WO2003084945A1 - Composition pharmaceutique antispasmodique, analgesique, son procede de preparation et technique de controle de la qualite pour la preparation de ladite composition - Google Patents

Composition pharmaceutique antispasmodique, analgesique, son procede de preparation et technique de controle de la qualite pour la preparation de ladite composition Download PDF

Info

Publication number
WO2003084945A1
WO2003084945A1 PCT/CN2003/000255 CN0300255W WO03084945A1 WO 2003084945 A1 WO2003084945 A1 WO 2003084945A1 CN 0300255 W CN0300255 W CN 0300255W WO 03084945 A1 WO03084945 A1 WO 03084945A1
Authority
WO
WIPO (PCT)
Prior art keywords
solution
test
acid
paeoniflorin
preparation
Prior art date
Application number
PCT/CN2003/000255
Other languages
English (en)
Chinese (zh)
Inventor
Benxiang Wang
Shengwu Chen
Lianzhu Zhang
Hairi Li
Donghua Yang
Original Assignee
Jilin Tianyao Science And Technology Co. Ltd.
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 Jilin Tianyao Science And Technology Co. Ltd. filed Critical Jilin Tianyao Science And Technology Co. Ltd.
Priority to AU2003236118A priority Critical patent/AU2003236118A1/en
Publication of WO2003084945A1 publication Critical patent/WO2003084945A1/fr

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/90—Plate chromatography, e.g. thin layer or paper chromatography
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/191—Carboxylic acids, e.g. valproic acid having two or more hydroxy groups, e.g. gluconic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/785—Polymers containing nitrogen
    • A61K31/787—Polymers containing nitrogen containing heterocyclic rings having nitrogen as a ring hetero atom
    • A61K31/79—Polymers of vinyl pyrrolidone
    • 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
    • A61K36/484—Glycyrrhiza (licorice)
    • 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)
    • A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
    • C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography

Definitions

  • the invention relates to a combination medicine, in particular to a combination medicine for antispasmodic and analgesic, its preparation method and quality control method.
  • Shaoyao Gancao Decoction is a well-known prescription in the field of traditional Chinese medicine.
  • Traditional Chinese medicine is mainly used to treat abdominal smooth muscle cramps such as menstrual pain, uterine cramps and stomach pain.
  • Shaoyao Gancao Decoction has unique curative effect, its dosage form is still traditional decoction. Obviously, it cannot be produced industrially, but the users themselves cook it. Because the whole material is used for medicine, the active ingredients of the drug are unclear, and no effective or even harmful impurities are mixed in it. Therefore, the pharmacological analysis of Chinese herbal medicines, the isolation of medicinal active substances, and the production of modern medicines without impurities, small size, easy circulation and convenient taking through large-scale production are the development trends of Chinese medicine.
  • the drug concentration was significantly higher than that of glycyrrhizic acid.
  • glycyrrhetic acid can be used as an antispasmodic component in a combination medicine.
  • paeoniflorin and paeoniflorin metabolites are effective ingredients for analgesia and sedation. Although paeoniflorin metabolites have stronger analgesic effects than paeoniflorin, it is difficult to mass preparation.
  • paeoniflorin metabolites are products of inhaled blood after paeoniflorin is metabolized by enteric bacteria, so paeoniflorin can be used as an analgesic component in medicine.
  • An object of the present invention is to disclose a new drug combination with antispasmodic and analgesic effects. Another object of the present invention is to disclose a method for preparing a new pharmaceutical composition having antispasmodic and analgesic effects; and the object of the present invention is to disclose a new method for quality control of a pharmaceutical composition.
  • composition and formulation of the drug substance of the pharmaceutical composition of the present invention are as follows (by parts by weight): 200-110 parts by weight of glycyrrhizic acid 140-60 parts by weight of total glucosides of paeony, preferably 170-140 parts by weight of glycyrrhizic acid 110-70 Parts by weight of the pharmaceutical composition of the present invention may also be composed of the following drug substances, which are formulated as follows (by parts by weight):
  • Glycyrrhetinic acid 180-130 parts by weight Paeoniflorin 120-70 parts by weight
  • glycyrrhetic acid 110-80 parts by weight of paeoniflorum 165-145 parts by weight of glycyrrhetic acid 110-80 parts by weight of paeoniflorum
  • the medicament of the present invention can also be added to pharmaceutically acceptable carriers and / or excipients to make clinically acceptable dosage forms, such as tablets, capsules, pills, granules, suspensions, drip pills, oral liquid preparations, injections, gas Aerosols and suppositories.
  • pharmaceutically acceptable carriers and / or excipients to make clinically acceptable dosage forms, such as tablets, capsules, pills, granules, suspensions, drip pills, oral liquid preparations, injections, gas Aerosols and suppositories.
  • the preparation method of the pharmaceutical composition of the present invention is:
  • Glycyrrhetinic acid preparation Glycyrrhiza uralensis powder is boiled with water for 2 to 4 times, and the medicinal solution is filtered, and concentrated sulfuric acid is added so that no precipitate can be precipitated.
  • Paeoniflorin extraction take Paeonia lactiflora with 3-8 times the amount of 30%-60% ethanol for hot reflux or cold dip extraction 2-3 times, and concentrate the ethanol extract to a relative density of 40-60 ° C 1.1, Then add 90-96% ethanol to an alcohol concentration of 70%-90%, let it stand overnight, filter, add 1%-2% (M / V) activated carbon to the ethanol filtrate, stir, filter, ethanol filtrate Concentrated until no alcohol taste, the above-mentioned extracts were purified on two macroporous resins D101 and D201, washed with water until the Molish reaction was negative, and then eluted with 10%-30% ethanol, collected 10%-30% The ethanol eluate was concentrated under reduced pressure and dried to give pale yellow paeoniflorin.
  • the quality control method of the pharmaceutical preparation of the composition includes identification and / or content determination. Identification methods include one and / or several of the following methods:
  • Content determination includes one and / or several of the following methods:
  • Glycyrrhetinic acid determined according to high performance liquid chromatography (Appendix VI D of the Chinese Pharmacopoeia 2000 Edition); chromatographic conditions and system suitability tests, using octadecylsilane bonded silica gel as a filler; 85-100 : 8-14 methanol-water (H 3 7 adjusted by phosphoric acid) is the mobile phase; the detection wavelength is 250nm and the column temperature is room temperature; the theoretical number of plates calculated from the glycyrrhetic acid peak should not be less than 2000; the preparation of the reference solution, Lg : , Take an appropriate amount of glycyrrhetic acid reference substance, accurately weigh, add methanol to make a solution containing 25 g of glycyrrhetic acid per 1 ml, as a reference solution; for the preparation of the test solution, take the composition preparation 0.
  • the unit amount refers to an amount equivalent to one capsule preparation.
  • composition of the present invention has a small volume, good curative effect, no toxic and side effects, convenient taking, and good smooth muscle antispasmodic and analgesic effects.
  • mice tail vein injection doses 5 and 10 ml / kg (after intravenous injection, make the drug serum concentration reach its original serum respectively. 1 and 2 times), 5 minutes after dosing, after intraperitoneal injection of 1% acetic acid 10 ml / kg, record the number of writhing times for 10 minutes immediately; antispasmodic experiments, using isolated mouse uterus to test the solution of each sample according to literature methods Spasm effect. Take female mice weighing about 28g and inject estradiol at a rate of 0.4ml / subcutaneously once a day for 3 consecutive days.
  • mice will be killed by cutting their heads, the uterus will be removed, and the uterus will be washed with Typhoon's solution. Suspend the uterus in a 50ml bath and equilibrate for 30 minutes to test the sample. Take each of the experimental samples prepared from each of the serum fractions and serum residues above, and test each sample for 2 concentrations, that is, the original drug in the serum Medium concentration and half concentration. The volume of the actual test sample added to the serum is 2.5 and 1.25ml. Before adding the serum, the same volume of Tyrode's solution is released from the bath. The antispasmodic effect of each sample on spasm of the mouse uterus induced by pituitary hormone was recorded. 4.
  • Serum residue (residue 2) preparation of test samples take serum residue and add 27 ml of 10% Tween-80 aqueous solution, stir to dissolve, centrifuge 1000 g for 10 minutes, take the supernatant, and determine with 10% Tween-80 aqueous solution. The content is up to 27ml (that is, the concentration is 20 times of the original serum). For pharmacological activity test. In the analgesic and antispasmodic experiment, the dosage of the medicinal solution is the same as that of the serum sample.
  • the contents of paeoniflorin, glycyrrhizic acid and glycyrrhetic acid in the serum were measured, and the results showed that the content of paeoniflorin, glycyrrhizic acid and glycyrrhetic acid in the serum basically reached a high level 2 hours after the administration. Therefore, in the following study, when the rats were given gastric peony licorice soup to absorb the active ingredients into blood, the blood collection time was set to 2 hours after the administration.
