CN103417481A - Preparation methods for multiple breviscapinum lipid carriers and gels thereof - Google Patents
Preparation methods for multiple breviscapinum lipid carriers and gels thereof Download PDFInfo
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Abstract
The invention belongs to the technical field of medicines, and discloses preparation methods for multiple breviscapinum lipid carriers and gels thereof. The invention discloses breviscapinum lipid carrier gels and a general gel which are both mainly prepared by the following raw materials: breviscapinum, a lipid material, carbomer, glycerin, anyhydrous ethanol, a phosphoric acid buffer with pH of 6-8. The entrapment rate of breviscapinun transfersomes is more than 50%, the entrapment rate of other three breviscapinun lipid carriers are more than 70%, the particle size are all less than 200 nm, and solid balls with uniform size are observed under an electron microscope. The four breviscapinun lipid carrier gels and the general gel all have uniform light-yellow color and pH of about 5.4, and are suitable for applying on skin surface; and the five gels have breviscapinun content of 0.048-0.057.
Description
Technical field
The invention belongs to medical technical field, relate to the preparation method of several breviscapine lipid carriers and gel thereof.
Technical background
The dry herb that Herba Erigerontis is the short booth Herba Erigerontis aceris of Compositae Herba Erigerontis aceris platymiscium, have good therapeutic effect to cerebral embolism, cerebral hemorrhage, cerebral thrombosis, hypertension, angina pectoris, polyneuritis, chronic arachnoiditis and sequela thereof, rheumatism, coronary heart disease.Breviscapine is the Flavonoid substances in Herba Erigerontis, comprises scutellarin and breviscapine, and scutellarin is the active component to the cardiovascular and cerebrovascular vessel onset.
Liposome is to be sealed the microsphere formed with concentrically ringed form by the single or multiple lift lipid bilayer, its structure and cell membrane are similar, and it has the drug targeting of making reticuloendothelial system, extends drug effect, reduces drug toxicity, avoids toleration, improves the advantages such as curative effect as pharmaceutical carrier; Carrier claims again deformable body, flexible nano-liposomes, is a kind of lipid vesicle with high deformation.With conventional liposome, compare, carrier under pressure, can be out of shape that to clamp-on and pass on horny layer be the micropore of itself diameter 1/5, and its diameter becomes hardly before and after this.This character of carrier comes from the inhomogeneities of lipid membrane, and reason is to have added the surfactant that contributes to its deformation in its lipid membrane.
Solid lipid nanoparticle is that natural or synthetic lipid materials is the submicron drug-supplying system that pharmaceutical carrier is made, can improve the penetrance of medicine to skin for the local skin administration, increase the hydration of skin, reduce the untoward reaction that medicine brings because of systemic Absorption; Nano structured lipid carrier is that inconsistent liquid fatty on solid lipid and space is mixed with to the nanoparticle drug administration carrier obtained at a certain temperature.Nano structured lipid carrier has replaced the solid lipid in the solid lipid nanoparticle with a certain proportion of liquid lipid or mixing lipid, the shortcomings such as the drug loading that has solved solid lipid nanoparticle is low, physical stability is poor, higher drug loading and physical stability are preferably not only arranged, and there is the control drug release same with solid lipid nanoparticle, avoid drug degradation and the characteristics such as toxicity is low.
Transdermal delivery system refers to that medicine passes through skin with constant speed, enter the body circulation and a class drug-supplying system of generation curative effect through blood capillary, can avoid the destruction to medicine of the first pass effect of liver and gastrointestinal enzymolysis, make to enter blood circulation after the diffusion of drug percutaneous skin, osmotic absorption, maintain for a long time stable blood drug level, but its application is limited to the physicochemical property of medicine and the barrier of skin.The percutaneous gel is semisolid or the glop preparation that medicine and suitable substrate are made, and has good biocompatibility and stability, to the skin nonirritant.Lipid carrier is prepared into to gel, can reduces the bimolecular mobility of lipid, prevent that medicine from oozing out carrier and the suspending effect is arranged, can increase the stability of carrier and medicine, thereby improve drug bioavailability, promote the osmosis of skin to medicine.
