CN105997959B - A kind of Sinomenine imbedibility liquid preparation and preparation method thereof - Google Patents
A kind of Sinomenine imbedibility liquid preparation and preparation method thereof Download PDFInfo
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Abstract
The present invention discloses a kind of Sinomenine imbedibility liquid preparation, and said preparation is made of the following raw material: 15~35 parts by weight of Sinomenine, 0.1~3 parts by weight of sodium hydrogensulfite, 0.1~3 parts by weight of natrium adetate, sodium chloride 7-10 parts by weight；The Sinomenine is made using organic solvent；Said preparation atomization inspiration treatment sphagitis, rheumatoid arthritis, chronic nephritis or pulmonary interstitial fibrosis have curative effect outstanding.
Description
Technical field
The present invention relates to a kind of imbedibility liquid preparations and preparation method thereof, and in particular to a kind of salt of organic solvent preparation
Sour cucoline is the imbedibility liquid preparation and preparation method thereof of raw material.
Background technique
Cucoline is by Ishiwari etc. earliest from menispermaceous plants caulis sinomenii Sinomenium acutum (Thunb.)
It is separated in the rhizome of Rehd.et Wils., there are the pharmacology such as anti-inflammatory, immunosupress, analgesia, decompression, anti-arrhythmia
Effect.
Main component is alkaloid in caulis sinomenii, and the ingredient having now been found that has cucoline (Sinomenine), different sinomenium acutum
Alkali (Igoginomenine), magnificent cucoline (SinoAcutine), short sinomenium acutum time alkali (Acutumidine), sharp cucoline
(Sinaetine) and disinomenine (Diginomenine), ethyl cucoline (ethylsinomenine), tetrahydro epiberberine
(sinactine), tetrahydro epiberberine, menispermum dauricum wave phenol alkali, bianfugenine, Tetrahydropalmatine etc..
Industrial production Sinomenine mostly uses alkalization water extraction process at present, for the addition water in caulis sinomenii and centainly
White lime is measured, alkalization a period of time, a certain amount of technical benzene is then added, the refluxing extraction in water-bath is finally acidified, stands, analysis
It is brilliant.Also document report introduces extraction and the purification process of cucoline, caulis sinomenii dilute sulfuric acid percolate, with limewash tune pH value 9,
Benzene carries out Anticountra flow extraction in 50 DEG C of progress counter-current extractions, benzene extracting solution with 1% hydrochloric acid, and active carbon decoloring, crystallization is in the hot water
It is recrystallized, obtains sterling.(Chen Yukun " extracting technique of Chinese medicine ", 1992)
The benzene that these types of method uses toxicity very big is as Extraction solvent, and benzene is level-one toxic solvent, in pharmaceutical industry
It is disabled, and need to can be only achieved environmental requirement by very cumbersome technique in terms of the recovery processing of solvent, and chloroform is
Second level toxic solvent, thus should avoid as far as possible in traditional Chinese medicine extraction using benzene and chloroform solvent.
Fog inhalation therapy be with atomising device by atomization preparation such as imbedibility liquid preparation be dispersed into small droplet or
Particle is suspended in it in gas and enters respiratory tract and intrapulmonary, achievees the purpose that quickly absorption and local treatment.
Summary of the invention
It is an object of that present invention to provide a kind of Sinomenine imbedibility liquid preparations and preparation method thereof.
Object of the present invention is to what is be achieved through the following technical solutions:
Sinomenine imbedibility liquid preparation of the present invention is made of the following raw material:
15~35 parts by weight of Sinomenine, 0.1~3 parts by weight of sodium hydrogensulfite, 0.1~3 parts by weight of natrium adetate,
Sodium chloride 7-10 parts by weight.
The preparation method of Sinomenine imbedibility liquid preparation of the present invention may is that
Take water for injection, nitrogen charging is added Sinomenine and is stirred to dissolve, add sodium hydrogensulfite, natrium adetate,
Sodium chloride is stirred to dissolve, and continues nitrogen charging, and 0.10~0.20% active carbon is added, and 35~45 DEG C keep the temperature 5~15 minutes, filtering
Carbon removal adds water for injection to 1000 parts by volume, examines, and refined filtration is clear and bright to solution, nitrogen charging encapsulating, and 100~120 DEG C of sterilizings 20~
40 minutes to get.
Sinomenine of the present invention is made by the following method:
Step A: 500 parts by weight of caulis sinomenii coarse powder are small with the 0.1-0.3mol/L HCL wetting 1.5-2.5 of 500 parts by volume
When, percolator is filled, liquid level covers medicinal powder 2-4cm when adding 0.3-0.6mol/L HCL, and dipping is after 18-28 hours, diacolation,
Stop diacolation after 12-16 hours, obtains percolate, it is spare；
Step B: milk of lime tune PH to 10-12, filtration is added in above-mentioned percolate, filtrate adds hydrochloric acid tune PH to 8, uses chloroform
Extraction 2-4 times；Merge chloroform layer to be rinsed with water to neutrality, adds the anhydrous Na SO of 2-5% times of weight4Recycling is concentrated under reduced pressure in dehydration
Chloroform；
Step C: concentrate instills HCL tune PH to 3, and stirring to floating solids disperses, and refrigerates, and filters, discards filtrate, dries
Dry filter cake obtains yellow Sinomenine coarse-grain；
D step: taking 7 parts by weight of Sinomenine crude product, is heated to reflux with the 60-90% ethyl alcohol of 40-70 parts by volume to complete
The active carbon of 3-5% times of weight is added in fully dissolved, and heat preservation reflux 15-25 minutes filters while hot, filtrate concentration, cooling, crystallization,
It is colourless to filter cake to clean filter cake with the ethanol solution of 80-95%, obtains Sinomenine for filtering；
Sinomenine of the present invention is preferably made by the following method:
Step A: 500 parts by weight of caulis sinomenii coarse powder are soaked two hours with the 0.1mol/L HCL of 500 parts by volume, fill diacolation
Cylinder, liquid level covers medicinal powder 3cm when adding 0.5mol/L HCL, and dipping started diacolation by the speed of 3ml/min after 24 hours,
Stop diacolation after 15 hours, obtains percolate, it is spare；
Step B: milk of lime tune PH to 11.6, filtration is added in above-mentioned percolate, filtrate adds hydrochloric acid tune PH to 8, uses chloroform
Extraction 4 times；Merge chloroform layer to be rinsed with water to neutrality, adds the anhydrous Na SO of 3% times of weight4Recycling chloroform is concentrated under reduced pressure in dehydration；
Step C: concentrate instills 6moL/L HCL tune PH to 3, and stirring to floating solids disperses, and refrigerates, and filters, discards
Filtrate, 65 DEG C of drying filter cakes, obtains yellow Sinomenine coarse-grain；
D step: taking 7 parts by weight of Sinomenine crude product, is heated to reflux with 75% ethyl alcohol of 60 parts by volume to being completely dissolved,
The active carbon of 4% times of weight is added, heat preservation reflux 20 minutes filters while hot, filtrate concentration, cooling, crystallization, filtering, with 95%
Ethanol solution cleaning filter cake it is colourless to filter cake, obtain Sinomenine；
Sinomenine imbedibility liquid preparation raw material can be preferably as follows in the present invention:
35 parts by weight of Sinomenine, 4.5 parts by weight of sodium hydrogensulfite, 1 parts by weight of natrium adetate, 9 weight of sodium chloride
Part；
25 parts by weight of Sinomenine, 1 parts by weight of sodium hydrogensulfite, 0.3 parts by weight of natrium adetate, 9 weight of sodium chloride
Part；
20 parts by weight of Sinomenine, 0.6 parts by weight of sodium hydrogensulfite, 0.2 parts by weight of natrium adetate, 9 weight of sodium chloride
Measure part；
Sinomenine imbedibility liquid preparation preparation method can be in the present invention are as follows:
Suitable water for injection is taken, nitrogen charging is added recipe quantity Sinomenine and is stirred to dissolve；Add bisulfite
Sodium, natrium adetate, sodium chloride, corrigent are stirred to dissolve, continuation nitrogen charging, the active carbon of addition 0.10~0.20%, 35~
45 DEG C heat preservation 8-12 minutes, filter carbon removal, add water for injection to 1000 parts by volume, examine, refined filtration to clear and bright, nitrogen charging encapsulating,
100 DEG C sterilizing 30 minutes to get.
Sinomenine imbedibility liquid preparation preparation method can be preferred in the present invention are as follows:
Suitable water for injection is taken, nitrogen charging is added recipe quantity Sinomenine and is stirred to dissolve；Add bisulfite
Sodium, natrium adetate, sodium chloride, corrigent are stirred to dissolve, and continue nitrogen charging, and 0.1% active carbon, 35~45 DEG C of heat preservations are added
10 minutes, carbon removal is filtered, 1000 parts by volume are added water for injection to, examined, refined filtration to clear and bright, nitrogen charging encapsulating, 100 DEG C of sterilizings 30
Minute to get.
The relationship of parts by weight and parts by volume of the present invention is g/ml.
Pharmaceutical preparation of the present invention directly acts on part, absorbs rapidly, sufficiently, drug dose is small, and drug is only other administrations
The 1/10 of approach.Systemic adverse reactions are small, highly-safe, increase the effective concentration that drug reaches lesion, and atomizing particle has
10% can enter intrapulmonary, reach the amount of target tissue up to 90%.
Fluid present invention sucking preparation is mainly used for oral cavity and nasal cavity, and can be also used for treatment includes flu and other factors
Cause bottleneck throat discomfort, acute/chronic pharyngitis, laryngitis, allergic rhinitis, tracheitis, bronchial asthma, various pneumonia, chronic obstruction
The treatment of the diseases such as property pulmonary emphysema.Suitable blast atomizer can be used using imbedibility liquid preparation made from the method for the present invention
Neulized inhalation achieves unexpected effect for treating rheumatoid arthritis, chronic nephritis and pulmonary interstitial fibrosis.
Detailed description of the invention
Fig. 1 is device figure (unit is mm after number).
Specific embodiment
The preparation method of Sinomenine imbedibility liquid preparation provided by the invention, the advantage is that using percolation
Sinomenine is prepared, easy to operate, it is cold treatment that extraction process, which does not have to heating,；High income, mother liquid disposal are simple；Safety
Reliably, pollution is low, plays positive effect to environmental protection.
Following experiment case studies are for further illustrating the present invention but being not limited to the present invention.Clinical or medicine can be added in the present invention
The customary adjuvants such as acceptable corrigent on.
Experimental example 1:
The preparation for treating rheumatoid arthritis prepared using injecting type atomizer Neulized inhalation embodiment 2, patient take seat
Or semireclining position, by Sinomenine imbedibility liquid preparation 2ml normal saline dilution to 5ml, in injecting jet formula atomizer,
Nebulizer connects on the oxygen cathete of port connection air tank or center inhalation device, adjusts oxygen flow 6-8L/min.Suffer from
Person holds atomizer, Neulized inhalation mouth containing mouth is contained in mouth, finger blocks gas outlet when air-breathing, closes lip depth air-breathing, exhales
It is unclamped when gas, sucks 15~25min, 2 times a day.Rheumatoid arthritis total effective rate is treated up to 92%.
Experimental example 2:
The preparation for treating chronic nephritis prepared using injecting type atomizer Neulized inhalation embodiment 2, patient take seat or half
Seat, by Sinomenine imbedibility liquid preparation 2ml normal saline dilution to 5ml, in injecting jet formula atomizer, atomization
Inhalator connects on the oxygen cathete of port connection air tank or center inhalation device, adjusts oxygen flow 6-8L/min.Patient's hand
Atomizer is held, Neulized inhalation mouth containing mouth is contained in mouth, finger blocks gas outlet when air-breathing, lip depth air-breathing is closed, when expiration
It unclamps, sucks 15~25min, 2 times a day.Chronic nephritis total effective rate is treated up to 92%
Experimental example 3:
The preparation for treating pulmonary interstitial fibrosis prepared using injecting type atomizer Neulized inhalation embodiment 2, patient take seat
Or semireclining position, by Sinomenine imbedibility liquid preparation 2ml normal saline dilution to 5ml, in injecting jet formula atomizer,
Nebulizer connects on the oxygen cathete of port connection air tank or center inhalation device, adjusts oxygen flow 6-8L/min.Suffer from
Person holds atomizer, Neulized inhalation mouth containing mouth is contained in mouth, finger blocks gas outlet when air-breathing, closes lip depth air-breathing, exhales
It is unclamped when gas, sucks 15~25min, 2 times a day.Pulmonary interstitial fibrosis total effective rate is treated up to 93%.
