CN1742966A - Fuyanling preparation for treating gynaecologic inflammationa nd preparing method - Google Patents

Fuyanling preparation for treating gynaecologic inflammationa nd preparing method Download PDF

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Publication number
CN1742966A
CN1742966A CN 200410046735 CN200410046735A CN1742966A CN 1742966 A CN1742966 A CN 1742966A CN 200410046735 CN200410046735 CN 200410046735 CN 200410046735 A CN200410046735 A CN 200410046735A CN 1742966 A CN1742966 A CN 1742966A
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grams
fuyanling
fine powder
weight portion
weight portions
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CN 200410046735
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毛友昌
毛晓敏
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Abstract

The present invention discloses a Fuyanling preparation and its preparation process. On the basis of existent Fuyanling capsule and effervescent tablet said invention adopts the modern pharmaceutical technology to develop the invented series Fuyanling preparation products, such as guick disintegrant tablet and suppository, etc.

Description

FUYANLING preparation and preparation method thereof
Technical field
The present invention relates to a kind of Chinese medicine, specifically FUYANLING preparation and preparation method thereof.
Background technology
The FUYANLING preparation of forming by Folium Callicarpae Formosanae, Herba Agrimoniae, Fructus Cnidii, Radix Sophorae Flavescentis, the Radix Stemonae, boric acid, Alumen, Camphora, Borneolum Syntheticum, benzalkonium bromide ten flavors, function with heat clearing and damp drying, killing parasites for relieving itching, be used for pudendal pruritus that damp invasion of lower energizer causes, causalgia, leucorrhea with red and white discharge or doublely see diseases such as frequent micturition, urgent micturition, dysurea, and mycotic, infusorian property, bacterial vaginitis see that above-mentioned patient has significant curative effect.FUYANLING JIAONANG (recording for the 17 of the Sanitation Ministry medicine standard " Chinese traditional patent formulation preparation ") and FUYANLING effervescent tablet (new Chinese medicine) are arranged at present.The hard capsule softgel shell dissolves slowly; Though effervescent tablet has curative effect preferably because foamy generation can increase contacting of medicine and agents area, owing to include the soda acid effervescent, use often inflammation mucosa generation zest, influence its Clinical Application.
Summary of the invention
The objective of the invention is to provide a kind of scalable, good effect that has, the FUYANLING preparation of nonirritant, compliance advantages of higher further satisfies and ensures the medication demand of vast female patient.
Purpose of the present invention can take following method to realize:
The FUYANLING preparation is characterized in that it is that component is formed or made other various preparations except that capsule, effervescent tablet that active component and pharmaceutically acceptable additives are formed by the extract of following main materials by following main materials, as ordinary tablet, fast disintegrating tablet, dispersible tablet, common bolt, soft capsule suppository, type of effervescent suppository, gel, membrane, ointment etc.
Folium Callicarpae Formosanae 50-500 weight portion, Herba Agrimoniae 50-500 weight portion, Fructus Cnidii 50-500 weight portion, Radix Sophorae Flavescentis 50-500 weight portion, Radix Stemonae 50-500 weight portion, boric acid 30-300 weight portion, Alumen 5-50 weight portion, Camphora 5-50 weight portion, Borneolum Syntheticum 2-20 weight portion, benzalkonium bromide 3-30 weight portion.
Formula optimization is:
Folium Callicarpae Formosanae 100 weight portions, Herba Agrimoniae 100 weight portions, Fructus Cnidii 100 weight portions, Radix Sophorae Flavescentis 100 weight portions, the Radix Stemonae 100 weight portions, boric acid 60 weight portions, Alumen 10 weight portions, Camphora 10 weight portions, Borneolum Syntheticum 5 weight portions, benzalkonium bromide 6 weight portions.
Described pharmaceutically acceptable additives are following one or more:
Dextrin, starch, methylcellulose, pregelatinized Starch, sodium alginate, magnesium stearate, 30 POVIDONE K 30 BP/USP 30, microcrystalline Cellulose, carboxymethylstach sodium, micropowder silica gel, hydroxypropyl cellulose, sodium carboxymethyl cellulose, carboxymethylcellulose calcium, ethylparaben, carbomer, vaseline, liquid Paraffin, tween 80, lecithin, sodium lauryl sulphate, stearic acid, semi-synthetic fatty acid ester, glycerol, gelatin, Polyethylene Glycol, Oleum Sesami, soybean oil, Semen arachidis hypogaeae wet goods.
