CN112494449A - Sinomenine hydrochloride sustained release agent prepared by inorganic solvent - Google Patents

Sinomenine hydrochloride sustained release agent prepared by inorganic solvent Download PDF

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CN112494449A
CN112494449A CN202010356714.1A CN202010356714A CN112494449A CN 112494449 A CN112494449 A CN 112494449A CN 202010356714 A CN202010356714 A CN 202010356714A CN 112494449 A CN112494449 A CN 112494449A
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sinomenine hydrochloride
solution
weight
hours
percolation
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滕健
许李
彭祖仁
付世和
王小伟
曾颖
杨远香
仇萍
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Hunan Zhengqing Pharmaceutical Group Co ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
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    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
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    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • A—HUMAN NECESSITIES
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    • 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]
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    • A61P9/00—Drugs for disorders of the cardiovascular system
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    • A—HUMAN NECESSITIES
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    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/22—Bridged ring systems
    • C07D221/28—Morphinans

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Abstract

The invention discloses a sinomenine hydrochloride sustained release preparation which is prepared from the following raw materials: 60 parts of sinomenine hydrochloride, 96 parts of hydroxypropyl methylcellulose, 64 parts of lactose, 19.3 parts of starch, 70.7 parts of dextrin, a proper amount of 80% ethanol and 0.64 part of magnesium stearate; the sinomenine hydrochloride is prepared by using an inorganic solvent, and the preparation has an outstanding curative effect on rheumatoid arthritis.

