CN105748408A - Micro-emulsion and micro-emulsion preparation, and preparation methods thereof - Google Patents
Micro-emulsion and micro-emulsion preparation, and preparation methods thereof Download PDFInfo
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Abstract
The invention discloses a micro-emulsion, a preparation method thereof, a micro-emulsion preparation containing the micro-emulsion, and a preparation method of the preparation, and belongs to the field of medicinal preparations. The micro-emulsion is prepared from traditional Chinese medicine extract, an oil phase, an emulsifier, a co-emulsifier and a water phase. The micro-emulsion is processed to preferably prepare an external use gel. The traditional Chinese medicine extract transdermal drug delivery external preparation has unique advantages, and a novel vesicle administration system is applied to increase the transdermal absorption of medicines, enhance clinic curative effects and avoid toxic and side effects of oral administration and injection administration.
Description
Technical field
The present invention relates to a kind of Chinese medicine extract microemulsion and preparation method thereof, the preparation containing Chinese medicine extract microemulsion and preparation method thereof, belong to field of pharmaceutical preparations.
Background technology
Percutaneous dosing (TransdermalDeliverySystem, TDS) system is referred to and is administered by skin surface, to reach a kind of route of administration of locally or systemically therapeutical effect.Suitable percutaneous drug administration preparation, can control speed and the degree of percutaneous penetration of drugs so that it is can rapidly, specifically be delivered to shallow table infection site after administration and play curative effect, have certain targeting meaning；Simultaneously, owing to drug targeting is enriched in epidermal area, so that it is less or penetrate into skin corium hardly, medicine is avoided to be absorbed into rapidly systemic circulation by blood capillary further after penetrating into skin corium, reduce the toxic and side effects caused by systemic Absorption and untoward reaction, improve medication safely, effectively and clinical compliance.
Microemulsion (Microemulsion) is to be mixed and the isotropism spontaneously formed, colloidal dispersion system transparent, thermodynamically stable by proper proportion by water, oil, emulsifying agent and co-emulsifier, in recent years, microemulsion obtains research widely and application with the application advantage of its uniqueness in transdermal delivery system.Additionally, as pharmaceutical carrier, microemulsion also has the advantage that microemulsion is more stable, having increase drug effect, the advantage reducing toxic and side effects, is a kind of novel pharmaceutical carrier.Owing to microemulsion containing larger amount of surfactant, so having excellent transdermal penetration performance, for the research and development of Chinese medicine especially toxic traditional Chinese medicine transdermal targeting Novel Drug Delivery Systems, significant.
Notable for Chinese medicine especially toxic traditional Chinese medicine effective site or composition clinical efficacy, but it is oral very big with drug administration by injection toxic and side effects, dangerous, significantly limit it in clinical application, percutaneous dosing external preparation has the advantage of uniqueness, application novel microemulsion gel delivery system, improve the Transdermal absorption of medicine, solve the medicine toxic and side effects when being administered orally with drug administration by injection, after effective ingredient in Chinese or composition are encapsulated with microemulsion, targeting due to self, liver, spleen site concentration is higher, Chinese medicine extract can be avoided the heart, the infringement of the organs such as kidney, alleviate the toxic action to central nervous system, and curative effect can be reached by less dosage, improve the safety of medication simultaneously, increase the compliance of clinical administration patient, to have broad application prospects, good social benefit and considerable economic benefit can be produced.
Summary of the invention
It is an object of the invention to provide preparation of Chinese medicine extract microemulsion and preparation method thereof and Chinese medicine extract microemulsion and preparation method thereof.
The present invention is achieved by the following technical solutions:
Chinese medicine extract microemulsion is made up of following weight parts prescription:
Preferably it is made up of following weight parts prescription:
More preferably it is made up of following weight parts prescription:
Described Chinese medicine extract can be the one in Strychnos alkaloid, strychnine, Venenum Bufonis total lactones, Venenum Bufonis total alkaloids, sinomenine, sinoacutine, cantharidin, tripterygium total terpenoids, podophyllotoxin, Rhizoma Curcumae extract, Oleum Curcumae, Fructus Capsici extract, capsaicin, arteannuin, Fructus Psoraleae extract.
Oil phase refers to one or more in soybean oil, Oleum Arachidis hypogaeae semen, Oleum Ricini, oleic acid, linoleic acid, ethyl oleate, Ethyl linoleate, isopropyl myristate, isopropyl laurate, Monooctamoin, medium-chain triglycerides；
Preferred oil acetoacetic ester, Ethyl linoleate, oleic acid, medium-chain triglycerides；Wherein, medium-chain triglycerides belongs to fatty acid mixed triglyceride, refers to the supersaturation fatty acid (C that carbochain is longer8H17COOH～C18H37COOH) triglyceride, specifically refers to caprylic/capric triglyceride.
Emulsifying agent refers to one or more in polyoxyethylene-type and polyol type, specifically refers to one or more in soybean phospholipid, lecithin, caprylic/capric polyethyleneglycol glyceride, polyoxyethylene castor oil, polyoxyethylene aliphatic alcohol ether, polyoxyethylene hydrogenated Oleum Ricini, tween, span；Wherein, it is preferable that tween, polyoxyethylene castor oil, span；Polyoxyethylene castor oil refers to polyoxyethylene castor oil RH40, polyoxyethylene castor oil EL-35, more preferably polyoxyethylene castor oil EL-35；Tween refers to polysorbas20, polysorbate40, polysorbate60, Tween 80, more preferably Tween 80；Span refers to span 20, span 40, sorbester p18, sorbester p17, more preferably sorbester p17.Co-emulsifier refers to one or more in propylene glycol, glycerol, isopropanol, n-butyl alcohol, ethanol, ethylene glycol, tween, glycerol, Polyethylene Glycol, preferred propylene glycol, ethanol, Polyethylene Glycol, wherein Polyethylene Glycol more preferably PEG400 (PEG400).
The best is preferably:
Oil phase is ethyl oleate, emulsifying agent be polyoxyethylene castor oil EL-35, co-emulsifier is PEG400；
Or oil phase is caprylic/capric triglyceride, emulsifying agent is Tween 80, co-emulsifier is PEG400.
Aqueous phase refers to one or more in water for injection, phosphate buffer, carbonate buffer solution, normal saline and G/NS injection, preferred water for injection, pH7.4 phosphate buffer, pH6.8 phosphate buffer, the more preferably phosphate buffer of water for injection, pH7.4.
The ratio Km of the minimum emulsifying agent and co-emulsifier that can form microemulsion in the present invention is 2: 8-8: 2, it is preferable that Km is 4: 6-7: 3；More preferably Km is 4: 6-5: 5, and best preferably Km is 4.5: 5.5.