  • Serum residue 10 23. 0 ⁇ 4. 6> 0. 05
  • the serum part 2 was separated and identified by HPLC-MS.
  • the original part 2 was single-absorbed.
  • the retention time of the HPLC chromatogram peak was also consistent with the standard of paeoniflorin ( Figure 1-1).
  • the ion peak m / z is 481.3 ( Figure 1-2), which is consistent with paeoniflorin, so part 2 is initially identified as paeoniflorin.
  • Serum fraction 3-C was detected by HPLC-MS and was absorbed by paeoniflorin into the blood metabolite PM-I (paeonimetabolin I) because of the retention time of some 3-c peaks in HPLC and molecular ions given by HPLC-MS.
  • the peak m / z amounts are all the same as PM-1, so it is preliminarily considered that part 3-c is the same compound as PM-1, and part 3-b may be glycyrrhizic acid ( Figure 2-1, 2, 3)
  • mice weighing about 28g were taken and injected subcutaneously with 0.4ml / estradiol once a day for 3 consecutive days. The head was sacrificed, the uterus was taken out, and the uterus was rinsed with Typhoon's solution. The uterus was suspended in a bath with a volume of 50 ml. After equilibration for 30 minutes, it was used to detect the sample.
  • Each of the above-mentioned serum fractions and serum residues were prepared as experimental samples. each sample detection 2 concentration, i.e. half the original concentration and the concentration of drug in the serum. the actual volume of 2.5 and the addition of 1.25 ml.
  • mice Ninety mice were divided into 9 groups, each group was divided into male and female, and the drug was administered once according to the dosage and administration route shown in Table 1.
  • the first group was the gastric control group, and the gastric 0.2% CMC aqueous suspension 10 ml / kg.
  • the sixth group is a control group for injection administration, and the saline is injected subcutaneously at 10 ml / kg.
  • the mice in the 1-5 group are administered for 1 hour after the administration, and the mice in the 6-9 group are administered for 30 minutes after the administration.
  • the number of spontaneous activities of every eight mice within 5 minutes was recorded. The results are shown in Table 3. It can be seen from Table 3 that both the glutinous capsules and ganzhi injection significantly inhibit the spontaneous activity of mice. ⁇
  • mice were grouped and administered in the same manner as in the experimental 1.1-5 group. Chlorine was administered 1 hour after administration, and the 6-9 group was administered 30 minutes after administration. The mice were injected with Evan's blue (2%, 5ml / kg), 2 minutes after the injection of Evans blue, the mice were injected intraperitoneally with 1% 'acetic acid 10ml / kg. The number of twists in each mouse within 10 minutes after the injection of acetic acid was recorded, and then the mice : Sacrifice by pushing, laparotomy with saline 4 ml / mouse flush the abdominal cavity to exudate the dye. With photoelectric colorimeter (620 nm) measurement to determine the amount of dye bleeding. The results are shown in Table 4.
  • Intraperitoneal penetration number of twisted body inhibition rate group dose (mg / kg)
  • Apparatus Powerlab / 8s data recording analyzer and related accessories (products of Australia Ede Company); YSD-4G multi-purpose instrument for pharmacological and physiological experiments and its constant temperature water bath device (product of Anhui Bengbu Radio 2 Factory).
  • Methods Rats were sacrificed after fasting for 48 hours. The abdominal cavity was opened. A section of the intestine was cut in the upper part of the small intestine and placed in culture medium I with Typhoon's solution. The mesentery was gently separated along the intestinal wall and rinsed with Typhoon «tube After that, cut into several small pieces of about 2cm for later use.
  • factor A was the main influencing factor, that is, the amount of total glucosides of paeony had a great effect on the analgesic effect
  • factor B was the secondary influencing factor
  • the optimal ratio was A, but combined with the test results
  • prescription 7 is A, but it is not as good as prescription 1 and prescription 9 for analgesic effect.
  • prescription 1 is selected.
  • Glycyrrhetinic acid preparation Glycyrrhiza uralensis powder is boiled 3 times with water, the liquid medicine is filtered, and concentrated sulfur is added The acid is no longer precipitated, placed, filtered, brown precipitate, washed and dried to obtain crude glycyrrhizic acid.
  • Paeoniflorin extraction take Paeonia lactiflora materials for 5 times the amount of 45% ethanol for hot reflux or cold dip extraction once, concentrate the ethanol extract to a relative density of 1.1 (50 ° C), and add 95% ethanol to the alcohol concentration 80%, leave it overnight, filter, add 1.5% (M / V) activated carbon to the ethanol filtrate, stir, filter, and concentrate the ethanol filtrate until it has no alcohol.
  • M / V 1.5% activated carbon to the ethanol filtrate
  • the above extracts are obtained in D101 and D201. Purify on the porous resin, first wash with water until the Molllious reaction is negative, and then elute with 10%-30% ethanol. Collect the 20% ethanol eluate, concentrate under reduced pressure, and dry to obtain pale yellow paeoniflorin.
  • Preparation method Paeoniflorin and glycyrrhetic acid are thoroughly mixed with an appropriate amount of starch and filled into capsules. Each capsule contains 0.25g of medicine.
  • Abdomen Abdominal smooth muscle cramps (menstrual pain, uterine cramps, gastrointestinal cramps due to gastric ulcers) and headaches.
  • Preparation method Paeoniflorin and glycyrrhetic acid are thoroughly mixed with an appropriate amount of starch, and granulated and compressed. each
  • 1 tablet contains 0.25g of medicine.
  • Abdomen Abdominal smooth machine spasm pain (menstrual pain, uterine spasm pain, gastrointestinal spasm pain caused by gastric ulcer) and headache.
  • Dosage and dosage Take 1-2 tablets orally at a time for pain.
  • Preparation method Dissolve peony licorice and glycyrrhetic acid in an appropriate amount of propylene glycol, filter, separate, and sterilize. Each contains 50mg of drug.
  • Indications Abdominal smooth machine spasm pain (menstrual pain, uterine spasm pain, gastrointestinal spasm pain due to gastric ulcers, and headache.
  • Usage and dosage When using, dilute one Ganzhi injection in 500ml physiological saline and inject it intravenously. Every time a 1 2.
  • Glycyrrhetinic acid determined according to high performance liquid chromatography (Appendix VI D of the Chinese Pharmacopoeia 2000 Edition); color ridge condition and system suitability test, using octadecylsilane bonded silica as a filler ; 90: 10 methanol-water (pH 3.
  • each capsule contains essential glycyrrhetic acid to 70. Omg; b.
  • Total glucosides of paeony determined according to high performance liquid chromatography (Appendix VI D of the Chinese Pharmacopoeia 2000 Edition); chromatographic conditions and system suitability tests, using octadecylsilane bonded silica as a filler 30: 70 methanol-water as mobile phase, detection wavelength 230nm; theoretical plate number should be not less than 2000 calculated from paeoniflorin peak; preparation of reference solution, take appropriate amount of paeoniflorin reference, accurately weigh and add methanol A solution containing 25pg of paeoniflorin per 1ml is used as the paeoniflorin reference solution; the preparation of the test solution, the preparation of the test solution under the same content determination item 1; the test method, the above reference solution and the test solution 0mg ⁇ Inject 10 ⁇ , inject high-performance liquid chromatography "i universal instrument, determine the peak area, calculated by external standard method, that is; each capsule of paeoniflorin should not be less than 48.0mg.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Pathology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Medical Informatics (AREA)
  • Botany (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

