CN105997959A - Sinomenine-hydrochloride inhalational liquid preparation and preparing method thereof - Google Patents
Sinomenine-hydrochloride inhalational liquid preparation and preparing method thereof Download PDFInfo
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Abstract
The invention discloses a sinomenine-hydrochloride inhalational liquid preparation. The sinomenine-hydrochloride inhalational liquid preparation is prepared from, by weight, 15-35 parts of sinomenine hydrochloride, 0.1-3 parts of sodium hydrogen sulfite, 0.1-3 parts of edetate disodium and 7-10 parts of sodium chloride. The sinomenine-hydrochloride inhalational liquid preparation is prepared with an organic solvent. The preparation is subjected to aerosol inhalation, and has the prominent curative effect on treating sphagitis, rheumatoid arthritis, chronic nephritis or pulmonary interstitial fibrosis.
Description
Technical field
The present invention relates to a kind of imbedibility liquid preparation and preparation method thereof, be specifically related to imbedibility liquid preparation that sinomenine hydrochloride is raw material prepared by a kind of organic solvent and preparation method thereof.
Background technology
Sinomenine is to be separated from the rhizome of menispermaceous plants Caulis Sinomenii Sinomenium acutum (Thunb.) Rehd.et Wils. by Ishiwari etc. the earliest, has the pharmacological actions such as antiinflammatory, immunosuppressant, analgesia, blood pressure lowering, arrhythmia.
In Caulis Sinomenii, main component is alkaloid, the composition having now been found that has sinomenine (Sinomenine), isosinomenine (Igoginomenine), China's sinomenine (SinoAcutine), short Sinomenium acutum time alkali (Acutumidine), point sinomenine (Sinaetine) and disinomenine (Diginomenine), ethyl sinomenine (ethylsinomenine), tetrahydrochysene epiberberine (sinactine), tetrahydrochysene epiberberine, Caulis menispermi ripple phenol alkali, bianfugenine, Tetrahydropalmatine etc..
At present commercial production sinomenine hydrochloride uses alkalization water extraction process, and it be to add water and a certain amount of Calx in Caulis Sinomenii, alkalization a period of time, is subsequently adding a certain amount of technical benzene, reflux, extract, in water-bath, is finally acidified, stands, crystallize.Also there is document report to introduce extraction and the purification process of sinomenine, Caulis Sinomenii dilute sulfuric acid percolate, adjust pH value 9 with lime water, benzene carries out counter-current extraction at 50 DEG C, and benzene extraction liquid carries out Anticountra flow extraction, activated carbon decolorizing with 1% hydrochloric acid, crystallization carries out recrystallization in the hot water, obtains sterling.(Chen Yukun " extracting technique of Chinese medicine ", 1992)
This several method all uses benzene that toxicity is the biggest as Extraction solvent, benzene is one-level toxic solvent, the most disabled at pharmaceutical industry, and environmental requirement need to be can be only achieved by the most cumbersome technique in terms of the recycling of solvent, and chloroform is two grades of toxic solvents, thus should avoid using benzene and chloroform solvent in Chinese medicine extraction as far as possible.
Fog inhalation therapy is, with atomising device, atomization preparation such as imbedibility liquid preparation is dispersed into small droplet or microgranule so that it is be suspended in gas in entrance respiratory tract and lung, reaches quickly to absorb and the purpose of local treatment.
Summary of the invention
Present invention aim at providing a kind of sinomenine hydrochloride imbedibility liquid preparation and preparation method thereof.
The present invention seeks to be achieved through the following technical solutions:
Sinomenine hydrochloride imbedibility liquid preparation of the present invention is made up of following raw material:
Sinomenine hydrochloride 15～35 weight portion, sodium sulfite 0.1～3 weight portion, disodium edetate 0.1～3 weight portion, sodium chloride 7-10 weight portion.
The preparation method of sinomenine hydrochloride imbedibility liquid preparation of the present invention may is that
Take water for injection, nitrogen charging, add sinomenine hydrochloride and be stirred to dissolve, add sodium sulfite, disodium edetate, sodium chloride are stirred to dissolve, and continue nitrogen charging, add 0.10～the activated carbon of 0.20%, 35～45 DEG C are incubated 5～15 minutes, filter carbon removal, add water for injection to 1000 parts by volume, inspection, fine straining is clear and bright to solution, nitrogen charging embedding, 100～120 DEG C of sterilizings 20～40 minutes, to obtain final product.