Described tablet can be risen other outer various suitable tablets of sheet for de-bubble, and as ordinary tablet, fast disintegrating tablet etc., available suitable coating material coating is coating not also.
Described suppository can be the suppository of ordinary suppository, capsule bolt, type of effervescent suppository or other type.
The preparation method of FUYANLING preparation is characterized in that it may further comprise the steps:
(1) in the prescription Radix Sophorae Flavescentis pulverize superfine powder is broken into that alcohol extraction is directly used or adopted to fine powder or water is carried or alcohol extraction after medicinal residues again water carry or acid extraction or other suitable method are extracted;
(2) in the prescription Fructus Cnidii pulverize superfine powder is broken into that alcohol extraction is directly used or adopted to fine powder or water is carried or alcohol extraction after the medicinal residues method that water is carried or other is suitable again extract;
(3) in the prescription Folium Callicarpae Formosanae, Herba Agrimoniae, the Radix Stemonae pulverize superfine powder is broken into that alcohol extraction is directly used or adopted to fine powder or water is carried or alcohol extraction after the medicinal residues method that water is carried or other is suitable again extract;
(4) prescription mesoboric acid, Alumen pulverizing or superfine powder are broken into fine powder or other suitable method processing;
(5) Borneolum Syntheticum, Camphora pulverize separately or superfine powder are broken into fine powder or grind altogether or add or handle with other suitable method with The suitable solvent dissolving back in the prescription;
(6) benzalkonium bromide pulverizing or superfine powder are broken into fine powder or other suitable method processing in the prescription;
(7) be ground into fine powder in the step and be ground into 100-160 purpose fine powder usually, the best is broken into 200-300 purpose fine powder for superfine powder;
(8) condition of alcohol extraction is in the step: with 50-95% ethanol is solvent, can adopt heating reflux method or percolation or other suitable method to extract;
(9) condition that water is carried in the step is: decoct with water at 90-98 ℃ and extract each 1-3 hour 2-4 time;
(10) extracting gained water extract in the step can adopt precipitate with ethanol or add the flocculating agent sedimentation or method that other is suitable is further handled;
(11) concentrate, adopt concentrating under reduced pressure or thin film concentration or vacuum film to concentrate or other proper method;
(12) drying can adopt vacuum drying or spray drying or lyophilization or other suitable method;
(13) add different additives as required, adopt suitable moulding process, be prepared from other the various preparations except that capsule, effervescent tablet, as ordinary tablet, fast disintegrating tablet, dispersible tablet, common bolt, soft capsule suppository, type of effervescent suppository, gel, membrane, ointment etc.
The specific embodiment
Embodiment 1:
Get Folium Callicarpae Formosanae 100 grams, Herba Agrimoniae 100 grams, Fructus Cnidii 100 grams, Radix Sophorae Flavescentis 100 grams, the Radix Stemonae 100 grams, boric acid 60 grams, Alumen 10 grams, Camphora 10 grams, Borneolum Syntheticum 5 grams, benzalkonium bromide 6 grams.
Ten flavor medicines are up to the standards standby respectively in will filling a prescription; Getting Fructus Cnidii, to be ground into fine powder standby; Folium Callicarpae Formosanae, Radix Sophorae Flavescentis, the Radix Stemonae, Herba Agrimoniae decoct with water secondary, are 2 hours for the first time, are 1.5 hours for the second time, and collecting decoction filters, and filtrate is concentrated into the thick paste shape, adds Fructus Cnidii fine powder and benzalkonium bromide, stirs evenly, and drying is ground into fine powder, sieves; Boric acid, Alumen are ground into fine powder, with above-mentioned powder and appropriate amount of auxiliary materials mixing, alcohol granulation, drying, camphorate, Borneolum Syntheticum fine powder mixing, and tabletting, coating, packing promptly gets the FUYANLING sheet.
Embodiment 2:
Get Folium Callicarpae Formosanae 500 grams, Herba Agrimoniae 500 grams, Fructus Cnidii 500 grams, Radix Sophorae Flavescentis 500 grams, the Radix Stemonae 500 grams, boric acid 300 grams, Alumen 50 grams, Camphora 50 grams, Borneolum Syntheticum 20 grams, benzalkonium bromide 30 grams.
