KR100805865B1 - Anti-thrombus agent comprising extract of herbal mixture - Google Patents
Anti-thrombus agent comprising extract of herbal mixture Download PDFInfo
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- KR100805865B1 KR100805865B1 KR1020060070391A KR20060070391A KR100805865B1 KR 100805865 B1 KR100805865 B1 KR 100805865B1 KR 1020060070391 A KR1020060070391 A KR 1020060070391A KR 20060070391 A KR20060070391 A KR 20060070391A KR 100805865 B1 KR100805865 B1 KR 100805865B1
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Abstract
본 발명은 혼합 생약재 추출물을 유효성분으로 함유하는 항혈전용 조성물에 관한 것으로, 황백, 천궁, 부자, 및 남성으로 구성되며, 혈소판 응집 억제율이 우수하여 동맥경화증, 뇌출혈, 뇌졸중, 및 뇌경색과 같은 혈전 형성을 수반하는 질환의 예방 및 치료에 유용하게 사용될 수 있다. The present invention relates to an anti-thrombotic composition containing an extract of a mixed herbal medicine as an active ingredient, and is composed of yellowish white, cheonsung, rich, and male, and has excellent platelet aggregation inhibition rate, such as atherosclerosis, cerebral hemorrhage, stroke, and cerebral infarction It can be usefully used for the prevention and treatment of diseases involving.
항혈전제 Antithrombotics
Description
본 발명은 혼합 생약재 추출물을 유효성분으로 함유하는 항혈전용 조성물에 관한 것으로, 더욱 상세하게는 황백 18 ~ 22 중량부, 천궁 8 ~ 12 중량부, 부자 4 ~ 8 중량부, 및 남성 3 ~ 7 중량부를 포함하는 것을 특징으로 한다.The present invention relates to an anti-thrombotic composition containing the mixed herbal medicine extract as an active ingredient, more specifically, 18 to 22 parts by weight, 8 to 12 parts by weight, 8 to 12 parts by weight, 4 to 8 parts by weight, and 3 to 7 parts by weight of males. It is characterized by including a wealth.
최근 선진국뿐 아니라 우리 나라에서도 동맥경화증, 뇌출혈, 고혈압, 심장병, 뇌졸중, 뇌경색 등 순환기 질환이 사망원인 1, 2위를 차지하게 되었다. 이러한 성인병은 현대사회로 발전하면서 식생활 양식의 변화 및 내, 외부적인 환경 스트레스로 인해 중, 장년층에서 빈번하게 발생하고 있다. 다양한 원인에 의해 혈관이 막혀 상기 질병들이 발생할 수 있는데, 심장 혈관이 막힐 경우 심근 경색증이 일어날 수 있고, 뇌의 혈관이 막혔을 때 뇌경색이 발병된다. 뇌경색의 경우 질병이 계속 진행되어 뇌졸중 증세가 나타나 목숨을 잃게 될 수 있다. 미국의 경우 뇌졸중이 성인의 사망 원인 중 3번째로 높은 순위를 차지하고 있으며 운동성이 무력 하게 되는 가장 큰 요인으로 알려져 있다. 이들 질환의 주요 발병원인으로는 혈전(thrombus)으로 알려져 있는데, 혈전이란 과잉 혈소판 응집에 의해 매개 되는 병리현상으로 인식되고 있다. Recently, circulatory diseases such as arteriosclerosis, cerebral hemorrhage, hypertension, heart disease, stroke and cerebral infarction have become the leading causes of death in Korea as well as developed countries. As the adult disease develops into a modern society, it frequently occurs in middle-aged and middle-aged people due to changes in dietary habits and internal and external environmental stresses. Vascular blockages may occur due to various causes, and cardiovascular blockage may cause myocardial infarction, and cerebral infarction may occur when blood vessels in the brain are blocked. In cerebral infarction, the disease can continue and cause strokes that can lead to death. In the United States, stroke is the third leading cause of death among adults and is known to be the biggest contributor to mobility. The main cause of these diseases is known as thrombus (thrombus), which is recognized as a pathology mediated by excess platelet aggregation.
지혈은 원래의 형태가 파괴된 혈관으로부터 출혈을 막기 위한 기전으로 혈소판의 활성화 과정, 혈소판과 혈관성분과의 부착, 그에 수반된 혈액응고인자들의 복잡한 상호작용을 거쳐 이루어지며 손상된 혈관을 복원하고 남은 혈관은 섬유소 분해 과정을 거쳐 제거된다(Harlan and Harker, Med . Clin . North . Am., 65:855, 1981).Hemostasis is a mechanism to prevent bleeding from blood vessels whose original shape has been destroyed. It is a process of activation of platelets, adhesion of platelets to vascular components, and the complex interactions of accompanying blood coagulation factors. Removed through fibrin digestion (Harlan and Harker, Med . Clin . North . Am ., 65: 855, 1981).
한편, 혈소판은 혈관 손상시 콜라겐(collagen), 아라키도닉산(arachidonic acid), 및 ADP(adenosine diphosphate) 등과 같은 각종 응집유도체(agonist)의 자극에 의해 활성화되어 접착 반응(adhesion), 방출 반응(secretion) 및 응집 반응(aggregation)을 일으킨다. 이러한 반응들은 지혈(haemostasis)에 관련되어 있으며, 혈전증(thrombosis) 등을 포함하는 순환계 질환의 발병에도 중요한 역할을 한다. On the other hand, platelets are activated by stimulation of various agglomerates such as collagen, arachidonic acid, and ADP (adenosine diphosphate) during vascular injury, thereby adhering to adhesion and secretion. ) And aggregation. These reactions are related to haemostasis and play an important role in the development of circulatory diseases, including thrombosis and the like.
