KR100637263B1 - A pharmaceutical composition comprising the extract of Sorbus amurensis KOEHNE for treating or preventing cerebrovascular system disease - Google Patents
A pharmaceutical composition comprising the extract of Sorbus amurensis KOEHNE for treating or preventing cerebrovascular system disease Download PDFInfo
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- KR100637263B1 KR100637263B1 KR1020040002641A KR20040002641A KR100637263B1 KR 100637263 B1 KR100637263 B1 KR 100637263B1 KR 1020040002641 A KR1020040002641 A KR 1020040002641A KR 20040002641 A KR20040002641 A KR 20040002641A KR 100637263 B1 KR100637263 B1 KR 100637263B1
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- 239000011719 vitamin A Substances 0.000 description 1
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Abstract
본 발명은 정공피 추출물을 포함하는 뇌혈관계 질환의 치료 및 예방을 위한 약학조성물에 관한 것으로서, 상세하게는 본 발명의 정공피 추출물은 혈관 평활근(vascular smooth muscle)의 수축과 이완을 조절하는 가장 중요한 기전 중 하나인 혈관 내피세포 유래 산화질소(NO)의 합성을 증가시켜 혈관이완 효과를 나타내므로, 본 발명의 정공피 추출물을 포함하는 조성물은 뇌혈관계 질환의 예방 및 치료를 위한 의약품 또는 건강기능식품으로 유용하게 이용될 수 있다.The present invention relates to a pharmaceutical composition for the treatment and prevention of cerebrovascular diseases, including a hole blood extract, specifically, the hole blood extract of the present invention is the most important to control the contraction and relaxation of vascular smooth muscle Since one of the mechanisms increases the synthesis of vascular endothelial cell-derived nitric oxide (NO), and thus exhibits a vasorelaxant effect, the composition comprising the hole-derived extract of the present invention is a medicine or health functional food for preventing and treating cerebrovascular diseases It can be usefully used as.
정공피, 산화질소, 뇌혈관계 질환, 혈관 평활근, 의약품, 건강기능식품Hole skin, nitric oxide, cerebrovascular disease, vascular smooth muscle, medicine, health functional food
Description
도 1a는 정공피 각 용매별 추출물(100 ㎍/㎖) 즉, 정공피 헥산 가용추출물, 정공피 에틸아세테이트 가용 추출물 및 정공피 n-부탄올 가용 추출물의 혈관 이완 활성을 측정한 도이고, 도 1b는 정공피 n-부탄올 가용 추출물의 각 농도별 혈관 이완 효과를 측정한 도이다. Figure 1a is a measure of the vascular relaxation activity of each solvent extract (100 ㎍ / ㎖), that is, hole hexane soluble extract, hole extract ethyl acetate soluble extract and hole extract n-butanol soluble extract, Figure 1b Figure 1 shows the measurement of blood vessel relaxation effect at each concentration of hole-derived n-butanol soluble extract.
본 발명은 정공피 추출물을 포함하는 뇌혈관계 질환의 예방 및 치료를 위한 약학조성물에 관한 것이다.The present invention relates to a pharmaceutical composition for the prevention and treatment of cerebrovascular diseases comprising a hole blood extract.
혈관 평활근(vascular smooth muscle)에서 수축과 이완을 조절하는 기전은 매우 다양하다. 이러한 기전 중에서 가장 중요한 기전 중 하나는 혈관 내피세포 유래 이완인자(endothelium-derived relaxing factor)로서 본체는 산화질소(NO)이다. 혈관에서의 산화질소는 L-아르기닌(L-arginine)을 기질로 해서 산화질소 합성효소(Nitric Oxide Synthase, NOS)에 의해 혈관 내피세포에서 생성된다. 이러한 NOS의 이소형태(isoform)는 적어도 3 종류가 존재하는데, 첫 번째 유형은 뇌형 산화질소 합성 효소(bNOS, nNOS, NOS Ⅰ)로 뇌 조직에서 처음 발견되었고 주로 신경 전달 물질로서의 산화질소를 합성하는 역할을 하고 있다. 두 번째 동위 효소는 유도형 산화질소 합성효소(iNOS, NOS Ⅱ)로서 주로 면역계에 작용하는 산화질소를 합성하고 있으며, 세 번째 동위 효소는 혈관 내피 세포에 주로 분포하면서 혈관을 이완시키는데 작용하는 혈관 내피 세포형 산화질소 합성 효소(ecNOS, eNOS, NOS Ⅲ)로서 아세틸콜린(acetylcholine)에 의해 활성화되어 혈관을 이완시킨다(Arnold WP, Mittal CK et al., Proc. Natl. Acad. Sci. USA, 74(8), pp3203-3207, 1977). 이러한 산화질소는 세포질의 구아닐산 시클라아제(guanylate cyclase)를 활성화시켜 cGMP의 생성을 증가시켜서 신호 전달체계를 통해 혈관 평활근을 이완시킨다(Arnold WP, Mittal CK et al., Proc. Natl. Acad. Sci. USA, 74(8), pp3203-3207, 1977). The mechanisms that control contraction and relaxation in vascular smooth muscles vary widely. One of the most important of these mechanisms is the endothelium-derived relaxing factor (vascular endothelial cell), the body is nitric oxide (NO). Nitric oxide in blood vessels is produced in vascular endothelial cells by nitric oxide synthase (NOS) using L-arginine as a substrate. There are at least three isoforms of NOS, the first of which is the brain-type nitric oxide synthase (bNOS, nNOS, NOS I), first discovered in brain tissue and primarily synthesizing nitric oxide as a neurotransmitter. Playing a role. The second isoenzyme is an inducible nitric oxide synthase (iNOS, NOS II), which synthesizes nitric oxide, which mainly acts on the immune system, and the third isozyme is distributed mainly in vascular endothelial cells and acts to relax blood vessels. Cellular nitric oxide synthase (ecNOS, eNOS, NOS III) is activated by acetylcholine to relax blood vessels (Arnold WP, Mittal CK et al., Proc. Natl. Acad. Sci. USA, 74 ( 8) , pp 3203-3207, 1977). This nitric oxide activates cytoplasmic guanylate cyclase, increases the production of cGMP, and relaxes vascular smooth muscle through signal transduction systems (Arnold WP, Mittal CK et al., Proc. Natl. Acad. Sci). USA, 74 (8) , pp 3203-3207, 1977).
혈관 내피세포 유래 이완인자는 내피세포에서 정상 상태에서도 합성 및 분비가 이루어지고 아세틸콜린, 히스타민(histamine), 물질 P(substance P) 및 이소프로테레놀(isoproterenol) 등의 효능제에 의해서 합성 및 분비가 증가된다. 혈관 내피 세포에서 산화질소의 생성을 증가시켜 혈관을 이완시키는 한약이나 생약 또한 최근에 몇 가지 보고된 바 있는데, 쿠라모키(Kuramochi) 등(Kuramochi T. et al., Life Sci., 54(26), pp2061-2069, 1994)은 조구등 전탕액이 산화질소 의존적으로 혈관이완 효과를 증가시킨다는 보고를 한 바 있고, 고토(Goto) 등(Goto H. et al., Am. J. Chinese Med., 27(3-4), pp339-345, 1999)은 연속되는 연구 결과에서 조구등 전탕액이 자연발증 고혈압의 혈압을 강하시키고 메탄올 추출물이 산화질소 의존적으로 흉부 대동맥의 혈관을 이완시킨다고 보고하였다. 또한 단삼의 리토스페르민산 B(lithospermic acid B), 동충하초의 단백질 성분 등도 산화질소 의존적으로 혈관 이완을 증가시키는 것으로 알려졌다. 특히 첸(Chen) 등(Chen ZY et al., Life Sci., 63(22), pp1983-1991, 1998)은 산사의 에탄올 추출물이 장간막 동맥을 산화질소 의존적으로 이완시킨다고 보고하였고, 김(Kim) 등은 산사로부터 분리한 프로시아니딘(procyanidins)이 산화질소 의존적으로 혈관을 이완시키고 혈관 cGMP의 생성을 증가시킨다고 보고하였으며, 강(Kang) 등 또한 황련으로부터 분리한 알칼로이드 화합물인 베르베린(berberine)이 NO/cGMP계 의존적으로 혈관을 이완시킨다고 보고하였고, 또한 겨우살이, 은행잎, 방풍, 당귀, 익모초 등의 한약재 추출물도 혈관 내피세포 의존적 또는 비의존적으로 혈관 이완 효과를 보이고, 이들의 유효 성분으로는 글리코시드(glycoside), 프로시아니딘(procyanidine), 플라보노이드(flavonoid) 및 세스퀴테르펜 락톤(sesquiterpene lactone) 화합물들이 밝혀졌다(Nishida S et al., Life Sci., 72(23), pp2659-67, 2003; Lee TH et al., Planta. Med., 68(6), pp492-6, 2002; Yuzurihara M et al., Eur. J. Pharmacol., 444(3), pp183-9, 2002). 이러한 혈관 이완 효과의 약리적 의의는 고혈압, 동맥경화증, 뇌-혈관 질환, 심장 질환을 완화시켜 주는 효과가 있을 뿐만 아니라, 신장 질환과 발기부전 등을 억제하는 효과도 있다는 것이다. Vascular endothelial cell-derived relaxors are synthesized and secreted in endothelial cells even under normal conditions and synthesized and secreted by agonists such as acetylcholine, histamine, substance P, and isoproterenol. Is increased. Herbal medicines and herbal medicines that relax blood vessels by increasing the production of nitric oxide in vascular endothelial cells have also recently been reported, such as Kuramochi et al. (Kuramochi T. et al., Life Sci., 54 (26)). , pp2061-2069, 1994) reported that lyophilized solution increased nitric oxide-dependent vasorelaxant effect, and Goto et al. (Goto H. et al., Am. J. Chinese Med., 27) . (3-4) , pp339-345, 1999), in a series of studies reported that precoating fluids decreased the blood pressure of spontaneous hypertension and methanol extracts relaxed the blood vessels of the thoracic aorta in a nitric oxide-dependent manner. In addition, lithospermic acid B (lithospermic acid B) and protein components of Cordyceps sinensis are known to increase vascular relaxation depending on nitric oxide. In particular, Chen et al. (Chen ZY et al., Life Sci., 63 (22) , pp1983-1991, 1998) reported that the ethanol extract of the hawthorn relaxes the mesenteric artery nitric oxide-dependently, Kim. Et al. Reported that procyanidins isolated from hawthorn have nitric oxide-dependent relaxation of blood vessels and increased production of vascular cGMP.Kang et al. Also reported that berberine, an alkaloid compound isolated from rhubarb, is NO / cGMP. It has been reported to relax blood vessels in a system-dependent manner, and herbal extracts such as mistletoe, ginkgo biloba, windproof, Angelica and motherwort also exhibit vascular endothelial-dependent or independence-dependent vascular relaxation, and their active ingredient is glycoside (glycoside). , Procyanidine, flavonoid and sesquiterpene lactone compounds have been identified (Nishida S et al., Life Sci., 72 (23) , pp2 659-67, 2003; Lee TH et al., Planta.Med ., 68 (6) , pp492-6, 2002; Yuzurihara M et al., Eur. J. Pharmacol., 444 (3) , pp183-9, 2002). The pharmacological significance of the vascular relaxation effect is not only to alleviate hypertension, arteriosclerosis, brain-vascular disease, heart disease, but also to inhibit kidney disease and erectile dysfunction.
정공피는 당마 가목 및 동속 근연 식물의 경피로써 조피를 제거하고 그대로 사용하는 한약재로 강장, 진해, 거풍, 거담의 효과가 알려져 있다(정보섭, 신민교. 도해 향약(生藥)대사전, 영림사, p618, 1990). 국내산 성분으로는 트리테르펜(triterpene)계인 루페올(lupeol)와 루에프논(luepnone)(이상명, 이철규, Analytical Science & Technology, 12(2), pp.136-140, 1999) 등이 알려져 있고, 유럽산의 성분으로는 트리테르펜계인 루페올(Davy LG, Chem and Ind., p732, 1950), β-시토스테롤(sitosterol)(Narasinhachari N, Von Rudlof E, Can. J. Chem., 40, p11189, 1962) 등이 발견되었고, 페닐(phenyl)계 화합물로 아쿠파린(aucuparin)(Narasinhachari N, Von Rudlof E, Can. J. Chem., 40, p11189, 1962), 메톡시아쿠파린(methoxyacuparin)(Erdtman H, Eriksson G, et al., Acta. Chem. Scand, 17, p1151, 1963), 디하이드로신아믹 알데하이드(dihydrocinnamic aldehyde)(Malterud KE, Opheim et al., Phytochemistry, 28(5), p1548, 1989) 등이 주성분으로 보고되어 있다. 정공피에 대한 약리 활성 연구로는 간암 및 페암 세포에 대한 생육 억제 활성(이미경 등, 한국 약용 작물학회지, 10(5), 403-408, 2002)만 연구되었을 뿐 다른 약리 작용에 대한 연구는 미미한 편이다.Holes blood dangma gamok and dongsok relatives can remove jopi as transdermal of plants and known to the Chinese medicine effect of the tonic, Jinhae, geopung, geodam as that used as (jeongboseop, sinmingyo. Diagrams hyangyak (生藥) Dictionary, Younglim four, p618, 1990 ). Triterpene-based lupeol (lupeol) and luepnone (Lee Sang-myung, Lee Chul-kyu, Analytical Science & Technology , 12 (2) , pp.136-140, 1999) are known as domestic ingredients. European components include triterpene-based rufeols (Davy LG, Chem and Ind. , P732, 1950), β-sitosterol (Narasinhachari N, Von Rudlof E, Can. J. Chem. , 40 , p11189, 1962 ), And aphenyl phenyl compounds such as acoufarin (aucuparin) (Narasinhachari N, Von Rudlof E, Can. J. Chem. , 40 , p11189, 1962), methoxyacuparin (Erdtman H) , Eriksson G, et al., Acta. Chem. Scand , 17 , p1151, 1963), dihydrocinnamic aldehyde (Malterud KE, Opheim et al., Phytochemistry , 28 (5) , p1548, 1989) Etc. are reported as the main component. The pharmacological activity of hole skins has been studied only against growth inhibitory activity against liver cancer and lung cancer cells (Lee, Mi-Kyung et al., Korean Journal of Medicinal Crop Science, 10 (5), 403-408, 2002). On the side.
또한, 상기 문헌 중 정공피 추출물에 대한 혈관 이완 효과에 대해서는 어떠한 개시나 교시된 바 없다. In addition, there is no disclosure or teaching about the vasorelaxant effect on hole extracts.
이에 본 발명자들은 활혈, 거어 효과가 있는 20 여종의 한약재를 대상으로 혈관 이완 효과를 검색하던 중, 본 발명의 정공피 추출물의 탁월한 혈관 이완 효과 를 확인함으로써 본 발명을 완성하였다.Accordingly, the present inventors completed the present invention by confirming the excellent vascular relaxation effect of the hole blood extract of the present invention while searching for the vascular relaxation effect of about 20 kinds of herbal medicines having an effect of blood and squeezing.
본 발명의 목적은 혈관 평활근(vascular smooth muscle)의 수축과 이완을 조절하는 가장 중요한 기전 중 하나인 혈관 내피세포 유래 산화질소(NO)의 합성을 증가시켜 혈관 이완 효과를 갖는 정공피 추출물을 포함하는 뇌혈관계 질환의 치료 및 예방을 위한 약학조성물을 제공하는 것이다.
It is an object of the present invention to increase the synthesis of vascular endothelial cell-derived nitric oxide (NO), which is one of the most important mechanisms for controlling the contraction and relaxation of vascular smooth muscle, including a hole-derived extract having a vascular relaxation effect. To provide a pharmaceutical composition for the treatment and prevention of cerebrovascular diseases.
상기 목적을 달성하기 위하여, 본 발명은 정공피(Sorbus amurensis KOEHNE) 조추출물 또는 비극성 용매 가용 추출물을 유효성분으로 함유하는 뇌혈관계 질환의 예방 및 치료용 약학조성물을 제공한다.In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of cerebrovascular disease, containing as an active ingredient (Sorbus amurensis KOEHNE) crude extract or non-polar solvent soluble extract.
상기 조추출물은 물 및 메탄올, 에탄올, 부탄올 등과 같은 C1 내지 C4의 저급알콜 및 이들의 혼합용매, 바람직하게는 메탄올에 가용한 추출물을 포함한다.The crude extract includes water and C 1 to C 4 lower alcohols such as methanol, ethanol, butanol and the like, and a mixed solvent thereof, preferably extracts soluble in methanol.