Ten flavor medicines are up to the standards standby respectively in will filling a prescription; Get Radix Sophorae Flavescentis, Fructus Cnidii is ground into coarse powder, extracts secondary with 85% alcohol heat reflux, each 1 hour, merge extractive liquid, filtered, filtrate recycling ethanol is condensed into the thick paste shape, adds appropriate amount of starch and mixes 60 ℃ of dry for standby thoroughly; The medicinal residues of Folium Callicarpae Formosanae, the Radix Stemonae, Herba Agrimoniae and above-mentioned Radix Sophorae Flavescentis etc. decoct with water secondary, are 2 hours at every turn, and collecting decoction filters, and filtrate is concentrated into the thick paste shape, add appropriate amount of starch and mix 80 ℃ of dry for standby thoroughly; Boric acid, Alumen are ground into fine powder, with above-mentioned powder and appropriate amount of auxiliary materials mixing, add 6% 30 POVIDONE K 30 BP/USP 30Alcoholic solution, mixing is granulated, drying camphorates, the ethanol solution of Borneolum Syntheticum, benzalkonium bromide, mix thoroughly, airtight 24 hours, tabletting, coating, packing promptly gets the FUYANLING sheet.
Embodiment 3:
Get Folium Callicarpae Formosanae 50 grams, Herba Agrimoniae 50 grams, Fructus Cnidii 50 grams, Radix Sophorae Flavescentis 50 grams, the Radix Stemonae 50 grams, boric acid 30 grams, Alumen 5 grams, Camphora 5 grams, Borneolum Syntheticum 2 grams, benzalkonium bromide 3 grams.
Ten flavor medicines are up to the standards standby respectively in will filling a prescription; Get Radix Sophorae Flavescentis, Fructus Cnidii is ground into coarse powder, extracts secondary with 85% alcohol heat reflux, each 1 hour, merge extractive liquid, filtered, filtrate recycling ethanol is concentrated into standby in right amount; The medicinal residues of Folium Callicarpae Formosanae, the Radix Stemonae, Herba Agrimoniae and above-mentioned Radix Sophorae Flavescentis etc. decoct with water secondary, are 2 hours at every turn, and collecting decoction filters, and filtrate is concentrated in right amount, stir evenly with above-mentioned concentrated solution, and spray drying, it is standby to collect dried cream powder; Boric acid, Alumen are ground into fine powder, and with above-mentioned dried cream powder and an amount of fast disintegrating tablet auxiliary materials and mixing, dehydrated alcohol is granulated, drying, camphorate, the ethanol solution of Borneolum Syntheticum, benzalkonium bromide, mix thoroughly, airtight 24 hours, tabletting, coating, packing promptly gets FUYANLING speed disintegrating tablet.
Embodiment 4:
Get Folium Callicarpae Formosanae 275 grams, Herba Agrimoniae 275 grams, Fructus Cnidii 275 grams, Radix Sophorae Flavescentis 275 grams, the Radix Stemonae 275 grams, boric acid 165 grams, Alumen 27.5 grams, Camphora 27.5 grams, Borneolum Syntheticum 11 grams, benzalkonium bromide 16.5 grams.
Ten flavor medicines are up to the standards standby respectively in will filling a prescription; The eight flavor medicated powder of getting in the prescription except that Camphora, Borneolum Syntheticum are broken into fine powder, and with an amount of fast disintegrating tablet auxiliary materials and mixing, dehydrated alcohol is granulated, and drying camphorates, the ethanol solution of Borneolum Syntheticum, mix thoroughly, and airtight 24 hours, tabletting, coating, packing promptly get the fast disintegrating tablet of FUYANLING.
Embodiment 5:
Get Folium Callicarpae Formosanae 100 grams, Herba Agrimoniae 100 grams, Fructus Cnidii 100 grams, Radix Sophorae Flavescentis 100 grams, the Radix Stemonae 100 grams, boric acid 60 grams, Alumen 10 grams, Camphora 10 grams, Borneolum Syntheticum 5 grams, benzalkonium bromide 6 grams.
Ten flavor medicines are up to the standards standby respectively in will filling a prescription; Get Radix Sophorae Flavescentis, Fructus Cnidii is ground into coarse powder, extracts secondary with 85% alcohol heat reflux, each 1 hour, merge extractive liquid, filtered, filtrate recycling ethanol is concentrated into standby in right amount; The medicinal residues of Folium Callicarpae Formosanae, the Radix Stemonae, Herba Agrimoniae and above-mentioned Radix Sophorae Flavescentis etc. decoct with water secondary, are 2 hours at every turn, and collecting decoction filters, and filtrate is concentrated in right amount, stir evenly with above-mentioned concentrated solution, and spray drying, it is standby to collect dried cream powder; Boric acid, Alumen, Camphora, Borneolum Syntheticum, benzalkonium bromide are ground into fine powder, with above-mentioned dried cream powder mixing, add liquid Paraffin and stir evenly standby in right amount; Other gets vaseline, lecithin is an amount of, and heat fused, temperature are reduced to about 50 ℃,, add above-mentioned spares, fully stir evenly, be pressed into soft capsule, packing promptly gets the FUYANLING soft capsule suppository.
