CN102451159A - Superfine vinpocetine composite particle and preparation method thereof - Google Patents
Superfine vinpocetine composite particle and preparation method thereof Download PDFInfo
- Publication number
- CN102451159A CN102451159A CN2010105264243A CN201010526424A CN102451159A CN 102451159 A CN102451159 A CN 102451159A CN 2010105264243 A CN2010105264243 A CN 2010105264243A CN 201010526424 A CN201010526424 A CN 201010526424A CN 102451159 A CN102451159 A CN 102451159A
- Authority
- CN
- China
- Prior art keywords
- vinpocetine
- composite particles
- fine
- solution
- pharmaceutic adjuvant
- 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
The invention discloses a superfine vinpocetine composite particle and a preparation method thereof, and belongs to the field of micronization of insoluble medicaments. The particle comprises the following components in percentage by mass: 5 to 50 percent of vinpocetine, and 50 to 95 percent of water-soluble medicinal auxiliary materials, wherein the average particle diameter of the vinpocetine is 500-2,000nm. The preparation method comprises the following steps: dissolving a vinpocetine medicament in acid; quickly placing in an alkaline solution containing water-soluble medicinal auxiliary materials to perform a neutralization reaction to obtain a nano-vinpocetine medicinal suspension; and filtering and cleaning the prepared nano-vinpocetine medicinal suspension, and dispersing into an aqueous solution containing water-soluble medicinal auxiliary materials once again for spray drying to obtain the superfine vinpocetine composite particles to realize micronization of the medicament. The composite particle has the advantages of small medicinal particle diameter, high dissolving speed and the like; and the method provided by the invention is simple in operation, is easy in scale and industrial production, and is excellent in application prospect.
Description
Technical field
The present invention relates to a kind of method for preparing of ultra-fine vinpocetine medicine composite particles, particularly adopt reaction-crystallization method to prepare the method for ultra-fine vinpocetine medicine composite particles, belong to insoluble drug micronization field.
Technical background
Vinpocetine (vinpocetine), chemical name: ethyl (13as, 13bs)-13a-ethyl-2,3,5,6-13a, 13b six hydrogen-1H-indole [3,2,1-de] pyridines [3,2,1-ij] [1,5]-benzodiazine-12-carboxylic acid, its structural formula is:
Vinpocetine is the alkaloid that from the Apocynaceae periwinkle, extracts; The apovincamine acid ethyl ester of developing through synthetic, a series of derivants of screening; Be cerebral vasodilator, can keep or recover cerebrovascular physiological expansion, increase the normal brain activity blood flow of ischemic region; Improve the utilization rate of brain, improve the metabolism of anoxia cerebral tissue blood oxygen.Since 1978 are succeeded in developing by Hungary Gedeon Richter company, because of clinical effectiveness significantly and safety good with toleration, clinical application range constantly enlarges, and has become American-European countries and Japanese routine administration at present.In decades, a large amount of scientific researches confirm that vinpocetine is to the selective effect of cerebral blood vessel; The blood circulation that can selectivity improves brain; Promote the energy metabolism of brain, regulate the neurotransmitter systemic-function, many-sided protection brain is avoided the infringement of hypoxic-ischemic.Prevention and treatment apoplexy sequela, cerebral arteriosclerosis and high blood viscosity there are good curative effect, and the memory of improvement is arranged, improve emotion, improve effects such as senile audition and visual abnormality.
But vinpocetine belongs to the medicine of slightly water-soluble, and the dissolubility in water is extremely low, and oral administration biaavailability is relatively poor.Report that cause the low reason of vinpocetine bioavailability to have: 1. the dissolubility of vinpocetine in water is extremely low, has had a strong impact on the stripping and the absorption of medicine; 2. the first pass effect of liver; 3. food effect to the drug absorption influence obviously.In above-mentioned factor, process in leaching is the key factor of its bioavailability of restriction.According to Ostwald Freundrich equation, medicine dissolution rate and size of pharmaceutical particles are inverse ratio, reduce the drug particles particle diameter and can significantly improve its dissolution rate, thereby significantly improve bioavailability of medicament, reduce individual variation, reduce toxic and side effects.
