.The ester derivative can be obtained by methylation of the compound of formula (1).
본 발명의 일 실시형태에 따르면, 상기 화합물은 황칠(Dendropanax morbifera)로부터 분리될 수 있다.According to one embodiment of the present invention, the compound can be isolated from Dendropanax morbifera .
본 발명의 다른 실시형태는 (a) 황칠을 추출용매로 추출하고, 여과 및 농축하여 황칠 추출물을 수득하는 단계;Another embodiment of the present invention relates to a method for the production of a fermented soybean milk, comprising: (a) extracting yellowing with an extraction solvent, filtering and concentrating to obtain a yellowish extract;
(b) 상기 황칠 추출물을 유기용매로 분획하고, 컬럼 크로마토그래피를 수행하여 분획물을 수득하는 단계; 및(b) fractionating the Huangchil extract with an organic solvent and performing column chromatography to obtain a fraction; And
(c) 상기 분획물로부터 고성능 액체크로마토그래피를 수행하여 16-아세틸-9,17-옥타데카디엔-12,14-디노익산 (16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물을 분리하는 단계;(c) High performance liquid chromatography was performed on the fractions to obtain 16-acetyl-9,17-octadecadiene-12,14-diynoic acid (16-acetyl-9,17-octadecadiene- ;
를 포함하는 요산 배출용 화합물 또는 이의 유도체의 제조방법을 제공한다.And a method for producing the compound for uric acid discharge or a derivative thereof.
본 발명의 일 실시형태에 따르면, 상기 화합물의 분리 단계 이후에 상기 화합물의 메틸레이션에 의하여 16-아세틸-9,17-옥타데카디엔-12,14-디노익 메틸 에스테르를 얻는 단계;를 추가로 포함할 수 있다.According to one embodiment of the present invention, there is provided a process for the preparation of 16-acetyl-9,17-octadecadien-12,14-dinoxime methyl ester by methylation of the compound after the step of separating the compound, .
또한, 본 발명의 일 실시형태에 따르면, 상기 황칠 추출물을 수득하는 단계 이후에 상기 황칠 추출물을 미생물 발효하여 황칠 발효 추출물을 얻고, 상기 황칠 발효 추출물로 상기 분획물 수득 단계를 수행할 수 있다.Also, according to an embodiment of the present invention, after the step of obtaining the Huangchil extract, the Huangchil extract may be fermented by microbial fermentation to obtain a Huangchu fermentation extract, and the Huangchil fermentation extract may be subjected to the step of obtaining the fraction.
본 발명의 또 다른 실시형태는 16-아세틸-9,17-옥타데카디엔-12,14-디노익산(16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물 또는 이의 에스테르 유도체 및 이의 약제학적으로 허용가능한 염을 포함하는 요산 배출용 약제학적 조성물을 제공한다.Another embodiment of the present invention relates to a method for producing 16-acetyl-9,17-octadecadiene-12,14-diynoic acid or an ester derivative thereof, A pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable salt thereof.
본 발명의 또 다른 실시형태는 16-아세틸-9,17-옥타데카디엔-12,14-디노익산(16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물 또는 이의 에스테르 유도체를 포함하는 요산 배출용 의약외품 조성물을 제공한다.Another embodiment of the present invention relates to a method for producing 16-acetyl-9,17-octadecadiene-12,14-diynoic acid or an ester derivative thereof, which comprises reacting 16-acetyl-9,17-octadecadiene- A quasi-drug composition for uric acid release.
본 발명의 또 다른 실시형태는 16-아세틸-9,17-옥타데카디엔-12,14-디노익산(16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물 또는 이의 에스테르 유도체를 포함하는 요산 배출용 건강기능식품 조성물을 제공한다.Another embodiment of the present invention relates to a method for producing 16-acetyl-9,17-octadecadiene-12,14-diynoic acid or an ester derivative thereof, which comprises reacting 16-acetyl-9,17-octadecadiene- And a health functional food composition for uric acid discharge.
본 발명의 또 다른 실시형태는 16-아세틸-9,17-옥타데카디엔-12,14-디노익산 (16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물 또는 이의 에스테르 유도체를 포함하는 요산 배출용 화장료 조성물을 제공한다.Another embodiment of the present invention relates to a method for producing 16-acetyl-9,17-octadecadiene-12,14-diynoic acid or an ester derivative thereof, which comprises reacting 16-acetyl-9,17-octadecadiene- The present invention provides a cosmetic composition for uric acid discharge.
본 발명은 16-아세틸-9,17-옥타데카디엔-12,14-디노익산(16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물, 상기 화합물의 메틸레이션에 의해 얻어지는 16-아세틸-9,17-옥타데카디엔-12,14-디노익 메틸 에스테르(16-acetyl-9,17-octadecadiene-12,14-diynoic methyl ester)를 제공할 수 있다.The present invention relates to 16-acetyl-9,17-octadecadiene-12,14-diynoic acid compound, 16-acetyl-9,17-octadecadiene- -Acetyl-9,17-octadecadien-12,14-dinomethyl methyl ester (16-acetyl-9,17-octadecadiene-12,14-diynoic methyl ester).
본 발명에 따른 16-아세틸-9,17-옥타데카디엔-12,14-디노익산(16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물은 요산의 결정화를 저해할 수 있고, 요산의 배출을 촉진할 수 있다. The 16-acetyl-9,17-octadecadiene-12,14-diynoic acid compound according to the present invention can inhibit the crystallization of uric acid , And uric acid emissions can be promoted.
또한, 본 발명에 따른 상기 디노익산 화합물들은 천연물질에서 분리될 수 있고, 신체에 독성이 없으며, 부작용이 없어 요산 배출을 필요로 다양한 분야에 사용될 수 있다. In addition, the above-mentioned dinnoic acid compounds according to the present invention can be isolated from natural materials, have no toxicity to the body, have no side effects, and can be used in various fields requiring uric acid discharge.
본 발명에 따르면, 상기 디노익산 화합물 또는 이의 유도체를 포함하는 조성물은 약제학적 조성물, 의약외품 조성물, 건강기능식품 조성물, 또는 화장료 조성물로 사용될 수 있다.According to the present invention, the composition comprising the dinnoic acid compound or a derivative thereof can be used as a pharmaceutical composition, a quasi-drug composition, a health functional food composition, or a cosmetic composition.
도 1은 본 발명의 일 실시형태에 따라 황칠 추출물에서 분리한 화합물 1 내지 9의 화학식 및 명칭을 나타낸다.
도 2는 본 발명의 일 실시형태에 따라 얻어진 16-아세틸-9,17-옥타데카디엔-12,14-디노익산 및 이의 메틸화에 의해 얻어진 16-아세틸-9,17-옥타데카디엔-12,14-디노익 메틸 에스테르의 H-NMR 분석 그래프이다.
도 3은 본 발명의 일 실시형태에 따라 얻어진 16-아세틸-9,17-옥타데카디엔-12,14-디노익산 및 이의 메틸화에 의해 얻어진 16-아세틸-9,17-옥타데카디엔-12,14-디노익 메틸 에스테르의 C-NMR 분석 그래프이다.
도 4는 분무 건조된 황칠 추출물에 대한 크산틴 옥시다제의 저해율을 나타내는 그래프이다.
도 5는 본 발명의 실험예에 따라 대조군 및 본 발명의 일 실시형태에 따른 화합물의 처리에 따른 혈액 및 오줌 내의 요산 수치를 나타내는 그래프이다.BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows the chemical formulas and names of
Fig. 2 is a graph showing the activity of 16-acetyl-9,17-octadecadien-12, 14-dinoic acid and 16-acetyl-9,17-octadecadien-12 obtained by its methylation obtained according to an embodiment of the present invention, ≪ 1 > H-NMR analysis of 14-dinioxime methyl ester.
Fig. 3 is a graph showing the activity of 16-acetyl-9,17-octadecadien-12, 14-dinoic acid obtained according to an embodiment of the present invention and 16- C-NMR analysis of 14-dinioxime methyl ester.
4 is a graph showing inhibition rates of xanthine oxidase to spray-dried Huangchil extract.
Figure 5 is a graph showing uric acid levels in the blood and urine following treatment of a control group and compounds according to one embodiment of the invention, according to an experimental example of the present invention.