Description

Sinomenine hydrochloride sustained release agent prepared by inorganic solvent
Technical Field
The invention relates to a pharmaceutical preparation prepared by using sinomenine hydrochloride prepared by a sinomenine hydrochloride inorganic solvent extraction process as a raw material medicine, in particular to a sustained-release agent prepared by using sinomenine hydrochloride prepared by an inorganic solvent extraction process as a raw material medicine.
Background
Sinomenine was originally isolated from the rhizome of Sinomenium acutum (Thunb.) rehd. et wils. of Menispermaceae by Ishiwari, etc., and has pharmacological actions such as anti-inflammatory, immunosuppressive, analgesic, antihypertensive, antiarrhythmic, etc.
The main component of caulis sinomenii is alkaloid, and the currently found components include Sinomenine (Sinomenine), isocsinomenine (Igoginomenine), Sinomenine (Sinoactine), Sinomenine (Acutidine), Sinomenine (Sinacetine) and bispsinomenine (Diginomenine), ethyl Sinomenine (ethylsinomenine), tetrahydroepiberberine, batroxobin, tetrahydropalmatine and the like.
At present, the sinomenine hydrochloride is industrially produced by adopting an alkalized water extraction process, which comprises the steps of adding water and a certain amount of hydrated lime into sinomenine, alkalizing for a period of time, then adding a certain amount of industrial benzene, carrying out reflux extraction in a water bath, and finally acidifying, standing and crystallizing. The extraction and purification method of sinomenine is also reported in literature, wherein sinomenine dilute sulfuric acid percolate is subjected to pH 9 adjustment by lime water, benzene is subjected to countercurrent extraction at 50 ℃, benzene extract is subjected to countercurrent extraction by 1% hydrochloric acid, activated carbon is used for decoloring, and crystallization is performed in hot water for recrystallization to obtain a pure product.
The method uses benzene with high toxicity as an extraction solvent, the benzene is a first-grade toxic solvent which is forbidden in the pharmaceutical industry, and the solvent recovery treatment needs a very complicated process to meet the environmental protection requirement, and the chloroform is a second-grade toxic solvent, so that the benzene and chloroform solvents are avoided as much as possible in the traditional Chinese medicine extraction.
Disclosure of Invention
The invention aims to provide a sinomenine hydrochloride sustained release agent and a preparation method thereof.
The purpose of the invention is realized by the following technical scheme:
the sinomenine hydrochloride sustained release preparation is prepared by the following method:
raw materials:
Figure BDA0002473713340000021
the preparation method comprises the following steps:
mixing sinomenine hydrochloride, hypromellose, lactose, starch and dextrin, granulating with 80% ethanol, drying, adding magnesium stearate, mixing, tabletting, and coating.
The coating is as follows: ethyl cellulose water dispersion (B type), coating film coating premix (gastric soluble type) 7:3, coating, and increasing weight by 3%;
wherein, the sinomenine hydrochloride is prepared by the following method:
A. extraction: 100-1000 parts by weight of caulis sinomenii coarse powder, wetting with 60-1000 ml of 0.1-1 moL/L HCL for 0.5-8 hours, filling a percolation cylinder, adding 0.1-1 moL/L HCL to enable the liquid surface to cover the medicinal powder by 2cm, soaking for 6-48 hours, starting percolation at the speed of 2-5 ml/min, stopping percolation after 6-24 hours, and obtaining percolation liquid for later use;
B. and (3) eluting on a column: applying the treated cation exchange resin or 152 type resin on the percolate at a diameter-height ratio of 1:8-12 at a sample application speed of 2-5 times of column volume/hour until the effluent is detected to have precipitate by using silicotungstic acid test solution and no alkaloid spot is detected by thin layer chromatography, eluting with purified water until the eluate is colorless, soaking the resin or the 152 type resin in 8-15% ammonia solution for 12 hours, then eluting with ammonia-ethanol solution with pH value of 8-11 or the 152 type resin in 3-10% hydrochloric acid solution at an elution speed of 2-5 BV/hour, receiving the eluate when the eluate is detected to have precipitate by using the silicotungstic acid test solution, merging the eluents, neutralizing with hydrochloric acid or ammonia water until the pH value is 6-8, desalting, concentrating and drying, obtaining a sinomenine hydrochloride crude product;
C. refining: removing 5-10 parts by weight of crude sinomenine hydrochloride, heating and refluxing with 30-120 ml of 10-95% ethanol or purified water until the sinomenine hydrochloride is completely dissolved, adding 3-6% by weight of activated carbon, preserving heat and refluxing for 10-30 minutes, filtering while hot, concentrating the filtrate, cooling, crystallizing, filtering, and cleaning the filter cake with 75-95% ethanol solution until the filter cake is colorless to obtain sinomenine hydrochloride.
The sinomenine hydrochloride is preferably prepared by the following method:
A. extraction: wetting 500 parts by weight of caulis sinomenii coarse powder with 500ml of 0.5moL/L HCL for 4 hours, filling a percolation cylinder, adding 0.3moL/L HCL to enable the liquid level to cover the medicinal powder by 2cm, soaking for 24 hours, starting percolation at the speed of 3ml/min, stopping percolation after 18 hours, and obtaining a percolation solution for later use;