Current; Concentrate on mostly about the research that improves the vinpocetine bioavailability in the development and improvement of ordinary preparation, like preparation vinpocetine slow releasing tablet (patent CN1810242), Vinpocetine drop pills agent (patent CN1919195), Vinpocetine freeze-dried powder for injection (patent CN101264064) etc.Pass through said method; The bioavailability that makes vinpocetine that has has obtained certain raising; But these methods all exist process complicacy, less stable, problem that method for preparing is outmoded; The more important thing is that said method drug prepared granule is bigger, the bioavailability of vinpocetine is not improved fully.
Prior art is to select for use the different pharmaceutical adjuvant that pharmaceutical dosage form is improved mostly, but obviously not progressive on method for preparing.Difference of the present invention is, uses reaction-crystallization method that the vinpocetine medicine is carried out micronization improving its specific surface area, thereby significantly improves the dissolution rate of medicine.And the present relevant report that improves vinpocetine medicine dissolution rate through this method of not seeing as yet.
Reaction-crystallization method, its principle is: the chemical reaction through two kinds or more kinds of components produces degree of supersaturation and carries out crystalline process.In this process, can produce novel substance through adding reactant or regulating the soda acid ratio., the concentration of this material in solution will crystallization separate out when surpassing its dissolubility.Can reach the purpose that generates subparticle through control to response parameter such as reaction temperature, kinds of surfactants and consumption, soda acid volume ratio in the process.
Summary of the invention
The new method that the purpose of this invention is to provide a kind of ultra-fine vinpocetine medicine composite particles preparation; Mix the suspension that obtains with the aqueous slkali that contains pharmaceutic adjuvant through the vinpocetine raw material medicine solution and carry out spray drying and make ultra-fine vinpocetine medicine composite particles, thereby improve the dissolution rate and the oral administration biaavailability of medicine.
A kind of ultra-fine vinpocetine medicine composite particles provided by the present invention is to be active component, to be the micron order composite particles of carrier with the water solublity pharmaceutic adjuvant with the vinpocetine nano-particle; The quality percentage composition that said vinpocetine quality percentage composition is 5-50%, water solublity pharmaceutic adjuvant is 50-95%, grain diameter 500-2000nm.
Described water solublity pharmaceutic adjuvant is a kind of in Polyethylene Glycol, poloxamer, polyvinylpyrrolidone, polyethylene oxide, hydroxypropyl emthylcellulose, mannitol, sodium lauryl sulphate, chitosan, sodium alginate, the lactose or their mixture.
Ultra-fine vinpocetine medicine composite particles of the present invention is prepared by reaction-crystallization method; With the drug solution of vinpocetine crude drug with the acid preparation; Mix with the aqueous slkali that contains the water solublity pharmaceutic adjuvant; The washing of vinpocetine suspension, the filtration that will obtain after will mixing again also is distributed to spray drying in the aqueous solution that contains the water solublity pharmaceutic adjuvant once more, promptly obtains ultra-fine vinpocetine medicine composite particles.Concrete step and method are following:
A: crude drug is dissolved in the acid solution, removes impurity through filtering with microporous membrane, being mixed with concentration is 1-100mg/mL clarification drug solution;
B: pharmaceutic adjuvant is dissolved in the aqueous slkali, and being made into concentration is the adjuvant aqueous slkali of 0.1-15mg/mL;
C: in the reactive crystallization temperature under 0-30 ℃; The drug solution of A step is mixed with the pharmaceutic adjuvant aqueous slkali of B step and stirs simultaneously; Obtain vinpocetine drug particles suspension; Wherein the volume ratio of raw material medicine solution and pharmaceutic adjuvant aqueous slkali is 1: 5-1: 20, and mixing speed is 1000rpm-10000rpm;
D: the washing of drug particles suspension, the filtration of C step also are distributed to spray drying in the aqueous solution that contains the water solublity pharmaceutic adjuvant once more, promptly obtain ultra-fine vinpocetine medicine composite particles.The control inlet temperature is 100-150 ℃ during spray drying, and outlet temperature is 60-90 ℃, and charging rate is 5-40mL/min, and compressed air pressure is 0.4-0.8Mpa.
Above-mentioned described acid is for having the material of certain solubility to medicine, can be a kind of in the following material or their mixture: hydrochloric acid, acetic acid, citric acid, but be not limited to above-mentioned substance.
Above-mentioned described alkali can be a kind of in the following material or their mixture: potassium hydroxide, sodium hydroxide, ammonia, but be not limited to above-mentioned substance.
