CN1559407A - Self-micro emulsion solft capsule of dihydropyridine type calcium ion agonist, and its prepn. method - Google Patents
Self-micro emulsion solft capsule of dihydropyridine type calcium ion agonist, and its prepn. method Download PDFInfo
- Publication number
- CN1559407A CN1559407A CNA2004100211780A CN200410021178A CN1559407A CN 1559407 A CN1559407 A CN 1559407A CN A2004100211780 A CNA2004100211780 A CN A2004100211780A CN 200410021178 A CN200410021178 A CN 200410021178A CN 1559407 A CN1559407 A CN 1559407A
- Authority
- CN
- China
- Prior art keywords
- self
- calcium ion
- oil
- dihydropyridine calcium
- soft capsules
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Medicinal Preparation (AREA)
Abstract
A self-microemulsified softcapsule of nimodipine or nitrendipine is prepared from nimodipine or nitrendipine, coemulsifier, self emulsifier, oil and antioxidizing agent through proportionally mixing nimodipine or nitrendipine, coemulsifier and self emulsifier, constant-temp oscillating, adding oil and antioxidizing agent, stirring, cooling, and shaping.
Description
Technical field:
The present invention relates to medical technical field, exactly it is the self-emulsification soft capsules and preparation method thereof of the dihydropyridine calcium ion antagonist of a kind of nitrendipine or nimodipine.
Background technology:
Nitrendipine (nitrendipine) is a dihydropyridine type calcium antagonists, and vascular smooth muscle is had stronger selectivity, and a little less than the effect to cardiac muscle, so can cause whole body blood vessel, comprise coronary artery, kidney small artery, make it expansion, produce hypotensive effect, and less to the normal arterial pressure influence.Be mainly used in the various types of hypertension of treatment, and hypotensive effect significantly and lastingly, especially be fit to the senile hypertension patient, and can improve the blood supply and the myocardial function of the heart, kidney, brain in blood pressure lowering simultaneously.
The nitrendipine oral administration biaavailability is little, t
1/2Be 6-15 hour.By metabolism, the non-activity metabolite generates, mainly through renal excretion in liver.
Nimodipine (nimodipine) also is a dihydropyridine type calcium antagonists, and main selectivity expansion of cerebral vascular is removed cerebral vasospasm, the cerebral blood flow increasing amount.Ischemia is had protective effect, and can suppress and resist the contraction of various blood vessels.Document thinks that the nimodipine main pharmacological shows as: suppress the cerebral vasospasm that causes by subarachnoid hemorrhage, and the nervous symptoms after dwindling the infarction size after the cerebral ischemia and alleviating cerebral ischemia, but metabolism does not have influence to brain.Also have the function that promotes or protect memory simultaneously, also can anticoagulant and antithrombotic formation.The posthemorrhagic cerebral vasospasm of subarachnoid space and the convalescent blood circulation of acute cerebrovascular disease that are applicable to a variety of causes improve, and also are used as sudden deafness, hypertension, migraine and dull-witted treatment.
The oral Nimoldipine bioavailability is little, can pass blood-cerebrospinal fluid barrier rapidly, and the drug level in the cerebrospinal fluid is about 10% in the blood plasma.T
1/2It is 2～9 hours.
Existing nitrendipine, oral Nimoldipine preparation have preparations such as tablet, common hard capsule and soft capsule, and because of its poorly water-soluble causes dissolution low, bioavailability is low.The present invention adopts the self-emulsifying microemulsion technology to be made into self-emulsification soft capsules, can form microemulsion rapidly after oral, has improved the dissolution of medicine and gastrointestinal tract mucous permeability greatly, thereby improves bioavailability of medicament, reduces untoward reaction.
Summary of the invention:
The self-emulsification soft capsules and preparation method thereof that the purpose of this invention is to provide the dihydropyridine calcium ion antagonist of a kind of nitrendipine or nimodipine, can form microemulsion rapidly after the present invention is oral, the dissolution of medicine and gastrointestinal tract mucous permeability have been improved greatly, thereby the raising bioavailability of medicament reduces untoward reaction.The self-emulsification soft capsules of dihydropyridine calcium ion antagonist, it is made up of dihydropyridine calcium ion antagonist and drug delivery system.Self-emulsifying drug delivery system (Self-Emulsifying Drug Delivery System, SEDDS) be the solution of the transparent and homogeneous that forms by oil phase, emulsifying agent and co-emulsifier, under the condition of stirring of ambient temperature (being often referred to about 37 ℃) and gentleness, because the existence of emulsifying agent, spontaneous emulsification forms the Emulsion of particle about 5 microns.Along with increasing of emulsifying agent consumption, this self-emulsifying drug delivery systems can be in gastrointestinal tract spontaneous formation microemulsion, be referred to as the self-emulsifying microemulsion drug delivery system (Self-Microemulsifying Drug DeliverySystem, SMEDDS).Medicine is present in these tiny oil droplets, is distributed in fast in the whole gastrointestinal tract, and medicine distributes between oil/water is biphase, and the stripping that relies on the huge specific surface area of tiny oil droplet to improve water-insoluble drug has greatly improved bioavailability of medicament.
The mass fraction (w/w) of oil phase in SEDDS is generally 20%-70%, oil phase as SEDDS, requirement can be with the medicine of less consumption dissolving recipe quantity, and does not also have medicine separate out under the cryopreservation condition, meets simultaneously behind the water easily by the emulsifying agent emulsifying in the prescription.The oil that SEDDS uses the earliest is crude vegetal, but the ability and the automatic emulsifying performance of these oil dissolving fat-soluble medicines are not strong.In the presence of non-ionic surface active agent that can be oral, easily form SEDDS through the vegetable oil after structure of modification and the hydrolysis, as soybean oil, Oleum Arachidis hypogaeae semen, safflower oil, the Fructus Canarii albi wet goods after the improvement.The flowability of fatty acid ester, dissolubility and self emulsifying are better, especially medium chain fatty glyceride (the medium-chain glyceride of chain length between C8～C10, be called for short MCT), be everlasting and preferentially used among the SEDDS, its safety, stable, can make Emulsion under different temperatures with multiple composition, MCT also can promote the little intestinal absorption of medicine.At present often adopt long-chain and medium-chainly have in various degree that the triglyceride oils of saturation designs the self emulsifying dosage form.Except that vegetable oil that can be oral commonly used, following oils is good to the insoluble drug dissolubility, and automatic emulsifying performance is good:
Arlacel 80 (HLB=4.3) oleic acid sorbitol ester
Arlacel 86 (HLB=2.8) olein: propylene glycol (90: 10)
Capmul MCM (HLB=5.5-6.0) Oleum Cocois C8/C10 monoglyceride or dibasic acid esters
Captex 200 (oil) Oleum Cocois C8/C10 propylene glycol dibasic acid esters
Captex 355 (oil) Oleum Cocois C8/C10 triglyceride
Miglyol 812 (oil) Oleum Cocois C8/C10 triglyceride
The acetylizad monoglyceride of Myvacet (oil) purification
Myverol 18-92 (HLB=3-7) purification Oleum helianthi monoglyceride (contains 90%
Glyceryl linoleate)
Soybean oil contains oleic acid (25%) and linoleic acid
(54%) triglyceride
Peceol (HLB=3) olein
Maisine (HLB=3) olein
Gelucire 44/14 (HLB=14) Polyethylene Glycol glyceryl laurate ester
