CN102805732A - Tanshinone IIA lipid microsphere preparation and preparation method thereof - Google Patents
Tanshinone IIA lipid microsphere preparation and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a tanshinone IIA lipid microsphere preparation and a preparation method thereof. 1000 ml of the preparation is prepared according to a formula, wherein the formula comprises, by weight, 0.01-1.0 g of tanshinone IIA, 10-200.0 g of oil for injection, 2.0-20 g of an emulsifying agent, 4.0-10.0 g of an isotonic regulator and the balance of water. According to the preparation method, a drug and phospholipid are firstly dissolved in a suitable solvent, then the solvent is removed, and the resulting material is added to an oil phase, wherein entrapment rate of the prepared product is significantly improved, a disadvantages of poor water solubility of the tanshinone IIA is overcome with the preparation method, a lipid microsphere preparation with characteristics of low toxic reaction, low irritation, long effect time, sustaining and targeting is provided, a process is simple process, cost is low, and the method is applicable for industrial production.
Description
Technical field
Key in technical field herein and describe paragraph.The present invention relates to preparation of a kind of tanshinone IIA lipoid microsphere and preparation method thereof.
Background technology
[0002] tanshinone (tanshinone IIA) is the main effective ingredient of China's Chinese medicine Radix Salviae Miltiorrhizae.Have the coronary artery circulation of improvement, suppress thrombus disease and take place, improve myocardial contraction, promote cardiac muscle regeneration, expansion arteriole, many-sided pharmacological actions such as microcirculation improvement obstacle.But tanshinone dissolubility in water is very low, and oral administration biaavailability is low.At present; Clinical preparation only has the sodium tanshinone IIA sulfate injection, because it has changed the structure of tanshinone, pharmacological action changes to some extent, can't pass blood brain barrier; And the generation of untoward reaction such as local pain, swelling sense, erythra appears in administration often, and clinical practice receives great restriction.Press for and select a kind of new drug-supplying system, solve the problem of its existence, bring into play the curative effect of medicine to greatest extent.The tanshinone IIA lipid microsphere injection adopts the medicine carrying mode of lipoid microsphere, and drug encapsulation in oil phase, has been significantly reduced irritating generation; Improved the dissolubility of tanshinone simultaneously; Optionally build up at diseased regions such as inflammation, blood vessel endothelium system, arteriosclerosis, make the medicine several times that concentration exceeds conventional formulation in the target area to hundreds of times, therapeutic effect is obvious.If but prescription or method for preparing are unreasonable, can cause envelop rate low, the free tanshinone of aqueous phase still possibly cause the generation of untoward reaction.Secondly, free medicine can not optionally arrive diseased region, and the targeting effect reduces.Therefore, be necessary to control,, realize the purpose of said preparation to reach higher entrapment from tanshinone IIA lipoid microsphere prescription and technology.
Lipoid microsphere is medicine to be dissolved in the fatty oil be scattered in a kind of preparation that water is processed through phospholipid emulsifying, and mean diameter is at 200nm.Can medicine directly be transported to the novel targeted preparation at human lesion position, like this type preparation of some anticarcinogens and anti-inflammatory medicaments, microcirculation disturbance medicine.The report that does not also have at present the tanshinone fat micro sphere preparation.
Oil such as the Semen sojae atricolor wet goods used always in the fat milk are long-chain fatty acid ester, and life-time service possibly bring out hyperlipidemia, infringement immune system and reticuloendothelial system and liver function.Medium chain triglyceride (MCT) is that fat contains a kind or multiple triglyceride or its mixture with medium-chain fatty acid of about 6 to 14 carbon atom length.Medium chain triglyceride and lipoprotein lipase affinity are high and rapid, are easy in blood, degraded by lipoprotein lipase, are difficult for by reticuloendothelial system phagocytic.The life-time service toxic and side effects is less than long-chain fatty acid ester.
The formation theory of present lipoid microsphere is immaturity still, and according to the Interfacial Adsorption membrane theory, emulsifying agent is reducing the tensile while of two-phase interface, and directed commentaries on classics of emulsifying agent listed in around the drop, forms adsorbed film.According to the molecular structure of tanshinone, the affinity of inferring itself and phospholipid is less than its dissolubility in oil, and therefore, it should mainly be dispersed in oil reservoir, possibly have only less part can be distributed to aqueous phase.