Nano-particle has very high surface energy, very easily reunites, and does not reach nanometer size effect.The nanoparticle of medicine activity component is dispersed in processes composite particles in the water-solubility carrier, then avoided the reunion of nanoparticle, drug particles can demonstrate good water-redispersible.Simultaneously composite particles have good stability, easy to carry and transport, be beneficial to advantage such as storage.
The association reaction sedimentation method of the present invention and spray drying technology have been prepared the ultra-fine vinpocetine medicine of crystal type composite particles.Product Chinese medicine granule mean diameter is little, has good dissolving out capability.The ultra-fine vinpocetine medicine of prepared crystal type composite particles, grain diameter 500-2000nm, crystal formation is identical with crude drug; Crystal type composite particles 15min stripping can reach more than 90%.This method technology is simple, is easy to large-scale production, has a good application prospect.
The invention has the beneficial effects as follows:
1, the vinpocetine nano-particle is through the reaction precipitation method preparation, and this method is novel simple, and easy operating, and is less demanding to stirring condition.Under general stirring intensity, drug solution is mixed the back just can obtain vinpocetine nanometer suspension liquid with the adjuvant aqueous slkali that contains surfactant.
2, the prepared ultra-fine vinpocetine medicine composite particles of the present invention; Drug particles particle diameter wherein is little; Has good dissolving out capability; Be leachable 91% in 15 minutes, and the sieve stripping quantity of physical mixed powder body in 120 minutes of mixing of vinpocetine crude drug and adjuvant is merely 70% in proportion.
3, the prepared ultra-fine vinpocetine medicine composite particles of the present invention can be prepared into different dosage form, as required like tablet, granule, capsule and suspensoid.
4, the composition of ultra-fine vinpocetine medicine composite particles of the present invention is fairly simple, and carrier material is pharmaceutic adjuvant commonly used.
5, the method that the present invention adopted is novel simple, is easy to suitability for industrialized production, has a good application prospect.
Description of drawings
Fig. 1 is the sem photograph of vinpocetine crude drug.
Fig. 2 is the particulate sem photograph of vinpocetine in instance 3 slurries of the present invention.
Fig. 3 is the sem photograph of instance 3 ultra-fine vinpocetine medicine composite particles of the present invention.
Fig. 4 is Fourier infrared spectrum (FT-IR) figure of instance 4 adjuvants of the present invention, ultra-fine vinpocetine medicine composite particles and vinpocetine crude drug.
Fig. 5 is X-ray diffraction (XRD) figure of vinpocetine crude drug, physical mixed powder body and the ultra-fine vinpocetine medicine composite particles of embodiment 8.
Fig. 6 is the stripping curve figure of ultra-fine vinpocetine medicine composite particles, physical mixed powder body and the vinpocetine crude drug of embodiment 3.
Below in conjunction with the accompanying drawing and the specific embodiment the present invention is described further.
The specific embodiment
A: take by weighing 0.1g vinpocetine crude drug and be dissolved in the 5ml acetic acid, the crude drug pattern is seen Fig. 1, and visible vinpocetine crude drug granule-morphology is different, and particle diameter is also very inhomogeneous, does not wait to 120 μ m from 5 μ m;
B: take by weighing 0.1g polyvinylpyrrolidone, 0.75g sodium lauryl sulphate and 4g sodium hydroxide and be dissolved in the 75mL deionized water, fully dissolve and will be equipped with the beaker ice-water bath of this solution, control this solution temperature about 15 ℃;
C: under the stirring condition of 3000rpm, the raw material medicine solution of preparing in the steps A is poured into fast in the solution of B step preparation, reactive crystallization obtains vinpocetine nanometer suspension liquid, continues to stir ageing 10min;
D: gained vinpocetine nanometer suspension liquid among the step C is filtered, and use the deionized water wash filter cake;
E: above-mentioned filter cake is placed in the beaker and adds 0.1g polyvinylpyrrolidone, 0.75g sodium lauryl sulphate and 75mL deionized water, under ultrasonication, make the filter cake redispersion in water;
F: control spray dryer (SD-Basic, Labplant, Britain) inlet temperature is 120 ℃; Outlet temperature is 60 ℃, and charging rate is 5mL/min, and compressed air pressure is 0.6MPa; With vinpocetine nanometer suspension liquid spray drying, obtain ultra-fine vinpocetine medicine composite particles.
