CN102188377B - Method for preparing medicine encapsulating liposome - Google Patents
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- CN102188377B CN102188377B CN201010131244.5A CN201010131244A CN102188377B CN 102188377 B CN102188377 B CN 102188377B CN 201010131244 A CN201010131244 A CN 201010131244A CN 102188377 B CN102188377 B CN 102188377B
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Abstract
The invention relates to a method for preparing a medicine encapsulating liposome, which comprises: preparing medicine solid dispersion; and uniformly dispersing the medicine solid dispersion and a liposome film-forming material in an organic solvent to prepare the medicine encapsulating liposome. When the method is used, a medicine can be uniformly encapsulated in the liposome, the medicine encapsulating rate is improved, and sudden release of the medicine encapsulating liposome is reduced. The liposome is suitable for encapsulating various medicines and can be used in a wide formulation range.
Description
[technical field]
The invention belongs to pharmaceutics field, more particularly, the present invention relates to a kind of preparation method of wrapping medicine carrying composite lipidosome.
[background technology]
Liposome (liposomes) is a kind of single or multiple lift microcapsule being comprised of the orderly lipid bilayer of arrangement.Liposome belongs to colloid system, has the cytoid structure of class, strong with cell membrane affinity, can increase the ability of encapsulated medicine permeate through cell membranes.Liposome good biocompatibility, can realize targeted delivery in medicine body, there is prolong drug action time, increase medicine inside and outside stability, reduce drug toxicity, strengthen the plurality of advantages such as pharmacological action.
The method of preparing liposome is a lot, has film dispersion method, reverse phase evaporation, freeze-drying, injection method, ultrasound wave dispersion method etc.Directly use at present liposome entrapment medicine, particularly during water soluble medicament-entrapping, envelop rate is conventionally lower.In addition due to polar drugs reason, cause medicine skewness in liposome, burst effect is obvious, can not meet pharmacopeia and stipulate accordingly.
Adopt the active drug delivery technologies such as pH gradient method can improve liposome for water soluble drug bag carrying capacity, but initiatively drug delivery technologies operation is comparatively loaded down with trivial details, poor reproducibility, is difficult to industrial mass preparation.
The concept of solid dispersion is the earliest in propositions such as Sekiguchi in 1961.The effect feature of solid dispersion: the dissolubility and the dissolution rate that 1. increase insoluble drug: insoluble drug is made after solid dispersion, medicine is dispersed in carrier with molecule, colloid, unformed or microcrystalline state, and specific surface area increases, and dissolution rate is accelerated.2. drug loosed time speed: solid dispersions technique has been applied in the product development of slow releasing preparation, by selecting suitable carrier material, can obtain the slow-release solid dispersion of different drug release rates.3. improve the bioavailability of insoluble drug: insoluble drug is difficult for being absorbed by body, in clinical practice, be subject to certain limitation, adopted solid dispersions technique, can make insoluble drug reach high degree of dispersion homogeneous state, thereby guarantee absorption and the utilization of its preparation, improve bioavailability.4. improve the stability of medicine: labile drug can increase stability after making solid dispersion, make the quality of preparation be easy to control, and can reduce costs.
At present, be to be applied in solid orally ingestible more than solid dispersions technique, have no the report applying it in particulate carrier technology of preparing.
[summary of the invention]
The technical problem to be solved in the present invention is for the weak point of existing preparation bag medicine carrying composite lipidosome, and a solution is provided.
We find in the liposome experiment of preparation bag medicine carrying thing, and because polar drugs difference is large, medicine is difficult to evenly bag and is loaded in liposome.When water soluble drug is made liposome, because drug distribution is in surface of liposome, easily produce burst effect; But when fat-soluble medicine is made liposome, because medicine is embedded in liposome interior completely, medicine is difficult to discharge, thereby do not reach the release concentration of regulation.But there are some amphipathy macromolecule materials as Polyethylene Glycol, poloxamer, polyvidone etc., high with liposome affinity, and be easy to be scattered in water, middle polarity even in weakly polar organic solvent.Therefore first we prepare medicine solid dispersion, then medicine solid dispersion and Liposome film-forming material is dispersed in and in organic solvent, prepares drug-loaded liposome.Found that entrapment efficiency improves, burst effect reduces.
