CN106176577A - Sinomenine hydrochloride gel prepared by a kind of inorganic solvent and preparation method thereof - Google Patents

Sinomenine hydrochloride gel prepared by a kind of inorganic solvent and preparation method thereof Download PDF

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Publication number
CN106176577A
CN106176577A CN201610633830.7A CN201610633830A CN106176577A CN 106176577 A CN106176577 A CN 106176577A CN 201610633830 A CN201610633830 A CN 201610633830A CN 106176577 A CN106176577 A CN 106176577A
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gel
sinomenine hydrochloride
solution
add
eluent
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董绍象
滕健
文迎艺
彭祖仁
许李
付世和
曾颖
仇萍
黄宇明
吴飞驰
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ZHENGQING PHARMACEUTICAL GROUP CORP Ltd HUNAN PROV
CHANGSHA YUANDAO PHARMACEUTICAL TECHNOLOGY DEVELOPMENT Co Ltd
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ZHENGQING PHARMACEUTICAL GROUP CORP Ltd HUNAN PROV
CHANGSHA YUANDAO PHARMACEUTICAL TECHNOLOGY DEVELOPMENT Co Ltd
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Priority to CN201610633830.7A priority Critical patent/CN106176577A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/485Morphinan derivatives, e.g. morphine, codeine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/51Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/53Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/55Liquid-liquid separation; Phase separation

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Dermatology (AREA)
  • Emergency Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention discloses a kind of sinomenine hydrochloride ointment, and said preparation is made up of following raw material: sinomenine hydrochloride 12 weight portion, Acritamer 940 0.2 0.6 weight portion, glycerol 8 13 weight portion, Mentholum 14 weight portion, propylparaben 0.1 0.6 weight portion, water adds to 100 weight portions;Described sinomenine hydrochloride uses inorganic solvent to prepare, and said preparation treatment rheumatoid arthritis has prominent curative effect.