Embodiment 6:
Get Folium Callicarpae Formosanae 100 grams, Herba Agrimoniae 50 grams, Fructus Cnidii 50 grams, Radix Sophorae Flavescentis 50 grams, the Radix Stemonae 50 grams, boric acid 30 grams, Alumen 5 grams, Camphora 5 grams, Borneolum Syntheticum 2 grams, benzalkonium bromide 3 grams.
Ten flavor medicines are up to the standards standby respectively in will filling a prescription; Get Radix Sophorae Flavescentis, Fructus Cnidii is ground into coarse powder, extracts secondary with 85% alcohol heat reflux, each 1 hour, merge extractive liquid, filtered, filtrate recycling ethanol is concentrated into standby in right amount; The medicinal residues of Folium Callicarpae Formosanae, the Radix Stemonae, Herba Agrimoniae and above-mentioned Radix Sophorae Flavescentis etc. decoct with water secondary, are 2 hours at every turn, and collecting decoction filters, and filtrate is concentrated in right amount, stir evenly with above-mentioned concentrated solution, and spray drying, it is standby to collect dried cream powder; Boric acid, Alumen, Camphora, Borneolum Syntheticum, benzalkonium bromide are ground into fine powder, and be standby with above-mentioned dried cream powder mixing; It is an amount of to get polyoxyethylene stearate (40) ester, Polyethylene Glycol-1500, Polyethylene Glycol-6000, when heat fused, temperature are reduced to 70 ℃, adding above-mentioned medicated powder, citric acid and an amount of tween 80 stirs evenly, temperature is reduced to about 50 ℃, adds sodium bicarbonate again and stirs evenly, and injection molding is made the FUYANLING type of effervescent suppository.
Embodiment 7:
Get Folium Callicarpae Formosanae 500 grams, Herba Agrimoniae 100 grams, Fructus Cnidii 100 grams, Radix Sophorae Flavescentis 100 grams, the Radix Stemonae 100 grams, boric acid 60 grams, Alumen 10 grams, Camphora 10 grams, Borneolum Syntheticum 5 grams, benzalkonium bromide 6 grams.
Ten flavor medicines are up to the standards standby respectively in will filling a prescription; Get Radix Sophorae Flavescentis, Fructus Cnidii is ground into coarse powder, extracts secondary with 85% alcohol heat reflux, each 1 hour, merge extractive liquid, filtered, filtrate recycling ethanol is concentrated into standby in right amount; The medicinal residues of Folium Callicarpae Formosanae, the Radix Stemonae, Herba Agrimoniae and above-mentioned Radix Sophorae Flavescentis etc. decoct with water secondary, are 2 hours at every turn, and collecting decoction filters, and filtrate is concentrated in right amount, stir evenly with above-mentioned concentrated solution, and drying under reduced pressure is pulverized, and it is standby to collect dried cream powder; Boric acid, Alumen, Camphora, Borneolum Syntheticum, benzalkonium bromide are ground into fine powder, and be standby with above-mentioned dried cream powder mixing; With the Myrj 45 heating and melting, after the anhydrous calcium chloride dehydration, filtering calcium chloride is standby; After getting the Myrj 45 heating and melting, under agitation add above-mentioned standby medicated powder respectively, fully stir evenly, injection molding, cooling, demoulding, packing promptly gets the FUYANLING bolt.
Embodiment 8:
Get Folium Callicarpae Formosanae 100 grams, Herba Agrimoniae 100 grams, Fructus Cnidii 100 grams, Radix Sophorae Flavescentis 100 grams, the Radix Stemonae 100 grams, boric acid 60 grams, Alumen 10 grams, Camphora 10 grams, Borneolum Syntheticum 5 grams, benzalkonium bromide 6 grams.
Ten flavor medicines are up to the standards standby respectively in will filling a prescription; Get Radix Sophorae Flavescentis, Fructus Cnidii is ground into coarse powder, extracts secondary with 85% alcohol heat reflux, each 1 hour, merge extractive liquid, filtered, filtrate recycling ethanol is concentrated into standby in right amount; The medicinal residues of Folium Callicarpae Formosanae, the Radix Stemonae, Herba Agrimoniae and above-mentioned Radix Sophorae Flavescentis etc. decoct with water secondary, are 2 hours at every turn, and collecting decoction filters, and filtrate is concentrated in right amount, stir evenly with above-mentioned concentrated solution, and spray drying, it is standby to collect dried cream powder; Boric acid, Alumen, Camphora, Borneolum Syntheticum, benzalkonium bromide are ground into fine powder, and be standby with above-mentioned dried cream powder mixing; Get lanoline, paraffin, semi-synthetic fatty acid glyceride (38 type) heat fused, stir evenly, temperature is reduced to about 50 ℃, adds above-mentioned medicated powder, fully stir evenly, and injection molding, cooling, demoulding, packing promptly gets the FUYANLING bolt.