Through test of many times, for improving the preparation method of liposome entrapment medicine, the present invention has adopted following technical scheme:
A kind of preparation method of improving liposome entrapment medicine of the present invention, that medicine is scattered in the amphipathy macromolecule material system of dissolving or molten condition, rapid cooling is processed and is obtained medicine solid dispersion, then medicine solid dispersion and Liposome film-forming material are dispersed in organic facies system, according to method for preparing lipidosome, make the liposome of bag medicine carrying thing, realizing medicine evenly wraps and is loaded in liposome, improve medicine at the envelop rate of liposome, reduce the burst effect of bag medicine carrying composite lipidosome.
Above-mentioned medicine refers to Effective Component of Chinese Medicine, chemicals, aminoacid, polypeptide or the protein drug of performance prevention, treatment, health care, clean, beautification function.
Above-mentioned amphipathy macromolecule material refers to pharmaceutically generally acknowledged natural macromolecular material, semi-synthetic macromolecular material and synthesized polymer material, comprises polyvidone, Polyethylene Glycol, poloxamer and polyvinyl alcohol.
Above-mentioned Liposome film-forming material comprises hydrogenated phospholipid, synthetic phospholipid, cholesterol and surfactant, and hydrogenated phospholipid comprises: hydrogenation egg yolk lecithin and/or hydrogenated soya phosphatide; Synthetic phospholipid refers to the known synthetic phospholipid of pharmacy and polyethyleneglycol modified derivant thereof, comprising: DPPE, dipalmitoyl phosphatidyl choline, distearoyl phosphatidylcholine, dimyristoyl phosphatidyl choline, DOPE, DPPG, DPPA be the polyethyleneglycol modified derivant of one or more and they wherein; Surfactant comprises: tween series, span are serial, oleic acid, hexadecanol, octadecanol, glycerol, propylene glycol.
Above-mentioned organic facies refers to that carbon number 10, with alcohol, ketone, ester, ether and the alkyl halide of interior straight chain, side chain, comprises ethanol, the tert-butyl alcohol, acetone, ethyl acetate, ether, petroleum ether, chloroform, dichloromethane.
In above-mentioned organic facies system, can contain the known surfactant of pharmacy, polyhydric alcohol or saccharide, macromolecular scaffold proppant, antioxidant, stabilizing agent, pH adjusting agent.
The liposome particle diameter of above-mentioned bag medicine carrying thing can be micron order or nanoscale.
The liposome of above-mentioned bag medicine carrying thing can further be removed lipid fragment and unnecessary salt ion by dialysis, processing method centrifugal, chromatography.
Above-mentioned bag medicine carrying composite lipidosome can further be processed, and forms the raw material of oral, mucosa, injection, percutaneous drug delivery preparation, makes the concrete preparation of performance prevention, treatment, health care, clean, beautification function.
The preparation method of above-mentioned bag medicine carrying composite lipidosome has the following advantages:
1. the preparation method of bag medicine carrying composite lipidosome of the present invention improves medicine at the envelop rate of liposome, obviously reduces the seepage of bag medicine carrying thing.
2. the preparation method of bag medicine carrying composite lipidosome of the present invention reduces the burst effect of bag medicine carrying composite lipidosome, improves the release behavior of medicine, is conducive to obtain the drug-loaded liposome of different drug release rates, improves the bioavailability of medicine.
3. the preparation method of bag medicine carrying composite lipidosome of the present invention is suitable for wrapping up multi-medicament, is particularly useful for bag and carries oxidizable little medicine, water soluble drug and the insoluble drug of medicine, therapeutic dose.
4. the bag medicine carrying composite lipidosome finished product that prepared by the present invention is solid-state, stability is high, and applicable dosage form is extensive, can further process, form the raw material of oral, mucosa, injection, percutaneous drug delivery preparation, make the concrete preparation of performance prevention, treatment, health care, clean, beautification function.
Note: burst effect (dumping or burst effect), first drug release is the quick release that sticks to a small amount of medicine early period of origination of microparticle surfaces, is called burst effect.Pharmacopoeia of People's Republic of China (2005 editions) regulation, the burst size of the medicine carrying microgranules such as liposome in starting 0.5h should be lower than 40%.
[specific embodiment]
Now in conjunction with following example, further describe the present invention.
Embodiment 1: diclofenac sodium lipidosome
It is target medicine that first embodiment of the present invention adopts water soluble drug diclofenac sodium, amphipathy macromolecule material selection polyvidone (PVP), adopt fusion method to prepare diclofenac sodium-PVP Solid Dispersions, Liposome film-forming material selection hydrogenated soya phosphatide, cholesterol, Tween 80 and hexadecanol, adopt freeze-drying method preparation bag to carry the liposome of diclofenac sodium.
