CN1449761A - Medicine for relieving spasm and pain and preparation process thereof - Google Patents
Medicine for relieving spasm and pain and preparation process thereof Download PDFInfo
- Publication number
- CN1449761A CN1449761A CN02109466A CN02109466A CN1449761A CN 1449761 A CN1449761 A CN 1449761A CN 02109466 A CN02109466 A CN 02109466A CN 02109466 A CN02109466 A CN 02109466A CN 1449761 A CN1449761 A CN 1449761A
- Authority
- CN
- China
- Prior art keywords
- enoxolone
- ethanol
- peoniflorin
- add
- medicine
- 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.)
- Granted
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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Medical Informatics (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Alternative & Traditional Medicine (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention relates to a medicine for relieving spasm and pain and its preparation method. It utilizes medicine active matter glycyrrhetinic acid extracted from licorice and paenoiflorin extracted from peony root, and uses their respective effective amount and medicinal carrier and/or excpient to make them into the modern medicine with small volume, easy storage, convenient administration and therapeutic effect identical to that of peony licorice decoction. Said medicine also has no toxic effect.
Description
Technical field:
The present invention relates to a kind of composition of medicine, specifically a kind of composition of medicine and preparation method for the treatment of abdominal part smooth muscle spasm pain, headache.
Background technology:
Peony and licorice decoction is well-known name side, domestic traditional Chinese medical science field, and tcm clinical practice is mainly used in abdominal part smooth muscle spasm pains such as treatment menstrual pain, hysterospasm and stomachache.
Though peony and licorice decoction has unique curative effect, its dosage form still is traditional decoction.Obviously can not suitability for industrialized production, but the user oneself decoct.Because be that full material is used as medicine, medicament active composition is unclear again, and inefficacy even deleterious impurity are mixed in wherein.Therefore, Chinese herbal medicine being carried out pharmacology analysis, isolate active medicinal matter, and make the modern medicines of free from admixture, little, the easy circulation of dosage, taking convenience by large-scale production, is the trend of Chinese medicine development.
For inquiring into the pharmaceutically active of peony and licorice decoction, we are after giving the rats gavaged peony and licorice decoction, get the rat blood serum of taking medicine, with instrument detecting such as HPLC and the HPLC-MS animal serum of taking medicine, drawing the active ingredient that mainly is absorbed into blood is enoxolone (glycyrrhetinic acid, or glycyrrhetic acid), glycyrrhizic acid (glycyrrhizic acid, or glycyrrhizin), peoniflorin (paeoniflorin) and peoniflorin metabolite (paeonimetaboline1, PM-1) prove through further experiment, glycyrrhizic acid in the above-claimed cpd and enoxolone are the antiphlogistic active ingredient of spasmolytic, and enoxolone wherein is the suction blood metabolite of oral administration of compound glycyrrhizic acid, its spasmolysis obviously is better than glycyrrhizic acid, and enoxolone blood drug level is apparently higher than glycyrrhizic acid.For this reason can be with enoxolone as spasmolytic composition in the combination medicine, above-mentioned experiment proves that also peoniflorin and peoniflorin metabolite are analgesia and calm active ingredient, though peoniflorin metabolite analgesic activity is better than peoniflorin, are difficult to a large amount of preparations.And the peoniflorin metabolite is the product of the suction blood of peoniflorin after the intestinal flora metabolism, thereby can be with peoniflorin as the analgesia composition in the medicine.
Summary of the invention:
The objective of the invention is to have spasmolytic, a kind of spasmolytic, an analgesic medicine of being used for of analgesic pharmaceutically active substance combination with what analyze that peony and licorice decoction finds.
Another object of the present invention is to provide a kind of to be raw material with Radix Glycyrrhizae and Radix Paeoniae, to prepare the method for said medicine.
The technical scheme of medicine of the present invention by the enoxolone that contains abdominal part smooth muscle spasmolysis effective dose and the analgesia peoniflorin of effective dose and pharmaceutically useful carrier/or excipient form.
According to the present invention, this pharmaceutical composition can be made common tablet (sweet Chinese herbaceous peony sheet), capsule (sweet Chinese herbaceous peony capsule) and other solid dosage forms or injection.The preparation solid dosage forms can add excipient materials such as starch.Can add conventional solvent and make injection.
The preparation method of medicine of the present invention is:
1, the preparation of enoxolone: the Radix Glycyrrhizae coarse powder adds water boil, and the leaching medicinal liquid adds concentrated sulphuric acid to no longer separating out precipitation, place, and leaching, brown precipitate, washing and drying gets glycyrrhizic acid inclusion compound.Use the acetone reflux, extract,, get acetone extract, put coldly, stir and to add KOH ethanol liquid down to alkalescence, place, separate out crystallization, filtering crystallization (GLYCYRRHIZIC ACID POTASSIUM), drying adds the glacial acetic acid thermosol, puts cold, separate out crystallization, filter, get monopotassium glycyrrhizunate, add dilute sulfuric acid, heating, sucking filtration, be washed to neutrality, drying gets white enoxolone crude product, it is dissolved in the hot chloroform, filtered while hot is put chloroformic solution cold again, peroxidating aluminum chromatographic column is used the chloroform eluting, gets enoxolone, the ethanol thermosol is poured in the boiling water while hot, places, get crystallization, filter, promptly get medicinal enoxolone crystallization.
2, peoniflorin extracts: get white Peony Root and add alcoholic solution hot reflux or merceration extraction, ethanol extract is concentrated, add again ethanol put to, filter, in ethanol filtrate, add activated carbon again, stir, filter, ethanol filtrate is concentrated into not to be had till the alcohol flavor, gained said extracted thing purification on macroporous resin, wash with water earlier to Mollious reaction and be negative, the reuse ethanol elution, Fractional Collections ethanol elution, concentrating under reduced pressure, dry light yellow peoniflorin.
3, formulation preparation:
Enoxolone and peoniflorin were mixed by weight in 1: 1 to 1: 2, add pharmaceutical carrier and/or excipient again and make sheet, capsule or injection.
It at first is to obtain little, the good effect of a kind of volume that good effect of the present invention is embodied in, have no side effect, and taking convenience, the smooth muscle spasmolysis analgesic, next has finished a kind of treatment abdominal part smooth muscle spasmolysis analgesic active substance that extracts from the Radix Glycyrrhizae Radix Paeoniae.The experimentation and the result of curative effect of the present invention are as follows:
1. to the influence of spontaneous activity in mice: divide 9 groups with 90 mices are even, every group of male and female half and half press dosage shown in the table 1 and route of administration administration 1 time, and first group be a jar stomach matched group, jar stomach 0.2%CMC aqueous suspension 10ml/kg.The 6th group is the drug administration by injection matched group, subcutaneous injection normal saline 10ml/kg.1-5 group mice after administration 1 hour, 6-9 organizes after administration 30 minutes, and mice is placed in the spontaneous activity scope, writes down the spontaneous activity number of times of every mice in 5 minutes.The result is as shown in table 1, and by table 1 as seen, sweet Chinese herbaceous peony capsule and sweet Chinese herbaceous peony injection all have the effect of obvious suppression spontaneous activity in mice.(movable number of times (5min) suppression ratio of n=10 group dosage (mg/kg) mice (%) of X ± S) 1. contrast 0.2%CMC po 144.8 ± 22.52. and stabilizes 5 po 56.8 ± 23.1 to the influence of spontaneous activity in mice for sweet Chinese herbaceous peony capsule of table 1. and sweet Chinese herbaceous peony injection
* *60.73. sweet Chinese herbaceous peony capsule 300 po 45.2 ± 9.9
* *68.84. 150 po 53.5 ± 20.8
*63.15. 75 po 73.5 ± 22.5
*49.26. normal saline 10ml/kg im 132.7 ± 36.77 sweet Chinese herbaceous peony injection 60 sc 50.4 ± 12.9
* *62.08. 30 sc 64.3 ± 16.5
*51.59. 15 sc 71.4 ± 13.6
*Annotate: compare * P＜0.05, * * P＜0.01, * * * p＜0.001 with negative control group
2. to the influence of lumbar injection acetic acid induced mice writhing response and abdominal cavity exudative inflammation reaction:
Grouping of this experiment mice and administration are same as experiment 1.1-5 group mice after administration 1 hour, 6-9 organizes in administration 30 minutes, give the mouse tail vein injection AZO-blue (2%, 5ml/kg), after 2 minutes, inject 1% acetic acid 10ml/kg to mouse peritoneal in the injection AZO-blue.Write down every mice and behind injection acetic acid, turn round the body number of times in 10 minutes, immediately mice is broken cervical vertebra then and put to death, cut open the belly and ooze out dyestuff with normal saline 4ml/ Mus flushing abdominal cavity.Measure the dyestuff seepage discharge with electrophotometer (620nm).The results are shown in Table 2.The influence of table 2. glycosides Chinese herbaceous peony capsule and sweet Chinese herbaceous peony injection Dichlorodiphenyl Acetate induced mice writhing response and abdominal cavity exudative inflammation.( X±S)，n＝10。Body number of times suppression ratio is turned round in dying that group dosage intraperitoneal penetrates
(mg/kg) material amount μ g/ml 10min %1. contrast 0.2%CMC po 56 ± 8 15.6 ± 2.92. aspirin 400 po 33 ± 11
*4.7 ± 2.2
* *69.93. sweet Chinese herbaceous peony capsule 300 po 26 ± 8
* *3.1 ± 0.9
*80.14. 150 po 28 ± 8
* *5.3 ± 1.9
*66.05. 75 po 33 ± 3
*6.1 ± 1.6
*60.96. contrast normal saline 10 (ml, kg) sweet Chinese herbaceous peony injection 60 im 27 ± 5 of im 57 ± 11 14.1 ± 2.47.
* *3.7 ± 1.6
* *70.88 30 im 32 ± 3
*5.0 ± 1.2
*64.59 15 im 35 ± 4
*6.0 ± 1.5
*57.5 annotate: with matched group comparison separately, * p＜0.05, * * p＜0.01, * * * p＜0.001.
3. sweet Chinese herbaceous peony capsule spasmolytic test-to the active influence of isolated rat intestinal smooth muscle
Materials and methods:
Animal Wistar rat, body weight 250 ± 20g, female, male dual-purpose.
The paeoniflorin of medicine variable concentrations, enoxolone, sweet Chinese herbaceous peony injection is carried by natural drug institute plant chamber, Jilin; Acecoline (1g/ props up, east, Beijing ring amalgamation factory); Atropine sulfate injection (specification: 0.5mg/mL, Kaifeng, Henan Province pharmaceutical factory).
Instrument Powerlab/8s data record analyser and related accessories (Australian Ai De company product); YSD-4G type pharmacology Physiological Experiment is used instrument and constant temperature water bath apparatus (Bengbu radio two factory's products) thereof more.
The fasting of method rat was put to death after 48 hours, open the abdominal cavity, place the culture dish that fills tyrode's solution, separate mesentery gently along intestinal wall at one section intestinal tube of upper part of small intestine clip, with after rinsing well in the intestinal tube, the segment that is cut into about several 2cm is standby with tyrode's solution.By reconcile, control the temperature of constant temperature water bath with the mercury contact thermometers that link to each other with instrument more than the YSD-4G type pharmacology Physiological Experiment, make it constant at 37 ± 0.5 ℃, the tyrode's solution volume is about 50mL in the maxwell bath pipe, the liquid level of tyrode's solution liquid level and water bath is basic identical, air feeding amount is controlled at about 50 bubbles/minute, choose one section small intestinal, an end is tightened with line on the crotch that is fixed on breather, and the other end is connected with the glass capillary of filling water.When intestine in vitro was shunk, water column rose in the glass capillary. and the amplitude that liquid level rises is relevant with the intestine in vitro contraction intensity.Stablized 20 minutes, liquid level in the capillary tube is transferred to " 0 " position, in the maxwell bath pipe, add 0.001% acecoline 0.1ml subsequently, make intestinal tube generation spasm and be in nervous contraction state, shrink the most obvious place at intestinal tube, divide three kinds of method administrations: 1. add tyrode's solution 1mL; 2. add Ah bundle's product 1mL; 3. the enoxolone that adds variable concentrations subsequently, paeoniflorin, sweet Chinese herbaceous peony injection. observe the spasmolysis of medicine.Whenever finish a step, intestinal tube that more renews and nutritional solution are stablized and are carried out next step after 20 minutes again.
Experimental result
Enoxolone and sweet Chinese herbaceous peony injection all have in various degree inhibitory action to the spastic activity of rat intestinal tube due to the acecoline, and the spasmolysis of sweet Chinese herbaceous peony injection is more obvious.But peoniflorin spasmolysis not obvious (table 3).
Table 3. enoxolone, peoniflorin and sweet Chinese herbaceous peony injection are to the influence of isolated rat intestinal tube contractile motion.(X±S)，n＝3。Drug level (g/ml) mm % acecoline 4 25 ± 3.0 atropine 10 6 in the group intestinal tube shrinkage amplitude suppression ratio bath ± 1.0 76 enoxolone 40 8 ± 2.0 68
20 12±2.0 52
10 16±1.7 36
5 24±2.0 4
Acecoline 4 20 ± 1.0
Atropine 10 7 ± 1.0 65
Peoniflorin 40 19 ± 3.0 5
20 20±2.0 0
10 20±2.0 0
Acecoline 4 24 ± 2
Atropine 10 6 ± 2 75
Sweet Chinese herbaceous peony injection agent 40 6 ± 2 75
20 8±2 67
10 12±2 58
5 20±1 17
2.5 23±1 4
Embodiment:
1, enoxolone preparation: the Radix Glycyrrhizae coarse powder adds water boil 3 times, and the leaching medicinal liquid adds concentrated sulphuric acid to no longer separating out precipitation, place, and leaching, brown precipitate, washing and drying gets glycyrrhizic acid inclusion compound.With acetone reflux, extract, 3 times, acetone extract, put coldly, stir and to add 20% KOH ethanol liquid down to alkalescence, place, separate out crystallization, filtering crystallization (GLYCYRRHIZIC ACID POTASSIUM), drying adds the glacial acetic acid thermosol, puts cold, separate out crystallization, filter, get monopotassium glycyrrhizunate, add 5% sulphuric acid, heated sucking filtration 10 hours, be washed to neutrality, drying gets white enoxolone crude product, it is dissolved in the hot chloroform, filtered while hot is put chloroformic solution cold again, peroxidating aluminum chromatographic column is used the chloroform eluting, gets enoxolone, the ethanol thermosol is poured in the 1/2 volume boiling water while hot, places, get crystallization, filter, promptly get medicinal enoxolone crystallization.
2, peoniflorin extracts: get that white Peony Root is doubly measured the 30%-60% alcohol heat reflux with 3-8 or merceration extracts 2 times, ethanol extract is concentrated into relative density 1.1 (50 ℃), it is 70%-90% that reuse 95% ethanol adds to determining alcohol, placement is spent the night, filter, (M/V) activated carbon that adds 1%-2% again in the ethanol filtrate, stir, filter, ethanol filtrate is concentrated into not to be had till the alcohol flavor, and gained said extracted thing is at D101, purification on two kinds of macroporous resins of D201, wash with water earlier to Mollious reaction and be negative, reuse 10%-30% ethanol elution is collected the 10%-30% ethanol elution, concentrating under reduced pressure, dry light yellow peoniflorin.3, the sweet Chinese herbaceous peony capsule of preparation and preparation thereof (1) (tablet) prescription:
Peoniflorin (purity 90%) 153g
Enoxolone (purity 95%) 97g
Starch is an amount of
Make 1000 (sheets)
Method for making:, incapsulate or make with peoniflorin and enoxolone and the abundant mixing of appropriate amount of starch
The grain tabletting.Pastille 0.25g in per 1 capsules or per 1 tablet.
Indication: abdominal part smooth muscle Crampy Pain (menstrual pain, hysterospasm pain, stomach due to the gastric ulcer
Enterospasm is bitterly) and headache.
Usage and consumption: 1 oral 1-2 grain (sheet) during pain.(2.) sweet Chinese herbaceous peony injection
Peoniflorin (purity 90%) 30g
Enoxolone (purity 95%) 20g
1, the 2-propylene glycol is an amount of
Make 1000 of 2ml peace bottle injections
Method for making: peoniflorin and enoxolone dissolved in be dissolved in an amount of propylene glycol, filter, divide
Dress, sterilization is promptly. and per 1 contains medicine 50mg.
Indication: abdominal part smooth muscle Crampy Pain (menstrual pain, hysterospasm pain, stomach due to the gastric ulcer
Enterospasm pain and headache.
Usage and consumption: the time spent is diluted in the 500ml normal saline with 1 sweet Chinese herbaceous peony injection liquid
In, intravenous drip.Each 1-2 props up.
Claims (3)
1, a kind of spasmolytic, analgesic medicine is characterized in that: by the enoxolone that contains abdominal part smooth muscle spasmolysis effective dose and the analgesia peoniflorin of effective dose and pharmaceutically useful carrier/or excipient form.
2, according to a kind of spasmolytic, the analgesic medicine of claim 1, it is characterized in that: use enoxolone that from liquorice root, proposes and the peoniflorin that from Radix Paeoniae, extracts to add sheet, capsule or injection that carrier and/or excipient are made.
3, the preparation method of a kind of spasmolytic, analgesic is characterized in that:
(1), the preparation of enoxolone: the Radix Glycyrrhizae coarse powder adds water boil, and the leaching medicinal liquid adds concentrated sulphuric acid to no longer separating out precipitation, place, leaching, brown precipitate, washing and drying, glycyrrhizic acid inclusion compound.Use the acetone reflux, extract,, get acetone extract, put coldly, stir and to add KOH ethanol liquid down to alkalescence, place, separate out crystallization, filtering crystallization (GLYCYRRHIZIC ACID POTASSIUM), drying adds the glacial acetic acid thermosol, puts cold, separate out crystallization, filter, get monopotassium glycyrrhizunate, add dilute sulfuric acid, heating, sucking filtration, be washed to neutrality, drying gets white enoxolone crude product, it is dissolved in the hot chloroform, filtered while hot is put chloroformic solution cold again, peroxidating aluminum chromatographic column is used the chloroform eluting, gets enoxolone, the ethanol thermosol is poured in the boiling water while hot, places, get crystallization, filter, promptly get medicinal enoxolone crystallization.
(2), peoniflorin extracts: get white Peony Root and add alcoholic solution hot reflux or merceration extraction, ethanol extract is concentrated, add again ethanol put to, filter, in ethanol filtrate, add activated carbon again, stir, filter, ethanol filtrate is concentrated into not to be had till the alcohol flavor, gained said extracted thing purification on macroporous resin, wash with water earlier to Mollious reaction and be negative, the reuse ethanol elution, Fractional Collections ethanol elution, concentrating under reduced pressure, dry light yellow peoniflorin.
(3), formulation preparation:
Enoxolone and peoniflorin were mixed by weight in 1: 1 to 1: 2, add pharmaceutical carrier and/or excipient again, make sheet, capsule or injection.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021094667A CN1241574C (en) | 2002-04-10 | 2002-04-10 | Medicine for relieving spasm and pain and preparation process thereof |
| 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 |
| PCT/CN2003/000255 WO2003084945A1 (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 (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021094667A CN1241574C (en) | 2002-04-10 | 2002-04-10 | Medicine for relieving spasm and pain and preparation process thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1449761A true CN1449761A (en) | 2003-10-22 |
| CN1241574C CN1241574C (en) | 2006-02-15 |
Family
ID=28680443
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB021094667A Expired - Lifetime CN1241574C (en) | 2002-04-10 | 2002-04-10 | Medicine for relieving spasm and pain and preparation process thereof |
Country Status (3)
| Country | Link |
|---|---|
| CN (1) | CN1241574C (en) |
| AU (1) | AU2003236118A1 (en) |
| WO (1) | WO2003084945A1 (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009070917A1 (en) * | 2007-11-30 | 2009-06-11 | Chi, Yu-Fen | An oral pharmaceutical composition for treating barythymia |
| CN106543261A (en) * | 2016-10-27 | 2017-03-29 | 深圳市新阳唯康科技有限公司 | A kind of enoxolone crystal-form substances and preparation method thereof |
| CN106565817A (en) * | 2016-11-09 | 2017-04-19 | 深圳市新阳唯康科技有限公司 | Amorphous glycyrrhetinic acid and preparation method thereof |
| CN106632575A (en) * | 2016-12-20 | 2017-05-10 | 深圳市新阳唯康科技有限公司 | Novel glycyrrhetinic acid crystal form and preparation method thereof |
| CN106749485A (en) * | 2016-11-25 | 2017-05-31 | 深圳市新阳唯康科技有限公司 | A kind of enoxolone novel crystal forms and preparation method thereof |
| CN114306211A (en) * | 2021-12-29 | 2022-04-12 | 中国药科大学 | Glycyrrhizic acid supermolecule self-assembly temperature-sensitive interpenetrating network gel and preparation method and application thereof |
| CN115040633A (en) * | 2022-07-25 | 2022-09-13 | 中国中医科学院中医基础理论研究所 | New use of protein extract of peony and licorice decoction |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2000272667A1 (en) | 2000-09-13 | 2002-04-29 | Jiangsu Kanion Pharmaceutical Co. | Pharmaceutical composition treating gynecological blood stasis diseases, cardio and cerebral vascular diseases, respiratory diseases and the like |
| CN1327217C (en) * | 2004-05-26 | 2007-07-18 | 江西江中药业股份有限公司 | Quality control of Jianweixiaoshi tablets for promotnig digest |
| CN1295503C (en) * | 2004-08-27 | 2007-01-17 | 广州中一药业有限公司 | Quality control method for Ruhesanjie table |
| CN100370251C (en) * | 2004-09-23 | 2008-02-20 | 江西江中药业股份有限公司 | Quality control method for liuwei Dihuang soft extract |
| CN100334446C (en) * | 2005-11-09 | 2007-08-29 | 中国科学院长春应用化学研究所 | Method for detecting constituents of liquorice-ginseng capsule |
| WO2008090410A2 (en) | 2006-10-18 | 2008-07-31 | Jiangsu Kanion Pharmaceuticals Co. Ltd. | Cinnamomi and poria composition and uses thereof |
| CN103520298B (en) * | 2013-10-10 | 2014-08-06 | 北京康远制药有限公司 | Traditional Chinese medicine granules having effects of harmonizing liver and spleen, resisting inflammation and alleviating pains and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4759776B2 (en) * | 1999-04-01 | 2011-08-31 | 大正製薬株式会社 | Liquid composition |
-
2002
- 2002-04-10 CN CNB021094667A patent/CN1241574C/en not_active Expired - Lifetime
-
2003
- 2003-04-10 AU AU2003236118A patent/AU2003236118A1/en not_active Abandoned
- 2003-04-10 WO PCT/CN2003/000255 patent/WO2003084945A1/en not_active Application Discontinuation
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009070917A1 (en) * | 2007-11-30 | 2009-06-11 | Chi, Yu-Fen | An oral pharmaceutical composition for treating barythymia |
| CN106543261A (en) * | 2016-10-27 | 2017-03-29 | 深圳市新阳唯康科技有限公司 | A kind of enoxolone crystal-form substances and preparation method thereof |
| CN106565817A (en) * | 2016-11-09 | 2017-04-19 | 深圳市新阳唯康科技有限公司 | Amorphous glycyrrhetinic acid and preparation method thereof |
| CN106749485A (en) * | 2016-11-25 | 2017-05-31 | 深圳市新阳唯康科技有限公司 | A kind of enoxolone novel crystal forms and preparation method thereof |
| CN106632575A (en) * | 2016-12-20 | 2017-05-10 | 深圳市新阳唯康科技有限公司 | Novel glycyrrhetinic acid crystal form and preparation method thereof |
| CN114306211A (en) * | 2021-12-29 | 2022-04-12 | 中国药科大学 | Glycyrrhizic acid supermolecule self-assembly temperature-sensitive interpenetrating network gel and preparation method and application thereof |
| CN114306211B (en) * | 2021-12-29 | 2023-12-22 | 中国药科大学 | Glycyrrhizic acid supermolecule self-assembled temperature-sensitive interpenetrating network gel and preparation method and application thereof |
| CN115040633A (en) * | 2022-07-25 | 2022-09-13 | 中国中医科学院中医基础理论研究所 | New use of protein extract of peony and licorice decoction |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003084945A1 (en) | 2003-10-16 |
| CN1241574C (en) | 2006-02-15 |
| AU2003236118A1 (en) | 2003-10-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1241574C (en) | Medicine for relieving spasm and pain and preparation process thereof | |
| CN1684699A (en) | Extraction and purification method of active constituents from stem of lonicera japonica thunb., its usage for anti-inflammatory and analgesic drug | |
| CN102342945A (en) | Application of Cortex Ilicis Rotundae saponin compound in preparing anti-inflammatory and analgetic medicament | |
| CN101549010B (en) | A preparing method and application of malaytea scurfpea fruit total glycosides extract | |
| CN1748748A (en) | Little leaf deervetch herb preparation for pregnant woman and new preparing method | |
| CN1319538C (en) | Preparation method of Astragaloside material medicine, the material medicine and preparation | |
| CN1579408A (en) | Medicine for spasmolysis and relieving pain and preparation method | |
| CN101822705A (en) | Total platycodin and application of monomer platycodin D in antialcoholic drugs | |
| CN101040891A (en) | Method of preparing tripterygium hypoglaucum (Levl) hutch alkaloids | |
| CN101040896A (en) | Flavone of astragalus extract, the medicine use and the compound thereof | |
| CN1590383A (en) | Rod sage root extract and making method of its preparation | |
| CN101199572B (en) | Medicament of expectorant anti-asthma, preparing method and function thereof | |
| CN101167798B (en) | Method for preparing active parts in scutellaria decoction for treating ulcer colonitis and uses | |
| CN1150918C (en) | Medicine containing active components of Panax japonicum root and preparing process thereof | |
| CN108864128A (en) | Four kinds of guassin industrial production process and its prepare drug, health food new application | |
| CN1475222A (en) | Vine leaf extract and its preparation process | |
| CN102070700A (en) | Marsdenia tenacissima saponins H and preparation method and application thereof | |
| CN100421685C (en) | Chinese material medica preparation in use for treating infection of influenza virus, and preparation method | |
| CN101181336A (en) | Method for refining valid target of bitter gourd for dropping blood sugar | |
| CN106377651A (en) | Preparation method for extracting pharmaceutical monomer for preventing and treating hyperuricemia and gout from rhizoma smilacis glabrae | |
| CN1207009C (en) | Antirheumatic medicine and its preparing method | |
| CN1316992C (en) | Medicine for treating heart brain embulus disease and its preparation method | |
| CN1846763A (en) | Medicine composition for treating coronary heart disease and its prepn process | |
| CN1795901A (en) | Medication for removing toxic heat, eliminating wetness and treating jaundice | |
| CN1391928A (en) | Medicine Qingyedan for curing hepatitis and its preparing method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: TONGHUA WANTONG PHARMACY CO., LTD. Free format text: FORMER OWNER: TIANYAO SCIENCE AND TECHNOLOGY CO LTD, JILIN Effective date: 20080328 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20080328 Address after: No. 66, Wan Tong Road, Jilin, Tonghua Patentee after: Tonghua Wantong Pharmaceutical Co., Ltd. Address before: No. 509 Mao Xiang street, hi tech Development Zone, Jilin, Changchun Patentee before: Tianyao Science and Technology Co., Ltd., Jilin |
|
| CX01 | Expiry of patent term |
Granted publication date: 20060215 |
|
| CX01 | Expiry of patent term |