EP1044011A1 - Composition pharmaceutique a activite antitumorale et son procede de preparation - Google Patents

Composition pharmaceutique a activite antitumorale et son procede de preparation

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Publication number
EP1044011A1
EP1044011A1 EP99954463A EP99954463A EP1044011A1 EP 1044011 A1 EP1044011 A1 EP 1044011A1 EP 99954463 A EP99954463 A EP 99954463A EP 99954463 A EP99954463 A EP 99954463A EP 1044011 A1 EP1044011 A1 EP 1044011A1
Authority
EP
European Patent Office
Prior art keywords
powdered
radix
lyophilizing
filtering
auxiliaries
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP99954463A
Other languages
German (de)
English (en)
Inventor
Song Bae Kim
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of EP1044011A1 publication Critical patent/EP1044011A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • composition having antitumor activity and process for the preparation thereof
  • the present invention relates to a pharmaceutical composition having antitumor activity which contains herb medicines as the main ingredients, and process for the preparation thereof.
  • the inventor had invented a pharmaceutical composition of herb medicines having antitumor activity and process for the preparation thereof, and the invention was granted the Korean patent No. 72982.
  • the above-mentioned patent discloses a pharmaceutical composition containing PulsatiUae Radix ( Pulsatilla koreana Nakai, P. cernua, P. danurica, P. ratensis, Chinese PulsatiUae, Mongolian PulsatiUae ) and/or Clematis Chinensis Osbeclo ( so called, Chinese clematis) as the main ingredients, and optionally Ulmaceae Cortex, Armeniacae Semen, Ginseng Radix and Glycyrrhizae Radix and process for the preparation thereof.
  • PulsatiUae Radix Pulsatilla koreana Nakai, P. cernua, P. danurica, P. ratensis, Chinese PulsatiUae, Mongolian PulsatiUae
  • Clematis Chinensis Osbeclo so called, Chinese clematis
  • PulsatiUae species are grown wild all over the world, and the PulsatiUae Radix has been used as an antiphlogistic agent, astringent and hemostatic agent and thus for the treatment of dysentery in Korea. It is known that the PulsatiUae Radix contains anemonin, protoanemonin and saponin. Protoanemonin is the precursor of anemonin, and both may be dissolved in water, alcohol, chloroform, methylene chloride and the like. Clematis Radix contains anemonin, anemonol and saponin. It has been used as an agent for gout, diuretic agent and agent for difficult menstruum.
  • Ulmaceae Cortex contains mucin and tannin, and has been used as a lenitive and adhesive.
  • Ginseng Radix has been known from ancient times as a admirelous medicine in the Far East. It has been used as a tonic, agent for acute gastritis and agent for various bleeding diseases. Recently, it is reported that Ginseng Radix has antitumor activity and contains Ginseng alkaloids, Ginseng saponins, essence oil, etc.
  • Glycyrrhizae Radix contains glycyrrhizin, liquiritin, licoricidin and liquiritoside and has been used as a cough remedy, expectorant, diaphoretic and agent for gastritis.
  • the above invention by the present inventor relates to a pharmaceutical composition having excellent antitumor activity and containing extract or powder of PulsatiUae Radix and/or Clematis Radix as the main ingredients, and optionally extract or powder of Ulmaceae Cortex, Armeniacae Semen, Ginseng Radix and Glycyrrhizae Radix.
  • the composition may be prepared by drying and finely powdering each herb ingredients ; by extracting the herb ingredients in a solvent selected from water, lower alcohol, chloroform, methylene chloride and the others which may dissolve the effective ingredients of the herbs at the temperature of 0 ° C - the boiling point of the used solvent for 30 minutes to 24 hours and then vaporizing the used solvent to give the extract ; or dissolving said extract in water, alcohol or the mixed solvent thereof.
  • a solvent selected from water, lower alcohol, chloroform, methylene chloride and the others which may dissolve the effective ingredients of the herbs at the temperature of 0 ° C - the boiling point of the used solvent for 30 minutes to 24 hours and then vaporizing the used solvent to give the extract ; or dissolving said extract in water, alcohol or the mixed solvent thereof.
  • each herb may be extracted independently or two or more herbs may be extracted together.
  • the extract is powdered and formulated to a pharmaceutical preparation by using vehicles such as lactose, various starches, sucrose, mannitol, sorbitol and inorganic salts such as calcium phosphate, calcium sulfate, aluminiun silicate and calcium carbonate ; binders such as sucrose, glucose, starch, gelatin, carboxymethylcelluose, methylcellulose, gum arabic, gum tragacanth, ethylcellulose, sodium alginate, hydroxypropylmethylcellulose, polyvinylpyrrolidone and soluble cellulose ; disintegrators such as starch, carboxymethylcellulose, methylcellulose and crystalline cellulose ; lubricants such as magnesium stearate and calcium stearate ; wetting agents such as glycerine, propylene glycol and sorbitol I preservatives such as sodium benzoate, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, benzalkonium chloride