The general nonionic emulsifier that adopts high HLB of emulsifying agent among the SEDDS.Nonionic emulsifier is lower than ionic emulsifying agent toxicity, and they only cause that the infiltrative reversibility of gastrointestinal tract wall changes.The strongly hydrophilic of high HLB emulsifying agent is to form oil-in-water emulsion droplet and self emulsifying liquid immediately to spread necessaryly in aqueous environment, and it can make the self emulsifying process faster.Emulsifying agent is amphiphatic, and they itself also can dissolve a large amount of relatively hydrophobic drugs, can prevent that medicine from depositing in gastrointestinal tract and the dissolved state of prolong drug molecule, and this is extremely important to effective absorption.When the emulsifier content height arrives to a certain degree, will cause the formation of self-emulsifying microemulsion system.Different types of liquid or solid ethyoxyl polyoxyethylene glyceride, polyoxyethylene oleate, Tween80 are the most frequently used emulsifying agents.In order to reach good emulsifying effectiveness, adopt the emulsifying agent more than 30% usually.Below be preparation self-emulsifiable preparation some emulsifier commonly used:
Ophase 31 (HLB=4.0) liquid egg phospholipid
Cremophor EL (HLB=13.5) polyoxyethylene castor oil
Labrafac CM 10 (HLB=10) Oleum Cocois C8/C10 polyethyleneglycol glyceride
Labrafil M 1944 CSD (HLB=3-4) mainly are almond oil acid polyethylene glycol glyceride
Labrafil M 2125 CS (HLB=3-4) mainly are almond oil acid polyethylene glycol glyceride
Tagat TO (HLB=11.3) polyoxyethylene (25) triolein
Tween 80 (HLB=11.0) polyoxyethylene (20) sorbitan oleate
Labrasol (HLB=14) Polyethylene Glycol-8-glycerol is sad/decanoin
Co-emulsifier agent among the SEDDS, its existing hydrophilic also has lipophile.Co-emulsifier helps active component to form uniform Emulsion and keeps the stability of Emulsion in storage process.Spendable cosurfactant has ethanol, propylene glycol, Polyethylene Glycol (molecular weight is at 200-600), propylene carbonate (propylene carbonate), ethylene glycol monomethyl ether (transcutol), glycerol furfural, dimethyl Soquad or above mixture in this invention.The present invention is made up of dihydropyridine calcium ion antagonist, co-emulsifier, self-emulsifier and oil phase, and its weight ratio is 1: 1～20: 1～20: 0.5～10.Dihydropyridine calcium ion is nitrendipine or nimodipine.Described co-emulsifier is ethanol, propylene glycol, Polyethylene Glycol, propylene carbonate, ethylene glycol monomethyl ether, glycerol furfural, dimethyl Soquad or above-mentioned mixture.Described oil phase can be vegetable oil or the medium chain fatty glyceride of chain length between C8～C10 after crude vegetal, process structure of modification and the hydrolysis.Described vegetable oil can be soybean oil, Oleum Arachidis hypogaeae semen, safflower oil, olive oil, and spendable oil phase has Arlacel 80, Arlacel 86, Capmul MCM, Captex 200 (oil), Captex355 (oil), Miglyol 812 (oil), Myvacet (oil), Myverol 18-92, olein, glyceryl linoleate, Polyethylene Glycol glyceryl laurate ester, ethyl oleate, Ethyl linoleate etc.The general nonionic emulsifier that adopts high HLB of emulsifying agent in the self-emulsifying microemulsion drug delivery system, liquid egg phospholipid, hydrogenation polyoxyethylene, Oleum Ricini, Labrafac CM 10, LabrafilM 1944 CSD, Labrafil M 2125 CS, Tagat TO, Tween 80, Labrasol.Its preparation method is as follows: take by weighing an amount of nitrendipine or nimodipine, the co-emulsifier that adds recipe quantity, emulsifying agent, at 40 ℃, vibration made its dissolving in about 1 hour during 100 rev/mins of constant temperature vibrations were bathed, add the oil phase of recipe quantity again, antioxidant stirs, and treats to be pressed into capsule after medicinal liquid is reduced to room temperature.
Advantage of the present invention is: the present invention has good water solubility, and the advantage that dissolution is high can form microemulsion rapidly after oral, has improved the dissolution of medicine and gastrointestinal tract mucous permeability greatly, thereby improves drug bioavailability, reduces untoward reaction.
