US2009123559A1PendingUtilityA1
Medicine to Treat Drug Addiction and Preparation Method Thereof
Assignee: SHANXI YABAO PHARMACEUTICAL GRPriority: Jul 26, 2005Filed: Jul 26, 2006Published: May 14, 2009
Est. expiryJul 26, 2025(expired)· nominal 20-yr term from priority
A61P 43/00A61P 25/30A61K 36/8968A61K 36/258A61K 36/232A61K 36/59A61P 25/36A61K 36/481
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Claims
Abstract
The present invention declares a pharmaceutical extract, composition that has effect to treat drug addiction, and its preparation method and quality control method. This extract is extracted from Radix Stephaniae Epigaeae. Starting medicine material of said composition is Radix Ginseng, Radix Astragali, Rhizoma Corydalis, Radix Angelicae Sinensis and Radix Ophiopogonis; and said composition also can prepared by ethanol extract of Radix Ginseng, ethanol extract of Radix Angelicae Sinensis, total alkaloids of Radix Stephaniae Epigaeae, water extract of Radix Astragali and water extract of Radix Ophiopogonis. Quality control method of said pharmaceutical composition includes one of or several of identifications and content determinations. The present invention also declares the use of said pharmaceutical extract, composition in the preparation of a medicine to treat drug addiction.
Claims
exact text as granted — not AI-modified1 . A total alkaloid of Radix Stephaniae Epigaeae to treat drug addiction, wherein said total alkaloid produced through following method:
Pulverize Radix Stephaniae Epigaeae to coarse power, add 35-100% ethanol at 4-10 times amount of stating material's, extract by reflux extraction from one to four times, 1-3 hours each time, filter, combine the filtrates of ethanol extract, recover ethanol, then concentrate to obtain the thick extract with relative density of 1.18-1.30 at 80° C.; acidify this thick extract until the pH value up to 1-4 by 3-18% HCl solution, filter, basify the filtrate until the pH value up to 8-11 by 8-20% NaOH solution, stand, collect the precipitate, wash the precipitate with water by filter, take the precipitate, dry it, then obtain total alkaloid of Radix Stephaniae Epigaeae.
2 . The said total alkaloid of Radix Stephaniae Epigaeae of claim 1 , wherein said total alkaloid produced through following method:
Pulverize Radix Stephaniae Epigaeae to coarse power, add ethanol at 5 times amount of stating material's, extract by reflux extraction twice, 2 hours each time, filter, combine the filtrates of ethanol extract, recover ethanol, then concentrate to obtain the thick extract with relative density of 1.18-1.30 at 80° C.; acidify this thick extract until the pH value up to 2-3 by 5% HCl solution, filter, basify the filtrate until the pH value up to 9-10 by 10% NaOH solution, stand, collect the precipitate, wash the precipitate with water by filter, take the precipitate, dry it, then obtain total alkaloid of Radix Stephaniae Epigaeae.
3 . The said total alkaloid of Radix Stephaniae Epigaeae of claim 1 , adding general adjuvant, is prepared to capsule, pill, tablet, granule, honey refined extract, sustained-release preparation, rapid-release preparation, controlled-release preparation, oral liquid or injection.
4 . The use of said total alkaloid of Radix Stephaniae Epigaeae of claim 1 in the preparation of a medicine to treat drug addiction.
5 . The use of claim 4 , wherein the medicine to treat drug addiction can raise expression of Penk mRNA or expression of POMC mRNA in arcuate nucleus.
6 . A pharmaceutical composition to treat drug addiction, wherein starting medicine material of said pharmaceutical composition is composed of:
Radix Ginseng
1-10 parts by weight
Radix Stephaniae Epigaeae
5-60 parts by weight
Radix Astragali
3-40 parts by weight
Radix Angelicae Sinensis
2-25 parts by weight
Radix Ophiopogonis
1-10 parts by weight.
7 . A pharmaceutical composition of claim 6 , wherein starting medicine material of said pharmaceutical composition is composed of:
Radix Ginseng
1 part by weight
Radix Stephaniae Epigaeae
35 parts by weight
Radix Astragali
7 parts by weight
Radix Angelicae Sinensis
8 parts by weight
Radix Ophiopogonis
2 parts by weight.
8 . A pharmaceutical composition of claim 6 , wherein starting medicine material of said pharmaceutical composition is composed of:
Radix Ginseng
8 parts by weight
Radix Stephaniae Epigaeae
12 parts by weight
Radix Astragali
13 parts by weight
Radix Angelicae Sinensis
5 parts by weight
Radix Ophiopogonis
8 parts by weight.
9 . A pharmaceutical composition of claim 6 , wherein starting medicine material of said pharmaceutical composition is composed of:
Radix Ginseng
5 parts by weight
Radix Stephaniae Epigaeae
26 parts by weight
Radix Astragali
20 parts by weight
Radix Angelicae Sinensis
5 parts by weight
Radix Ophiopogonis
5 parts by weight.
10 . A pharmaceutical composition of claim 6 , wherein starting medicine material of said pharmaceutical composition is composed of:
Radix Ginseng
3 parts by weight
Radix Stephaniae Epigaeae
16 parts by weight
Radix Astragali
10 parts by weight
Radix Angelicae Sinensis
5 parts by weight
Radix Ophiopogonis
3 parts by weight.
11 . A pharmaceutical composition of claim 6 , wherein starting medicine material of said pharmaceutical composition is composed of:
Radix Ginseng
8 parts by weight
Radix Stephaniae Epigaeae
40 parts by weight
Radix Astragali
25 parts by weight
Radix Angelicae Sinensis
10 parts by weight
Radix Ophiopogonis
8 parts by weight.
12 . The said pharmaceutical composition of claim 6 , wherein Radix Ginseng in starting material of said pharmaceutical composition can replace with equal weight parts Radix-Panacis Quinquefolii.
13 . A preparation method of said pharmaceutical composition preparation of claim 6 , wherein said method is:
A. Pulverize Radix Stephaniae Epigaeae to coarse power, add 35-100% ethanol at 4-10 times amount of stating material's, extract by reflux extraction form one to four times, 1-3 hours each time, filter, combine the filtrates of ethanol extract, recover ethanol, then concentrate to obtain the thick extract with relative density of 1.18-1.30 at 80° C.; acidify this thick extract until the pH value up to 1-4 by 3-18% HCl solution, filter, basify the filtrate until the pH value up to 8-11 by 8-20% NaOH solution, stand, collect the precipitate, wash the precipitate with water by filter, take the precipitate, dry it, then obtain total alkaloids of Radix Stephaniae Epigaeae, stand it by service; B. Add 35-95% ethanol at 4-10 times amount to Radix Ginseng, Radix Angelicae Sinensis, then extract by reflux extraction from one to three times, 1-4 hours each time, combine the filtrates of ethanol extract, recover ethanol, then concentrate to obtain the thick extract I with relative density of 1.18-1.30 at 80° C., stand it by service; decoct Radix Astragali and Radix Ophiopogonis with water at 5-10 times amount from one to four times, 1-3 hours each time, combine all the decoction, filter, concentrate the filtrate to obtain the thick extract with relative density of 1.18-1.30 at 80° C., add ethanol until ethanol concentration up to 50-90%, stand, filter, take the filtrates, recover ethanol, then concentrate to obtain the thick extract II with relative density of 1.18-1.30 at 80° C., stand it by service; C. Take said total alkaloids of Radix Stephaniae Epigaeae, the thick extract I, the thick extract II, combine them, add general adjuvant, mix uniformly, according to usual process, produce to tablet, capsule, soft capsule, drop pill, pill, granule, honey refined extract, sustained-release preparation, rapid-release preparation, controlled-release preparation, oral liquid or injection.
14 . A preparation method of said pharmaceutical composition preparation of claim 13 , wherein said method is:
A. Add 5 times amount ethanol to Radix Stephaniae Epigaeae, then extract by reflux extraction for three times, 1 hour each time, filter, combine the filtrates of ethanol extract, recover ethanol, then concentrate to obtain the thick extract with relative density of 1.22 at 80° C.; acidify this thick extract until the pH value up to 2-3 by 5% HCl solution, filter, basify the filtrate until the pH value up to 9-10 by 10% NaOH solution, stand, collect the precipitate, wash the precipitate with water by filter, take the precipitate, dry it, then obtain total alkaloids from Radix Stephaniae Epigaeae, stand it by service; B. Add 60% ethanol at 5 times amount to Radix Ginseng, Radix Angelicae Sinensis, then extract by reflux extraction for three times, 2 hours each time, combine the filtrates of ethanol extract, recover ethanol, then concentrate to obtain the thick extract I with relative density of 1.18-1.22 at 80° C., stand it by service; decoct Radix Astragali and Radix-Ophiopogonis with water at 6 times amount for three times, 2 hours each time, combine all the decoctions, filter, concentrate the filtrate to obtain the thick extract with relative density of 1.22 at 80° C., add ethanol until ethanol concentration up to 80%, stand, filter, take the filtrates, recover ethanol, then concentrate to obtain the thick extract II with relative density of 1.22 at 80° C., stand it by service; C. Take the said total alkaloids of Radix Stephaniae Epigaeae, the thick extract I, the thick extract II, combine them, add 1-10% sodium carboxymethyl starch, mix uniformly, recover solvent until dry, dry at 80° C. or dry by vacuum, crush and sieve, make granules, press tablet, coating.
15 . A pharmaceutical composition to treat drug addiction, wherein starting medicine material of said pharmaceutical composition is composed of:
ethanol extract of Radix Ginseng
5-15 parts by weight
ethanol extract of Radix Angelicae Sinensis
20-40 parts by weight
total alkaloids of Radix Stephaniae Epigaeae
5-15 parts by weight
water extract of Radix Astragali
20-60 parts by weight
water extract of Radix Ophiopogonis
5-15 parts by weight;
said ginsenoside content in the said ethanol extract of Radix Ginseng is not less than 50 g/Kg; angelica lactone content in the ethanol extract of Radix Angelicae Sinensis is not less than 2 g/Kg; (−) tetrahydropalmatine content in the total alkaloids of Radix Stephaniae Epigaeae is not less: than 20%; astragaloside content in the water extract of Radix Astragali is not less than 0.2 g/Kg; ophiopogonin content in the water extract of Radix Ophiopogonis is not less than 0.9 g/Kg.
16 . A pharmaceutical composition of claim 15 , wherein starting medicine material of said pharmaceutical composition is composed of:
ethanol extract of Radix Ginseng
11 parts by weight
ethanol extract of Radix Angelicae Sinensis
31 parts by weight
total alkaloids of Radix Stephaniae Epigaeae
10 parts by weight
water extract of Radix Astragali
36.5 parts by weight
water extract of Radix Ophiopogonis
11 parts by weight.
17 . A pharmaceutical composition of claim 15 , wherein starting medicine material of said pharmaceutical composition is composed of:
ethanol extract of Radix Ginseng
5 parts by weight
ethanol extract of Radix Angelicae Sinensis
16 parts by weight
total alkaloids of Radix Stephaniae Epigaeae
20 parts by weight
water extract of Radix Astragali
40 parts by weight
water extract of Radix Ophiopogonis
19 parts by weight.
18 . A pharmaceutical composition of claim 15 , wherein starting medicine material of said pharmaceutical composition is composed of:
ethanol extract of Radix Ginseng
15 parts by weight
ethanol extract of Radix Angelicae Sinensis
30 parts by weight
total alkaloids of Radix Stephaniae Epigaeae
15 parts by weight
water extract of Radix Astragali
30 parts by weight
water extract of Radix Ophiopogonis
10 parts by weight.
19 . The said pharmaceutical composition of claim 6 , wherein said pharmaceutical composition is prepared to capsule, pill, tablet, granule, honey refined extract, sustained-release preparation, rapid-release preparation, controlled-release preparation, oral liquid or injection.
20 . Quality control method of said pharmaceutical composition preparation of claim 6 , wherein said identification in this method includes one of or several following methods:
A. Take 3.5 g-6 g capsule, pill, tablet, granule, honey refined extract, sustained-release preparation or rapid-release preparation of the pharmaceutical composition, grind fine, add methanol 50 ml, heat and reflux for 30 minutes, take it out, stand it cold, filter, evaporate filtrate 20 ml until dry, add 10 ml water and 5 drops hydrochloric acid into residue, shake up, extract twice by adding ethyl ether, 15 ml each time, combine ether extract, stand it by service; add ammonia to water layer until pH≈10, shake up, extract twice by adding chloroform, 20 ml each time, remove chloroform extract, extract for three times by adding n-butyl alcohol saturated with water to water layer, 20 ml each time, combine n-butyl alcohol extract, wash for three times by adding ammonia reagent, 10 ml dosage each time, take n-butyl alcohol extract, evaporate until dry, dissolve residue by add 1 ml methanol into it, as test sample solution; take Ginsenoside Rb1 and Ginsenoside Rg1 respectively as reference substance, add methanol to produce mix solution containing 1 mg reference substance per 1 ml respectively, as reference substance solution; According to the thin layer Chromatography test, 5˜10 μl each of the said two solutions were loaded onto the same TLC plate of silica gel G respectively, the upper layer solution is a mixture of n-butyl alcohol, ethyl acetate and water (4:1:5), according to ratio 10:1, a mix solution of this upper layer solution and methanol is used as developer, in developing, the development chamber is saturated by ammonia for 30 minutes, and developed distance is more than 15 cm, the plate was removed and air dried, and sprayed with ethanol solution of 10% sulfuric acid, then heated in 105° C. until visualize the chromatogram, the chromatogram produced by the test sample solution showed the same color spots as that displayed by the two reference substance solutions in their respectively corresponding areas; B. Take astragaloside reference substance, add methanol to produce mix solution containing 1 mg reference substance per 1 ml, as reference substance solution, according to the thin layer Chromatography test, 5˜10 μl each of reference substance solutions and test sample solutions- produced by the identification method A are respectively loaded onto the same TLC plate of silica gel G. The upper layer solution is a mixture of n-butyl alcohol, ethyl acetate and water (4:1:5), according to ratio 10:1, a mix solution of this upper layer solution and methanol is used as developer, in developing, the development chamber is saturated by ammonia for 30 minutes, and developed distance is more than 15 cm, the plate was removed and air dried, and sprayed with ethanol solution of 10% sulfuric acid, then heated in 105° C. until visualize the chromatogram, the chromatogram produced by the test sample solution showed the same color spots as that displayed by the reference substance solution in its respectively corresponding-area; C. Produce ethyl ether extract according to the identification A method, evaporate solvent to dry, dissolve residue by adding 1 ml ethyl acetate, as test sample solution; take another 0.5 g reference starting material of Radix Angelicae Sinensis, add ethyl ether 20 ml, heat and reflux for 1 hour, filter, evaporate ethyl ether in filtrate to dry, produce reference starting material solution by same method; according to the thin layer Chromatography test, 5˜10 μl each of the said two solutions is loaded onto the same TLC plate of silica gel G respectively, a mixture of hexane and ethyl acetate (9:1) is used as developer. After development, the plate was removed and dried in air, and it was exam under 365 nm ultraviolet lamp, the chromatogram produced by the sample solution showed the same color spots as that displayed by the reference substance solution in its respectively corresponding areas; D. Take 1.75-3.5 g capsule, pill, tablet, granule, honey refined extract, sustained-release preparation or rapid-release preparation of a pharmaceutical composition, grind fine, decoct by adding water 100 ml for 30 minutes-until rest volume up to 20 ml, stand it cold, add methanol until methanol content up to 50%, shake up, stay for 1 hour at lower than 10° C., filter, pressure reduction concentrate the filtrate to dry, dissolve the residue by adding 10 ml water, add 2 ml hydrochloric acid, shake up, reflux with boil water bath for 1 hour, take out and stand it cold, extract twice by ethyl ether, dosage 25 ml, combine ethyl ether extract, stand for 0.30 minutes, evaporate solvent until dry, dissolve residue by adding 1 ml methanol, shake up, as test sample solution; take another 0.5 g reference starting material of Radix Ophiopogonis, add water 20-30 ml, boil for 10 minutes, filter, produce reference starting material solution by same method; according to the thin layer Chromatography test, 2˜5 μl each of the said two solutions is loaded onto the same TLC plate of silica gel G respectively, a mixture of chloroform and acetone (4:1) is used as developer, after development, the plate was removed and air dried, and sprayed with ethanol solution of 10% sulfuric acid, then heated in 105° C. until visualize the chromatogram, the chromatogram produced by the test sample solution showed the same color spots as that displayed by the two reference substance solutions in their respectively corresponding areas.
21 . Quality control method of said pharmaceutical composition preparation of claim 6 , wherein content determination in said method is:
An applicability test of chromatogram condition and system Use octadecylsilanized silica gel as packing; add ammonia 0.025 mol/L into potassium dihydrogen phosphate and acetonitrile (1:1) solution until pH≈7 as the mobile phase; detection wavelength is 225 nm, theoretical plate number counted according to (−) tetrahydropalmatine peak is not less than 3000; Preparation of reference substance solution Pressure reduction dry 5.5 mg (−) tetrahydropalmatine reference substance at 60° C. until constant weight, weight it accurately, put it into 10 ml volumetric flask, dissolve by methanol, dilute to the volume, shake up, measure 1 ml the said solution accurately, put it into 10 ml volumetric flask, and dilute with the mobile phase to the volume, shake up, that is; Preparation of test sample solution Accurately weight 0.35-0.45 g capsule, pill, tablet, granule, honey refined. extract, sustained-release preparation or rapid-release preparation of the said pharmaceutical composition, grind fine, put it into conical flask, add 50 ml methanol accurately, shake up, weight it up, put it into ultrasonic cleaner, deal with ultrasound for 30 minutes, take it out, complement weight with methanol, shake up, filter, abandon first filtrate, measure 1 ml the following filtrate accurately and put it into 10 ml volumetric flask, dilute with the mobile phase to the volume, shake up, filter it with 0.45 μm microporous membrane filter, take the following filtrate as test sample solution; Determination method Accurately suck reference substance solution and test sample solution 10 μl respectively, inject into liquid chromatogram instrument, determine, that is;
(−) Tetrahydropalmatine regarded as Radix Stephaniae Epigaeae is not less than 20 mg in each of 0.35-0.45 g capsule, pill, tablet, granule, honey refined extract, sustained-release preparation or rapid-release preparation of the said pharmaceutical composition.
22 . The use of said pharmaceutical composition of claim 6 , in the preparation of a medicine to treat drug addiction.
23 . The use of claim 22 , wherein said medicine to treat drug addiction can alleviate drug withdrawal symptom, inhibit psychology craving or reduce relapse ration.
24 . The use of Radix Stephaniae Epigaeae in the preparation of a medicine to treat drug addiction.
25 . The use of claim 24 , wherein said medicine to treat drug addiction can raise expression of Penk mRNA or expression of POMC mRNA in arcuate nucleus.
26 . The said pharmaceutical composition preparation of claim 12 , wherein said pharmaceutical composition preparation is capsule, pill, tablet, granule, honey refined extract, sustained-release preparation, rapid-release preparation, controlled-release preparation, oral liquid or injection.Join the waitlist — get patent alerts
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