KR100312622B1 - Stabilized anticancer composition mainly composed of herbal medicine and its manufacturing method - Google Patents
Stabilized anticancer composition mainly composed of herbal medicine and its manufacturing method Download PDFInfo
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Abstract
본 발명은 할미꽃 뿌리 및/또는 유피를 주제로 하는 항암제 조성물로서, 세절하거나 분말화한 백두옹뿌리(Pulsatillae Radix: 한국 할미꽃 뿌리, 분홍할미꽃 뿌리, 중국할미꽃 뿌리, 몽고할미꽃 뿌리, 서양할미꽃 뿌리) 및/또는 유피(Ulmaceae Cortex)에 필요하면 인삼(Ginseng Radix )과 감초(Glycyrrhizae Radix)에서 선택된 보조성분 1종 이상을 60℃ 이하의 온도에서 용매로 추출한 후 여과하고 동결건조시킨 동결건조물에 보조제를 첨가하거나, 또는 추출한 추출액을 여과하고 보조제를 첨가하고 동결건조시켜서 얻어진 동결건조물을 약제학적으로 통상으로 사용되는 제제화 방법으로 제제화시킨 항암제 조성물을 제공한다.The present invention is an anticancer composition based on pasqueflower roots and / or hides, and is fine or powdered Pulsatillae Radix (Korean Pasqueflower Root, Pink Pasqueflower Root, Chinese Pasqueflower Root, Mongolian Pasqueflower Root, Western Pasqueflower Root) and // Or if necessary for the Ulm Cortex, extract one or more of the auxiliary ingredients selected from Ginseng Radix and Glycyrrhizae Radix with a solvent at a temperature below 60 ° C., then add the adjuvant to the lyophilized lyophilized product. Alternatively, an anticancer composition is prepared by formulating a lyophilized product obtained by filtering the extracted extract, adding an adjuvant, and lyophilizing by a pharmaceutical method.
본 발명에 따른 함암조성물은 이를 수년간까지 보관하여도 안정하고 약효가 전혀 떨어지지 않는 안정화된 약학적 조성물이다.The hamam composition according to the present invention is a stabilized pharmaceutical composition that is stable even if stored for several years and does not drop at all.
Description
본 발명은 생약을 주성분으로 한 안정화된 항암제 조성물 및 그 제조방법에 관한 것이다.The present invention relates to a stabilized anticancer composition comprising a herbal medicine as a main component and a method for producing the same.
본 발명자는 생약을 주제로 한 신규 항암작용을 가지는 약학적 제제 및 그 제조방법에 관한 발명을 완성하여 특허 제 72982호로서 특허를 취득하였다.This inventor completed the invention about the pharmaceutical agent which has the novel anticancer effect based on the herbal medicine, and its manufacturing method, and acquired patent as patent 72982.
이 발명에 의하면, 백두옹 뿌리[Pulsatillae Radix: 한국할미꽃(Pulsatilla Koreana Nakai), 일본할미꽃(Pursatilla cernua), 분홍할미꽃(P. danurica), 서양할미꽃(P. ratcnsis), 중국할미꽃, 몽고할미꽃] 및/또는 위령선(Clematis Chinensis Osbeclo: 일명 중국 으아리)을 주제로 하고, 여기에 유피(느릅나무의 껍질: Ulmaceae Cortex), 행인(Armeniacae Semen), 인삼(Ginseng Radix) 및 감초(Glycyrrhizae Radix)에서 선택된 보조성분을 첨가하여 제조된 약학적 조성물 및 그 제조방법을 제공하였다.According to the invention, Pulsatillae Radix (Pulsatilla Koreana Nakai), Japanese Pasqueflower (Pursatilla cernua), P. danurica, P. ratcnsis, Chinese Pasqueflower, Mongolian Pasqueflower and Or a supplement selected from the skins of the Clermatis Chinensis Osbeclo (aka Chinese Eur), which is selected from the bark (elm bark: Ulmaceae Cortex), Armeniacae Semen, Ginseng Radix and Glycyrrhizae Radix. To provide a pharmaceutical composition prepared by the addition and a method for producing the same.
할미꽃은 세계각지에 분포하여 자생하고 있으며, 그 뿌리는 한방에서 소염, 수렴 및 지혈약으로 이질에 이용되어 왔으며, 아네모닌 및 프로토아네모닌과 사포닌 등을 함유하고 있음이 밝혀졌다. 아네모닌의 전구물질이 프로토아네모닌이며 아네모닌 및 프로토아네모닌은 물, 알코올, 클로로포름, 염화메틸렌 등에 용해한다.Pasqueflower is distributed throughout the world, and its root has been used for dysentery as an anti-inflammatory, astringent, and hemostatic drug in oriental medicine, and has been found to contain anemonin, protoanemonine, and saponin. The precursor of anemonin is protoanemonine, and anemonine and protoanemonine are soluble in water, alcohol, chloroform, methylene chloride and the like.
위령선은 그 뿌리에 아네모닌, 아네모놀, 사포닌 등을 함유하고 있으며, 한방에서 중풍, 이뇨 및 통경제로 사용되어 왔다.The lieutenant line contains anemonine, anemonol, saponin, etc. in its roots, and has been used for stroke, diuresis, and tonic economy in Chinese medicine.
유피는 점액 및 탄닌을 함유하고 있음이 알려져 있으나, 기타 성분에 대하여서는 밝혀진 바 없으나, 한방에서 완하제 및 점착약으로 사용되어 왔다.It is known that the dermis contains mucus and tannin, but other ingredients are not known, but it has been used as a laxative and adhesive in herbal medicine.
인삼은 고대로부터 영약으로 알려져 왔으며, 강장, 급성위염, 여러 출혈성 질환에 사용되어 왔으며, 최근에는 제암효과가 있는 것으로 보고되고 있으며, 인삼알칼로이드, 인삼사포닌 및 정유 등을 함유하고 있는 것이 밝혀져 있으나, 아직까지도 밝혀지지 않은 성분이 많은 것으로 알려져 있다.Ginseng has been known as an elixir since ancient times, and has been used for tonic, acute gastritis, and various hemorrhagic diseases. Recently, ginseng has been reported to have anticancer effects, and it has been found to contain ginseng alkaloids, ginseng saponins, and essential oils. Many components are not known until now.
감초는 글리시리진, 리퀴리틴, 리코리시딘, 리퀴리토시드 등을 함유하고 있음이 밝혀졌고, 진해, 거담, 발한, 위염 등에 널리 사용되어 오고 있다.Licorice has been found to contain glycyrrhizin, liqueurine, lycopiridine, liqueuridide, and the like, and has been widely used for antitussive, expectorant, sweating, and gastritis.