혈소판은 휴지기(resting) 상태에서 특징적인 원형(discoid) 형태를 가지지만 활성화되면 고유의 모양을 상실하고 허족을 가진 불규칙한 모양을 띄는 모양 변형을 거치게 되며, 세포골격(cytoskeleton)류의 중합(polymerization), 포스포릴레이션(phosphorylation) 및 이에 따른 상호작용의 결과를 나타낸다(Nachmias et al., Nature, 313:70, 1985). 지금까지 개발된 항혈소판제로는 데오필린(theopylline), 몰시도민(molsidomin), 베라파밀(verapamil), 니페디 핀(nifedipine) 등이 있다. 이들은 cAMP와 cGMP의 생성을 촉진하여 Ca2 +의 동원을 억제하는 것으로 알려져 있다. 또한, 아스피린, 이미다졸, 인도메타신 등의 비스테로이드계 화합물들은 트롬복산 A2의 생성을 저해함으로써 항혈소판 작용을 가지는 약물들로 알려져 있다. 그러나 상기 약물들은 화학 물질로 의약품이긴 하지만 인체에 지혈 과다 억제, 불임, 소화기 장애 등의 여러 부작용을 야기하는 문제점이 있다. Platelets have a characteristic discoid form at rest, but when activated, they lose their intrinsic shape and undergo an irregular shape with fictitious shapes, and polymerize cytoskeletons. , Results of phosphorylation and subsequent interactions (Nachmias et al., Nature , 313: 70, 1985). Antiplatelet agents developed so far include theopylline, molsidomin, verapamil, and nifedipine. It is known for promoting the formation of cAMP and cGMP inhibit the mobilization of Ca + 2. In addition, nonsteroidal compounds such as aspirin, imidazole, and indomethacin are known as drugs having antiplatelet action by inhibiting the production of thromboxane A 2 . However, although the drugs are chemicals, there are problems that cause various side effects such as excessive hemostasis, infertility, digestive disorders, etc. in the human body.
이에 따라, 부작용이 적은 천연물 또는 한방처방으로부터 항혈전 작용을 하는 물질에 대한 탐색연구가 많이 진행되고 있다. 항혈전 효능을 갖는 한약재 조성물인 심적환은 혈관 확장, 진정, 진통 작용을 가지는 단삼과 관상동맥 혈류량 증가, 지혈 및 소염작용을 가진 삼칠과 중추신경 흥분 및 항균 작용을 가진 용뇌로 이루어져 있으며, 특히 단삼은 "신농본초경(神農本草經)"에 수록되어 수 천년 간 관상동맥경화증을 예방하고 치료하는 약재로 사용되어 왔다.Accordingly, many researches have been conducted on substances having antithrombotic effects from natural products or herbal prescriptions with few side effects. Shim Jakhwan, an herbal composition with antithrombotic effect, consists of saliva, which has vasodilatation, sedation, and analgesic action, and ginseng that has coronary blood flow, hemostasis and anti-inflammatory effect, and cerebellum with central nervous excitability and antibacterial activity. It has been included in the "New Nongbon Carbide" and has been used as a medicine for preventing and treating coronary atherosclerosis for thousands of years.
한편, 한의학에서 황백(黃柏)은 황경피 나무의 수건피로 성질이 차고, 독이 없으며, 맛이 쓰다. 해독, 살균, 소염 이뇨제로 부종, 신장염, 방광염, 요도염 등에 사용된다. 천궁(川芎)은 성질이 따뜻하고 독이 없으며, 맛은 맵고 쓰다. 흥분성 화혈 조경제로 신경쇠약, 혈행 장애, 두통, 어지러움 등의 효과가 있다. 부자(附子)는 바곳의 구근으로 강심이뇨, 흥분작용이 있어 제질환에 수족이 차고, 만성 관절 질환, 각기 등에 사용된다. 남성(南星)은 천남성과의 근경으로 거담 작용과 뭉쳐진 혈맥을 풀어주는 작용이 있어, 두현, 두통, 오십견 등에 사용된다. On the other hand, in oriental medicine, Hwangbaek (黃柏) is the towel blood of the hwangpikje wood nature is cold, non-toxic, bitter taste. Detoxification, sterilization, anti-inflammatory diuretics, used for edema, nephritis, cystitis, urethritis. The shrine is warm and nonpoisonous, and the taste is hot and bitter. Excitatory hypertonic economy, such as nervous breakdown, blood circulation disorders, headaches, dizziness and other effects. The rich (附子) is a bulb of the gourd heart, diuretic, excitable action is a cold limbs in the disease, chronic joint disease, each is used. The male (南 星) is a root of the chunnamseong castle and acts to release the blood vessels are united, it is used for duhyeon, headache, fifty dogs.
이에 본 발명자들은 생약재를 이용한 항혈전제를 연구하던 중 황백, 천궁, 부자, 및 남성으로 이루어진 조성물이 혈소판 응집 억제 효능이 있음을 발견하여 본 발명을 완성하였다. Accordingly, the present inventors have completed the present invention by finding that the composition consisting of yellow, yellow, zigzag, rich, and male is effective in inhibiting platelet aggregation while studying antithrombogenic agents using herbal medicines.
본 발명의 목적은 황백, 천궁, 부자 및 남성의 혼합 생약 조성물을 유효성분으로 함유하는 항혈전용 조성물을 제공하는 것이다.It is an object of the present invention to provide a composition for anti-thrombosis containing a mixed herbal composition of yellow, yellow, rich and male as an active ingredient.
본 발명은 황백 18 ~ 22 중량부, 천궁 8 ~ 12 중량부, 부자 4 ~ 8 중량부, 및 남성 3 ~ 7 중량부를 포함하는 항혈전용 조성물을 제공한다.The present invention provides an anti-thrombotic composition comprising 18 to 22 parts by weight of yellow, 8 to 12 parts by weight, 4 to 8 parts by weight of rich, and 3 to 7 parts by weight of male.
또한, 본 발명은 황백 20 중량부, 천궁 10 중량부, 부자 6 중량부, 및 남성 5 중량부를 포함하는 항혈전용 조성물을 제공한다.In addition, the present invention provides a composition for anti-thrombosis comprising 20 parts by weight of sulfur white, 10 parts by weight of uterus, 6 parts by weight of rich, and 5 parts by weight of male.