Summary of the invention
The present invention is intended to overcome the difficult point of research tanshinone preparation, overcomes its water-insoluble, provides a kind of toxic reaction and zest little, and EDD is long, and has the tanshinone lipoid microsphere ejection preparation of persistence and targeting property.The present invention simultaneously overcomes the defective of prior art, and a kind of method for preparing of tanshinone lipoid microsphere of high envelop rate is provided.
Technical scheme of the present invention is following:
A kind of tanshinone fat micro sphere preparation, it comprises active component tanshinone and pharmaceutic adjuvant solvent, it is characterized in that: it is to process 1000ml according to following prescription proportioning.
Tanshinone IIA 0.01～1.0g
Oil for injection 10.0～200.0g
Emulsifying agent 2.0～20g
Isoosmotic adjusting agent 4.0～10.0g
Cumulative volume adds the injection water to 1000ml
The preferential prescription proportioning of above-mentioned lipoid microsphere is: process 1000ml according to following prescription proportioning.
Tanshinone IIA 0.02～0.2g
Oil for injection 50～150.0g
Emulsifying agent 1.0～12g
Isoosmotic adjusting agent 2.0～5.0g
Also can add membrane stabilizer in the said fat micro sphere preparation, like oleic acid or oleate.
Also can add antioxidant vitamin E etc. in the said fat micro sphere preparation.
Vegetable oil is selected from one or more the combination in soybean oil, Semen Maydis oil, safflower oil, the Fructus Canarii albi wet goods Vegetable oil lipoprotein in the said fat micro sphere preparation.
Emulsifying agent is selected at least a among soybean lecithin, Ovum Gallus domesticus Flavus lecithin, cholesterol, poloxamer, the injection Tween-80 etc. for use in the said fat micro sphere preparation.
Can not add or add isoosmotic adjusting agent in the said fat micro sphere preparation and select a kind of in glycerol, xylitol, sorbitol, fructose, the glucose etc. for use.
The method for preparing of fat micro sphere preparation of the present invention is processed by tanshinone IIA, oil for injection, emulsifying agent, stabilizing agent, isotonic agent and water for injection, it is characterized in that, may further comprise the steps:
(1) gets phospholipid and be dissolved in the suitable solvent, add the tanshinone IIA dissolving, decompression and solvent recovery, drying;
(2) preparation of oil phase: add emulsifying agent in the oil for injection respectively, stabilizing agent and step (1) tanshinone IIA stirs and makes its dissolving;
(3) preparation of water: isotonic agent added in the entry dissolve;
(4) preparation of colostrum: step (3) oil phase is added step (2) aqueous phase, and high speed shear is disperseed, and forms colostrum;
(5) high pressure homogenize: with step (4) colostrum through the homogenize of high pressure homogenizer high pressure;
(6) all operations under nitrogen protection of step (1) to (5).
The method for preparing of tanshinone IIA lipoid microsphere of the present invention is characterized in that, the described high speed shear jitter time of step (4) is 10～80 minutes, and shear rate is 2000～10000rpm, and temperature is 40～75 ℃.
The method for preparing of tanshinone IIA lipoid microsphere of the present invention is characterized in that, the described high pressure homogenize of step (5) pressure is 500～2500bar, homogenize number of times 2～6 times, 12～35 ℃ of temperature.
The method for preparing of tanshinone IIA lipoid microsphere of the present invention is characterized in that, the described solvent of step (1) is one or more the combination in ethanol, ethyl acetate, chloroform, dichloromethane, the acetone.
The method for preparing of tanshinone IIA lipoid microsphere of the present invention is characterized in that, the weight ratio of described phosphide consumption of step (1) and tanshinone IIA is 1～15:1.
The method for preparing of tanshinone IIA lipoid microsphere of the present invention; It is characterized in that described oil for injection is one or more the combination in refined soybean oil, Semen Maydis oil, Oleum Arachidis hypogaeae semen, medium chain glycerol glyceride, safflower oil, Oleum Gossypii semen, olive oil, Oleum Sesami, fish oil, medium chain glycerol dibasic acid esters, medium chain triglyceride, ethyl oleate, acetylated monoglyceride, propylene glycol dibasic acid esters, glyceryl linoleate, the Polyethylene Glycol glyceryl laurate ester.