In the breviscapine dosage form of listing, conventional tablet and granule oral administration biaavailability are low at present, and normal injection and injectable powder injection administration half-life are short, in body, eliminate rapidly, and patient compliance is poor.Breviscapine water solublity and fat-soluble all not good, its physicochemical property and body expert are for having limited its clinical practice.The technical problem to be solved in the present invention has been to provide the preparation method of several breviscapine lipid carriers and gel thereof, by the percutaneous dosing approach, strengthens breviscapine stability, improves its bioavailability.
Summary of the invention
The purpose of this invention is to provide that several Transdermal absorption are effective, bioavailability is high, the breviscapine lipid carrier gel of good stability and ordinary gel and preparation method thereof, to strengthen breviscapine stability, promote the absorption of skin to breviscapine, improve its bioavailability.
The present invention, according to the carrier characteristic, selects the mixture of a certain proportion of phospholipid, surfactant to prepare the carrier of sealing a certain proportion of breviscapine.Film material phospholipid can be used the commodity phospholipid gone on the market, and comprises natural phospholipid, synthetic phospholipid, and surfactant can be used cholic acid salt etc.
The present invention, according to the solid lipid nanoparticle characteristic, selects the mixture of a certain proportion of solid lipid material, emulsifying agent, non-ionic surface active agent to prepare the solid lipid nanoparticle of sealing a certain proportion of breviscapine.The solid lipid material can be used saturated fatty acid glyceride class, fatty acid, mixing lipid etc.; Emulsifying agent can use phospholipid, comprises natural phospholipid, synthetic phospholipid; Non-ionic surface active agent can be used poloxamer series, polysorbate series, cholic acid salt etc.
The present invention, according to the nano structured lipid carrier characteristic, selects the mixture of a certain proportion of solid lipid material, liquid lipoid material, emulsifying agent, non-ionic surface active agent to prepare the nano structured lipid carrier of sealing a certain proportion of breviscapine.The solid lipid material can be used saturated fatty acid glyceride class, fatty acid, mixing lipid etc.; Liquid lipoid material can be used sad capric acid triglyceride, isopropyl palmitate, isopropyl myristate, liquid paraffin, soybean oil, oleic acid etc.; Emulsifying agent can use phospholipid, comprises natural phospholipid, synthetic phospholipid; Non-ionic surface active agent can be used poloxamer series, polysorbate series, cholic acid salt etc.
The phospholipid of described preparation carrier is soybean lecithin, and surfactant is sodium cholate, and each raw material weight umber is: breviscapine 1, soybean lecithin 2～10, sodium cholate 1～5.
Described carrier preparation method adopts film dispersion method, preparation method realizes according to the following steps: one, by the methanol-dichloromethane mixed solution that is 1～2: 1 with surfactant dissolves 1～5 parts by weight in appropriate ratio the lecithin of the breviscapine of 1 parts by weight, 2～10 parts by weight, 30～40 ℃ revolve to steam and remove organic reagent, make filmogen form the uniform lipid membrane of one deck on the round-bottomed flask wall; Two, the phosphate buffer solution of appropriate pH6～8 is slowly poured in the lipid membrane in step 1,30～40 ℃ revolve steaming hydration 0.5～2h lipid membrane are come off fully; Three, liquid freon water-bath Probe Ultrasonic Searching 2～8min step 2 obtained, the phosphate buffer solution standardize solution of appropriate pH6～8, obtain breviscapine carrier suspension, is positioned under 0～5 ℃ of condition and keeps in Dark Place.
The present invention makes carrier and observes under transmission electron microscope, and for real spherical, size evenly.The average envelop rate of breviscapine carrier is 53.90%, and mean diameter is 99.26nm.