  • the inventor has continued intensive study to improve the antitumor composition and found that the composition by the prior invention is very unstable for preservation whereby it may easily lose its pharmaceutical effects in 3-6 months.
  • an object of the present invention is to provide an improved pharmaceutical composition which is stable and maintains its pharmaceutical efficacy even if it is preserved for several years, comprising lyophilized powder of PulsatiUae Radix, Ulmaceae Cortex, or mixture thereof as the main herb ingredients, and optionally one or more auxiliary herb ingredients selected from Ginseng Radix and Glycyrrhizae Radix, and conventional auxiliaries such as used in the prior invention ( Korean patent No. 72982 ).
  • the inventor has completed the present invention by discovering that herb ingredients should be extracted in a solvent at the temperature of below 60 °C and promptly lyophilized in order to maintain efficacy of the composition and preserve it for a long time.
  • the pharmaceutical composition in the present invention comprises as the main active herb ingredients 0-100wt of PulsatiUae Radix and 0-100wt% of Ulmaceae Cortex, and optionally as the auxiliary herb ingredients 0 ⁇ 70wt% of Ginseng Radix and 0-70wt% of Glycyrrhizae
  • the content of PulsatiUae Radix and/or Ulmaceae Cortex is over 30wt%.
  • the pharmaceutical composition having antitumor activity according to the present invention may be prepared by : extracting powdered PulsatiUae Radix and/or powdered Ulmaceae cortex, and optionally one ore more herb ingredients selected from powdered Ginseng Radix and powdered Glycyrrhizae Radix in a solvent at the temperature of below 60 ° C, filtering and lyophilizing the extract, and admixing the lyophilized powder with conventional auxiliaries, alternatively admixing the above extracted solution with auxiliaries, then filtering and lyophilizing the mixture, and then formulating the lyophilized powder to a pharmaceutical preparation by a conventional method used in the pharmaceutics.
  • composition is to be used by injection, before lyophilization, it is advisable that the extracted solution is premixed with conventional auxiliaries including a preservative such as methylparaben, ethylparaben and propylparaben, an isotonic agent such as sodium chloride and an indolent agent such as benzylalcohol.
  • a preservative such as methylparaben, ethylparaben and propylparaben
  • an isotonic agent such as sodium chloride
  • an indolent agent such as benzylalcohol.
  • the extracted solution of the herb ingredients is lyophilized and then the lyophilized powder is admixed with conventional auxiliaries such as used in the invention of the Korean patent No. 72982 by a conventional method in the pharmaceutics to give a pharmaceutical preparation.
  • the solvent for extraction of herb ingredients may include water, lower alcohol, acetone, ethyl acetate, hexane and mixtures thereof.
  • the herb ingredients are extracted in a solvent at the temperature of below 60 °C , and immediately lyophilized.
  • the lyophilized powder of the herb ingredients as above may be filled into a vial and it may be applied by adding distilled water for injection thereinto, or the lyophilized powder may be formulated to a form of capsule, tablet or ointment by a conventional method in the pharmaceutics.
  • About lOOmg to 5g of the present composition on the basis of the lyophilized powder may be administered in a day, once a week to 1 - 3 times for a day.
  • the dose of the composition may be varied in consideration of sex, age, condition of disease, etc. of the patients
  • Comparative example 1 6.26g of powdered PulsatiUae Radix was added into 90ml of purified water and the mixture was warmed to 60 ° C and stirred for 60 minutes, and then centrifuged at 3,500 rpm for 30 minutes. 50ml of the centrifuged solution was filtered in a sterilized room at below 60 °C . The resulting solution was made to isotonic solution by adding NaCl under the aseptic condition, then sterile-filtered once again and divided to each 2.5 ml of the solution in an ampoule of 3ml under the aseptic condition, and sealed to obtain injection ampoules.
  • Comparative example 2 4g of powdered PulsatiUae Radix, 2g of powdered Ulmaceae cortex, 2g of powdered Ginseng Radix and lg of powdered Glycyrrhizae Radix were added to 90ml of purified water and the mixture was stirred for 60 minutes at about 80 ° C by adding purified water corresponding to the water distilled off. The resulting solution was cooled to room temperature, centrifuged with 3,500 rpm for 30 minutes to obtain 46ml of the extracted solution. NaCl was added to the extract to obtain isotonic solution. The isotonic solution was filtered by a conventional method in a sterilized room, sterile- filtered and divided into each 2ml of the solution in an ampoule of 3ml, sealed and stored in a refrigerator.
  • Example 2 6g of powdered PulsatiUae Radix, 4g of powdered Ulmaceae cortex and 0.9g of powdered Glycyrrhizae Radix were added to 100ml of distilled water and extracted for 60 minutes at a temperature of below 60 ° C with stirring. After the extracted solution was centrifuged with 5000 rpm, 900mg of NaCl as an isotonic agent and 160mg of methyl paraoxybenzoate as a preservative were added thereto. The resulting mixture was sterile-filtered in a sterilized room, divided into 20 vials of 5ml, promptly lyophilized at below -40 °C , sealed to obtain injectable powder.
  • Example 4 60g of powdered PulsatiUae Radix, 40g of powdered Ulmaceae cortex and 9g of powdered Glycyrrhizae Radix were added to 1000ml of distilled water and extracted with stirring for 60 minutes at the temperature of below 60 ° C with adding distilled water corresponding to the water distilled off. The extracted solution was centrifuged with 5000 rpm and promptly lyophilized at below -40 °C to give 38,150mg of the lyophilized powder.
  • Example 5 60g of powdered PulsatiUae Radix, 60g of powdered Ulmaceae cortex and 9g of powdered Glycyrrhizae Radix were added to 1000ml of 50%(v/v) ethanol and extracted for 60 minutes at the temperature of 50 - 60 ° C with adding the alcohol corresponding to that distilled off. The 5 extracted solution was centrifuged with 5000 rpm and promptly lyophilized at below -40 ° C to give 45,150mg of the lyophilized powder.
  • Example 6 60g of powdered PulsatiUae Radix, 30g of powdered Ginseng Radix
  • Example 8 lOg of powdered Ulmaceae cortex was added to 100ml of 50%(v/v) ethanol and extracted for 60 minutes at the temperature of below 60 ° C with stirring. The extracted solution was centrifuged with 5000 rpm, and 5 900mg of NaCl as an isotonic agent and thereto 160mg of methyl paraoxybenzoate as a preservative were added. The resulting mixture was sterile-filtered in a sterilized room, divided into 20 vials of 5ml, promptly lyophilized at below -40 ° C , sealed to obtain injectable powder.
  • 60g of powdered PulsatiUae Radix, 60g of powdered Ulmaceae cortex and 9g of powdered Glycyrrhizae Radix were added to 1000ml of hexane and extracted for 90 minutes at the temperature of below 60 ° C with stirring and adding the hexane corresponding to the amount distilled off. 5
  • the extracted solution was centrifuged with 5000 rpm and the resulting solution was promptly lyophilized at below -40 ° C to obtain the lyophilized powder.
  • the lyophilized powder obtained by the example 1 was administered to 8 rats of 234-276g, whereby the LD50 was 800mg/kg.
  • 0.1ml of suspension of Sarcoma 180 cellsQxlO 6 cells was injected (s.c.) into 30 rats of about 25g to develop tumors.
  • 0.15ml of injection prepared by dissolving the injectable powder of the example 1 in 5ml of distilled water for injection was injected (s.c.) to 10 rats once a day and 0.15ml of injection of the comparative example 1 was injected (s.c.) to another 10 rats once a day.
  • 0.15ml of physiological saline solution was injected to the other 10 rats for 10 days as the control group.
  • Each 9 rats of the groups which were treated with the injection of the example 1 and the comparative example 1 were cured by injection for 15 days, and each 1 rat of the groups died at the 16th day, while 10 rats of the control group died all off beginning at the 10th day till to the 15th day.
  • Antitumor effect 0.1ml of suspension of Sarcoma 180 cellsQxlO 6 cells) was injected(s.c) into 30 rats of about 25g to develop tumors. After 6 days, 0.15ml of injection prepared by dissolving the injectable powder of the example 1 in 5ml of distilled water for injection was injected (s.c.) to 10 rats ( group 1 ) once a day, and 0.15ml of injection of the comparative example 1 preserved for 6 months in a refrigerator was injected (s.c.) to another 10 rats ( group 2 ) once a day, and 0.15ml of physiological saline solution was injected to the other 10 rats for 10 days as the control group ( group 3 ),
  • 0.1ml of suspension of Sarcoma 180 cellsQxlO 6 cells was injected (s.c.) into 48 rats of about 25g to develop tumors.
  • 0.15ml of sample injection prepared by dissolving the injectable powder of the example 3 in 5ml of distilled water for injection was injected (s.c.) to 7 rats once a day ( group 1 )
  • each 0.15ml of the sample injection of the example 3 was injected (s.c.) to another 7 rats twice a day( group 2 )
  • 0.15ml of sample injection of the comparative example 1 was injected (s.c.) to another 7 rats once a day ( group 3 )
  • each 0.15ml of sample injection of the comparative example 1 was injected (s.c.) to another 7 rats twice a day ( group 4 )
  • 0.15ml of injection of the comparative example 1 which was preserved for 3 months in a refrigerator was injected (s.c.) to another 7 rats once a day ( group 5 ), each
  • 1 rat died at the 15th day of carcinogenesis 1 rat died at the 17th day, 1 rat died at the 18th day, 1 rat died at the 19th day, and 1 rat died at the 21th day, while 2 rats were cured by injection for 21 days.
  • Diagnosis General hospital affiliated to the Youngnam University in Taegu on May 7, 1992.
  • Medication 12ml of the injection was injected (i.v.) once a day for 4 days, while each 10ml of the injection was injected into the protruded tumor twice a day for 8 days ( totally 15 times ), and then no treatment of injection was performed for 25 days. After that, medication was repeated by i.v. injection and direct injection into the protruded tumor as the same method above, whereby the tumor disappeared completely. After 5 years, the General hospital affiliated to the Youngnam University and the General hospital affiliated to the Chungnam University decided that the patient was completely cured.
  • Medication 10ml of the injection was injected (i.v.) once a day for 4 days, and then no treatment was performed for 3 weeks. Same medication was repeated for 7 months of the above period, whereby the tumor and related symptoms disappeared completely. After 6 years, the General hospital affiliated to the Yonsei University and the General hospital affiliated to the Chungnam University decided that the patient was completely cured.
  • Experiment 7 Clinical Test on a volunteer by administration of the injection prepared by dissolving the injectable powder of the example 2 in distilled water for injection.
  • Medication 12ml of the injection was injected (i.v.) once a day for 4 days, and then no treatment was performed for 3 weeks. Same medication was repeated for 7 months of the above period, whereby the residual tumor disappeared completely. After 6 years from the medication, the Goshin Medical Center in Pusam and the General hospital affiliated to the Chungnam University decided that the patient was completely cured.
  • Subject Name : PARK, Ju-Sang ( 45 years old at the treatment, male) Address : 15/2, 387-3, Bugok 1-dong, Kumjeong-gu, Pusan, Korea kind of disease : Progressed stomach cancer. Feeling heavy on the stomach, Dyspepsia and Weight loss.
  • Medication 12ml of the injection was injected (i.v.) once a day for 4 days, and simultaneously each 173mg of the sample was taken internally four times a day.
  • the i.v. injection was perform in such a manner that the injection was i.v. injected for 4 days and then no injection was made for 4 weeks, while the internal administration was continued. As the result, the symptoms disappeared completely and he was ascertained to be normal by the biopsy. After 6 years, the Goshin Medical Center decided that the patient was completely cured.
  • Diagnosis Goshin Medical Center in Pusan on April 8, 1994. Period of medication : From May 31, 1994 to December 30, 1994
  • Medication 9ml of the injection was injected (i.v.) once a day for 4 days, and simultaneously 4ml of the sample was injected directly into the residual tumor in liver once a day for 3 days and then for 3 weeks no treatment was performed. The same medication was performed three times, and then from the 4th cycle of medication, only i.v. injection was performed, whereby the residual tumor disappeared completely. After 3 years, the Goshin Medical Center and the Hospital affiliated to Chungnam University decided that the patient was completely cured.
  • Samples of the lyophilized power for injection prepared by the examples according to the present invention were preserved for 2 years and then dissolved in distilled water for injection. The resulting solution was transparent light brown and no precipitation settled.
  • Stability test 2 Samples of injection prepared by the comparative example 2 were stored for 1 month, 2 months and 3 months respectively. In the resulting solutions precipitate settled in 1 month and in three months the solutions was turbid whereby it was unable to be used for injection.
  • the antitumor compositions by the prior invention are sensitive to moisture, and even if stored in a refrigerator, they are easily deteriorated and efficacy thereof is severely decreased, whereby they cannot be preserved for a long time and then they cannot be used as a medicine.
  • compositions which are prepared by extracting the herb ingredients at the temperature of below 60 °C and after extraction immediately lyophilizing the extract have no change in quality and efficacy thereof after long preservation, whereby they may be used safely.

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medical Informatics (AREA)
  • Botany (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Engineering & Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une composition pharmaceutique à activité antitumorale, caractérisée en ce qu'elle comprend du Pulsatillae Radix et/ou du Ulmaceae cortex, et en ce qu'elle est plus particulièrement préparée par extraction de Pulsatillae Radix en poudre et/ou de Ulmaceae cortex en poudre, facultativement, avec un ou plusieurs ingrédients choisis à partir de Ginseng Radix et de Glycyrrhizae Radix en poudre, dans un solvant à une température inférieure à 60 °C, filtration et lyophilisation de l'extrait, ou en mélangeant la solution extraite précitée avec des auxiliaires conventionnels, puis en filtrant et en lyophilisant le mélange résultant, et en formulant la poudre lyophilisée ainsi obtenue en une préparation pharmaceutique selon un procédé conventionnel utilisé dans l'industrie pharmaceutique. La composition antitumorale selon l'invention est stable et conserve son efficacité même si elle est conservée pendant plusieurs années.
EP99954463A 1998-11-03 1999-11-03 Composition pharmaceutique a activite antitumorale et son procede de preparation Withdrawn EP1044011A1 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
KR19980047025 1998-11-03
KR9847025 1998-11-03
KR1019980048277A KR100312622B1 (ko) 1998-11-03 1998-11-11 생약을주성분으로한안정화된항암제조성물및그제조방법
KR9848277 1998-11-11
PCT/KR1999/000659 WO2000025802A1 (fr) 1998-11-03 1999-11-03 Composition pharmaceutique a activite antitumorale et son procede de preparation

Publications (1)

Publication Number Publication Date
EP1044011A1 true EP1044011A1 (fr) 2000-10-18

Family

ID=26634281

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99954463A Withdrawn EP1044011A1 (fr) 1998-11-03 1999-11-03 Composition pharmaceutique a activite antitumorale et son procede de preparation

Country Status (11)

Country Link
EP (1) EP1044011A1 (fr)
JP (1) JP2002528511A (fr)
KR (1) KR100312622B1 (fr)
CN (1) CN1179729C (fr)
AU (1) AU1080400A (fr)
BR (1) BR9907168A (fr)
CA (1) CA2317113A1 (fr)
HU (1) HUP0101256A3 (fr)
PL (1) PL341650A1 (fr)
RU (1) RU2201759C2 (fr)
WO (1) WO2000025802A1 (fr)

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WO2000033858A1 (fr) * 1998-12-07 2000-06-15 Ecosmart Technologies, Inc. Composition anticancereuse et procede utilisant des huiles essentielles vegetales naturelles avec des modulateurs de transduction de signal
US7378408B2 (en) * 2001-11-30 2008-05-27 Pfizer Inc. Methods of treatment and formulations of cephalosporin
KR100568607B1 (ko) * 2002-07-22 2006-04-07 김송배 헤데라게닌3-Ｏ-α-Ｌ-람노피라노실(1→2)-[β-Ｄ-글루코피라노실(1→4)]-α-Ｌ-아라비노피라노사이드 또는 그를 함유하는백두옹 추출물의 고형암 치료제로서의 용도
KR100515206B1 (ko) * 2002-09-23 2005-09-16 김종석 백두옹 추출물을 주성분으로 함유하는 미백 화장용 조성물
MD2231C2 (ro) * 2003-03-05 2004-02-29 Ион КАЛМЫК Compozitie pentru tratamentul patologiilor oncologice
KR100628334B1 (ko) * 2004-07-30 2006-09-27 김송배 백두옹의 항암효과를 증진시키는 방법 및 이 방법으로제조된 항암 조성물
JP4892833B2 (ja) * 2004-12-17 2012-03-07 大正製薬株式会社 脂肪吸収抑制剤
JP2012246311A (ja) * 2012-09-05 2012-12-13 Sk Chemicals Co Ltd 脳機能改善効果を有するオキナグサ抽出物
RU2759382C2 (ru) 2017-07-07 2021-11-12 Ци Лю Препарат для инъекций на основе сапонина b4 pulsatilla
CN107468747A (zh) * 2017-10-10 2017-12-15 刘建明 一种有利于抗癌、防癌的人参组合物及其制备方法
CN111466484A (zh) * 2020-04-15 2020-07-31 四川中地油科技有限公司 一种黑水虻软腐病防治复合配方及其制作方法

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KR940000234B1 (ko) * 1989-09-04 1994-01-12 김송배 신규 항암작용을 가지는 약학적 제제 및 제조방법
KR100205045B1 (ko) * 1996-12-05 1999-06-15 김송배 신규한 트리테르펜 글리코사이드 화합물, 그의 제조방법 및 그를 함유하는 항암제 조성물

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Also Published As

Publication number Publication date
AU1080400A (en) 2000-05-22
HUP0101256A2 (hu) 2004-05-28
RU2201759C2 (ru) 2003-04-10
JP2002528511A (ja) 2002-09-03
BR9907168A (pt) 2000-10-17
CN1179729C (zh) 2004-12-15
CN1287490A (zh) 2001-03-14
CA2317113A1 (fr) 2000-05-11
HUP0101256A3 (en) 2006-02-28
WO2000025802A1 (fr) 2000-05-11
KR20000031989A (ko) 2000-06-05
KR100312622B1 (ko) 2002-02-28
PL341650A1 (en) 2001-04-23

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