본 발명자의 상기 특허는 할미꽃뿌리 및/또는 위령선 뿌리를 주제로 하고 여기에 유피, 행인, 인삼 및 감초에서 선택된 1종 이상의 생약을 분말 또는 그 엑스를 첨가하여 항암효과가 대단히 우수한 생약조성물에 관한 것이다. 이 특허에서는 각각의 생약을 건조시킨 후 그대로 미세분말화하거나, 또는 물이나 저급알코올, 클로로포름, 염화메틸렌 및 기타 유효성분을 용해할 수 있는 용제로 0℃ 내지 사용되는 용제의 비점온도 사이의 온도에서 30분 내지 24시간 침출한 후 용제를 휘발시킨 엑스를 사용하거나 또는 이 엑스를 물이나 알코올 또는 이들의 혼합용제에 용해하여 사용되어 왔다. 이들 유효성분의 추출에는 각각의 생약을 각각 추출하거나 또는 생약성분을 2종 이상 합하여 함께 엑스로 추출할 수도 있으며, 이렇게 분말화한 엑스를 부형제로 유당, 각종의 전분, 백당, 만니톨, 솔비톨, 인산칼슘, 알루미늄시리케이트, 칼슘설페이트, 탄산칼슘 등과 같은 무기염류; 결합제로 서당, 글루코스, 전분, 젤라틴, 카복시메틸셀룰로오스, 메틸셀룰로오스, 아라비아고무, 트라가칸트고무, 에틸셀룰로오스, 알기닌산소다, 하이드록시프로필메틸셀룰로오스, 폴리비닐피롤리돈, 용성 셀룰로오스; 붕해제로 전분, 카복시메틸셀룰로오스, 메틸세룰로오스, 결정 셀룰로오스; 활택제로 스테아린산 마그네슘, 스테아린산칼슘; 보습제로 글리세린, 프로필렌글리콜, 솔비톨; 보존제로 소디움 벤조에이트, 메틸파라하이드록시벤조에이트, 프로필파라하이드록시벤조에이트, 벤잘코늄클로라이드와 같은 양이온 계면활성제, 클로로부타놀, 소디움데하이드로아세테이트; 용해보조제로 수용성 알코올류 및 그 유도체, 각종의 계면활성제; 산화방지제로 아황산소다, 소디움피로설페이트, 소디움메타설페이트, 소디움비설파이트, 롱가리트, 아스코르빈산; 등장화제로 염화나트륨, 덱스트로오스; 무통화제로 벤질알코올, 클로로부타놀; 연고기제로 바셀린, 유동파라핀, 각종의 식물유, 왁스 라놀린 등을 사용하여 통상의 제제로 제제화하여 사용되어 왔다.The above patent of the inventors relates to a herbal composition with the anti-cancer effect by adding powder or extract thereof to at least one herb selected from skins, algae, ginseng and licorice, subject to pasqueflower roots and / or gastric roots. . In this patent, each herbal medicine is dried and then micropowdered as it is, or a solvent capable of dissolving water, lower alcohol, chloroform, methylene chloride and other active ingredients at a temperature between 0 ° C. and the boiling point temperature of the solvent used. After leaching for 30 minutes to 24 hours, the solvent is volatilized, or the extract is dissolved in water, alcohol or a mixed solvent thereof. Extracting these active ingredients may be performed by extracting each herbal medicine individually or by combining two or more herbal ingredients, and extracting them together as an excipient. The powdered extract is excipient with lactose, various starches, white sugar, mannitol, sorbitol, and phosphoric acid. Inorganic salts such as calcium, aluminum silicate, calcium sulfate, calcium carbonate and the like; As a binder, sucrose, glucose, starch, gelatin, carboxymethyl cellulose, methyl cellulose, gum arabic, tragacanth rubber, ethyl cellulose, sodium arginate, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, soluble cellulose; Starch, carboxymethyl cellulose, methyl cellulose, crystalline cellulose as disintegrants; Magnesium stearate and calcium stearate as lubricants; Humectants such as glycerin, propylene glycol, sorbitol; As a preservative, cationic surfactants such as sodium benzoate, methylparahydroxybenzoate, propylparahydroxybenzoate, benzalkonium chloride, chlorobutanol, sodium dehydroacetate; Water-soluble alcohols and derivatives thereof, and various surfactants as dissolution aids; Antioxidants such as sodium sulfite, sodium pyrosulfate, sodium metasulfate, sodium bisulfite, longgarite, ascorbic acid; Isotonic agents sodium chloride, dextrose; Benzyl alcohol, chlorobutanol; It has been formulated into a conventional formulation using petrolatum, liquid paraffin, various vegetable oils, wax lanolin, and the like as a broth.
그러나, 본 발명자는 오랜 연구결과, 상기의 제제는 매우 불안정하여 제제화하여 통상으로 약 3 내지 6개월 이내에 사용되지 않으면, 그 약효를 충분히 발휘할 수 없는 사실을 발견하였다.However, the inventors have found a long study that the above formulations are very unstable and cannot be sufficiently exerted unless they are formulated and usually used within about 3 to 6 months.
따라서 본 발명의 목적은 백두옹 뿌리, 유피 또는 백두옹 뿌리와 유피의 동결건조 분말을 주제로 하고 여기에 감초, 인삼 등에서 선택된 1종 이상의 보조생약의 동결건조 분말과 특허 제 72982호에서 사용되는 동상의 보조제를 첨가하여 제조되는 생약조성물에서 이를 수년간까지 보관하여도 안정하고 약효가 전혀 떨어지지 않는 안정화된 약학적 조성물과 이 조성물의 제조방법을 제공하는 것이다.Therefore, an object of the present invention is the lyophilized powder of baekduong root, dermis or baekduong root and dermis and the lyophilized powder of one or more auxiliary herbs selected from licorice, ginseng and frostbite adjuvant used in Patent No. 72982. It is to provide a stabilized pharmaceutical composition and a method of preparing the composition that is stable even if stored for several years in the herbal composition prepared by the addition of no medicinal effect.
본 발명자는 각각의 생약은 60℃ 이하에서 용제로 추출하여야 하며, 이렇게 추출된 용액은 즉시 동결건조시켜야만 약효가 떨어지지 않고 장기간 보존할 수 있음을 발견하여 본 발명을 완성하였다.The present inventors have completed the present invention by discovering that each herbal medicine should be extracted with a solvent at 60 ° C. or lower, and thus the extracted solution should be lyophilized immediately so that the drug can be stored for a long period of time without losing its efficacy.