Embodiment 2
A: taking by weighing 0.8g vinpocetine crude drug, to be dissolved in 100ml concentration be in the 0.1mol/L hydrochloric acid;
B: take by weighing 1.6g poloxamer and 0.56g potassium hydroxide and be dissolved in the 1000mL deionized water, fully dissolve and will be equipped with the beaker ice-water bath of this solution, control this solution temperature about 20 ℃;
C: under the stirring condition of 5000rpm, the raw material medicine solution of preparing in the steps A is poured into fast in the solution of B step preparation, reactive crystallization obtains vinpocetine nanometer suspension liquid, continues to stir ageing 10min;
D: gained vinpocetine nanometer suspension liquid among the step C is filtered, and use the deionized water wash filter cake;
E: above-mentioned filter cake is placed in the beaker and adds the 1.6g poloxamer and the 500mL deionized water, under ultrasonication, make the filter cake redispersion in water;
F: control spray dryer (SD-Basic, Labplant, Britain) inlet temperature is 130 ℃; Outlet temperature is 69 ℃, and charging rate is 20mL/min, and compressed air pressure is 0.5MPa; With vinpocetine nanometer suspension liquid spray drying, obtain ultra-fine vinpocetine medicine composite particles.
Embodiment 3
A: taking by weighing 0.15g vinpocetine crude drug, to be dissolved in 50ml concentration be in the 0.1mol/L hydrochloric acid;
B: take by weighing 0.3g hydroxypropyl emthylcellulose and 0.4g sodium hydroxide and be dissolved in the 500mL deionized water, fully dissolve and will be equipped with the beaker ice-water bath of this solution, control this solution temperature about 3 ℃;
C: under the stirring condition of 8000rpm, the raw material medicine solution of preparing in the steps A is poured into fast in the solution of B step preparation, reactive crystallization obtains vinpocetine nanometer suspension liquid, continues to stir ageing 10min.Granule-morphology is seen Fig. 2 in the vinpocetine nanometer suspension liquid, contrasts visiblely with Fig. 1, and the vinpocetine granule of this method preparation is the square particle diameter and the even particle size of regular shape, and mean diameter is that 150nm is much smaller than the crude drug granule;
D: gained vinpocetine nanometer suspension liquid among the step C is filtered, and use the deionized water wash filter cake;
E: above-mentioned filter cake is placed in the beaker and adds the 0.3g hydroxypropyl emthylcellulose and the 500mL deionized water, under ultrasonication, make the filter cake redispersion in water;
F: control spray dryer (SD-Basic, Labplant, Britain) inlet temperature is 130 ℃; Outlet temperature is 67 ℃; Charging rate is 15mL/min, and compressed air pressure is 0.6MPa, with vinpocetine nanometer suspension liquid spray drying; Obtain ultra-fine vinpocetine medicine composite particles, its stereoscan photograph is seen Fig. 3.Visible by Fig. 3, the ultra-fine vinpocetine medicine composite particles that makes is more regular and caves in spherically, and size is 1-5 μ m.The ultra-fine vinpocetine medicine composite particles that makes and the stripping curve of vinpocetine crude drug are seen Fig. 6.Wherein the crude drug cumulative leaching rate is minimum, and ultra-fine vinpocetine medicine composite particles dissolution rate is fast and cumulative leaching rate is high, is leachable more than 90% in the 15min.
Embodiment 4
A: take by weighing 1g vinpocetine crude drug and be dissolved in the 10ml acetic acid;
B: take by weighing 0.8g Polyethylene Glycol, 0.4g sodium lauryl sulphate and 5.2g sodium hydroxide and be dissolved in the 200mL deionized water, fully dissolve and will be equipped with the beaker ice-water bath of this solution, control this solution temperature about 25 ℃;
C: under the stirring condition of 5000rpm, the raw material medicine solution of preparing in the steps A is poured into fast in the solution of B step preparation, reactive crystallization obtains vinpocetine nanometer suspension liquid, continues to stir ageing 10min;
D: gained vinpocetine nanometer suspension liquid among the step C is filtered, and use the deionized water wash filter cake;
E: above-mentioned filter cake is placed in the beaker and adds 0.8g Polyethylene Glycol, 0.4g sodium lauryl sulphate and 200mL deionized water, under ultrasonication, make the filter cake redispersion in water;
F: control spray dryer (SD-Basic, Labplant, Britain) inlet temperature is 110 ℃; Outlet temperature is 60 ℃, and charging rate is 5mL/min, and compressed air pressure is 0.6MPa; With vinpocetine nanometer suspension liquid spray drying, obtain ultra-fine vinpocetine medicine composite particles.
Fig. 4 is the Fourier infrared spectrum figure of ultra-fine vinpocetine medicine composite particles and vinpocetine crude drug, and is visible by figure, and two spectrograms are corresponding good, explain that this method does not change original chemical constitution of vinpocetine medicine.
Embodiment 5
A: taking by weighing 1g vinpocetine crude drug, to be dissolved in 50ml concentration be in the 0.2mol/L citric acid;
B: take by weighing 0.4g polyvinylpyrrolidone, 1.1g lactose and 1.4g sodium hydroxide and be dissolved in the 500mL deionized water, fully dissolve and will be equipped with the beaker ice-water bath of this solution, control this solution temperature about 20 ℃;
C: under the stirring condition of 3000rpm, the raw material medicine solution of preparing in the steps A is poured into fast in the solution of B step preparation, reactive crystallization obtains vinpocetine nanometer suspension liquid, continues to stir ageing 10min;
D: gained vinpocetine nanometer suspension liquid among the step C is filtered, and use the deionized water wash filter cake;
E: above-mentioned filter cake is placed in the beaker and adds 0.4g polyvinylpyrrolidone, 1.1g lactose and 500mL deionized water, under ultrasonication, make the filter cake redispersion in water;
F: control spray dryer (SD-Basic, Labplant, Britain) inlet temperature is 140 ℃; Outlet temperature is 70 ℃, and charging rate is 10mL/min, and compressed air pressure is 0.6MPa; With vinpocetine nanometer suspension liquid spray drying, obtain ultra-fine vinpocetine medicine composite particles.
Embodiment 6
A: taking by weighing 0.3g vinpocetine crude drug, to be dissolved in 100ml concentration be in the 0.15mol/L hydrochloric acid;
B: take by weighing 0.3g sodium alginate and 0.84g potassium hydroxide and be dissolved in the 1500mL deionized water, fully dissolve and will be equipped with the beaker ice-water bath of this solution, control this solution temperature about 3 ℃;
C: under the stirring condition of 5000rpm, the raw material medicine solution of preparing in the steps A is poured into fast in the solution of B step preparation, reactive crystallization obtains vinpocetine nanometer suspension liquid, continues to stir ageing 10min;
D: gained vinpocetine nanometer suspension liquid among the step C is filtered, and use the deionized water wash filter cake;
E: above-mentioned filter cake is placed in the beaker and adds the 0.3g sodium alginate and the 500mL deionized water, under ultrasonication, make the filter cake redispersion in water;
F: control spray dryer (SD-Basic, Labplant, Britain) inlet temperature is 130 ℃; Outlet temperature is 65 ℃, and charging rate is 20mL/min, and compressed air pressure is 0.6MPa; With vinpocetine nanometer suspension liquid spray drying, obtain ultra-fine vinpocetine medicine composite particles.
Embodiment 7
A: taking by weighing 2g vinpocetine crude drug, to be dissolved in 40ml concentration be in the 0.15mol/L citric acid;
B: take by weighing 1.7g hydroxypropyl emthylcellulose, 0.5g sodium lauryl sulphate and 0.4g potassium hydroxide and be dissolved in the 500mL deionized water, fully dissolve and will be equipped with the beaker ice-water bath of this solution, control this solution temperature about 20 ℃;
C: under the stirring condition of 8000rpm, the raw material medicine solution of preparing in the steps A is poured into fast in the solution of B step preparation, reactive crystallization obtains vinpocetine nanometer suspension liquid, continues to stir ageing 10min;
D: gained vinpocetine nanometer suspension liquid among the step C is filtered, and use the deionized water wash filter cake;
E: above-mentioned filter cake is placed in the beaker and adds 1.7g hydroxypropyl emthylcellulose, 0.5g sodium lauryl sulphate and 500mL deionized water, under ultrasonication, make the filter cake redispersion in water;
F: control spray dryer (SD-Basic, Labplant, Britain) inlet temperature is 120 ℃; Outlet temperature is 60 ℃, and charging rate is 5mL/min, and compressed air pressure is 0.6MPa; With vinpocetine nanometer suspension liquid spray drying, obtain ultra-fine vinpocetine medicine composite particles.
Embodiment 8
A: take by weighing 1g vinpocetine crude drug and be dissolved in the 10ml acetic acid;
B: take by weighing 3g sodium alginate, 2g polyvinylpyrrolidone and 7.8g sodium hydroxide and be dissolved in the 1500mL deionized water, fully dissolve and will be equipped with the beaker ice-water bath of this solution, control this solution temperature about 25 ℃;
C: under the stirring condition of 3000rpm, the raw material medicine solution of preparing in the steps A is poured into fast in the solution of B step preparation, reactive crystallization obtains vinpocetine nanometer suspension liquid, continues to stir ageing 10min;
D: gained vinpocetine nanometer suspension liquid among the step C is filtered, and use the deionized water wash filter cake;
E: above-mentioned filter cake is placed in the beaker and adds 3g sodium alginate, 2g polyvinylpyrrolidone and 500mL deionized water, under ultrasonication, make the filter cake redispersion in water;
F: control spray dryer (SD-Basic, Labplant, Britain) inlet temperature is 140 ℃; Outlet temperature is 70 ℃, and charging rate is 15mL/min, and compressed air pressure is 0.6MPa; With vinpocetine nanometer suspension liquid spray drying, obtain ultra-fine vinpocetine medicine composite particles.Fig. 5 is the X-ray diffractogram of vinpocetine crude drug and ultra-fine vinpocetine medicine composite particles; It is corresponding good to go out the peak position by visible made ultra-fine vinpocetine medicine composite particles of figure and vinpocetine crude drug, explains that the made ultra-fine vinpocetine medicine composite particles of this method is identical with the crude drug crystal formation and is crystal type.
Claims (8)
1. ultra-fine vinpocetine medicine composite particles; Be active component, be the composite granule of carrier with the water solublity pharmaceutic adjuvant with the vinpocetine nano-particle for a kind of; It is characterized in that; The quality percentage composition that said vinpocetine quality percentage composition is 5-50%, water solublity pharmaceutic adjuvant is 50-95%, and the vinpocetine mean diameter is 500-2000nm.
2. according to the ultra-fine vinpocetine medicine composite particles of claim 1, it is characterized in that: the water solublity pharmaceutic adjuvant is a kind of in Polyethylene Glycol, poloxamer, polyvinylpyrrolidone, polyethylene oxide, hydroxypropyl emthylcellulose, mannitol, sodium lauryl sulphate, chitosan, sodium alginate, the lactose or their mixture.
3. the method for preparing of claim 1 or 2 ultra-fine vinpocetine medicine composite particles; It is characterized in that: prepare by reaction-crystallization method; With the drug solution of vinpocetine crude drug with the acid preparation, mix with the aqueous slkali that contains the water solublity pharmaceutic adjuvant, the washing of vinpocetine suspension, the filtration that will obtain after will mixing again also is distributed to spray drying in the aqueous solution that contains the water solublity pharmaceutic adjuvant once more; Promptly obtain ultra-fine vinpocetine medicine composite particles, specifically may further comprise the steps:
A: crude drug is dissolved in the acid solution, removes impurity through filtering with microporous membrane, being mixed with concentration is 1-100mg/mL clarification drug solution;
B: pharmaceutic adjuvant is dissolved in the aqueous slkali, and being made into concentration is the adjuvant aqueous slkali of 0.1-15mg/mL;
C:, under 0-30 ℃, the drug solution of A step is mixed with the pharmaceutic adjuvant aqueous slkali of B step and stirs simultaneously in the reactive crystallization temperature, obtain vinpocetine drug particles suspension;
D: the washing of drug particles suspension, the filtration of C step also are distributed to spray drying in the aqueous solution that contains the water solublity pharmaceutic adjuvant once more, promptly obtain ultra-fine vinpocetine medicine composite particles.
4. according to the method for preparing of claim 3, it is characterized in that: acid described in the A step is a kind of in the hydrochloric acid, acetic acid, citric acid or their mixture.
5. according to the method for preparing of claim 3, it is characterized in that: alkali described in the B step is a kind of in potassium hydroxide, sodium hydroxide, the ammonia or their mixture.
6. method for preparing according to claim 3 is characterized in that: the volume ratio of raw material medicine solution and pharmaceutic adjuvant aqueous slkali is 1 in the C step: 5-1: 20.
7. method for preparing according to claim 3 is characterized in that: the stirring described in the C step is characterized in that: mixing speed is 1000rpm-10000rpm.
8. method for preparing according to claim 3 is characterized in that: spray drying time control inlet temperature is 100-150 ℃ in the D step, and outlet temperature is 60-90 ℃, and charging rate is 5-40mL/min, and compressed air pressure is 0.4-0.8Mpa.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105264243A CN102451159A (en) | 2010-11-01 | 2010-11-01 | Superfine vinpocetine composite particle and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105264243A CN102451159A (en) | 2010-11-01 | 2010-11-01 | Superfine vinpocetine composite particle and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102451159A true CN102451159A (en) | 2012-05-16 |
Family
ID=46035103
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010105264243A Pending CN102451159A (en) | 2010-11-01 | 2010-11-01 | Superfine vinpocetine composite particle and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102451159A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106309371A (en) * | 2015-06-30 | 2017-01-11 | 北京万生药业有限责任公司 | Cefixime nanodispersion and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101081214A (en) * | 2007-07-06 | 2007-12-05 | 北京化工大学 | Methodc for preparing sub-micron gemfibrozil medicament powder |
| CN101780047A (en) * | 2009-01-16 | 2010-07-21 | 北京化工大学 | Nano-micro structure silibinin drug composite powder and preparation method thereof |
-
2010
- 2010-11-01 CN CN2010105264243A patent/CN102451159A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101081214A (en) * | 2007-07-06 | 2007-12-05 | 北京化工大学 | Methodc for preparing sub-micron gemfibrozil medicament powder |
| CN101780047A (en) * | 2009-01-16 | 2010-07-21 | 北京化工大学 | Nano-micro structure silibinin drug composite powder and preparation method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106309371A (en) * | 2015-06-30 | 2017-01-11 | 北京万生药业有限责任公司 | Cefixime nanodispersion and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4964585B2 (en) | Ferric organic compounds, their use, and methods for their production | |
| CN104650091B (en) | The micronization of ticagrelor and crystal formation thereof, and preparation method and medicinal application | |
| CN103395826B (en) | Preparation method of aluminum doped zinc oxide nano powder | |
| JP5867771B1 (en) | Powdered tobermorite-type calcium silicate material and method for producing the same | |
| CN101074116B (en) | Production of superfine mono-dispered nano-zirconium dioxide | |
| CN102188372A (en) | Medicinal transparent nano dispersant and preparation method thereof | |
| CN101015558A (en) | Preparation of superfine prednisolone powder | |
| Song et al. | Preparation and characterization of calcium carbonate microspheres and their potential application as drug carriers | |
| CN104887633B (en) | A kind of razaxaban tablet and preparation method thereof | |
| CN100490796C (en) | Methodc for preparing sub-micron gemfibrozil medicament powder | |
| CN101780047B (en) | Nano-micro structure silibinin drug composite powder and preparation method thereof | |
| Li et al. | One-step hydrothermal synthesis of CuO hollow spheres with high photocatalytic activity | |
| CN102451159A (en) | Superfine vinpocetine composite particle and preparation method thereof | |
| US20120258036A1 (en) | Method for preparing barium titanate | |
| CN100441196C (en) | Process for preparing micro Azithromycin powder | |
| CN100448879C (en) | Method for preparing unformed cefuroxime axetil | |
| CN101292958B (en) | Method of preparing ultra-fine danazol powder | |
| CN101780046B (en) | Itraconazole composite powder and preparation method thereof | |
| CN105688223A (en) | Preparation process of small-grain-diameter microcrystalline cellulose pellets | |
| Lian et al. | Manufacturing of high quality hydrotalcite by computational fluid dynamics simulation of an impinging jet crystallizer | |
| CN102407345B (en) | Method for preparing porous gold micron sheet | |
| CN101973967B (en) | Method for preparing negative pressure anti-solvent of water-soluble nano-taxol powder | |
| CN106309371B (en) | Cefixime nano dispersion and preparation method thereof | |
| CN113679675B (en) | Calcium granules and preparation method and application thereof | |
| CN106063778A (en) | A kind of preparation method of beclometasone transparent aqueous phase Nanodispersion |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120516 |