B. and (3) eluting on a column: and (2) applying the treated cation exchange resin or 152 type resin on the percolate at a diameter-height ratio of 1:10 at a sample application speed of 3 times of column volume/hour until an effluent liquid is detected to have a precipitate by using a silicotungstic acid test solution, stopping applying the sample when no alkaloid spot is detected by thin-layer chromatography, eluting by using purified water until an eluent is colorless, soaking the resin by using 8-15% of ammonia solution or soaking the 152 type resin by using 3-10% of hydrochloric acid solution for 12 hours, then eluting by using an ammonia water-ethanol solution with a pH value of 11 or eluting the 152 type resin by using 6% of hydrochloric acid solution at an elution speed of 2-5 BV/hour, receiving the eluent when the eluent is detected to have the precipitate by using the silicotungstic acid test solution, stopping receiving the eluent when the eluent is detected to have no precipitate, merging the eluent, neutralizing by using hydrochloric acid or ammonia water until the pH value is 8, removing salt, concentrating and drying.
C. Refining: removing 7 parts by weight of sinomenine crude product, heating and refluxing with 60ml of 95% ethanol or purified water until the sinomenine crude product is completely dissolved, adding 4% of activated carbon by weight, preserving heat and refluxing for 20 minutes, filtering while hot, concentrating the filtrate, cooling, crystallizing, filtering, and cleaning the filter cake with 80% ethanol solution until the filter cake is colorless to obtain sinomenine hydrochloride;
the method preferably comprises the following steps: the strong cation exchange resin is preferably 001 × 2.5 and 001 × 4, and the macroporous adsorption resin is preferably 152 type; the ratio of the diameter to the height of the resin is preferably 1: 10; the sample loading speed is preferably 3 times of column volume/hour; soaking the resin preferably in a 10% ammonia solution (or 5% hydrochloric acid solution); taking an ammonia water-ethanol solution with the pH value of 8-11 as an elution solution of the cation exchange resin, and neutralizing the elution solution with hydrochloric acid until the pH value is 6-8; 5% hydrochloric acid solution is used as the elution solution of 152 type macroporous absorption resin;
preferably, step C: adding 4 weight percent of activated carbon; preferably 40%, 55%, 60%, 75% or 80% ethanol is heated to reflux.
The sinomenine hydrochloride sustained-release preparation of the invention can be preferably prepared from the following raw materials:
Figure BDA0002473713340000031
Figure BDA0002473713340000041
the relationship between the parts by weight and the parts by volume is g/ml.
The following experimental examples are provided to further illustrate the present invention but are not limited thereto.
Experimental example 1: small test of Zhengqing Fengtongning sustained-release preparation
1. The experimental prescription is as follows:
Figure BDA0002473713340000042
Figure BDA0002473713340000051
2. experimental methods
Mixing sinomenine hydrochloride with hypromellose, starch, dextrin and lactose, adding 80% ethanol, high-shear granulating (16 mesh), drying at 55 deg.C, grading (14 mesh), adding magnesium stearate, making into 1000 tablets, coating (ethyl cellulose water dispersion (type B): film coating premix (stomach soluble type): 7:3, weight increased by 3%), and measuring content and release degree.
3. Results of the experiment
(1) And the results of tabletting test
Tablet weight Sheet diameter Pressure of Hardness of Tablet speed Degree of friability
320mg 9mm 1.4-1.8t About 70N 14rpm —
(2) Coating parameters
Figure BDA0002473713340000052
(3) And content determination: 101.3%, limit range: 90 to 110 percent
(4) And release degree:
Figure BDA0002473713340000061
as a result: the measured release degrees meet the standard regulation, the RSD of the 2h and 12h release degrees is less than 2%, and the RSD value of the 4h release degree is less than 4%.
Coating formula test:
sample 1: ethyl cellulose water dispersion (type B), film coating premix (gastric soluble type) 8:2, coating weight increase 3%, 5%, sampling about 50 tablets, and finally weight increase 8%;
sample 2: ethyl cellulose water dispersion (type B), film coating premix (gastric soluble) 7:3, coating weight gain 3%, 5%, sampling about 50 tablets, and final weight gain 8%.
Examination result of Zhengqing Fengtongning sustained-release tablet
Figure BDA0002473713340000062
Figure BDA0002473713340000071
Coating sample content data of sustained release tablet
Figure BDA0002473713340000072
Coating-like release data of sustained release tablet
Figure BDA0002473713340000073
Figure BDA0002473713340000074
Figure BDA0002473713340000081
Figure BDA0002473713340000082
Figure BDA0002473713340000083
Figure BDA0002473713340000084
Figure BDA0002473713340000091
Figure BDA0002473713340000092
Experimental example 2: pilot test using the sustained release formulation prepared in example 1
According to the coating material determined by the experimental example 1, pilot study was carried out on the ethyl cellulose aqueous dispersion (type B) and the film coating premix (gastric soluble type) of 7:3, and the coating weight was increased by 3%, and the formulation and process parameters were determined.
1. Preparation process
a) Feeding material
Figure BDA0002473713340000093
Figure BDA0002473713340000101
b) Granulating and tabletting
Preparation of 80% ethanol: adding purified water 7.5kg into 95% ethanol 40kg, and mixing well for use.