Description

Sinomenine hydrochloride gel prepared by a kind of inorganic solvent and preparation method thereof
Technical field
The present invention relates to a kind of sinomenine hydrochloride made with sinomenine hydrochloride inorganic solvent extraction process for crude drug system The external preparation become, is specifically related to a kind of sinomenine hydrochloride made with sinomenine hydrochloride inorganic solvent extraction process as crude drug The gel made.
Background technology
Sinomenine is from menispermaceous plants Caulis Sinomenii Sinomenium acutum (Thunb.) the earliest by Ishiwari etc. The rhizome of Rehd.et Wils. is separated, there is the pharmacology such as antiinflammatory, immunosuppressant, analgesia, blood pressure lowering, arrhythmia Effect.
In Caulis Sinomenii, main component is alkaloid, and the composition having now been found that has sinomenine (Sinomenine), different Sinomenium acutum Alkali (Igoginomenine), China's sinomenine (SinoAcutine), short Sinomenium acutum time alkali (Acutumidine), point sinomenine And disinomenine (Diginomenine), ethyl sinomenine (ethylsinomenine), tetrahydrochysene epiberberine (Sinaetine) (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 necessarily in Caulis Sinomenii Amount Calx, alkalizes a period of time, is subsequently adding a certain amount of technical benzene, and reflux, extract, in water-bath is finally acidified, stands, analyses Brilliant.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, and crystallization is in the hot water Carry out recrystallization, obtain sterling.
This several method all uses benzene that toxicity is the biggest as Extraction solvent, and benzene is one-level toxic solvent, at pharmaceutical industry The most disabled, 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.
Transdermal drug delivery system (Transdermal Drug Delivery Systems, TDDS) refer to skin surface to Medicine, makes medicine with constant rate of speed (or close to constant rate of speed) by skin, enters blood circulation and reach effective blood drug concentration, Realize eventually producing whole body or the novel form of local therapeutic effects.It is advantageous that avoiding contingent first mistake of oral administration imitates Bioavailability should be improved with the impact of the factor such as pH, food, transhipment time in digestive tract;The blood medicine keeping stable and lasting is dense Degree, overcomes the untoward reaction caused because the too fast generation blood drug level of absorption is too high, improves safety;Sustainable control is administered Speed, is administered flexibly, reduces administration number of times, improves the compliance etc. of patient.
Summary of the invention
Present invention aim at providing a kind of sinomenine hydrochloride gel and preparation method thereof.
The present invention seeks to be achieved through the following technical solutions:
Sinomenine hydrochloride gel of the present invention is made up of following raw material:
The preparation method of sinomenine hydrochloride gel of the present invention may is that
Being scattered in glycerol by Acritamer 940, it is the most swelling to add appropriate distilled water, stirs into clear gel substrate; Transdermal enhancer Mentholum, propylparaben and sinomenine hydrochloride are added in appropriate distilled water, dissolve, this solution is added extremely In gel-type vehicle, quickly stir, add distilled water to 100 weight portions, be stirred into clear gel agent.
Sinomenine hydrochloride of the present invention is made by the following method:
A, extraction: Caulis Sinomenii coarse powder 100~1000 weight portion, with the 0.1~1moL/L HCL moistening 0.5 of 60~1000ml ~8 hours, fill percolator, add 0.1~1moL/L HCL and make liquid level cover medicated powder 2cm, after impregnating 6~48 hours, by 2~ The speed of 5ml/min starts percolation, stops percolation, obtain percolate after 6~24 hours, standby;
B, upper prop eluting: by good cation exchange resin processed on percolate or 152 type resins, blade diameter length ratio is 1:8- 12, loading speed be 2~5 times of column volumes/hour, have a precipitation to effluent silico-tungstic acid test solution inspection, and a thin layer chromatography detection During inanimate object alkaline spot point stop loading, with purified water be eluted to eluent without during color stop, with 8~15% ammonia solution soak set Fat or 3~10% hydrochloric acid solution soak 152 type resin 12 hours, then with the ammonia that pH value is 8~11-ethanol solution eluting or 152 type resins are with 3~10% hydrochloric acid solution eluting, and elution speed is 2-5BV/h, and eluent silico-tungstic acid test solution inspection has precipitation Time receive, receive eluent with silico-tungstic acid test solution check without precipitation time stop, merge eluent, be neutralized to PH with hydrochloric acid or ammonia For 6-8, desalination, concentrate drying, obtain sinomenine hydrochloride crude product.
C, refined: to remove sinomenine hydrochloride crude product 5~10 weight portion, by 10~95% ethanol or the purified water of 30~120ml Being heated to reflux to being completely dissolved, add the activated carbon of 3-6% times of weight, insulation backflow 10-30 minute, filter while hot, filtrate is dense Contracting, cooling, crystallize, filter, clean filter cake with the ethanol solution of 75-95% colourless to filter cake, obtain sinomenine hydrochloride.