L'invention concerne une composition pharmaceutique antispasmodique, analgésique, son procédé de préparation, ainsi qu'une technique de contrôle de la qualité pour la préparation de ladite composition. Cette composition contient 80-130 parties en poids d'acide glycyrrhétinique et 120-70 parties en poids de paeoniflorine. L'acide glycyrrhétinique et la paeoniflorine, extraits respectivement de racines de réglisse et de racines de paeoniae alba, sont ajoutés à un ou à plusieurs excipients pharmaceutiquement acceptables et mis sous une forme galénique cliniquement acceptable, telle que des comprimés, gélules, pilules, granules, pilules à avaler, préparations buvables, injections, aérosols, suppositoires. L'invention concerne également une technique de contrôle de la qualité pour identifier les ingrédients et déterminer la concentration de la composition. Ladite composition selon l'invention peut être facilement dosée et présente un bon effet curatif, est non toxique, dépourvue d'effets secondaires. Elle présente par conséquent un excellent effet antispasmodique et analgésique.
PCT/CN2003/000255 2002-04-10 2003-04-10 Composition pharmaceutique antispasmodique, analgesique, son procede de preparation et technique de controle de la qualite pour la preparation de ladite composition WO2003084945A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003236118A AU2003236118A1 (en) 2002-04-10 2003-04-10 An antispastic, analgetic pharmaceutical composition and the preparation method thereof as well as the quality control technique therefor