And (3) granulating: the lactose, starch, dextrin, sinomenine hydrochloride and hydroxypropyl methylcellulose with the prescription amount are added into a whole-grain wet mixing granulator, and are dry-mixed for 600S, the stirring speed is 100rpm, and the granulating cutter speed is 1000 rpm. After dry mixing, setting the stirring speed to be 100rpm and the granulating cutter to be 1000rpm, adding 80% ethanol, taking the soft material, observing the soft material properly, adjusting the stirring speed to be 100rpm, and mixing for 480s at the granulating cutter rotating speed of 1200 rpm.
Drying and granulating: setting the frequency of a fan to be 25-50HZ, the temperature of materials to be 50-55 ℃, the bed pressure to be-4.0 KPa-6.0 KPa, the bag shaking time to be 16s, the bag shaking interval time to be 20s, and the absolute humidity of inlet air to be 8 g/kg; loading a 14-mesh screen into a whole grain wet mixing machine, setting the rotating speed of a whole grain cutter to be 800rpm, starting discharging and whole grain finishing, conveying the whole grain wet granules to a boiling granulator by using negative pressure for drying, adjusting the air supply quantity to fluidize the wet granules in a material pot and a diffusion chamber, and checking whether the fluidization state of the granules is good or not by using a sight glass; drying the granules for 6min to make water content less than 7%, granulating at 800rpm with a granulating knife, and granulating with 14 mesh sieve.
Total mixing: adding the sized granules into the magnesium stearate with the prescription amount, and totally mixing at the rotating speed of 8rpm for 3 min.
Tabletting: tabletting with theoretical weight of 0.31 g. 74.42kg of intermediate particles, 12.5 kg-15.0 kg of spot check hardness and 0.1% of friability.
Coating: the weight of the plain tablets is 70.02kg, the dosage of the coating solution is calculated according to the weight increment of 3 percent, and the concentration of the coating solution is 15 percent.
Pilot test results:
Figure BDA0002473713340000102
Figure BDA0002473713340000111
and (3) knotting: the overall situation is good, with the release being at the middle of the range specified by the quality standard release.
Example 1:
Figure BDA0002473713340000112
the preparation method comprises the following steps:
mixing sinomenine hydrochloride, hypromellose, lactose, starch and dextrin, granulating with 80% ethanol, drying, adding magnesium stearate, mixing, tabletting, and coating.
The coating is as follows: and (3) coating the ethyl cellulose aqueous dispersion (B) with a film coating premix (gastric soluble) of 7:3, wherein the weight is increased by 3%.
EXAMPLE 2
Figure BDA0002473713340000113
Figure BDA0002473713340000121
The preparation method comprises the following steps:
mixing sinomenine hydrochloride, hypromellose, lactose, starch and dextrin, granulating with 80% ethanol, drying, adding magnesium stearate, mixing, tabletting, and coating.
The coating is as follows: and (3) coating the ethyl cellulose aqueous dispersion (B) with a film coating premix (gastric soluble) of 7:3, wherein the weight is increased by 3%.
Example 3:
Figure BDA0002473713340000122
the preparation method comprises the following steps:
mixing sinomenine hydrochloride, hypromellose, lactose, starch and dextrin, granulating with 80% ethanol, drying, adding magnesium stearate, mixing, tabletting, and coating.
The coating is as follows: and (3) coating the ethyl cellulose aqueous dispersion (B) with a film coating premix (gastric soluble) of 7:3, wherein the weight is increased by 3%.
Examples 1-3 sinomenine hydrochloride was prepared as follows:
A. extraction: wetting caulis Sinomenii coarse powder 500g with 500ml of 0.5moL/L HCL for 4 hr, placing in a percolation canister, adding 0.3moL/L HCL to make the liquid surface cover the medicinal powder 2cm, soaking for 24 hr, percolating at 3ml/min, stopping percolating after 18 hr to obtain percolate;
B. and (3) eluting on a column: and (2) applying the treated cation exchange resin or 152 type resin on the percolate at a diameter-height ratio of 1:10 at a sample application speed of 3 times of column volume/hour until an effluent liquid is detected to have a precipitate by using a silicotungstic acid test solution, stopping applying the sample when no alkaloid spot is detected by thin-layer chromatography, eluting by using purified water until an eluent is colorless, soaking the resin by using 8-15% of ammonia solution or soaking the 152 type resin by using 3-10% of hydrochloric acid solution for 12 hours, then eluting by using an ammonia water-ethanol solution with a pH value of 11 or eluting the 152 type resin by using 6% of hydrochloric acid solution at an elution speed of 2-5 BV/hour, receiving the eluent when the eluent is detected to have the precipitate by using the silicotungstic acid test solution, stopping receiving the eluent when the eluent is detected to have no precipitate, merging the eluent, neutralizing by using hydrochloric acid or ammonia water until the pH value is 8, removing salt, concentrating and drying.
C. Refining: 7g of the sinomenine hydrochloride crude product is removed, 60ml of 95 percent ethanol or purified water is used for heating and refluxing until the sinomenine hydrochloride crude product is completely dissolved, 4 percent activated carbon with the weight of weight is added, the heat preservation and the refluxing are carried out for 20 minutes, the hot filtration is carried out, the filtrate is concentrated, cooled, crystallized and filtered, and the filter cake is washed by 80 percent ethanol solution until the filter cake is colorless, thus obtaining the sinomenine hydrochloride.