Experimental group: 30mg polyvidone (PVP) melting in 65 ℃ of water-baths, add 8mg diclofenac sodium to be uniformly dispersed, go to quenching in 0 ℃ of ice bath and process, make diclofenac sodium-PVP Solid Dispersions.20mg hydrogenated soya phosphatide, 6mg cholesterol, 2mg Tween 80 and 2mg hexadecanol are dissolved in the 20ml tert-butyl alcohol jointly, in 65 ℃ of water-baths, dissolve, add diclofenac sodium-PVP Solid Dispersions, dissolve completely, add 120mg mannitol (PVP), be uniformly dispersed, be loaded in cillin bottle-30 ℃ freezing 5 hours, lyophilization (5 * 10
-4pa, 24h) obtain the solid-state dried frozen aquatic products of liposome that bag carries diclofenac sodium.
Matched group: 20mg hydrogenated soya phosphatide, 6mg cholesterol, 2mg Tween 80 and 2mg hexadecanol are dissolved in the 20ml tert-butyl alcohol jointly, in 65 ℃ of water-baths, dissolve, add 8mg diclofenac sodium micropowder (particle diameter is below 15 μ m) to be uniformly dispersed, add 120mg mannitol, mix completely, be loaded in cillin bottle-30 ℃ freezing 5 hours, lyophilization (5 * 10
-4pa, 24h) obtain the solid-state dried frozen aquatic products of liposome that bag carries diclofenac sodium.
Experimental group and matched group inject respectively distilled water 5ml, slightly shake, and obtain the liposome turbid liquor that bag carries diclofenac sodium, then carry out following mensuration.
Entrapment efficiency determination: get diclofenac sodium liposome turbid liquor through the centrifugal 1min of 10000r/min, the upper solution 2ml that absorption contains free diclofenac sodium, with ultraviolet-visible spectrophotometer, in 274nm, survey trap, substitution diclofenac sodium standard curve, utilizes " envelop rate (%)=[(diclofenac sodium total amount-free diclofenac sodium amount)/diclofenac sodium total amount] * 100 " formula to calculate the envelop rate of diclofenac sodium lipidosome.After 25 ℃ of placement 0.5h of diclofenac sodium liposome turbid liquor sample, again measure envelop rate.
Diclofenac sodium standard curve: precision takes diclofenac sodium standard substance, with distilled water, be mixed with 0.1,0.2,0.5,1.0, the series standard solution of 2.5mg/ml, in 274nm, survey trap, obtain the standard curve of diclofenac na concn and trap, utilize this standard curve to calculate the concentration of diclofenac sodium.
Result: experimental group diclofenac sodium liposome encapsulation meansigma methods is 85%, and matched group envelop rate meansigma methods is 51%.25 ℃ place experimental group diclofenac sodium liposome encapsulation meansigma methods after 0.5h be burst size in 72%, 0.5h lower than 40%, avoided the burst effect of liposome.And envelop rate meansigma methods reduces to 28% after 25 ℃ of placement 0.5h of matched group, the burst size in 0.5h surpasses 40%, and liposome exists burst effect.Result shows that diclofenac sodium lipidosome prepared by the present invention has effectively improved the envelop rate of diclofenac sodium, has avoided the burst effect of liposome, thereby has extended the release action of diclofenac sodium lipidosome.
Embodiment 2: Paclitaxel liposome
It is target medicine that second embodiment of the present invention adopts fat-soluble medicine paclitaxel, amphipathy macromolecule material Polyethylene Glycol (PEG 2000), adopt solvent-fusion method to prepare paclitaxel-Polyethylene Glycol solid dispersion, DSPE (DSPE-PEG2000) and the Tween 80 of Liposome film-forming material selection dipalmitoyl phosphatidyl choline (DPPC), Macrogol 2000 grafting, adopt injection method preparation bag to carry the liposome of paclitaxel.
Experimental group: 30mg Polyethylene Glycol (PEG 2000) adds in 0.5ml dehydrated alcohol, melting in 65 ℃ of water-baths adds 5mg paclitaxel to be uniformly dispersed, and goes to quenching in 0 ℃ of ice bath and processes, and makes paclitaxel-Polyethylene Glycol solid dispersion.The DSPE (DSPE-PEG2000) of 5mg dipalmitoyl phosphatidyl choline (DPPC), the grafting of 1mg Macrogol 2000 adds 20ml chloroform: methanol (3: 1, V/V) in mixed solvent, dissolve, add paclitaxel-Polyethylene Glycol solid dispersion to be uniformly dispersed, form organic facies.Get in the 20ml 0.02mol/L phosphate buffer (PBS) that 10mg Tween 80 adds pH=7, mix, form water.The water that organic facies is injected to (25 ± 2) that 1000r/min stirs ℃, 1000r/min stirs 10min, forms liposome turbid liquor, and 25 ℃ of rotary evaporations of water-bath eliminate organic solvent, obtain the liposome of bag year paclitaxel.
Matched group: the DSPE (DSPE-PEG2000) of 5mg dipalmitoyl phosphatidyl choline (DPPC), the grafting of 1mg Macrogol 2000 adds 20ml chloroform: methanol (3: 1, V/V) in mixed solvent, dissolve, add 5mg paclitaxel, form organic facies.Get in the 20ml 0.02mol/L phosphate buffer (PBS) that 10mg Tween 80 adds pH=7, mix, form water.The water that organic facies is injected to (25 ± 2) that 1000r/min stirs ℃, 1000r/min stirs 10min, forms liposome turbid liquor, and 25 ℃ of rotary evaporations of water-bath eliminate organic solvent, obtain the liposome of bag year paclitaxel.
Entrapment efficiency determination: get Paclitaxel liposome suspension through the centrifugal 1min of 10000r/min, draw the upper solution that 0.5ml contains free paclitaxel, with ultraviolet-visible spectrophotometer, in 480nm, survey trap, substitution paclitaxel standard curve, utilizes " envelop rate (%)=[(paclitaxel total amount-free paclitaxel amount)/paclitaxel total amount] * 100 " formula to calculate the envelop rate of Paclitaxel liposome.After 25 ℃ of placement 0.5h of Paclitaxel liposome suspension sample, again measure envelop rate.
Paclitaxel standard curve: precision takes paclitaxel standard substance, is mixed with 0.25,0.5,1.0 with distilled water, the series standard solution of 2.0,5.0mg/ml, surveys trap in 480nm, obtain the standard curve of paclitaxel concentration and trap, utilize this standard curve to calculate the concentration of paclitaxel.
Result: Paclitaxel liposome envelop rate meansigma methods is 84%, and matched group envelop rate meansigma methods is 85%, without significant difference.After 25 ℃ of placement 0.5h, experimental group Paclitaxel liposome envelop rate meansigma methods is 72%, discharges certain medicine and does not show burst effect.After 25 ℃ of placement 0.5h of matched group, envelop rate meansigma methods is 82%, and drug release is very slow.Result shows that Paclitaxel liposome prepared by the present invention does not have the burst effect of liposome, and has good release behavior, improves the effectiveness of its treatment.
Embodiment 3: irinotecan hydrochloride liposome
It is target medicine that the 3rd embodiment of the present invention adopts irinotecan hydrochloride, amphipathy macromolecule material selection poloxamer (Poloxamer 188), adopt fusion method to prepare irinotecan hydrochloride-poloxamer solid dispersion, Liposome film-forming material selection hydrogenation egg yolk lecithin, cholesterol, Tween 80 and glycerol, adopt the even method preparation of high pressure breast bag to carry the nanometer liposome of irinotecan hydrochloride.
Experimental group: 55mg poloxamer (Poloxamer 188) melting in 65 ℃ of water-baths, add 5mg irinotecan hydrochloride to be uniformly dispersed, obtain irinotecan hydrochloride-poloxamer solid dispersion.20mg hydrogenation egg yolk lecithin, 6mg cholesterol, 2mg Tween 80,6mg glycerol join in 80 ℃ of water of 10ml, add irinotecan hydrochloride-poloxamer solid dispersion, with high pressure dispersing emulsification machine emulsifying four times, microporous filter membrane by 0.22 μ m carries out granulate, obtains the nanometer liposome that bag carries irinotecan hydrochloride.
Matched group: 20mg hydrogenation egg yolk lecithin, 6mg cholesterol, 2mg Tween 80,6mg glycerol join in 80 ℃ of water of 10ml, add 5mg irinotecan hydrochloride, with high pressure dispersing emulsification machine emulsifying four times, microporous filter membrane by 0.22 μ m carries out granulate, obtains the nanometer liposome that bag carries irinotecan hydrochloride.
Entrapment efficiency determination: get irinotecan hydrochloride liposome turbid liquor through the centrifugal 1min of 10000r/min, draw the upper solution that 2ml contains free hydrochloric acid irinotecan, with ultraviolet-visible spectrophotometer, in 370nm, survey trap, substitution irinotecan hydrochloride standard curve, utilizes " envelop rate (%)=[(irinotecan hydrochloride total amount-free hydrochloric acid irinotecan amount)/irinotecan hydrochloride total amount] * 100 " formula to calculate the envelop rate of irinotecan hydrochloride liposome.After 25 ℃ of placement 0.5h of irinotecan hydrochloride liposome turbid liquor sample, again measure envelop rate.
Irinotecan hydrochloride standard curve: precision takes irinotecan hydrochloride standard substance, with distilled water, be mixed with 0.25,0.5,1.0,2.0, the series standard solution of 5.0mg/ml, in 370nm, survey trap, obtain the standard curve of irinotecan hydrochloride concentration and trap, utilize this standard curve to calculate the concentration of irinotecan hydrochloride.
Result: irinotecan hydrochloride liposome encapsulation meansigma methods is 84%, and matched group envelop rate meansigma methods is 30%.After 25 ℃ of placement 0.5h, irinotecan hydrochloride liposome encapsulation meansigma methods is 67%, does not show burst effect.And envelop rate meansigma methods reduces to 14% after 25 ℃ of placement 0.5h of matched group, there is obvious burst effect.Result shows that irinotecan hydrochloride liposome prepared by the present invention effectively improves the envelop rate of medicine, has avoided the burst effect of liposome.
Embodiment 4: irinotecan hydrochloride lipidosome injection
The 4th embodiment of the present invention adopts the irinotecan hydrochloride liposome of embodiment 3 preparations further to process and prepare irinotecan hydrochloride lipidosome injection.
The irinotecan hydrochloride liposome turbid liquor that embodiment 3 experimental grouies are made, through sephadex column eluting, separates free irinotecan hydrochloride and the liposome that bag carries irinotecan hydrochloride.Bag is carried to irinotecan hydrochloride liposome and is packaged in the ampoule of 5ml,
60co radiation sterilization (RAD=150～1,800,000), makes irinotecan hydrochloride lipidosome injection.Electron microscopic morphology observation is carried out in the sampling of irinotecan hydrochloride lipidosome injection, and bag carries the liposome form rounding of irinotecan hydrochloride, evenly, without agglomerate, particle size distribution 100-250nm.Result shows that the liposome that bag carries irinotecan hydrochloride can make the concrete preparations such as injection, and form keeps better, and stability is higher.
In the above-described embodiments, only the present invention has been carried out to exemplary description, but those skilled in the art can carry out various modifications to the present invention without departing from the spirit and scope of the present invention after reading present patent application.
Claims (1)
1. a preparation method of wrapping medicine carrying composite lipidosome, it is characterized in that: medicine is scattered in the amphipathy macromolecule material system of dissolving or molten condition, rapid cooling is processed and is obtained medicine solid dispersion, then medicine solid dispersion and Liposome film-forming material are dispersed in organic facies system, according to method for preparing lipidosome, make the liposome of bag medicine carrying thing, realize medicine and evenly wrap and be loaded in liposome, described amphipathy macromolecule material is the synthesized polymer material of pharmaceutically generally acknowledging.
2. preparation method according to claim 1, is characterized in that: described medicine refers to Effective Component of Chinese Medicine, chemicals, aminoacid, polypeptide or the protein drug of performance prevention, therapeutical effect.
3. preparation method according to claim 1, is characterized in that: described pharmaceutically generally acknowledged synthesized polymer material, is selected from polyvidone, Polyethylene Glycol, poloxamer and polyvinyl alcohol.
4. preparation method according to claim 1, is characterized in that: described Liposome film-forming material comprises hydrogenated phospholipid, synthetic phospholipid, cholesterol and surfactant, and hydrogenated phospholipid is selected from: hydrogenation egg yolk lecithin and hydrogenated soya phosphatide; Synthetic phospholipid refers to the known synthetic phospholipid of pharmacy and polyethyleneglycol modified derivant thereof, is selected from: DPPE, dipalmitoyl phosphatidyl choline, distearoyl phosphatidylcholine, dimyristoyl phosphatidyl choline, DOPE, DPPG, DPPA be the polyethyleneglycol modified derivant of one or more and they wherein; Surfactant is selected from: tween series, span are serial, one or more in oleic acid, hexadecanol, octadecanol, glycerol, propylene glycol.
5. preparation method according to claim 1, it is characterized in that: described organic facies refers to that carbon number 10 is with alcohol, ketone, ester, ether and the alkyl halide of interior straight chain, side chain, be selected from one or several the mixed solvent in methanol, ethanol, the tert-butyl alcohol, acetone, ethyl acetate, ether, petroleum ether, chloroform, dichloromethane.
6. preparation method according to claim 1, is characterized in that: in described organic facies system, also contain one or more in the known surfactant of pharmacy, polyhydric alcohol or saccharide, macromolecular scaffold proppant, antioxidant, stabilizing agent, pH adjusting agent.
7. preparation method according to claim 1, is characterized in that: the liposome particle diameter of described bag medicine carrying thing is micron order or nanoscale.
8. preparation method according to claim 1, is characterized in that: the liposome of described bag medicine carrying thing is further removed lipid fragment and unnecessary salt ion by dialysis, processing method centrifugal, chromatography.
9. preparation method according to claim 1, it is characterized in that: described bag medicine carrying composite lipidosome is further processed, form the raw material of oral, mucosa, injection, percutaneous drug delivery preparation, make the concrete preparation of performance prevention, treatment, health care, clean, beautification function.
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Families Citing this family (12)
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| CN102935068B (en) * | 2012-10-19 | 2014-12-17 | 浙江海正药业股份有限公司 | Preparation method of liposome entrapping water-soluble medicines |
| CN111346072B (en) * | 2018-12-21 | 2022-05-27 | 宜昌人福药业有限责任公司 | Transdermal drug delivery pharmaceutical composition and preparation method thereof |
| CN111346073B (en) * | 2018-12-21 | 2022-06-10 | 宜昌人福药业有限责任公司 | Transdermal drug delivery pharmaceutical composition and preparation method and application thereof |
| CN111346104B (en) * | 2018-12-21 | 2022-06-10 | 宜昌人福药业有限责任公司 | Morphine-6-glucuronide transdermal drug delivery pharmaceutical composition, preparation method and application thereof |
| CN111419827B (en) * | 2018-12-21 | 2022-06-10 | 宜昌人福药业有限责任公司 | Pharmaceutical composition for alfentanil transdermal administration and preparation method and application thereof |
| CN111419826B (en) * | 2018-12-21 | 2022-06-10 | 宜昌人福药业有限责任公司 | Sufentanil transdermal drug delivery pharmaceutical composition, preparation method and application thereof |
| CN111346058B (en) * | 2018-12-21 | 2022-05-17 | 宜昌人福药业有限责任公司 | Pharmaceutical composition for nasal administration of benzodiazepine compound, and preparation method and use thereof |
| CN111346098B (en) * | 2018-12-21 | 2022-05-27 | 宜昌人福药业有限责任公司 | Benzodiazepine compound local pharmaceutical composition and preparation method and use thereof |
| CN111346078B (en) * | 2018-12-21 | 2022-06-10 | 宜昌人福药业有限责任公司 | Pharmaceutical composition for nasal mucosa administration of tapentadol or pharmaceutically acceptable salt thereof, and preparation method and application thereof |
| CN111346077B (en) * | 2018-12-21 | 2022-06-10 | 宜昌人福药业有限责任公司 | Tapentadol transdermal drug delivery pharmaceutical composition, preparation method and application thereof |
| CN110090205B (en) * | 2019-05-15 | 2021-03-23 | 蚌埠学院 | Preparation method of chlorogenic acid lipid nanoparticle solid dispersion |
| CN116807976B (en) * | 2023-08-22 | 2023-11-17 | 昆明时光肌生物技术有限公司 | Drug-entrapped liposome, preparation method thereof and method for improving secretion of exosomes |
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Effective date of registration: 20121211 Address after: Jiaojiang District of Taizhou City, Zhejiang province 318000 road outside No. 46 Applicant after: Zhejiang Hisun Pharmaceutical Co., Ltd. Address before: 100021 Beijing city Chaoyang District Wu San RI 8 Building 2 403 Applicant before: Lu Cuitao |
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