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN02109466.7 2002-04-10
CNB021094667A CN1241574C (zh) 2002-04-10 2002-04-10 一种解痉、镇痛药及制备方法

Publications (1)

Publication Number Publication Date
WO2003084945A1 true WO2003084945A1 (fr) 2003-10-16

Family

ID=28680443

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2003/000255 WO2003084945A1 (fr) 2002-04-10 2003-04-10 Composition pharmaceutique antispasmodique, analgesique, son procede de preparation et technique de controle de la qualite pour la preparation de ladite composition

Country Status (3)

Country Link
CN (1) CN1241574C (fr)
AU (1) AU2003236118A1 (fr)
WO (1) WO2003084945A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1295503C (zh) * 2004-08-27 2007-01-17 广州中一药业有限公司 一种采用薄层色谱法检测乳核散结片的方法
CN1327217C (zh) * 2004-05-26 2007-07-18 江西江中药业股份有限公司 健胃消食片的质量控制方法
CN100334446C (zh) * 2005-11-09 2007-08-29 中国科学院长春应用化学研究所 甘参胶囊的成分检测方法
CN100370251C (zh) * 2004-09-23 2008-02-20 江西江中药业股份有限公司 六味地黄膏的质量控制方法
US7691387B2 (en) * 2000-09-13 2010-04-06 Jiangsu Kanion Pharmaceutical Co., Ltd Cinnamomi and poria composition, method to prepare same and uses thereof
US8067040B2 (en) 2006-10-18 2011-11-29 Jiangsu Kanion Pharmaceuticals, Co. Ltd. Cinnamomi and poria composition and uses thereof