또한, 본 발명은 상기 조성물을 유효성분으로 함유하는 동맥경화, 뇌출혈, 뇌졸중 또는 뇌경색 예방 및 치료제를 제공한다. The present invention also provides an agent for preventing and treating arteriosclerosis, cerebral hemorrhage, stroke or cerebral infarction, containing the composition as an active ingredient.
아울러, 본 발명은 상기 조성물을 유효성분으로 포함하는 건강식품을 제공한다.In addition, the present invention provides a health food comprising the composition as an active ingredient.
이하, 본 발명에 대해 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명의 혼합 생약 조성물은 황백, 천궁, 부자 및 남성이 5 내지 20 중량부로 구성되는 항혈전 조성물을 제공한다.The mixed herbal composition of the present invention provides an antithrombotic composition composed of 5 to 20 parts by weight of yellowish white, uterus, rich and male.
본 발명에 따른 생약 조성물의 추출방법은 하기와 같다.Extraction method of the herbal composition according to the present invention is as follows.
상기 생약 조성물의 조성비는, 황백 18 ~ 22 중량부, 천궁 8 ~ 12 중량부, 부자 4 ~ 8 중량부, 남궁 3 ~ 7 중량부로 제조하는 것이 바람직하며, 황백 20 중량부, 천궁 10 중량부, 부자 6 중량부, 남궁 5 중량부로 제조하는 것이 가장 바람직하다. 상기와 같은 중량부로 정량한 다음, 분쇄 혼합시료 10 g을 증류수 150 ㎖에 넣어 30분간 환류 추출한 후 실온에서 방치하고 여지로 여과하고, 여액을 10,000 rpm에서 15분간 원심분리를 한 후, 상층액을 취하여 여과한 후 -70℃에서 동결 건조시켜 가루상태의 생약 조성물의 추출물을 얻었다. 본 발명의 효과와 비교하기 위하여 건조된 황백, 천궁, 부자 및 남성을 각각 표 3과 같이 정량한 다음 상기 방법과 같이 제조하였다.The composition ratio of the herbal composition is preferably 18 to 22 parts by weight of sulfur white, 8 to 12 parts by weight, rich 4 to 8 parts by weight, 3 to 7 parts by weight of male arch, 20 parts by weight of sulfur white, 10 parts by weight of archery, It is most preferable to prepare it by 6 parts by weight of rich and 5 parts by weight of male arch. After quantifying by the above weight parts, 10 g of the pulverized mixed sample was added to 150 ml of distilled water, and extracted under reflux for 30 minutes. The mixture was left at room temperature and filtered through a filtrate. The filtrate was centrifuged at 10,000 rpm for 15 minutes, and then the supernatant was separated. The mixture was filtered, and then freeze-dried at -70 ° C to obtain an extract of the herbal composition in powder form. In order to compare the effects of the present invention, dried yellow white, cheonggung, rich and male were each quantified as shown in Table 3, and then prepared as described above.
본 발명에 따른 생약 조성물의 추출물의 혈소판 응집 억제율은 시험관 내에서 콜라겐과 ADP 및 아라키도닉산 같은 응집유도체를 사람의 혈액에 처리했을 때, 황백, 천궁, 부자 및 남성 각각의 억제율보다 뛰어날 뿐 아니라, 심적환의 억제율보다 뛰어났다(표 4, 표 5 및 표 6 참조).The platelet aggregation inhibition rate of the extract of the herbal composition according to the present invention is superior to the inhibition rate of yellow white, uterus, rich and male, respectively, when the coagulation derivatives such as collagen and ADP and arachidonic acid are treated in human blood in vitro. It was superior to the inhibition rate of cardiac ring (see Table 4, Table 5 and Table 6).
혈소판이 활성화되면, 인지질 막(Phospholipid membrane)으로부터 아라키도닉산(arachidonic acid)을 기질로 싸이클로옥시게네이즈(cyclooxygenase)에 의해 생성되는 PGH2(Prostaglandin H2)로부터 트롬복산 A2(TxA2)가 만들어진다. 상기 트롬복산 A2는 불안정한 물질로서 반감기가 짧기 때문에, 안정한 대사체인 트롬복산 B2를 정량함으로써 간접적으로 측정하는데, 생약 조성물의 추출물을 트롬복산 생성억제 확인 결과 유의성 있게 억제됨이 확인되었다. 따라서, 생약 조성물의 추출물의 트롬복산 생성 억제 효과는 음성대조군에 대해서 유의성 있게 나타난다(표 7 참조). When platelets are activated, thromboxane A 2 (TxA 2 ) from PGH 2 (Prostaglandin H 2 ) produced by cyclooxygenase from arachidonic acid to the substrate from the Phospholipid membrane Is made. Since thromboxane A 2 has a short half-life as an unstable substance, it was indirectly measured by quantitating thromboxane B 2 , which is a stable metabolite. Therefore, the inhibitory effect of thromboxane production of the extract of the herbal composition is shown to be significant for the negative control group (see Table 7).
또한, 급성 혈전 동물모델의 생체 내에서 본 발명에 따른 생약 조성물의 추출물의 항혈전률은 672.9 mg/kg을 투여하였을 때 55%를 나타낸다(표 8 참조). 따라서, 본 발명의 조성물은 동맥경화증, 뇌출혈, 뇌졸중 또는 뇌경색과 같은 혈전형성을 수반하는 질환의 예방 및 치료에 유용하게 사용될 수 있다.In addition, the antithrombotic rate of the extract of the herbal composition according to the present invention in vivo in the acute thrombosis animal model is 55% when 672.9 mg / kg is administered (see Table 8). Therefore, the composition of the present invention can be usefully used for the prevention and treatment of diseases involving thrombosis such as atherosclerosis, cerebral hemorrhage, stroke or cerebral infarction.
