CN1762333A - Microemulsion formulation and its preparation process - Google Patents
Microemulsion formulation and its preparation process Download PDFInfo
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Abstract
The invention discloses a microemulsion and the preparing method, especially relating to a microemulsion containing traditional Chinese medicine active component and the preparing method. The microemulsion is composed of surface activator, cosurfactant, oil phase and water phase, the oil phase comprises the volatile oil extracted from single and/ or compound traditional Chinese medicine, and the water phase comprises extractive liquid from single and / or compound traditional Chinese medicine. One and / or several solid traditional Chinese medicine active component can be added into the above said microemulsion. The invention provides a new medicine carrier system for the traditional Chinese medicine preparation, the said microemulsion can increase the solubility of the indissoluble medicine as well as the biological availability; microemulsion can contain medicines of different liposolubility at the same time and thus improves the stability of some unstable medicine.
Description
Invention field
The present invention relates to a kind of microemulsion formulation and preparation method thereof, particularly a kind of microemulsion formulation that contains active ingredient of Chinese herbs and preparation method thereof.
Background technology
The microemulsion structure is found in nineteen forty-three first by Englishize scholar Sculman and Hoar.And formally name in nineteen fifty-nine and to be microemulsion (microemulsion).The microemulsion structure is the homogeneous system of thermodynamically stable oil-water-surfactant-cosurfactant, appearance transparent or approximate transparent, also with-as Emulsion equally be divided into W/O and O/W type, particle diameter is little, usually between 10-100nm, thus also be referred to as microemulsion (Nanoemulsion, NE).This special construction of microemulsion is all being obtained suitable progress in a lot of fields, it is important and be very active branch to become of surface chemistry.Micro-emulsion technology has been penetrated into fields such as daily-use chemical industry, fine chemistry industry, petrochemical industry, material science, biotechnology and environmental science, becomes current popular, that have the huge applications potentiality in the world research field.Microemulsion also causes people's attention gradually as the application of pharmaceutical carrier, and microemulsion has great application potential as a kind of new drug carrier.Cyclosporin, cancer therapy drug camptothecine, antipyretic and anti-inflammatory medicine indometacin cloth, the fragrant monooctyl ester micro-emulsion injecta in Lip river, flurbiprofen injection or the like all have the result to show, and above medicine is made after the microemulsion formulation, and dissolubility obviously improves, and bioavailability increases greatly.Microemulsion is used as pharmaceutical carrier bigger potentiality and wide prospect, but at the field of Chinese medicines, domestic and international research does not seldom still have the product appearance of Chinese medicine microemulsion formulation now, and it is to have a extensive future and far reaching work that microemulsion formulation is applied to the field of Chinese medicines.
Summary of the invention
The object of the invention is to provide a kind of microemulsion formulation and preparation method thereof, and a kind of microemulsion formulation that contains active ingredient of Chinese herbs and preparation method thereof is provided especially.
Microemulsion formulation of the present invention is by surfactant, cosurfactant, oil phase, water four phase compositions, and the proportion relation of surfactant, cosurfactant, oil phase, water four phases is: 1-10: 1-20: 0.2-5: 0.5-15.
Best proportion relation is: 10: 20: 1: 10; 10: 20: 2: 10; 5.5: 2: 2.5: 0.5; 6: 3: 2.5: 1; 5: 20: 1: 15.
When above-mentioned surfactant, cosurfactant, oil phase or water all were liquid, its ratio unit was a volume ratio; When above-mentioned surfactant, cosurfactant, oil phase or aqueous portion are solid, when part was liquid, its ratio unit was that w/v is L/Kg.
Can also add pharmaceutically active substance in a kind of and/or several solid in above-mentioned microemulsion formulation, the amount that adds pharmaceutically active substance in the solid is to contain conventional effective dose in the microemulsion formulation.
Surfactant in the microemulsion formulation is ionic surfactant or nonionic surfactant, as tween, lecithin, one or more in the polyoxyethylene castor oil; Cosurfactant is a short chain alcohol, and in ethanol, propylene glycol, glycerol, sorbitol etc. one or more; Oil phase is an isopropyl myristate, Oleum Glycines, Oleum Arachidis hypogaeae semen, oleic acid, one or more in the volatilization wet goods that single or herbal mixture extract; Water is a distilled water, one or more in single or the herbal mixture water extract etc.
Single in the oil phase of microemulsion formulation of the present invention or herbal mixture volatile oil comprise the volatile oil that extracts in any single that contains volatile oil and the herbal mixture, as Herba Menthae, and Flos Rosae Rugosae, Radix Angelicae Sinensis, Cortex Magnoliae Officinalis, the Radix Aucklandiae, Flos Carthami, Borneolum Syntheticum, Semen Myristicae, Cortex Cinnamomi, guizhi decoction, Ephedrae Decoction, GEGEN TANG, decoction of four noble drugs, SIWU TANG, in classical Chinese medicine prescription such as Decoction of Four-Drug Juice and the volatile oil that extracts according to the new prescription of forming of theory of Chinese medical science one or more, described volatile oil contains the active ingredient of conventional effective dose;
The Chinese traditional medicine water extract of the aqueous phase of microemulsion formulation of the present invention comprises the water extract that extracts in any single that contains water-soluble components or the herbal mixture, as Herba Menthae, and Flos Rosae Rugosae, Radix Angelicae Sinensis, Cortex Magnoliae Officinalis, the Radix Aucklandiae, Flos Carthami, Borneolum Syntheticum, Semen Myristicae, Cortex Cinnamomi, guizhi decoction, Ephedrae Decoction, GEGEN TANG, decoction of four noble drugs, SIWU TANG, classical Chinese medicine prescription such as Decoction of Four-Drug Juice and according to the new prescription of forming of theory of Chinese medical science extract the water extract in one or more, described water extract contains the active ingredient of conventional effective dose.
When the single in the above-mentioned microemulsion formulation oil phase or herbal mixture volatile oil when being several, the ratio of various volatile oil is equal volume or need carries out proportioning by the tcm clinical practice prescription; When the Chinese traditional medicine water extract of above-mentioned microemulsion formulation aqueous phase when being several, the ratio of various Chinese traditional medicine water extracts is equal volume or need carries out proportioning by the tcm clinical practice prescription.In comprising single or herbal mixture volatile oil in the oil phase of above-mentioned microemulsion formulation when a kind of and/or several, when aqueous phase comprises a kind of and/or several in the Chinese traditional medicine water extract, or when comprising in a kind of and/or several solid pharmaceutically active substance in the microemulsion formulation, the medication rule of combination of above-mentioned volatile oil, water extract or active substance is followed the clinical compatibility principle.
Microemulsion formulation of the present invention is Water-In-Oil (O/W) type or oil-in-water (W/O) type, contains the active ingredient of conventional effective dose in the unit formulation.
The above-mentioned microemulsion formulation of the present invention is meant various clinical acceptable forms, includes but not limited to a kind of in the middle of the following dosage form: as soft capsule, and liquid preparations such as suspensoid, oral liquid, enema, injection.
The preparation method of microemulsion formulation of the present invention is a kind of in the following method:
Under the temperature of 25 degree-65 degree Celsius, get surfactant, cosurfactant, oil phase and water in proportion, mix forming microemulsion formulation.
Under the temperature of 25 degree-65 degree Celsius, get surfactant, cosurfactant, oil phase and water in proportion; Oil phase is dissolved in makes its dissolving in the cosurfactant, under the gentle agitation condition, add surfactant, water and mix and form microemulsion formulation.
The preparation method of the microemulsion formulation of pharmaceutically active substance is a kind of in the following method in the adding solid of the present invention:
Get pharmaceutically active substance in surfactant, cosurfactant, oil phase, water and the solid in proportion; Under the temperature of 25 degree-65 degree Celsius, surfactant, cosurfactant, oil phase, water are mixed the formation microemulsion formulation; Add pharmaceutically active substance in the solid, form the pastille microemulsion formulation.
Get pharmaceutically active substance in surfactant, cosurfactant, oil phase, water and the solid in proportion; Under the temperature of 25 degree-65 degree Celsius, oil phase is dissolved in makes its dissolving in the cosurfactant, under the gentle agitation condition, add surfactant, water and mix and form microemulsion formulation; Add pharmaceutically active substance in the solid, form the pastille microemulsion formulation.
Get pharmaceutically active substance in surfactant, cosurfactant, oil phase, water and the solid in proportion; Under the temperature of 25 degree-65 degree Celsius with solid in pharmaceutically active substance be dissolved in cosurfactant, oil phase and/or aqueous phase and make its dissolving, under the gentle agitation condition, add the surfactant that does not add again, cosurfactant, oil phase and/or water mix the microemulsion formulation that forms pastille.
Pharmaceutically active substance microemulsion preparation method is molten or insoluble and dissolve in active component in alcohol, the wet goods organic solvent applicable to all shipwrecks in the solid of the present invention.Comprise alkaloidss such as Herba Ephedrae alkaloid, Rhizoma Coptidis alkaloid, Rhizoma Corydalis alkaloid, matrine, andrographolide (diterpene); Arteannuin (sesquiterpene); Paclitaxel (diterpene); Toosendanin (triterpene); Bilobalide (diterpene); Solatene terpenoid such as (tetraterpenes), Radix Ginseng total saponins, saponinss such as arasaponin, Radix Salviae Miltiorrhizae flavone, flavonoids such as Radix Puerariae flavone, tea polyphenols; Polysaccharides such as Polyphenols such as agrimonine and astragalus polysaccharides, ginseng polysaccharide.
In the above-mentioned microemulsion formulation, when oil phase was in the volatile oil that extracts of single or herbal mixture one or more, the preparation method of its volatile oil was to extract total volatile oil and/or volatile oil with conventional method from unit and/or herbal mixture; When water in the microemulsion formulation was in single or the herbal mixture water extract one or more, the preparation method of its water extract was to extract aqueous extract with conventional method from unit and/or herbal mixture, and aqueous extract should be through the filtration clarifying treatment of routine.
Microemulsion technology of the present invention provides new medicine-carried system for Chinese medicine preparation, and described microemulsion formulation can improve the dissolubility of insoluble drug, promotes the macromolecule water-solubility medicine in the intravital absorption of people, improves these bioavailability of medicament; Microemulsion can contain different fat-soluble medicines simultaneously, improves the stability of some labile drugs;
Because the particle diameter of microemulsion is little and even, makes the medicine dispersion height that is encapsulated in wherein, has promoted the Transdermal absorption of medicine; Microemulsion formulation viscosity of the present invention is low, and particle diameter is little, can be used as injection, and injection can not cause pain; The medicine that is easy to hydrolysis is made the water-in-oil type microemulsion effectively restrain its hydrolysis, play a protective role; Microemulsion formulation of the present invention has prolonged the drug release time of water soluble drug; Microemulsion formulation preparation method of the present invention is simple, and preparation has the transparency liquid of each homogeny, Thermodynamically stable, and particle diameter is little, can filter, and is easy to preparation and preservation.
Following experimental example is used for explanation but is not limited to the present invention.
Experimental example 1: the investigation of the physicochemical property of andrographolide microemulsion formulation
Assay: the content of measuring andrographolide in the andrographolide microemulsion formulation with the HPLC method.Mobile phase is that the content that methanol-water (50: 50) records andrographolide is 7.8447mg/ml.
The mensuration of heat stability: the andrographolide microemulsion was at room temperature placed 30 days, observed its clarity, and regularly surveyed its OD value, and the result shows under the andrographolide microemulsion formulation room temperature and has good stability, no lamination, and the OD value did not have significant difference in 30 days.In addition, at 40 ℃, 60 ℃, 80 ℃ of constant temperature were placed 10 days, observed its outward appearance every day, and in 1,3, measured its OD value respectively in 5,7,10 days with the lactone breast, and the result shows that the andrographolide microemulsion formulation at high temperature also has good stable.
Particle size determination:, obtain its particle size range between 30-60nm with the particle diameter of transmission electron microscope observing andrographolide microemulsion formulation and the measurement of taking pictures.
Andrographolide has fine solubility in microemulsion.Andrographolide is water-soluble hardly, and is solvable in ethanol, and dissolubility is fine in microemulsion, 8 milliliters of andrographolide of solubilized in every milliliter of microemulsion.
Experimental example 2: andrographolide microemulsion formulation pharmacodynamics is tentatively investigated
Andrographolide microemulsion formulation and andrographolide sheet are carried out pharmacodynamics relatively, and the result shows, the andrographolide microemulsion causes in the toes swelling experiment suppressing rat Ovum Gallus domesticus album, and effect obviously is better than the andrographolide sheet, shows as rapid-actionly, and action effect is obvious.
The andrographolide microemulsion is to the influence of toes swelling due to the rat Ovum Gallus domesticus album
| Blank group | The aspirin group | Andrographolide sheet group | The microemulsion small dose group | Dosage group in the microemulsion | The heavy dose of group of microemulsion | |
| Original volume 05h 1h 2h 4h 6h 8h | 1.59±0.06 1.038±0.157 0.863±0.115 0.724±0.121 0.567±0.096 0.460±0.094 0.385±0.076 | 1.60±0.09 0.768±0.141** 0.583±0.137** 0.436±0.115** 0.311±0.123** 0.208±0.117** 0.122±0.101** | 1.58±0.09 0.788±0.158** 0.645±0.150** 0.520±0.112** 0.416±0.112** 0.277±0.099** 0.188±0.095** | 1.54±0.06 0.606±0.128** ##^^ 0.560±0.147** 0.398±0.132** 0.294±0.133**^^ 0.175±0.120**^ 0106±0.068** | 1.56±0.05 0.603±0.158** ## 0.457±0.166**^ 0.328±0.143**^ 0.242±0.139**^ 0.132±0.106**^^ 0.085±0.081**^^ | 160±0.08 0.567±0.169** ##^^ 0.417±0154**^^ 0.349±0.132** 0.220±0.104**^^ 0121±0.079**^^ 0.060±0.038**^^ |
* compares p＜0.01 with blank group; ## and aspirin group be p＜0.01 relatively; ^^ and andrographolide sheet group be p＜0.01 relatively.
Experimental example 3: the extraction efficiency comparative test of microemulsion
Get tween 80, ethanol, isopropyl myristate, distilled water, ratio is 5: 20: 1: 15, be mixed with the blank microemulsion of 500m1, and get 100g Herba Andrographis, flooded 4 days with blank microemulsion, filter impregnation liquid, get the microemulsion extracting solution.Other gets 65% ethanol 500ml, gets 100g Herba Andrographis, uses alcohol dipping 4 days, filters impregnation liquid, gets ethanol extract.Measure the content of andrographolide in two kinds of extracting solution respectively, wherein the yield of microemulsion extracting solution is 0.08%, and the yield of ethanol extract is 0.06%, and the extraction efficiency that microemulsion is described is than ethanol height.
Experimental example 4: the investigation of other drug effective ingredient dissolubility in microemulsion
Baicalin dissolubility in water and ethanol is all very poor, and is water-soluble hardly, is slightly soluble in ethanol, but in microemulsion 3.3 milligrams of every milliliter of solubilized.
The specific embodiment is as follows:
Embodiment 1: Borneolum Syntheticum microemulsion capsule
Be 10: 20: 2 in proportion: 10 get tween 80 10L, ethanol 20L, Borneolum Syntheticum 2Kg, distilled water 10L; Get Borneolum Syntheticum and be dissolved in the ethanol, after fully stirring is treated to dissolve fully; Add tween 80 according to aforementioned proportion, distilled water fully stirs; Add conventional other adjuvants and make capsule.
Embodiment 2: the Herba Menthae microemulsion soft capsules
Be 5.5: 2: 2.5 in proportion: 0.5 gets tween 5.5L, ethanol 2L, Oleum menthae 2.5L, aqua methnae extract 0.5L; get Oleum menthae 2.5L; under fully stirring it is dissolved in the 2L ethanol; and then add surfactant in proportion; oil phase; water and other adjuvants, fully stir, make soft capsule and get final product.
Embodiment 3: Herba Menthae microemulsion liniment
Be 5.5: 2: 2.5 in proportion: 20 get tween 5.5L, ethanol 2L, Oleum menthae 2.5L, aqua methnae extract 20L, get Oleum menthae 2.5L, under fully stirring it are dissolved in the 2L ethanol, and then add surfactant in proportion, oil phase, water and other adjuvants, fully stir, make liniment and get final product.
Embodiment 4: the Chinese medicine compound collateral dredging is rescued the brain soft capsule
Be 5.5: 2: 2.5 in proportion: 20 get tween 5L, ethanol 5L, collateral dredging rescues volatile oil 2.5L, the collateral dredging that the brain compound recipe extracts and rescues the water extract 20L that the brain compound recipe extracts, get collateral dredging and rescue the volatile oil 2.5L that the brain compound recipe extracts, under fully stirring it is dissolved in the 5L ethanol, and then add surfactant in proportion, oil phase, water and other adjuvants fully stir, and make soft capsule.
Embodiment 5: Flos Rosae Rugosae microemulsion liniment
Be 6: 3: 2.5 in proportion: 1 gets tween 6L, ethanol 3L, Oleum Rosae Rugosae 5L, rose water extract 1L, gets Oleum Rosae Rugosae 5L, under fully stirring it is dissolved in the 3L ethanol, and then add surfactant in proportion, oil phase, water and other adjuvants are made liniment after fully stirring..
Embodiment 6: Flos Rosae Rugosae microemulsion cream
Be 6: 3: 2.5 in proportion: 20 get tween 6L, ethanol 3L, Oleum Rosae Rugosae 2.5L, rose water extract 20L, get Oleum Rosae Rugosae 2.5L, make it be dissolved in 3L ethanol under fully stirring, and then add surfactant in proportion, oil phase, water and other adjuvants are made cream after fully stirring..
Embodiment 7: Radix Angelicae Sinensis microemulsion capsule
Be 5: 20: 0.2 in proportion: 10 get the volatile oil 0.2L of tween 80 5L, ethanol 20L, Radix Angelicae Sinensis extraction, the water extract 10L that Radix Angelicae Sinensis extracts, get Radix Angelicae Sinensis volatile oil, make it be dissolved in ethanol under fully stirring, add surfactant then in proportion, water and other adjuvants, encapsulated after fully stirring..
Concrete operations are as follows:
Get Radix Angelicae Sinensis 50Kg, steam distillation extracts volatile oil 0.2L; Aqueous solution after the extraction is concentrated into 100L, adds 95% ethanol 200L, stirs, and standing over night is filtered, and filtrate is concentrated into 10L, adds volatile oil 0.2L in the filtrate respectively, ethanol 20L, and tween 80 5L fully stirs, and makes soft capsule.
Embodiment 8: Rhizoma Chuanxiong microemulsion capsule
Be 10: 20: 0.5 in proportion: 20 get the volatile oil 0.5L of tween 80 10L, ethanol 20L, Rhizoma Chuanxiong extraction, the water extract 20L that Rhizoma Chuanxiong extracts, get Rhizoma Chuanxiong volatile oil 0.5L, under fully stirring it is dissolved in the 20L ethanol, add surfactant then in proportion, water and other adjuvants, encapsulated after fully stirring.
Embodiment 9: foshousan microemulsion capsule
Be 5: 10: 0.6 in proportion: the water extract 20L that 20 volatile oil 0.6L, Radix Angelicae Sinensis and the Rhizoma Chuanxiongs of getting tween 80 5L, ethanol 10L, Radix Angelicae Sinensis (18Kg) and Rhizoma Chuanxiong (12Kg) extraction extract, get the volatile oil of extraction, under fully stirring it is dissolved in the 10L ethanol, add surfactant then in proportion, water and other adjuvants, encapsulated after fully stirring.
Embodiment 10: Liang Fu Wan microemulsion capsule
Be 10: 5: 1 in proportion: the water extract 20L that 20 volatile oil 1L, Rhizoma Alpiniae Officinarum and the Rhizoma Cyperis of getting tween 80 10L, ethanol 5L, Rhizoma Alpiniae Officinarum (500Kg) and Rhizoma Cyperi (500Kg) extraction are extracted, get the volatile oil of extraction, under fully stirring it is dissolved in the 5L ethanol, add surfactant then in proportion, water and other adjuvants, encapsulated after fully stirring.
Embodiment 11: the andrographolide microemulsion soft capsules
Be 10: 20: 1 in proportion: 10 get tween 80 10L, ethanol 20L, isopropyl myristate 1L, distilled water 10L, get andrographolide 320Kg, place the 20L dehydrated alcohol, fully stir, ultrasonic short molten, treat to dissolve fully the back and add surfactant, oil phase and water and other adjuvants, fully stir the back packing and make capsule according to aforementioned proportion.
Embodiment 12: andrographolide microemulsion capsule
Be 5: 20: 1 in proportion: 15 get tween 80 5L, ethanol 20L, isopropyl myristate 1L, distilled water 15L, get andrographolide 320Kg, be dissolved in the 20L ethanol, after fully stirring is treated to dissolve fully, add surfactant according to aforementioned proportion, oil phase, water and other adjuvants, fully stir, make capsule.
Embodiment 13: arasaponin microemulsion capsule
Be 10: 20: 1 in proportion: 15 get tween 80 10L, ethanol 20L, isopropyl myristate 1L, distilled water 15L, get arasaponin 10g, be dissolved in the 20L ethanol, after fully stirring is treated to dissolve fully, add surfactant according to aforementioned proportion, oil phase, water and other adjuvants, fully stir, make capsule.
Embodiment 14: arasaponin microemulsion capsule
Be 6: 2.5: 1.1 in proportion: 10 get tween 80 6L, sorbitol 2.5Kg, Oleum Glycines 1.1L, distilled water 10L; Get arasaponin 8g, under fully stirring it is dissolved in the 10L distilled water, and then adds surfactant in proportion, cosurfactant, oil phase and other adjuvants, encapsulated after fully stirring.
Embodiment 15: the microemulsion containing matrine capsule
Be 2: 3: 0.5 in proportion: 12; Get polyoxyethylene castor oil 2L, ethanol 3L, Oleum Arachidis hypogaeae semen 0.5L, distilled water 12L; Get matrine 5.5g, under fully stirring it is dissolved in the 12L distilled water; And then add polyoxyethylene castor oil in proportion, and ethanol, Oleum Arachidis hypogaeae semen adds conventional other adjuvants and makes capsule.
Embodiment 16: Radix Paeoniae Alba total glucosides microemulsion capsule
Be 3: 3: 1.5 in proportion: 10 get lecithin 3L, ethanol 3L, oleic acid 1.5L, distilled water 10L, get Radix Paeoniae Alba total glucosides 0.85g, under fully stirring it are dissolved in the 10L water, and then add surfactant in proportion, cosurfactant, oil phase and other adjuvants, encapsulated after fully stirring.
Embodiment 17: TANSHINONES microemulsion capsule
Be 10: 5: 2 in proportion: 10 get polyoxyethylene castor oil 10L, propylene glycol 5L, Oleum Glycines 2L, distilled water 10L, get TANSHINONES 0.55Kg, make it be dissolved in propylene glycol 5L under fully stirring, and then add surfactant in proportion, oil phase, water and other adjuvants, encapsulated after fully stirring.
Embodiment 18: the arteannuin microemulsion soft capsules
Be 6: 3: 2.5 in proportion: 1 gets tween 6L, ethanol 3L, oleic acid 2.5L, distilled water 1L, gets arteannuin 120g, makes it be dissolved in 3L ethanol under fully stirring, and then add surfactant in proportion, oil phase, water and other adjuvants, fully stir, make soft capsule.
Embodiment 19: the yew alcohol micro-emulsion soft capsule
Be 6: 3: 2.5 in proportion: 1 gets tween 6L, ethanol 3L, oleic acid 2.5L, distilled water 1L, gets paclitaxel 80g, under fully stirring it is dissolved in the 3L ethanol, and then add surfactant in proportion, oil phase, water and other adjuvants, fully stir, make soft capsule.
Embodiment 20:
1: 20: 0.2 in proportion: 15 got tween 1L, ethanol 20L, decoction of four noble drugs volatile oil 0.2L, Xiao Chengqi Tang water extract 10L and peony and licorice decoction water extract 5L, add conventional adjuvant, and soft capsule is made in packing.
Embodiment 21:
1: 1: 5 in proportion: 15 got lecithin 1L, propylene glycol 1L, GEGEN TANG volatile oil 3L and Radix Angelicae Sinensis, Rhizoma Chuanxiong volatile oil 2L, Ramulus Cinnamomi soup extract 15L mixing formation microemulsion, add conventional adjuvant, and suspensoid is made in packing.
Embodiment 22:
1: 20: 5 in proportion: 0.5 got polyoxyethylene castor oil 1L, glycerol 20L, SIWU TANG volatile oil 5L, the very light blue soup extract of Radix Bupleuri 0.5L, mixed to form microemulsion, added conventional adjuvant, and oral liquid is made in packing.
Embodiment 23:
1: 1: 0.2 in proportion: 15 got tween 1L, sorbitol 1Kg, Cortex Cinnamomi volatile oil 0.2L, Borneolum Syntheticum aqueous solution 15L (get 3kg Borneolum Syntheticum be dissolved in the 15L water make), mix forming microemulsion, add conventional adjuvant, and injection is made in packing.
Embodiment 24:
1: 20: 0.2 in proportion: 0.5 got lecithin 1L, ethanol 20L, Semen Myristicae volatile oil 0.2L, Cortex Cinnamomi water extract 0.5L, mixed to form microemulsion, added conventional adjuvant, and enema is made in packing.
Embodiment 25:
1: 1: 5 in proportion: 0.5 got polyoxyethylene castor oil 1L, propylene glycol 1L, Ephedrae Decoction volatile oil 5L, Herba Ephedrae soup extract 0.5L, mixed to form microemulsion, added conventional adjuvant, and oral liquid is made in packing.
Embodiment 26:
1: 20: 5 in proportion: 15 got tween 1L, glycerol 20L, Borneolum Syntheticum 5Kg, saffron aqueous solution 15L, mixed to form microemulsion, added conventional adjuvant, and suspensoid is made in packing.
Embodiment 27:
1: 1: 0.2 in proportion: 0.5 got lecithin 1L, sorbitol 1Kg, Flos Carthami volatile oil 0.2L, decoction of four noble drugs water extract 0.5L, mixed to form microemulsion, added conventional adjuvant, and the injection soft capsule is made in packing.
Embodiment 28:
10: 20: 0.2 in proportion: 15 got polyoxyethylene castor oil 10L, ethanol 20L, Decoction of Four-Drug Juice volatile oil 0.2L, Decoction of Four-Drug Juice water extract 15L, mixed to form microemulsion, added conventional adjuvant, and enema is made in packing.
Embodiment 29:
10: 1: 5 in proportion: 15 got tween 10L, propylene glycol 1L, volatile oil of Radix Aucklandiae 5L, Semen Myristicae water extract 15L, mixed to form microemulsion, added conventional adjuvant, and oral liquid is made in packing.
Embodiment 30:
10: 20: 5 in proportion: 0.5 got lecithin 10L, glycerol 20L, Cortex Magnoliae Officinalis volatile oil 5L, Radix Aucklandiae water extract 0.5L, mixed to form microemulsion, added conventional adjuvant, and suspensoid is made in packing.
Embodiment 31:
10: 1: 0.2 in proportion: 15 got polyoxyethylene castor oil 10L, sorbitol 1Kg, guizhi decoction volatile oil 0.2L, YUPINGFENG SAN water extract 15L, mixed to form microemulsion, added conventional adjuvant, and soft capsule is made in packing.
Embodiment 32:
10: 20: 0.2 in proportion: 0.5 got tween 10L, propylene glycol 20L, Radix Angelicae Sinensis volatile oil 0.2L, distilled water 0.5L, mixed to form microemulsion, added conventional adjuvant, and injection is made in packing.
Embodiment 33:
10: 1: 5 in proportion: 0.5 got lecithin 10L, glycerol 1L, oleic acid 5L, Cortex Magnoliae Officinalis water extract 0.5L, mixed to form microemulsion, added conventional adjuvant, and enema is made in packing.
Embodiment 34:
10: 20: 5 in proportion: 15 got polyoxyethylene castor oil 10L, sorbitol 20Kg, Oleum Arachidis hypogaeae semen 5L, Radix Angelicae Sinensis water extract 15L, mixed to form microemulsion, added conventional adjuvant, and oral liquid is made in packing.
Embodiment 35:
10: 1: 0.2 in proportion: 0.5 got lecithin 10L, sorbitol 1L, Oleum Glycines 0.2L, rose water extract 0.5L, mixed to form microemulsion, added conventional adjuvant, and the soft capsule suspensoid is made in packing.
Embodiment 36:
10: 20: 5 in proportion: 15 got polyoxyethylene castor oil 10L, sorbitol 20kg, Oleum Arachidis hypogaeae semen 5L, Radix Angelicae Sinensis water extract 15L, mixed to form microemulsion, added agrimonine 4Kg again, added conventional adjuvant, and oral liquid is made in packing.
Embodiment 37:
10: 1: 0.2 in proportion: 0.5 got lecithin l0L, sorbitol 1Kg, Oleum Glycines 0.2L, rose water extract 0.5L, mixed to form microemulsion, added astragalus polysaccharides 100g again, added conventional adjuvant, and the soft capsule suspensoid is made in packing.
Embodiment 38:
10: 20: 0.2 in proportion: 0.5 got tween 10L, propylene glycol 20L, Radix Angelicae Sinensis volatile oil 0.2L, distilled water 0.5L, Radix Angelicae Sinensis volatile oil 0.2L is dissolved among the propylene glycol 20L, add tween 10L, distilled water 0.5L, matrine 100g again, add conventional adjuvant, injection is made in packing.
Embodiment 39:
10: 1: 5 in proportion: 0.5 got lecithin 10L, glycerol 1L, oleic acid 5L, Cortex Magnoliae Officinalis water extract 0.5L, oleic acid 5L is dissolved among the glycerol 1L, add lecithin 10L, Cortex Magnoliae Officinalis water extract 0.5L, solatene 20g mixing formation microemulsion again, add conventional adjuvant, enema is made in packing.
Embodiment 40:
Be 10: 20: 1 in proportion: 10 get tween 80 10L, ethanol 20L, isopropyl myristate 1L, distilled water 10L, mix to form microemulsion, add Quercetin 0.6Kg again, and arteannuin 0.5Kg adds conventional adjuvant, and capsule is made in packing.
Embodiment 41:Liujunzi Tang microemulsion capsule
Liujunzi Tang: Radix Ginseng (9 gram) Rhizoma Atractylodis Macrocephalae (9 gram) Poria (9 gram) Radix Glycyrrhizae Preparata (6 gram) Pericarpium Citri Reticulatae (3 gram) Rhizoma Pinelliae (4.5 gram)
Volatile oil in the Liujunzi Tang can be prepared by following method: get Rhizoma Atractylodis Macrocephalae 9kg, Pericarpium Citri Reticulatae 3kg, Rhizoma Pinelliae 4.5kg, place volatile oil extractor to extract volatile oil 0.8L;
Water extract in the Liujunzi Tang can be prepared by following method: get Radix Ginseng 9kg, Poria 9kg, Radix Glycyrrhizae Preparata 6kg, extract with distilled water 100L, extracting solution 20L adds 65% ethanol 100L, leaves standstill, and filters, and filtrate is concentrated into 10L;
10: 20: 0.8 in proportion: 10 got tween 80 10L, ethanol 20L, the volatile oil 0.8L in the Liujunzi Tang; Water extract 10L in the Liujunzi Tang; Volatile oil in the Liujunzi Tang is dissolved in the ethanol, adds tween 80 more respectively, the water extract in the Liujunzi Tang mixes forming microemulsion, adds conventional dressing, encapsulated getting final product.
Embodiment 42:The compound Chinese angelica-root microemulsion capsule that looses
Compound Chinese angelica-root looses: Radix Angelicae Sinensis 9 grams, Rhizoma Chuanxiong 9 grams, the Radix Paeoniae Alba 20 grams, Poria 12 grams, the Rhizoma Atractylodis Macrocephalae 12 grams, Rhizoma Alismatis 9 grams
Volatile oil during compound Chinese angelica-root looses can be prepared by following method: get Radix Angelicae Sinensis 9kg, Rhizoma Chuanxiong 9kg, Rhizoma Atractylodis Macrocephalae 12kg, extract volatile oil with steam distillation respectively, getting Radix Angelicae Sinensis volatile oil is 0.18L, Rhizoma Chuanxiong volatile oil 0.2L, Rhizoma Atractylodis Macrocephalae volatile oil 0.3L;
Water extract during compound Chinese angelica-root looses can be prepared by following method: get Radix Paeoniae Alba 20kg, and Poria 12kg, Rhizoma Alismatis 9kg uses 6 times of water extraction respectively, and precipitate with ethanol is concentrated into 10L more respectively;
10: 20: 0.18 in proportion: 0.2: 0.3: 10: get tween 80 at 10: 10, ethanol, above-mentioned Radix Angelicae Sinensis volatile oil 0.18L, Rhizoma Chuanxiong volatile oil 0.2L, Rhizoma Atractylodis Macrocephalae volatile oil 0.3L, Radix Paeoniae Alba water extract 10L, Poria water extract 10L, Rhizoma Alismatis water extract 10L; Earlier three kinds of volatile oil all are dissolved in ethanol; Add tween 80 and three kinds of medicine water extracts again, be stirred to evenly, form microemulsion; Add conventional dressing, make capsule.
Claims (20)
1, a kind of microemulsion formulation of being made up of surfactant, cosurfactant, oil phase, water is characterized in that the proportion relation of surfactant, cosurfactant, oil phase, water is: surfactant: cosurfactant: oil phase: water is 1-10: 1-20: 0.2-5: 0.5-15.
2, microemulsion formulation as claimed in claim 1, the proportion relation that it is characterized in that surfactant, cosurfactant, oil phase, water is 5: 20: 1: 15.
3, microemulsion formulation as claimed in claim 1, the proportion relation that it is characterized in that surfactant, cosurfactant, oil phase, water is 10: 20: 1: 10.
4, microemulsion formulation as claimed in claim 1, the proportion relation that it is characterized in that surfactant, cosurfactant, oil phase, water is 10: 20: 2: 10.
5, microemulsion formulation as claimed in claim 1, the proportion relation that it is characterized in that surfactant, cosurfactant, oil phase, water is 5.5: 2: 2.5: 0.5.
6, microemulsion formulation as claimed in claim 1, the proportion relation that it is characterized in that surfactant, cosurfactant, oil phase, water is 6: 3: 2.5: 1.
7, as claim 1,2,3,4,5 or 6 described microemulsion formulations, it is characterized in that in microemulsion formulation, adding pharmaceutically active substance in a kind of and/or several solid, the amount that adds pharmaceutically active substance in the solid is to contain conventional effective dose in the preparation.
8,, it is characterized in that oil phase wherein is a kind of and/or several in the volatile oil that extracts of isopropyl myristate, Oleum Glycines, Oleum Arachidis hypogaeae semen, oleic acid, single or herbal mixture as claim 1,2,3,4,5 or 6 described microemulsion formulations; Water is a kind of and/or several in distilled water, single and/or the herbal mixture water extract.
9, microemulsion formulation as claimed in claim 7 is characterized in that oil phase wherein is a kind of and/or several in the volatile oil that extracts of isopropyl myristate, Oleum Glycines, Oleum Arachidis hypogaeae semen, oleic acid, single or herbal mixture; Water is a kind of and/or several in distilled water, single or the herbal mixture water extract.
10, microemulsion formulation as claimed in claim 8 is characterized in that single in the oil phase and/or herbal mixture volatile oil in the microemulsion formulation, and/or the content of the single of aqueous phase and/or herbal mixture water extract is conventional effective dose.
11,, it is characterized in that described microemulsion formulation is meant soft capsule, suspensoid, oral liquid, enema or injection as claim 9 or 10 described microemulsion formulations.
12, the preparation method of microemulsion formulation as claimed in claim 9 is characterized in that this method is a kind of in the following method:
A, get pharmaceutically active substance in surfactant, cosurfactant, oil phase, water and the solid in proportion; Under the temperature of 25 degree-65 degree Celsius, surfactant, cosurfactant, oil phase, water are mixed the formation microemulsion formulation; Add pharmaceutically active substance in the solid, form the pastille microemulsion formulation;
B, get pharmaceutically active substance in surfactant, cosurfactant, oil phase, water and the solid in proportion; Under the temperature of 25 degree-65 degree Celsius, oil phase is dissolved in makes its dissolving in the cosurfactant, under stirring condition, add surfactant, water and mix and form microemulsion formulation; Add pharmaceutically active substance in the solid, form the pastille microemulsion formulation;
C, get pharmaceutically active substance in surfactant, cosurfactant, oil phase, water and the solid in proportion; Under the temperature of 25 degree-65 degree Celsius with solid in pharmaceutically active substance be dissolved in cosurfactant, oil phase and/or aqueous phase and make its dissolving, under stirring condition, add the surfactant that does not add again, cosurfactant, oil phase and/or water mix the microemulsion formulation that forms pastille.
13, the preparation method of microemulsion formulation as claimed in claim 10 is characterized in that this method is a kind of in the following method:
A, under the temperature of 25 degree-65 degree Celsius, get surfactant, cosurfactant, oil phase and water in proportion, mix to form microemulsion formulation;
B, Celsius 25 the degree-65 the degree temperature under, get surfactant, cosurfactant, oil phase and water in proportion; Oil phase is dissolved in makes its dissolving in the cosurfactant, under stirring condition, add surfactant, water and mix and form microemulsion formulation.
14, microemulsion formulation as claimed in claim 1 is characterized in that this microemulsion formulation by tween 80, ethanol, Borneolum Syntheticum, distilled water, and be 10 parts by volume in proportion: 20 parts by volume: 2 weight portions: 10 parts by volume are made.
15, microemulsion formulation as claimed in claim 1 is characterized in that this microemulsion formulation by the volatile oil of tween 80, ethanol, Radix Angelicae Sinensis extraction, the water extract that Radix Angelicae Sinensis extracts, and be 5: 20: 0.2 by volume: 10 make.
16, microemulsion formulation as claimed in claim 1 is characterized in that this microemulsion formulation by the volatile oil of tween 80, ethanol, Rhizoma Chuanxiong extraction, the water extract that Rhizoma Chuanxiong extracts, and be 10: 20: 0.5 by volume: 20 make.
17, microemulsion formulation as claimed in claim 7 is characterized in that this microemulsion formulation by tween 80, sorbitol, Oleum Glycines, distilled water, is 6 parts by volume in proportion: 2.5 weight portions: 1.1 parts by volume: 10 parts by volume; Adding in the solid pharmaceutically active substance arasaponin 8 weight portions again makes.
18, microemulsion formulation as claimed in claim 7 is characterized in that this microemulsion formulation by lecithin, ethanol, oleic acid, distilled water, is 3 parts by volume in proportion: 3 parts by volume: 1.5 parts by volume: 10 parts by volume; Adding in the solid pharmaceutically active substance Radix Paeoniae Alba total glucosides 0.85 weight portion again makes.
19, microemulsion formulation as claimed in claim 7 is characterized in that this microemulsion formulation by polyoxyethylene castor oil, propylene glycol, Oleum Glycines, distilled water, is 10: 5: 2 by volume: 10; Adding in the solid pharmaceutically active substance TANSHINONES 0.55 weight portion again makes.
20, microemulsion formulation as claimed in claim 7, it is characterized in that this microemulsion formulation is by tween 80, ethanol, isopropyl myristate, distilled water, be 5: 20: 1 by volume: 15, add in the solid pharmaceutically active substance andrographolide 0.32 weight portion again and make.
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