이하, 본원의 발명이 속하는 기술분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있도록 본 발명의 실시형태를 들어 상세히 설명한다. 본 발명의 실시형태는 당업계에서 평균적인 지식을 가진 자에게 본 발명을 더욱 완전하게 설명하기 위해서 제공되는 것이다. 따라서, 본 발명의 실시형태는 여러 가지 다른 형태로 변형될 수 있으며, 본 발명의 범위가 이하 설명하는 실시형태로 한정되는 것은 아니다. Hereinafter, embodiments of the present invention will be described in detail so that those skilled in the art can easily carry out the present invention. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art. Therefore, the embodiments of the present invention can be modified into various other forms, and the scope of the present invention is not limited to the following embodiments.
본 발명에서 사용되는 모든 기술용어는, 달리 정의되지 않는 이상, 하기의 정의를 가지며 본 발명의 관련 분야에서 통상의 당업자가 일반적으로 이해하는 것과 부합된다. 또한, 본 명세서에는 바람직한 방법이나 시료가 기재되나, 이와 유사하거나 동등한 것들도 본 발명의 범주에 포함된다. 본 명세서에 참고문헌으로 기재되는 모든 간행물의 내용은 본 발명에 도입된다.All technical terms used in the present invention have the following definitions and are consistent with what is generally understood by those of ordinary skill in the art to which this invention pertains, unless otherwise defined. In addition, preferred methods or samples are described in this specification, but similar or equivalent ones are also included in the scope of the present invention. The contents of all publications referred to herein are incorporated herein by reference.
용어 “약”이라는 것은 참조 양, 수준, 값, 수, 빈도, 퍼센트, 치수, 크기, 양, 중량 또는 길이에 대해 30, 25, 20, 25, 10, 9, 8, 7, 6, 5, 4, 3, 2 또는 1% 정도로 변하는 양, 수준, 값, 수, 빈도, 퍼센트, 치수, 크기, 양, 중량 또는 길이를 의미한다.The term " about " is used herein to refer to a reference quantity, a level, a value, a number, a frequency, a percent, a dimension, a size, a quantity, a weight, or a length of 30, 25, 20, 25, 10, 9, 8, 7, Level, value, number, frequency, percent, dimension, size, quantity, weight or length of a variable, such as 4, 3, 2 or 1%.
본 명세서를 통해, 문맥에서 달리 필요하지 않으면, “포함하다” 및 “포함하는”이란 말은 제시된 단계 또는 구성요소, 또는 단계 또는 구성요소들의 군을 포함하나, 임의의 다른 단계 또는 구성요소, 또는 단계 또는 구성요소들의 군이 배제되지는 않음을 내포하는 것으로 이해하여야 한다.Throughout this specification, the words " comprises " and " comprising ", unless the context requires otherwise, include the steps or components, or groups of steps or elements, Steps, or groups of elements are not excluded.
본 발명은 요산의 배출용 디노익산 화합물 및 이의 유도체, 및 이를 포함하는 조성물에 관한 것이다.The present invention relates to a dinnoic acid compound for the discharge of uric acid, a derivative thereof, and a composition containing the same.
본 발명에 따르면, 16-아세틸-9,17-옥타데카디엔-12,14-디노익산(16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물은 요산의 결정화를 저해할 수 있고, 요산의 배출을 촉진할 수 있다. 또한, 천연물질에서 분리될 수 있고, 신체에 독성이 없으며, 부작용이 없어 요산 배출을 필요로 다양한 분야에 사용될 수 있다. 이에 제한되지 않으나, 예를 들면, 상기 디노익산 화합물 또는 이의 유도체를 포함하는 조성물은 약제학적 조성물, 의약외품 조성물, 건강기능식품 조성물, 또는 화장료 조성물로 사용될 수 있다.According to the present invention, 16-acetyl-9,17-octadecadiene-12,14-diynoic acid compounds can inhibit the crystallization of uric acid And can promote the discharge of uric acid. It can also be used in a variety of fields that can be separated from natural materials, are non-toxic to the body, have no side effects and require uric acid emissions. For example, the composition containing the dino-acid compound or a derivative thereof may be used as a pharmaceutical composition, a quasi-drug composition, a health functional food composition, or a cosmetic composition.
본 발명의 일 실시형태는 16-아세틸-9,17-옥타데카디엔-12,14-디노익산(16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물(이하, ‘디노익산 화합물’이라고도 함) 을 제공하며, 상기 디노익산 화합물은 하기 화학식 1로 표시될 수 있다.One embodiment of the present invention relates to a method for producing 16-acetyl-9,17-octadecadiene-12,14-diynoic acid (hereinafter, Compound "), and the dinnoic acid compound may be represented by the following general formula (1).
[화학식 1][Chemical Formula 1]
상기 화학식 1로 표시되는 화합물은 (9Z, 16S)-16-아세틸-9,17-옥타데카디엔-12,14-디노익산((9Z, 16S)-16-acetyl-9,17-octadecadiene-12,14-diynoic acid)으로 명명될 수 있다.(9Z, 16S) -16-acetyl-9,17-octadecadien-12,14-dinoic acid ((9Z, , 14-diynoic acid).
본 발명의 일 실시형태에 따르면, 상기 화학식 1의 입체 이성질체도 본 발명의 범위에 속할 수 있다.According to one embodiment of the present invention, the stereoisomers of the above formula (1) may also fall within the scope of the present invention.
또한, 본 발명의 일 실시형태는 상기 16-아세틸-9,17-옥타데카디엔-12,14-디노익산(16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물의 에스테르 유도체를 제공할 수 있다.Further, an embodiment of the present invention is an ester derivative of the above-mentioned 16-acetyl-9,17-octadecadiene-12,14-diynoic acid compound Can be provided.
본 발명의 일 실시형태에 따르면, 상기 디노익산 화합물의 에스테르 유도체는 하기 화학식 2로 표시될 수 있다.According to one embodiment of the present invention, the ester derivative of the dinnoic acid compound may be represented by the following general formula (2).
[화학식 2](2)
상기 화학식 2의 화합물은 (9Z, 16S)-16-아세틸-9,17-옥타데카디엔-12,14-디노익 메틸 에스테르((9Z, 16S)-16-acetyl-9,17-octadecadiene-12,14-diynoic methyl ester)로 명명될 수 있다.(9Z, 16S) -16-acetyl-9,17-octadecadien-12,14-dinoxymethyl ester ((9Z, 16S) -16-acetyl-9,17-octadecadiene- 12 , 14-diynoic methyl ester).
본 발명의 일 실시형태에 따르면, 상기 화학식 2의 입체 이성질체도 본 발명의 범위에 속할 수 있다.According to one embodiment of the present invention, the stereoisomers of Formula 2 may also fall within the scope of the present invention.
상기 화학식 2의 화합물은 에스테르 화합물로써, 화학식 1로 표시되는 디노익산 화합물의 에스테르 유도체로 지칭될 수 있다. The compound of formula (2) is an ester compound and may be referred to as an ester derivative of the dinnoic acid compound represented by formula (1).
상기 디노익산 화합물의 에스테르 유도체는 상기 화학식 1의 화합물의 메틸레이션(methylation)에 의하여 얻어질 수 있다.The ester derivative of the dinoic acid compound can be obtained by methylation of the compound of formula (1).
상기 메틸레이션(methylation) 반응은 하기 반응식과 같이 나타낼 수 있다.The above methylation reaction can be represented by the following reaction formula.
[반응식][Reaction Scheme]
본 발명의 일 실시형태에 따르면, 상기 디노익산 화합물 및 이의 유도체는 신규한 물질로써, 일반적인 화학 합성에 의해서 얻어질 수 있다. 또한, 천연물로부터 분리될 수 있다.According to one embodiment of the present invention, the above-mentioned dinnoic acid compound and its derivative are novel materials and can be obtained by general chemical synthesis. It can also be isolated from natural products.
이에 제한되는 것은 아니나, 예를 들면, 상기 디노익산 화합물 및 이의 유도체는 황칠(Dendropanax morbifera)과 같은 천연물로부터 분리될 수 있다.For example, but not limited to, the above-mentioned dinnoic acid compound and its derivatives may be separated from natural products such as Dendropanax morbifera .