또한, 상기 비극성 용매 가용 추출물은 헥산, 클로로포름, 메틸렌클로라이드 또는 에틸아세테이트와 같은 비극성 용매, 바람직하게는 에틸아세테이트에 가용한 추출물을 포함한다. The non-polar solvent soluble extract also includes extracts soluble in non-polar solvents, preferably ethyl acetate, such as hexane, chloroform, methylene chloride or ethyl acetate.
상기 뇌혈관계 질환은 일과성 뇌허혈 발작, 혈전성 뇌경색, 색전성 뇌경색, 혈류역학적 뇌경색, 열공경색 또는 뇌출혈 등을 포함한다.The cerebrovascular disease includes transient cerebral ischemic attack, thrombotic cerebral infarction, embolic cerebral infarction, hemodynamic cerebral infarction, tearing infarction or cerebral hemorrhage and the like.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명의 정공피 조추출물 또는 비극성 용매 가용 추출물은 하기와 같이 수득될 수 있다.The hole skin crude extract or nonpolar solvent soluble extract of the present invention can be obtained as follows.
본 발명의 정공피를 채집하여 건조하고 마쇄기로 마쇄하여 분말화한 후, 정공피 시료 중량의 약 2 내지 10배, 바람직하게는 약 3 내지 5배에 달하는 부피의 물 및 메탄올, 에탄올, 부탄올 등과 같은 C1 내지 C4의 저급알콜의 극성 용매 또는 이들의 약 1:0.1 내지 1:10의 혼합비를 갖는 혼합용매로, 바람직하게는 메탄올로 실온에서 약 1일 내지 5주간, 바람직하게는 1주 내지 3주간 동안 열수 추출, 냉침 추출, 환류 냉각 추출 또는 초음파 추출 등의 추출방법을 사용하여, 진공여과에 의해 상층액을 회수한 다음, 상기의 과정을 2 내지 5회, 바람직하게는 3회 반복 수행하여 상층액을 모으고 감압농축하여 정공피 조추출물을 수득할 수 있다.After collecting and drying the hole skin of the present invention, pulverized with a crusher and powdered, the volume of water and methanol, ethanol, butanol and the like of about 2 to 10 times, preferably about 3 to 5 times the weight of the hole skin sample Polar solvents of the same C 1 to C 4 lower alcohols or mixed solvents having a mixing ratio thereof of about 1: 0.1 to 1:10, preferably methanol for about 1 to 5 weeks at room temperature, preferably 1 week The supernatant was recovered by vacuum filtration using an extraction method such as hot water extraction, cold needle extraction, reflux cooling extraction or ultrasonic extraction for 2-3 weeks, and then the above procedure was repeated 2 to 5 times, preferably 3 times. The supernatant may be collected and concentrated under reduced pressure to obtain a hole extract.
또한 본 발명의 비극성 용매 가용 추출물은 상기 조추출물을 증류수에 현탁한 후, 이를 현탁액의 약 1 내지 100배, 바람직하게는 약 1 내지 5배 부피의 헥산, 에틸아세테이트, 클로로포름과 같은 비극성 용매를 가하여 1회 내지 10회, 바람직하게는 2회 내지 5회 비극성용매 가용층을 추출, 분리하여 수득할 수 있다. 또한 추가로 통상의 분획 공정을 수행할 수도 있다(Harborne J.B., Phytochemical methods: A guide to modern techniques of plant analysis, 3rd Ed., pp6-7, 1998). In addition, the non-polar solvent soluble extract of the present invention is suspended by distilled water and then added to the non-polar solvent, such as hexane, ethyl acetate, chloroform in about 1 to 100 times, preferably about 1 to 5 times the volume of the suspension. It can be obtained by extracting and separating the nonpolar solvent soluble layer 1 to 10 times, preferably 2 to 5 times. It is also possible to further carry out conventional fractionation processes (Harborne JB, Phytochemical methods: A guide to modern techniques of plant analysis, 3rd Ed. , Pp 6-7, 1998).
더욱 바람직하게는 상기 공정으로 수득된 정공피 조추출물, 바람직하게는 정 공피 메탄올 추출물에 물 및 n-부탄올, 헥산, 에틸아세테이트 등의 유기용매를 극성이 낮은 용매부터 극성이 높은 용매순으로, 바람직하게는 헥산, 에틸아세테이트, n-부탄올, 물의 순으로 순차적으로 용매분획, 감압농축하여 정공피 헥산, 에틸아세테이트, n-부탄올 분획물을 수득할 수 있다. More preferably, water and organic solvents such as n-butanol, hexane, ethyl acetate, and the like are extracted from the low pore solvent to the high polar solvent in the hole skin crude extract obtained by the above process, preferably the hole skin methanol extract. Preferably, hexane, ethyl acetate, n-butanol, and water may be sequentially separated into a solvent and concentrated under reduced pressure to obtain a hole-peel hexane, ethyl acetate, and n-butanol fractions.
본 발명은 상기의 제법으로 얻어진 정공피 조추출물 또는 비극성 용매 가용 추출물을 유효성분으로 함유하는 뇌혈관계 질환의 예방 및 치료용 약학조성물을 제공한다.The present invention provides a pharmaceutical composition for the prevention and treatment of cerebrovascular diseases, which contains the crude extract or non-polar solvent soluble extract obtained by the above method as an active ingredient.
또한, 정공피는 오랫동안 생약으로 사용되어 오던 약재로서 이로부터 추출된 본 발명의 추출물들 역시 독성 및 부작용 등의 문제가 없다. In addition, the hole pill has been used as a herbal medicine for a long time, the extracts of the present invention extracted therefrom also have no problems such as toxicity and side effects.
상기와 같은 방법으로 얻어진 정공피 메탄올 추출물 및 용매 분획물들의 혈관 이완 효과를 검색한 결과, 모든 분획에서 혈관 이완 효과를 확인할 수 있었으며, 에틸아세테이트 분획물의 혈관 이완 효과가 가장 탁월함을 확인할 수 있었다.As a result of retrieving the vascular relaxation effect of the methanol extract and solvent fractions obtained by the above method, it was confirmed that the vascular relaxation effect in all fractions, the vascular relaxation effect of the ethyl acetate fraction was the most excellent.
본 발명의 뇌혈관계 질환의 예방 및 치료용 약학조성물은, 조성물 총 중량에 대하여 상기 추출물을 0.01 내지 90 중량 %로 포함한다. The pharmaceutical composition for preventing and treating cerebrovascular diseases of the present invention comprises the extract in an amount of 0.01 to 90% by weight based on the total weight of the composition.
본 발명의 추출물을 포함하는 약학조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.Pharmaceutical compositions comprising the extract of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
본 발명의 추출물의 약학적 투여 형태는 이들의 약학적 허용가능한 염의 형태로도 사용될 수 있고, 또한 단독으로 또는 타 약학적 활성 화합물과 결합뿐만 아니라 적당한 집합으로 사용될 수 있다. Pharmaceutical dosage forms of the extracts of the present invention may be used in the form of their pharmaceutically acceptable salts, or may be used alone or in combination with other pharmaceutically active compounds, as well as in any suitable collection.
본 발명에 따른 추출물을 포함하는 약학조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 추출물을 포함하는 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로즈, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트 (calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 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. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈 (tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.Pharmaceutical compositions comprising extracts according to the invention, in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterile injectable solutions, respectively, according to conventional methods. Can be formulated and used. Carriers, excipients and diluents that may be included in the composition comprising the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like, and such solid preparations may include at least one excipient such as starch, calcium carbonate and sucrose in the extract. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
본 발명의 추출물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나, 바람직한 효과를 위해서, 본 발명의 추출물은 1일 0.0001 내지 100 mg/kg으로, 바람직하게는 0.001 내지 100 mg/kg으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위을 한정하는 것은 아니다.Preferred dosages of the extracts of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, the extract of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably 0.001 to 100 mg / kg per day. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.
본 발명의 추출물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내 (intracerebroventricular) 주사에 의해 투여될 수 있다. The extract of the present invention can be administered to mammals such as mice, mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
본 발명은 뇌혈관계 질환의 예방 효과를 나타내는 상기 추출물 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 건강기능식품을 제공한다. 정공피 추출물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강 기능성 식품류 등이 있다.The present invention provides a health functional food comprising the extract and a food acceptable food supplement additive exhibiting a prophylactic effect of cerebrovascular disease. Examples of the food to which the hole-skin extract can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods.
또한, 뇌혈관계 질환의 예방 효과를 목적으로 식품 또는 음료에 첨가될 수 있다. 이 때, 식품 또는 음료 중의 상기 추출물의 양은 전체 식품 중량의 0.01 내지 15 중량 %로 가할 수 있으며, 건강 음료 조성물은 100 ㎖를 기준으로 0.02 내지 5 g, 바람직하게는 0.3 내지 1g의 비율로 가할 수 있다. It may also be added to foods or beverages for the purpose of preventing the effects of cerebrovascular disease. At this time, the amount of the extract in the food or beverage may be added in 0.01 to 15% by weight of the total food weight, the health beverage composition may be added in a ratio of 0.02 to 5 g, preferably 0.3 to 1g based on 100 ml. have.
본 발명의 건강 기능성 음료 조성물은 지시된 비율로 필수 성분으로서 상기 추출물을 함유하는 외에는 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ㎖당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.The health functional beverage composition of the present invention is not particularly limited to other ingredients except for containing the extract as an essential ingredient in the indicated proportions, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of said natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 추출물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 추출물들은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 추출물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the extract of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the extracts of the present invention may contain flesh for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is usually selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.
이하, 본 발명을 하기 실시예 및 실험예에 의해 상세히 설명한다.Hereinafter, the present invention will be described in detail by the following Examples and Experimental Examples.
단, 하기 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실험예에 의해 한정되는 것은 아니다.However, the following Examples and Experimental Examples are only illustrative of the present invention, and the content of the present invention is not limited by the following Experimental Examples.
실시예 1. 정공피 조추출물의 제조Example 1 Preparation of Hole Extract
정공피 1.2 ㎏을 구입하여 마쇄기로 갈아 분말화한 후, 메탄올 5 ℓ를 가하여 상온에서 3주간 추출한 다음, 진공 여과하여 상층액을 회수하였다. 이 과정을 3회 반복하여 상층액을 모은 후, 감압 농축하여 정공피 메탄올 추출물 63.2 g을 수득하였다. After purchasing 1.2 kg of hole skin and grinding it with a grinding machine to powder it, 5 L of methanol was added thereto, extracted at room temperature for 3 weeks, and then vacuum filtered to recover the supernatant. This process was repeated three times to collect the supernatant, and then concentrated under reduced pressure to obtain 63.2 g of a hole methanol extract.
실시예 2. 정공피 각 용매별 추출물의 제조Example 2 Preparation of Extract for Each Solvent
상기 실시예 1에서 얻은 정공피 메탄올 추출물 63.2 g을 물 1 ℓ에 현탁시킨 후에, 각각 헥산, 에틸아세테이트, n-부탄올, 물순으로 극성이 낮은 용매부터 극성이 높은 용매순으로 순차적으로 용매분획하였다. 먼저 물 1 ℓ에 현탁시킨 정공피 메탄올 추출물에 헥산 1 ℓ를 첨가하여 용해한 다음, 이를 분획여두에서 헥산층에 용해되는 성분만 분리해서 진공건조하였다. 이 과정을 3회 반복 수행하여 헥산 분획물(헥산 가용 추출물)을 수득하였다(11.7 g). 남은 수층에 에틸아세테이트 1 ℓ를 첨가하여 분획여두에서 에틸 아세테이트층에 용해되는 성분만 분리해서 진공건조하였다. 이 과정을 3회 반복 수행하여 에틸아세테이트 분획물(에틸아세테이트 가용 추출물)을 수득하였으며(15.3 g), 남은 수층에 부탄올 1 ℓ를 가하여 상기와 같은 방법으로 수행하여 부탄올 분획물(부탄올 가용 추출물)을 수득하였다(17.2 g). 마지막으로 남은 수층을 감압 농축하여 수층 분획물(수 가용 추출물)을 수득하였다(12.4 g). After 63.2 g of the hole extract methanol extract obtained in Example 1 was suspended in 1 L of water, hexane, ethyl acetate, n-butanol, and water were each sequentially fractionated from low polar solvents to high polar solvents. First, 1 L of hexane was added to the hole-peel methanol extract suspended in 1 L of water, and then dissolved. Then, only components dissolved in the hexane layer were separated and dried in a vacuum to dry in vacuo. This process was repeated three times to obtain a hexane fraction (hexane soluble extract) (11.7 g). 1 L of ethyl acetate was added to the remaining aqueous layer, and only the components dissolved in the ethyl acetate layer were separated in the fractional filter and dried in vacuo. This procedure was repeated three times to obtain an ethyl acetate fraction (ethyl acetate soluble extract) (15.3 g), and 1 liter of butanol was added to the remaining aqueous layer to obtain a butanol fraction (butanol soluble extract). (17.2 g). Finally, the remaining aqueous layer was concentrated under reduced pressure to give an aqueous layer fraction (water soluble extract) (12.4 g).
실험예 1. 시약 및 실험준비Experimental Example 1. Reagent and Preparation
1-1. 시약1-1. reagent
본 발명에서 사용한 페닐에프린 HCl(phenylephrine HCl), L-NAME(NG-nitroarginine methyl ester), 메틸렌 블루(methylene blue), ODQ, 인도메타신(indomethacin), 글리벤클라미드(glibenclamide), TEA, 베라파밀(verapamil), 아트로핀(atropine), 프로프라놀롤(propranolol) 및 요힘빈(yohimbine) 등은 시그마 케미컬사(Sigma Chemical Co., St. Louis, MO, 미국)로부터 구입하여 사용하였으며, Y-27632 디히드로클로라이드(trans-4-[(1R)-1-aminoethyl]-N-4-pyridinylcyclohexanecarboxamide dihydrochloride) 및 자프리나스트(Zaprinast; 2-(2-propyloxyphenyl)- 8-azapurin-6-one)는 토크리스 쿡손사(Tocris Cookson Ltd., Bristol, 영국)로부터 구입하여 사용하였다. Phenylephrine HCl (phenylephrine HCl), NG-nitroarginine methyl ester (L-NAME), methylene blue (methylene blue), ODQ, indomethacin (glibenclamide), TEA, Verapamil, atropine, propranolol and yohimbine were purchased from Sigma Chemical Co., St. Louis, MO, USA, and used Y-27632 dihydrochloride. ( trans- 4-[(1R) -1-aminoethyl] -N-4-pyridinylcyclohexanecarboxamide dihydrochloride) and Zaprinast (2- (2-propyloxyphenyl) -8-azapurin-6-one) are torqueless Cookson (Tocris Cookson Ltd., Bristol, UK).
1-2. 흉부 대동맥의 분리1-2. Isolation of the thoracic aorta
몸무게 약 250 내지 300 g의 건강한 스프라그-도울리(Sprague-Dawley) 백서를 의식이 있는 상태에서 단두한 후, 흉부 대동맥을 분리하였다. 분리된 흉부 대동맥을 118 mM NaCl, 4.7 mM KCl, 1.1 mM MgSO4, 1.2 mM KH2PO4, 1.5 mM CaCl 2, 25 mM NaHCO3, 10 mM 글루코스가 들어있는 차가운 크렙스(Krebs) 용액(pH 7.4)에 넣고 연결 조직과 지방을 제거한 후 약 3 ㎜ 길이의 절편으로 만들었다. A healthy Sprague-Dawley white paper weighing about 250-300 g was consciously decapitated and the thoracic aorta isolated. The isolated thoracic aorta was transferred to a cold Krebs solution (pH 7.4) containing 118 mM NaCl, 4.7 mM KCl, 1.1 mM MgSO 4 , 1.2 mM KH 2 PO 4 , 1.5 mM CaCl 2 , 25 mM NaHCO 3 , and 10 mM glucose. ), The connective tissue and fat were removed, and then cut into sections of about 3 mm in length.
실험예 2. 정공피 각 용매별 분획물의 혈관 이완효과 측정Experimental Example 2 Measurement of Vascular Relaxation Effect of Fractions by Solvents
상기 실험예 1-2에서 준비한 흉부 대동맥 절편을 95 % O2 및 5 % CO2 기체로 포화시킨 37 ℃의 크렙스 용액에서 고정시킨 후, 등척성 장력(isometric tension)을 힘-변위 변환기(force-displacement transducer, Grass FT 03, USA)가 장착된 생리기록계(Grass physiograph, Model 7E, USA)를 이용하여 측정하였다. 먼저 1 x 10-6 의 페닐에프린(phenylephrine) 으로 수축시키고 10분 후, 1 x 10-6 M의 아세틸콜린(acetylcheoline, ACh)으로 이완 반응을 시켜 혈관 내피 세포의 안전성을 측정한 다음, 크렙스 용액으로 3회 세척하고 실험을 수행하였다. 여러 가지 약물들에 의한 정공피 추출물들의 혈관 이완 효과 변화 측정은 먼저 약물을 20 분간 전처리하고 페닐에프린으로 수축한 후, 이어서 상기 실시예 2의 정공피 각 용매별 추출물에 의한 이완 반응을 농도 의존적(1×10-6 g/㎖ 내지 1×10-4 g/㎖)으로 시켰다. 혈관 내피 세포 비의존형 실험을 수행할 때에는 혈관 내피세포를 작은 면봉으로 제거한 후, 페닐에프린으로 수축과 ACh로 이완 반응을 하여 혈관 내피 세포의 제거를 확인한 다음 실험을 수행하였다. The thoracic aortic section prepared in Experimental Example 1-2 was fixed in a Krebs solution at 37 ° C. saturated with 95% O 2 and 5% CO 2 gas, and then the isometric tension was force-displacement. Measurement was performed using a physiological recorder (Grass physiograph, Model 7E, USA) equipped with a transducer, Grass FT 03, USA. First and contracted in the printer (phenylephrine) in phenyl of 1 x 10 -6 After 10 minutes, followed by a relaxation response to 1 x 10 -6 acetylcholine (acetylcheoline, ACh) of M measuring the safety of the vascular endothelial cells, and then, Krebs The solution was washed three times and the experiment was performed. The measurement of the vascular relaxation effect of the hole skin extracts by various drugs was first pretreated for 20 minutes and contracted with phenylephrine, followed by concentration-dependent relaxation of the relaxation reactions by the solvents of each of the hole skin extracts of Example 2. (1 × 10 −6 g / ml to 1 × 10 −4 g / ml). When vascular endothelial cell-independent experiments were performed, vascular endothelial cells were removed with a small swab, and then contracted with phenylephrine and relaxed with ACh to confirm the removal of vascular endothelial cells.
도 1a에 상기 실시예 2의 정공피 각 용매별 추출물 즉, 정공피 헥산 가용 추출물, 정공피 에틸아세테이트 가용 추출물 및 정공피 n-부탄올 가용 추출물의 혈관 이완효과를 측정한 결과를 나타내었다. 도 1a에서 알 수 있는 것처럼, 모든 추출물에서 혈관 이완효과를 보였으며, 100 ㎍/㎖의 농도에서 헥산 가용 추출물, 에틸아세테이트 가용 추출물 및 n-부탄올 가용 추출물이 각각 39.5 ±1.5, 71.1 ±4.15 및 57.8 ±6.2 %의 이완 효과를 나타내어 에틸아세테이트 가용 추출물의 활성이 가장 높게 나타남을 확인할 수 있었다.Figure 1a shows the results of measuring the vascular relaxation effect of each solvent extract of the hole extract, that is, hole hexane soluble extract, hole extract ethyl acetate soluble extract and hole extract n-butanol soluble extract of Example 2. As can be seen in Figure 1a, all extracts showed a vascular relaxation effect, hexane soluble extract, ethyl acetate soluble extract and n-butanol soluble extract at a concentration of 100 ㎍ / ㎖, respectively 39.5 ± 1.5, 71.1 ± 4.15 and 57.8 The relaxation effect of ± 6.2% was found to be the highest activity of the ethyl acetate soluble extract.
또한, 도 1b에 정공피 n-부탄올 가용 추출물의 각 농도별 혈관 이완 효과를 나타내었다. 도 1b에서 알 수 있는 것처럼, 정공피 부탄올 가용 추출물은 용량-의존적으로 혈관을 이완하였으며, 이러한 이완 효과는 혈관 내피의 제거나 NO계의 억제에 의하여 없어졌다. 따라서 정공피 부탄올 가용 추출물의 혈관 이완 효과는 혈관 내피세포 의존적이고 NO계 의존적임을 알 수 있었다.In addition, Fig. 1b shows the vascular relaxation effect of each concentration of the hole extract n-butanol soluble extract. As can be seen in Figure 1b, the hole-derived butanol soluble extract was dose-dependent to relax the blood vessels, this relaxation effect was eliminated by removal of the vascular endothelium or inhibition of NO system. Therefore, it was found that the vasorelaxant effect of the soluble extract of butanol butanol was vascular endothelial cell dependent and NO system dependent.
실험예 3. 통계처리 Experimental Example 3. Statistical Processing
실험 결과의 유의성은 실험 결과를 스튜던트 t-테스트 및 일원분산 분석(one-way ANOVA test)을 통하여 p가 0.05 이하인 경우 유의한 차이로 판정하였고, 실험치의 표현은 평균 ±표준편차(MEAN ±SE)로 나타내었다.The significance of the experimental results was judged to be a significant difference when the p was less than 0.05 through Student's t-test and one-way ANOVA test, and the expression of the experimental values was mean ± standard deviation (MEAN ± SE). Represented by.
실험예 4. 급성독성 실험Experimental Example 4. Acute Toxicity
3-1. 경구투여3-1. Oral administration
ICR계 마우스와 스프라그 도올리 랫트를 각각 10마리씩 4군으로 나누어 본 발명의 상기 실시예 1의 정공피 메탄올 추출물을 각각 100, 250, 500 및 1000 ㎎/㎏의 용량으로 경구 투여한 후 2주간 독성여부를 관찰한 결과 4군 모두에서 사망한 예가 한 마리도 없었고 외견상 대조군과 별다른 증상을 찾아볼 수 없었다. ICR-based mice and Sprague dooli rats were divided into four groups of 10 rats each, followed by oral administration of the hole extract methanol extract of Example 1 of the present invention at 100, 250, 500 and 1000 mg / kg, respectively, for 2 weeks. No toxicities were observed in all four groups and no symptoms were apparent from the control group.
3-2. 복강투여3-2. Intraperitoneal administration
ICR계 마우스(몸무게 25 ±5 g)와 스프라그 도올리 랫트를 각각 10마리씩 4군으로 나누어 본 발명의 상기 실시예 1의 정공피 메탄올 추출물을 각각 25, 50, 100 및 200 ㎎/㎏의 용량으로 복강투여한 후 24시간 동안 독성여부를 관찰한 결과 4군 모두에서 사망한 예가 한 마리도 없었고 외견상 대조군과 별다른 증상을 찾아볼 수 없었다. 실험 결과, 본 발명의 정공피 추출물은 급성독성이 거의 없음이 확인되었다. ICR-based mice (weight 25 ± 5 g) and Sprague dooli rats were divided into four groups of 10 rats each, and the doses of 25, 50, 100 and 200 mg / kg, respectively, of the hole extract methanol extract of Example 1 of the present invention. Toxicity was observed for 24 hours after intraperitoneal administration, and none of the four groups died. As a result, it was confirmed that the hole extract of the present invention has little acute toxicity.
본 발명의 추출물을 포함하는 약학조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.One example of the formulation of the pharmaceutical composition comprising the extract of the present invention, but the present invention is not intended to limit it, but is intended to explain in detail.
제제예 1. 산제의 제조Formulation Example 1 Preparation of Powder
정공피 추출물 분말 20 mg
유당 100 mg
탈크 10 mgTalc 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.The above ingredients are mixed and filled in an airtight cloth to prepare a powder.
제제예 2. 정제의 제조Formulation Example 2 Preparation of Tablet
정공피 추출물 분말 10 mgHole Extract Powder 10 mg
옥수수전분 100 mg
유당 100 mg
스테아린산 마그네슘 2 mg2 mg magnesium stearate
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.
제제예 3. 캅셀제의 제조Formulation Example 3 Preparation of Capsule
정공피 추출물 분말 10 mgHole Extract Powder 10 mg
결정성 셀룰로오스 3 mg3 mg of crystalline cellulose
락토오스 14.8 mgLactose 14.8 mg
마그네슘 스테아레이트 0.2 mgMagnesium Stearate 0.2 mg
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.
제제예 4. 주사제의 제조Formulation Example 4 Preparation of Injection
정공피 추출물 분말 10 mgHole Extract Powder 10 mg
만니톨 180 mgMannitol 180 mg
주사용 멸균 증류수 2974 mgSterile distilled water for injection 2974 mg
Na2HPO4,12H2O 26 mgNa 2 HPO 4, 12H 2 O 26 mg
통상의 주사제의 제조방법에 따라 1 앰플당(2 ㎖) 상기의 성분 함량으로 제조한다.According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).
제제예 5. 액제의 제조Formulation Example 5 Preparation of Liquid
정공피 추출물 분말 20 mg
이성화당 10 g10 g of isomerized sugar
만니톨 5 g5 g of mannitol
정제수 적량Purified water
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100 ㎖로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.According to the conventional method of preparing a liquid solution, each component is added to the purified water to dissolve it, the lemon flavor is added appropriately, the above components are mixed, purified water is added, the whole is adjusted to 100 ml by the addition of purified water, and then filled in a brown bottle. The solution is prepared by sterilization.
제제예 6. 건강 음료의 제조Formulation Example 6 Preparation of Healthy Drink
정공피 추출물 분말 100 ㎎Hole Extract Powder 100mg
비타민 C 15 g15 g of vitamin C
비타민 E(분말) 100 g100 g of vitamin E (powder)
젖산철 19.75 gIron lactate 19.75 g
산화아연 3.5 g3.5 g of zinc oxide
니코틴산아미드 3.5 gNicotinamide 3.5 g
비타민 A 0.2 g0.2 g of vitamin A
비타민 B1 0.25 g0.25 g of vitamin B 1
비타민 B2 0.3 g0.3 g of vitamin B 2
물 정량Water quantification
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간동안 85 ℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2 ℓ 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다. After mixing the above components in accordance with the conventional healthy beverage manufacturing method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and refrigerated Used to prepare the healthy beverage composition of the invention.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만 수요계층이나, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
상술한 바와 같이, 본 발명의 정공피 조추출물 및 비극성 용매 가용 추출물은 혈관 내피세포 유래 산화질소(NO)의 합성을 증가시킴으로써 혈관 이완 효과를 나타내므로, 뇌혈관계 질환의 예방 및 치료를 위한 약학조성물 또는 건강기능식품으로써 이용될 수 있다.
As described above, the hole extract and non-polar solvent soluble extract of the present invention exhibit a vascular relaxation effect by increasing the synthesis of vascular endothelial cell-derived nitric oxide (NO), so that the pharmaceutical composition for the prevention and treatment of cerebrovascular diseases Or as a dietary supplement.
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