Forming the aqueous phase of microemulsion with the ratio (W/A) of co-emulsifier is 0.21-0.62, and more preferably (W/A) is 0.40-0.62, and more preferably (W/A) is 0.5-0.6.
Chinese medicine extract microemulsion of the present invention can take paddling process, ultrasonic method, high pressure homogenization to be prepared from, it is preferable that following preparation method:
Weigh appropriate emulsifying agent, co-emulsifier mixing, add Chinese medicine extract, mixing, stirring so that it is fully dissolve, then mix with oil phase, stir, be slowly added into appropriate aqueous phase, stir simultaneously, obtain Chinese medicine extract microemulsion.
The preparation method of Chinese medicine extract microemulsion of the present invention can also be:
Weigh appropriate emulsifying agent, co-emulsifier mixing, add Chinese medicine extract, ultrasonic so that it is fully to dissolve, then mix with oil phase, ultrasonic uniformly after, continue ultrasonic, be slowly added into appropriate aqueous phase simultaneously, to obtain final product.
The preparation method of Chinese medicine extract microemulsion of the present invention can also be:
Weigh appropriate emulsifying agent, co-emulsifier, oil phase, aqueous phase and Chinese medicine extract, add in high pressure homogenizer and carry out high pressure homogenize, obtain Chinese medicine extract microemulsion.
The mean diameter of the microemulsion that method made above prepares is 10-100nm, and Zeta potential is-10 to-50mV.
The Chinese medicine extract microemulsion obtained can be prepared for oral formulations or external preparation further, it is preferable that external preparation, it is preferred that gel, ointment, patch, spray, aerosol etc., is further preferably gel.
Chinese medicine extract micro emulsion gels is made up of the component of following weight parts:
Chinese medicine extract microemulsion 0.5-150 part, thickening agent 0.1-30 part, wetting agent 0.1-80 part, pH adjusting agent 0-30 part, transdermal agent 0-15 part, preservative 0-10 part, aqueous phase 1-100 part.
Preferably it is made up of the component of following weight parts:
Chinese medicine extract microemulsion 1-100 part, thickening agent 0.5-10 part, wetting agent 1-30 part, pH adjusting agent 0.1-10 part, transdermal agent 1-10 part, preservative 0.1-1.5 part, aqueous phase 1-100 part.
Wherein, thickening agent is one or more in cross-linked polypropylene resin class, cross-linked polypropylene resin variety classes salt and derivant, hydroxypropyl methylcellulose, xanthan gum；Cross-linked polypropylene resin class thickening agent refers to Carbopol 941, Carbomer974, carbomer940, Carbopol, Carbomer981.
Wetting agent refers to one or more in glycerol, propylene glycol, isopropanol, hyaluronic acid, it is preferable that glycerol, propylene glycol.
PH adjusting agent refers to organic bases or inorganic base；Organic bases pH adjusting agent refers to triethanolamine, triethylamine, diethylamine, lauryl amine；Inorganic base pH adjusting agent refers to sodium hydroxide, sodium bicarbonate, sodium carbonate.Preferred sodium hydroxide, triethylamine.
Transdermal agent refers to one or more in azone, menthol, quintessence oil, dimethyl sulfoxide, propylene glycol, Semen Myristicae isopropyl acid esters, N-Methyl pyrrolidone, Gelucire 44/14, polyglyceryl fatty acid ester, oleic acid polyethyleneglycol glyceride, Labraso, it is preferable that azone, N-Methyl pyrrolidone.
Preservative refers to one or more in potassium sorbate, sorbic acid, ethyl hydroxybenzoate, propyl hydroxybenzoate, methyl hydroxybenzoate, phenol, it is preferable that ethyl hydroxybenzoate, propyl hydroxybenzoate, methyl hydroxybenzoate.
The preparation method of Chinese medicine extract micro emulsion gels is:
Take thickening agent, wetting agent, transdermal agent, preservative, add water, pH adjusting agent, make gel-type vehicle and obtained Chinese medicine extract microemulsion mixing, stir, obtain Chinese medicine extract micro emulsion gel.
The preparation method of Chinese medicine extract microemulsion formulation can also be:
Take Chinese medicine extract microemulsion appropriate, prepare into various external preparation according to a conventional method.
Particularly as follows:
Take Chinese medicine extract microemulsion appropriate, prepare into ointment according to a conventional method.
Take Chinese medicine extract microemulsion appropriate, prepare into patch according to a conventional method.
Take Chinese medicine extract microemulsion appropriate, prepare into spray according to a conventional method.
Take Chinese medicine extract microemulsion appropriate, prepare into aerosol according to a conventional method.
The crucial index evaluating microemulsion is the medication amount in microemulsion and drug loading, and in usual microemulsion, drug loading is more many, and osmotic gradient is more high, and percutaneous rate is more high accordingly.The present invention, for Strychnos alkaloid, has carried out experimentation with regard to above-mentioned microemulsion formulation composition and process conditions, specific as follows:
1, the primary dcreening operation of oil phase/emulsifying agent/co-emulsifier
Relatively Strychnos alkaloid dissolubility in different oil phase/emulsifying agent/co-emulsifier, oil phase, emulsifying agent and the co-emulsifier that screening dissolubility is bigger, result is in Table 1:
Table 1 Strychnos alkaloid dissolubility in different oil phase/emulsifying agent/co-emulsifier compares
As shown in Table 1, Strychnos alkaloid all has certain dissolubility at the above-mentioned oil phase/emulsifying agent/co-emulsifier enumerated, difference according to its solubility values, preferred oil acetoacetic ester, caprylic/capric triglyceride, oleic acid, Ethyl linoleate are as oil phase, preferred Tween 80, polyoxyethylene caster RH40/ polyoxyethylene castor oil EL-35, sorbester p17 are as emulsifying agent, it is preferable that propylene glycol, ethanol and PEG400 are as co-emulsifier.
2, the screening of microemulsion combination
Respectively above preferred oil phase, emulsifying agent and co-emulsifier are adopted the combination (tentative proportions is oil phase: emulsifying agent: co-emulsifier=1: 6: 3) that the mode of independent assortment carries out blank microemulsion, oil phase stirring is added after emulsifying agent and co-emulsifier being mixed in proportion, while stirring, it is added dropwise over water for injection, observe the formation of microemulsion situation of its whole system: clear and bright, the colloid solution of opalescence (light blue) is formation microemulsion, and milky white liquid is Emulsion state.Clarification agalactia light state is gel state.Adding and adopt different emulsifiers, co-emulsifier to prepare blank microemulsion with oil phase combination respectively, investigate formation of microemulsion situation, result is in Table 2:
The different oil phase of table 2, emulsifying agent and co-emulsifier form microemulsion situation
As shown in Table 2, above combination continuously adds aqueous phase after all can forming microemulsion or forming gel state to be occurred without muddiness, according to above-mentioned experimental technique, it is preferred that other possible independent assortments of oil phase, emulsifying agent and co-emulsifier have also been obtained similar result.