Claims (6)

1, the FUYANLING preparation is characterized in that it is that component is formed or made other various preparations except that capsule, effervescent tablet that active component and pharmaceutically acceptable additives are formed by the extract of following main materials by following main materials, as ordinary tablet, fast disintegrating tablet, common bolt, soft capsule suppository, type of effervescent suppository, gel, membrane, ointment;
Folium Callicarpae Formosanae 50-500 weight portion, Herba Agrimoniae 50-500 weight portion, Fructus Cnidii 50-500 weight portion, Radix Sophorae Flavescentis 50-500 weight portion, Radix Stemonae 50-500 weight portion, boric acid 30-300 weight portion, Alumen 5-50 weight portion, Camphora 5-50 weight portion, Borneolum Syntheticum 2-20 weight portion, benzalkonium bromide 3-30 weight portion.
2, FUYANLING preparation according to claim 1 is characterized in that formula optimization is:
Folium Callicarpae Formosanae 100 weight portions, Herba Agrimoniae 100 weight portions, Fructus Cnidii 100 weight portions, Radix Sophorae Flavescentis 100 weight portions, the Radix Stemonae 100 weight portions, boric acid 60 weight portions, Alumen 10 weight portions, Camphora 10 weight portions, Borneolum Syntheticum 5 weight portions, benzalkonium bromide 6 weight portions.
3, FUYANLING preparation according to claim 1 is characterized in that described pharmaceutically acceptable additives are following one or more:
Dextrin, starch, methylcellulose, pregelatinized Starch, sodium alginate, magnesium stearate, 30 POVIDONE K 30 BP/USP 30, microcrystalline Cellulose, carboxymethylstach sodium, micropowder silica gel, hydroxypropyl cellulose, sodium carboxymethyl cellulose, carboxymethylcellulose calcium, ethylparaben, carbomer, vaseline, liquid Paraffin, tween 80, lecithin, sodium lauryl sulphate, stearic acid, semi-synthetic fatty acid ester, glycerol, gelatin, Polyethylene Glycol, Oleum Sesami, soybean oil, Oleum Arachidis hypogaeae semen.
4, FUYANLING preparation according to claim 1 is characterized in that described tablet can rise other outer various suitable tablets of sheet for de-bubble, and as ordinary tablet, fast disintegrating tablet etc., available suitable coating material coating is coating not also.
5, FUYANLING preparation according to claim 1 is characterized in that described suppository can be the suppository of ordinary suppository, capsule bolt, type of effervescent suppository or other type.
6, the preparation method of FUYANLING preparation is characterized in that it may further comprise the steps:
(1) in the prescription Radix Sophorae Flavescentis pulverize superfine powder is broken into that alcohol extraction is directly used or adopted to fine powder or water is carried or alcohol extraction after medicinal residues again water carry or acid extraction or other suitable method are extracted;
(2) in the prescription Fructus Cnidii pulverize superfine powder is broken into that alcohol extraction is directly used or adopted to fine powder or water is carried or alcohol extraction after the medicinal residues method that water is carried or other is suitable again extract;
(3) in the prescription Folium Callicarpae Formosanae, Herba Agrimoniae, the Radix Stemonae pulverize superfine powder is broken into that alcohol extraction is directly used or adopted to fine powder or water is carried or alcohol extraction after the medicinal residues method that water is carried or other is suitable again extract;
(4) prescription mesoboric acid, Alumen pulverizing or superfine powder are broken into fine powder or other suitable method processing;
(5) Borneolum Syntheticum, Camphora pulverize separately or superfine powder are broken into fine powder or grind altogether or add or handle with other suitable method with The suitable solvent dissolving back in the prescription;
(6) benzalkonium bromide pulverizing or superfine powder are broken into fine powder or other suitable method processing in the prescription;
(7) be ground into fine powder in the step and be ground into 100-160 purpose fine powder usually, the best is broken into 200-300 purpose fine powder for superfine powder;
(8) condition of alcohol extraction is in the step: with 50-95% ethanol is solvent, can adopt heating reflux method or percolation or other suitable method to extract;
(9) condition that water is carried in the step is: decoct with water at 90-98 ℃ and extract each 1-3 hour 2-4 time;
(10) extracting gained water extract in the step can adopt precipitate with ethanol or add the flocculating agent sedimentation or method that other is suitable is further handled;
(11) concentrate, adopt concentrating under reduced pressure or thin film concentration or vacuum film to concentrate or other proper method;
(12) drying can adopt vacuum drying or spray drying or lyophilization or other suitable method;
(13) add different additives as required, adopt suitable moulding process, be prepared from other the various preparations except that capsule, effervescent tablet, as ordinary tablet, fast disintegrating tablet, common bolt, soft capsule suppository, type of effervescent suppository, gel, membrane, ointment etc.
CN 200410046735 2004-09-05 2004-09-05 Fuyanling preparation for treating gynaecologic inflammationa nd preparing method Pending CN1742966A (en)

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CN1742966A true CN1742966A (en) 2006-03-08

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103520603A (en) * 2013-10-11 2014-01-22 哈尔滨欧替药业有限公司 Fuyanling expandable vaginal suppository, and preparation method and detection method thereof
CN103520604A (en) * 2013-10-11 2014-01-22 哈尔滨欧替药业有限公司 Baicao expandable vaginal suppository for clearing gynecologic inflammation, and preparation method and detection method thereof
CN105169153A (en) * 2015-08-27 2015-12-23 浙江苏泊尔南洋药业有限公司 Dampness removing and parasite destroying traditional Chinese medicine composition and preparation method thereof
CN105169163A (en) * 2015-10-20 2015-12-23 贵州长生药业有限责任公司 Composite suppository and preparation method thereof

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103520603A (en) * 2013-10-11 2014-01-22 哈尔滨欧替药业有限公司 Fuyanling expandable vaginal suppository, and preparation method and detection method thereof
CN103520604A (en) * 2013-10-11 2014-01-22 哈尔滨欧替药业有限公司 Baicao expandable vaginal suppository for clearing gynecologic inflammation, and preparation method and detection method thereof
CN105169153A (en) * 2015-08-27 2015-12-23 浙江苏泊尔南洋药业有限公司 Dampness removing and parasite destroying traditional Chinese medicine composition and preparation method thereof
CN105169153B (en) * 2015-08-27 2019-04-23 杭州苏泊尔南洋药业有限公司 A kind of Chinese medicine composition of removing dampness and destroying parasites and preparation method thereof
CN105169163A (en) * 2015-10-20 2015-12-23 贵州长生药业有限责任公司 Composite suppository and preparation method thereof
CN105169163B (en) * 2015-10-20 2019-02-22 贵州长生药业有限责任公司 A kind of compound suppository and preparation method thereof

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