본 발명에서 사용되는 주제생약으로서는 건조생약으로서 백두옹뿌리(Pulsatillae Radix) 0 - 100중량부 및 유피(Ulmaceae Cortex) 0 - 100중량부(단, 두 성분이 동시에 0은 아니다.)의 양을 사용하며, 보조성분으로서 인삼(Ginseng Radix) 0 - 70중랑부 및 감초(Glycyrrhixae Radix) 0 - 70중량부를 사용할 수 있다. 이때, 바람직하게는 총 생약성분중 백두옹뿌리, 유피 또는 백두옹 뿌리와 유피의 합은 30중량부 이상으로 한다.As the main medicine used in the present invention, the dry medicine uses 0-100 parts by weight of Pulsatillae Radix and 0-100 parts by weight of Ulmaceae Cortex (but the two components are not 0 at the same time). As a supplement, ginseng (Ginseng Radix) 0-70 weight parts and licorice (Glycyrrhixae Radix) 0-70 parts by weight can be used. At this time, preferably, the sum of the baekduong root, buckwheat or baekduong root and the dermis of the total herbal ingredients is 30 parts by weight or more.
주사제로 사용되는 경우에는 생약의 침출액을 동결건조시키기 전에 방부제로 메틸파라벤, 에틸파라벤, 프로필파라벤, 등장화제로 염화나트륨, 무통화제로 벤질알코올 등을 통상의 상용량만큼 첨가한 후에 동결건조시키는 것이 바람직하다.In the case of injection, it is preferable to add lyophilized methylparaben, ethylparaben, propylparaben as preservative, sodium chloride as isotonic agent, benzyl alcohol as non-solvent agent, and then freeze-dried before lyophilizing the leaching solution of the herbal medicine. .
주사제 이외의 캅셀제나 정제 또는 연고제로 사용될 경우에는 생약을 침출한 후 침출액을 동결건조시킨 동결건조된 분말에 특허 제 72982호에서 사용되는 통상의 부형제를 첨가하여 통상의 제제화 방법으로 제제화하여 제조할 수 있다.When used as capsules or tablets or ointments other than injections, the medicinal product may be prepared by conventional formulation method by adding a conventional excipient used in Patent No. 72982 to lyophilized powder after leaching the herbal medicine. have.
본 발명에서 사용될 수 있는 추출용 용제로는 물, 저급알코올, 아세톤, 초산에틸, 헥산 또는 이들의 혼합용제를 사용하는 것이 바람직하다.As the extraction solvent that can be used in the present invention, it is preferable to use water, lower alcohol, acetone, ethyl acetate, hexane or a mixed solvent thereof.
이렇게 60℃ 이하의 온도에서 추출되고 동결건조시켜서 얻어진 건조분말은 이를 바이알에 넣어서 사용시에 주사용 증류수를 가하고 주사하거나, 또는 캡슐에 충진하거나 정제로 타정하거나 또는 연고제로 제제화하여 사용된다.The dry powder thus obtained by extraction and freeze-drying at a temperature of 60 ° C. or lower is put into a vial and added with distilled water for injection when in use, or filled into capsules, tableted or tableted or formulated into an ointment.
본 발명의 조성물은 생약의 동결건조 분말성분으로 환산하여 일일 100mg 내지 5g을 7일에 1회 내지 일일 1회 내지 3회 분할하여 투여할 수 있다, 이 양은 환자의 성별, 나이, 질병의 진행정도 등에 따라서 증감될 수 있다.The composition of the present invention can be administered by dividing 100mg to 5g per day divided into 1 to 3 times a day in 7 days in terms of lyophilized powder component of the herbal medicine, the amount is the sex, age, disease progression of the patient It may increase or decrease depending on the like.
다음에 본 발명을 실시예 및 실험예로서 상세히 설명한다.Next, the present invention will be described in detail as Examples and Experimental Examples.
비교예 1Comparative Example 1
정제수 90ml에 분말화한 백두옹뿌리 6.26g을 약 60℃로 가열하여 약 60분간 교반한다. 3,500rpm의 원심분리기로 약 30분간 원심분리하여 얻어진 분리액 약 50ml를 60℃ 이하의 저온 무균박스안에서 여과한 후 무균상태에서 염화나트륨을 가하여 등장액으로 한 후 다시 세균 여과기로 여과한 후 무균상태로 2.5ml씩 3ml의 앰플에 충진하고 밀전하여 주사제를 제조한다.6.26 g of powdered Baekduong root in 90 ml of purified water was heated to about 60 ° C. and stirred for about 60 minutes. About 50ml of the separated solution obtained by centrifugation for 30 minutes with a 3,500rpm centrifuge was filtered in a low-temperature sterile box below 60 ° C, then added with sodium chloride in aseptic state to make isotonic solution, and then filtered through a bacterial strainer, followed by 2.5 sterile conditions. 3 ml ampoules were filled in ml and tightly prepared to prepare an injection.
비교예 2Comparative Example 2
정제수 90ml에 분말화한 백두옹뿌리 4g, 건조 유피 2g, 건조인삼 2g 및 건조감초 1g을 증발하는 량만큼 정제수를 보충하며 약 80℃에서 60분간 교반한다. 혼합물을 실온에서 냉각시키고 3,500rpm의 원심분리기로 약 30분간 원심분리하여 침출액 46ml를 얻는다. 여기에 염화나트륨을 적당량 가하여 등장액으로 조절한 후 저온무균박스안에서 일반여과한 후 다시 세균여과기로 여과한 후 무균상태로 2ml의 앰플에 충진하고 냉장고에 보관한다.90 ml of purified water is supplemented with the amount of evaporated 4 g of powdered baekduong root, 2 g of dried skin, 2 g of dried ginseng and 1 g of dried licorice, and stirred at about 80 ° C. for 60 minutes. The mixture is cooled at room temperature and centrifuged for about 30 minutes with a 3,500 rpm centrifuge to give 46 ml of leachate. After adding an appropriate amount of sodium chloride to adjust the isotonic solution, and then filtered through a general filter in a low-temperature aseptic box, filtered again with a bacterial filter, and filled into 2ml ampoules aseptically and stored in the refrigerator.
비교예 3Comparative Example 3
분말화한 백두옹뿌리 62.6g, 인삼 31.3g, 감초 10g을 정제수 900ml에 넣고 증발되는 물의 양만큼 정제수를 보충하며 약 60℃에서 60분간 추출한다. 추출액 약 40ml를 여과한 후 농축하여 엑스 약 26.4g을 얻는다.62.6g of powdered Baekduonggup root, 31.3g of ginseng, and 10g of licorice are added to 900ml of purified water and supplemented with purified water as much as evaporated water and extracted at about 60 ℃ for 60 minutes. About 40 ml of the extract was filtered and concentrated to give x 26.4 g.