The method for preparing of tanshinone IIA lipoid microsphere of the present invention is characterized in that, described oil for injection is refined soybean oil and medium chain triglyceride, and both weight ratios are 1:3～3:1.
The method for preparing of tanshinone IIA lipoid microsphere of the present invention is characterized in that, described emulsifying agent is soybean phospholipid or Ovum Gallus domesticus Flavus lecithin, and wherein the content of phosphatidylcholine is more than 80%.
The method for preparing of tanshinone IIA lipoid microsphere of the present invention is characterized in that, described stabilizing agent is one or more the combination in oleic acid or its salt, cholic acid or its salt, deoxycholic acid or its salt.
The method for preparing of tanshinone IIA lipoid microsphere of the present invention is characterized in that, described isotonic agent is one or more the combination in glycerol, mannitol, sorbitol, glucose, sucrose, the trehalose.
The present invention is dissolved into medicine and phospholipid earlier in the The suitable solvent through the adjustment method for preparing, removes then and desolvates; The envelop rate of finding medicine significantly improves, and its reason can be interpreted as, through this reaction; Medicine is embedded in the phospholipid uniformly; Form the structure of similar complex, thus increased medicine and phospholipid and with the affinity of oil phase, and then improved the envelop rate of tanshinone IIA.
Route of administration of the present invention mainly adopts the vein mode.
Specific embodiment
Be the convenient technology of investigating, the present invention drafts prescription as follows, is somebody's turn to do concrete prescription but technology of the present invention is not limited only to adaptation.
The comparative example 1
Prescription:
Tanshinone IIA 0.05g
Refining injection soybean oil 100.0g
Lecithin 12.0g
Glycerol 25 g
Enuatrol 0.5 g
Cumulative volume adds the injection water to 1000ml
Technical process:
(1) preparation of oil phase: will make with extra care the injection soybean oil and be heated to 70 ℃, enuatrol and tanshinone IIA stir and make its dissolving;
(2) preparation of water: glycerol added in the entry dissolve, be heated to 70 ℃;
(3) preparation of colostrum: step (1) oil phase is added step (2) aqueous phase, 70 ℃ of temperature, high speed shear is disperseed, shear rate 8000rpm, 10 minutes time, form colostrum, pH value 4.0～6.0 is regulated with sodium hydroxide in fast cooling to 15～30 ℃;
(4) high pressure homogenize: through high pressure homogenizer homogenize number of times 2～6 times, pressure is 500～2500bar, 12～35 ℃ of temperature with step (3) colostrum;
(5) all operations under nitrogen protection of step (1) to (4).
The comparative example 2
Prescription:
Tanshinone IIA 0.05g
Refining injection soybean oil 50.0g
Medium chain triglyceride 50.0g
Lecithin 12.0g
Glycerol 25 g
Enuatrol 0.5 g
Cumulative volume adds the injection water to 1000ml
Technical process:
(1) preparation of oil phase: will make with extra care injection soybean oil and medium chain triglyceride and be heated to 70 ℃, and add lecithin, enuatrol and tanshinone IIA stirring respectively and make its dissolving;
(2) preparation of water: glycerol added in the entry dissolve, be heated to 70 ℃;
(3) preparation of colostrum: step (1) oil phase is added step (2) aqueous phase, 70 ℃ of temperature, high speed shear is disperseed, shear rate 8000rpm, 10 minutes time, form colostrum, pH value 4.0～6.0 is regulated with sodium hydroxide in fast cooling to 15～30 ℃;
(4) high pressure homogenize: through high pressure homogenizer homogenize number of times 2～6 times, pressure is 500～2500bar, 12～35 ℃ of temperature with step (3) colostrum;
(5) all operations under nitrogen protection of step (1) to (4).
Embodiment 1
Prescription:
Tanshinone IIA 0.05g
Refining injection soybean oil 100.0g
Lecithin 12.0g
Glycerol 25 g
Enuatrol 0.5 g
Cumulative volume adds the injection water to 1000ml
Technical process:
(1) get lecithin 20mg, add dissolve with ethanol, add tanshinone IIA 0.05g, stir and make dissolving, one connects stirring, and a logotype nitrogen volatilizes ethanol;
(2) preparation of oil phase: will make with extra care the injection soybean oil and be heated to 70 ℃, and add lecithin, enuatrol and step (1) tanshinone IIA respectively, and stir and make its dissolving;
(2) preparation of water: glycerol added in the entry dissolve, be heated to 70 ℃;
(3) preparation of colostrum: step (2) oil phase is added step (3) aqueous phase, 70 ℃ of temperature, high speed shear is disperseed, shear rate 8000rpm, 10 minutes time, form colostrum, pH value 4.0～6.0 is regulated with sodium hydroxide in fast cooling to 15～30 ℃;
(5) high pressure homogenize: through high pressure homogenizer homogenize number of times 2～6 times, pressure is 500～2500bar, 12～35 ℃ of temperature with step (4) colostrum;
(6) all operations under nitrogen protection of step (1) to (4).
Embodiment 2
Prescription:
Tanshinone IIA 0.05g
Refining injection soybean oil 50.0g
Medium chain triglyceride 50.0g
Lecithin 12.0g
Glycerol 25 g
Enuatrol 0.5 g
Cumulative volume adds the injection water to 1000ml
Technical process:
(1) get lecithin 20mg, add dissolve with ethanol, add tanshinone IIA 0.05g, stir and make dissolving, decompression volatilizes ethanol;
(2) preparation of oil phase: will make with extra care injection soybean oil and medium chain triglyceride and be heated to 70 ℃, and add the stirring of lecithin, enuatrol and step (1) tanshinone IIA respectively and make its dissolving;
(3) preparation of water: glycerol added in the entry dissolve, be heated to 70 ℃;
(4) preparation of colostrum: step (2) oil phase is added step (3) aqueous phase, 70 ℃ of temperature, high speed shear is disperseed, shear rate 8000rpm, 10 minutes time, form colostrum, pH value 4.0～6.0 is regulated with sodium hydroxide in fast cooling to 15～30 ℃;
(5) high pressure homogenize: through high pressure homogenizer homogenize number of times 2～6 times, pressure is 500～2500bar, 12～35 ℃ of temperature with step (4) colostrum;
(6) all operations under nitrogen protection of step (1) to (5).
Embodiment 3
Prescription:
Tanshinone IIA 0.05g
Semen Maydis oil 100.0g
Ovum Gallus domesticus Flavus lecithin 15.0g
Sucrose 100 g
Sodium hydroxide is an amount of
Cumulative volume adds the injection water to 1000ml
Technical process:
(1) get Ovum Gallus domesticus Flavus lecithin 20mg, add acetic acid ethyl dissolution, add tanshinone IIA 0.05g, stir and make dissolving, one connects stirring, and a logotype nitrogen volatilizes ethanol;
(2) preparation of oil phase: Semen Maydis oil is heated to 60 ℃, adds the stirring of Ovum Gallus domesticus Flavus lecithin, enuatrol and step (1) tanshinone IIA respectively and make its dissolving;
(3) preparation of water: sucrose added in the entry dissolve, be heated to 60 ℃;
(4) preparation of colostrum: step (2) oil phase is added step (3) aqueous phase, 60 ℃ of temperature, high speed shear is disperseed, shear rate 6000rpm, 40 minutes time, form colostrum, pH value 4.0～6.0 is regulated with sodium hydroxide in fast cooling to 15～30 ℃;
(5) high pressure homogenize: through high pressure homogenizer homogenize number of times 2～6 times, pressure is 800～2000bar, 12～35 ℃ of temperature with step (4) colostrum;
(6) aseptic filtration: with the Emulsion warp 0.22 μ m filtering with microporous membrane degerming that step (4) makes, aseptic embedding, lyophilization promptly gets.
(7) all operations under nitrogen protection of step (1) to (6).