Claims (6)

1. A sinomenine hydrochloride sustained release agent is characterized by being prepared by the following method:
raw materials:
Figure FDA0002473713330000011
the preparation method comprises the following steps:
mixing sinomenine hydrochloride, hypromellose, lactose, starch and dextrin, granulating with 80% ethanol, drying, adding magnesium stearate, mixing, tabletting, and coating.
The coating is as follows: ethyl cellulose water dispersion (B type), coating film coating premix (gastric soluble type) 7:3, coating, and increasing weight by 3%;
wherein, the sinomenine hydrochloride is prepared by the following method:
A. extraction: 100-1000 parts by weight of caulis sinomenii coarse powder, wetting with 60-1000 ml of 0.1-1 moL/L HCL for 0.5-8 hours, filling a percolation cylinder, adding 0.1-1 moL/L HCL to enable the liquid surface to cover the medicinal powder by 2cm, soaking for 6-48 hours, starting percolation at the speed of 2-5 ml/min, stopping percolation after 6-24 hours, and obtaining percolation liquid for later use;
B. and (3) eluting on a column: applying the treated cation exchange resin or 152 type resin on the percolate at a diameter-height ratio of 1:8-12 at a sample application speed of 2-5 times of column volume/hour until the effluent is detected to have precipitate by using silicotungstic acid test solution and no alkaloid spot is detected by thin layer chromatography, eluting with purified water until the eluate is colorless, soaking the resin or the 152 type resin in 8-15% ammonia solution for 12 hours, then eluting with ammonia-ethanol solution with pH value of 8-11 or the 152 type resin in 3-10% hydrochloric acid solution at an elution speed of 2-5 BV/hour, receiving the eluate when the eluate is detected to have precipitate by using the silicotungstic acid test solution, merging the eluents, neutralizing with hydrochloric acid or ammonia water until the pH value is 6-8, desalting, concentrating and drying, obtaining a sinomenine hydrochloride crude product;
C. refining: removing 5-10 parts by weight of crude sinomenine hydrochloride, heating and refluxing with 30-120 ml of 10-95% ethanol or purified water until the sinomenine hydrochloride is completely dissolved, adding 3-6% by weight of activated carbon, preserving heat and refluxing for 10-30 minutes, filtering while hot, concentrating the filtrate, cooling, crystallizing, filtering, and cleaning the filter cake with 75-95% ethanol solution until the filter cake is colorless to obtain sinomenine hydrochloride.
2. The sustained-release formulation according to claim 1, wherein the raw materials are:
Figure FDA0002473713330000021
3. the sustained-release formulation according to claim 1, wherein the raw materials are:
Figure FDA0002473713330000022
4. the sustained-release formulation according to any one of claims 1 to 3, wherein the sinomenine hydrochloride is prepared by a method comprising:
A. extraction: wetting 500 parts by weight of caulis sinomenii coarse powder with 500ml of 0.5moL/L HCL for 4 hours, filling a percolation cylinder, adding 0.3moL/L HCL to enable the liquid level to cover the medicinal powder by 2cm, soaking for 24 hours, starting percolation at the speed of 3ml/min, stopping percolation after 18 hours, and obtaining a percolation solution for later use;
B. and (3) eluting on a column: and (2) applying the treated cation exchange resin or 152 type resin on the percolate at a diameter-height ratio of 1:10 at a sample application speed of 3 times of column volume/hour until an effluent liquid is detected to have a precipitate by using a silicotungstic acid test solution, stopping applying the sample when no alkaloid spot is detected by thin-layer chromatography, eluting by using purified water until an eluent is colorless, soaking the resin by using 8-15% of ammonia solution or soaking the 152 type resin by using 3-10% of hydrochloric acid solution for 12 hours, then eluting by using an ammonia water-ethanol solution with a pH value of 11 or eluting the 152 type resin by using 6% of hydrochloric acid solution at an elution speed of 2-5 BV/hour, receiving the eluent when the eluent is detected to have the precipitate by using the silicotungstic acid test solution, stopping receiving the eluent when the eluent is detected to have no precipitate, merging the eluent, neutralizing by using hydrochloric acid or ammonia water until the pH value is 8, removing salt, concentrating and drying.
C. Refining: 7 parts by weight of the crude sinomenine hydrochloride product is removed, 60ml of 95 percent ethanol or purified water is used for heating and refluxing until the sinomenine hydrochloride product is completely dissolved, 4 percent activated carbon by weight is added, the heat preservation and the refluxing are carried out for 20 minutes, the hot filtration is carried out, the filtrate is concentrated, cooled, crystallized and filtered, and the filter cake is washed by 80 percent ethanol solution until the filter cake is colorless, thus obtaining the sinomenine hydrochloride.
5. Use of a sustained release formulation as claimed in any one of claims 1 to 3 in the manufacture of a medicament for the treatment of rheumatoid arthritis.
6. Use of a sustained release formulation as claimed in claim 4 in the manufacture of a medicament for the treatment of rheumatoid arthritis.
CN202010356714.1A 2020-04-29 2020-04-29 Sinomenine hydrochloride sustained release agent prepared by inorganic solvent Pending CN112494449A (en)