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009070917A1 (fr) * 2007-11-30 2009-06-11 Chi, Yu-Fen Composition pharmaceutique orale pour le traitement de la barythymie
CN103520298B (zh) * 2013-10-10 2014-08-06 北京康远制药有限公司 一种具有调和肝脾、抗炎止痛作用的中药颗粒剂及其制备方法
CN106543261A (zh) * 2016-10-27 2017-03-29 深圳市新阳唯康科技有限公司 一种甘草次酸晶型物质及其制备方法
CN106565817A (zh) * 2016-11-09 2017-04-19 深圳市新阳唯康科技有限公司 一种无定型甘草次酸及其制备方法
CN106749485A (zh) * 2016-11-25 2017-05-31 深圳市新阳唯康科技有限公司 一种甘草次酸新晶型及其制备方法
CN106632575A (zh) * 2016-12-20 2017-05-10 深圳市新阳唯康科技有限公司 一种甘草次酸新晶型及其制备方法
CN114306211B (zh) * 2021-12-29 2023-12-22 中国药科大学 一种甘草酸超分子自组装温敏互穿网络凝胶及其制备方法和应用
CN115040633A (zh) * 2022-07-25 2022-09-13 中国中医科学院中医基础理论研究所 芍药甘草汤蛋白提取物的新用途

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000290186A (ja) * 1999-04-01 2000-10-17 Taisho Pharmaceut Co Ltd 液体組成物

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000290186A (ja) * 1999-04-01 2000-10-17 Taisho Pharmaceut Co Ltd 液体組成物

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
CAI GUANGMING ET AL.: "Assay of paconiflorin in fufang ruanganplan by dual wavelength thin-layer scanning technique", J. OF PHARMACEUTICS ANALYSIS, CHIN., vol. 18, no. SUPPL., pages 192 *
GUAN RONGEAL ET AL.: "Determination of the glycyrrhetinic acid content in zicao oral liquid", J. OF BASIC PHARMACEUTICS, CHIN., vol. 8, no. 3, 1994, pages 23 *
LI XINRONG ET AL.: "Assay of paconiflorin in jiangzhi yihao oral solution", J. OF CHINA HOSPITAL PHARMACEUTICS, vol. 16, no. 6, 1999 *
LIU WEI ET AL.: "Protective effect of TGP on acute cerebral ischemia in mice and rats", ACTA UNIVERSITATIS MEDICINALIS ANHUI, vol. 36, no. 3, June 2001 (2001-06-01), pages 186 *
RESEARCH OF ACTIVE INGREDIENTS IN CHINESE HERBS, FASCICULE 1, PEOPLE'S MEDICAL HEALTHY PRESS, 1972, pages 231 - 232 *
SUN XIAOJIE ET AL.: "Pharmacological research of paconia and glycyrrhizae rad. decoction", HEILONGILANG CHINESE TRADITIONAL MEDICINE, no. 3, June 2001 (2001-06-01), pages 57 *
XIANG QI ET AL.: "Pharmacokinetics and bioavailability of paconia and glycyrrhizae rad. decoction in rats", CHIN. PHARM. J., vol. 35, no. 9, September 2000 (2000-09-01), pages 617 - 618 *
ZHANG GUOGANG ET AL.: "Quantitative determination of glycyrrhetinic acid in 'Qizhiweitong granule' by HPLC", J. OF SHENYANG PHARMACEUTIAL UNIVERSITY, vol. 16, no. 1, June 1999 (1999-06-01), pages 65 - 66 *
ZHANG GUOGANG ET AL.: "Quantitative determination of the content of paconiflorin in the 'Qizhiweitong granule' by HPLC", J. OF SHENYANG PHARMACEUTICAL UNIVERSITY, vol. 15, no. 4, October 1998 (1998-10-01), pages 260 - 261 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7691387B2 (en) * 2000-09-13 2010-04-06 Jiangsu Kanion Pharmaceutical Co., Ltd Cinnamomi and poria composition, method to prepare same and uses thereof
US8119141B2 (en) 2000-09-13 2012-02-21 Jiangsu Kanion Pharmaceutical Co. Ltd. Cinnamomi and poria composition, method to prepare same and uses thereof
CN1327217C (zh) * 2004-05-26 2007-07-18 江西江中药业股份有限公司 健胃消食片的质量控制方法
CN1295503C (zh) * 2004-08-27 2007-01-17 广州中一药业有限公司 一种采用薄层色谱法检测乳核散结片的方法
CN100370251C (zh) * 2004-09-23 2008-02-20 江西江中药业股份有限公司 六味地黄膏的质量控制方法
CN100334446C (zh) * 2005-11-09 2007-08-29 中国科学院长春应用化学研究所 甘参胶囊的成分检测方法
US8067040B2 (en) 2006-10-18 2011-11-29 Jiangsu Kanion Pharmaceuticals, Co. Ltd. Cinnamomi and poria composition and uses thereof