본 발명의 조성물은 혈전 형성을 수반하는 질환의 예방 및 치료를 위하여 단독으로, 또는 수술, 방사선 치료, 호르몬 치료, 화학 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The compositions of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers for the prevention and treatment of diseases involving thrombus formation.
본 발명의 조성물은, 투여를 위해서 상기 기재한 유효성분 이외에 추가로 약제학적으로 허용 가능한 담체를 1종 이상 포함하여 제조할 수 있다. 약제학적으로 허용 가능한 담체는 식염수, 멸균수, 링거액, 완충 식염수, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한, 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다. 더 나아가 당 분야의 적정한 방법으로 또는 Remington's Pharmaceutical Science(최근판), Mack Publishing Company, Easton PA에 개시되어 있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제화할 수 있다.The composition of the present invention may be prepared by including one or more pharmaceutically acceptable carriers in addition to the above-described active ingredients for administration. Pharmaceutically acceptable carriers may be used in combination with saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol and one or more of these components, if necessary, as antioxidants, buffers And other conventional additives such as bacteriostatic agents can be added. In addition, diluents, dispersants, surfactants, binders and lubricants may be additionally added to formulate injectable formulations, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. Furthermore, it may be preferably formulated according to each disease or component by an appropriate method in the art or using a method disclosed in Remington's Pharmaceutical Science (Recent Edition), Mack Publishing Company, Easton PA.
본 발명의 조성물은 목적하는 방법에 따라 경구 투여하거나 비경구 투여(예를 들어, 정맥 내, 피하, 복강 내 또는 국소에 적용) 할 수 있으며, 투여량은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설률 및 질환의 중증도 등에 따라 그 범위가 다양하다. 본 발명의 생약 조성물 추출물의 일일 투여량은 100 ~ 150 mg/kg이며, 바람직하게는 130 ~ 135 mg/kg이고, 하루 1회 내지 3회에 나눠 투여하는 것이 바람직하다.The composition of the present invention can be administered orally or parenterally (eg, applied intravenously, subcutaneously, intraperitoneally or topically) according to the desired method, and the dosage is based on the weight, age, sex and health of the patient. The range varies depending on the diet, the time of administration, the method of administration, the rate of excretion and the severity of the disease. The daily dosage of the herbal composition extract of the present invention is 100 to 150 mg / kg, preferably 130 to 135 mg / kg, preferably administered once to three times a day.
본 발명은 항혈전 조성물을 포함하는 항혈전용 건강 식품을 제공한다.The present invention provides an anti-thrombotic health food comprising an anti-thrombotic composition.
본 발명의 항혈전용 조성물은 항혈전으로 인한 질병 개선을 목적으로 하는 건강식품에 첨가할 수 있다. 본 발명의 혼합 생약 재를 식품 첨가물로 사용할 경우, 상기 혼합 생약 재를 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합양은 사용목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조시에 본 발명의 혼합 생약 재는 원료에 대하여 15 중량부 이하, 바람직하게는 10 중량부 이하의 양으로 첨가된다. 그러나 건강 및 위생을 목적으로 하거나 건강 조절을 목적으로 하는 장기간의 섭취의 경우에 상기 양은 상기 범위 이하일 수 있으며, 안정성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.The antithrombotic composition of the present invention can be added to health foods for the purpose of improving diseases caused by antithrombosis. When the mixed herbal medicine of the present invention is used as a food additive, the mixed herbal medicine may be added as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method. The blending amount of the active ingredient may be appropriately determined depending on the purpose of use (prevention, health or therapeutic treatment). In general, the mixed herbal medicine of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less based on the raw material in the manufacture of food or beverage. However, in the case of long-term intake for health and hygiene or health control purposes, the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of stability.
상기 식품의 종류에는 특별한 제한이 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸컬릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함하는 낙농제품, 각종 수프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.There is no particular limitation on the kind of food. Examples of the food to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, beverages, tea, and drinks. , Alcoholic beverages and vitamin complexes, and includes all of the health food in the conventional sense.
본 발명의 건강 음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에르트리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 중량부 당 일반적으로 약 0.01 ~ 0.04 중량부, 바람직하게는 0.02 ~ 0.03 중량부이다. The health beverage composition of the present invention may contain various flavors, natural carbohydrates, and the like as additional components, as in a conventional beverage. The above-mentioned natural carbohydrates are glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 parts by weight, preferably 0.02 to 0.03 parts by weight per 100 parts by weight of the composition of the present invention.
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 중점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 조성물은 천연 과일 주스, 과일 주스 음 료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있으며, 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다. In addition to the above, the composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols. And carbonation agents used in carbonated beverages. In addition, the composition of the present invention may contain the flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination, and the proportion of the additive is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
이하, 본 발명을 다음의 실시예, 실험예 및 제제예에 의해 보다 상세하게 설명한다. Hereinafter, the present invention will be described in more detail with reference to the following Examples, Experimental Examples and Formulation Examples.
단, 하기 실시예, 실험예 및 제제예는 본 발명의 내용을 예시하는 것일 뿐 발명의 범위가 실시예 및 실험예에 의해 한정되는 것은 아니다.However, the following Examples, Experimental Examples and Formulation Examples are merely illustrative of the contents of the present invention, and the scope of the present invention is not limited by the Examples and Experimental Examples.
< 실시예 1> 생약 조성물의 추출물의 제조 Example 1 Preparation of Extract of Herbal Medicine Composition
생약 조성물의 제조 단계는 하기와 같다.The manufacturing steps of the herbal composition are as follows.
1) 하기 표 1에 명시되어 있는 것과 같은 중량부 즉, 황백 20 g, 천궁 10 g, 부자 6 g, 남성 5 g을 백제당 한약(대전, 대한민국)에서 구입하여 한국한의학연구원에서 외부 형태를 비교검사 확인한 후 실시예에 사용하였다; 2) 단계 1)의 한약재를 표 1과 같이 일정량 정량한 다음 가정용 믹서(mixer)를 이용하여 가루로 만들어 혼합 제조하였다; 3) 혼합시료 10 g을 증류수 150 ㎖에 넣어 30분간 환류 추출한 후 실온에서 방치하고 여지로 여과하였다; 4) 여액을 10,000 rpm에서 15분간 원심분리하여 상층액을 취하여 여과한 후 -70℃에서 동결 건조시켜 가루상태(수율 14.7%, 0.489 g)로 만들어 실험에 사용할 때까지 냉 암소에 보관하였다.1) By weight, such as specified in Table 1, that is, 20g yellow baek, 10g Cheongung, 6g rich, 5g male was purchased from Baekje-Dang Herbal Medicine (Daejeon, South Korea) and compared the external shape in Korea Institute of Oriental Medicine The test was confirmed and used in the examples; 2) The medicinal herb of step 1) was quantified as shown in Table 1 and then mixed into a powder using a domestic mixer to prepare a mixture; 3) 10 g of the mixed sample was added to 150 ml of distilled water, followed by extraction under reflux for 30 minutes, and the mixture was left at room temperature and filtered with filtration; 4) The filtrate was centrifuged at 10,000 rpm for 15 minutes, the supernatant was collected, filtered, and lyophilized at -70 ° C to obtain a powder (yield 14.7%, 0.489 g) and stored in a cold place until it was used for experiments.
<< 실시예Example 2 내지 2 to 실시예Example 5> 조성비가 다른 추출물 제조 5> Manufacture extract with different composition ratio
하기의 표 2와 같은 구성비로 이루어진 추출물을 실시예 1과 같은 방법으로 제조하였다.An extract consisting of the following composition ratios was prepared in the same manner as in Example 1.
<< 비교예Comparative example 1 내지 5> 단일 성분만을 포함하는 추출물 제조 1 to 5> Preparation of extract containing only a single component
하기의 표 3과 같은 구성물로 이루어진 추출물을 실시예 1과 같은 방법으로 제조하였다. 대조군으로 사용한 심적환[단삼(약전) :17.5 ㎎, 삼칠(생규) 3.4 ㎎, 용외(생규) 0.2 ㎎]은 삼천당 제약(대한민국)에서 구입하여 사용하였다.An extract consisting of the components shown in Table 3 below was prepared in the same manner as in Example 1. Shim red pill [Dansam (Pharmaceutical): 17.5mg, Samchil (raw)) 3.4mg, Extracorporeal (fresh) 0.2mg] used as a control was purchased from Samcheondang Pharmaceutical (Korea).
<< 실험예Experimental Example 1> 1> 전혈whole blood 혈소판 응집 억제 효과( Platelet aggregation inhibitory effect ( InIn vitroin vitro ))
본 발명의 상기 추출물의 전혈 혈소판 응집 억제 효과를 알아보기 위하여, 하기와 같은 실험예를 수행하였다. In order to determine the effect of inhibiting whole blood platelet aggregation of the extract of the present invention, the following experimental example was performed.
20 ~ 30대 사이의 성인여자 13명을 무작위로 선정하고, 채혈하기 일주일 전부터 아스피린이나 비스테로이드 항염증 약을 복용시키지 않았다. 일정한 시간에 혈액을 5 ㎖ 용량의 1회용 플라스틱 주사기로 채혈한 후, 응고가 일어나지 않도록 3.2%의 소듐 시트레이트 항혈액응고제가 포함되어 있는 베큐테이너(vaccutainer)(BD, USA)에 분주하였다. 이후 전혈 혈소판 응집분석기(aggregometer)(Chrono Log, USA)를 이용하여 혈소판 응집 억제활성을 측정하였다. 혈소판 수가 4×108 cell/㎖이 되도록 생리식염수로 희석한 후 37℃에서 10분간 배양하고 여기에 시료현탁액 50 ㎕(50 ㎎/㎖ 시료 농도)를 가하여 5분간 반응시켰다. 혈소판 응집 유도제를 첨가하고 1,000 rpm으로 저으면서 37℃에서 반응을 시켜 임피던스(impedance) 변화로서 혈소판 응집 정도를 판정하였다. 시료는 정량한 후 생리식염수에 현탁하여 준비하였으며 혈소판 응집 유도제는 콜라젠 2 ㎕(collagen)(1 mg/㎖, Chrono Log, USA), ADP 15 ㎕(1 mM, Chrono Log, USA) 및 아라키도닉산 10 ㎕(Arachidonic acid)(50 mM, Chrono Log, USA)을 사용하였다. Thirteen adult women between the ages of 20 and 30 were randomly selected and no aspirin or nonsteroidal anti-inflammatory drugs were given for a week prior to blood collection. At a given time, blood was drawn with a 5 ml disposable plastic syringe and then dispensed into a vaccutainer (BD, USA) containing 3.2% sodium citrate anticoagulant to prevent coagulation. Then, platelet aggregation inhibitory activity was measured using a whole blood platelet aggregation (aggregometer) (Chrono Log, USA). The platelets were diluted with physiological saline to 4 × 10 8 cells / ml, incubated at 37 ° C. for 10 minutes, and 50 μl (50 mg / ml sample concentration) of the sample suspension was added thereto for 5 minutes. The platelet aggregation inducing agent was added and reacted at 37 ° C. while stirring at 1,000 rpm to determine the degree of platelet aggregation as a change in impedance. Samples were quantified and suspended in physiological saline, and platelet aggregation inducers were prepared using 2 μl collagen (1 mg / ml, Chrono Log, USA), 15 μl ADP (1 mM, Chrono Log, USA) and arachidonic acid. 10 μl (Arachidonic acid) (50 mM, Chrono Log, USA) was used.
실험예 결과의 통계 처리는 SPSS 패키지를 이용하였으며, 모든 측정값은 평균±표준편차로 표시하였고, 분석 수치에 대한 유의성 검증은 독립표본 T-TEST를 실시하여, 분석결과에 대한 p<0.05 수준에서 평균치에 대한 유의성을 분석하였다.Statistical analysis of the experimental results was carried out using the SPSS package, all the measured values were expressed as mean ± standard deviation, and the significance test for the analytical value was performed by an independent sample T-TEST, at the p <0.05 level for the analytical result. The significance for the mean was analyzed.
콜라겐을 혈소판 응집 유도제로 사용한 경우 결과는 표 4와 같다. When collagen is used as a platelet aggregation inducer, the results are shown in Table 4.
P *<0.05, P **<0.01, P ***<0.001 P * <0.05, P ** <0.01, P *** <0.001
상기와 같이 본 발명에 따른 생약 조성물의 추출물의 인체 전혈 혈소판 응집 억제율은, 실시예 1 내지 실시예 5가 음성대조군보다 뛰어나며, 실시예 1의 농도가 2.5 mg/㎖에서 2.0±2.8 Ω을 나타내었고, p값이 0.00으로 가장 뛰어난 효과를 보였다. 또한 황백, 천궁, 부자 및 남성 단일 추출물(비교예 1 내지 4)보다 전혈 혈소판 응집 억제율이 뛰어나며, 대조군인 심적환(비교예 5)의 경우 5 mg/㎖에서 14.8±3.6 Ω보다 높았다. Human whole blood platelet aggregation inhibition rate of the extract of the herbal composition according to the present invention as described above, Examples 1 to 5 was superior to the negative control group, the concentration of Example 1 was 2.0 ± 2.8 Ω at 2.5 mg / ㎖ , p value was 0.00, the most effective. In addition, the inhibition of whole blood platelet aggregation was superior to that of the extract of Hwangbaek, Cheongung, the rich and the male (Comparative Examples 1 to 4), and was higher than 14.8 ± 3.6 Ω at 5 mg / ml for the control group Shim-hwan (Comparative Example 5).
ADP를 혈소판 응집 유도제로 사용한 경우 결과는 표 5와 같다.When ADP is used as a platelet aggregation inducer, the results are shown in Table 5.
P *<0.05, P **<0.01, P ***<0.001 P * <0.05, P ** <0.01, P *** <0.001
상기와 같이 본 발명에 따른 생약 조성물의 추출물의 인체 전혈 혈소판 응집 억제율은, 실시예 1 내지 실시예 5가 음성대조군보다 뛰어나며, 그 중 실시예 1의 농도가 2.5 mg/㎖에서 5.25±5.0 Ω을 나타내었고, p값이 0.012으로 가장 뛰어난 효과를 보였다. 또한 황백, 천궁, 부자 및 남성 단일 추출물(비교예 1 내지 4)보다 전혈 혈소판 응집 억제율이 뛰어나며, 대조군인 심적환(비교예 5)의 경우 5 mg/㎖에서 9.0±2.8 Ω보다 높았다.Human whole blood platelet aggregation inhibition rate of the extract of the herbal composition according to the present invention as described above, Examples 1 to 5 is superior to the negative control group, the concentration of Example 1 is 5.25 ± 5.0 Ω at 2.5 mg / ㎖ P value was 0.012, showing the most excellent effect. In addition, the inhibition of whole platelet aggregation was superior to that of the yellowish white, the uterus, the rich and the male single extract (Comparative Examples 1 to 4), and the control group, Shim Red Ring (Comparative Example 5), was higher than 9.0 ± 2.8 Ω at 5 mg / ml.
아라키도닉산을 혈소판 응집 유도제로 사용한 경우 결과는 표 6과 같다. When arachidonic acid was used as a platelet aggregation inducer, the results are shown in Table 6.
p * < 0.05, p **< 0.01, p ***< 0.001 p * <0.05, p ** <0.01, p *** <0.001
상기와 같이 본 발명에 따른 생약 조성물의 추출물의 인체 전혈 혈소판 응집 억제율은, 실시예 1 내지 실시예 5가 음성대조군보다 뛰어나며, 그 중 실시예 1의 농도가 2.5 mg/㎖에서 9.0±3.6 Ω을 나타내었고, p값이 0.046으로 가장 뛰어난 효과를 보였다. 또한 황백, 천궁, 부자 및 남성 단일 추출물(비교예 1 내지 4)보다 전혈 혈소판 응집 억제율이 뛰어나며, 대조군인 심적환(비교예 5)의 경우 5 mg/㎖에서 13.5±3.7 Ω보다 높았다. Human whole blood platelet aggregation inhibition rate of the extract of the herbal composition according to the present invention as described above, Examples 1 to 5 is superior to the negative control group, the concentration of Example 1 is 9.0 ± 3.6 Ω at 2.5 mg / ㎖ P value was 0.046, showing the most excellent effect. In addition, the inhibition of whole blood platelet aggregation was superior to that of the yellowish white, the uterus, the rich and the male single extract (Comparative Examples 1 to 4), and was higher than 13.5 ± 3.7 Ω at 5 mg / ml for the control group Shim-hwan.
<< 실험예Experimental Example 2> 2> 트롬복산Thrombox B B 22 생성 억제 효과 Generation suppression effect
본 발명의 추출물의 트롬복산 B2 생성 억제 효과를 알아보기 위하여, 하기와 같은 실험을 수행하였다. In order to determine the inhibitory effect of thromboxane B 2 production of the extract of the present invention, the following experiment was performed.
오전 8 ~ 9시 사이에 지원자 혈액을 vaccutainer 채혈 주사기로 채혈한 후 혈소판수가 4×108 cell/㎖이 되도록 생리식염수로 적당히 희석한 후 혈소판 응집분석기(aggregometer)(Chrono Log, USA)를 이용하여 37℃에서 10분간 배양하고 여기에 시료현탁액 50 ㎕를 가하여 5분간 반응시켰다. 혈소판 응집 유도제인 콜라젠을 넣고 저어주지 않는 상태에서 37℃에서 반응시킨 후에 2000×g에서 15분간 4℃에서 원심분리한 후 상층액을 얻어 -20℃에 즉시 보관하여 시료로 사용하였다. Thromboxane B2 Immunoassay(R&D systems, Inc. USA) 방법에 따라서 ELISA reader(Molecular Devices, USA)를 이용하여 405 nm에서 측정하여 트롬복산 B2 농도를 pg/㎖로 수치화하였다. Between 8 am and 9 am, the volunteer blood was collected with a vaccutainer collection syringe, then diluted appropriately with physiological saline so that the platelet count was 4 × 10 8 cells / ml, followed by a platelet aggregator (Chrono Log, USA). Incubated at 37 ° C. for 10 minutes, and 50 μl of sample suspension was added thereto and allowed to react for 5 minutes. After collagen, which is a platelet aggregation inducer, was reacted at 37 ° C. without stirring, centrifuged at 4 ° C. for 15 minutes at 2000 × g, and the supernatant was immediately stored at −20 ° C. to be used as a sample. The thromboxane B 2 concentration was quantified in pg / ml by measuring at 405 nm using an ELISA reader (Molecular Devices, USA) according to the Thromboxane B 2 Immunoassay (R & D systems, Inc. USA) method.
상기 실험예 결과는 표 7에 나타내었다. The experimental results are shown in Table 7.
p * < 0.05, p **< 0.01, p ***< 0.001 p * <0.05, p ** <0.01, p *** <0.001
상기와 같이 본 발명에 따른 생약 조성물의 추출물의 트롬복산 생체 억제율은, 실시예 1 내지 실시예 5가 음성대조군보다 뛰어나며, 그중 실시예 1의 농도가 2.5 mg/㎖에서 337.6±30.1 pg/㎖을 나타내었고, p값이 0.000으로 가장 뛰어난 효과를 보였다. 이는 추출물 중 황백, 천궁, 부자 및 남성 각각 추출물(비교예 1 내지 4)의 트롬복산 생산 억제율보다 뛰어나며, 대조군인 심적환(비교예 5)의 경우 5 mg/㎖에서 407.6±2.0 pg/㎖ 보다 높았다. As described above, the thromboxane bioinhibition rate of the extract of the herbal composition according to the present invention, Examples 1 to 5 is superior to the negative control group, wherein the concentration of Example 1 is 337.6 ± 30.1 pg / ㎖ at 2.5 mg / ㎖ P value was 0.000, showing the best effect. It is superior to the inhibition rate of thromboxane production of the extracts of yellowish white, cheonggung, rich and male extracts (Comparative Examples 1 to 4) of the extract, and 407.6 ± 2.0 pg / ml at 5 mg / ml for the control Shimhwan (Comparative Example 5) High.
<< 실험예Experimental Example 3> 3> 생체내In vivo 항혈전Antithrombotic 효과 effect
상기 실험예 1과 실험예 2에서 혈소판 응집 및 혈소판 활성 억제 효과가 우수한 본 발명의 추출물의 항혈전 효과를 알아보기 위하여, 하기와 같은 실험예를 수행하였다.In order to determine the antithrombotic effect of the extract of the present invention excellent in platelet aggregation and platelet activity inhibitory effect in Experimental Example 1 and Experimental Example 2, the following experimental example was performed.
급성 혈전동물모델인 20 ~ 25 g의 웅성 ICR 마우스(오리엔트, 대한민국)에 약재 현탁액 또는 생리 식염수를 체중에 비례하여 경구 투여하였다. 콜라겐(1,200 ㎍/㎏)과 에피네프린(120 ㎍/㎏)을 생리식염수 100 ㎕에 넣은 혼합용액을, 약 1시간 후 꼬리정맥에 주사하고 15분간 마비의 지속, 사망 또는 마비로부터의 회복 여부를 관찰하여 시료의 항혈전 효과를 판정하였다. 음성대조군으로는 생리식염수를 사용하였다.20-25 g male ICR mice (Orient, Korea), an acute thrombosis model, were orally administered with a pharmaceutical suspension or physiological saline in proportion to body weight. A mixed solution containing collagen (1,200 μg / kg) and epinephrine (120 μg / kg) in 100 μl of physiological saline was injected into the tail vein after about 1 hour and observed for 15 minutes of continued paralysis, recovery from death or paralysis. The antithrombotic effect of the sample was determined. Saline was used as a negative control group.
본 실험예 결과는 표 8로 나타내었다.The results of this experiment are shown in Table 8.
상기와 같이 본 발명에 따른 생약 조성물의 추출물인 실시예 1 내지 5 모두 음성대조군보다 높은 회복률을 보였고, 실시예 1의 경우 급성혈전 동물모델의 생체내에서 55% 회복률로 가장 뛰어난 효과를 보였다. 이는 추출물 중 황백, 천궁, 부자 및 남성 각각의 회복률(비교예 1 내지 4)보다 뛰어나며, 대조군인 심적환(비교예 5)의 경우 62.5 mg/kg에서의 33.3%의 회복률보다 높았다. As described above, all of the extracts of the herbal composition according to the present invention, Examples 1 to 5, showed a higher recovery rate than the negative control group, and Example 1 showed the most excellent effect with a recovery rate of 55% in vivo in an animal model of acute thrombosis. This was better than the recovery rate of each of the extracts yellow, cheongung, rich and male (Comparative Examples 1 to 4), and higher than the recovery rate of 33.3% at 62.5 mg / kg for the control Shim Shikhwan (Comparative Example 5).
<< 제제예Formulation example 1> 약학적 제제의 제조 1> Preparation of Pharmaceutical Formulations
1. 환의 제조 1. Manufacture of rings
본 발명의 조성물 70 중량부70 parts by weight of the composition of the present invention
벌꿀 20 중량부20 parts honey
전분 1 중량부1 part by weight of starch
상기 조성 및 함량으로 통상적인 방법을 사용하여 환을 제조하였다.The ring was prepared using the conventional method with the said composition and content.
2. 정제의 제조 2. Preparation of Tablets
본 발명의 조성물 100 mg100 mg of the composition of the present invention
옥수수전분 100 mgCorn starch 100 mg
유당 100 mgLactose 100 mg
스테아린산 마그네슘 2 mg2 mg magnesium stearate
상시의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing the usual ingredients, tablets were prepared by tableting according to a conventional method for producing tablets.
3. 캡슐제의 제조3. Preparation of Capsule
본 발명의 조성물 100 mg100 mg of the composition of the present invention
옥수수 전분 100 mgCorn starch 100 mg
유당 100 mgLactose 100 mg
스테아린산 마그네슘 2 mg2 mg magnesium stearate
상기의 성분을 혼합한 후, 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.
<< 제제예Formulation example 2> 음료의 제조 2> Manufacture of beverage
1. 탄산음료의 제조1. Preparation of carbonated drinks
설탕 5 ~ 10 중량부, 구연산 0.05 ~ 0.3 중량부, 카라멜 0.005 ~ 0.02 중량부, 비타민 C 0.1 ~ 1 중량부의 첨가물을 혼합하고, 여기에 본 발명의 조성물 79 ~ 94 중량부를 섞어서 시럽을 만들고, 상기 시럽을 85 ~ 98℃에서 20 ~ 180초간 살균하여 냉각수와 1:4의 비율로 혼합한 다음 탄산가스를 0.5 ~ 0.82 중량부를 주입하여 본 발명의 조성물을 함유하는 탄산음료를 제조하였다.5 to 10 parts by weight of sugar, 0.05 to 0.3 parts by weight of citric acid, 0.005 to 0.02 parts by weight of caramel, 0.1 to 1 parts by weight of vitamin C are mixed, and 79 to 94 parts by weight of the composition of the present invention are mixed to make a syrup, and The syrup was sterilized at 85 to 98 ° C. for 20 to 180 seconds, mixed with cooling water at a ratio of 1: 4, and 0.5 to 0.82 parts by weight of carbon dioxide was injected to prepare a carbonated beverage containing the composition of the present invention.
2. 건강 음료의 제조2. Manufacture of health drinks
액상과당(0.5 중량부), 올리고당(2 중량부), 설탕(2 중량부), 식염(0.5 중량부), 물(75 중량부)과 같은 부재료와 본 발명의 조성물 79 ~ 90 중량부를 균일하게 배합하여 순간 살균을 한 후 이를 유리병, 패트병 등 소포장 용기에 포장하여 건강 음료를 제조하였다.Substances such as liquid fructose (0.5 parts by weight), oligosaccharides (2 parts by weight), sugar (2 parts by weight), salt (0.5 parts by weight), water (75 parts by weight) and 79 to 90 parts by weight of the composition of the present invention are uniformly After sterilization by mixing, it was packaged in small packaging containers such as glass bottles and plastic bottles to prepare healthy drinks.
3. 야채 쥬스의 제조3. Preparation of Vegetable Juice
본 발명의 조성물 5 g을 토마토 또는 당근 쥬스 1,000 ㎖에 가하여 건강 증진용 야채쥬스를 제조하였다.5 g of the composition of the present invention was added to 1,000 ml of tomato or carrot juice to prepare a vegetable juice for health promotion.
4. 과일 쥬스의 제조4. Preparation of Fruit Juice
본 발명의 조성물 1 g을 사과 또는 포도 쥬스 1,000 ㎖에 가하여 건강 증진용 과일쥬스를 제조하였다. 1 g of the composition of the present invention was added to 1,000 ml of apple or grape juice to prepare fruit juice for health promotion.
본 발명의 추출물은 콜라젠에 의해 유도된 사람의 전혈 혈소판응집 억제뿐만 아니라 다양한 응집 유도제에 의한 인체 전혈 혈소판응집 억제율이 우수하고, 트롬복산 B2의 생성억제 효과가 우수하며, 급성 혈전동물 모델의 생체 내에서도 항혈전 활성이 측정되므로, 동맥경화증, 뇌출혈, 뇌졸중 또는 뇌경색과 같은 혈전 형성을 수반하는 질환의 예방 및 치료에 유용하게 사용될 수 있다. The extract of the present invention is excellent in inhibiting whole blood platelet aggregation of humans induced by collagen as well as human whole blood platelet aggregation by various aggregation inducing agents, and excellent in inhibiting the production of thromboxane B 2 , and living body of acute thrombosis model. Since anti-thrombotic activity is measured in-house, it can be usefully used for the prevention and treatment of diseases involving blood clot formation such as atherosclerosis, cerebral hemorrhage, stroke or cerebral infarction.
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
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CN103948882A (en) * | 2014-02-27 | 2014-07-30 | 香港嘉峰医药血栓科技开发有限公司 | Traditional Chinese medicine for treating thrombus |
CN104189738A (en) * | 2014-08-12 | 2014-12-10 | 黄太锋 | Traditional Chinese medicine composition for treating sequel of cerebral infarction |
KR101543760B1 (en) * | 2014-05-12 | 2015-08-11 | 조춘일 | Pharmaceutical composition for preventing and treatmenting stroke and thrombus containing traditional medical herbs |
CN104998075A (en) * | 2015-07-31 | 2015-10-28 | 蒋魏 | Hemostatic drug |
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2006
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Title |
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대한한방내과학회지 21(5), 819-27 (2000) |
대한한방내과학회지 21(5), 829-37 (2000) |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103948882A (en) * | 2014-02-27 | 2014-07-30 | 香港嘉峰医药血栓科技开发有限公司 | Traditional Chinese medicine for treating thrombus |
KR101543760B1 (en) * | 2014-05-12 | 2015-08-11 | 조춘일 | Pharmaceutical composition for preventing and treatmenting stroke and thrombus containing traditional medical herbs |
CN104189738A (en) * | 2014-08-12 | 2014-12-10 | 黄太锋 | Traditional Chinese medicine composition for treating sequel of cerebral infarction |
CN104998075A (en) * | 2015-07-31 | 2015-10-28 | 蒋魏 | Hemostatic drug |
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