The described solid lipid material for preparing solid lipid nanoparticle is glyceryl monostearate, emulsifying agent is soybean lecithin, non-ionic surface active agent is PLURONICS F87, and each raw material weight umber is: breviscapine 1, solid lipid material 2～8, emulsifying agent 2～8, non-ionic surface active agent 15～25.
Described solid lipid nanoparticle preparation method adopts solvent diffusion method, preparation method realizes according to the following steps: one, by the emulsifying agent of the solid lipid material of the breviscapine of 1 parts by weight, 2～8 parts by weight and 2～8 parts by weight, in 60～80 ℃ of water-baths, dissolve in appropriate methanol, form organic facies; Two, the non-ionic surface active agent of 15～25 parts by weight is dissolved in the appropriate water of uniform temp, insulation, form water; Three, with syringe, water is slowly injected to organic facies under stirring condition; stir 1～2h; vacuum rotary steam is until the organic solvent volatilization is complete; place room temperature; be transferred in measuring bottle; add the suitable quantity of water standardize solution, obtain breviscapine solid lipid nanoparticle suspension, be positioned under 0～5 ℃ of condition and keep in Dark Place.
The present invention makes solid lipid nanoparticle and observes under transmission electron microscope, and for real spherical, size evenly.The average envelop rate of breviscapine solid lipid nanoparticle is 76.62%, and mean diameter is 132.13nm.
The described nano structured lipid carrier solid lipid material for preparing is glyceryl monostearate, liquid lipoid material is soybean oil, emulsifying agent is soybean lecithin, non-ionic surface active agent is PLURONICS F87, and each raw material weight umber is: breviscapine 1, solid lipid material 2～8, liquid lipoid material 2～25, emulsifying agent 2～8, non-ionic surface active agent 15～25.
Described nano structured lipid carrier preparation method adopts solvent diffusion method, preparation method realizes according to the following steps: one, the emulsifying agent of the liquid lipoid material of the solid lipid material of the breviscapine of 1 parts by weight, 2～8 parts by weight, 2～25 parts by weight and 2～8 parts by weight is dissolved in 60～80 ℃ of water-baths in appropriate methanol, form organic facies; Two, the non-ionic surface active agent of 15～25 parts by weight is dissolved in the appropriate water of uniform temp, insulation, form water; Three, with syringe, water is slowly injected to organic facies under stirring condition, stir 1～2h, vacuum rotary steam is until the organic solvent volatilization is complete, place room temperature, be transferred in measuring bottle, add the suitable quantity of water standardize solution, obtain breviscapine nano structured lipid carrier suspension, be positioned under 0～5 ℃ of condition and keep in Dark Place.
The present invention makes nano structured lipid carrier and observes under transmission electron microscope, and for real spherical, size evenly.The average envelop rate of breviscapine solid lipid nanoparticle is 76.38%, and mean diameter is 198.77nm.
The present invention, according to percutaneous gel characteristic, selects the phosphate buffer solution of a certain proportion of lipid carrier suspension or drug solution, gel-type vehicle, wetting agent, solubilizing agent, antiseptic, pH adjusting agent and pH6～8.Gel-type vehicle is carbomer series, and wetting agent is glycerol, and solubilizing agent is dehydrated alcohol, and antiseptic is the Pyrusussuriensis acids, and pH adjusting agent is triethanolamine.Each raw material weight umber is: lipid carrier suspension or drug solution are appropriate, carbomer 0.5～5%, glycerol 0.5～2%, dehydrated alcohol 0.5～2%, sorbic acid 0.1～0.3%, triethanolamine are appropriate.
Addition method after described gel forming process using matrix-forming, preparation method realizes according to the following steps: one, the preparation of blank gel-type vehicle: take appropriate carbomer powder, fully dissolve swelling with the phosphate buffer solution of appropriate pH6～8, drip appropriate triethanolamine and regulate pH5～7, obtaining concentration is 3～8% blank gel-type vehicles; Two, take the blank gel of the described carbomer of appropriate step 1, add recipe quantity glycerol, fully stir; Take the recipe quantity sorbic acid, add in the recipe quantity dehydrated alcohol ultrasonic dissolution; The ethanol solution that is dissolved with sorbic acid is added in gel-type vehicle, fully stir; Three, slowly in the described substrate of step 2, add lipid carrier suspension or drug solution, fully stir; Supplement the phosphate buffer solution of pH6～8 to appropriate, fully stir swelling, obtaining concentration is lipid carrier gel or the ordinary gel that 0.5～2% carbomer, breviscapine content are 0.5～1%.
The accompanying drawing explanation
Fig. 1 breviscapine carrier particle size distribution figure
Fig. 2 breviscapine carrier Electronic Speculum figure
Fig. 3 breviscapine solid lipid nanoparticle particle size distribution figure
Fig. 4 breviscapine solid lipid nanoparticle Electronic Speculum figure
Fig. 5 breviscapine nano structured lipid carrier particle size distribution figure
Fig. 6 breviscapine nano structured lipid carrier Electronic Speculum figure
Fig. 7 breviscapine lipid carrier gel and ordinary gel outward appearance
The specific embodiment
Technical solution of the present invention is not limited to the following cited specific embodiment, also comprises the combination in any between each specific embodiment.
The specific embodiment one:
A kind of preparation method of breviscapine liposome, step is as follows: precision takes soybean lecithin 50mg, cholesterol 25mg, breviscapine 10mg puts in the 1000ml round-bottomed flask, add methanol-dichloromethane (1: 1) solution 30ml, ultrasonicly make its dissolving, form faint yellow troubled liquor, 35 ℃ revolve to steam and remove organic reagent, make filmogen form the uniform lipid membrane of one deck on the round-bottomed flask wall, add normal saline 12.5ml, revolve steaming hydration 1h lipid membrane is come off fully, obtain faint yellow suspension; Ice-water bath Probe Ultrasonic Searching 5min, be transferred in 20ml scale test tube, adds normal saline dilution to 12.5ml, obtains.
The specific embodiment two:
A kind of preparation method of breviscapine carrier, step is as follows: precision takes soybean lecithin 50mg, sodium cholate 25mg, breviscapine 10mg puts in the 1000ml round-bottomed flask, add methanol-dichloromethane (1: 1) solution 30ml, ultrasonic dissolution forms weak yellow liquid, 35 ℃ revolve to steam and remove organic reagent, make filmogen form the uniform lipid membrane of one deck on the round-bottomed flask wall, add pH6.8 phosphate buffer solution 12.5ml, revolving steaming hydration 1h comes off lipid membrane fully, obtain faint yellow suspension, ice-water bath Probe Ultrasonic Searching 5min, be transferred in 20ml scale test tube, add the pH6.8 phosphate buffer solution and be diluted to 12.5ml, obtain.
The specific embodiment three:
A kind of preparation method of breviscapine solid lipid nanoparticle, step is as follows: precision takes breviscapine 10mg, monoglyceride 40mg, lecithin 20mg is dissolved in 10ml methanol in (70 ± 1) ℃, forms organic facies; Another precision takes in the 10ml water that PLURONICS F87 0.2g is dissolved in uniform temp, and insulation, form water; With syringe, water is slowly injected to organic facies under stirring condition, stir 2h, vacuum rotary steam, until the organic solvent volatilization fully, is placed room temperature, is transferred in the 10ml measuring bottle, is diluted with water to scale, obtains.
The specific embodiment four:
A kind of preparation method of breviscapine nano structured lipid carrier, step is as follows: precision takes breviscapine 10mg, monoglyceride 40mg, lecithin 20mg, soybean oil 60mg are dissolved in 10ml methanol in (70 ± 1) ℃, forms organic facies; Another precision takes in the 10ml water that the 0.2g PLURONICS F87 is dissolved in uniform temp, and insulation, form water; In under stirring condition, organic facies slowly being splashed into to water, stir 2h; Vacuum rotary steam, until the organic solvent volatilization fully, is placed room temperature, is transferred in the 10ml measuring bottle, is diluted with water to scale, obtains.
The specific embodiment five:
The preparation method of breviscapine liposome gel and carrier gel, step is as follows:
Precision takes appropriate carbomer powder, adds appropriate pH7.4 phosphate buffer solution and fully stirs, and with triethanolamine, regulates pH to 6.0～6.5, supplements the pH7.4 phosphate buffer solution to weight, fully stirs, and making its concentration is 5%, and swelling is spent the night.
Precision takes 5% carbomer substrate 1.6g, and glycerol adding 1ml, stir; Precision takes sorbic acid 0.02g ultrasonic dissolution in the 1ml dehydrated alcohol, adds in substrate and stirs; Precision measures liposome/carrier suspension 6.25ml, slowly adds in above-mentioned substrate, and the limit edged stirs, and supplements the pH7.4 phosphate buffer solution to 10g, fully stirs, and swelling is spent the night, and obtains.
The specific embodiment six:
The preparation method of breviscapine solid lipid nanoparticle gel and nano structured lipid carrier gel, step is as follows:
Precision takes appropriate carbomer powder, adds appropriate pH7.4 phosphate buffer solution and fully stirs, and with triethanolamine, regulates pH to 6.0～6.5, supplements the pH7.4 phosphate buffer solution to weight, fully stirs, and making its concentration is 5%, and swelling is spent the night.
Precision takes 5% carbomer substrate 1.6g, and glycerol adding 1ml, stir; Precision takes sorbic acid 0.02g ultrasonic dissolution in the 1ml dehydrated alcohol, adds in substrate and stirs; Precision measures solid lipid nanoparticle/nano structured lipid carrier suspension 5ml, slowly adds in above-mentioned substrate, and the limit edged stirs, and supplements the pH7.4 phosphate buffer solution to 10g, fully stirs, and swelling is spent the night, and obtains.
The specific embodiment seven:
The preparation method of breviscapine ordinary gel: step is as follows:
Precision takes appropriate carbomer powder, adds appropriate pH7.4 phosphate buffer solution and fully stirs, and with triethanolamine, regulates pH to 6.0～6.5, supplements the pH7.4 phosphate buffer solution to weight, fully stirs, and making its concentration is 5%, and swelling is spent the night.
Precision takes 5% carbomer substrate 1.6g, and glycerol adding 1ml, stir; Precision takes sorbic acid 0.02g ultrasonic dissolution in the 1ml dehydrated alcohol, adds in substrate and stirs; Precision takes breviscapine active pharmaceutical ingredient powder 5mg, and ultrasonic dissolution, in appropriate pH7.4 phosphate buffer solution, slowly adds in above-mentioned substrate, and the limit edged stirs, and supplements the pH7.4 phosphate buffer solution to 10g, fully stirs, and swelling is spent the night, and obtains.
Claims (8)
1. a breviscapine carrier, is characterized in that, it is mainly made by the raw material of following parts by weight: the phosphate buffer solution of breviscapine 1, lecithin 2～10, surfactant 1～5, pH6～8.
2. a breviscapine solid lipid nanoparticle, is characterized in that, it is mainly made by the raw material of following parts by weight: breviscapine 1, solid lipid material 2～8, emulsifying agent 2～8, non-ionic surface active agent 15～25.
3. a breviscapine nano structured lipid carrier, is characterized in that, it is mainly made by the raw material of following parts by weight: breviscapine 1, solid lipid material 2～8, liquid lipoid material 2～25, emulsifying agent 2～8, non-ionic surface active agent 15～25.
4. four kinds of breviscapine lipid carrier gels, is characterized in that, described gel is comprised of the phosphate buffer solution of breviscapine lipid carrier A, gel-type vehicle B, wetting agent C, solubilizing agent D, antiseptic E, pH adjusting agent F and pH6～8.
5. a breviscapine gel, is characterized in that, described gel is comprised of the phosphate buffer solution of breviscapine, gel-type vehicle B, wetting agent C, solubilizing agent D, antiseptic E, pH adjusting agent F and pH6～8.
6. according to claim 4,5 described four kinds of breviscapine lipid carrier gels and breviscapine gels, it is characterized in that, described gel-type vehicle B 0.5～5% carbomer, wetting agent C 0.5～2% glycerol, solubilizing agent D be weight percentage 0.1～0.3% sorbic acid, pH adjusting agent F of 0.5～2% dehydrated alcohol, antiseptic E that be weight percentage that be weight percentage that be weight percentage is a certain amount of triethanolamine.
7. according to claim 1,2,3 described breviscapine carriers, solid lipid nanoparticle and nano structured lipid carrier, it is characterized in that described lipid carrier preparation method comprises following method and step:
(1) preparation of breviscapine carrier:
1. by the methanol-dichloromethane mixed solution that is 1～2: 1 with surfactant dissolves 1～5 parts by weight in appropriate ratio the lecithin of the breviscapine of 1 parts by weight, 2～10 parts by weight, 30～40 ℃ revolve to steam and remove organic reagent, make filmogen form the uniform lipid membrane of one deck on the round-bottomed flask wall;
2. the phosphate buffer solution of appropriate pH6～8 is slowly poured in the lipid membrane of step in 1., 30～40 ℃ revolve and steam hydration 0.5～2h lipid membrane is come off fully;
3. the liquid freon water-bath Probe Ultrasonic Searching 2～8min 2. step obtained, the phosphate buffer solution standardize solution of appropriate pH6～8, obtain breviscapine carrier suspension.
(2) preparation of breviscapine solid lipid nanoparticle:
1. by the emulsifying agent of the solid lipid material of the breviscapine of 1 parts by weight, 2～8 parts by weight and 2～8 parts by weight, in 60～80 ℃ of water-baths, dissolve in appropriate methanol, form organic facies;
2. the non-ionic surface active agent of 15～25 parts by weight is dissolved in the appropriate water of uniform temp, insulation, form water;
3. with syringe, water is slowly injected to organic facies under stirring condition, stir 1～2h, vacuum rotary steam, until the organic solvent volatilization fully, is placed room temperature, is transferred in measuring bottle, adds the suitable quantity of water standardize solution, obtains breviscapine solid lipid nanoparticle suspension.
(4) preparation of breviscapine nano structured lipid carrier:
1. the emulsifying agent of the liquid lipoid material of the solid lipid material of the breviscapine of 1 parts by weight, 2～8 parts by weight, 2～25 parts by weight and 2～8 parts by weight is dissolved in 60～80 ℃ of water-baths in appropriate methanol, form organic facies;
2. the non-ionic surface active agent of 15～25 parts by weight is dissolved in the appropriate water of uniform temp, insulation, form water;
3. with syringe, water is slowly injected to organic facies under stirring condition, stir 1～2h, vacuum rotary steam, until the organic solvent volatilization fully, is placed room temperature, is transferred in measuring bottle, adds the suitable quantity of water standardize solution, obtains breviscapine nano structured lipid carrier suspension.
8. four kinds of breviscapine lipid carrier gels according to claim 6 and breviscapine gel is characterized in that described lipid carrier gel and ordinary gel preparation method comprise following method and step:
(1) preparation of breviscapine lipid carrier gel:
1. the preparation of blank gel-type vehicle: take appropriate carbomer powder, with the phosphate buffer solution of appropriate pH6～8, fully dissolve swelling, drip appropriate triethanolamine and regulate pH5～7, obtaining concentration is 3～8% blank gel-type vehicles;
2. take in right amount the 1. blank gel of described carbomer, add recipe quantity glycerol, fully stir; Take the recipe quantity sorbic acid, add in the recipe quantity dehydrated alcohol ultrasonic dissolution; The ethanol solution that is dissolved with sorbic acid is added in gel-type vehicle, fully stir;
3. slowly to 2. in described substrate, adding lipid carrier suspension or drug solution, fully stir; Supplement the phosphate buffer solution of pH6～8 to appropriate, fully stir swelling, obtaining concentration is lipid carrier gel or the ordinary gel that 0.5～2% carbomer, breviscapine content are 0.5～1%.
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| CN104546974A (en) * | 2014-12-24 | 2015-04-29 | 昆明振华制药厂有限公司 | Erigeron phenol eye preparation and preparation method thereof |
| CN105534881A (en) * | 2015-12-31 | 2016-05-04 | 齐齐哈尔医学院 | Roxithromycin-loaded nanostructure lipid carrier gel and preparation method thereof |
| CN106344512A (en) * | 2016-10-10 | 2017-01-25 | 上海辰松新材料科技有限公司 | Breviscapine injection |
| CN106963977A (en) * | 2017-05-26 | 2017-07-21 | 广东海洋大学 | A kind of Breviscapinun/chitosan composite aquogel for suppressing cicatrization and preparation method thereof |
| CN108066315A (en) * | 2016-11-11 | 2018-05-25 | 天津中医药大学 | Puerarin and scutellarin lipid nano particle eye-drops preparations and preparation method thereof |
| CN110898011A (en) * | 2019-11-27 | 2020-03-24 | 西南医科大学 | Etomidate nano preparation and preparation method thereof |
| CN112315946A (en) * | 2020-11-02 | 2021-02-05 | 苏州凯祥生物科技有限公司 | Breviscapine inhalant and preparation method thereof |
| CN116509916A (en) * | 2023-06-15 | 2023-08-01 | 云南德彩堂生物医药科技有限公司 | Erigeron breviscapus active site liposome, and preparation method and application thereof |
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2012
- 2012-05-14 CN CN2012101473605A patent/CN103417481A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104546974A (en) * | 2014-12-24 | 2015-04-29 | 昆明振华制药厂有限公司 | Erigeron phenol eye preparation and preparation method thereof |
| CN105534881A (en) * | 2015-12-31 | 2016-05-04 | 齐齐哈尔医学院 | Roxithromycin-loaded nanostructure lipid carrier gel and preparation method thereof |
| CN105534881B (en) * | 2015-12-31 | 2019-04-05 | 齐齐哈尔医学院 | A kind of load roxithromycin nano structured lipid carrier gelling agent and preparation method thereof |
| CN106344512A (en) * | 2016-10-10 | 2017-01-25 | 上海辰松新材料科技有限公司 | Breviscapine injection |
| CN108066315A (en) * | 2016-11-11 | 2018-05-25 | 天津中医药大学 | Puerarin and scutellarin lipid nano particle eye-drops preparations and preparation method thereof |
| CN106963977A (en) * | 2017-05-26 | 2017-07-21 | 广东海洋大学 | A kind of Breviscapinun/chitosan composite aquogel for suppressing cicatrization and preparation method thereof |
| CN106963977B (en) * | 2017-05-26 | 2018-03-30 | 广东海洋大学 | A kind of Breviscapinun/chitosan composite aquogel for suppressing cicatrization and preparation method thereof |
| CN110898011A (en) * | 2019-11-27 | 2020-03-24 | 西南医科大学 | Etomidate nano preparation and preparation method thereof |
| CN110898011B (en) * | 2019-11-27 | 2022-02-08 | 西南医科大学 | Etomidate nano preparation and preparation method thereof |
| CN112315946A (en) * | 2020-11-02 | 2021-02-05 | 苏州凯祥生物科技有限公司 | Breviscapine inhalant and preparation method thereof |
| CN116509916A (en) * | 2023-06-15 | 2023-08-01 | 云南德彩堂生物医药科技有限公司 | Erigeron breviscapus active site liposome, and preparation method and application thereof |
| CN116509916B (en) * | 2023-06-15 | 2024-04-19 | 云南德彩堂生物医药科技有限公司 | Erigeron breviscapus active site liposome, and preparation method and application thereof |
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Application publication date: 20131204 |