Embodiment 4
Prescription:
Tanshinone IIA 0.05g
Refining injection soybean oil 50.0g
Medium chain triglyceride 50.0g
Soybean phospholipid 12.0g
Enuatrol 0.5 g
Trehalose 50g
Sodium hydroxide is an amount of
Cumulative volume adds the injection water to 1000ml
Technical process:
(1) get Semen sojae atricolor ovum phosphorus 20mg, add the dissolving of dichloromethane and methanol mixed solvent (volume ratio 1:1), add tanshinone IIA 0.05g, stir and make dissolving, decompression volatilizes dichloromethane and methanol;
(2) preparation of oil phase: will make with extra care injection soybean oil and medium chain triglyceride and be mixed and heated to 55 ℃, and add soybean lecithin, enuatrol dissolving respectively, and add step (1) tanshinone IIA, and stir and make its dissolving;
(3) preparation of water: trehalose added in the entry dissolve, be heated to 55 ℃;
(4) preparation of colostrum: step (2) oil phase is added step (3) aqueous phase, 55 ℃ of temperature, high speed shear is disperseed, shear rate 4000rpm, 50 minutes time, form colostrum, pH value 4.0～6.0 is regulated with sodium hydroxide in fast cooling to 15～30 ℃;
(5) high pressure homogenize: through high pressure homogenizer homogenize number of times 2～6 times, pressure is 800～1200bar, 12～35 ℃ of temperature with step (4) colostrum;
(6) aseptic filtration: with the Emulsion warp 0.22 μ m filtering with microporous membrane degerming that step (4) makes, aseptic embedding, lyophilization promptly gets.
(7) all operations under nitrogen protection of step (1) to (6).
Embodiment 5
Adopt the low temperature supercentrifugation to measure envelop rate
1, medicine is at the assay of aqueous phase
Adopt two step centrifuging, get these article and place the low temperature supercentrifuge, design temperature is 25 ℃, regulates rotating speed to 5000rpm for the first time; Place the centrifugal 3h of 10mL centrifuge tube high speed respectively, take out, it is an amount of carefully to draw lower floor's solution (thin emulsion), places the low temperature supercentrifuge respectively; For the second time regulating rotating speed is 8000rpm, continues centrifugal 1h, to lower floor be clear aqueous solution; With above-mentioned operation, draw lower floor's clear aqueous solution respectively, with 0.22 μ m filtering with microporous membrane; Get subsequent filtrate,, measure the content of medicine at aqueous phase according to method under the assay item.
2, the mensuration of medicine total content
According to method under the assay item, the result is the medicine total content of these article.
3, the mensuration of envelop rate
Because medicine is difficult to measure at the content of oil, oil-water interfaces, so the envelop rate of these article is as shown in the formula calculating
Promptly get.
4、
5, measure the result
Get three lot sample article, detect according to the said determination method, the result sees the following form, and can find out three lot samples by table
The envelop rate of article is all more than 85%.
| ? | Total content (%) | Aqueous phase content (%) | Envelop rate (%) |
| The comparative example 1 | 104.3 | 16.2 | 85.1 |
| The comparative example 2 | 103.2 | 3.3 | 89.9 |
| Embodiment 1 | 107.7 | 2.2 | 95.5 |
| Embodiment 2 | 110.1 | 3.4 | 98.7 |
| Embodiment 3 | 109.8 | 2.2 | 97.6 |
| Embodiment 4 | 106.2 | 3.8 | 96.4 |
Among the comparative example, the sealing of tanshinone IIA through about 87%, the tanshinone IIA lipoid microsphere that the present invention is prepared, the envelop rate of medicine be more than 95%, be free in the water less than 5%.
The invention has the advantages that:
1, fat micro sphere preparation of the present invention is to be carrier with the fat milk, and at soybean phospholipid, Ovum Gallus domesticus Flavus lecithin
Cholesterol etc. are as emulsifying agent.
2, because as soybean oil, the corn wet goods composition of oil phase, and as the compositions such as phospholipid of emulsifying agent all to human non-toxic, its clinical application is for many years, and is safe and reliable, and can be the metabolism of human body institute, therefore can be satisfactorily as the carrier of tanshinone IIA.
3, after tanshinone IIA is made into lipoid microsphere, solve its dissolubility, stability and prolongation action time in vivo well, had targeting property, persistence and high efficiency, thereby improved curative effect, reduced dosage.So said preparation has novelty, practicality and novelty, has solved an indeterminable in the past difficult problem.
4, fat micro sphere preparation envelop rate of the present invention is higher, and process repeatability is better.
5, fat micro sphere preparation of the present invention has played positive effect to the formation of thrombosis in cardiovascular and cerebrovascular microcirculation disturbance and treatment and the inhibition blood vessel.
Claims (10)
1. tanshinone IIA fat micro sphere preparation and preparation method thereof is prepared from tanshinone IIA, oil for injection, emulsifying agent, stabilizing agent, isotonic agent and water for injection, and its system is levied and is:
(1) prescription 1
Tanshinone IIA 0.01～1.0g
Oil for injection 10.0～200.0g
Emulsifying agent 2.0～20g
Isoosmotic adjusting agent 4.0～10.0g
Cumulative volume adds the injection water to 1000ml
(2) prescription 2
According to lipoid microsphere prescription optimum ratio in the claim prescription 1 be:
Tanshinone IIA 0.02～0.2g
Oil for injection 50～150.0g
Emulsifying agent 1.0～12g
Isoosmotic adjusting agent 2.0～5.0g
Cumulative volume adds the injection water to 1000ml.
2. according to the fat micro sphere preparation of two prescriptions in the claim 1, its preparation process is characterised in that:
(1) get phospholipid and be dissolved in the suitable solvent, add Alprostadil, stir and make its dissolving, remove and desolvate, subsequent use;
(2) preparation of oil phase: add emulsifying agent in the oil for injection respectively, the tanshinone IIA and the mixture of phospholipids of stabilizing agent and step (1) gained stir and make its dissolving, as oil phase;
(3) preparation of water: isotonic agent is added to the water, and stirs and makes its dissolving, as water;
(4) preparation of colostrum: step (3) oil phase is added step (2) aqueous phase, shear from speed and disperse, form colostrum;
(5) tripping homogenize:, promptly get with the homogenize of step (4) colostrum high pressure;
(6) all operations under nitrogen protection of step (1) to (5).
3. the method for preparing of tanshinone IIA lipoid microsphere according to claim 2 is characterized in that, the described high speed shear of step (4) is separated into 10～80 minutes, and shear rate is 2000～10000rpm, and temperature is 40～75 ℃.
4. the method for preparing of tanshinone IIA lipoid microsphere according to claim 3 is characterized in that, the described high pressure homogenize of step (5) pressure is 500～2500bar, homogenize number of times 2～6 times, 12～35 ℃ of temperature.
5. according to the method for preparing of the arbitrary described tanshinone IIA lipoid microsphere of claim 2～4, it is characterized in that the described solvent of step (1) is one or more the combination in ethanol, ethyl acetate, chloroform, dichloromethane, the acetone.
6. according to the method for preparing of the arbitrary described tanshinone IIA lipoid microsphere of claim 2～4, it is characterized in that the weight ratio of described phosphide consumption of step (1) and tanshinone IIA is 1～15:1.
7. according to the method for preparing of the arbitrary described tanshinone IIA lipoid microsphere of claim 2～4; It is characterized in that described oil for injection is one or more the combination in refined soybean oil, Semen Maydis oil, Oleum Arachidis hypogaeae semen, medium chain glycerol glyceride, safflower oil, Oleum Gossypii semen, olive oil, Oleum Sesami, fish oil, medium chain glycerol dibasic acid esters, medium chain triglyceride, ethyl oleate, acetylated monoglyceride, propylene glycol dibasic acid esters, glyceryl linoleate, the Polyethylene Glycol glyceryl laurate ester; To use method for preparing according to the described tanshinone IIA lipoid microsphere of this claim, it is characterized in that described oil for injection is refined soybean oil and medium chain triglyceride, both weight ratios are 1:3～3:1.
8. according to the method for preparing of the arbitrary described tanshinone IIA lipoid microsphere of claim 2～4, it is characterized in that described emulsifying agent is soybean phospholipid or Ovum Gallus domesticus Flavus lecithin, wherein the content of phosphatidylcholine is more than 80%.
9. according to the method for preparing of the arbitrary described tanshinone IIA lipoid microsphere of claim 2～4, it is characterized in that described stabilizing agent is one or more the combination in oleic acid or its salt, cholic acid or its salt, deoxycholic acid or its salt.
10. according to the method for preparing of the arbitrary described tanshinone IIA lipoid microsphere of claim 2～4, it is characterized in that described isotonic agent is one or more the combination in glycerol, mannitol, sorbitol, glucose, sucrose, the trehalose.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104906050A (en) * | 2015-06-30 | 2015-09-16 | 武汉大学 | Liensinine lipid microsphere preparation and preparation method and application thereof |
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2011
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104906050A (en) * | 2015-06-30 | 2015-09-16 | 武汉大学 | Liensinine lipid microsphere preparation and preparation method and application thereof |
| CN104906050B (en) * | 2015-06-30 | 2018-03-02 | 武汉大学 | A kind of liensinine fat micro sphere preparation and its production and use |
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Application publication date: 20121205 |