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Cited By (1)

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Publication number Priority date Publication date Assignee Title
CN112999226A (en) * 2021-03-22 2021-06-22 广州白云山光华制药股份有限公司 Pharmaceutical composition for treating rheumatoid arthritis

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CN102600099A (en) * 2012-03-29 2012-07-25 湖南正清制药集团股份有限公司 Method for preparing sinomenine hydrochloride sustained release tablets by non-organic solvents
CN106137949A (en) * 2016-08-04 2016-11-23 长沙原道医药科技开发有限公司 Sinomenine hydrochloride ointment prepared by a kind of inorganic solvent and preparation method thereof

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CN1226424A (en) * 1998-12-24 1999-08-25 湖南正清制药集团股份有限公司 Slow releasing agent of tuduvanine and its preparing method
CN102600099A (en) * 2012-03-29 2012-07-25 湖南正清制药集团股份有限公司 Method for preparing sinomenine hydrochloride sustained release tablets by non-organic solvents
CN106137949A (en) * 2016-08-04 2016-11-23 长沙原道医药科技开发有限公司 Sinomenine hydrochloride ointment prepared by a kind of inorganic solvent and preparation method thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112999226A (en) * 2021-03-22 2021-06-22 广州白云山光华制药股份有限公司 Pharmaceutical composition for treating rheumatoid arthritis

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