실시예 1Example 1
정제수 100ml에 백두옹뿌리 건조분말 6g을 넣고 증발하는 량만큼 정제수를 보충하며 60℃ 이하의 온도에서 약 60분간 교반하여 침출시킨다. 침출액을 rpm 5000의 원심분리기로 분리한 후, 등장화제로 염화나트륨 900mg 및 방부제로 파리옥시안식향산 메틸 160mg을 넣은 다음 무균실에서 세균여과기초 여과한 후 5ml 용량의 바이알 20개에 나누어 넣고 신속하게 -40℃ 이하에서 동결건조시킨 후 밀전하여 분말주사제를 제조하였다.Put 100g of dried powder of Baekduong-root into 100ml of purified water and replenish purified water as much as evaporated. Leave it by stirring for 60 minutes at the temperature below 60 ℃. The leachate was separated by centrifugation at rpm 5000, 900 mg of sodium chloride as a tonicity agent and 160 mg of paroxyoxybenzoic acid as preservatives were added. After filtration of bacteria in a clean room, the mixture was divided into 20 vials of 5 ml volume and rapidly -40 ° C. After freeze-drying below and tightly prepared to prepare a powder injection.
실시예 2Example 2
증류수 100ml에 분말화 백두옹뿌리 6g, 유피 4g, 감초 0.9g을 넣고 증발하는 량만큼 정제수를 보충하며 60℃ 이하의 온도에서 약 60분간 교반하여 침출시킨다. 침출액을 rpm 5000의 원심분리기로 분리한 후, 등장화제로 염화나트륨 900mg 및 방부제로 파라옥시안식향산 메틸 160mg을 넣은 무균실에서 세균여과기로 여과한 다음 5ml 용량의 바이알 20개에 나누어 넣고 신속하게 -40℃ 이하에서 동결건조시킨 후 밀전하여 분말주사제를 제조하였다.Add 100 g of powdered Baekduong root, 100 g of distilled water, 0.9 g of licorice, and add 0.9 g of licorice to replenish the purified water as much as evaporated. Leave it by stirring for about 60 minutes at a temperature below 60 ℃. The leachate was separated by a centrifuge at rpm 5000, filtered through a bacterial filter in a clean room containing 900 mg of sodium chloride as the isotonic agent and 160 mg of methyl paraoxybenzoate as an antiseptic agent, and then divided into 20 vials of 5 ml volume and rapidly below -40 ° C. After lyophilization at and tightly prepared powder injection.
실시예 3Example 3
증류수 100ml에 분말화 백두옹뿌리 6g, 인삼 3g 및 감초 0.9g을 넣고 증발하는 량만큼 증류수를 보충하며 60℃ 이하의 온도에서 약 60분간 교반하여 침출시킨다. 침출액을 rpm 5000의 원심분리기로 분리한 후 여기에 등장화제로 염화나트륨 900mg과 방부제로 파라옥시안식향산 프로필 120mg 및 무통화로 벤질알코올 500mg을 첨가하고 무균실에서 세균여과기로 여과한 후 5ml용량의 바이알 20개에 나누어넣고 신속하게 -40℃ 이하에서 동결건조시킨 후 밀전하여 분말주사제를 제조하였다.Add 100 g of powdered baekduong root, 100 g of ginseng, and 0.9 g of licorice in 100 ml of distilled water to replenish distilled water as much as evaporated. Leave it by stirring for 60 minutes at a temperature below 60 ℃. The leachate was separated by centrifugation at rpm 5000, and 900 mg of sodium chloride as an isotonic agent, 120 mg of paraoxybenzoic acid propyl as an antiseptic and 500 mg of benzyl alcohol as a non-cementing agent were filtered through a bacterial filter in a clean room, followed by 20 vials of 5 ml volume. After dividing into and rapidly freeze-dried at -40 ℃ or less and tightly prepared a powder injection.
실시예 4Example 4
정제수 1000ml에 분말화 백두옹뿌리 60g, 유피 40g 및 감초 9g을 넣고 증발하는 양만큼의 증류수를 보충하며 60℃ 이하의 온도에서 약 60분간 침출시킨다. 침출액을 rpm 5000의 원심분리기로 분리한 후 -40℃ 이하에서 신속하게 동결건조시켜서 38.150mg(약 38g)의 동결건조된 분말을 얻는다.Add 60 g of powdered Baekduong root, 40 g of yupi and 9 g of licorice to 1000 ml of purified water, and replenish with distilled water as much as evaporated. Leave it for 60 minutes at a temperature below 60 ℃. The leachate is separated by centrifugation at rpm 5000 and then quickly lyophilized at -40 ° C or lower to obtain 38.150 mg (about 38 g) of lyophilized powder.
실시예 5Example 5
50%(v/v)의 알코올 1000ml에 분말화 백두옹뿌리 60g, 유피 60g 및 감초 9g을 넣고 증발하는 량만큼 같은 알코올수용액을 보충하면서 약 50 내지 60℃에서 약 60분간 침출시킨다. 침출액을 rpm 5000의 원심분리기로 분리한 후 -40℃ 이하에서 동결건조시켜서 동결건조된 분말 45.150mg(약 45g)을 얻는다.To 1000 ml of 50% (v / v) alcohol, add 60 g of powdered baekduongroot, 60 g of skin, and 9 g of licorice, and leach it for about 60 minutes at about 50-60 ° C. while supplementing the same aqueous alcohol solution. The leachate is separated by centrifugation at rpm 5000 and then lyophilized at -40 ° C or lower to obtain 45.150 mg (about 45 g) of lyophilized powder.
실시예 6Example 6
50%(v/v)의 아세톤수용액에 분말화된 백두옹뿌리 60g, 인삼 30g 및 감초 9g을 넣고 증발하는 량만큼 같은 아세톤수용액을 보충하면서 약 50 - 60℃에서 약 60분간 침출시킨다, 침출액을 rpm 5000의 원심분리기로 분리한 후 -40℃ 이하에서 동결건조시켜서 동결건조된 분말 34.650mg(약 35g)을 얻는다.Add 50 g (v / v) of acetone solution to 60 g of powdered white beans, 30 g of ginseng and 9 g of licorice, and leach it for about 60 minutes at 50-60 ° C. while adding the same acetone solution as the amount of evaporation. Separation with a centrifuge of 5000 followed by lyophilization at −40 ° C. or below yields 34.650 mg (about 35 g) of lyophilized powder.
실시예 7Example 7
70%(v/v)의 에탄올에 분말화 백두옹뿌리 6g, 유피 4g 및 감초 0.9g을 넣고 증발하는 량만큼 70%(v/v)의 에탄올을 보충하면서 60℃ 이하의 온도에서 약 60분간 교반하여 침출시킨다. 침출액을 rpm 5000의 원심분리기로 분리한 등장화제로 염화나트륨 900mg 및 방부제로 파라옥시안식향산 메틸 160mg을 넣은 후, 무균실에서 세균여과기로 여과시키고, 다음 5ml 용량의 바이알 20개에 나누어 넣고 신속하게 -40℃ 이하에서 동결건조시킨 후 밀전하여 분말주사제를 제조하였다.Add 6 g of powdered Baekduong root, 4 g of skin, and 0.9 g of licorice in 70% (v / v) ethanol and add about 70% (v / v) ethanol as much as evaporation and stir for about 60 minutes at a temperature below 60 ℃ To leach. 900 ml of sodium chloride and 160 mg of methyl paraoxybenzoate as preservatives were added to the leachate by centrifugation at a rpm of 5000, and then filtered through a bacterial filter in a clean room, and then divided into 20 vials of 5 ml volume and rapidly -40 ° C. After freeze-drying below and tightly prepared to prepare a powder injection.