3, prepared by the phasor of microemulsion combination
The combination of the microemulsion of table 2 is carried out pseudo-ternary phase diagram respectively prepare, compare the size in each microemulsion region.
Method: fixing emulsifying agent: ratio=2 of co-emulsifier: 1, after obtaining blended emulsifier according to this ratio blended emulsifier and co-emulsifier, according to oil phase: mixed emulsifier proportion 1: 9,2: 8,3: 7,4: 6,3: 7,2: 8,9: 1 ratio mixing, under room temperature, drip water for injection while stirring, until formation of microemulsion, record consumes the weight of water.Calculate the percentage ratio of three-phase (water, oil, mixed emulsifying agent), prepare the ternary phase diagrams of microemulsion.
By comparing, it is preferable that the following combination that microemulsion region is bigger:
(1) ethyl oleate, polyoxyethylene castor oil EL-35, propylene glycol, water for injection；
(2) ethyl oleate, polyoxyethylene castor oil EL-35, ethanol, water for injection；
(3) ethyl oleate, polyoxyethylene castor oil EL-35, PEG400, water for injection；
(4) caprylic/capric triglyceride, polyoxyethylene castor oil EL-35, PEG400, water for injection；
(5) ethyl oleate, Tween 80, PEG400, water for injection；
(6) caprylic/capric triglyceride, Tween 80, PEG400, water for injection；
(7) caprylic/capric triglyceride, sorbester p17, propylene glycol, water for injection.
(8) Ethyl linoleate, Tween 80, PEG400, water for injection；
(9) oleic acid, polyoxyethylene castor oil RH40, PEG400, water for injection；
(10) Ethyl linoleate, polyoxyethylene castor oil EL-35, propylene glycol, water for injection；
4, microemulsion combination is preferably
According to oil phase: emulsifying agent: co-emulsifier: aqueous phase=4: the ratio of 6: 3: 6 will prepare microemulsion sample with 5 combinations of going forward, and carry out the comparison of Drug loading capacity.
Method: after emulsifying agent, co-emulsifier being mixed in proportion, overdose of medicine thing is added stirring after wherein mixing and makes it abundant, after carrying out mixing with oil phase again and stirring, while stirring is slowly added into water for injection simultaneously, supernatant microemulsion is taken appropriate after being centrifuged 30min by 5000rpm after preparing microemulsion, add after methanol is cleared up completely and measure content, relatively the drug loading of different microemulsion combination, is specifically shown in table 3.
The drug loading of the different microemulsion combination of table 3 is investigated
As shown in Table 3, ethyl oleate is as oil phase, oxygen ethylene castor oil EL-35 is as emulsifying agent, PEG400 is as co-emulsifier, and water for injection is relatively big as the micro emulsion drug carrying amount that aqueous phase is obtained, according to above-mentioned experimental technique, the combination of above-mentioned 6-10 is carried out equally the investigation of drug loading, result caprylic/capric triglyceride is as oil phase, and Tween 80 is as emulsifying agent, PEG400 as co-emulsifier, and water for injection is bigger as the micro emulsion drug carrying amount that aqueous phase is obtained.Below this microemulsion formulation is carried out ratio optimization.
5, microemulsion formulation ratio optimization
Using ethyl oleate as oil phase, oxygen ethylene castor oil EL-35 is as emulsifying agent, and PEG400 is as co-emulsifier, and water for injection is chosen as aqueous phase, carries out the screening of microemulsion formulation emulsifying agent weight ratio, co-emulsifier weight ratio, oil phase weight ratio, aqueous phase weight ratio.
(1) Km value (forming minimum emulsifying agent and the co-emulsifier of microemulsion) is determined
The ratio Km of minimum emulsifying agent and the co-emulsifier that can form microemulsion is determined by tradition ternary phase diagrams.Method: weigh polyoxyethylene castor oil EL-35: PEG400 (w/w) and be about 9: 1,8: 2,7: 3,6: 4,5: 5,4: 6,3: 7,2: 8 and 1: 9, total amount is fixed, add the amount stirring of ethyl oleate 50%, distillation is added in (25 ± 1) DEG C, observe change of shape, the classical ternary phase diagrams of polyoxyethylene castor oil EL-35/PEG400/ water can be obtained.Determine the ratio (Km) of polyoxyethylene castor oil EL-35/PEG400 according to phasor situation, be specifically shown in table 4.
Spade-shaped farm tool used in ancient China and the character excessively of each ratio formation of microemulsion of table 4
As shown in Table 4, the ratio Km of the emulsifying agent and co-emulsifier that can form microemulsion is 2: 8-8: 2, it is preferable that 4: 6-7: 3.
In order to it is preferred that Km value, it is contemplated that the microemulsion region of 2: 8,3: 7 is less, contrasts emulsifying agent respectively: co-emulsifier=5: 5,4.5: 5.5,4.3: 5.7,4: 6, relatively different km form consumption and the character of the required emulsifying agent of microemulsion, are specifically shown in table 5.
Table 5 compares different km and prepares character and the emulsifier of microemulsion
As shown in Table 5, form the ratio of the emulsifying agent of microemulsion and co-emulsifier preferably 4: 6-5: 5, form the character of microemulsion and the ratio of required emulsifying agent according to above four microemulsion formulation, be more preferably Km=4.5: 5.5.
(2) W/A (forming the aqueous phase of microemulsion and the ratio-of co-emulsifier) determines
Fixing Km, investigates the ratio (W/A) of the water for injection in ethyl oleate, polyoxyethylene castor oil EL-35, PEG400, water for injection system formation microemulsion with co-emulsifier.
Fixing Km=4.5: 5.5, after obtaining mixed emulsifying agent in this ratio blended emulsifier and co-emulsifier standby, take oil phase (ethyl oleate) and mixed emulsifying agent (polyoxyethylene castor oil respectively, PEG400) (w/w) is about 9: 1, 8: 2, 7: 3, 6: 4, 5: 5, 4: 6, 3: 7, 2: 8, 1: 9, fixed total amount, in dropwise at room temperature instillation water for injection to Character change, form microemulsion, the water yield that record adds, calculate the percentage ratio of each phase, ethyl oleate/mixed emulsifying agent (polyoxyethylene castor oil can be obtained, the classical triangle phasor of PEG400)/water for injection.Calculate the ratio (W/A) determining water for injection/PEG400 according to phasor situation, be specifically shown in table 6.
Table 6 is prepared the character of microemulsion and forms the W/A investigation of microemulsion
As shown in Table 6, the oil phase of microemulsion and the ratio of blended emulsifier are between 1: 9-5: 5, ratio (W/A) 0.21-0.62 of water for injection and co-emulsifier, it is more preferably that the oil phase of microemulsion and the ratio of blended emulsifier are 1: 9-4: 6, ratio (W/A) 0.40-0.62 of water for injection and co-emulsifier, more preferably 0.5-0.6.
(3) prescription it is preferred that
Method: fixing W/A=0.4, W/A=0.5, W/A=0.6, after proportionally hybrid injection water and co-emulsifier obtain mixed solution respectively, according to emulsifying agent: the ratio of oil phase is 1: 9,2: 8,3: 7,4: 6,3: 7,2: 8,9: 1 ratio mixing, total amount is fixed, the mixed solution of dropping water for injection and co-emulsifier while stirring, examine Character change and record the water for injection of consumption and the amount of co-emulsifier mixed solution, until solution character is constant, record final state, it is determined that optimization formula, is specifically shown in table 7.
The comparison of the Strychnos alkaloid microemulsion that the supplementary material of table 7 Different Weight part prepares
From above research, the supplementary material of Different Weight part described in the present invention all can prepare that drug loading is higher, the good Strychnos alkaloid microemulsion of stability, wherein, with Chinese medicine extract 1-5 part, oil phase 15-25 part, emulsifying agent 20-40 part, co-emulsifier 10-20 part, aqueous phase 30-75 part the Strychnos alkaloid micro emulsion drug carrying amount for preparing of usage ratio high, good stability, particle diameter is little.
6, the selection of aqueous phase
According to preferred best prescription portfolio ratio blended emulsifier, co-emulsifier, oil phase and same amount of medicine above, add different aqueous phases (water for injection, phosphate buffer (pH7.4, pH6.8), carbonate buffer solution, normal saline) while stirring to quantitatively, it is centrifuged 30min by 5000rpm after preparing microemulsion, observe the state of centrifugal rear microemulsion, medicine whether is had to precipitate out, and measure its stability parameter KE by centrifugation spectrophotometry, it is specifically shown in table 8.
The microemulsion of the preparation of the different aqueous phase of table 8 compares
As shown in Table 8, the stability of microemulsion prepared by relatively above different aqueous phases, it is more or less the same, therefore aqueous phase optional water for injection, pH7.4 phosphate buffer, pH6.8 phosphate buffer, carbonate buffer solution, normal saline.Afterwards its particle size distribution is investigated and find, it is preferred that aqueous phase is water for injection, phosphate buffer.Preferred aqueous phase is the phosphate buffer of water for injection, pH7.4.
7, preparation method
The preparation method of microemulsion mainly has paddling process, ultrasonic method, high pressure homogenization method etc., using ethyl oleate, polyoxyethylene castor oil EL, PEG400, water for injection as adjuvant, fixing above preferred ratio investigates Strychnos alkaloid microemulsion prepared by distinct methods respectively, using stability and particle size distribution as inspection target, investigate its preparation method, be specifically shown in table 9.
Microemulsion prepared by the different preparation method of table 9 compares
As shown in Table 9, paddling process, ultrasonic method, three kinds of methods of high pressure homogenization method all can be prepared microemulsion, but consider in conjunction with production according to size and distribution, it is preferable that paddling process and high pressure homogenization method, and from producing angle, paddling process and high pressure homogenization method are all relatively suitable for big production.
Detailed description of the invention
Compared with prior art, microemulsion gel preparation of the present invention has the advantages that
1) present invention passes through prescription screening and optimization, and under selected prescription composition, the microemulsion that Chinese medicine extract, emulsifying agent, co-emulsifier, oil phase, aqueous phase are formed under the process conditions is uniform, clear and bright, Thermodynamically stable；
2) Chinese medicine extract microemulsion is prepared into gel preparation by the present invention, improves its adhesiveness to skin, and percutaneous dosing is convenient, it is easy to coating uniformly, and not pollution clothes, it is easy to clean；
3) Chinese medicine extract microemulsion gel preparation of the present invention, compare with Chinese medicine extract gel, absorb to peak concentration rapidly in the articular cavity of 0-1.625h inherence after percutaneous dosing, start after 2 hours slowly to eliminate, at the 8h drug level kept relative stability, the Transdermal absorption of medicine can be more beneficial for；
4) Chinese medicine extract microemulsion gel preparation of the present invention, compares with Chinese medicine extract gel, and effective dose is relatively low, improves the safety of Chinese medicine extract clinical practice；
5) Chinese medicine extract microemulsion gel preparation of the present invention, compares rapid-action with Chinese medicine extract gel, and release is steady, has certain slow releasing function；
Secondly 6) Chinese medicine extract microemulsion gel preparation of the present invention, compares with Chinese medicine extract gel, and after percutaneous dosing, Chinese medicine extract is distributed mainly on liver, kidney, lung, stomach, small intestinal, is heart, joint, little in brain, muscle, Fat Distribution.After 6h, except hepatic and renal tissue, the drug level in stomach, small intestinal raises, targeting due to microemulsion is described, medicine liver, the enrichment of spleen tissue can being helped, reducing its concentration in heart, brain, thus reducing maincenter toxicity and the cardiac toxicity of Chinese medicine extract；
7) present invention application microemulsion this there is the pharmaceutical carrier of good biocompatibility, first Chinese medicine extract is prepared for microemulsion, then prepare into gel preparation percutaneous dosing again, compare with Chinese medicine extract gel, microemulsion gel preparation has the feature of transdermal target slow-release, and drug effect dosage is low, it is contemplated that untoward reaction greatly reduce, clinical safety improves, and integrated application index is high.
The beneficial effect of of the present invention compositions is expanded on further below by test example for Strychnos alkaloid micro emulsion gel.
Experimental example 1: Freund's complete adjuvant is caused the acute swelling of rat paw and the impact of pain index of Response by Strychnos alkaloid micro emulsion gel
1, experimental technique
1.1 rat AA model inductions
By BCG80 DEG C, 1h inactivation after, be made into 10mg.ml with autoclaved liquid paraffin-1Emulsion, be fully ground, mix, obtain Freund's complete adjuvant (FCA) skin injection FCA0.1ml in the left back whole toe of every Mus and cause inflammation.
1.2 animal packet and dosage regimens
Rat random packet 8 groups: normal group；AA model group；Strychnos alkaloid micro emulsion gel high dose (25mg.kg-1) group；Dosage (12.5mg.kg in Strychnos alkaloid micro emulsion gel-1) group；Strychnos alkaloid micro emulsion gel low dosage (6.25mg.kg-1) group；Strychnos alkaloid gel high dose (25mg.kg-1) group；Dosage group (12.5mg.kg in Strychnos alkaloid gel-1) group；Strychnos alkaloid gel low dosage (6.25mg.kg-1) group.Except normal group, all the other are respectively organized and all cause inflammation with skin injection FCA0.1ml in the left back whole toe of the every Mus of FCA.
Namely occurring acute local inflammation after Yu Zhiyan, within the 2nd day, give oilpaper parcel ointment, spread on the left back foot of rat, then wrap up with medical proof fabric, it is prevented that medicine comes off, normal group and model group are not administered.Remove adhesive plaster after 6h, clean the left foot of rat.
1.3 Articular swelling measure
Rat measured on foot volumetric type meter respectively to scorching forward and backward 3rd day and causes scorching parapodum volume, was rat paw edema degree time this with the difference to scorching front foot volume sometime to inflammation.
1.4 bend arthralgia scoring
Ankle joint pain experiments methods of marking: put into by rat in special Mus cylinder, retreats and afterbody stretches out outside cylinder, measures after stablizing a few minutes, and to sole side, the side ankle joint of slow flexing animal, carried out once every 5 seconds, totally 5 times.When bending joint, there is very brief and significantly contracting lower limb reaction or shout and comment 1 point in animal, and reactionless 0 point, the scoring of every side ankle joint is that 0-5 divides.
2, result
2.1 impacts on AA rat articular swelling
AA model after immunity 1d, former parapodum swelling and the obvious increase of normal group；Compared with model group, 3 dosage groups of Strychnos alkaloid micro emulsion gel (6.25,12.5 and 25mg.kg-1) at d3, AA rat primary is sent out parapodum swelling by inhibitory action；Strychnos alkaloid gel high dose group (25mg.kg-1) also can alleviate AA rat primary foot swelling.Suppress AA rat primary foot swelling effect obvious.
FCA is caused the impact of former side acute ankle swelling of rat paw inflammation by 1 two kinds of gels of table
* P < 0.5vsAAgroup, * * * P < 0.001vsAAgroup
As shown in Table 1, Strychnos alkaloid micro emulsion gel basic, normal, high dosage group all can suppress the acute pedal swelling caused by FCA, and ordinary gel only has high dose group could suppress the acute pedal swelling caused by FCA, show that the effective dose relatively ordinary gel of Strychnos alkaloid micro emulsion gel is low, improve the safety of Strychnos alkaloid clinical practice.
AA rat is bent the impact of arthralgia scoring by 2.2
In the same time, the pain scores difference of AA model group and normal group has highly significant (P < 0.01)；3 dosage groups of Strychnos alkaloid micro emulsion gel (6.25,12.5 and 25mg.kg-1) and Strychnos alkaloid gel high dose group (25mg.kg-1) can substantially ease the pain reaction.
FCA is caused the impact of former lateroflexion arthralgia scoring of rat paw inflammation by 2 two kinds of gels of table
* P < 0.5vsAAgroup, * * * P < 0.001vsAAgroup
As shown in Table 2, the basic, normal, high dosage group of Strychnos alkaloid micro emulsion gel all can suppress to bend arthralgia, and ordinary gel only has high dose group could suppress to bend arthralgia, show that the effective dose relatively ordinary gel of Strychnos alkaloid micro emulsion gel is low, improve the safety of its Strychnos alkaloid clinical practice.
Experimental example 2: Strychnos alkaloid micro emulsion gel transdermal test in vitro is studied
1, experimental technique
Take healthy SD rat 6, be randomly divided into 2 groups (micro emulsion gel group and ordinary gel groups), often group 3.After rat anesthesia, lying on the back and be fixed on the fixing plate of rat, losing hair or feathers in rat knee joints place, disinfects in alcohol, probe catheter is carefully thrust rat articular intracavity, make one section of conduit stay in articular cavity, to protect the heeling-in of probe.Linear probe is entered from one end of conduit, slowly pulls out from the conduit other end, to the film entrance articular cavity of linear probe, carefully probe catheter is pulled out from articular cavity, make the film of linear probe stay in articular cavity.Adjusting infusion pump speed makes perfusate with the flow velocity perfusion 5min of 0.4ml/h, afterwards, adjusting flow velocity is 0.2ml/h perfusion 30min, smear micro emulsion gel and drug gel (25mg/kg), uniformly the micro emulsion gel of dosage is spread upon on joint, cover preservative film, start simultaneously at collection dialysis solution, calculate drug level.It is specifically shown in table 3.
3 two kinds of gel percutaneous dosing articular cavity microdialysis drug concentration data of table
2, experiment conclusion
Above-mentioned experiments show that, after Strychnos alkaloid micro emulsion gel percutaneous dosing, 0-1.625h absorbs to peak concentration rapidly in articular cavity, starts slowly to eliminate, it is possible at the 8h drug level kept relative stability after 2 hours；And after Strychnos alkaloid gel percutaneous dosing, it is few that medicine enters articular cavity, eliminate fast, be almost difficult to measure.Prompting Strychnos alkaloid micro emulsion gel is more beneficial for the Transdermal absorption of medicine compared with ordinary gel, it is possible to be effectively promoted the Transdermal absorption of medicine.
Brucine Microemulsion gel, Venenum Bufonis total lactones micro emulsion gel, Venenum Bufonis total alkaloids micro emulsion gel, Sinomenine microemulsion gel, sinoacutine micro emulsion gel, cantharidin micro emulsion gel, tripterygium total terpenoids micro emulsion gel, podophyllotoxin micro emulsion gel, Rhizoma Curcumae extract micro emulsion gel, Oleum Curcumae micro emulsion gel, Fructus Capsici extract micro emulsion gel, capsaicin micro emulsion gel, arteannuin micro emulsion gel, Fructus Psoraleae extract micro emulsion gel has all carried out the similar test of pesticide effectiveness, result shows that above Chinese medicine extract micro emulsion gel all has good curative effect in respective treatment field, and it is more beneficial for the Transdermal absorption of medicine.
The detailed description of the invention of form by the following examples, is described in further detail the foregoing of the present invention.But this should not being interpreted as, the scope of the above-mentioned theme of the present invention is only limitted to below example.All technology realized based on foregoing of the present invention belong to the scope of the present invention.
Embodiment 1
Take polyoxyethylene castor oil EL-3520g, PEG40028g and add Strychnos alkaloid 1g, mixing, stirring so that it is fully dissolve, then mix with ethyl oleate 50g, stir, be slowly added into water for injection 20g, stir simultaneously, obtain Strychnos alkaloid microemulsion.
Embodiment 2
Take Tween 80 20g, PEG40025g mixing, add Venenum Bufonis total alkaloids 5g, mixing, stirring so that it is fully dissolve, then mix with ethyl oleate 30g, stir, be slowly added into water for injection 22g, stir simultaneously, obtain Venenum Bufonis total alkaloids microemulsion.
Embodiment 3
Weigh polyoxyethylene castor oil EL-3517g, PEG40037g, caprylic/capric triglyceride 25g, water for injection 21g and cantharidin 2g, add in high pressure homogenizer and carry out high pressure homogenize, obtain cantharidin microemulsion.
Embodiment 4
Take polyoxyethylene castor oil EL-3519g, PEG40030g mixing, add Venenum Bufonis total lactones 5g, mixing, stirring, make it fully dissolve, then mix with ethyl oleate 29g, stir, it is slowly added into water for injection 15g, stirs simultaneously, obtain Venenum Bufonis total lactones microemulsion.
Embodiment 5
Take polyoxyethylene castor oil EL-3525g, PEG40030g mixing, add Strychnos alkaloid 8g, mixing, stirring, make it fully dissolve, then mix with ethyl oleate 30g, stir, it is slowly added into water for injection 15g, stirs simultaneously, obtain Strychnos alkaloid microemulsion.
Embodiment 6
Take polyoxyethylene castor oil EL-3522g, PEG40030g mixing, add strychnine 10g, mixing, stirring, make it fully dissolve, then mix with ethyl oleate 16g, ultrasonic uniformly after, continue ultrasonic, be slowly added into water for injection 44g simultaneously, obtain Brucine Microemulsion.
Embodiment 7
Take polyoxyethylene castor oil EL40g, PEG40010g mixing, add podophyllotoxin 15g, mixing, stirring so that it is fully dissolve, then mix with ethyl oleate 25g, stir, be slowly added into water for injection 52g, stir simultaneously, obtain podophyllotoxin microemulsion.
Embodiment 8
Take polyoxyethylene castor oil EL-3540g, propylene glycol 50g mixing, add tripterygium total terpenoids 25g, mixing, stirring, make it fully dissolve, then mix with ethyl oleate 15g, ultrasonic uniformly after, continue ultrasonic, be slowly added into water for injection 75g simultaneously, obtain tripterygium total terpenoids microemulsion.
Embodiment 9
Weigh polyoxyethylene castor oil EL-3520g, PEG40020g, ethyl oleate 15g, water for injection 30g and Rhizoma Curcumae extract 0.5g, add in high pressure homogenizer and carry out high pressure homogenize, obtain Rhizoma Curcumae extract microemulsion.
Embodiment 10
Take polyoxyethylene castor oil EL-3530g, PEG40015g mixing, add sinomenine 3g, mixing, stirring so that it is fully dissolve, then mix with ethyl oleate 20g, stir, be slowly added into water for injection 50g, stir simultaneously, obtain Sinomenine microemulsion.
Embodiment 11
Take polyoxyethylene castor oil RH4019g, PEG40030g mixing, add Fructus Capsici extract 5g, mixing, stirring, make it fully dissolve, then mix with Ethyl linoleate 29g, stir, it is slowly added into water for injection 15g, stirs simultaneously, obtain Fructus Capsici extract microemulsion.
Embodiment 12
Take sorbester p17 25g, propylene glycol 30g mixing, add Venenum Bufonis total lactones 0.1g, mixing, stirring so that it is fully dissolve, then mix with caprylic/capric triglyceride 30g, stir, be slowly added into water for injection 15g, stir simultaneously, obtain total lactones microemulsion.
Embodiment 13
Take medium-chain triglycerides 40g, PEG4008g mixing, add arteannuin 12g, mixing, stirring so that it is fully dissolve, then mix with ethyl oleate 8g, stir, be slowly added into water for injection 75g, stir simultaneously, obtain arteannuin microemulsion.
Embodiment 14
Take lecithin 1g, ethanol 80g mixing, add strychnine 15g, mixing, stirring so that it is fully dissolve, then mix with isopropyl myristate 80g, stir, be slowly added into phosphate buffer 1 0g, stir simultaneously, obtain Brucine Microemulsion.
Embodiment 15
Take polyoxyethylene castor oil EL21g, propylene glycol 27g mixing, add sinoacutine 3g, mixing, stirring so that it is fully dissolve, then mix with Ethyl linoleate 30g, stir, be slowly added into water for injection 22g, stir simultaneously, obtain sinoacutine microemulsion.
Embodiment 16
Take polyoxyethylene castor oil EL-355g, PEG400100g mixing, add Fructus Psoraleae extract 50g, mixing, stirring, make it fully dissolve, then mix with ethyl oleate 50g, ultrasonic uniformly after, continue ultrasonic, be slowly added into water for injection 20g simultaneously, obtain Fructus Psoraleae extract microemulsion.
Embodiment 17
Take Tween 80 22g, PEG40011g mixing, add Strychnos alkaloid 0.1g, mixing, stirring so that it is fully dissolve, then mix with Ethyl linoleate 16g, ultrasonic uniformly after, continue ultrasonic, be slowly added into water for injection 44g simultaneously, obtain Strychnos alkaloid microemulsion.
Embodiment 18
Take soybean phospholipid 22g, glycerol 30g mixing, add podophyllotoxin 6g, mixing, stirring so that it is fully dissolve, then mix with soybean oil 29g, stir, be slowly added into water for injection 45g, stir simultaneously, obtain podophyllotoxin microemulsion.
Embodiment 19
Take Tween 80 22g, PEG40026g and add cantharidin 2g, mixing, stirring so that it is fully dissolve, then mix with caprylic/capric triglyceride 40g, stir, be slowly added into water for injection 12g, stir simultaneously, obtain cantharidin microemulsion.
Embodiment 20
Weigh Labraso 0.5g, n-butyl alcohol 80g mixing, add tripterygium total terpenoids 0.5g, ultrasonic, it is made fully to dissolve, mix with isopropyl myristate 0.5g again, ultrasonic uniformly after, continue ultrasonic, it is slowly added into normal saline solution 200g simultaneously, obtains tripterygium total terpenoids microemulsion.
Embodiment 21
Weigh polyoxyethylene castor oil EL-3525g, polysorbate40 g mixing, add Venenum Bufonis total alkaloids 7g, ultrasonic, make it fully dissolve, then mix with ethyl oleate 40g, ultrasonic uniformly after, continue ultrasonic, be slowly added into G/NS injection 45g simultaneously, obtain Venenum Bufonis total alkaloids microemulsion.
Embodiment 22
Weigh medium-chain triglycerides 100g, ethanol 0.5g mixing, add cantharidin 25g, ultrasonic so that it is fully to dissolve, then mix with linoleic acid 100g, ultrasonic uniformly after, continue ultrasonic, be slowly added into glucose injection 1g simultaneously, obtain cantharidin microemulsion.
Embodiment 23
Take caprylic/capric polyethyleneglycol glyceride 50g, glycerol 1g mixing, add Strychnos alkaloid 3g, mixing, stirring, make it fully dissolve, then mix with oleic acid 1g, stir, it is slowly added into carbonate buffer solution 100g, stirs simultaneously, obtain Strychnos alkaloid microemulsion.
Embodiment 24
Weigh Rhizoma Curcumae extract 12g, ethyl oleate 50g, sorbester p17 50g, isopropanol 40g, water for injection 100g, after stirring, obtain Rhizoma Curcumae extract microemulsion.
Propyl hydroxybenzoate 10g is dissolved in propylene glycol 50g, weigh Carbomer981 25g and add appropriate water-soluble swollen, add sodium hydroxide and regulate pH value to about 7, with glycerol 15g, menthol 10g, gel-type vehicle is uniformly obtained with the mixed with propylene glycol adding preservative, add Rhizoma Curcumae extract microemulsion 30g, water 50g, stir, obtain Rhizoma Curcumae extract micro emulsion gel.
Embodiment 25
Weigh polyoxyethylene castor oil EL23g, PEG40012g, isopropyl laurate 23g, normal saline 20g, carbonate buffer solution 20g and Strychnos alkaloid 2g, add in high pressure homogenizer and carry out high pressure homogenize, obtain Strychnos alkaloid microemulsion.
Embodiment 26
Propyl hydroxybenzoate 0.2g is dissolved in propylene glycol 10g, weigh Carbopol 1g and add appropriate water-soluble swollen, add sodium hydroxide and regulate pH value to about 7, with glycerol 5g, azone 3g, gel-type vehicle is uniformly obtained with the mixed with propylene glycol adding preservative, add Strychnos alkaloid microemulsion 30g, water 50g, stir, obtain Strychnos alkaloid micro emulsion gel.
Embodiment 27
Weigh polyoxyethylene aliphatic alcohol ether 24g, ethanol 12g mixing, add Strychnos alkaloid 2g, mixing, stirring so that it is fully dissolve, then mix with ethyl oleate 12g, stir, be slowly added into water for injection 50g, stir simultaneously, obtain Strychnos alkaloid microemulsion.
Embodiment 28
Weigh polyoxyethylene hydrogenated Oleum Ricini 21g, PEG40011g mixing, add podophyllotoxin 3g, ultrasonic, make it fully dissolve, then mix with ethyl oleate 20g, ultrasonic uniformly after, continue ultrasonic, be slowly added into water for injection 25g, G/NS 20g simultaneously, obtain podophyllotoxin microemulsion.
Embodiment 29
Weigh arteannuin 50g, ethyl oleate 80g, Tween 80 120g, ethanol 80g, phosphate buffer (pH7.4) 200g, add in high pressure homogenizer and carry out high pressure homogenize, obtain arteannuin microemulsion.
Ethyl hydroxybenzoate 1.5g is dissolved in isopropanol 25g, weigh Carbomer974 10g and add appropriate water-soluble swollen, add sodium bicarbonate and regulate pH value to about 7, with glycerol 5g, N-Methyl pyrrolidone 20g, gel-type vehicle is obtained with the isopropanol mix homogeneously adding preservative, add arteannuin microemulsion 100g, water 100g, stir, obtain arteannuin micro emulsion gel.
Embodiment 30
Weigh Fructus Psoraleae extract 0.5g, ethyl oleate 0.5g, polyoxyethylene castor oil EL0.5g, propylene glycol 0.5g, water for injection 1g, after stirring, obtain Fructus Psoraleae extract microemulsion.
Methyl hydroxybenzoate 0.1g is dissolved in glycerol 1g, weigh carbomer940 0.5g and add appropriate water-soluble swollen, add sodium carbonate and regulate pH value to about 7, menthol 1g, gel-type vehicle is obtained with the glycerol mix homogeneously adding preservative, add Fructus Psoraleae extract microemulsion 1g, water 1g, stir, obtain Fructus Psoraleae extract micro emulsion gel.
Embodiment 31
Weigh strychnine 10g, oleic acid 30g, polyoxyethylene castor oil RH4040g, ethanol 30g, water for injection 150g, after stirring, obtain Brucine Microemulsion.
Potassium sorbate 0.8g is dissolved in hyaluronic acid 15.5g, weigh hypromellose 5.25g and add appropriate water-soluble swollen, Labraso 10.5g, gel-type vehicle is obtained with the hyaluronic acid mix homogeneously adding preservative, add Brucine Microemulsion 50.5g, water 80g, stir, obtain Brucine Microemulsion gel.
Embodiment 32
Take xanthan gum 30g, propylene glycol 80g, menthol 50g, phenol 10g, add suitable quantity of water, add triethylamine and regulate pH value to about 7, make gel-type vehicle and Venenum Bufonis total lactones microemulsion 150g mixing, stir, obtain Venenum Bufonis total lactones micro emulsion gel.
Embodiment 33
Sorbic acid 3g is dissolved in propylene glycol 50g, weigh Carbomer981 25g and add appropriate water-soluble swollen, add triethylamine and regulate pH value to about 7, Gelucire 44/14 40g, gel-type vehicle is uniformly obtained with the mixed with propylene glycol adding preservative, add podophyllotoxin microemulsion 100g, stir, obtain podophyllotoxin micro emulsion gel.
Embodiment 34
Take carbomer 98115.2g, propylene glycol 40.2g, quintessence oil 25.2g, sorbic acid 5g, add suitable quantity of water, add triethanolamine and regulate pH value to about 7, make gel-type vehicle and cantharidin microemulsion 75.3g mixing, stir, obtain cantharidin micro emulsion gel.
Embodiment 35
Take carbomer 9819g, propylene glycol 25g, Semen Myristicae isopropyl acid esters 18g, sorbic acid 1g, add suitable quantity of water, add lauryl amine and regulate pH value to about 7, make gel-type vehicle and Sinomenine microemulsion 80g mixing, stir, obtain Sinomenine microemulsion gel.
Embodiment 36
Potassium sorbate 1.2g is dissolved in propylene glycol 18g, weigh hypromellose 8g and add appropriate water-soluble swollen, add sodium carbonate and regulate pH value to about 7, polyglyceryl fatty acid ester 7g, gel-type vehicle is uniformly obtained with the mixed with propylene glycol adding preservative, add tripterygium total terpenoids microemulsion 45g, stir, obtain tripterygium total terpenoids micro emulsion gel.
Embodiment 37
Take carbomer 9410.1g, glycerol 0.1g, dimethyl sulfoxide 0.1g, add suitable quantity of water, add diethylamine and regulate pH value to about 7, make gel-type vehicle and Venenum Bufonis total alkaloids microemulsion 0.5g mixing, stir, obtain Venenum Bufonis total alkaloids micro emulsion gel.
Embodiment 38
Phenol 0.8g is dissolved in propylene glycol 22g, weigh Carbopol 941 9g and add appropriate water-soluble swollen, add triethylamine and regulate pH value to about 7, oleic acid polyethyleneglycol glyceride 18g, gel-type vehicle is uniformly obtained with the mixed with propylene glycol adding preservative, add sinoacutine microemulsion 75g, stir, obtain sinoacutine micro emulsion gel.
Embodiment 39
Take Strychnos alkaloid microemulsion appropriate, prepare into various oral formulations according to a conventional method.
Embodiment 40
Take Strychnos alkaloid microemulsion appropriate, prepare into ointment, patch, spray, aerosol according to a conventional method.
Claims (10)
1. a Chinese medicine extract microemulsion, it is characterised in that it is made up of following weight parts prescription:
2. microemulsion according to claim 1, it is characterised in that it is made up of the prescription of following weight parts:
3. microemulsion according to claim 1, it is characterised in that it is made up of the prescription of following weight parts:
4. the microemulsion according to any one in claim 1-3, it is characterized in that, oil phase refers to one or more in soybean oil, Oleum Arachidis hypogaeae semen, Oleum Ricini, oleic acid, linoleic acid, ethyl oleate, Ethyl linoleate, isopropyl myristate, isopropyl laurate, Monooctamoin, medium-chain triglycerides；
Emulsifying agent refers to one or more in polyoxyethylene-type, polyol type, specifically refers to one or more in soybean phospholipid, lecithin, caprylic/capric polyethyleneglycol glyceride, polyoxyethylene castor oil, polyoxyethylene aliphatic alcohol ether, polyoxyethylene hydrogenated Oleum Ricini, tween, span；
Co-emulsifier refers to one or more in propylene glycol, glycerol, isopropanol, n-butyl alcohol, ethanol, ethylene glycol, tween, glycerol, Polyethylene Glycol；
Aqueous phase refers to one or more in water for injection, phosphate buffer, carbonate buffer solution, normal saline solution, G/NS injection.
5. microemulsion according to claim 4, it is characterised in that oil phase refers to ethyl oleate, Ethyl linoleate, oleic acid, medium-chain triglycerides；
Emulsifying agent refers to polyoxyethylene castor oil, tween, span；
Co-emulsifier refers to propylene glycol, ethanol, Polyethylene Glycol；
Aqueous phase refers to water for injection, phosphate buffer.
6. the microemulsion according to any one in claim 1-3, it is characterised in that it is to be obtained by any one preparation method following:
(1) weigh appropriate emulsifying agent, co-emulsifier mixing, add Chinese medicine extract, mixing, stirring so that it is fully dissolve, then mix with oil phase, stir, be slowly added into appropriate aqueous phase, stir simultaneously, obtain Chinese medicine extract microemulsion；
(2) weigh appropriate emulsifying agent, co-emulsifier mixing, add Chinese medicine extract, ultrasonic so that it is fully to dissolve, then mix with oil phase, ultrasonic uniformly after, continue ultrasonic, be slowly added into appropriate aqueous phase simultaneously, obtain Chinese medicine extract microemulsion；
(3) weigh appropriate emulsifying agent, co-emulsifier, oil phase, aqueous phase and Chinese medicine extract, add in high pressure homogenizer and carry out high pressure homogenize, obtain Chinese medicine extract microemulsion.
7. the preparation of microemulsion described in any one in claim 1-3, it is characterised in that for peroral dosage form or external preparation；Wherein, external preparation refers to gel, ointment, patch, spray, aerosol.
8. the preparation of microemulsion according to claim 7, it is characterised in that described gel is made up of the component of following weight parts:
Chinese medicine extract microemulsion 0.5-150 part, thickening agent 0.1-30 part, wetting agent 0.1-80 part, pH adjusting agent 0-30 part, transdermal agent 0.1-50 part, preservative 0-10 part, aqueous phase 1-100 part.
9. preparation according to claim 8, it is characterized in that, described thickening agent refers to one or more in cross-linked polypropylene resin class, cross-linked polypropylene resin variety classes salt and derivant, hydroxypropyl methylcellulose, xanthan gum, wherein, cross-linked polypropylene resin class refers to Carbopol 941, Carbomer974, carbomer940, Carbopol, Carbomer981；
Wetting agent refers to one or more in glycerol, propylene glycol, isopropanol, ethanol, hyaluronic acid；
PH adjusting agent refers to one or more in triethanolamine, triethylamine, diethylamine, lauryl amine, sodium hydroxide, sodium bicarbonate, sodium carbonate；
Transdermal agent refers to one or more in azone, menthol, quintessence oil, dimethyl sulfoxide, propylene glycol, Semen Myristicae isopropyl acid esters, N-Methyl pyrrolidone, Gelucire 44/14, polyglyceryl fatty acid ester, oleic acid polyethyleneglycol glyceride, Labraso；
Preservative refers to one or more in potassium sorbate, sorbic acid, ethyl hydroxybenzoate, propyl hydroxybenzoate, methyl hydroxybenzoate, phenol.
10. the preparation of microemulsion described in claim 8, it is characterised in that the preparation method of this Chinese medicine extract micro emulsion gels is:
Take thickening agent, wetting agent, transdermal agent, preservative, add water, pH adjusting agent, make gel-type vehicle and obtained Chinese medicine extract microemulsion mixing, stir, obtain Chinese medicine extract micro emulsion gel.
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Address after: Double camp 102299 West Road Beijing city Changping District Science Park No. 79, No. 24 building 6 layer cloud Valley Park Applicant after: Beijing Kerui pharmaceutical Limited by Share Ltd profit innovation Address before: 100088 Beijing city Xicheng District, New Street No. 2 Tiancheng Technology building block B room 4002 Applicant before: BEIJING INCREASE PHARMACEUTICAL INSTITUTE CO., LTD. |
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Application publication date: 20160713 |