Description of drawings:
Fig. 1 is nitrendipine SMEDDS of the present invention and the capsular stripping of Bay e 5009
Fig. 2 is a nimodipine SMEDDS capsule stripping curve of the present invention
Fig. 3 is the logical stripping curve of soft gelatin capsule in different dissolution mediums of grace of the present invention
The specific embodiment:
Embodiment 1:
It is composed as follows to write out a prescription: (g)
Nitrendipine 10
Dimethyl Soquad 115
Ethyl oleate 65
Tween80 150
Vitamin E 10
Make 1000 soft capsules altogether
Preparation technology: take by weighing an amount of nitrendipine, the dimethyl Soquad that adds recipe quantity, Tween80, at 40 ℃, vibration made its dissolving in about 1 hour during 100 rev/mins of constant temperature vibrations were bathed, add the ethyl oleate of recipe quantity again, vitamin E stirs, and treats to be pressed into capsule after medicinal liquid is reduced to room temperature.
Embodiment 2:
It is composed as follows to write out a prescription: (g)
Nitrendipine 10
Dimethyl Soquad 100
Miglyol?812 50
Tween80 185
Vitamin E 10
Make 1000 soft capsules altogether
Preparation technology is with embodiment 1.
Embodiment 3:
It is composed as follows to write out a prescription: (g)
Nitrendipine 10
Laborosol 120
Ethyl oleate 65
Tween80 145
Vitamin E 10
Make 1000 soft capsules altogether
Preparation technology is with embodiment 1.
Embodiment 4:
It is composed as follows to write out a prescription: (g)
Nitrendipine 10
Laborosol 135
Ethyl oleate 65
Tween80 135
Vitamin E 10
Make 1000 soft capsules altogether
Preparation technology is with embodiment 1.
Embodiment 5:
It is composed as follows to write out a prescription: (g)
Nitrendipine 10
Miglyol?812 50
Tween80 185
Vitamin E 10
Make 1000 soft capsules altogether
Embodiment 6:
It is composed as follows to write out a prescription: (g)
Dimethyl Soquad 140
Tween80 180
Vitamin E 10
Make 1000 soft capsules altogether
Preparation technology: take by weighing an amount of nimodipine, the dimethyl Soquad that adds recipe quantity, Tween80, at 40 ℃, vibration made its dissolving in about 1 hour during 100 rev/mins of constant temperature vibrations were bathed, add the ethyl oleate of recipe quantity again, vitamin E stirs, and treats to be pressed into capsule after medicinal liquid is reduced to room temperature.
Embodiment 7:
It is composed as follows to write out a prescription: (g)
Dimethyl Soquad 140
Miglyol?812 60
Tween80 200
Vitamin E 10
Make 1000 soft capsules altogether
Preparation technology is with embodiment 1.
Embodiment 8:
It is composed as follows to write out a prescription: (g)
Laborosol 140
Tween80 180
Vitamin E 10
Make 1000 soft capsules altogether
Preparation technology is with embodiment 1.
Embodiment 9:
It is composed as follows to write out a prescription: (g)
Laborosol 160
Tween80 160
Vitamin E 10
Make 1000 soft capsules altogether
Preparation technology is with embodiment 1.
Embodiment 10:
It is composed as follows to write out a prescription: (g)
Laborosol 140
Miglyol?812 60
Tween80 200
Vitamin E 10
Make 1000 soft capsules altogether
The nitrendipine SMEDDS capsule and the commercially available nitrendipine capsule Bay e 5009 that make according to embodiment 1 carry out the dissolution test, the results are shown in Figure 1.
Dissolution determination method: get this product, according to dissolution method (two appendix X of Chinese Pharmacopoeia version in 2000 C, first method), respectively with distilled water, 0.1mol/L hydrochloric acid, pH6.8 buffer salt solution 500mL is a solvent, rotating speed is 100r/min, operation in accordance with the law, respectively 5,10,20,30,45, during 60min, get solution an amount of (replenishing the fresh medium of equality of temperature simultaneously) with volume, filter, get subsequent filtrate according to spectrophotography (two appendix IV of Chinese Pharmacopoeia version in 2000 A), wavelength place at 356nm measures trap, it is an amount of that other gets the nitrendipine reference substance, respectively with water 0.1mol/L hydrochloric acid, the pH6.8 buffer salt solution is that solvent is made the nitrendipine solution that concentration is about 18 μ g/mL, measures with method, calculates the accumulation stripping quantity of every capsules.As seen from Figure 1, homemade nitrendipine SMEDDS capsule obviously improves than commercially available nitrendipine capsule Bay e 5009 dissolution.The nimodipine SMEDDS capsule that makes according to embodiment 6, carry out the dissolution test, the results are shown in Figure 2,3,4 with the logical soft gelatin capsule of commercially available nimodipine soft gelatin capsule grace.Dissolution determination method: get this product, according to dissolution method (two appendix X of Chinese Pharmacopoeia version in 2000 C, first method), respectively with distilled water, 0.1mol/L hydrochloric acid, pH6.8 buffer salt solution 900mL is a solvent, rotating speed is 100r/min, operation in accordance with the law, respectively 5,10,20,30,45, during 60min, get solution an amount of (replenishing the fresh medium of equality of temperature simultaneously) with volume, filter, get subsequent filtrate according to spectrophotography (two appendix IV of Chinese Pharmacopoeia version in 2000 A), wavelength place at 359nm measures trap, it is an amount of that other gets the nimodipine reference substance, respectively with water 0.1mol/L hydrochloric acid, the pH6.8 buffer salt solution is that solvent is made the nimodipine solution that concentration is about 20 μ g/mL, measures with method, calculates the accumulation stripping quantity of every capsules.By Fig. 2,3 as seen, homemade nimodipine SMEDDS capsule obviously improves than commercially available nimodipine soft gelatin capsule (grace is led to soft gelatin capsule) dissolution, and downward trend do not occur.
Claims (9)
1, the self-emulsification soft capsules of dihydropyridine calcium ion antagonist is characterized in that: it is made up of dihydropyridine calcium ion antagonist and drug delivery system.
2, the self-emulsification soft capsules of dihydropyridine calcium ion antagonist according to claim 1, it is characterized in that: drug delivery system is the solution of the transparent and homogeneous that formed by oil phase, emulsifying agent and co-emulsifier, under the condition of stirring of ambient temperature and gentleness, because the existence of emulsifying agent, spontaneous emulsification forms the Emulsion of particle about 5 microns.Along with increasing of emulsifying agent consumption, this self-emulsifying drug delivery systems can be in gastrointestinal tract spontaneous formation microemulsion, be referred to as the self-emulsifying microemulsion drug delivery system.
3, the self-emulsification soft capsules of dihydropyridine calcium ion antagonist according to claim 1, it is characterized in that: dihydropyridine calcium ion antagonist, co-emulsifier, self-emulsifier and oil phase are formed, and its weight ratio is 1: 1～20: 1～20: 0.5～10.
4, the self-emulsification soft capsules of dihydropyridine calcium ion antagonist according to claim 3 is characterized in that: dihydropyridine calcium ion is nitrendipine or nimodipine.
5, the self-emulsification soft capsules of dihydropyridine calcium ion antagonist according to claim 3 is characterized in that: described co-emulsifier is ethanol, propylene glycol, Polyethylene Glycol, propylene carbonate, ethylene glycol monomethyl ether, glycerol furfural, dimethyl Soquad or above-mentioned mixture.
6, the self-emulsification soft capsules of dihydropyridine calcium ion antagonist according to claim 3 is characterized in that: described oil phase can be vegetable oil or the medium chain fatty glyceride of chain length between C8～C10 after crude vegetal, process structure of modification and the hydrolysis.
7, the self-emulsification soft capsules of dihydropyridine calcium ion antagonist according to claim 6, it is characterized in that: described vegetable oil can be soybean oil, Oleum Arachidis hypogaeae semen, safflower oil, olive oil, and spendable oil phase has Arlacel 80, Arlacel 86, Capmul MCM, Captex 200 (oil), Captex 355 (oil), Miglyol 812 (oil), Myvacet (oil), Myverol 18-92, olein, glyceryl linoleate, Polyethylene Glycol glyceryl laurate ester, ethyl oleate, Ethyl linoleate etc.
8, the self-emulsification soft capsules of dihydropyridine calcium ion antagonist according to claim 3, it is characterized in that: the nonionic emulsifier of the general high HLB of employing of the emulsifying agent in the self-emulsifying microemulsion drug delivery system, liquid egg phospholipid, hydrogenation polyoxyethylene, Oleum Ricini, Labrafac CM 10, LabrafilM 1944 CSD, Labrafil M 2125 CS, Tagat TO, Tween 80, Labrasol.
9, a kind of preparation method of self-emulsification soft capsules of dihydropyridine calcium ion antagonist as claimed in claim 1, it is characterized in that: take by weighing an amount of nitrendipine or nimodipine, the co-emulsifier that adds recipe quantity, emulsifying agent, at 40 ℃, vibration made its dissolving in about 1 hour during 100 rev/mins of constant temperature vibrations were bathed, and added the oil phase of recipe quantity again, antioxidant stirs, and treats to be pressed into capsule after medicinal liquid is reduced to room temperature.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2004100211780A CN1559407A (en) | 2004-02-23 | 2004-02-23 | Self-micro emulsion solft capsule of dihydropyridine type calcium ion agonist, and its prepn. method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2004100211780A CN1559407A (en) | 2004-02-23 | 2004-02-23 | Self-micro emulsion solft capsule of dihydropyridine type calcium ion agonist, and its prepn. method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1559407A true CN1559407A (en) | 2005-01-05 |
Family
ID=34440806
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2004100211780A Pending CN1559407A (en) | 2004-02-23 | 2004-02-23 | Self-micro emulsion solft capsule of dihydropyridine type calcium ion agonist, and its prepn. method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1559407A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101780056A (en) * | 2010-04-29 | 2010-07-21 | 中国药科大学 | Self-assembling proliposome soft capsule and preparation method thereof |
| CN102008471A (en) * | 2010-12-13 | 2011-04-13 | 沈阳药科大学 | Lacidipine self-microemulsifying soft capsules and preparation method thereof |
| CN1771949B (en) * | 2005-11-06 | 2011-04-20 | 沈阳药科大学 | Soft nimodipine capsule and its preparation |
| CN102178056A (en) * | 2011-05-05 | 2011-09-14 | 王宏雁 | Dihydropyridine clathrate compound |
| CN102302470A (en) * | 2011-09-05 | 2012-01-04 | 澳诺（青岛）制药有限公司 | Nitrendipine soft capsule |
| CN101738455B (en) * | 2008-11-26 | 2013-04-10 | 江苏吉贝尔药业有限公司 | Dissolution detection method of nitrendipine and atenolol compound composition |
| CN103054834A (en) * | 2013-01-30 | 2013-04-24 | 广东药学院 | Preparation method of nimodipine self-microemulsion osmotic pump controlled-release capsule |
| CN101618020B (en) * | 2009-06-17 | 2014-05-21 | 沈阳药科大学 | Solid self-emulsifying oral administration system of dihydropyridine calcium ion antagonist and preparation method thereof |
| CN104706593A (en) * | 2013-12-16 | 2015-06-17 | 天津迈迪瑞康生物医药科技有限公司 | Nimodipine fat emulsion concentrate and preparation method and use thereof |
-
2004
- 2004-02-23 CN CNA2004100211780A patent/CN1559407A/en active Pending
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1771949B (en) * | 2005-11-06 | 2011-04-20 | 沈阳药科大学 | Soft nimodipine capsule and its preparation |
| CN101738455B (en) * | 2008-11-26 | 2013-04-10 | 江苏吉贝尔药业有限公司 | Dissolution detection method of nitrendipine and atenolol compound composition |
| CN101618020B (en) * | 2009-06-17 | 2014-05-21 | 沈阳药科大学 | Solid self-emulsifying oral administration system of dihydropyridine calcium ion antagonist and preparation method thereof |
| CN101780056A (en) * | 2010-04-29 | 2010-07-21 | 中国药科大学 | Self-assembling proliposome soft capsule and preparation method thereof |
| CN102008471B (en) * | 2010-12-13 | 2012-12-19 | 沈阳药科大学 | Lacidipine self-microemulsifying soft capsules and preparation method thereof |
| CN102008471A (en) * | 2010-12-13 | 2011-04-13 | 沈阳药科大学 | Lacidipine self-microemulsifying soft capsules and preparation method thereof |
| CN102178056A (en) * | 2011-05-05 | 2011-09-14 | 王宏雁 | Dihydropyridine clathrate compound |
| CN102178056B (en) * | 2011-05-05 | 2012-08-08 | 王宏雁 | Dihydropyridine clathrate compound |
| CN102302470B (en) * | 2011-09-05 | 2013-01-02 | 澳诺（青岛）制药有限公司 | Nitrendipine soft capsule |
| CN102302470A (en) * | 2011-09-05 | 2012-01-04 | 澳诺（青岛）制药有限公司 | Nitrendipine soft capsule |
| 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 |
| CN104706593A (en) * | 2013-12-16 | 2015-06-17 | 天津迈迪瑞康生物医药科技有限公司 | Nimodipine fat emulsion concentrate and preparation method and use thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1174741C (en) | Surface modified particulate compositions of biologically active substances | |
| RU2266121C2 (en) | N-benzoylstaurosporin-containing spontaneously dispersing compositions | |
| CN1273526A (en) | Microdisperse drug delivery systems | |
| CN1353613A (en) | Pharmaceutical compositions | |
| CN1857222A (en) | Submicron docetaxel emulsion for intravenous injection and its preparing process | |
| CN1261796A (en) | Self-emulsifying formulation for lipophilic compounds | |
| CN1180840C (en) | Cyclosphorin-containing soft capsule preparation | |
| JP2019514995A (en) | Combined preparation of dutasteride and tadalafil containing glycerin fatty acid ester derivative or propylene glycol fatty acid ester derivative and oral capsule preparation containing the same | |
| CN1256939C (en) | Coenzyme Q10 containing microemulsion preconcentrates and microemulsions | |
| CN1823729A (en) | Butyl benzene phthalein vein emulsion and its application | |
| CN101057829A (en) | Supersaturated cationic self-emulsified drug delivery system and its preparation method | |
| CN1559407A (en) | Self-micro emulsion solft capsule of dihydropyridine type calcium ion agonist, and its prepn. method | |
| CN1127350C (en) | Cyclosporin-containing soft capsule preparations | |
| CN1893932A (en) | Microemulsion preconcentrate comprising a renin inhibitor | |
| JP4083985B2 (en) | New pharmaceutical composition | |
| Kazi | Lipid‐based nano‐delivery for oral administration of poorly water soluble drugs (PWSDs): design, optimization and in-vitro assessment | |
| CN1555802A (en) | Cinnarizone self micro emulsified soft capsule and its preparation method | |
| CN1457776A (en) | Self emulsified soft capsule of ginkgo leaf extract and its preparing method | |
| CN1593449A (en) | self emulsifying soft capsule of breviscapine and its preparation | |
| CN100525775C (en) | Pueraria root flavone self-microemulsified soft capsule and its preparing method | |
| RU2397759C2 (en) | Microemulsion compositions including substance p antagonists | |
| CN1161150C (en) | Pharmaceutical compositions | |
| CN1827632A (en) | Process for purifying zidovudine palmitate raw materials and preparations thereof | |
| CN1660257A (en) | Soft capsule of extractive from leaves of persimmon and self-emulsifying system for releasing drug | |
| CN1771949A (en) | Soft nimodipine capsule and its prepn |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |