CN102178661B - Levo-tetrahydropalmatine transdermal drug delivery preparation - Google Patents
Levo-tetrahydropalmatine transdermal drug delivery preparation Download PDFInfo
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- CN102178661B CN102178661B CN2011101004523A CN201110100452A CN102178661B CN 102178661 B CN102178661 B CN 102178661B CN 2011101004523 A CN2011101004523 A CN 2011101004523A CN 201110100452 A CN201110100452 A CN 201110100452A CN 102178661 B CN102178661 B CN 102178661B
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Abstract
The invention discloses a levo-tetrahydropalmatine transdermal drug delivery preparation which comprises the following raw materials in percent by weight: 0.05-10 percent of levo-tetrahydropalmatine and 2-40 percent of transdermal absorption promoting agent. The levo-tetrahydropalmatine transdermal drug delivery preparation comprises formulations including solution, transdermal plaster, gel, ointment and the like, and has better application prospect. The invention also discloses a preparation method of the levo-tetrahydropalmatine transdermal drug delivery preparation. The preparation method has the advantages of convenience for operation, easiness in control, low cost and no need of special equipment, and is suitable for industrialized production.
Description
Technical field
The present invention relates to the medicine percutaneous drug administration preparation field in the pharmaceutics, be specifically related to a kind of rotundine percutaneous drug administration preparation.
Background technology
Tetrahydropalmatine (dltetrahydropalmatine, tetrahydropalmatine, tetrahydropalmatine; Dl-THP) be the main effective ingredient of papaveraceae plant corydalis, a chiral centre is arranged in the dl-THP structure, enantiomer shows different pharmacologically actives after getting in the body; Pharmacological research thinks that its live part is that (rotundine l-THP), works through the retardance central dopaminergic receptor its levo form at present; D-isomer (dextrorotation tetrahydropalmatine) does not then have obvious analgesic activity (Jin nation's chapter; The pharmacological research progress of rotundin and its second filial generation new drug-l-spd, Acta Pharmaceutica Sinica 1987,22 (6): 472-480.).
Rotundine is claimed rotundine, rotundine, rotundin again, mainly is present in the tuber of Menispermaceae Radix Stephaniae Japonicae and garden leaf Radix Stephaniae Japonicae at occurring in nature; Clinically mainly as analgesia and calm neuroleptic agent, analgesic activity than dolantin a little less than, but stronger than general antipyretic analgesic, better to chronic rest pain effect.The great advantage of rotundine is no addiction property, is a non-narcotic analgesics, does not also belong to analgesic anti-inflammatory analgesic category, and the antalgic and sedative effect is better than dltetrahydropalmatine.
At present, the clinical preparation of rotundine is injection and oral.These two administrations, blood concentration fluctuation is big, and the brain concentration also can fluctuate thereupon, thereby is prone to produce untoward reaction such as drowsiness, dizzy, nauseating, and curative effect is of short duration.During oral administration, gastrointestinal tract is had certain zest in addition, gastrointestinal factors also has considerable influence to the absorption of medicine; Particularly, need take medicine for a long time, and oral drugs all pass through liver catabolism, so the long-term oral medication of chronic very easily causes drug induced hepatic injury treating chronic rest pain.The percutaneous dosing mode has the control medicine and sees through in the skin entering body with zero level speed, and blood drug level is steady; Avoid the influence of liver " first pass effect " and gastrointestinal tract physiologic factor; Keep long action time, reduce administration number of times; Convenient drug administration also can stop the distinct advantages of safe, long-acting, easy to use and Noninvasive such as administration at any time.Treat chronic rest pain, be fit to if can rotundine be processed transdermal delivery system, can improve the compliance of patient's medication with the steady administration of percutaneous dosing mode long time.In addition, the molecular weight of rotundine is 355.43, and 141～144 ℃ of fusing points are dissolved in chloroform, are slightly soluble in ethanol and ether, and are water insoluble, are soluble in dilute sulfuric acid, and the profit partition coefficient is 1.22, is comparatively ideal percutaneous dosing drug candidate.
Summary of the invention
The invention provides the respond well rotundine percutaneous drug administration preparation of a kind of drug osmotic.
The present invention also provides a kind of method for preparing of rotundine percutaneous drug administration preparation, and it is simple to have technology, is easy to control, is suitable for the advantage of suitability for industrialized production.
The present invention finds that rotundine is than dltetrahydropalmatine preparation percutaneous drug administration preparation preferably; The rotundine percutaneous drug administration preparation obviously is superior to existing dltetrahydropalmatine percutaneous drug administration preparation through the drug osmotic effect of skin, thereby has carried out further studying in great detail for the rotundine percutaneous drug administration preparation.
A kind of rotundine percutaneous drug administration preparation comprises following raw materials by weight percent: rotundine 0.05%-10% and Percutaneous absorption enhancer 2%-40%.
In order to reach better invention effect, preferably:
Described rotundine percutaneous drug administration preparation comprises following raw materials by weight percent: rotundine 0.5%-6% and Percutaneous absorption enhancer 4%-20%.
Described Percutaneous absorption enhancer can be selected one or more in azone, ethanol, Oleum menthae, menthol, eucalyptus oil, Borneolum Syntheticum, the propylene glycol etc. for use.
The dosage form of described rotundine percutaneous drug administration preparation can be solution (like supersaturated solution), percutaneous plaster, gel or ointment etc., considers the preferred percutaneous plaster of described dosage form, gel or ointment from the angle of being convenient to administration.
The method for preparing of described solution can adopt the conventional method for preparing of this area solution, processes the rotundine supersaturated solution as rotundine being dissolved in normal saline, adds Percutaneous absorption enhancer, makes solution.
Described percutaneous plaster is by backing layer, adherent layer and the drug storing layer between backing layer and adherent layer, and the framework material of described drug storing layer can be selected the polyacrylic acid pressure sensitive adhesive for use.
The method for preparing of described percutaneous plaster can adopt the conventional method for preparing of this area percutaneous plaster; As with framework material such as rotundine, Percutaneous absorption enhancer, polyacrylic acid pressure sensitive adhesive and an amount of solvent (like ethyl acetate) mix homogeneously and make medicine dissolution; Be coated on the backing that is tiled in horizontal glass plate after leaving standstill the degassing; After the oven dry, adherent layer gets final product in the covering.
Described gel is made up of following raw materials by weight percent:
Described ointment is made up of following raw materials by weight percent:
Described gel-type vehicle can be selected Carboxymethyl cellulose sodium or carbomer etc. for use.
Described oil phase substance is selected in vaseline, glyceryl monostearate, stearic acid, Cera Flava, liquid paraffin, the lanoline etc. one or more for use;
Described emulsifying agent is selected one or more in polysorbas20, polysorbate60, Tween 80, sorbester p18, sorbester p17, the sodium lauryl sulphate etc. for use;
Described other auxiliary agents comprise one or more in wetting agent, antiseptic, stabilizing agent, solubilizing agent, the pH regulator agent etc.
It is in the dilute sulfuric acid etc. of 1%-5% one or both that described solvent is selected water, concentration expressed in percentage by volume for use.
Described wetting agent is selected one or more in glycerol, propylene glycol, the carbamide etc. for use.
Described antiseptic is selected one or more among methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben, sodium benzoate, sorbitol, chlorobutanol, the sulfur Liu Gong etc. for use.
Described stabilizing agent is selected one or more in beta cyclodextrin, the beta cyclodextrin alkyl substituent (like hydroxypropyl beta cyclodextrin, dimethyl beta cyclodextrin etc.) etc. for use.
One or more among polyvinylpyrrolidone K30, polyvinylpyrrolidone K60, the polyvinylpyrrolidone K90 etc. are selected in described solubilizing agent for use.
Triethanolamine is selected in described pH regulator agent for use.
The adding of other auxiliary agents can increase stability of drug and dissolubility, simultaneously the toughness of scalable preparation.
The method for preparing of described gel may further comprise the steps:
(1) gel-type vehicle is used the partial solvent swelling, obtain the gel-type vehicle after the swelling;
(2) with rotundine with remaining dissolution with solvents after with step (1) in gel-type vehicle, Percutaneous absorption enhancer and other auxiliary agent mix homogeneously after the swelling, make gel.
The method for preparing of described ointment may further comprise the steps:
With rotundine with dissolution with solvents after with fusion after the oil phase substance mix homogeneously, make ointment after adding the Percutaneous absorption enhancer mix homogeneously;
Perhaps, rotundine is even with the solvent of emulsifying agent, other auxiliary agents and remainder with partial solvent dissolving back, add Percutaneous absorption enhancer, obtain water; Oil phase substance after the fusion is dropped to aqueous phase be stirred to coldly, make ointment.
Can be adding below 40 ℃, to reduce the volatilization of raw material as far as possible in the described raw material like volatile components such as Percutaneous absorption enhancer Oleum menthae, menthol, eucalyptus oil, Borneolum Syntheticums.
Compared with prior art, the present invention has following advantage:
Rotundine percutaneous drug administration preparation of the present invention has the advantages of good skin permeability, and transdermal effect is good, and percutaneous rate can reach 5-200 μ gcm
-2H
-1, can be used for analgesia and calm.The present invention at first investigated the Transdermal absorption situation of rotundine water saturation solution, yet the infiltration rate of its water saturation solution is merely 1.28 μ gcm in the transdermal dosage form design
-2H
-1(like Comparative Examples 1), and as external preparation, its water saturation solution uses very inconvenience.The present invention has obtained making medicine to have the rotundine percutaneous drug administration preparation that better transdermal penetration is formed through to the investigation of each component and the use of short penetrating agent, and the maximum infiltration rate of its paster dosage form can reach 7.83 μ gcm
-2H
-1(like embodiment 2), gel dosage form infiltration rate can reach 139.23 μ gcm
-2H
-1(like embodiment 5), ointment dosage form infiltration rate can reach 158.25 μ gcm
-2H
-1(like embodiment 7).
After the rotundine percutaneous preparation of the present invention administration, medicine sees through skin and gets in the body, can avoid liver first-pass effect and gastrointestinal is stimulated, and blood drug level is steady simultaneously, can reduce untoward reaction such as drowsiness, dizzy, nauseating.
Rotundine percutaneous drug administration preparation of the present invention, dosage form comprises percutaneous plaster, gel, ointment, dosage form is various, has a good application prospect.
The method for preparing of rotundine percutaneous drug administration preparation of the present invention is easy, is easy to control, and cost is low, need not special devices, is suitable for suitability for industrialized production.
Description of drawings
Drug accumulation infiltration capacity-the time graph (n=4) of the rotundine percutaneous plaster that Fig. 1 makes for embodiment 1.
Drug accumulation infiltration capacity-the time graph (n=4) of the rotundine percutaneous plaster that Fig. 2 makes for embodiment 2.
Drug accumulation infiltration capacity-the time graph (n=4) of the rotundine gel that Fig. 3 makes for embodiment 3.
Drug accumulation infiltration capacity-the time graph (n=4) of the rotundine gel that Fig. 4 makes for embodiment 4.
Drug accumulation infiltration capacity-the time graph (n=4) of the rotundine gel that Fig. 5 makes for embodiment 5.
Drug accumulation infiltration capacity-the time graph (n=4) of the rotundine ointment that Fig. 6 makes for embodiment 6.
Drug accumulation infiltration capacity-the time graph (n=4) of the rotundine ointment that Fig. 7 makes for embodiment 7.
Fig. 8 is the drug accumulation infiltration capacity-time graph (n=4) of rotundine supersaturated solution in the Comparative Examples 1.
Fig. 9 is the drug accumulation infiltration capacity-time graph (n=4) of dltetrahydropalmatine percutaneous plaster in the Comparative Examples 2.
The specific embodiment
Embodiment 1
Paster 100cm
2Inventory following:
Method for making: take by weighing rotundine; Add azone, menthol and eucalyptus oil, add polyacrylic acid pressure sensitive adhesive and an amount of ethyl acetate again, stirring is dissolved medicine fully; Be coated on the backing that is tiled in horizontal glass plate after leaving standstill the degassing; Dry about half an hour in the room temperature held, adherent layer in the covering makes 100cm
2The rotundine percutaneous plaster.
The permeability of male SD rat (by Zhejiang Academy of Medical Sciences Experimental Animal Center provide) the rat back isolated skin of the rotundine percutaneous plaster that adopts Valian-Chien two-chamber osmotic pool device to measure to make about to body weight 230g; Skin corium is towards receiving chamber; Stratum corneum side applies the pastille preparation; And fix the twoport of two Room with alligator clamp, in receiving chamber, add normal saline 4mL.Water temperature is respectively put one of starlike stirrer, electromagnetic agitation rotating speed 500rmin at 37 ± 0.5 ℃ in the control osmotic cell interlayer in the pond
-1Take out in the receiving chamber all liq as liquid to be measured in certain hour, and add into the isothermal normal saline of equivalent.Centrifugal (behind the 10000rpm * 6min), measure the content of rotundine in the acceptable solution and calculate infiltration rate with HPLC, the HPLC condition is: chromatographic column is C with the liquid of obtaining to be measured
18Column (Diamonsil, 4.6mm * 150mm, 5 μ m, Dikma), mobile phase is methanol-0.1% (percent by volume) phosphoric acid (transferring pH to 6.0 with triethylamine) (methanol and 0.1% phosphoric acid volume ratio are 75: 25), flow velocity is 1mLmin
-1The detection wavelength is 281nm.The rotundine percutaneous plaster infiltration rate that makes is 5.09 μ gcm
-2H
-1, its drug accumulation infiltration capacity-time graph such as Fig. 1.
Paster 100cm
2Inventory following:
Method for making: operation makes 100cm with embodiment 1
2The rotundine percutaneous plaster.
The body outer osmotic experimental implementation is with embodiment 1, and the rotundine percutaneous plaster infiltration rate that makes is 7.83 μ gcm
-2H
-1, its drug accumulation infiltration capacity-time graph such as Fig. 2.
Embodiment 3
Composition of raw materials is:
Method for making: get 0.4g carbomer 974 usefulness distilled water and be swelled into 10g; Other gets rotundine 1g is dissolved into 5g with 5% (mass percent) dilute sulfuric acid, stirs in the carbomer after the adding swelling, adds water solublity azone 0.8g again; Stir, drip triethanolamine 2g and make gel, stir; Become the translucent gels shape, make 17.8g rotundine gel.
The body outer osmotic experimental implementation is with embodiment 1, and the infiltration rate of the rotundine gel that makes is 10.23 μ gcm
-2H
-1, its drug accumulation infiltration capacity-time graph such as Fig. 3.
Composition of raw materials is:
Method for making: get rotundine 0.3g and be dissolved into 4g with 3% (percent by volume) dilute sulfuric acid; Adding 0.5g hydroxypropyl beta cyclodextrin, 1g polyvinylpyrrolidone K30 stir, and add water solublity azone 0.7g again, Oleum menthae 0.3g; Stir; Other gets the 1.0g sodium carboxymethyl cellulose and is swelled into the 7.5g adding with distilled water, stirs, and makes 14g rotundine gel.
The body outer osmotic experimental implementation is with embodiment 1, and the infiltration rate of the rotundine gel that makes is 57.06 μ gcm
-2H
-1, its drug accumulation infiltration capacity-time graph such as Fig. 4.
Composition of raw materials is:
Method for making: get rotundine 0.5g and be dissolved into 2.5g with 5% (mass percent) dilute sulfuric acid; Add 0.9g polyvinylpyrrolidone K90 and stir, other gets the 0.7g sodium carboxymethyl cellulose and is swelled into 5.5g with distilled water, adds; Stir; Add water solublity azone 0.8g again, stir, make 9.7g rotundine gel.
The body outer osmotic experimental implementation is with embodiment 1, and the infiltration rate of the rotundine gel that makes is 139.23 μ gcm
-2H
-1, its drug accumulation infiltration capacity-time graph such as Fig. 5.
Composition of raw materials is:
Method for making: get 8g white vaseline, 1g lanoline and 0.8g liquid paraffin and grind well with mortar; Other gets the 0.8g rotundine and becomes 5g with 4% (percent by volume) sulfuric acid dissolution, adds in the mortar to grind well, and adds azone 1g again; Grind well, make 15.8g rotundine ointment.
The body outer osmotic experimental implementation is with embodiment 1, and the infiltration rate of the rotundine ointment that makes is 11.01 μ gcm
-2H
-1, its drug accumulation infiltration capacity-time graph such as Fig. 6.
Embodiment 7
Composition of raw materials is:
Method for making: get 2.8g white vaseline and 1.8g glyceryl monostearate, in 80 ℃ water-bath, be fused into liquid, as oil phase; Other gets the 1.2g rotundine and becomes 6g with 4% (percent by volume) sulfuric acid dissolution, adds 2.8g Tween 80,4g carbamide, 2.4g glycerol and sodium benzoate 0.001g, stirs, and adds water solublity azone (being aqueous Azone) 1.8g, becomes water.Oil phase dripped constantly be stirred to coldly in synthermal aqueous phase, make 21.6g rotundine ointment.
The body outer osmotic experimental implementation is with embodiment 1, and the infiltration rate of the rotundine ointment that makes is 158.25 μ gcm
-2H
-1, its drug accumulation infiltration capacity-time graph such as Fig. 7.
Comparative Examples 1
Take by weighing rotundine 50mg and be dissolved in the normal saline, make the rotundine supersaturated solution.The body outer osmotic experimental implementation except skin corium towards receiving chamber; And fix the twoport of two chambers with alligator clamp; In receiving chamber, add normal saline 4mL; Add outside the supersaturation medicinal liquid 4mL to be measured in the supply chamber, all the other are with embodiment 1, and the infiltration rate of the rotundine supersaturated solution that makes is 1.28 μ gcm
-2H
-1, see table 1, its drug accumulation infiltration capacity-time graph such as Fig. 8.
Comparative Examples 2
The comparison of patch formulation:
Dltetrahydropalmatine is pressed the high formulated (embodiment 2) of permeability of rotundine, compares.Indicate: dltetrahydropalmatine prepares the high-load of paster can only reach 40mg/100cm
2, having crystallization above this content and separate out, infiltration rate can be lower.
Paster 100cm
2Inventory following:
Method for making: operation makes 100cm with embodiment 1
2The dltetrahydropalmatine percutaneous plaster.
The body outer osmotic experimental implementation is with embodiment 1, and the dltetrahydropalmatine percutaneous plaster infiltration rate that makes is 3.16 μ gcm
-2H
-1, its drug accumulation infiltration capacity-time graph such as Fig. 9.
Comparative Examples 3
Dltetrahydropalmatine is dissolved in the normal saline, makes the dltetrahydropalmatine supersaturated solution.The body outer osmotic experimental implementation is with Comparative Examples 1, and infiltration rate is seen table 1.
Comparative Examples 4
In the dltetrahydropalmatine supersaturated solution that Comparative Examples 3 makes, add a kind of in ethanol, azone, the propylene glycol respectively or add azone and propylene glycol simultaneously, obtain containing the alcoholic acid dltetrahydropalmatine supersaturated solution of 10% (percentage by weight) respectively, contain 1% (percentage by weight) azone the dltetrahydropalmatine supersaturated solution, contain 2% (percentage by weight) azone the dltetrahydropalmatine supersaturated solution, contain 5% (percentage by weight) azone the dltetrahydropalmatine supersaturated solution, contain 8% (percentage by weight) azone the dltetrahydropalmatine supersaturated solution, contain 10% (percentage by weight) azone the dltetrahydropalmatine supersaturated solution, contain 5% (percentage by weight) propylene glycol the dltetrahydropalmatine supersaturated solution, contain the dltetrahydropalmatine supersaturated solution of 10% (percentage by weight) propylene glycol, the dltetrahydropalmatine supersaturated solution that contains the dltetrahydropalmatine supersaturated solution of 5% (percentage by weight) azone+5% (percentage by weight) propylene glycol and contain 8% (percentage by weight) azone+5% (percentage by weight) propylene glycol.The body outer osmotic experimental implementation is with Comparative Examples 1, and infiltration rate is seen table 1.
In the rotundine supersaturated solution that Comparative Examples 1 makes, add a kind of in ethanol, azone, the propylene glycol respectively or add azone simultaneously and propylene glycol, simultaneously add azone and Oleum menthae, simultaneously add azone and eucalyptus oil, simultaneously add azone and menthol, add azone and Borneolum Syntheticum simultaneously, obtain containing the alcoholic acid rotundine supersaturated solution of 10% (percentage by weight) respectively, contain 1% (percentage by weight) azone the rotundine supersaturated solution, contain 2% (percentage by weight) azone the rotundine supersaturated solution, contain 5% (percentage by weight) azone the rotundine supersaturated solution, contain 8% (percentage by weight) azone the rotundine supersaturated solution, contain 10% (percentage by weight) azone the rotundine supersaturated solution, contain 5% (percentage by weight) propylene glycol the rotundine supersaturated solution, contain 10% (percentage by weight) propylene glycol the rotundine supersaturated solution, contain 5% (percentage by weight) azone+5% (percentage by weight) propylene glycol the rotundine supersaturated solution, contain 8% (percentage by weight) azone+5% (percentage by weight) propylene glycol the rotundine supersaturated solution, contain 2% (percentage by weight) Oleum menthae+8% (percentage by weight) azone the rotundine supersaturated solution, contain 5% (percentage by weight) Oleum menthae+8% (percentage by weight) azone the rotundine supersaturated solution, contain 2% (percentage by weight) eucalyptus oil+8% (percentage by weight) azone the rotundine supersaturated solution, contain 5% (percentage by weight) eucalyptus oil+8% (percentage by weight) azone the rotundine supersaturated solution, contain 5% (percentage by weight) menthol+8% (percentage by weight) azone the rotundine supersaturated solution, contain the rotundine supersaturated solution of 5% (percentage by weight) Borneolum Syntheticum+8% (percentage by weight) azone.The body outer osmotic experimental implementation is with Comparative Examples 1, and infiltration rate is seen table 1.
Table 1 penetration enhancer is to dl-THP and the short effect relatively (n=4) of passing through of l-THP
Can find out that from the result of table 1 under identical condition, rotundine obviously is superior to dltetrahydropalmatine through the drug osmotic effect of skin.
The present invention describes through above description and embodiment, more than is described as nonrestrictively, does not limit claim scope of the present invention.
Claims (5)
1. a rotundine percutaneous drug administration preparation comprises following raw materials by weight percent: rotundine 0.05%-10% and Percutaneous absorption enhancer 2%-40%;
Described Percutaneous absorption enhancer is one or more in azone, ethanol, Oleum menthae, menthol, eucalyptus oil, Borneolum Syntheticum, the propylene glycol;
The dosage form of described rotundine percutaneous drug administration preparation is solution, percutaneous plaster, gel or ointment;
Described percutaneous plaster is made up of backing layer, adherent layer and the drug storing layer between backing layer and adherent layer, and the framework material of described drug storing layer is the polyacrylic acid pressure sensitive adhesive;
Described gel is made up of following raw materials by weight percent:
Described gel-type vehicle is Carboxymethyl cellulose sodium or carbomer;
Described other auxiliary agents comprise one or more in wetting agent, antiseptic, stabilizing agent, solubilizing agent, the pH regulator agent;
Described solvent is that water, concentration expressed in percentage by volume are one or both in the dilute sulfuric acid of 1%-5%;
Described ointment is made up of following raw materials by weight percent:
Described oil phase substance be in vaseline, glyceryl monostearate, stearic acid, Cera Flava, liquid paraffin, the lanoline one or more;
Described emulsifying agent is one or more in polysorbas20, polysorbate60, Tween 80, sorbester p18, sorbester p17, the sodium lauryl sulphate;
Described other auxiliary agents comprise one or more in wetting agent, antiseptic, stabilizing agent, the solubilizing agent;
Described solvent is that water, concentration expressed in percentage by volume are one or both in the dilute sulfuric acid of 1%-5%.
2. rotundine percutaneous drug administration preparation according to claim 1 is characterized in that, comprises following raw materials by weight percent: rotundine 0.5%-6% and Percutaneous absorption enhancer 4%-20%.
3. rotundine percutaneous drug administration preparation according to claim 1 is characterized in that, described wetting agent is one or more in glycerol, propylene glycol, the carbamide;
Perhaps, described antiseptic is one or more in methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben, sodium benzoate, sorbitol, chlorobutanol, the tribute of sulfur willow;
Perhaps, described stabilizing agent is one or more in beta cyclodextrin, the beta cyclodextrin alkyl substituent;
Perhaps, described solubilizing agent is one or more among polyvinylpyrrolidone K30, polyvinylpyrrolidone K60, the polyvinylpyrrolidone K90;
Perhaps, described pH regulator agent is a triethanolamine.
4. the method for preparing of rotundine percutaneous drug administration preparation according to claim 1 is characterized in that, the dosage form of described rotundine percutaneous drug administration preparation is a gel, may further comprise the steps:
(1) gel-type vehicle is used the partial solvent swelling, obtain the gel-type vehicle after the swelling;
(2) with rotundine with remaining dissolution with solvents after with step (1) in gel-type vehicle, Percutaneous absorption enhancer and other auxiliary agent mix homogeneously after the swelling, make gel.
5. the method for preparing of rotundine percutaneous drug administration preparation according to claim 1 is characterized in that, the dosage form of described rotundine percutaneous drug administration preparation is an ointment, may further comprise the steps:
With rotundine with dissolution with solvents after with fusion after the oil phase substance mix homogeneously, make ointment after adding the Percutaneous absorption enhancer mix homogeneously;
Perhaps, rotundine is even with the solvent of emulsifying agent, other auxiliary agents and remainder with partial solvent dissolving back, add Percutaneous absorption enhancer, obtain water; Oil phase substance after the fusion is dropped to aqueous phase be stirred to coldly, make ointment.
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| CN101518531A (en) * | 2009-01-21 | 2009-09-02 | 甘肃奇正藏药有限公司 | Analgesic anti-inflammatory composite medicament and method for preparing same |
| CN101703492A (en) * | 2009-01-14 | 2010-05-12 | 甘肃奇正藏药有限公司 | Tetrahydropalmatine transdermal patch and preparation method thereof |
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| CN101703492A (en) * | 2009-01-14 | 2010-05-12 | 甘肃奇正藏药有限公司 | Tetrahydropalmatine transdermal patch and preparation method thereof |
| CN101518531A (en) * | 2009-01-21 | 2009-09-02 | 甘肃奇正藏药有限公司 | Analgesic anti-inflammatory composite medicament and method for preparing same |
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| 徐剑等.延胡索乙素贴剂处方研究.《中南药学》.2008,第6卷(第2期),第148-150页. * |
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