Sinomenine hydrochloride of the present invention is made by the following method:
Step A: Caulis Sinomenii coarse powder 500 weight portion, with 0.1-0.3mol/L HCL moistening 1.5-2.5 hour of 500 parts by volume, fills percolator, when adding 0.3-0.6mol/L HCL, liquid level covers medicated powder 2-4cm, after impregnating 18-28 hour, and percolation, stop percolation after 12-16 hour, obtain percolate, standby；
Step B: above-mentioned percolate is added lime cream and adjusts PH to 10-12, filter, filtrate adds hydrochloric acid and adjusts PH to 8, extracts 2-4 time with chloroform；Combined chloroform layer use water rinses to neutral, adds anhydrous Na SO of 2-5% times of weight4Dehydration, concentrating under reduced pressure reclaims chloroform；
Step C: concentrated solution instills HCL and adjusts PH to 3, stirs to the dispersion of floating solids, cold preservation, sucking filtration, discards filtrate, dry filter cake, obtain yellow sinomenine hydrochloride coarse-grain；
D step: take sinomenine hydrochloride crude product 7 weight portion, with the 60-90% alcohol heating reflux of 40-70 parts by volume to being completely dissolved, add the activated carbon of 3-5% times of weight, insulation backflow 15-25 minute, filters while hot, and filtrate concentrates, cooling, crystallize, filter, clean filter cake with the ethanol solution of 80-95% colourless to filter cake, obtain sinomenine hydrochloride；
Sinomenine hydrochloride of the present invention is made the most by the following method:
Step A: Caulis Sinomenii coarse powder 500 weight portion, with the 0.1mol/L HCL moistening two hours of 500 parts by volume, fills percolator, when adding 0.5mol/L HCL, liquid level covers medicated powder 3cm, after impregnating 24 hours, starts percolation by the speed of 3ml/min, stop percolation after 15 hours, obtain percolate, standby；
Step B: above-mentioned percolate is added lime cream and adjusts PH to 11.6, filter, filtrate adds hydrochloric acid and adjusts PH to 8, extracts 4 times with chloroform；Combined chloroform layer use water rinses to neutral, adds anhydrous Na SO of 3% times of weight4Dehydration, concentrating under reduced pressure reclaims chloroform；
Step C: concentrated solution instills 6moL/L HCL and adjusts PH to 3, stirs to the dispersion of floating solids, cold preservation, sucking filtration, discards filtrate, dries filter cakes, obtains yellow sinomenine hydrochloride coarse-grain for 65 DEG C；
D step: take sinomenine hydrochloride crude product 7 weight portion, with 75% alcohol heating reflux of 60 parts by volume to being completely dissolved, add the activated carbon of 4% times of weight, insulation backflow 20 minutes, filters while hot, and filtrate concentrates, cooling, crystallize, filtering, it is colourless to filter cake that the ethanol solution with 95% cleans filter cake, obtains sinomenine hydrochloride；
In the present invention, sinomenine hydrochloride imbedibility liquid preparation raw material can be preferably as follows:
Sinomenine hydrochloride 35 weight portion, sodium sulfite 4.5 weight portion, disodium edetate 1 weight portion, sodium chloride 9 weight portion；
Sinomenine hydrochloride 25 weight portion, sodium sulfite 1 weight portion, disodium edetate 0.3 weight portion, sodium chloride 9 weight portion；
Sinomenine hydrochloride 20 weight portion, sodium sulfite 0.6 weight portion, disodium edetate 0.2 weight portion, sodium chloride 9 weight portion；
In the present invention, sinomenine hydrochloride imbedibility liquid preparation preparation method can be:
Take appropriate water for injection, nitrogen charging, add recipe quantity sinomenine hydrochloride and be stirred to dissolve；Add sodium sulfite, disodium edetate, sodium chloride, correctives are stirred to dissolve, continue nitrogen charging, addition 0.10～the activated carbon of 0.20%, 35～45 DEG C are incubated 8-12 minute, filter carbon removal, add water for injection to 1000 parts by volume, inspection, fine straining is the most clear and bright, nitrogen charging embedding, 100 DEG C of sterilizings 30 minutes, to obtain final product.