Sinomenine hydrochloride of the present invention is made the most by the following method:
A, extraction: Caulis Sinomenii coarse powder 500 weight portion, with the 0.5moL/L HCL moistening 4 hours of 500ml, fill percolator, then Adding 0.3moL/L HCL makes liquid level cover medicated powder 2cm, after impregnating 24 hours, starts percolation by the speed of 3ml/min, 18 hours Rear stopping percolation, obtains percolate, standby;
B, upper prop eluting: by good cation exchange resin processed on percolate or 152 type resins, blade diameter length ratio is 1: 10, loading speed be 3 times of column volumes/hour, have a precipitation to effluent silico-tungstic acid test solution inspection, and thin layer chromatography detection be without raw During alkaloids speckle stop loading, with purified water be eluted to eluent without during color stop, with 8~15% ammonia solution immersion resin or Person 3~10% hydrochloric acid solution soak 152 type resin 12 hours, then with the ammonia that pH value is 11-ethanol solution eluting or 152 type trees Fat is 2-5BV/h with 6% hydrochloric acid solution eluting, elution speed, and eluent silico-tungstic acid test solution inspection receives when having precipitation, receives Eluent stops when checking without precipitation with silico-tungstic acid test solution, merges eluent, and being neutralized to PH with hydrochloric acid or ammonia is 8, and desalination is dense Contracting is dried, and obtains sinomenine hydrochloride crude product.
C, refined: removing sinomenine hydrochloride crude product 7 weight portion, 95% ethanol or purified water with 60ml are heated to reflux to completely Dissolving, add the activated carbon of 4% times of weight, insulation backflow 20 minutes, filter while hot, filtrate concentrates, cooling, crystallize, filters, and uses It is colourless to filter cake that the ethanol solution of 80% cleans filter cake, obtains sinomenine hydrochloride;
The preferred step B of described method: strong cation-exchanging resin preferred 001*2.5,001*4, macroporous adsorbent resin is preferred 152 types;The preferred 1:10 of resin blade diameter length ratio;Preferably 3 times column volumes of loading speed/hour;Immersion resin preferably 10% ammonia solution (or 5% hydrochloric acid solution);Using ammonia-ethanol solution that pH value is 8~11 as the eluting solution of cation exchange resin, eluent Be neutralized with hydrochloric acid to PH be 6~8;5% hydrochloric acid solution is as the eluting solution of 152 type macroporous adsorbent resins;
Preferably step C: add 4% times of weight activated carbon;When being heated to reflux preferably 40%, 55%, 60%, 75% or 80% Ethanol.
In the present invention, sinomenine hydrochloride gel raw material can be preferably as follows:
Weight portion of the present invention is g/ml with the relation of parts by volume.
Sinomenine hydrochloride is fat-soluble poor, is difficult to Transdermal absorption, in atmosphere or easily aoxidizes and degraded, pole in aqueous solution The big stability affecting preparation.Screen the emphasis that suitable adjuvant is the present invention.
Following experiment case study is used for further illustrating the present invention but is not limited to the present invention:
Experimental example 1: the transdermal penetration amount of In vitro penetration test determination gel
Transdermal absorption instrument: TK-12D type Franz percutaneous dispersion test instrument;Franz diffusion cell: 6.5ml, infiltrating area 3.14cm2, the little Corium Mus anticipated is fixed between supply pool and the reception tank of Franz diffusion cell, stratum corneum side court On to administration, by containing different proportion PEG400, the sinomenine ointment of Macrogol 4000, carry out In vitro penetration Test.Sample 1 (0.25% carbomer), sample 2 (0.5% carbomer), sample 3 (1.0% carbomer), sample 4 (1.5% card Ripple nurse).Supply pool adds 1g sample, smears uniformly.Receiving liquid is the phosphate buffer of pH7.4, makes corium side and connects Receiving and completely attach between liquid, get rid of bubble, temperature 37 ± 1 DEG C, the speed of magnetic agitation is 600rpm, seals sample tap, prevents Acceptable solution evaporates.Sample 1.0mL in the 6th hour, detect sinomenine content.
The 6h of sinomenine adds up infiltration capacity and is respectively 11.28ug/cm2、16.74ug/cm2、11.07ug/cm2、5.37ug/ cm2.Result shows, when in substrate, Acritamer 940 content is 0.5%, sinomenine transdermal penetration amount is maximum, therefore uses The carbomer of 0.5% concentration is as main host material.
Experimental example 2: different accelerator add up the impact of infiltration capacity to the 6h of sinomenine:
Transdermal enhancer also includes azone, limonene, terpinolene, carvone, propylene glycol etc., and can use in prescription The mode of two kinds or the mixing of above transdermal enhancer increases the percutaneous permeation of preparation.Measure difference according to above method to promote Agent adds up the impact of infiltration capacity to the 6h of sinomenine:
The 6h of sinomenine adds up infiltration capacity and is respectively 12.75ug/cm2、16.14ug/cm2、18.78ug/cm2、17.61ug/ cm2、14.52ug/cm2、19.15ug/cm2.Result shows, uses Mentholum to ooze sinomenine percutaneous as during transdermal enhancer Facilitation is maximum thoroughly.
Experimental example 3:
Use the gel treatment of arthritis of embodiment 1 preparation
Male Wistar rat, body weight 180 ± 20g, to the right metapedes sole of the foot intradermal injection Freund ' s Freund's complete adjuvant 0.1ml, The injection adjuvant one parapodum sole of the foot is lasting swelling 4 days from the 1st day, then start detumescence.Swelling is again continued, in the in the 8th day Within 12 days, play generation secondary response, injection adjuvant offside (left hind) pedal swelling, afterbody, ear and forelimb joint fluid difference journey Degree ground swelling.After injection adjuvant the 17th day, select the obvious rat of secondary arthritis 20, be randomly divided into 2 groups, often group 10, First will rule at 0.5cm on left and right for rat hind leg ankle joint, coating under line, first group is coated with Blank gel, compares for Blank gel Group, second group is coated with sinomenine hydrochloride gel, successive administration 10 days, and meanwhile, every day is thick with the vernier caliper measurement left and right metapedes sole of the foot Degree, calculates foot sole of the foot thickness before and after swelling i.e. (foot sole of the foot thickness before and after metapedes sole of the foot thickness-injection adjuvant during treatment)/injection adjuvant × 100%.Result shows after 21 days, and the right average swelling of the metapedes sole of the foot of matched group is 71.6%, the left back sufficient sole of the foot of administration group Average swelling is 42.4%, and pedal swelling behind the adjuvant arthritis rats right side is had clearly by sinomenine hydrochloride gel Inhibitory action.
Embodiment 1:
Being scattered in glycerol by Acritamer 940, it is the most swelling to add appropriate distilled water, stirs into clear gel substrate; Transdermal enhancer Mentholum, propylparaben and sinomenine hydrochloride are added in appropriate distilled water, dissolve, this solution is added extremely In gel-type vehicle, quickly stir, add distilled water to 100g, be stirred into clear gel agent.
Implement 2
Being scattered in glycerol by Acritamer 940, it is the most swelling to add appropriate distilled water, stirs into clear gel substrate; Transdermal enhancer Mentholum, propylparaben and sinomenine hydrochloride are added in appropriate distilled water, dissolve, this solution is added extremely In gel-type vehicle, quickly stir, add distilled water to 100g, be stirred into clear gel agent.
Embodiment 3
Being scattered in glycerol by Acritamer 940, it is the most swelling to add appropriate distilled water, stirs into clear gel substrate; Transdermal enhancer Mentholum, propylparaben and sinomenine hydrochloride are added in appropriate distilled water, dissolve, this solution is added extremely In gel-type vehicle, quickly stir, add distilled water to 100g, be stirred into clear gel agent.
Embodiment 4
Being scattered in glycerol by Acritamer 940, it is the most swelling to add appropriate distilled water, stirs into clear gel substrate; Transdermal enhancer Mentholum, propylparaben and sinomenine hydrochloride are added in appropriate distilled water, dissolve, this solution is added extremely In gel-type vehicle, quickly stir, add distilled water to 100g, be stirred into clear gel agent.
Embodiment 1-4 sinomenine hydrochloride is made the most by the following method:
A, extraction: Caulis Sinomenii coarse powder 500g, with the 0.5moL/L HCL moistening 4 hours of 500ml, fill percolator, add 0.3moL/L HCL makes liquid level cover medicated powder 2cm, after impregnating 24 hours, starts percolation by the speed of 3ml/min, stops after 18 hours Only percolation, obtains percolate, standby;
B, upper prop eluting: by good cation exchange resin processed on percolate or 152 type resins, blade diameter length ratio is 1: 10, loading speed be 3 times of column volumes/hour, have a precipitation to effluent silico-tungstic acid test solution inspection, and thin layer chromatography detection be without raw During alkaloids speckle stop loading, with purified water be eluted to eluent without during color stop, with 8~15% ammonia solution immersion resin or Person 3~10% hydrochloric acid solution soak 152 type resin 12 hours, then with the ammonia that pH value is 11-ethanol solution eluting or 152 type trees Fat is 2-5BV/h with 6% hydrochloric acid solution eluting, elution speed, and eluent silico-tungstic acid test solution inspection receives when having precipitation, receives Eluent stops when checking without precipitation with silico-tungstic acid test solution, merges eluent, and being neutralized to PH with hydrochloric acid or ammonia is 8, and desalination is dense Contracting is dried, and obtains sinomenine hydrochloride crude product.
It is C, refined: removing sinomenine hydrochloride crude product 7g, 95% ethanol or purified water with 60ml are heated to reflux to being completely dissolved, Adding the activated carbon of 4% times of weight, insulation backflow 20 minutes, filter while hot, filtrate concentrates, cooling, crystallize, filters, with 80% Ethanol solution clean filter cake colourless to filter cake, obtain sinomenine hydrochloride.

Claims (9)

1. a sinomenine hydrochloride gel, it is characterised in that be made up of following raw material:
Described sinomenine hydrochloride is prepared by the following method:
A, extraction: Caulis Sinomenii coarse powder 100~1000 weight portion, with the 0.1~1moL/L HCL moistening 0.5~8 of 60~1000ml Hour, fill percolator, add 0.1~1moL/L HCL and make liquid level cover medicated powder 2cm, after impregnating 6~48 hours, by 2~ The speed of 5ml/min starts percolation, stops percolation, obtain percolate after 6~24 hours, standby;
B, upper prop eluting: by good cation exchange resin processed on percolate or 152 type resins, blade diameter length ratio is 1:8-12, Loading speed be 2~5 times of column volumes/hour, have a precipitation to effluent silico-tungstic acid test solution inspection, and thin layer chromatography detection be without raw During alkaloids speckle stop loading, with purified water be eluted to eluent without during color stop, with 8~15% ammonia solution immersion resin or Person 3~10% hydrochloric acid solution soak 152 type resin 12 hours, then with the ammonia that pH value is 8~11-ethanol solution eluting or 152 Type resin is with 3~10% hydrochloric acid solution eluting, and elution speed is 2-5BV/h, when eluent silico-tungstic acid test solution inspection has precipitation Receiving, receive when eluent silico-tungstic acid test solution checks without precipitation and stop, merging eluent, being neutralized to PH with hydrochloric acid or ammonia is 6-8, desalination, concentrate drying, obtain sinomenine hydrochloride crude product;
C, refined: to remove sinomenine hydrochloride crude product 5~10 weight portion, with 30~120ml 10~95% ethanol or purified water heat Being back to be completely dissolved, add the activated carbon of 3-6% times of weight, insulation backflow 10-30 minute, filter while hot, filtrate concentrates, cold But, crystallize, filter, clean filter cake with the ethanol solution of 75-95% colourless to filter cake, obtain sinomenine hydrochloride.
2. gel as claimed in claim 1, it is characterised in that wherein preparation raw material is:
3. gel as claimed in claim 1, it is characterised in that wherein preparation raw material is:
4. gel as claimed in claim 1, it is characterised in that wherein preparation raw material is:
5. gel as claimed in claim 1, it is characterised in that wherein preparation raw material is:
6. the gel as described in claim 1-5 is arbitrary, it is characterised in that wherein said sinomenine hydrochloride is made by the following method Become:
A, extraction: Caulis Sinomenii coarse powder 500 weight portion, with the 0.5moL/L HCL moistening 4 hours of 500ml, fill percolator, add 0.3moL/L HCL makes liquid level cover medicated powder 2cm, after impregnating 24 hours, starts percolation by the speed of 3ml/min, stops after 18 hours Only percolation, obtains percolate, standby;
B, upper prop eluting: by good cation exchange resin processed on percolate or 152 type resins, blade diameter length ratio is 1:10, on Sample speed be 3 times of column volumes/hour, have a precipitation to effluent silico-tungstic acid test solution inspection, and thin layer chromatography detection inanimate object alkali During speckle stop loading, with purified water be eluted to eluent without during color stop, with 8~15% ammonia solution immersion resin or 3 ~10% hydrochloric acid solution soak 152 type resin 12 hours, then with the ammonia that pH value is 11-ethanol solution eluting or 152 type resins With 6% hydrochloric acid solution eluting, elution speed is 2-5BV/h, and eluent silico-tungstic acid test solution inspection receives when having precipitation, and reception is washed De-liquid stops when checking without precipitation with silico-tungstic acid test solution, merges eluent, and being neutralized to PH with hydrochloric acid or ammonia is 8, desalination, concentrates It is dried, obtains sinomenine hydrochloride crude product.
C, refined: removing sinomenine hydrochloride crude product 7 weight portion, 95% ethanol or purified water with 60ml are heated to reflux to the most molten Solving, add the activated carbon of 4% times of weight, insulation backflow 20 minutes, filter while hot, filtrate concentrates, cooling, crystallize, filters, and uses It is colourless to filter cake that the ethanol solution of 80% cleans filter cake, obtains sinomenine hydrochloride.
7. the preparation method of the gel as described in claim 1-5 is arbitrary, it is characterised in that the method is:
Being scattered in glycerol by Acritamer 940, it is the most swelling to add appropriate distilled water, stirs into clear gel substrate;Will be thoroughly Skin accelerator Mentholum, propylparaben and sinomenine hydrochloride add in appropriate distilled water, dissolve, and add this solution to gel In substrate, quickly stir, add distilled water to 100 weight portions, be stirred into clear gel agent.
8. the application in the medicine of preparation treatment rheumatoid arthritis of the gel as described in claim 1-5 is arbitrary.
9. the gel as claimed in claim 6 application in the medicine of preparation treatment rheumatoid arthritis.
CN201610633830.7A 2016-08-04 2016-08-04 Sinomenine hydrochloride gel prepared by a kind of inorganic solvent and preparation method thereof Pending CN106176577A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108354898A (en) * 2018-05-08 2018-08-03 周继刚 A kind of Percutaneously administrable preparation and preparation method thereof for treating rheumatoid arthritis

Citations (6)

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Publication number Priority date Publication date Assignee Title
CN1457765A (en) * 2003-06-10 2003-11-26 中国人民解放军第二军医大学 Cetirizine hydrochloride gel
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