실시예 8Example 8
50%(v/v)의 에탄올 100ml에 분말화 유피 10g을 넣고 증발하는 량만큼 50%(v/v) 에탄올을 보충하며 60℃ 이하의 온도에서 약 60분간 교반하여 침출시킨다. 침출액을 rpm 5000의 원심분리기로 분리한 후 등장화제로 염화나트륨 900mg, 방부제로 파라옥시안식향산 메틸 160mg 및 무통화제로 벤질알코올 200mg을 넣은 후 무균실에서 세균여과기로 여과시키고, 5ml 용량의 바이알 20개에 나누어 넣고 신속하게 -40℃ 이하에서 동결건조시킨 후 밀전하여 분말주사제를 제조하였다.To 100 ml of 50% (v / v) ethanol, 10 g of powdered hides were added, and 50% (v / v) ethanol was replenished as much as evaporated and stirred for 60 minutes at a temperature of 60 ° C. or lower. The leachate was separated by centrifuge at rpm 5000, 900 mg of sodium chloride as isotonic agent, 160 mg of methyl paraoxybenzoate as preservative, and 200 mg of benzyl alcohol as antiseptic agent were filtered through a bacterial filter in a clean room and divided into 20 vials of 5 ml volume. Put quickly and freeze-dried at -40 ℃ or less and tightly prepared a powder injection.
실시예 9Example 9
헥산 1000ml에 분말화 백두옹 뿌리 60g, 유피 60g 및 감초 9g을 넣고 증발하는 양만큼 헥산을 보충하면서 60℃ 이하의 온도에서 약 90분간 교반하여 침출시킨다. 침출액을 rpm 5000의 원심분리기로 분리한 후 -40℃ 이하에서 동결건조시켜서 동결건조된 분말 45g을 얻는다.60 g of powdered baekduong root, 60 g of skins and 9 g of licorice are added to 1000 ml of hexane, and the mixture is leached by stirring for about 90 minutes at a temperature of 60 ° C. or less while supplementing hexane by the amount of evaporation. The leachate is separated by centrifugation at rpm 5000 and then lyophilized at -40 ° C or lower to obtain 45 g of lyophilized powder.
실시예 10Example 10
실시예 4에서 얻어진 동결건조된 엑스 150mgLyophilized X 150 mg obtained in Example 4
결정성 셀룰로오스 50mg50mg of crystalline cellulose
유당 50mgLactose 50mg
스테아린산 마그네슘 3mgMagnesium Stearate 3mg
상기의 처방을 통상의 정제의 제조방법으로 타정하고 알루미늄 포일에 포장한다.The above formulation is compressed into a conventional method for producing tablets and packaged in aluminum foil.
실시예 11Example 11
실시예 6에서 얻어진 동결건조된 엑스 150mgLyophilized X 150 mg obtained in Example 6
유당 30㎎Lactose 30mg
옥수수전분 30mgCorn Starch 30mg
탈크 5mgTalc 5mg
스테아린산 마그네슘 3mgMagnesium Stearate 3mg
상기의 처방을 통상의 캡슐제의 제조방법으로 젤라틴 경캡슐에 충진하고 알루미늄 포일에 포장한다.The above formulation is filled in gelatin light capsules by a conventional method for preparing capsules and packaged in aluminum foil.
실시예 12Example 12
실시예 5에서 얻어진 동결건조된 엑스 1000mgLyophilized extract 1000 mg obtained in Example 5
통상의 연고기제 적량Normal meat product
상기의 처방을 통상의 연고제의 제조방법에 따라 연고 10g을 제조하고 알루미늄 튜브에 충진하고 밀전하여 연고제를 제조한다.According to the conventional method for preparing an ointment, 10 g of ointment is prepared, filled into an aluminum tube, and tightly prepared to prepare an ointment.
실험예 1Experimental Example 1
(급성독성실험)(Acute Toxicity Test)
체중 234 - 276g의 래트 8마리로 행한 급성독성실험에서 실시예 1의 동결건조분말의 LD50값은 800mg/kg이었다.The LD 50 value of the lyophilized powder of Example 1 was 800 mg / kg in an acute toxicity test conducted with eight rats weighing 234-276 g.
실험예 2Experimental Example 2
(효능실험)Efficacy test
체중 약 25g의 마우스 30마리에 사르코마 180 세포 현탁액 0.1ml(1x106cell)을 각각 피하주사하여 암을 발생시키고 6일후에 10마리에는 일일 일회 실시예 1에서 제조된 분말주사제에 주사용증류수 5ml를 가하여 용해시킨 주사제를 0.15ml씩 피하주사하고, 10마리에는 비교예 1에서 제조된 주사제를 0.15ml씩 피하주사하고, 대조군 10마리에는 생리적 식염수만을 0.15ml씩 10일간 각각 피하주사 하였다. 실시예 1에서 제조된 주사제 및 비교예 1에서 제조된 주사제로 치료한 각각의 치료군 10마리중 9마리는 15일간의 주사로 모두 치료되었고, 1마리는 발암 16일만에 사망하였으며, 대조군 10마리는 발암 10일밤부터 사망을 시작하여 15일만에 모두 사망하였다.Cancer was generated by subcutaneous injection of 0.1 ml (1 × 10 6 cells) of Sarcoma 180 cell suspension into 30 mice weighing about 25 g each, and 6 ml of distilled water for injection into the powdered injection prepared in Example 1 once daily 0.15ml of each injection was dissolved by subcutaneous injection, 0.15ml of the injection prepared in Comparative Example 1 was injected subcutaneously, and 10 physiological saline only was injected 0.15ml each for 10 days. Nine out of 10 treatment groups in each treatment group treated with the injection prepared in Example 1 and the injection prepared in Comparative Example 1 were all treated with 15 days of injection, one died in 16 days of carcinogenesis, and 10 control groups Death began on the 10th night of carcinogenesis and died in 15 days.
실험예 3Experimental Example 3
(효능실험)Efficacy test
체중 약 25g의 마우스 30마리에 사르코마 180 세포 현탁액 0.1ml(1x106cell)을 각각 피하주사하여 암을 발생시키고 6일후에 10마리에는 실시예 1에서 제조된분말주사제에 주사용 증류수 5ml를 가하여 용해시킨 주사제를 0.15ml씩 피하주사하고( 제 1군), 10마리에는 비교예 1에서 제조된 주사제를 6개월간 냉장고에 보관한 주사제를 0.15ml씩 피하주사하고(제 2군), 10마리에는 생리적 식염수만을 0.15ml씩 10일간 각각 피하주사(제 3군)하였다. 제 1군에서는 10마리중 9마리는 15일간의 주사로 모두 치료되었고, 1마리는 발암 17일만에 사망하였으며, 제 2군에서는 15일간의 주사로 3마리는 완치되었고, 12일만에 1마리가 사망하고, 15일만에 3마리가 사망하고, 17일만에 3마리가 사망하였다. 제 3군의 10마리는 발암 10일부터 사망을 시작하여 15일만에 모두 사망하였다.Cancer was generated by subcutaneous injection of 0.1 ml (1 × 10 6 cells) of Sarcoma 180 cell suspension into 30 mice weighing about 25 g each. After 6 days, 5 ml of distilled water for injection was added to the powder injection prepared in Example 1 0.15ml of the dissolved injections were injected subcutaneously (Group 1), and 10 mice were injected subcutaneously by 0.15ml of injections stored in the refrigerator for 6 months in the injection preparation prepared in Comparative Example 1 (Group 2). Only physiological saline was injected by subcutaneous injection (0.13 ml) for 10 days (group 3). In group 1, 9 of 10 were all treated with 15 days of injection, 1 died in 17 days of carcinogenesis, and in group 2, 3 were cured by 15 days of injection and 1 in 12 days. Died, three died in 15 days, and three died in 17 days. Ten of the third group died on the 10th day of carcinogenesis and died in 15 days.
실험예 4Experimental Example 4
(효능실험)Efficacy test
체중 약 25g의 마우스 48마리에 사르코마 180 세포 현탁액 0.1ml(1x106cell)을 피하주사하고 발암 9일째(말기)에 7마리는 실시예 3의 주사제를 일일 일회 0.15ml씩 투여하고(제 1군), 7마리는 실시예 3의 주사제를 일일 2회 일회 0.15ml씩을 각각 피하주사하고(제 2군), 7마리는 비교에 1의 주사제를 일일 일회 0.15ml씩 투여하고(제 3군), 7마리에는 비교예 1의 주사제를 일일 2회 일회 0.15ml씩을 각각 투여하고(제 4군), 7마리에는 비교예 1의 주사제를 냉장고에 3개월보관한 주사제를 일일 일회 0.15ml씩을 투여하고( 제 5군), 7마리에는 비교예 1의 주사제를 냉장고에 6개월 보관한 주사제를 일일 2회 일회 0.15ml씩을 각각 투여( 제 6군)하고, 6마리는 대조군으로 하였다.( 제 7군).48 mice weighing about 25 g were injected subcutaneously with 0.1 ml (1 × 10 6 cells) of Sarcoma 180 cell suspension, and seven mice at day 9 (end) of carcinogenesis were administered 0.15 ml of the injection of Example 3 once daily (first 7) subcutaneously injected 0.15ml once daily with the injection of Example 3 twice (group 2), and 7 mice were administered 0.15ml once daily with comparison (group 3) , 7 mice each administered 0.15ml twice a day of the injection of Comparative Example 1 (Group 4), and 7 mice each administered 0.15ml of the injection of the comparative example 1 stored for 3 months in the refrigerator (Group 5), 7 mice were administered with 0.15 ml of the injections of Comparative Example 1 stored in the refrigerator for 6 months twice daily (Group 6), and 6 animals were used as controls. ).
제 1군 및 제 3군에서는 발암후 15일에 각각 1마리, 17일에 1마리, 18일에 1마리, 및 20일에 1마릭 각각 사망하고 3마리는 주사 20일만에(발암 29일)완치되었다.Group 1 and 3 died 1 on 15 days after carcinogenesis, 1 on 17 days, 1 on 18 days, and 1 on 20 days, respectively, and 3 died after 20 days of injection (29 carcinogenesis). It was cured.
제 2군 및 제 4군에서는 발암 16일만에 1마리, 18일만에 1마리, 19일만에 1마리 및 21일만에 1마리 사망하였고, 각각 3마리는 주사 19일만에(발망 28일) 완치되었다.In group 2 and 4, 1 died after 16 days of carcinogenesis, 1 in 18 days, 1 in 19 days and 1 in 21 days, 3 each cured after 19 days of injection (28 days of development). .
제 5군에서는 발암 15일만에 1마리, 17일만에 1마리, 18일만에 1마리, 19일만에 1마리, 21일만에 1마리 사망하였고, 2마리는 주사 21알만에 완치되었다.In group 5, 1 died after 15 days of carcinogenesis, 1 in 17 days, 1 in 18 days, 1 in 19 days, and 1 in 21 days, and 2 were cured after 21 injections.
제 6군에서는 발암 15일만에 1마리, 16일만에 1마리, 18일만에 1마리, 19일만에 1마리, 20일만에 2마리가 각각 사망하였으며, 1마리는 주사 20일만에 완치되었다.In group 6, one died after 15 days of carcinogenesis, one in 16 days, one in 18 days, one in 19 days, and two in 20 days, respectively. One was cured 20 days after injection.
제 7군에서는 발암 15일만에 모두 사망하였다.In Group 7, all died within 15 days of carcinogenesis.
실험예 5Experimental Example 5
(실시예 1의 주사제를 주사용증류수에 용해시키고 사용한 인체투여 실험: 자원자)(Human administration test using the injection of Example 1 in distilled water for injection: volunteer)
대상 : 김명원(당시 36세)(대구시 동구 신기동 모란2차 6동 501호)Target: Kim Myung-Won (age 36) (No. 501, Moran 2, 6-dong, Singi-dong, Dong-gu, Daegu)
병명 : 진행된 갑상선암Disease name: advanced thyroid cancer
진단 : 1992. 5. 7(대구 영남대학병원)Diagnosis: May 7, 1992 (Yeungnam University Hospital, Daegu)
투약기간 : 1992. 5. 16 - 1992. 10. 20Duration of medication: May 16, 1992-October 20, 1992
일일 일회 12ml씩 4일간 정맥주사 투여와 외부로 나온 종양내에 일일 2회, 1회에 10ml씩 직접주사. 종양내 직접주사는 일차 15회(8일간)주사후 25일간 쉬고 다시 정맥주사와 같은 방법의 직접주사를 시행한 후 완전 소실되어 치료완료하였음. 치료된 지 5년후 영남대학병원과 충남대학병원에서 완치판정.Inject intravenously for 12 days at a rate of 12ml once daily and inject 10ml once daily in twice-internal tumors. Intratumoral injections were rested for 25 days after the first 15 injections (8 days), followed by direct injection in the same manner as intravenous injection. Five years after treatment, he was cured by Yeungnam University Hospital and Chungnam University Hospital.
실험예 6Experimental Example 6
(실시예 2의 주사제에 주사용 증류수에 용해시킨 주사제로 인체투여 실험: 자원자)(Human administration experiment with an injection dissolved in distilled water for injection in the injection of Example 2: volunteer)
대상 : 김철기(당시 50세)(서울 양천구 신정동 목동아파트 1223동 404호Target: Kim Chul-ki (50 years old) (404, Mok-dong Apartment, Sinjeong-dong, Yangcheon-gu, Seoul, Korea)
병명 : 진행된 폐암, 수술후 잔류암으로 체중감소와 기침과 혈당, 호흡곤란Disease name: advanced lung cancer, residual cancer after surgery, weight loss, cough, blood sugar, dyspnea
진단 : 1989. 5. 18 연세의대 원주기독병원Diagnosis: May 18, 1989 Yonsei University Wonju Medical Center
투약기간 : 1989. 9. 3 - 1990. 3. 5Duration of medication: September 3, 1989-March 5, 1990
일일 일회에 10ml씩 4일간 정맥내 주사투여후 3주간 쉬었다 4일간 정맥내 주사투여를 증량하면서 7개월간 반복투여로 모든 증세와 암수치 정상으로 치료완료하였음. 치료된지 6년후 연세의대와 충남의대에서 완치판정.The patient was rested for 3 weeks after intravenous injection for 10 days at a daily dose of 10ml. The patient was treated with normal intravenous administration for 7 months with repeated intravenous administration for 4 months while increasing intravenous injection for 4 days. Six years after treatment, he was cured by Yonsei University and Chungnam University.
실험예 7Experimental Example 7
(실시예 2의 주사제를 주사용증류수로 용해하여 사용한 인체투여 실험)(Human administration experiment using the injection of Example 2 dissolved in distilled water for injection)
대상 : 서상봉(당시 35세)( 경남 거제군 장목면 시방리 756Subject: Seo Sangbong (age 35) (756 Sibang-ri, Jangmok-myeon, Geoje-gun, Gyeongnam)
병명 : 진행된 직장암. 부분적 수술후 잔류암으로 회복이 않되고 점점 체중감소와 통증이 심해져 가고 있었음.Disease name: advanced rectal cancer. After partial surgery, he was unable to recover from residual cancer and his weight loss and pain were getting worse.
진단 : 1991. 7. 19 부산 고신의료원Diagnosis: July 19, 1991 Busan Kosin Medical Center
투약기간 : 1991. 11. 19 - 1992. 5. 12Duration of medication: November 19, 1991-May 12, 1992
일일 일회에 12ml씩 4일간 정맥내 주사투여후 3주간 쉬었다 4일간 정맥주사투여를 약량을 증량하면서 7개월간 반복투여로 잔류암이 완전 소실되어 치료완료하였음. 치료된 지 5년후 부산 고신의료원과 충남의대에서 완치판정.After 4 days of intravenous injection (12ml) for 4 days, the patient was rested for 3 weeks. After 4 days of intravenous injection, the residual cancer completely disappeared after 7 months of repeated administration. Five years after treatment, he was cured by Busan Shinshin Medical Center and Chungnam Medical School.
실험예 8Experimental Example 8
(실시예 3의 주사제에 주사용 증류수로 용해시킨후 인체투여 실험 자원자)(Human administration test volunteer after dissolving in the injection of Example 3 with distilled water for injection)
대상 : 박주상 (당시 45세) : 부산시 금정구 부곡 1동 387-3 15/2Subject: Park Joo-sang (age 45): 387-3 Bugok 1-dong, Geumjeong-gu, Busan 15/2
병명 : 진행된 위암 더부룩함, 소화불량과 체중감소Disease name: advanced stomach cancer bloating, indigestion and weight loss
진단 : 1989. 12. 29 부산 고신의료원Diagnosis: Dec. 29, 1989 Busan Kosin Medical Center
투약기간 : 1990. 3. 1 - 1990. 9. 29Duration of medication: March 1, 1990-September 29, 1990
일일 일회 12ml씩 4일간 정맥내 주사하면서 일회 173mg씩 일일 4회 내복을 겸하여 7개월간 내복은 쉬지 않고 계속 복용하면서 주사는 4주간 쉬었다. 4일간 주사를 7개월간 반복투여로 모든 증세 치료와 조직검사에서 정상으로 나왔으므로 치료완료하였음. 치료된 지 6년후 부산 고신의료원에서 완치판정.Injecting 12ml once daily for 4 days, and taking 173mg once daily for 4 times. Four-day injections were repeated for seven months, and all of the symptoms and biopsies were normal. Six years after treatment, he was cured by Busan Kosin Medical Center.
실험예 9Experimental Example 9
(실시예 5의 주사제에 주사용 증류수로 용해시킨 후 인체투여 실험 자원자)(Human administration test volunteer after dissolving with distilled water for injection in the injection of Example 5)
대상 : 이복도 (당시 65세) : 경북 양산군 화곡면 초산리 322-81Subject: Lee Bok-do (age 65): 322-81, Chosan-ri, Hwagok-myeon, Yangsan-gun, Gyeongbuk
병명 : 진행된 간암 부분적 수술후 난류암으로 복수와 소화불량 체중감소.Pathology: Revised and indigestible weight loss due to turbulent cancer after partial liver cancer surgery.
진단 : 1994. 4. 8 부산 고신의료원Diagnosis: April 8, 1994 Busan Kosin Medical Center
투약기간 : 1994. 5. 31 - 1994. 12. 30Duration of medication: May 31, 1994-December 30, 1994
일일 일회 9ml씩 4일간 정맥주사와 간장의 잔류종양내에 직접주사를 일일 일회 4ml씩 3일간 정맥주사와 겸하여 투여하고 3주 쉬고 반복투여를 3차까지는 동시시행후 4차부터는 정맥주사만 7개월간 반복투여로 치료완료하였음. 치료된지 3년후 부산 고신의료원과 충남의대에서 모두 정상판정.Intravenous injection for 9 days each day for 4 days and intravenous injection directly into the remaining tumor of liver for 4 days once daily for 3 days with intravenous injection for 3 days, followed by 3 weeks of re-administration up to 3 times. Treatment completed by administration. Three years after the treatment, both the Busan Kosin Medical Center and Chungnam Medical College were judged normal.
안정성실험예 1Stability Test Example 1
본 발명의 실시예들에서 제조된 동결건조된 분말주사제를 2년간 보관한 후 주사용증류수를 각각 가하여 용해시킨 결과 침전물은 전혀 없었으며, 황갈색의 투명한 액이 되었다.After freeze-dried powder injection prepared in the embodiments of the present invention for two years and dissolved by adding distilled water for injection respectively, there was no precipitate, it became a yellowish-brown transparent liquid.
안정성 실험예 2Stability Experimental Example 2
비교예 2에서 제조된 주사제를 냉장고에 1개월, 2개월 3개월동안 저장하였다. 그 결과 1개월부터 침전물이 생성되기 시작하여 3개월동안 저장한 후에는 혼탁한 액이 되어 주사제로 사용이 어려울 정도로 변질되었다.The injection prepared in Comparative Example 2 was stored in the refrigerator for 1 month, 2 months and 3 months. As a result, precipitates began to form from 1 month, and after 3 months of storage, the solution became turbid and deteriorated so that it was difficult to use as an injection.
이상의 실헐예에서도 확인되는 바와 같이 종래 방법에 따른 항암 생약조성물은 수분에 매우 민감하고, 냉장고에 보관하여도 변질되어 장기간 저장할 수 없고, 약효가 떨어지므로 약물로 사용될 수 없는 것이 확인된다. 본 발명의 방법에 의하여 각각의 생약의 추출온도를 60℃ 이하의 온도로 하고 추출후 즉시 동결건조시켜서 제제화함으로써 장기간 보존하여도 약효의 변화가 없을 뿐만 아니라 성상의 변화도 없고, 안전하게 사용될 수 있다.As can be seen from the above example, the anticancer herbal composition according to the conventional method is very sensitive to moisture, and even if stored in the refrigerator, it can be deteriorated and stored for a long time, and it is confirmed that it can not be used as a drug because of poor efficacy. According to the method of the present invention, the extraction temperature of each herbal medicine is set at a temperature of 60 ° C. or lower, and is prepared by lyophilization immediately after extraction, so that there is no change in drug efficacy and no change in properties even when stored for a long time, and can be used safely.
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| KR1019980048277A KR100312622B1 (en) | 1998-11-03 | 1998-11-11 | Stabilized anticancer composition mainly composed of herbal medicine and its manufacturing method |
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| EP99954463A EP1044011A1 (en) | 1998-11-03 | 1999-11-03 | Pharmaceutical composition having antitumor activity and process for the preparation thereof |
| RU2000120474/14A RU2201759C2 (en) | 1998-11-03 | 1999-11-03 | Pharmaceutical composition of antitumor activity (versions) and method for its obtaining (versions) |
| AU10804/00A AU1080400A (en) | 1998-11-03 | 1999-11-03 | Pharmaceutical composition having antitumor activity and process for the preparation thereof |
| CNB998019763A CN1179729C (en) | 1998-11-03 | 1999-11-03 | Pharmaceutical composition having antitumor activity and process for the preparation thereof |
| HU0101256A HUP0101256A3 (en) | 1998-11-03 | 1999-11-03 | Pharmaceutical composition having antitumor activity and process for the preparation thereof |
| BR9907168-1A BR9907168A (en) | 1998-11-03 | 1999-11-03 | "anti-tumor pharmaceutical composition and process for the preparation of an anti-tumor pharmaceutical composition" |
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| CA002317113A CA2317113A1 (en) | 1998-11-03 | 1999-11-03 | Pharmaceutical composition having antitumor activity and process for the preparation thereof |
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| KR100568607B1 (en) * | 2002-07-22 | 2006-04-07 | 김송배 | Use of hederagenin 3-O-?-L-rhamnopyranosyl1?2-[?-D-glucopyranosyl1?4]-?-L-arabinopyranoside or extracts from Pulsatillae radix containing the same as therapeutic agents for solid tumors |
| KR100515206B1 (en) * | 2002-09-23 | 2005-09-16 | 김종석 | Cosmetic composition having whitening effect comprising extract of Pulsatilla Radix as main ingredient |
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| KR100628334B1 (en) * | 2004-07-30 | 2006-09-27 | 김송배 | A method of improving anticancer effect of Pulsatillae radix and a composition prepared by the method |
| JP4892833B2 (en) * | 2004-12-17 | 2012-03-07 | 大正製薬株式会社 | Fat absorption inhibitor |
| JP2012246311A (en) * | 2012-09-05 | 2012-12-13 | Sk Chemicals Co Ltd | Pulsatilla radix extract having brain function improving effect |
| AU2017422167B2 (en) | 2017-07-07 | 2021-06-24 | Qi Liu | Preparation of Pulsatilla saponin B4 for injection |
| CN107468747A (en) * | 2017-10-10 | 2017-12-15 | 刘建明 | A kind of ginseng composition for being advantageous to anticancer, anti-cancer and preparation method thereof |
| CN111466484A (en) * | 2020-04-15 | 2020-07-31 | 四川中地油科技有限公司 | Black soldier fly soft rot prevention and control compound formula and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR940000234B1 (en) * | 1989-09-04 | 1994-01-12 | 김송배 | Novel pharmaceutical composition having an antitumor activity and a process for preparation thereof |
| KR100205045B1 (en) * | 1996-12-05 | 1999-06-15 | 김송배 | Novel triterpene glycosidic compound process thereof |
-
1998
- 1998-11-11 KR KR1019980048277A patent/KR100312622B1/en not_active IP Right Cessation
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1999
- 1999-11-03 EP EP99954463A patent/EP1044011A1/en not_active Withdrawn
- 1999-11-03 BR BR9907168-1A patent/BR9907168A/en not_active IP Right Cessation
- 1999-11-03 CA CA002317113A patent/CA2317113A1/en not_active Abandoned
- 1999-11-03 CN CNB998019763A patent/CN1179729C/en not_active Expired - Fee Related
- 1999-11-03 PL PL99341650A patent/PL341650A1/en not_active Application Discontinuation
- 1999-11-03 AU AU10804/00A patent/AU1080400A/en not_active Abandoned
- 1999-11-03 HU HU0101256A patent/HUP0101256A3/en unknown
- 1999-11-03 JP JP2000579242A patent/JP2002528511A/en active Pending
- 1999-11-03 WO PCT/KR1999/000659 patent/WO2000025802A1/en not_active Application Discontinuation
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Also Published As
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|---|---|
| PL341650A1 (en) | 2001-04-23 |
| CN1287490A (en) | 2001-03-14 |
| EP1044011A1 (en) | 2000-10-18 |
| KR20000031989A (en) | 2000-06-05 |
| RU2201759C2 (en) | 2003-04-10 |
| CN1179729C (en) | 2004-12-15 |
| HUP0101256A2 (en) | 2004-05-28 |
| AU1080400A (en) | 2000-05-22 |
| CA2317113A1 (en) | 2000-05-11 |
| JP2002528511A (en) | 2002-09-03 |
| WO2000025802A1 (en) | 2000-05-11 |
| BR9907168A (en) | 2000-10-17 |
| HUP0101256A3 (en) | 2006-02-28 |
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