In the present invention, sinomenine hydrochloride imbedibility liquid preparation preparation method can be preferably:
Take appropriate water for injection, nitrogen charging, add recipe quantity sinomenine hydrochloride and be stirred to dissolve；Add sodium sulfite, disodium edetate, sodium chloride, correctives are stirred to dissolve, continue nitrogen charging, adding the activated carbon of 0.1%, 35～45 DEG C are incubated 10 minutes, filter carbon removal, add water for injection to 1000 parts by volume, inspection, fine straining is the most clear and bright, nitrogen charging embedding, 100 DEG C of sterilizings 30 minutes, to obtain final product.
Weight portion of the present invention is g/ml with the relation of parts by volume.
Pharmaceutical preparation of the present invention directly acts on local, absorbs rapid, abundant, and drug dose is little, and medicine is only the 1/10 of other administration route.Systemic adverse reactions is little, and safety is high, adds medicine and arrives the valid density of focus, and atomizing particle has 10% can enter in lung, and the amount arriving target tissue reaches 90%.
Fluid present invention sucks preparation and is mainly used in oral cavity and nasal cavity, it is also possible to include that flu and other factors cause the treatment of the diseases such as bottleneck throat discomfort, acute/chronic pharyngitis, laryngitis, allergic rhinitis, tracheitis, bronchial asthma, various pneumonia, chronic obstructive emphysema for treatment.The imbedibility liquid preparation using the inventive method to prepare can use suitable blast atomizer Neulized inhalation, is used for treating rheumatoid arthritis, chronic nephritis and interstitial pulmonary fibrosis, achieves beyond thought effect.
Accompanying drawing explanation
Fig. 1 is installation drawing (after numeral, unit is mm).
Detailed description of the invention
The preparation method of the sinomenine hydrochloride imbedibility liquid preparation that the present invention provides, has an advantage in that have employed percolation prepares sinomenine hydrochloride, and simple to operate, extraction process need not heat, and is cold treatment；Yield is high, and mother liquid disposal is simple；Safe and reliable, pollute low, positive role is played in environmental conservation.
Following experiment case study is used for further illustrating the present invention but is not limited to the present invention.The present invention can add clinic or the pharmaceutically customary adjuvant such as acceptable correctives.
Experimental example 1:
Use the preparation for treating rheumatoid arthritis of injecting type nebulizer Neulized inhalation embodiment 2 preparation, patient takes seat or semireclining position, by sinomenine hydrochloride imbedibility liquid preparation 2ml normal saline dilution to 5ml, in injecting jet formula nebulizer, nebulizer connects QI KOU and connects on the oxygen catheter of oxygen cylinder or center inhalation device, regulates oxygen flow 6-8L/min.The hand-held nebulizer of patient, sucks Neulized inhalation mouth and contains in mouth, and during air-breathing, finger blocks gas outlet, closes the deep air-breathing of lip, unclamps during expiration, suction 15～25min, 2 times on the one.Treatment rheumatoid arthritis total effective rate reaches 92%.
Experimental example 2:
Use the preparation for treating chronic nephritis of injecting type nebulizer Neulized inhalation embodiment 2 preparation, patient takes seat or semireclining position, by sinomenine hydrochloride imbedibility liquid preparation 2ml normal saline dilution to 5ml, in injecting jet formula nebulizer, nebulizer connects QI KOU and connects on the oxygen catheter of oxygen cylinder or center inhalation device, regulates oxygen flow 6-8L/min.The hand-held nebulizer of patient, sucks Neulized inhalation mouth and contains in mouth, and during air-breathing, finger blocks gas outlet, closes the deep air-breathing of lip, unclamps during expiration, suction 15～25min, 2 times on the one.Treatment chronic nephritis total effective rate reaches 92%
Experimental example 3:
Use the preparation for treating interstitial pulmonary fibrosis of injecting type nebulizer Neulized inhalation embodiment 2 preparation, patient takes seat or semireclining position, by sinomenine hydrochloride imbedibility liquid preparation 2ml normal saline dilution to 5ml, in injecting jet formula nebulizer, nebulizer connects QI KOU and connects on the oxygen catheter of oxygen cylinder or center inhalation device, regulates oxygen flow 6-8L/min.The hand-held nebulizer of patient, sucks Neulized inhalation mouth and contains in mouth, and during air-breathing, finger blocks gas outlet, closes the deep air-breathing of lip, unclamps during expiration, suction 15～25min, 2 times on the one.Treatment interstitial pulmonary fibrosis total effective rate reaches 93%.