Experimental example 4:
The preparation for treating rheumatoid arthritis prepared using injecting type atomizer Neulized inhalation embodiment 2, patient take seat
Or semireclining position, by Sinomenine imbedibility liquid preparation 2ml normal saline dilution to 5ml, in injecting jet formula atomizer,
Nebulizer connects on the oxygen cathete of port connection air tank or center inhalation device, adjusts oxygen flow 6-8L/min.Suffer from
Person holds atomizer, Neulized inhalation mouth containing mouth is contained in mouth, finger blocks gas outlet when air-breathing, closes lip depth air-breathing, exhales
It is unclamped when gas, sucks 15~25min, 2 times a day.Acpuei pharyngitis total effective rate is treated up to 96%.
Experimental example 5: optimization
The prescription of imbedibility liquid preparation generallys use injection water as solvent, and a small amount of ethyl alcohol or the third two are added when necessary
Alcohol.Common auxiliary material includes HCl, NaOH, tartaric acid, NaCl etc..For increase medicine stability, can also be added sodium hydrogensulfite or
EDTA。
Sinomenine is soluble easily in water, without adding cosolvent.But Sinomenine easily aoxidizes, and PH is excessively high can to make blueness
Rattan caustic digestion.Therefore, the pH value of imbedibility liquid preparation should be maintained between 3~4, and sodium hydrogensulfite and edetic acid(EDTA) is added
Disodium stabilizer is to guarantee the stability of drug.
The measurement of 1.1 deposition ratio in the effective position
Imbedibility liquid preparation means one or more kinds of drugs, through special drug delivery device, into respiratory tract depth
Lung of portion plays a kind of drug delivery system locally or systemically acted on.Drug particle in imbedibility liquid agent should be very fine
Nonetheless (0.5~5 μm), can reach site of action, but, also only 1%~20% drug can be deposited in active component,
Play curative effect.Therefore, British Pharmacopoeia, United States Pharmacopeia and Chinese Pharmacopoeia provide to need the active component to imbedibility liquid preparation
Deposition is measured.
1.1.1 instrument and equipment and operation
Using imitated TI device, Fig. 1 is seen, 1. rubber interface uses rubber stopper, selects different connect according to suction apparatus
Mouthful.2. plastic screw cap: needing mold to prepare, do not satisfy the requirements still at present, using easily causing device not parallel when rubber stopper, test
Poor reproducibility, therefore glass frit seal will be used herein.3. using small size polypropylene filter restructuring, with vertical tube at emulsion tube and H
Connect.4. simulating trunnion: being the first order (stage I) at round-bottomed flask and vertical tube c, be equivalent to main bronchus；Conical flask and
It is the second level (stage II) at bend pipe E, vertical tube H, is equivalent to lung bronchiole with lower portion, i.e. active component.
Operating method: 1. device should ensure that two vertical tubes are parallel as schemed.2. placing acceptable solution at first order round-bottomed flask
7ml, acceptable solution 30ml is placed at the conical flask of the second level, and acceptable solution kind is related with given the test agent.3. adjusting the height of G, make
It is exactly in contact at the protrusion of center with conical flask bottom.4. connecing vacuum pump, the speed of evacuation is adjusted to 60Lmin-1, guarantor unit
The drug of dosage discharges completely.5. with blank acceptable solution by the medicament elution at bend pipe E and vertical tube, and in conical flask
Acceptable solution closes, and measures the content of drug, calculates deposition percentage of the drug at the second level.
A- elastomer connector；B- simulates throat；C- neck；D- overburden bottle (stag e I)；E- connecting tube；The outlet F-, connects
Vacuum pump；G- spout；The lower part H- measures product bottle (stag e II)
1.1.2 experimental result
Using distilled water as acceptable solution, following three prescription is screened:
Prescription 1: 35 parts by weight of Sinomenine, 4.5 parts by weight of sodium hydrogensulfite, 1 parts by weight of natrium adetate, sodium chloride
1000 parts by volume are made in 9 parts by weight, appropriate water for injection；
Prescription 2: 25 parts by weight of Sinomenine, 1 parts by weight of sodium hydrogensulfite, 0.3 parts by weight of natrium adetate, sodium chloride
1000 parts by volume are made in 9 parts by weight, appropriate water for injection；
Prescription 3: 20 parts by weight of Sinomenine, 0.6 parts by weight of sodium hydrogensulfite, 0.2 parts by weight of natrium adetate, chlorination
9 parts by weight of sodium, appropriate water for injection, are made 1000 parts by volume；
As a result as shown in the table.
1 Sinomenine imbedibility liquid preparation deposition ratio in the effective position of table measures (%)
According to experimental result, screening prescription 2 is optimal formulation and technology.
2, stability test
2.1 illumination experiment
It takes sample to place 10d under conditions of illumination (4500 ± 500) lx, respectively at 0,1,5,10d sampling, investigates its property
Shape measures pH value, main ingredient (Sinomenine) content, measures related content of material by Self-control method.Using high-efficient liquid phase technique
Measure drug content, using octadecylsilane chemically bonded silica as stationary phase, using methanol-ethylenediamine (1000:0.1 as mobile phase, column
Temperature is 30 DEG C, flow velocity 1ml/min, Detection wavelength 262nm.When as a result to 10d, preparation character, pH value, drug content are equal
Have no significant change, see Table 2 for details.
2 sample illumination experiment result of table
The experiment of 2.2 high temperature
It takes sample to place 10d in 60 DEG C of waters bath with thermostatic control, respectively at 0,1,5,10d sampling, investigates its character, measure PH
Value, drug content, measure related content of material by Self-control method.When as a result to 10d, preparation character, pH value, drug content
It has no significant change, see Table 3 for details.
3 high-temperature sample experimental result of table
2.3 accelerated test
3 batches, sample are taken, avoid light place 6 months under the conditions of temperature (40 ± 2) DEG C, was taken respectively at the 0th, 1,2,3,6 month
Sample carries out character observation, pH value measurement, drug content measurement and limit test of microbe, indices and has no significant change,
As a result see Table 4 for details.
4 sample accelerated test result of table
2.4 conclusion
Sample stability experiments have shown that, Sinomenine imbedibility liquid preparation dimensionally stable obtained, high temperature resistant can be grown
Phase storage.
Embodiment！
Sinomenine 35g, sodium hydrogensulfite 4.5g, natrium adetate 1g, sodium chloride 9g；
Suitable water for injection is taken, nitrogen charging is added recipe quantity Sinomenine and is stirred to dissolve；Add bisulfite
Sodium, natrium adetate, sodium chloride, corrigent are stirred to dissolve, and continue nitrogen charging, and 0.1% active carbon, 35~45 DEG C of heat preservations are added
10 minutes, carbon removal is filtered, 1000ml is added water for injection to, examined, refined filtration to clear and bright, nitrogen charging encapsulating, 100 DEG C sterilize 30 points
Clock to get.
Embodiment 2
Sinomenine 25g, sodium hydrogensulfite 1g, natrium adetate 0.3g, sodium chloride 9g；
Suitable water for injection is taken, nitrogen charging is added recipe quantity Sinomenine and is stirred to dissolve；Add bisulfite
Sodium, natrium adetate, sodium chloride are stirred to dissolve, and continue nitrogen charging, and 0.1% active carbon is added, and 35~45 DEG C keep the temperature 10 minutes,
Filter carbon removal, add water for injection to 1000ml, examine, refined filtration to clear and bright, nitrogen charging encapsulating, 100 DEG C sterilizing 30 minutes to get.
Embodiment 3
Sinomenine 20g, sodium hydrogensulfite 0.6g, natrium adetate 0.2g, sodium chloride 9g；
Suitable water for injection is taken, nitrogen charging is added recipe quantity Sinomenine and is stirred to dissolve；Add bisulfite
Sodium, natrium adetate, sodium chloride are stirred to dissolve, and continue nitrogen charging, and 0.1% active carbon is added, and 35~45 DEG C keep the temperature 10 minutes,
Filter carbon removal, add water for injection to 1000ml, examine, refined filtration to clear and bright, nitrogen charging encapsulating, 100 DEG C sterilizing 30 minutes to get.
Embodiment 1-3 Sinomenine is made by the following method:
Step A: caulis sinomenii coarse powder 500g is soaked two hours with the 0.1mol/L HCL of 500ml, is filled percolator, add
Liquid level covers medicinal powder 3cm when 0.5mol/L HCL, and dipping starts diacolation by the speed of 3ml/min, stop after 15 hours after 24 hours
Only diacolation obtains percolate, spare；
Step B: milk of lime tune PH to 11.6, filtration is added in above-mentioned percolate, filtrate adds hydrochloric acid tune PH to 8, uses chloroform
Extraction 4 times；Merge chloroform layer to be rinsed with water to neutrality, adds the anhydrous Na SO of 3% times of weight4Recycling chloroform is concentrated under reduced pressure in dehydration；
Step C: concentrate instills 6moL/L HCL tune PH to 3, and stirring to floating solids disperses, and refrigerates, and filters, discards
Filtrate, 65 DEG C of drying filter cakes, obtains yellow Sinomenine coarse-grain；
D step: taking Sinomenine crude product 7g, is heated to reflux with 75% ethyl alcohol of 60ml to being completely dissolved, 4% weight is added
The active carbon of amount times, heat preservation reflux 20 minutes, filters while hot, filtrate concentration, cooling, crystallization, filtering, with 95% ethanol solution
It is colourless to filter cake to clean filter cake, obtains Sinomenine.
Claims (2)
1. a kind of Sinomenine imbedibility liquid preparation, it is characterised in that be made of the following raw material:
Sinomenine 25g, sodium hydrogensulfite 1g, natrium adetate 0.3g, sodium chloride 9g；
Suitable water for injection is taken, nitrogen charging is added recipe quantity Sinomenine and is stirred to dissolve；Add sodium hydrogensulfite, according to
Ground acid disodium, sodium chloride are stirred to dissolve, and continue nitrogen charging, and 0.1% active carbon is added, and 35 ~ 45 DEG C keep the temperature 10 minutes, are crossed and are filtered out
Charcoal adds water for injection to 1000ml, examine, refined filtration to clear and bright, nitrogen charging encapsulating, 100 DEG C sterilizing 30 minutes to get；
The Sinomenine is made by the following method:
Step A: caulis sinomenii coarse powder 500g is soaked two hours with the 0.1mol/L HCL of 500ml, is filled percolator, add
Liquid level covers medicinal powder 3cm when 0.5mol/L HCL, and dipping starts diacolation by the speed of 3ml/min, stop after 15 hours after 24 hours
Only diacolation obtains percolate, spare；
Step B: being added milk of lime tune PH to 11.6, filtration for above-mentioned percolate, and filtrate adds hydrochloric acid tune PH to 8, with chloroform extraction 4
It is secondary；Merge chloroform layer to be rinsed with water to neutrality, adds the anhydrous Na SO of 3% times of weight4Recycling chloroform is concentrated under reduced pressure in dehydration；
Step C: concentrate instills 6moL/L HCL tune PH to 3, and stirring to floating solids disperses, and refrigerates, and filters, discards filter
Liquid, 65 DEG C of drying filter cakes, obtains yellow Sinomenine coarse-grain；
D step: taking Sinomenine crude product 7g, is heated to reflux with 75% ethyl alcohol of 60ml to being completely dissolved, 4% times of weight is added
Active carbon, heat preservation reflux 20 minutes, filters while hot, filtrate concentration, cooling, crystallization, and filtering cleans filter with 95% ethanol solution
Cake is colourless to filter cake, obtains Sinomenine.
2. imbedibility liquid preparation as described in claim 1 preparation treatment sphagitis, rheumatoid arthritis, chronic nephritis or
Application in the drug of pulmonary interstitial fibrosis.
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| CN1142946A (en) * | 1995-08-09 | 1997-02-19 | 白云山正清制药股份有限公司 | Application of cucoline in preparing medicine for chronic nephritis |
| CN102552122A (en) * | 2011-11-15 | 2012-07-11 | 湖南正清制药集团股份有限公司 | Method for preparing sinomenine hydrochloride injection |
| CN102579445A (en) * | 2012-03-02 | 2012-07-18 | 李蕴麟 | Application of sinomenine or pharmaceutically acceptable salt thereof as medicament for preventing and treating pulmonary interstitial fibrosis |
| CN105250245A (en) * | 2015-10-15 | 2016-01-20 | 北京神州泰洁生物科技有限公司 | Atomized inhalant for treating respiratory system diseases |
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| US20060110468A1 (en) * | 2004-11-24 | 2006-05-25 | Liang Liu | Herbal formulations for arthritis |
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| CN102552122A (en) * | 2011-11-15 | 2012-07-11 | 湖南正清制药集团股份有限公司 | Method for preparing sinomenine hydrochloride injection |
| CN102579445A (en) * | 2012-03-02 | 2012-07-18 | 李蕴麟 | Application of sinomenine or pharmaceutically acceptable salt thereof as medicament for preventing and treating pulmonary interstitial fibrosis |
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