황칠나무는 최대 높이 15m에 달하는 두릅나무과 나무로 만병통치 나무라는 뜻의 학명 덴드로 파낙스(Dendropanax morbifera Nakai)를 가지고 있을 정도로 그 약리학적 효능이 매우 뛰어난 약용식물이다. 한국에서만 서식하며, 한국에서도 난대림이 펼쳐진 한반도 남해 도서지역과 해안지역, 특히 해남, 완도 등 서남해안에서 생산되는 것으로 매우 귀한 약용식물이다.It is a medicinal plant whose pharmacological effect is very good, so that it has a scientific name Dendropanax morbifera Nakai which means a tree with a maximum height of 15m and a tree with a panacea. It is a very valuable medicinal plant which is produced only in South Korea, and is produced in South Sea coast such as Haenam and Wando in southern sea island region and peninsula in Korea.
상기 황칠로부터 디노익산 화합물 및 이의 유도체를 분리하는 방법은 특별히 제한되지 않으나, 하기와 같은 방법으로 분리될 수 있다.The method for separating the dinnoic acid compound and its derivative from the sulfuric acid is not particularly limited, but may be separated by the following method.
우선, 황칠을 추출용매로 추출하고, 여과 및 농축하여 황칠 추출물을 수득할 수 있다.Firstly, Huangchil is extracted with an extraction solvent, filtered and concentrated to obtain Huangchil extract.
본 발명의 일 실시형태에 따르면, 황칠은 재배한 것 또는 시판되는 것 등을 제한 없이 사용할 수 있으며, 지상부, 뿌리, 종자를 모두 사용할 수 있다.According to one embodiment of the present invention, the horticulture can be cultivated or commercially available, and the ground, roots, and seeds can be used.
이에 제한되는 것은 아니나, 황칠나무의 뿌리, 줄기, 꽃, 잎 및 열매로 이루어진 군에서 선택되는 하나 이상을 추출한 것 일 수 있고, 또는 황칠나무의 지상부인 줄기, 꽃, 잎 및 열매로 이루어진 군에서 선택되는 하나 이상을 추출한 것일 수 있으며, 바람직하게는 황칠나무의 잎을 추출한 것일 수 있다.But may be one or more selected from the group consisting of roots, stems, flowers, leaves and fruits of Uchihaku, or a group consisting of stem, flower, leaf and fruit, And may be one obtained by extracting at least one selected leaf, preferably a leaf of a Japanese whitish tree.
황칠 추출물을 얻는 방법은 특별히 제한되지 않으며, 당업계에서 사용되는 방법을 사용할 수 있다. 이에 제한되는 것은 아니나, 예를 들면, 추출용매를 이용하여 황칠 추출물을 얻을 수 있다.The method for obtaining the Huangchil extract is not particularly limited, and the methods used in the art can be used. For example, an extract of Huangchil can be obtained by using an extraction solvent.
상기 추출용매는 당업계에서 통상적으로 사용하는 추출용매를 사용할 수 있으며, 이에 제한되지는 않으며, 예를 들면 물, 탄소수 1 내지 6의 알코올 또는 이들의 혼합 용매를 사용할 수 있으며, 바람직하게는 상기 알코올은 에탄올, 메탄올 또는 부탄올일 수 있다. 상기 추출용매는 이에 제한되지는 않으나, 바람직하게는 감수 분량의 2 내지 20배 첨가할 수 있으며, 보다 바람직하게는 4 내지 10배 첨가할 수 있으며, 보다 더 바람직하게는 5배 첨가할 수 있다. 상기 추출의 방법은 이에 제한되지는 않으나, 바람직하게는 열탕 추출, 열수추출, 냉침 추출, 환류 냉각 추출 또는 초음파 추출의 방법을 사용할 수 있으며, 보다 바람직하게는 열탕 추출 또는 냉침 추출 방법을 사용할 수 있다. 추출 시 추출용매의 온도는 이에 제한되지는 않으나, 바람직하게는 20 내지 100℃일 수 있으며, 보다 바람직하게는 상온일 수 있다. 추출시간은 이에 제한되지는 않으나, 바람직하게는 12시간 내지 10일일 수 있으며, 보다 바람직하게는 5일 내지 8일일 수 있으며, 보다 더 바람직하게는 7일일 수 있다. 추출횟수는 이에 제한되지는 않으나, 바람직하게는 1 내지 5회일 수 있으며, 보다 바람직하게는 3회일 수 있다. 상기와 같은 추출의 조건을 이용하여 황칠을 추출, 여과하고, 여과액을 농축 및 건조하여 황칠 추출물을 수득할 수 있다.The extraction solvent may be, for example, water, an alcohol having 1 to 6 carbon atoms, or a mixed solvent thereof, preferably an alcohol May be ethanol, methanol or butanol. The extraction solvent is not limited thereto, but may be added in an amount of 2 to 20 times, more preferably 4 to 10 times, and more preferably 5 times, in terms of the reduced amount. The method of extraction is not limited thereto, but it is preferable to use a method of hot water extraction, hot water extraction, cold extraction, reflux cooling extraction or ultrasonic extraction, more preferably hot water extraction or cold extraction . The temperature of the extraction solvent at the time of extraction is not limited thereto, but may be preferably 20 to 100 ° C, more preferably room temperature. The extraction time may be, but not limited to, preferably 12 hours to 10 days, more preferably 5 days to 8 days, and even more preferably 7 days. The number of times of extraction is not limited thereto, but may be preferably 1 to 5 times, more preferably 3 times. Using the conditions of extraction as described above, the yellow crush is extracted and filtered, and the filtrate is concentrated and dried to obtain a yellow crush extract.
또한, 본 발명의 일 실시형태에 따르면, 상기 여과 및 농축된 황칠 추출물을 미생물 발효하여 생물전환액을 얻고, 이를 다시 여과 및 농축하고, 건조하여 황칠 발효 추출물을 얻을 수 있다.According to an embodiment of the present invention, the filtered and concentrated Huangchil extract may be fermented by microbial fermentation to obtain a bioconversion liquid, which is then filtered and concentrated and dried to obtain a Huangchu fermented extract.
상기 생물전환액을 얻는 방법은 특별히 제한되지 않으며, 당업계에 공지된 방법을 사용할 수 있다. 이에 제한되는 것은 아니나, 예를 들면, 상기에서 얻어진 황칠 추출물에 배양된 균주를 접종하여 생물전환액을 얻을 수 있다. The method for obtaining the bioconversion liquid is not particularly limited, and a method known in the art can be used. For example, it is possible to obtain a bioconversion liquid by inoculating a strain cultured in the above-obtained yellowtail extract.
본 발명의 일 실시형태에 따르면, 이에 제한되는 것은 아니나, 예를 들면, Aspergillus oryzae , Saccharomyces cerevisiae , Phellinus baumii , Ganoderma lucidum등의 발효 미생물을 사용할 수 있다.According to one embodiment of the present invention, but not limited to, for example, Aspergillus oryzae , Saccharomyces cerevisiae , Phellinus baumii , Ganoderma lucidum and the like can be used.
다음으로, 상기 황칠 추출물을 유기용매로 분획하고, 컬럼 크로마토그래피를 수행하여 분획물을 수득할 수 있다. 또한, 본 발명의 일 실시형태에 따르면, 황칠 발효 추출물을 유기용매로 분획하여 분획물을 수득할 수 있다.Next, the Huangchil extract can be fractionated with an organic solvent, and then subjected to column chromatography to obtain fractions. In addition, according to one embodiment of the present invention, the fermented yellowtail extract can be fractionated with an organic solvent to obtain fractions.
상기 유기용매는 고체, 기체, 액체를 녹일 수 있는 액체 유기 화합물로서, 당업계에서 통상적으로 사용하는 유기용매를 사용할 수 있으며, 바람직하게는 메탄올, 클로로포름, 아세테이트, 헥산, 디클로로메탄, 아세톤, 아세토니트릴, 벤젠 또는 이들의 혼합 용매를 사용할 수 있다.The organic solvent is a liquid organic compound capable of dissolving a solid, a gas and a liquid. An organic solvent commonly used in the art can be used, and preferably an organic solvent such as methanol, chloroform, acetate, hexane, dichloromethane, acetone, acetonitrile , Benzene, or a mixed solvent thereof.
상기 컬럼 크로마토그래피는 고정상 알갱이를 크로마토관에 기둥 모양으로 채워서 넣고 진행하는 크로마토그래피법으로서, 필요에 따라 적절한 충진제를 선택하여 수차례 실시할 수 있으며, 바람직하게는 상기 충진제는 실리카겔, 세파덱스, RP-18, 폴리아미드, 도요펄(toyopearl) 또는 XAD 수지를 사용하여 분리 및 정제할 수 있다.The column chromatography is a chromatographic method in which a fixed-bed granule is filled in a column of a chromatographic column and proceeds. When necessary, an appropriate filler may be selected and performed several times. Preferably, the filler is silica gel, Sephadex, RP -18, polyamide, toyopearl or XAD resin.
다음으로, 상기 분획물로부터 고성능 액체크로마토그래피를 수행하여 화합물을 분리할 수 있다.Next, high performance liquid chromatography can be performed on the fractions to separate the compounds.
상기 고성능 액체크로마토그래피(HPLC)는 컬럼, 컬럼에 채우는 고정상의 충진제 그리고 장치의 개선, 개량에 의해 고속 및 고성능의 분리가 가능해진 크로마토그래피 방법으로서, 최종적으로 16-아세틸-9,17-옥타데카디엔-12,14-디노익산 (16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물을 분리할 수 있다.The high-performance liquid chromatography (HPLC) is a chromatographic method capable of high-speed and high-performance separation by improvement and improvement of a column, a fixed-bed filler filled in a column and an apparatus, and finally, 16-acetyl-9,17- (16-acetyl-9,17-octadecadiene-12,14-diynoic acid) can be isolated.
상기 화합물의 분자량 측정, 분자식 추정 및 핵자기 공명(nuclear magnetic resonance, NMR) 분석법에 의한 구조 확인 결과, 화학식 1로 표시되는 (9Z, 16S)-16-아세틸-9,17-옥타데카디엔-12,14-디노익산 화합물임을 확인하였다.(9Z, 16S) -16-acetyl-9,17-octadecadien-12 < / RTI > represented by the general formula (1) as a result of molecular weight measurement, molecular estimation and nuclear magnetic resonance , 14-dinoic acid compound.
또한, 상술한 바와 같이, 상기 디노익산 화합물을 메틸레이션 하여 화학식 2로 표시되는 화합물을 얻을 수 있다.Further, as described above, the compound represented by the general formula (2) can be obtained by methylation of the dinnoic acid compound.
메틸화시키는 방법 내지 조건은 특별히 제한되지 않고, 당업계에서 통상적으로 알려진 방법을 사용할 수 있다. 이에 제한되는 것은 아니나, 예를 들면, 화학식 1의 화합물을 다이아조메테인(diazomethane), 메탄올과 함께 0℃에서 반응시켜 16-아세틸-9,17-옥타데카디엔-12,14-디노익산 메틸 에스테르를 수득할 수 있다.The method or condition for methylation is not particularly limited, and a method commonly known in the art can be used. For example, the compound of formula (I) is reacted with diazomethane and methanol at 0 ° C to obtain 16-acetyl-9,17-octadecadien-12,14-dinoic acid methyl Ester can be obtained.
본 발명의 다른 실시형태는 16-아세틸-9,17-옥타데카디엔-12,14-디노익산 (16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물 또는 이의 에스테르 유도체 및 이의 약제학적으로 허용가능한 염을 포함하는 요산 배출용 약제학적 조성물을 제공한다.Another embodiment of the present invention is directed to a compound of 16-acetyl-9,17-octadecadiene-12,14-diynoic acid or an ester derivative thereof, There is provided a pharmaceutical composition for uric acid discharge comprising a pharmaceutically acceptable salt.
상술한 바와 같이, 상기 디노익산 화합물은 상기 화학식 1로 표시될 수 있고, 이의 에스테르 유도체는 16-아세틸-9,17-옥타데카디엔-12,14-디노익산 메틸 에스테르로, 상기 화학식 2로 표시될 수 있다.As described above, the above-mentioned dinnoic acid compound can be represented by the above formula (1), and its ester derivative is 16-acetyl-9,17-octadecadien-12,14-dinnoic acid methyl ester. .
또한, 상기 디노익산 화합물 또는 이의 에스테르 유도체의 약제학적으로 허용 가능한 염은 약학적으로 허용 가능한 유리산(free acid)에 의해 형성된 산 부가염일 수 있다.In addition, the pharmaceutically acceptable salt of the dinoic acid compound or an ester derivative thereof may be an acid addition salt formed by a pharmaceutically acceptable free acid.
상기 유리산으로는 유기산과 무기산을 사용할 수 있으며, 무기산으로는 예를 들면, 염산, 브롬산, 황산, 아황산, 인산 등을 사용할 수 있고, 유기산으로는 구연산, 초산, 말레산, 퓨마르산, 글루코산, 메탈설폰산, 아세트산, 글리콜산, 석신산, 타타르산, 4-톨루엔설폰산, 갈락투론산, 엠본산, 글루탐산, 시트르산, 아스파르탄산 등을 사용할 수 있다.As the free acid, organic acids and inorganic acids can be used. As the inorganic acids, for example, hydrochloric acid, bromic acid, sulfuric acid, sulfurous acid, phosphoric acid and the like can be used. Examples of the organic acids include citric acid, acetic acid, maleic acid, fumaric acid, Acid, metal sulfonic acid, acetic acid, glycolic acid, succinic acid, tartaric acid, 4-toluenesulfonic acid, galacturonic acid, embonic acid, glutamic acid, citric acid and arpartic acid.
본 발명의 일 실시형태에 따르면, 산 부가염은 통상의 방법으로 얻어질 수 있으며, 이에 제한되지 않으나, 예를 들면, 디노익산 화합물 또는 이의 에스테르 유도체를 수혼화성 유기용매, 예를 들면 아세톤, 메탄올, 에탄올, 또는 아세토니트릴 등에 녹이고 당량 또는 과량의 유기산을 가하거나 무기산의 산 수용액을 가한 후 침전시키거나 결정화시켜서 제조하거나, 또는 용매나 과량의 산을 증발시킨 후 건조하거나 석출된 염을 흡인 여과시켜 제조할 수 있다.According to one embodiment of the present invention, the acid addition salt can be obtained by a conventional method, but not limited thereto, for example, by reacting the dinnoic acid compound or its ester derivative with a water-miscible organic solvent such as acetone, methanol , Ethanol, or acetonitrile, or by adding an equivalent amount or an excess amount of an organic acid, or by adding an aqueous acid solution of an inorganic acid, followed by precipitation or crystallization, or by evaporating a solvent or an excessive acid, and drying or precipitating the salt by suction filtration Can be manufactured.
또한, 본 발명의 일 실시형태에 따르면, 상기 약제학적 조성물은 상기 디노익산 화합물 또는 이의 에스테르 화합물, 이의 약제학적으로 허용가능한 염과 이로부터 제조될 수 있는 가능한 용매화물, 수화물 및 입체 이성질체를 포함할 수 있다. In addition, according to one embodiment of the present invention, the pharmaceutical composition comprises the above-mentioned dinnoic acid compound or an ester compound thereof, a pharmaceutically acceptable salt thereof and possible solvates, hydrates and stereoisomers thereof which can be prepared therefrom .
본 발명의 일 실시형태에 따른 약제학적 조성물은 요산을 배출하는 효능을 가지는 것으로, 신체 내에서 요산으로 인한 다양한 질병의 치료 또는 예방의 목적으로 사용될 수 있다. The pharmaceutical composition according to one embodiment of the present invention has an efficacy of discharging uric acid and can be used for the purpose of treatment or prevention of various diseases caused by uric acid in the body.
본 발명에서 “예방”은 상기 조성물의 투여로 요산으로 인한 질환의 발병을 억제 또는 지연시키는 모든 행위를 의미할 수 있고, “치료”는 상기 조성물의 투여로 요산으로 인한 질환의 증세가 호전되거나 이롭게 되는 모든 행위를 의미할 수 있다.In the present invention, " prevention " may mean all actions that inhibit or delay the onset of the disease caused by uric acid upon administration of the composition, and " treatment " means that the administration of the composition improves the symptoms of the disease caused by uric acid, It can mean all the acts that are done.
이에 제한되는 것은 아니나, 요산으로 인한 질환은 통풍, 고요산혈증, 신장기능 장애, 신장 결석, 종양 용해 증후군, 및 조발성 고혈압 등일 수 있다.Diseases caused by uric acid can be, but are not limited to, gout, hyperuricemia, renal dysfunction, kidney stones, tumor dissolution syndrome, and premature hypertension.
또한, 본 발명의 일 실시형태에 따르면, 상기 약제학적 조성물은 약학적으로 허용 가능한 담체를 포함할 수 있다.Further, according to one embodiment of the present invention, the pharmaceutical composition may comprise a pharmaceutically acceptable carrier.
약학적으로 허용 가능한 담체를 포함하는 조성물은 경구 또는 비경구의 여러 가지 제형일 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. Compositions comprising a pharmaceutically acceptable carrier can be of various oral or parenteral formulations. In the case of formulation, it can be prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants and the like which are usually used.
경구투여를 위한 고형제제에는 정제환제, 산제, 과립제, 캡슐제 등이 포함될 수 있으며, 이러한 고형제제는 하나 이상의 화합물에 적어도 하나 이상의 부형제 예를 들면, 전분, 탄산칼슘, 수크로오스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 스테아린산 마그네슘, 탈크 등과 같은 윤활제들도 사용될 수 있다. 경구투여를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. Solid formulations for oral administration may include tablet pills, powders, granules, capsules and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have.
비경구투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함될 수 있다. 비수성용제, 현탁용제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테로 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있다.Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the non-aqueous solvent and the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.
또한, 본 발명의 약학적 조성물은 정제, 환제, 산제, 과립제, 캡슐제, 현탁제, 내용액제, 유제, 시럽제, 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제 및 좌제로 이루어진 군으로부터 선택되는 어느 하나의 제형을 가질 수 있다.The pharmaceutical composition of the present invention may also be in the form of tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, Or a pharmaceutically acceptable salt thereof.
본 발명의 약제학적 조성물은 그 투여용량에 특별한 제약은 없고, 체내 흡수도, 체중, 환자의 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설율 및 질환의 중증도 등에 따라 변화될 수 있다. 일반적으로, 일일 투여량은 바람직하게는 디노익산 화합물 또는 이의 유도체의 양을 기준으로 0.1 내지 100 mg/kg일 수 있으며, 보다 바람직하게는 30 내지 80 mg/kg일 수 있으며, 보다 더 바람직하게는 50 내지 60 mg/kg일 수 있다. 본 발명의 약학적 조성물은 유효량 범위를 고려하여 제조하도록 하며, 이렇게 제형화된 단위 투여형 제제는 필요에 따라 약제의 투여를 감시하거나 관찰하는 전문가의 판단과 개인의 요구에 따라 전문화된 투약법을 사용하거나 일정 시간 간격으로 수회 투여할 수 있다.The dosage form of the pharmaceutical composition of the present invention is not particularly limited, and may be varied depending on the degree of absorption, body weight, age, sex, health condition, diet, administration time, administration method, excretion rate, have. In general, the daily dosage may preferably be from 0.1 to 100 mg / kg, more preferably from 30 to 80 mg / kg, based on the amount of the dinnoic acid compound or derivative thereof, 50 to 60 mg / kg. The pharmaceutical composition of the present invention is prepared in consideration of an effective dose range, and the unit dosage formulations thus formulated are classified according to the judgment of the expert who monitors or observes the administration of the drug, if necessary, Or may be administered several times at a predetermined time interval.
본 발명의 또 다른 실시형태는 16-아세틸-9,17-옥타데카디엔-12,14-디노익산 (16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물 또는 이의 에스테르 유도체 및 이의 약제학적으로 허용가능한 염을 포함하는 요산 배출용 의약외품 조성물에 관한 것이다.Another embodiment of the present invention relates to a method for producing 16-acetyl-9,17-octadecadiene-12,14-diynoic acid or an ester derivative thereof, And a quasi-drug composition for uric acid discharge comprising a pharmaceutically acceptable salt thereof.
상기 화합물 및 유도체, 이의 약제학적으로 허용 가능한 염은 상술한 바와 같다.The above-mentioned compounds and derivatives and pharmaceutically acceptable salts thereof are as described above.
본 발명에서 “의약외품”은 사람이나 동물의 질병을 치료, 경감, 처치 또는 예방할 목적으로 사용되는 섬유, 고무제품 또는 이와 유사한 것, 인체에 대한 작용이 약하거나 인체에 직접 작용하지 아니하며, 기구 또는 기계가 아닌 것과 이와 유사한 것, 감염형 예방을 위하여 살균, 살충 및 이와 유사한 용도로 사용되는 제제 중 하나에 해당하는 물품으로서, 사람이나 동물의 질병을 진단, 치료, 경감, 처치 또는 예방할 목적으로 사용하는 물품 중 기구, 기계 또는 장치가 아닌 것 및 사람이나 동물의 구조와 기능에 약리학적 영향을 줄 목적으로 사용하는 물품 중 기구, 기계 또는 장치가 아닌 것을 제외한 물품을 의미한다.The term " quasi-drug product " in the present invention means a fiber, a rubber product or the like used for the purpose of treating, alleviating, treating or preventing a disease of a human or an animal, And similar preparations for the prevention of infectious diseases, products which are used for sterilization, insecticides and similar uses for the prevention of infectious diseases and which are used for the purpose of diagnosis, treatment, alleviation, treatment or prevention of diseases of human beings or animals Means goods, machinery, or apparatus other than articles, machinery, or apparatus of an article that is not an article, machine, or apparatus of an article and that is used to effect pharmacological effects on the structure and function of a person or animal;
본 발명의 조성물을 의약외품 첨가물로 사용할 경우, 상기 조성물을 그대로 첨가하거나 다른 의약외품 또는 의약외품 성분과 함께 사용할 수 있고, 통상적인 방법에 따라 적절하게 사용할 수 있다. 유효성분의 혼합량은 사용 목적에 따라 적합하게 결정될 수 있다.When the composition of the present invention is used as a quasi-drug additive, the composition may be added as it is or may be used together with other quasi-drugs or quasi-drugs, and may be appropriately used according to a conventional method. The amount of the active ingredient to be mixed can be appropriately determined depending on the purpose of use.
본 발명의 의약외품 조성물은 이에 제한되지는 않으나, 바람직하게는 소독청결제, 샤워폼, 가그린, 물티슈, 세제비누, 핸드워시, 가습기 충진제, 마스크, 연고제 또는 필터충진제일 수 있다.The quasi-drug composition of the present invention may be, but is not limited to, disinfectant cleaner, shower foam, gagrin, wet tissue, detergent soap, hand wash, humidifier filler, mask, ointment or filter filler.
본 발명의 또 다른 실시형태는 16-아세틸-9,17-옥타데카디엔-12,14-디노익산 (16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물 또는 이의 에스테르 유도체를 포함하는 요산 배출용 건강기능식품 조성물을 제공한다.Another embodiment of the present invention relates to a method for producing 16-acetyl-9,17-octadecadiene-12,14-diynoic acid or an ester derivative thereof, which comprises reacting 16-acetyl-9,17-octadecadiene- And a health functional food composition for uric acid discharge.
상기 디노익산 화합물 및 이의 에스테르 유도체는 상기에서 설명한 바와 같으며, 상기에서 설명한 약제학적으로 허용가능한 염을 포함할 수 있다.The above-mentioned dinnoic acid compound and its ester derivatives are as described above, and may include the pharmaceutically acceptable salts described above.
본 발명의 일 실시형태에 따른 요산 배출용 건강기능 조성물로 건강기능식품을 제조하는 경우, 상기 조성물을 그대로 첨가하거나 다른 건강기능식품 또는 건강기능식품 성분과 함께 사용할 수 있으며, 통상적인 방법에 따라 적절하게 사용할 수 있다. 본 발명에 따른 건강기능 조성물의 유효성분의 혼합량은 사용 목적에 따라 적합하게 결정될 수 있다. 이에 제한되는 것은 아니나, 예를 들면, 식품 또는 음료의 제조 시에 본 발명의 조성물은 원료에 대하여 0.1 중량부 내지 20 중량부의 양으로 첨가될 수 있다.When a health functional food is prepared from the health functional composition for uric acid discharge according to one embodiment of the present invention, the composition may be added as it is or may be used together with other health functional foods or health functional food ingredients, Can be used. The mixing amount of the active ingredient of the health functional composition according to the present invention can be appropriately determined depending on the intended use. For example, the composition of the present invention may be added in an amount of 0.1 part by weight to 20 parts by weight based on the raw material, for example, in the production of food or beverage.
그러나 건강 조절 및 위생을 목적으로 하는 장기간의 섭취 등의 특별한 경우에는 상기 범위 이하의 양 또는 이상의 범위로도 사용할 수 있다.However, in special cases such as long-term consumption for the purpose of health control and hygiene, it may be used in a range of not more than the above range.
본 발명의 일 실시형태에 따르면, 상기 조성물을 첨가할 수 있는 건강기능식품의 종류에는 특별한 제한은 없다. 이에 제한되는 것은 아니나, 상기 조성물을 첨가할 수 있는 건강기능식품의 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합제 등이 있고, 통상적인 의미에서의 건강기능식품을 모두 포함할 수 있으며, 동물을 위한 사료로 이용되는 식품을 포함할 수 있다.According to one embodiment of the present invention, the kind of the health functional food to which the composition can be added is not particularly limited. Examples of health functional foods to which the composition can be added include, but are not limited to, dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, Soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes, and may include foods used as food for animals, which may include all health functional foods in the conventional sense.
또한, 본 발명의 건강기능식품 조성물이 음료의 형태로 사용될 경우에는 통상의 음료와 같이 여러 가지 감미제, 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상기 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 수크로스와 같은 디사카라이드, 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 및 자일리톨, 소르비톨, 에리트리톨과 같은 당알콜일 수 있다. 상기 감미제는 타우마틴, 스테비아 추출물과 같은 천연 감미제 및 사카린, 아스파르탐과 같은 합성 감미제일 수 있다.In addition, when the health functional food composition of the present invention is used in the form of a drink, it may contain various sweetening agents, flavoring agents, or natural carbohydrates as additional components such as ordinary beverages. The natural carbohydrates may be polysaccharides such as disaccharides such as monosaccharides such as glucose and fructose, maltose, sucrose, dextrin, cyclodextrins, and sugar alcohols such as xylitol, sorbitol and erythritol. The sweeteners may be natural sweeteners such as tau martin and stevia extract, and synthetic sweeteners such as saccharin and aspartame.
상기 외에 본 발명의 건강기능식품 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 천연 과일쥬스, 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다.In addition to the above, the health functional food composition of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, , Alcohols, carbonating agents used in carbonated drinks, and the like. It may also contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks.
본 발명의 또 다른 실시형태는 16-아세틸-9,17-옥타데카디엔-12,14-디노익산 (16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물 또는 이의 에스테르 유도체를 포함하는 요산 배출용 화장료 조성물을 제공한다.Another embodiment of the present invention relates to a method for producing 16-acetyl-9,17-octadecadiene-12,14-diynoic acid or an ester derivative thereof, which comprises reacting 16-acetyl-9,17-octadecadiene- The present invention provides a cosmetic composition for uric acid discharge.
상기 화합물 또는 이의 에스테르 유도체는 상술한 바와 같으며, 상기 화장료 조성물은 상기 화합물 및 에스테르 유도체의 약제학적으로 허용 가능한 염을 포함할 수 있다.The compound or its ester derivative is as described above, and the cosmetic composition may include a pharmaceutically acceptable salt of the compound and the ester derivative.
본 발명의 일 실시형태에 따르면, 상기 화장료 조성물은 통상적으로 화장료 조성물로 사용되는 물질과 함께 사용될 수 있다.According to one embodiment of the present invention, the cosmetic composition can be used in combination with a material conventionally used as a cosmetic composition.
이에 제한되는 것은 아니나, 예를 들면, 상기 화장료 조성물은 추가적으로 지방 물질, 유기 용매, 용해제, 농축제 및 겔화제, 연화제, 항산화제, 현탁화제, 안정화제, 발포제, 방향제, 계면활성제, 물, 이온형 또는 비이온형 유화제, 충전제, 금속이온봉쇄제, 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 또는 친유성 활성제, 지질 소낭 등 화장료 조성물에 통상적으로 사용되는 임의의 다른 성분과 같은 통상적으로 사용되는 보조제를 함유할 수 있다.But are not limited to, for example, the cosmetic composition may further comprise at least one of a fatty substance, an organic solvent, a solubilizing agent, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a perfume, Which are conventionally used in cosmetic compositions such as cosmetics, cosmetics, cosmetics, cosmetics, cosmetics, cosmetics, cosmetics, cosmetics, cosmetics, ≪ / RTI > and other ingredients of the composition.
또한, 본 발명의 일 실시형태에 따르면, 상기 화장료 조성물은 일반적인 유화 제형 및 가용화 제형의 형태로 제조될 수 있다. 상기 유화 제형으로는 영양화장수, 크림, 에센스 등이 있으며, 상기 가용화 제형으로는 유연화장수 등이 있다. 적합한 제형은 이에 제한되지는 않으나, 예를 들어 용액, 겔, 고체 또는 반죽 무수 생성물, 수상에 유상을 분산시켜 얻은 에멀젼, 현탁액, 마이크로에멀젼, 마이크로캡슐, 미세과립구 또는 이온형(리포좀), 바이온형의 소낭 분산제의 형태, 크림, 스킨, 로션, 파우더, 연고, 스프레이 또는 콘실 스틱의 형태일 수 있다. 또한, 포말(foam)의 형태 또는 압축된 추진제를 더 함유한 에어로졸 조성물의 형태일 수 있다.Further, according to one embodiment of the present invention, the cosmetic composition may be prepared in the form of a general emulsified formulation and a solubilized formulation. Examples of the emulsified formulations include nutritive lotions, creams, essences, and the like, and the solubilization formulations include softening longevity. Suitable formulations include, but are not limited to, solutions, gels, solid or paste anhydrous products, emulsions obtained by dispersing the oil phase in water, suspensions, microemulsions, microcapsules, microgranules or ionic (liposomes) A cream, a skin, a lotion, a powder, an ointment, a spray, or a conical stick. It may also be in the form of a foam or in the form of an aerosol composition further containing a compressed propellant.
이하 본 발명을 실시예를 통하여 보다 상세하게 설명한다. 그러나, 이들 실시예는 본 발명을 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.
[[ 실시예Example ]]
황칠나무 추출물 및 이의 Houttuynia cordata extract and its object 분획물의Fraction 제조 Produce
건조된 황칠나무(Dendropanax morbifera) 지상부 5kg을 추출용기에 넣고, 70% 메탄올을 50 L 가하여 7일 동안 냉침시켜 추출하고 여과하였다. 상기 수득한 추출액은 진공회전증발기를 이용하여 감압농축 하였다. 상기 추출 및 농축 과정을 2회 반복하여 황칠나무 추출물을 950g 수득하였다.Dried yellowtail ( Dendropanax morbifera ) 5 kg of the above-ground portion was put into an extraction container, and 50 L of 70% methanol was added, followed by cooling for 7 days and extraction. The obtained extract was concentrated under reduced pressure using a vacuum rotary evaporator. The above extraction and concentration process was repeated twice to obtain 950 g of Hwangchujang extract.
상기 수득한 황칠나무 메탄올 추출물을 5L의 증류수에 현탁시킨 후, 동량의 에틸아세테이트로 추출하는 과정을 3회 반복하였고, 얻어진 추출액을 감압 농축하여 258g의 에틸아세테이트 분획물을 수득하였다. 상기 추출 과정으로부터 수득한 여액을 동량의 n-부탄올로 3회 반복하여 추출하고 추출액을 감압 농축하여 부탄올 분획물 159 g을 얻었다.The obtained methanol extract of Huchulchu was suspended in 5 L of distilled water and extracted with the same amount of ethyl acetate three times. The obtained extract was concentrated under reduced pressure to obtain 258 g of ethyl acetate fraction. The filtrate obtained from the above extraction procedure was repeatedly extracted three times with the same amount of n-butanol, and the extract was concentrated under reduced pressure to obtain 159 g of butanol fraction.
황칠나무 추출물로부터 유효성분의 분리 및 동정Isolation and Identification of Active Ingredients from Horticultural Extracts
상기 수득한 분획물 중 에틸아세테이트 분획물 220 g을 취하여, 디클로로메탄/메탄올 혼합 용액을 이동상으로 흘려주되 디클로로메탄/메탄올 혼합비를 100:1로부터 1:1까지 순차적으로 증가시키는 농도구배 용출방식으로 실리카겔 컬럼 크로마토그래피를 실시하여 총 4개의 분획 (제1분획~제5분획)을 획득하였다. 220 g of the ethyl acetate fraction of the obtained fractions was passed through a dichloromethane / methanol mixed solution as a mobile phase, and the dichloromethane / methanol mixing ratio was sequentially increased from 100: 1 to 1: 1. The concentration gradient elution was carried out by silica gel column chromatography To obtain a total of four fractions (first to fifth fractions).
수득한 제2분획(20g)을 재차 실리카겔 컬럼 크로마토그래피 (이동상: n-헥산/에틸아세테이트 (50:1~1:1))를 실시하여 5개의 분획 (제21분획~제25분획)으로 나누었다. 이 중, 제21분획을 재결정 (용매: n-헥산)하여 흰색 분말을 얻었고 이 분말을 실리카겔 컬럼 크로마토그래피 (이동상: 디클로로메탄/메탄올 (40:1))를 실시하여 화합물 3 (10.0 mg)과 화합물 4 (14.5 mg)를 분리하였다. 또한, 제22분획을 재결정 (용매: n-헥산)하여 화합물 5 (120.0 mg)을 얻었으며, 재결정 후 남은 모액은 다시 실리카겔 컬럼 크로마토그래피 (용매: n-헥산/에틸아세테이트(50:1~1:1))를 실시하여 5개의 소분획 (제221분획~제225분획)으로 나누었다. 제224분획을 재결정 (용매: n-헥산)하여 흰색 분말을 얻었고, 1H NMR과 13C NMR을 통하여 화합물 6과 화합물 7이 1:3.5의 비율로 섞여있는 혼합물 (490.7 mg)임을 확인하였다. The obtained second fraction (20 g) was again subjected to silica gel column chromatography (mobile phase: n-hexane / ethyl acetate (50: 1 to 1: 1)) to divide into five fractions (
상기 수득한 제3분획(34 g)을 실리카겔 컬럼 크로마토그래피 (이동상: n-헥산/에틸아세테이트(10:1~1:1))를 실시하여 5개의 분획 (제31분획~제35분획)으로 나누었다. 이 중, 제32분획을 재차 실리카겔 컬럼 크로마토그래피 (이동상: n-헥산/에틸아세테이트(30:1~5:1))로 두 차례 더 정제하여 흰색분말 70.0 mg을 얻었고, 1H NMR과 13C NMR을 통하여 화합물 8과 화합물 9가 1:1의 비율로 섞여있는 혼합물임을 확인하였다. 제34분획은 실리카겔 컬럼 크로마토그래피 (이동상: n-헥산/에틸아세테이트 (20:1~1:1))를 실시한 뒤, 70% 메탄올(이동상)로 역상 컬럼 크로마토그래피로 분리/정제하여 화합물 1 (201.0mg) 및 화합물 2(112.0 mg)를 각각 얻었고, 화합물 1은 신규화합물임을 확인하였다. 분리된 각각의 화합물들은 1H-NMR 및 13C-NMR을 사용하여 구조를 확인하였다.The obtained third fraction (34 g) was subjected to silica gel column chromatography (mobile phase: n-hexane / ethyl acetate (10: 1 to 1: 1)) to give five fractions (fractions 31 to 35) I divided it. The 32nd fraction was further purified twice by silica gel column chromatography (mobile phase: n-hexane / ethyl acetate (30: 1 to 5: 1)) to obtain 70.0 mg of white powder. 1 H NMR and 13 C NMR showed that
상기에서 분리된 9종의 화합물을 분리하였으며, 이들 화합물의 구조식과 명칭을 도 1에 나타내었다.The nine compounds separated from the above were isolated, and the structural formula and the names of these compounds are shown in FIG.
도 2는 본 발명의 일 실시형태에 따라 얻어진 16-아세틸-9,17-옥타데카디엔-12,14-디노익산 및 이의 메틸화에 의해 얻어진 16-아세틸-9,17-옥타데카디엔-12,14-디노익 메틸 에스테르의 H-NMR 분석 그래프이다.Fig. 2 is a graph showing the activity of 16-acetyl-9,17-octadecadien-12, 14-dinoic acid and 16-acetyl-9,17-octadecadien-12 obtained by its methylation obtained according to an embodiment of the present invention, ≪ 1 > H-NMR analysis of 14-dinioxime methyl ester.
도 3은 본 발명의 일 실시형태에 따라 얻어진 16-아세틸-9,17-옥타데카디엔-12,14-디노익산 및 이의 메틸화에 의해 얻어진 16-아세틸-9,17-옥타데카디엔-12,14-디노익 메틸 에스테르의 C-NMR 분석 그래프이다.Fig. 3 is a graph showing the activity of 16-acetyl-9,17-octadecadien-12, 14-dinoic acid obtained according to an embodiment of the present invention and 16- C-NMR analysis of 14-dinioxime methyl ester.
크산틴 Xanthine 옥시다제Oxidase (( XanthineXanthine OxidaseOxidase ) 저해 측정) Inhibition measurement
1. 시험용액 제조1. Preparation of Test Solution
1) 인산완충용액1) Phosphate buffer solution
NaH2PO4 .2H2O 3.12 g을 물에 녹이고 증류수로 100.0 mL을 만들어 A 용액(0.2 M NaH2PO4)을 만들고, Na2HPO4 28.39 g을 물에 녹이고 증류수로 1000mL을 만들어 B 용액(0.2 M Na2HPO4) 만들었다. 상기 A 용액 34mL과 B 용액 366mL 및 증류수 400mL를 혼합하여 0.1 M 인산완충용액 (pH 7.8)을 제조하였다. NaH 2 PO 4 . 2H 2 O 3.12 g were dissolved in water to make a 100.0 mL with distilled water A solution (0.2 M NaH 2 PO 4) is created, Na 2 HPO 4 28.39 g was dissolved in water to make a 1000mL of distilled water B solution (0.2 M Na 2 HPO 4 ) made. 34 mL of the A solution, 366 mL of the B solution and 400 mL of distilled water were mixed to prepare a 0.1 M phosphate buffer solution (pH 7.8).
2) 크산틴(Xanthine) 완충용액2) Xanthine buffer solution
크산틴(Xanthine) 12.20 mg을 처음에 0.25 N NaOH(200μL 정도)에 녹인 후 0.1 mM 인산완충용액으로 희석하여 200mL로 만들어 400μM 농도의 용액으로 제조하였다.12.20 mg of Xanthine was first dissolved in 0.25 N NaOH (200 μL) and diluted with 0.1 mM phosphate buffer to make 200 mL.
3) Xanthine oxidase 용액3) Xanthine oxidase solution
구입한 효소 시약(Xanthine oxidase from cow’s milk [Sigma-Aldrich]) 200.0μL에 인산완충용액을 넣어서 10mL를 만들고, 이에 0.1mM 인산완충용액(pH 7.8)으로 희석하여 최종 농도가 0.4 U/mL되게 제조하였다.10 mL of phosphate buffer solution was added to 200.0 μL of the purchased enzyme reagent (Xanthine oxidase from cow's milk [Sigma-Aldrich]) and diluted with 0.1 mM phosphate buffer (pH 7.8) to prepare a final concentration of 0.4 U / mL Respectively.
4) 시험 용액4) Test solution
상기에서 얻어진 황칠 추출물을 각각 동결건조 및 분무건조하여 만들어진 분말을 1mM 인산완충용액으로 농도가 1,000, 500, 300, 200, 100, 50μg/mL이 되도록 제조하였다.The powder obtained by lyophilization and spray drying of each of the above obtained Huangchil extract was prepared to have a concentration of 1,000, 500, 300, 200, 100 and 50 μg / mL with 1 mM phosphate buffer solution.
2. 크산틴 2. Xanthine 옥시다제Oxidase 저해 측정 Inhibition measurement
대조군으로 크산틴 옥시다제(Xanthine oxidase) 용액(0.4 U/mL) 7.0μL을 0.1 M 인산완충용액(pH 7.8) 127.0μL와 혼합하고 37℃에서 10분간 방치하였다. 그리고 66.0μL의 크산틴 완충용액(400μM)을 첨가하여 잘 섞은 후, 37℃에서 10분 후 295nm에서 흡광도를 측정하였다. Blank 용액은 효소 용액 대신 7μL의 인산완충용액을 넣었다. 대조군의 295nm에서의 흡광도는 0.563이였다.As a control, 7.0 μL of a solution of xanthine oxidase (0.4 U / mL) was mixed with 127.0 μL of 0.1 M phosphate buffer (pH 7.8) and left at 37 ° C. for 10 minutes. Then, 66.0 μL of xanthine buffer solution (400 μM) was added and mixed well. After 10 minutes at 37 ° C., the absorbance was measured at 295 nm. Blank solution was replaced with 7 μL of phosphate buffer solution instead of enzyme solution. The absorbance of the control group at 295 nm was 0.563.
시험군으로 크산틴 옥시다제(Xanthine oxidase) 용액(0.4 U/mL) 7.0μL을 0.1 M 인산완충용액(pH 7.8) 77.0μL와 각 시험 용액 50μL을 잘 혼합하고 대조군과 같은 방법으로 시험하고, 이의 결과를 하기 표 1 및 도 4에 나타내었다.7.0 μL of Xanthine oxidase solution (0.4 U / mL) was mixed with 77.0 μL of 0.1M phosphate buffer solution (pH 7.8) and 50 μL of each test solution as test groups and tested by the same method as the control group. The results are shown in Table 1 and FIG.
크산틴 옥시다제(Xanthine oxidase) 저해활성(%)은 하기 식과 같이 계산하였다. The inhibitory activity (%) of xanthine oxidase was calculated according to the following formula.
저해활성(%)=1-(B/A)×100Inhibitory activity (%) = 1- (B / A) x 100
상기 식에서, A는 대조군에서의 흡광도변화(Δabs with enzyme-Δ abs without enzyme)이고, B는 시험군에서의 흡광도변화(Δabs with enzyme - Δ abs without enzyme)이다.Where A is the change in absorbance in the control (Δabs with enzyme - Δ abs without enzyme) and B is the change in absorbance in the test group (Δabs with enzyme - Δ abs without enzyme).
(XO IR(%)Xanthine oxidase inhibition rate
(XO IR (%)
(동결건조)Huangchil extract powder
(Freeze-dried)
(분무건조)Huangchil extract powder
(Spray drying)
도 4는 황칠 분무 건조 분말에 대한 크산틴 옥시다제의 저해율을 나타내는 그래프이다. 상기 표 1 및 도 4에 도시된 바와 같이, 황칠 추출물은 크산틴 옥시다제의 활성을 저해하는 효과가 미비한 것으로 확인되었다.FIG. 4 is a graph showing the inhibition rate of xanthine oxidase to the powdery dried powder. As shown in Table 1 and FIG. 4, it was confirmed that the Huangchil extract had little effect of inhibiting the activity of xanthine oxidase.
요산 배출 실험Uric acid emission experiment
중앙실험동물로부터 구입한 8주령 수컷 ICR mice를 1주간 환경적응 시킨 후 고요산 유도물질인 PO(Potassium oxonate)를 200mg/kg로 ip 주사하였다. 1시간 후에 인산완충 생리식염수(PBS), BZM(Benzbromaron) 10mg/kg, HRCom8 10mg/kg(HRCom8-1), 및 HRCom8 50mg/kg(HRCom8-2)을 경구투여하고, 경구 투여 후 대사케이지에서 처리구별로 6시간 물만 공급하였다.8 weeks old male ICR mice purchased from the central laboratory animals were subjected to ip injection for 200 mg / kg of PO (Potassium oxonate), which is a high temperature inducing substance, for 1 week. After 1 hour, oral administration of phosphate buffered saline (PBS), BZM (Benzbromaron) 10 mg / kg,
6시간 후에 복대정맥으로부터 혈액을 채취하고, 오줌을 회수하였다. 혈액은 혈청을 분리하고 오줌은 불순물을 제거하여 분석 시까지 냉동 보관하였다. 혈액분석기로 요산수치를 측정하고, 이의 결과를 하기 표 2및 도 5에 나타내었다.After 6 hours, blood was collected from the abdominal vein and urine was collected. Blood was separated from serum and urine was removed free of impurities and stored frozen until analysis. The uric acid level was measured with a blood analyzer, and the results are shown in Table 2 and FIG.
상기 표 2 및 도 5를 참조하면, 대조군과 비교하여 황칠 추출물에서 분획된 신물질 HRCom8를 투여하는 경우 혈액에서 요산의 수치가 감소하고, 오줌에서 요산의 수치가 증가하여 요산 배출을 촉진하는 것을 확인할 수 있었다. 또한, 양성대조구로 사용된 BZM보다 요산 배출 효과가 우수하였고, 신물질 HRCom8는 농도 의존적으로 요산 배출을 촉진하는 것을 확인하였다.Referring to Table 2 and FIG. 5, when the fresh HRCom8 fraction isolated from Huangchil extract was compared with the control group, it was confirmed that the uric acid level in the blood decreased and the uric acid level in the urine increased, there was. In addition, the uric acid emission effect was better than BZM used as a positive control, and HRCom8, a new substance, was found to promote uric acid emission in a concentration dependent manner.
이상, 구현예 및 실시예를 들어 본 발명을 상세하게 설명하였으나, 본 발명은 상기 구현예들에 한정되지 않으며, 여러 가지 다양한 형태로 변형될 수 있으며, 본 발명의 기술적 사상 내에서 당 분야에서 통상의 지식을 가진 자에 의하여 여러 가지 많은 변형이 가능함이 명백하다. 또한, 청구범위에 기재된 본 발명의 기술적 사상을 벗어나지 않는 범위 내에서 당 기술분야의 통상의 지식을 가진 자에 의해 다양한 형태의 치환, 변형 및 변경이 가능할 것이며, 이 또한 본 발명의 범위에 속한다고 할 것이다.While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, but many variations and modifications may be made without departing from the scope of the present invention. It is evident that many variations are possible by those skilled in the art. It will be apparent to those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. something to do.
Claims (12)
(b) 상기 황칠 추출물을 유기용매로 분획하고, 컬럼 크로마토그래피를 수행하여 분획물을 수득하는 단계;
(c) 상기 분획물로부터 고성능 액체크로마토그래피를 수행하여 16-아세틸-9,17-옥타데카디엔-12,14-디노익산 (16-acetyl-9,17-octadecadiene-12,14-diynoic acid) 화합물을 분리하는 단계; 및
상기 화합물의 분리 단계 후에 상기 화합물의 메틸레이션에 의하여 16-아세틸-9,17-옥타데카디엔-12,14-디노익 메틸 에스테르를 얻는 단계;
를 포함하는 하기 화학식 1 및 이의 에스테르 유도체인 하기 화학식 2로 표시되는 요산 배출용 화합물의 제조방법.
[화학식 1]
[화학식 2]
(b) fractionating the Huangchil extract with an organic solvent and performing column chromatography to obtain a fraction;
(c) High performance liquid chromatography was performed on the fractions to obtain 16-acetyl-9,17-octadecadiene-12,14-diynoic acid (16-acetyl-9,17-octadecadiene- ; And
Obtaining the 16-acetyl-9,17-octadecadien-12,14-dinioxime methyl ester by methylation of the compound after the step of separating the compound;
(1) and an ester derivative thereof represented by the following general formula (2).
[Chemical Formula 1]
(2)
상기 황칠 추출물을 수득하는 단계 이후에 상기 황칠 추출물을 미생물 발효하여 황칠 발효 추출물을 얻고, 상기 황칠 발효 추출물로 상기 분획물 수득 단계를 수행하는 요산 배출용 화합물의 제조방법. The method according to claim 6,
Wherein the extract of Huangchil is fermented by microbial fermentation to obtain a Huangchil fermented extract, and the step of obtaining the fraction is carried out by using the Huangchil fermentation extract.
[화학식 2]
(2)
[화학식 2]
(2)
[화학식 2]
(2)
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