Experimental example 4:
Use the preparation for treating rheumatoid arthritis of injecting type nebulizer Neulized inhalation embodiment 2 preparation, patient takes seat or semireclining position, by sinomenine hydrochloride imbedibility liquid preparation 2ml normal saline dilution to 5ml, in injecting jet formula nebulizer, nebulizer connects QI KOU and connects on the oxygen catheter of oxygen cylinder or center inhalation device, regulates oxygen flow 6-8L/min.The hand-held nebulizer of patient, sucks Neulized inhalation mouth and contains in mouth, and during air-breathing, finger blocks gas outlet, closes the deep air-breathing of lip, unclamps during expiration, suction 15～25min, 2 times on the one.Treatment acute pharyngitis total effective rate reaches 96%.
Experimental example 5: optimization
The prescription of imbedibility liquid preparation generally uses injection water as solvent, adds a small amount of ethanol or propylene glycol if desired.Conventional adjuvant includes HCl, NaOH, tartaric acid, NaCl etc..For increasing medicine stability, sodium sulfite or EDTA also can be added.
Sinomenine hydrochloride is soluble in water, it is not necessary to add cosolvent.But sinomenine hydrochloride easily aoxidizes, PH is too high can make sinomenine decompose.Therefore, the pH value of imbedibility liquid preparation should be maintained between 3～4, and adds sodium sulfite and disodium edetate stabilizer to ensure the stability of medicine.
1.1 deposition ratio in the effective position measure
Imbedibility liquid preparation means one or more medicine, through special doser, enters respiratory tract deep lung, plays a kind of drug-supplying system locally or systemically acted on.Drug particle in imbedibility liquid agent should the finest (0.5～5 μm), site of action can be arrived, but nonetheless, the most only the medicine of 1%～20% can deposit in effective site, play curative effect.Therefore, British Pharmacopoeia, American Pharmacopeia and Chinese Pharmacopoeia all regulations need to be measured the deposition ratio in the effective position of imbedibility liquid preparation.
1.1.1 instrument and equipment and operation
Using imitated TI device, see Fig. 1,1. rubber interface uses rubber stopper, selects different interfaces according to suction apparatus.2. plastic screw cap: need mold to prepare, do not satisfy the requirements, easily causes device when using rubber stopper not parallel, tests poor reproducibility, therefore will use glass frit seal herein.3. use the small size polypropylene filter transformation of the way, connect with vertical tube at H with latex tubing.4. trunnion is simulated: for the first order (stage I) at round-bottomed flask and vertical tube c, be equivalent to main bronchus；Conical flask and bend pipe E, be the second level (stage II) at vertical tube H, is equivalent to lung bronchioles with lower portion, i.e. effective site.
Operational approach: 1. device such as figure, should ensure that two vertical tubes are parallel.2. placing acceptable solution 7ml at first order round-bottomed flask, place acceptable solution 30ml at the conical flask of the second level, acceptable solution kind is relevant with given the test agent.3. regulate the height of G, make just to contact with bottom conical flask at the protrusion of center.4. connecing vacuum pump, the speed of evacuation is adjusted to 60L min-1, it is ensured that the medicine of unit dose discharges completely.5. with blank acceptable solution by the medicament elution at bend pipe E and vertical tube, and close with the acceptable solution in conical flask, measure the content of medicine, calculate medicine deposition percentage rate at the second level.