Also Published As

Publication number Publication date
CN1449761A (zh) 2003-10-22
CN1241574C (zh) 2006-02-15
AU2003236118A1 (en) 2003-10-20

Similar Documents

Publication Publication Date Title
US10624938B2 (en) Total flavone extract of flower of abelmoschus manihot L. medic and preparation method thereof
WO2003084945A1 (fr) Composition pharmaceutique antispasmodique, analgesique, son procede de preparation et technique de controle de la qualite pour la preparation de ladite composition
CN100457139C (zh) 一种双黄连注射液的制备方法及其成分检测方法
AU2003260985B2 (en) Extraction and purification method of active constituents from stem of Lonicera japonica Thunb., its usage for anti-inflammatory and analgesic drug
CN1872106A (zh) 山香圆叶在治疗病毒性感冒疾病中的应用
CN104447904B (zh) 一种口服生物利用度高的稳定天麻素晶体及其制备方法、制剂与应用
CN101284031B (zh) 毛冬青提取物、其制备及应用
WO2006128337A1 (fr) Composition pharmaceutique destinee a prevenir et traiter le syndrome de la menopause et son procede de preparation
Su et al. Screening and analyzing the potential bioactive components from Shaofu Zhuyu decoction, using human umbilical vein endothelial cell extraction and high‐performance liquid chromatography coupled with mass spectrometry
CN1969923A (zh) 板蓝根抗病毒提取物和提取方法及用途以及含量测定方法
CN1951422A (zh) 一种主治肝胆系统疾病的药用组合物及其制剂和用途
CN103417597B (zh) 油菜花粉总甾醇有效部位及其制备方法和应用
CN101024004B (zh) 一种具有止咳、祛痰、消炎作用的药物组合物及其制备工艺
US20100311779A1 (en) Methods for preparing dehydrocavidine, dehydroapocavidine or their composition, their use and medicinal compositon containing them
CN110452110A (zh) 一种间苯三酚类天然药物及其制备方法和用途
CN101791353B (zh) 一种缓释骨架型复方喘平缓释片及其制备方法和应用
CN110467522B (zh) 一种青黛中具有抗肠炎活性的二苯乙烯类化合物及其制备方法、应用
CN102188497B (zh) 延胡索总碱的制备方法及延胡索制剂及其应用
WO2009049439A1 (fr) Procédé de préparation du f-25-o-acétate de dihydrocucurbitacine et utilisation de ce composé dans la fabrication de médicaments destinés à traiter des cancers
CN111588742A (zh) 没药倍半萜提取物在制备慢性阻塞性肺病药物中的应用
CN1939413B (zh) 一种复方北豆根药物组合物
CN113135968B (zh) 一种小花清风藤叶中的化合物及其制备方法和应用
CN1331475C (zh) 治疗胆囊炎、胆石症的药物及其制备方法
WO2014056167A1 (fr) Composition de médecine traditionnelle chinoise pour le traitement du rhume de cerveau, procédé de préparation et application associée
CN113694121B (zh) 一种中药组合物在制备抗凝血药物中的应用

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SC SD SE SG SK SL TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP