CN1823743A - Self emulsified osmotic pump controlled release administration system of liposoluble medicine and its preparation technology - Google Patents
Self emulsified osmotic pump controlled release administration system of liposoluble medicine and its preparation technology Download PDFInfo
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Abstract
A self-emulsifying medicine applying system with the releasing controlled by osmotic pump for lipo-soluble medicines is composed of a lipo-soluble medicine, self-emulsifying tablet core and coated film with one or more holes. It is prepared through mixing medicine with oil phase and surfactant or co-surfactant, dissolving, adding to kinds of solvent, mixing, tabletting, coating and perforating.
Description
Technical field
The present invention relates to medical technical field, is a kind of new drug-supplying system of fat-soluble medicine, i.e. a kind of self emulsified osmotic pump controlled release administration system of fat-soluble medicine and preparation technology thereof.
Background technology:
According to statistics, it is slightly water-soluble that there is 80% new drug in the whole world, and many promising poorly water soluble drugs cause oral administration biaavailability low because of its poorly water-soluble, bring very big difficulty to formulation development.In the new drug of these slightly water-solubles, have most of medicine owing to poorly water-soluble has good or certain lipotropy, can make self-emulsifiable preparation.
Self-emulsified drug delivery system in recent years, is widely used because can improve the bioavailability of fat-soluble medicine significantly.Self-emulsifying drug delivery system (Self-EmulsifyingDrug Delivery System; SEDDS) be under the situation that does not have water to exist, homogeneous, clarification, isotropic liquid oral dosage form or the solid dosage forms formed by medicine, oil phase, surfactant and cosurfactant.The topmost feature of this drug-supplying system is exactly under the body temperature condition, meet behind the body fluid can be under the impelling of gastrointestinal motility spontaneous formation oil in water emulsion.Self-emulsifying drug delivery systems generally has following characteristics:
(1) under ambient temperature (37 ℃) and gentle agitation, because the existence of surfactant, self-emulsifying drug delivery system's spontaneous emulsification becomes the Emulsion of particle about 5 μ m.Medicine is present in these tiny oil droplets, is distributed in fast in the whole gastrointestinal tract, has reduced owing to medicine directly contacts the stimulation that causes with gastrointestinal wall.
(2) medicine distributes between oil/water is biphase, relies on the huge surface area of tiny oil droplet to improve the dissolution and the bioavailability of medicament of water-insoluble drug, can avoid the hydrolysis of water-insoluble drug and medicine to the gastrointestinal pessimal stimulation simultaneously.
(3) self-emulsifiable preparation oral after, rapidly emulsifying in gastrointestinal tract, medicine directly enters the small intestinal lymph, the back arrives the transhipment of thymic lymphoma pipe, rather than enters hepatic portal vein.Therefore, Emulsion absorbs after the effect that was subjected to through liver is avoided in the lymph transhipment, can improve bioavailability of medicament.
(4) self-emulsifying drug delivery system generally is sub-packed in the soft capsule, oral back at the gastric juice aqueous phase since the existence of gastric peristalsis and emulsifying agent from issuing into Emulsion.Preparation technology is simple, stable in properties, the accurate and taking convenience of dosage.
Though self-emulsifying drug delivery systems has above having a few, and some shortcomings are also arranged.
Because the self emulsifying dosage form is emulsifying rapidly usually, it is a kind of quick releasing formulation, though can improve bioavailability significantly, but when improving bioavailability, also brought the wave phenomenon of the blood drug level higher than ordinary tablet, blood drug level reaches the peak fast, and also decay fast is unfavorable to the effect of treatment simultaneously.Especially for some specific diseases, as hypertension and diabetes, violent blood concentration fluctuation will inevitably be brought discomfort to the patient.
Adjuvant that self emulsifying is used such as oil phase, surfactant and cosurfactant are generally liquid, and the physics of preparation, chemical stability are relatively not as solid preparation.Patient takes inconvenience, and divided dose is inaccurate.
Summary of the invention
The objective of the invention is in order to overcome the above-mentioned deficiency of self-emulsifying drug delivery systems, and adopt new technology of preparing to prepare a kind of new formulation-self emulsified osmotic pump controlled release administration system.Self-emulsifiable oil is solidified with the form of absorption or enclose, add an amount of effervescent and osmotic pressure active substance, be pressed into the sheet heart of self emulsifying then with tablet machine, at sheet heart outsourcing one deck semipermeable membrane, on semipermeable membrane, make a call to a hole at least or do not punch and control the release of medicine.This class preparation is met water in gastrointestinal tract after, moisture diffuses to the sheet heart by semipermeable membrane, effervescent aerogenesis and gastrointestinal motility provide emulsifying power for the emulsifying of self-emulsifiable oil, like this under the effect of osmotic pressure active substance, medicine slowly discharges with the form of emulsion droplet, the deficiency of self-emulsifying drug delivery systems can be overcome, following effect can be reached:
(1) insoluble drug discharges with the emulsion droplet form in gastrointestinal tract (comprising Digestive system), accelerates the dissolution rate of insoluble drug, to improve the absorption and the bioavailability of medicine.
(2) medicine slowly discharges to reach the effect of slow release with the emulsion droplet form, makes blood drug level more steady.
(3) improve stability of formulation.
(4) raising patient's compliance.
(5) reach the target administration effect, or change the transporting mode and the approach of medicine, reduce the untoward reaction or the first pass effect of medicine.
According to the present invention, any fat-soluble medicine all can be prepared into the self emulsified osmotic pump controlled release preparation according to following method.
Method one: fat-soluble medicine is dissolved in the oil phase of recipe quantity, surfactant, or in cosurfactant or its mixture, add remaining recipe quantity solvent then, vortex, mix homogeneously make the pastille self-emulsifiable oil.With absorbent and osmotic pressure active substance and effervescent mix homogeneously, as binding agent, make soft material with self-emulsifiable oil, the granulation of sieving, dry back granulate, last compressed single sheet; Can not granulate yet, use direct powder compression; Wrap one deck semipermeable membrane in the heart at sheet then; On semipermeable membrane, beat at least one aperture at last or do not punch.
Method two: fat-soluble medicine is dissolved in the oil phase of recipe quantity, surfactant, or in cosurfactant or its mixture, add remaining recipe quantity solvent then, vortex, mix homogeneously make the pastille self-emulsifiable oil.With bag and material self-emulsifiable oil is solidified, add osmotic pressure active substance and effervescent, system soft material, the granulation of sieving, dry back granulate, last compressed single sheet; Can not granulate yet, use direct powder compression; Wrap one deck semipermeable membrane in the heart at sheet then; On semipermeable membrane, beat at least one aperture at last or do not punch.
Medicine can be selected from chemosynthesis medicine, Chinese medicine extract, biotechnology medicine.Its type comprises the medication of heart cardiovascular and cerebrovascular vessel, cancer medication, anti-AIDS class medicine, antibiotics, the medication of diabetes class, vitamin medicaments, antimalarial, respiratory medicine, digestive system medication, immune system medication, antipyretic analgesic, anesthetics, hormone medicine, Chinese medicine extract etc.
Oil phase can be selected from soybean oil, Oleum Arachidis hypogaeae semen, olive oil, Flos Carthami wet goods; Fatty acid ester can be oleic acid sorbitol ester, olein, Oleum Cocois C8/C10 monoglyceride or dibasic acid esters, Oleum Cocois C8/C10 propylene glycol dibasic acid esters, Oleum Cocois C8/C10 triglyceride, the acetylizad monoglyceride of purification, purification Oleum helianthi monoglyceride, olein, glyceryl linoleate, poly-second
A kind of, two or more mixture in these materials such as glycol glyceryl laurate ester, ethyl oleate, Ethyl linoleate.
Surfactant can be selected from liquid egg phospholipid, polyoxyethylene castor oil, Oleum Cocois C8/C10 polyethyleneglycol glyceride, almond oil polyethyleneglycol glyceride, polyoxyethylene (25) triglyceride, polyoxyethylene (20) sorbic acid oleate, Polyethylene Glycol-8-glycerol sad/a kind of, two or more mixture in these materials such as decanoin.
Cosurfactant can be selected from a kind of, two or more the mixture in these materials such as ethanol, propylene glycol, glycerol, Polyethylene Glycol (molecular weight is at 200-600), propylene carbonate, ethylene glycol monomethyl ether (transcutol P), glycerol furfural, dimethyl Soquad.
Absorbent and enclose material can be selected from calcium phosphate, magnesium oxide, magnesium carbonate, calcium carbonate,
Gel aluminum hydroxide powder, Radix Trichosanthis, Rhizoma dioscoreae, Bulbus Fritillariae Thunbergii, high territory, bentonite and cyclodextrin etc.
Coating material can be selected from cellulose acetate and/or ethyl cellulose and/or hydroxypropyl emthylcellulose and/or polyethylene and/or polyethylene glycols.
Porogen can be selected from the mixture of Polyethylene Glycol, glycerol, propylene glycol, dimethyl phthalate, triacetin and these materials.
A hole can not punched or make a call at least to small delivery aperture, and the aperture is between 0.2-2mm.
Dissolution in vitro method: get carvedilol self emulsified osmotic pump controlled release sheet, adopt second method in the dissolution method (2000 editions two appendix XC of Chinese Pharmacopoeia), with 0.1NHCl 500ml is dissolution medium, rotating speed is that per minute 50 changes, operation in accordance with the law, got solution 5ml respectively at 1,2,4,6,8,10,12 hour, 0.45 μ m filtering with microporous membrane, and in time in process container, mend medium 5ml.
Description of drawings
Fig. 1 is the stripping curve figure of carvedilol self emulsified osmotic pump controlled release sheet.
Fig. 2 is the plasma concentration curve figure of carvedilol self emulsified osmotic pump controlled release sheet.
The specific embodiment:
Embodiment 1 (release profiles is seen accompanying drawing 1):
Sheet heart prescription (following is weight proportion):
Carvedilol 3.5%
Gelucire?44/14 8.6％
Lutrol?F68 11.8％
Transcutol?P 8.4％
Silicon dioxide 30%
Mannitol 30%
Citric acid 2.4%
Sodium bicarbonate 3.7%
Pulvis Talci 1.6%
The semipermeable membrane prescription:
Cellulose acetate 72%
PEG400 28%
The square method one of preparation method.
Embodiment 2:
Carvedilol 2.1%
Ethyl oleate 5.1%
Tween 80 7.7%
Transcutol?P 5.1％
Silicon dioxide 35.5%
Mannitol 35.5%
Citric acid 3%
Sodium bicarbonate 4.6%
Pulvis Talci 1.4%
The semipermeable membrane prescription:
Cellulose acetate 72%
PEG400 28%
The square method one of preparation method.
Embodiment 3
Glipizide 0.1%
Labrafil?M?1944CS 1.4％
Tween?80 2.2％
Transcutol?P 1.4％
Beta-schardinger dextrin-48.8%
Sodium chloride 13.5%
Microcrystalline Cellulose 25.1%
Citric acid 2.2%
Sodium bicarbonate 3.3%
The semipermeable membrane prescription:
Cellulose acetate 72%
PEG400 28%
Preparation method is seen method two.
Silymarin 2.4%
Ethyl oleate 8.8%
Dehydrated alcohol 8.8%
Silicon dioxide 29.6%
Sodium chloride 14.8%
Microcrystalline Cellulose 14.8%
Citric acid 2.6%
Sodium bicarbonate 4.4%
The semipermeable membrane prescription:
Cellulose acetate 72%
PEG400 28%
The square method one of preparation method.
Adefovir ester 3%
Ethyl oleate 8.8%
Transcutol?P 8.8％
Silicon dioxide 29%
Sodium chloride 14.8%
Microcrystalline Cellulose 14.8%
Citric acid 2.6%
Sodium bicarbonate 4.4%
The semipermeable membrane prescription:
Cellulose acetate 72%
PEG400 28%
The square method one of preparation method.
Paclitaxel 3%
Ethyl oleate 8.8%
Transcutol?P 8.8％
Silicon dioxide 29%
Sodium chloride 14.8%
Microcrystalline Cellulose 14.8%
Citric acid 2.6%
Sodium bicarbonate 4.4%
The semipermeable membrane prescription:
Cellulose acetate 72%
PEG400 28%
The square method one of preparation method.
Embodiment 7
Vinpocetine 3%
Oleic acid 8.7%
PEG400 8.7%
Silicon dioxide 28.8%
Sodium chloride 15.4%
Microcrystalline Cellulose 15.4%
Citric acid 2.1%
Sodium bicarbonate 3.1%
Pulvis Talci 2.1%
The semipermeable membrane prescription:
Cellulose acetate 72%
PEG400 28%
The square method one of preparation method.
Embodiment 8
Lovastatin 2.4%
Ethyl oleate 8.8%
Dehydrated alcohol 8.8%
Silicon dioxide 29.6%
Sodium chloride 14.8%
Microcrystalline Cellulose 14.8%
Citric acid 2.6%
Sodium bicarbonate 4.4%
The semipermeable membrane prescription:
Cellulose acetate 72%
PEG400 28%
The square method one of preparation method.
Embodiment 9
Ethyl oleate 8.8%
Dehydrated alcohol 8.8%
Silicon dioxide 30%
Sodium chloride 14.8%
Microcrystalline Cellulose 14.8%
Citric acid 2.6%
Sodium bicarbonate 4.4%
The semipermeable membrane prescription:
Cellulose acetate 72%
PEG400 28%
The square method one of preparation method.
Estradiol 2.5%
Oleic acid 8.7%
PEG400 8.7%
Silicon dioxide 28.8%
Sodium chloride 15.9%
Microcrystalline Cellulose 15.4%
Citric acid 2.1%
Sodium bicarbonate 3.1%
Pulvis Talci 2.1%
The semipermeable membrane prescription:
Cellulose acetate 72%
PEG400 28%
The square method one of preparation method.
Embodiment 11
The carvedilol self emulsified osmotic pump sheet that embodiment 1 is made carries out pharmacokinetic studies in the body with the carvedilol ordinary tablet of identical dosage with the Beagle dog, and gained relative bioavailability is respectively 153.11%.Plasma concentration curve such as accompanying drawing 2 in the body.
Claims (10)
1. the self emulsified osmotic pump controlled release administration system of a fat-soluble medicine is characterized in that: comprise fat-soluble medicine, the self emulsifying label; At label outsourcing one deck coating membrane, can on film, beat at least one aperture, or the preparation of the preparation of not punching.
2. the self emulsified osmotic pump controlled release administration system of a kind of fat-soluble medicine according to claim 1, it is characterized in that: selected medicine is the low fat-soluble medicine of bioavailability.
3. fat-soluble medicine self emulsified osmotic pump controlled release administration system according to claim 1 and 2, it is characterized in that: selected medicine comprises chemosynthesis medicine, Chinese medicine extract, the biotechnology medicine, its type comprises the cardiovascular and cerebrovascular vessel medication, the cancer medication, anti-AIDS class medicine, antibiotics, the medication of diabetes class, vitamin medicaments, antimalarial, respiratory medicine, digestive system medication, the immune system medication, antipyretic analgesic, anesthetics, hormone medicine, Chinese medicine extract, the fat-soluble medicine carvedilol.
4. fat-soluble medicine self emulsified osmotic pump controlled release administration system according to claim 1, it is characterized in that: selected self emulsifying label is made jointly by self-emulsifiable oil and absorbent or enclose material, self-emulsifiable oil is by oil phase 0-70%, surfactant 0-95%, cosurfactant 0-95% forms, self-emulsifiable oil can be liquid under the room temperature, semisolid or solid-state self-emulsifiable oil, the selected oil phase of self-emulsifiable oil is vegetable oil or the fatty acid ester after crude vegetal or process structure of modification or the hydrolysis, especially the chain length long-chain fat acid glyceride that is C18 in the fatty glyceride or the chain length of the intermediary medium chain of C8-C10, crude vegetal can be soybean oil, Oleum Arachidis hypogaeae semen, olive oil, safflower oil; Fatty acid ester can be a kind of, two or more the mixture in these materials such as oleic acid sorbitol ester, olein, Oleum Cocois C8/C10 monoglyceride or dibasic acid esters, Oleum Cocois C8/C10 propylene glycol dibasic acid esters, Oleum Cocois C8/C10 triglyceride, the acetylizad monoglyceride of purification, purification Oleum helianthi monoglyceride, olein, glyceryl linoleate, Polyethylene Glycol glyceryl laurate ester, ethyl oleate, Ethyl linoleate; Surfactant generally is the non-ionic surface active agent of high HLB value, be generally liquid egg phospholipid, polyoxyethylene castor oil, Oleum Cocois C8/C10 polyethyleneglycol glyceride, the almond oil polyethyleneglycol glyceride, polyoxyethylene (25) triglyceride, polyoxyethylene (20) sorbic acid oleate, Polyethylene Glycol-8-glycerol is sad/a kind of in these materials such as decanoin, two or more mixture, cosurfactant generally are ethanol, propylene glycol, glycerol, Polyethylene Glycol (molecular weight is at 200-600), propylene carbonate, ethylene glycol monomethyl ether (transcutolP), the glycerol furfural, a kind of in these materials such as dimethyl Soquad, two or more mixture.
5. fat-soluble medicine self emulsified osmotic pump controlled release administration system according to claim 4 is characterized in that selected absorbent or bag and material are calcium phosphate, magnesium oxide, magnesium carbonate, calcium carbonate, gel aluminum hydroxide powder, Radix Trichosanthis, Rhizoma dioscoreae, Bulbus Fritillariae Thunbergii, Kaolin, bentonite and cyclodextrin.
6. according to claim 1 or 4 described fat-soluble medicine self emulsified osmotic pump controlled release administration systems, it is characterized in that: label inside provides self emulsifying power material and coating material, coating material contains into mold materials and porogen, coating material can be cellulose acetate and/or ethyl cellulose and/or hydroxypropyl emthylcellulose and/or polyethylene and/or polyethylene glycols, and selected porogen can be selected from the mixture of Polyethylene Glycol, glycerol, propylene glycol, dimethyl phthalate, triacetin and these materials.
7. according to claim 1 or 6 described fat-soluble medicine self emulsified osmotic pump controlled release administration systems, it is characterized in that: also contain the osmotic pressure active substance in the selected osmotic pumps, label inside provides the material and the coating material of self emulsifying power, and semipermeable membrane can be made a call to the aperture of a diameter between 0.2-2mm at least.
8. fat-soluble medicine self emulsified osmotic pump controlled release administration system according to claim 6 is characterized in that: it can be effervescent materials that selected label inside provides the material of self emulsifying power, the mixture of various weak organic acids and carbonate or bicarbonate.
9. one kind as claims 1 described fat-soluble medicine self emulsified osmotic pump controlled release administration system, it is characterized in that: selected preparation method is to get the medicine of recipe quantity, the oil phase that adds recipe quantity, any one dissolving of surfactant or cosurfactant, all the other two kinds of solvents that add recipe quantity again, mix homogeneously, or with the direct dissolved substance of self-emulsifiable oil, be prepared into the self-emulsifying drug delivery systems of pastille, self-emulsifiable oil with pastille is a binding agent then, be added in the absorbent and granulate, or, beat sheet after the oven dry with bag and material bag and granulation, make the label of self emulsifying, after again tablet being carried out coating, punching, the self emulsified osmotic pump controlled release preparation of gained, the osmotic pumps that makes is the single chamber mono-layer osmotic pump.
10. fat-soluble medicine self emulsified osmotic pump controlled release administration system according to claim 9, it is characterized in that: self-emulsifiable oil is as the method for binding agent, can directly make binding agent with the liquid self-emulsifiable oil, or in the liquid self-emulsifiable oil, add ethanol dilution as binding agent, perhaps will directly make binding agent after semisolid or the solid self-emulsifying melting, perhaps will in semisolid or solid self-emulsifying system, add ethanol dilution as binding agent.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200510136329 CN1823743A (en) | 2005-12-26 | 2005-12-26 | Self emulsified osmotic pump controlled release administration system of liposoluble medicine and its preparation technology |
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| CN 200510136329 CN1823743A (en) | 2005-12-26 | 2005-12-26 | Self emulsified osmotic pump controlled release administration system of liposoluble medicine and its preparation technology |
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Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670545A (en) * | 2011-03-09 | 2012-09-19 | 中国药科大学 | Carvedilol push-pull osmotic pump type controlled release preparation and preparation method thereof |
| CN103054834A (en) * | 2013-01-30 | 2013-04-24 | 广东药学院 | Preparation method of nimodipine self-microemulsion osmotic pump controlled-release capsule |
| CN105578900A (en) * | 2013-08-29 | 2016-05-11 | 雅培公司 | Nutritional composition having lipophilic compounds with improved solubility and bioavailability |
| CN106727382A (en) * | 2016-12-27 | 2017-05-31 | 中国药科大学 | A kind of Carvedilol supersaturated self-emulsion dispersible tablet and preparation method thereof |
| CN107049977A (en) * | 2016-12-08 | 2017-08-18 | 中国药科大学 | A kind of Carvedilol solid self-emulsifying sustained release tablets and preparation method thereof |
| CN110151730A (en) * | 2019-03-06 | 2019-08-23 | 安徽新华学院 | A kind of hesperetin Solid Self-microemulsion osmotic pumps capsule and preparation method thereof |
| CN111920766A (en) * | 2020-07-28 | 2020-11-13 | 中南林业科技大学 | Ellagic acid dispersion system and preparation method thereof |
| CN112715952A (en) * | 2019-10-29 | 2021-04-30 | 湖北真奥医药研究院有限公司 | Multi-vitamin calcium self-emulsifying composition and preparation method of preparation thereof |
| CN112741841A (en) * | 2019-10-29 | 2021-05-04 | 湖北真奥医药研究院有限公司 | Three-dimensional calcium self-emulsifying effervescent composition and preparation method of preparation thereof |
| CN112807277A (en) * | 2019-10-29 | 2021-05-18 | 湖北真奥医药研究院有限公司 | Fat-soluble vitamin self-emulsifying composition and preparation method of preparation thereof |
| CN114344309A (en) * | 2021-12-30 | 2022-04-15 | 南京迈诺威医药科技有限公司 | Allopregnanolone derivative self-emulsifying preparation and preparation method thereof |
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2005
- 2005-12-26 CN CN 200510136329 patent/CN1823743A/en active Pending
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670545A (en) * | 2011-03-09 | 2012-09-19 | 中国药科大学 | Carvedilol push-pull osmotic pump type controlled release preparation and preparation method thereof |
| CN103054834A (en) * | 2013-01-30 | 2013-04-24 | 广东药学院 | Preparation method of nimodipine self-microemulsion osmotic pump controlled-release capsule |
| CN103054834B (en) * | 2013-01-30 | 2014-04-23 | 广东药学院 | Preparation method of nimodipine self-microemulsion osmotic pump controlled-release capsule |
| CN105578900A (en) * | 2013-08-29 | 2016-05-11 | 雅培公司 | Nutritional composition having lipophilic compounds with improved solubility and bioavailability |
| CN107049977A (en) * | 2016-12-08 | 2017-08-18 | 中国药科大学 | A kind of Carvedilol solid self-emulsifying sustained release tablets and preparation method thereof |
| CN106727382A (en) * | 2016-12-27 | 2017-05-31 | 中国药科大学 | A kind of Carvedilol supersaturated self-emulsion dispersible tablet and preparation method thereof |
| CN110151730A (en) * | 2019-03-06 | 2019-08-23 | 安徽新华学院 | A kind of hesperetin Solid Self-microemulsion osmotic pumps capsule and preparation method thereof |
| CN112715952A (en) * | 2019-10-29 | 2021-04-30 | 湖北真奥医药研究院有限公司 | Multi-vitamin calcium self-emulsifying composition and preparation method of preparation thereof |
| CN112741841A (en) * | 2019-10-29 | 2021-05-04 | 湖北真奥医药研究院有限公司 | Three-dimensional calcium self-emulsifying effervescent composition and preparation method of preparation thereof |
| CN112807277A (en) * | 2019-10-29 | 2021-05-18 | 湖北真奥医药研究院有限公司 | Fat-soluble vitamin self-emulsifying composition and preparation method of preparation thereof |
| CN111920766A (en) * | 2020-07-28 | 2020-11-13 | 中南林业科技大学 | Ellagic acid dispersion system and preparation method thereof |
| CN111920766B (en) * | 2020-07-28 | 2022-06-21 | 中南林业科技大学 | Ellagic acid dispersion system and preparation method thereof |
| CN114344309A (en) * | 2021-12-30 | 2022-04-15 | 南京迈诺威医药科技有限公司 | Allopregnanolone derivative self-emulsifying preparation and preparation method thereof |
| CN114344309B (en) * | 2021-12-30 | 2024-02-06 | 南京迈诺威医药科技有限公司 | Allopregnanolone derivative self-emulsifying preparation and preparation method thereof |
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