A-elastomer connector；B-simulates throat；C-cervical region；D-overburden bottle (stag e I)；E-connecting tube；F-exports, and connects vacuum pump；G-spout；H-bottom measures long-pending bottle (stag e II)
1.1.2 experimental result
With distilled water as acceptable solution, following three prescription is screened:
Prescription 1: sinomenine hydrochloride 35 weight portion, sodium sulfite 4.5 weight portion, disodium edetate 1 weight portion, sodium chloride 9 weight portion, water for injection are appropriate, make 1000 parts by volume；
Prescription 2: sinomenine hydrochloride 25 weight portion, sodium sulfite 1 weight portion, disodium edetate 0.3 weight portion, sodium chloride 9 weight portion, water for injection are appropriate, make 1000 parts by volume；
Prescription 3: sinomenine hydrochloride 20 weight portion, sodium sulfite 0.6 weight portion, disodium edetate 0.2 weight portion, sodium chloride 9 weight portion, water for injection are appropriate, make 1000 parts by volume；
Result is as shown in the table.
Table 1 sinomenine hydrochloride imbedibility liquid preparation deposition ratio in the effective position measures (%)
According to experimental result, screening prescription 2 is optimum formulation and technology.
2, stability test
2.1 illumination experiment
Take sample under conditions of illumination (4500 ± 500) lx, place 10d, respectively at 0,1,5,10d sampling, investigate its character, measure pH value, principal agent (sinomenine hydrochloride) content, Self-control method measure relevant content of material.Using Syrups by HPLC drug content, with octadecylsilane chemically bonded silica for fixing phase, with methanol-ethylenediamine, (for flowing phase, column temperature is 30 DEG C to 1000:0.1, and flow velocity is 1ml/min, and detection wavelength is 262nm.When result is to 10d, preparation character, pH value, drug content are showed no significant change, refer to table 2.
Table 2 sample illumination experiment result
2.2 high temperature experiments
Take sample in 60 DEG C of waters bath with thermostatic control, place 10d, respectively at 0,1,5,10d sampling, investigate its character, measure pH value, drug content, Self-control method measure relevant content of material.When result is to 10d, preparation character, pH value, drug content have no significant change, and refer to table 3.
Table 3 high-temperature sample experimental result
2.3 accelerated test
Take 3 batches, sample, under the conditions of temperature (40 ± 2) DEG C, lucifuge is placed 6 months, respectively the 0th, 1,2,3, sampling in 6 months carries out character observation, pH value measures, drug content measures and limit test of microbe, indices has no significant change, the results detailed in Table 4.
Table 4 sample accelerated test result
2.4 conclusion
Sample stability test shows, the sinomenine hydrochloride imbedibility liquid preparation dimensionally stable prepared is high temperature resistant, can store for a long time.
Embodiment 1
Sinomenine hydrochloride 35g, sodium sulfite 4.5g, disodium edetate 1g, sodium chloride 9g；
Take appropriate water for injection, nitrogen charging, add recipe quantity sinomenine hydrochloride and be stirred to dissolve；Add sodium sulfite, disodium edetate, sodium chloride, correctives are stirred to dissolve, and continue nitrogen charging, add the activated carbon of 0.1%, and 35～45 DEG C are incubated 10 minutes, filter carbon removal, add water for injection to 1000ml, inspection, fine straining is to clear and bright, nitrogen charging embedding, 100 DEG C of sterilizings 30 minutes, to obtain final product.
Embodiment 2
Sinomenine hydrochloride 25g, sodium sulfite 1g, disodium edetate 0.3g, sodium chloride 9g；
Take appropriate water for injection, nitrogen charging, add recipe quantity sinomenine hydrochloride and be stirred to dissolve；Add sodium sulfite, disodium edetate, sodium chloride are stirred to dissolve, and continue nitrogen charging, add the activated carbon of 0.1%, and 35～45 DEG C are incubated 10 minutes, filter carbon removal, add water for injection to 1000ml, inspection, fine straining is to clear and bright, nitrogen charging embedding, 100 DEG C of sterilizings 30 minutes, to obtain final product.
Embodiment 3
Sinomenine hydrochloride 20g, sodium sulfite 0.6g, disodium edetate 0.2g, sodium chloride 9g；
Take appropriate water for injection, nitrogen charging, add recipe quantity sinomenine hydrochloride and be stirred to dissolve；Add sodium sulfite, disodium edetate, sodium chloride are stirred to dissolve, and continue nitrogen charging, add the activated carbon of 0.1%, and 35～45 DEG C are incubated 10 minutes, filter carbon removal, add water for injection to 1000ml, inspection, fine straining is to clear and bright, nitrogen charging embedding, 100 DEG C of sterilizings 30 minutes, to obtain final product.
Embodiment 1-3 sinomenine hydrochloride is made the most by the following method:
Step A: Caulis Sinomenii coarse powder 500g, with the 0.1mol/L HCL moistening two hours of 500ml, fills percolator, when adding 0.5mol/L HCL, liquid level covers medicated powder 3cm, after impregnating 24 hours, starts percolation by the speed of 3ml/min, stop percolation after 15 hours, obtain percolate, standby；
Step B: above-mentioned percolate is added lime cream and adjusts PH to 11.6, filter, filtrate adds hydrochloric acid and adjusts PH to 8, extracts 4 times with chloroform；Combined chloroform layer use water rinses to neutral, adds anhydrous Na SO of 3% times of weight4Dehydration, concentrating under reduced pressure reclaims chloroform；
Step C: concentrated solution instills 6moL/L HCL and adjusts PH to 3, stirs to the dispersion of floating solids, cold preservation, sucking filtration, discards filtrate, dries filter cakes, obtains yellow sinomenine hydrochloride coarse-grain for 65 DEG C；
D step: take sinomenine hydrochloride crude product 7g, with 75% alcohol heating reflux of 60ml to being completely dissolved, adds the activated carbon of 4% times of weight, insulation backflow 20 minutes, filtering while hot, filtrate concentrates, cooling, crystallize, filtering, it is colourless to filter cake that the ethanol solution with 95% cleans filter cake, obtains sinomenine hydrochloride.
Claims (8)
1. a sinomenine hydrochloride imbedibility liquid preparation, it is characterised in that be made up of following raw material:
Sinomenine hydrochloride 15～35 weight portion, sodium sulfite 0.1～3 weight portion, disodium edetate 0.1～3 weight portion, sodium chloride 7-10 weight portion；
Described sinomenine hydrochloride is made by the following method:
Step A: Caulis Sinomenii coarse powder 500 weight portion, with 0.1-0.3mol/L HCL moistening 1.5-2.5 hour of 500 parts by volume, fills percolator, when adding 0.3-0.6mol/L HCL, liquid level covers medicated powder 2-4cm, after impregnating 18-28 hour, and percolation, stop percolation after 12-16 hour, obtain percolate, standby；
Step B: above-mentioned percolate is added lime cream and adjusts PH to 10-12, filter, filtrate adds hydrochloric acid and adjusts PH to 8, extracts 2-4 time with chloroform；Combined chloroform layer use water rinses to neutral, adds anhydrous Na SO of 2-5% times of weight4Dehydration, concentrating under reduced pressure reclaims chloroform；
Step C: concentrated solution instills HCL and adjusts PH to 3, stirs to the dispersion of floating solids, cold preservation, sucking filtration, discards filtrate, dry filter cake, obtain yellow sinomenine hydrochloride coarse-grain；
D step: take sinomenine hydrochloride crude product 7 weight portion, with the 60-90% alcohol heating reflux of 40-70 parts by volume to being completely dissolved, add the activated carbon of 3-5% times of weight, insulation backflow 15-25 minute, filters while hot, and filtrate concentrates, cooling, crystallize, filter, clean filter cake with the ethanol solution of 80-95% colourless to filter cake, obtain sinomenine hydrochloride.
2. imbedibility liquid preparation as claimed in claim 1, it is characterised in that wherein preparation raw material is:
Sinomenine hydrochloride 35 weight portion, sodium sulfite 4.5 weight portion, disodium edetate 1 weight portion, sodium chloride 9 weight portion.
3. imbedibility liquid preparation as claimed in claim 1, it is characterised in that wherein preparation raw material is:
Sinomenine hydrochloride 25 weight portion, sodium sulfite 1 weight portion, disodium edetate 0.3 weight portion, sodium chloride 9 weight portion.
4. imbedibility liquid preparation as claimed in claim 1, it is characterised in that wherein preparation raw material is:
Sinomenine hydrochloride 20 weight portion, sodium sulfite 0.6 weight portion, disodium edetate 0.2 weight portion, sodium chloride 9 weight portion.
5. the imbedibility liquid preparation as described in claim 1-4 is arbitrary, it is characterised in that wherein said sinomenine hydrochloride is made by the following method:
Step A: Caulis Sinomenii coarse powder 500 weight portion, with the 0.1mol/L HCL moistening two hours of 500 parts by volume, fills percolator, when adding 0.5mol/L HCL, liquid level covers medicated powder 3cm, after impregnating 24 hours, starts percolation by the speed of 3ml/min, stop percolation after 15 hours, obtain percolate, standby；
Step B: above-mentioned percolate is added lime cream and adjusts PH to 11.6, filter, filtrate adds hydrochloric acid and adjusts PH to 8, extracts 4 times with chloroform；Combined chloroform layer use water rinses to neutral, adds anhydrous Na SO of 3% times of weight4Dehydration, concentrating under reduced pressure reclaims chloroform；
Step C: concentrated solution instills 6moL/L HCL and adjusts PH to 3, stirs to the dispersion of floating solids, cold preservation, sucking filtration, discards filtrate, dries filter cakes, obtains yellow sinomenine hydrochloride coarse-grain for 65 DEG C；
D step: take sinomenine hydrochloride crude product 7 weight portion, with 75% alcohol heating reflux of 60 parts by volume to being completely dissolved, add the activated carbon of 4% times of weight, insulation backflow 20 minutes, filters while hot, and filtrate concentrates, cooling, crystallize, filtering, it is colourless to filter cake that the ethanol solution with 95% cleans filter cake, obtains sinomenine hydrochloride.
6. the preparation method of the imbedibility liquid preparation as described in claim 1-4 is arbitrary, it is characterised in that the method is:
Take appropriate water for injection, nitrogen charging, add recipe quantity sinomenine hydrochloride and be stirred to dissolve；Add sodium sulfite, disodium edetate, sodium chloride are stirred to dissolve, and continue nitrogen charging, add 0.10～the activated carbon of 0.20%, and 35～45 DEG C are incubated 10 minutes, filter carbon removal, add water for injection to 1000 parts by volume, inspection, fine straining is to clear and bright, nitrogen charging embedding, 100 DEG C of sterilizings 30 minutes, to obtain final product.
7. the application in the medicine of preparation treatment pharyngolaryngitis, rheumatoid arthritis, chronic nephritis or interstitial pulmonary fibrosis of the imbedibility liquid preparation as described in claim 1-4 is arbitrary.
8. the imbedibility liquid preparation as claimed in claim 5 application in the medicine of preparation treatment class pharyngolaryngitis, rheumatic arthritis, chronic nephritis or interstitial pulmonary fibrosis.
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Denomination of invention: Sinomenine-hydrochloride inhalational liquid preparation and preparing method thereof Effective date of registration: 20191223 Granted publication date: 20190222 Pledgee: Huarong Xiangjiang Bank Co.,Ltd. Huaihua Branch Pledgor: Hunan Zhengqing Pharmaceutical Group Co.,Ltd. Registration number: Y2019980001222 |
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Date of cancellation: 20210426 Granted publication date: 20190222 Pledgee: Huarong Xiangjiang Bank Co.,Ltd. Huaihua Branch Pledgor: HUNAN ZHENGQING PHARMACEUTICAL GROUP Co.,Ltd. Registration number: Y2019980001222 |
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Denomination of invention: A liquid inhalation preparation of sinomenine hydrochloride and its preparation method Effective date of registration: 20230927 Granted publication date: 20190222 Pledgee: Huaihua Rural Commercial Bank Co.,Ltd. high tech Zone sub branch Pledgor: Hunan Zhengqing Pharmaceutical Group Co.,Ltd. Registration number: Y2023980059695 |