CN104840429A - Preparation method of acetic acid goserelin microspheres - Google Patents
Preparation method of acetic acid goserelin microspheres Download PDFInfo
- Publication number
- CN104840429A CN104840429A CN201510208322.XA CN201510208322A CN104840429A CN 104840429 A CN104840429 A CN 104840429A CN 201510208322 A CN201510208322 A CN 201510208322A CN 104840429 A CN104840429 A CN 104840429A
- Authority
- CN
- China
- Prior art keywords
- solution
- preparation
- benzyl alcohol
- colostrum
- hour
- 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.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention provides a preparation method of acetic acid goserelin microspheres. The preparation method includes: step 1), mixing acetic acid goserelin with water to obtain a drug solution A, and mixing PLGA (polylactic-co-glycolic acid) with an organic solution to obtain a solution B; step 2), mixing the solution A with the solution B to form colostrum through ultrasound, and adding the colostrum to a PVA (polyvinyl acetate) water solution saturated by an organic mixed solution to obtain a compound emulsion through homogeneous emulsification; step 3), stirring the compound emulsion at the room temperature for one hour, increasing the temperature to 40-45 DEG C, keeping the compound emulsion for one hour, reducing the temperature to 10 DEG C, sieving the compound emulsion to collect particles and subjecting the particles to freeze-frying. The preparation method has the advantages that the problem of adverse drug reaction increase caused by high sudden release effect of the acetic acid goserelin microspheres can be solved, and the microspheres prepared by the method have quite smooth and stable blood concentration and are beneficial to long-term medication.
Description
Technical field
The invention belongs to field of medicaments, specifically, the present invention relates to goserelin acetate sustained-release micro-spheres preparation method and goserelin acetate sustained-release micro-spheres prepared therefrom.
Background technology
Goserelin acetate is gonadotropin releasing hormone synthetic 10 peptide.Goserelin is used to the clinical symptoms and the sign that control endometriosis and adenomyosis, and prevention postoperative recurrence of endometriosis, all has good effect.Life-time service goserelin acetate can suppress the synthesis of hypophysis cerebri interstitialcellstimulating hormone (ICSH), thus cause the decline of male's Serum testosterone and women's serum estradiol, this reversible action after drug withdrawal, during initial stage medication, goserelin acetate temporarily can increase the concentration of male's Serum testosterone and women's serum estradiol.
According to the Medicinal Trait of goserelin acetate clinical indication, patient often needs long term administration, therefore in order to improve the compliance of patient, is developed to long-acting slow-release preparation.Common sustained-release micro-spheres preparation method has solvent evaporated method, phase separation method and spray drying method, and wherein solvent evaporated method comprises again oil-in-water method, oily bag oil process and multi-emulsion method.Multi-emulsion method prepares the most frequently used method of water soluble polypeptide, protein medicine microsphere at present, this method active component aqueous solution and Vicryl Rapide (PLGA) organic solution is mixed to break into colostrum, this colostrum is put into cold containing in emulsifier aqueous solution and is solidify to form microgranule, and collecting by filtration microgranule is dry.But prominent releasing adopts multi-emulsion method to prepare in water soluble drug process most FAQs, when preparing goserelin acetate microsphere with multi-emulsion method, active component easily spreads from ball interior, form a lot of hole on the surface of ball, a large amount of cavity can cause the prominent generation released and fast degradation understood by microsphere itself.The prominent common method released of process is that ball syringe is outside, but this way can cause the loss of medicine.Due to goserelin acetate costly, therefore adopt the method for washing that pharmacy cost can be made significantly to promote.
Therefore, need Dichlorodiphenyl Acetate goserelin microsphere production technology to carry out further Optimization Work, solution medicine is dashed forward and is released effect and improve the smoothness of microsphere surface thus make blood drug level more stable level and smooth
Summary of the invention
The invention provides a kind of preparation method of goserelin acetate microsphere, goserelin acetate microsphere can be overcome on the one hand due to the prominent problem releasing the adverse effect increase that effect causes greatly, on the other hand, the microsphere blood drug level using this legal system standby very smooth steady is conducive to long-term prescription.
The preparation method of a kind of goserelin acetate sustained-release micro-spheres that the present invention relates to, comprises the following steps:
Step 1) being added water by acetic acid goserelin acetate is made into drug solution A; PLGA is added organic solvent solution-forming B;
Step 2) solution A and solution B are mixed ultrasonic formation colostrum, colostrum joins in the PVA aqueous solution by the saturated mistake of organic mixed solvent, and emulsifying obtains emulsion.
Step 3) emulsion stirring at room temperature is warming up to 40 DEG C ~ 45 DEG C maintenances 1 hour after 1 hour, then be cooled to 10 DEG C, sieve collecting granules, lyophilizing.
Particularly, step 1) described in the concentration of drug solution A be 35%-45%, the concentration of solution B is 20%-40%.
Particularly, step 1) described in organic solvent be selected from one in ethyl acetate, benzyl alcohol mixed solution and dichloromethane, benzyl alcohol mixed solution;
Preferably, step 1) in ethyl acetate and the volume ratio of benzyl alcohol be 4 ~ 8: 1; The volume ratio of dichloromethane and benzyl alcohol is 4 ~ 8: 1.
Preferably, step 1) described in PLGA be PLGA7525.
Particularly, step 2) PVA concentration of aqueous solution is 0.5%.
Particularly, step 2) in organic mixed solvent be benzyl alcohol and ethyl acetate, the concentration of organic mixed solvent is 1%-2%;
Preferably, the volume ratio of benzyl alcohol and ethyl acetate is 1: 1.
Particularly, step 3) in emulsion stirring at room temperature be warming up to 45 DEG C after 1 hour and keep 1 hour, then be cooled to 10 DEG C.
The invention has the beneficial effects as follows:
1) while the present invention adopts dichloromethane, ethyl acetate to add benzyl alcohol dissolving PLGA, outer aqueous phase organic solvent is saturated, can obtain prominent releasing and acting on the goserelin acetate sustained-release micro-spheres little, elution profiles is mild.
2) the present invention adopts the mode of the solidification rate reducing emulsion process to reduce the diffusion of goserelin acetate, phase controls aqueous temperature more than the vitrification point of microsphere after hardening simultaneously, certain hour is kept to be undertaken resetting thus merging hole by microsphere macromolecular scaffold, make goserelin acetate microsphere features smooth surface, dashing forward, it is more level and smooth to release less release
3) goserelin acetate sustained-release micro-spheres drug loading greatly then can cause prominent releasing effect obviously, and the goserelin acetate microsphere that the present invention relates to prominent is released less, and drug loading reaches maximum.
4) by controlling solidification rate and aqueous temperature in the curing schedule of the goserelin acetate microspheres that the present invention relates to, decrease and initial prominently release effect, and the dash forward method released of conventional treatment is repeatedly that ball syringe is outside, but this way can cause the loss of medicine.In the expensive situation of goserelin, the goserelin acetate method for preparing microsphere that the present invention relates to greatly can reduce production cost.
Accompanying drawing explanation
Fig. 1: the outer releasing curve diagram of goserelin acetate microsphere of embodiment 1
Fig. 2: the outer releasing curve diagram of goserelin acetate microsphere of embodiment 2
Fig. 3: the goserelin acetate microsphere scanning electron microscope (SEM) photograph of embodiment 2
Fig. 4: the goserelin acetate microsphere scanning electron microscope (SEM) photograph of embodiment 13
Fig. 5: the goserelin acetate microsphere scanning electron microscope (SEM) photograph of embodiment 14
Specific embodiment
Embodiment 1
Take 1g goserelin acetate (Rayleigh Bachem company, 1307003) to add water and be made into the drug solution that concentration is 40%, 8gPLGA7525 20ml ethyl acetate and 5ml benzyl alcohol dissolve, and the two is mixed ultrasonic 2min, forms white homogenizing colostrum.Colostrum is joined by syringe in the PVA solution (containing 1% benzyl alcohol and 1% ethyl acetate) of the 1000ml 0.5% of 6 DEG C under the homogenizing of 1500rpm, and emulsifying 2min, obtains emulsion.Moved to by emulsion on cantilever blender, rotating speed is 600rpm, stirs 1h, and be then warmed up to 45 DEG C and keep 1 hour, then be reduced to 10 DEG C of screen filtrations, deionized water rinsing, lyophilizing obtains Powdered microsphere.Drug loading is that 10.3%, 1 Tiantu is interpreted as 7.67%.Microsphere hole is continuous whole, steadily release 28 days.
Embodiment 2
Take 1g goserelin acetate (Rayleigh Bachem company, 1307003) to add water and be made into the drug solution that concentration is 40%, 8gPLGA7525 20ml ethyl acetate and 5ml benzyl alcohol dissolve, and the two is mixed ultrasonic 2min, forms white homogenizing colostrum.Colostrum is joined by syringe in the PVA solution (containing 1% benzyl alcohol and 1% ethyl acetate) of the 1000ml 0.5% of 6 DEG C under the homogenizing of 1500rpm, and emulsifying 2min, obtains emulsion.Moved to by emulsion on cantilever blender, rotating speed is 600rpm, stirs 1h, and be then warmed up to 40 DEG C and keep 1 hour, then be reduced to 10 DEG C of screen filtrations, deionized water rinsing, lyophilizing obtains Powdered microsphere.Drug loading is that 10.1%, 1 Tiantu is interpreted as 7.14%.Microsphere hole is continuous whole, steadily release 28 days.
Embodiment 3
Take 1g goserelin acetate (Rayleigh Bachem company, 1307003) to add water and be made into the drug solution that concentration is 40%, 8gPLGA7525 24ml ethyl acetate and 3ml benzyl alcohol dissolve, and the two is mixed ultrasonic 2min, forms white homogenizing colostrum.Colostrum is joined by syringe in the PVA solution (containing 1% benzyl alcohol and 1% ethyl acetate) of the 1000ml 0.5% of 6 DEG C under the homogenizing of 1500rpm, and emulsifying 2min, obtains emulsion.Moved to by emulsion on cantilever blender, rotating speed is 600rpm, stirs 1h, and be then warmed up to 40 DEG C and keep 1 hour, then be reduced to 10 DEG C of screen filtrations, deionized water rinsing, lyophilizing obtains Powdered microsphere.Drug loading is that 10.8%, 1 Tiantu is interpreted as 4.05%.Microsphere hole is continuous whole, steadily release 28 days.
Embodiment 4
Take 1g goserelin acetate (Rayleigh Bachem company, 1307003) to add water and be made into the drug solution that concentration is 45%, 8gPLGA7525 24ml ethyl acetate and 3ml benzyl alcohol dissolve, and the two is mixed ultrasonic 2min, forms white homogenizing colostrum.Colostrum is joined by syringe in the PVA solution (containing 1% benzyl alcohol and 1% ethyl acetate) of the 1000ml 0.5% of 6 DEG C under the homogenizing of 1500rpm, and emulsifying 2min, obtains emulsion.Moved to by emulsion on cantilever blender, rotating speed is 600rpm, stirs 1h, and be then warmed up to 40 DEG C and keep 1 hour, then be reduced to 10 DEG C of screen filtrations, deionized water rinsing, lyophilizing obtains Powdered microsphere.Drug loading is that 10.9%, 1 Tiantu is interpreted as 4.2%.Microsphere hole is continuous whole, steadily release 28 days.
Embodiment 5
Take 1g goserelin acetate (Rayleigh Bachem company, 1307003) to add water and be made into the drug solution that concentration is 35%, 8gPLGA7525 24ml ethyl acetate and 3ml benzyl alcohol dissolve, and the two is mixed ultrasonic 2min, forms white homogenizing colostrum.Colostrum is joined by syringe in the PVA solution (containing 1% benzyl alcohol and 1% ethyl acetate) of the 1000ml 0.5% of 6 DEG C under the homogenizing of 1500rpm, and emulsifying 2min, obtains emulsion.Moved to by emulsion on cantilever blender, rotating speed is 600rpm, stirs 1h, and be then warmed up to 40 DEG C and keep 1 hour, then be reduced to 10 DEG C of screen filtrations, deionized water rinsing, lyophilizing obtains Powdered microsphere.Drug loading is that 10.1%, 1 Tiantu is interpreted as 4.13%.Microsphere hole is continuous whole, steadily release 28 days.
Embodiment 6
Take 1g goserelin acetate (Rayleigh Bachem company, 1307003) to add water and be made into the drug solution that concentration is 45%, 8gPLGA7525 24ml dichloromethane and 3ml benzyl alcohol dissolve, and the two is mixed ultrasonic 2min, forms white homogenizing colostrum.Colostrum is joined by syringe in the PVA solution (containing 1% benzyl alcohol and 1% ethyl acetate) of the 1000ml 0.5% of 6 DEG C under the homogenizing of 1500rpm, and emulsifying 2min, obtains emulsion.Moved to by emulsion on cantilever blender, rotating speed is 600rpm, stirs 1h, and be then warmed up to 45 DEG C and keep 1 hour, then be reduced to 10 DEG C of screen filtrations, deionized water rinsing, lyophilizing obtains Powdered microsphere.Drug loading is that 9.4%, 1 Tiantu is interpreted as 6.28%.Microsphere hole is continuous whole, steadily release 28 days.
Embodiment 7
Take 1g goserelin acetate (Rayleigh Bachem company, 1307003) to add water and be made into the drug solution that concentration is 35%, 8gPLGA7525 24ml dichloromethane and 3ml benzyl alcohol dissolve, and the two is mixed ultrasonic 2min, forms white homogenizing colostrum.Colostrum is joined by syringe in the PVA solution (containing 1% benzyl alcohol and 1% ethyl acetate) of the 1000ml 0.5% of 6 DEG C under the homogenizing of 1500rpm, and emulsifying 2min, obtains emulsion.Moved to by emulsion on cantilever blender, rotating speed is 600rpm, stirs 1h, and be then warmed up to 45 DEG C and keep 1 hour, then be reduced to 10 DEG C of screen filtrations, deionized water rinsing, lyophilizing obtains Powdered microsphere.Drug loading is that 9.3%, 1 Tiantu is interpreted as 6.5%.Microsphere hole is continuous whole, steadily release 28 days.
Embodiment 8
Take 1g goserelin acetate (Rayleigh Bachem company, 1307003) to add water and be made into the drug solution that concentration is 40%, 8gPLGA7525 24ml dichloromethane and 3ml benzyl alcohol dissolve, and the two is mixed ultrasonic 2min, forms white homogenizing colostrum.Colostrum is joined by syringe in the PVA solution (containing 1% benzyl alcohol and 1% ethyl acetate) of the 1000ml 0.5% of 6 DEG C under the homogenizing of 1500rpm, and emulsifying 2min, obtains emulsion.Moved to by emulsion on cantilever blender, rotating speed is 600rpm, stirs 1h, and be then warmed up to 45 DEG C and keep 1 hour, then be reduced to 10 DEG C of screen filtrations, deionized water rinsing, lyophilizing obtains Powdered microsphere.Drug loading is that 9.5%, 1 Tiantu is interpreted as 6.22%.Microsphere hole is continuous whole, steadily release 28 days.
Embodiment 9
Take 1g goserelin acetate (Rayleigh Bachem company, 1307003) to add water and be made into the drug solution that concentration is 40%, 8gPLGA7525 20ml dichloromethane and 5ml benzyl alcohol dissolve, and the two is mixed ultrasonic 2min, forms white homogenizing colostrum.Colostrum is joined by syringe in the PVA solution (containing 1% benzyl alcohol and 1% ethyl acetate) of the 1000ml 0.5% of 6 DEG C under the homogenizing of 1500rpm, and emulsifying 2min, obtains emulsion.Moved to by emulsion on cantilever blender, rotating speed is 600rpm, stirs 1h, and be then warmed up to 45 DEG C and keep 1 hour, then be reduced to 10 DEG C of screen filtrations, deionized water rinsing, lyophilizing obtains Powdered microsphere.Drug loading is that 9.2%, 1 Tiantu is interpreted as 6.15%.Microsphere hole is continuous whole, steadily release 28 days.
Embodiment 10
Take 1g goserelin acetate (Rayleigh Bachem company, 1307003) to add water and be made into the drug solution that concentration is 40%, 8g PLGA7525 24ml ethyl acetate and 2ml benzyl alcohol dissolve, and the two is mixed ultrasonic 2min, forms white homogenizing colostrum.Colostrum is joined by syringe in the PVA solution (containing 1% benzyl alcohol and 1% ethyl acetate) of the 1000ml 0.5% of 6 DEG C under the homogenizing of 1500rpm, and emulsifying 2min, obtains emulsion.Moved to by emulsion on cantilever blender, rotating speed is 600rpm, stirs 1h, and be then warmed up to 45 DEG C and keep 1 hour, then be reduced to 10 DEG C of screen filtrations, deionized water rinsing, lyophilizing obtains Powdered microsphere.Drug loading is that 9.7%, 1 Tiantu is interpreted as 12.4%, and plasma concentration curve is level and smooth not.
Embodiment 11
Take 1g goserelin acetate (Rayleigh Bachem company, 1307003) to add water and be made into the drug solution that concentration is 40%, 8g PLGA7525 18ml ethyl acetate and 6ml benzyl alcohol dissolve, and the two is mixed ultrasonic 2min, forms white homogenizing colostrum.Colostrum is joined by syringe in the PVA solution (containing 1% benzyl alcohol and 1% ethyl acetate) of the 1000ml 0.5% of 6 DEG C under the homogenizing of 1500rpm, and emulsifying 2min, obtains emulsion.Moved to by emulsion on cantilever blender, rotating speed is 600rpm, stirs 1h, and be then warmed up to 45 DEG C and keep 1 hour, then be reduced to 10 DEG C of screen filtrations, deionized water rinsing, lyophilizing obtains Powdered microsphere.Drug loading is that 8.2%, 1 Tiantu is interpreted as 14.5%, and plasma concentration curve is level and smooth not.
Embodiment 12
Take 1g goserelin acetate (Rayleigh Bachem company, 1307003) to add water and be made into the drug solution that concentration is 40%, 8gPLGA7525 24ml dichloromethane and 3ml dissolve with ethanol, mix ultrasonic 2min by the two, forms white homogenizing colostrum.Colostrum is joined by syringe in the PVA solution (containing 1% benzyl alcohol and 1% ethyl acetate) of the 1000ml 0.5% of 6 DEG C under the homogenizing of 1500rpm, and emulsifying 2min, obtains emulsion.Moved to by emulsion on cantilever blender, rotating speed is 600rpm, stirs 1h, and be then warmed up to 45 DEG C and keep 1 hour, then be reduced to 10 DEG C of screen filtrations, deionized water rinsing, lyophilizing obtains Powdered microsphere.Drug loading is that 8.5%, 1 Tiantu is interpreted as 11.7%, and microsphere surface hole is comparatively large, and burst drug release is too high.
Embodiment 13
Take 1g goserelin acetate (Rayleigh Bachem company, 1307003) to add water and be made into the drug solution that concentration is 35%, 8g PLGA7525 26ml acetic acid ethyl dissolution, mixes ultrasonic 2min by the two, forms white homogenizing colostrum.Colostrum joins in the PVA solution of 1000ml 0.5% of 6 DEG C by syringe under the homogenizing of 1500rpm, and emulsifying 2min, obtains emulsion.Moved to by emulsion on cantilever blender, rotating speed is 600rpm, and 5 DEG C are stirred 3h volatilization removing organic solvent; Screen filtration, deionized water rinsing, lyophilizing obtains Powdered microsphere.Drug loading is that 5.6%, 1 Tiantu is interpreted as 28%.Drug loading is low, and burst drug release is too high, the visible a large amount of microsphere hole of scanning electron microscope.
Embodiment 14
Take 1g goserelin acetate (Rayleigh Bachem company, 1307003) to add water and be made into the drug solution that concentration is 40%, 8gPLGA7525 26ml dichloromethane dissolves, and the two is mixed ultrasonic 2min, forms white homogenizing colostrum.Colostrum is joined by syringe in the PVA solution of the 1000ml0.5% of 6 DEG C under the homogenizing of 1500rpm, and emulsifying 2min, obtains emulsion.Moved to by emulsion on cantilever blender, rotating speed is 600rpm, and 5 DEG C are stirred 3h volatilization removing organic solvent; Screen filtration, deionized water rinsing, lyophilizing obtains Powdered microsphere.Drug loading is that 5.9%, 1 Tiantu is interpreted as 32%.Drug loading is low, and burst drug release is too high, the visible a large amount of microsphere hole of scanning electron microscope.
Claims (9)
1. a preparation method for goserelin acetate sustained-release micro-spheres, comprises the following steps:
Step 1) being added water by acetic acid goserelin acetate is made into drug solution A; PLGA is added organic solvent solution-forming B;
Step 2) solution A and solution B are mixed ultrasonic formation colostrum, colostrum joins in the PVA aqueous solution by the saturated mistake of organic mixed solvent, and emulsifying obtains emulsion;
Step 3) emulsion stirring at room temperature is warming up to 40 DEG C ~ 45 DEG C maintenances 1 hour after 1 hour, then be cooled to 10 DEG C, sieve collecting granules, lyophilizing.
2. preparation method as claimed in claim 1, is characterized in that, step 1) described in the concentration of drug solution A be 35%-45%, the concentration of solution B is 20%-40%.
3. preparation method as claimed in claim 2, is characterized in that, step 1) described in organic solvent be selected from one in ethyl acetate, benzyl alcohol mixed solution or dichloromethane, benzyl alcohol mixed solution.
4. preparation method as claimed in claim 3, is characterized in that, step 1) described in ethyl acetate and the volume ratio of benzyl alcohol be 4 ~ 8: 1 or the volume ratio of dichloromethane and benzyl alcohol be 4 ~ 8: 1.
5. preparation method as claimed in claim 4, is characterized in that, step 1) described in PLGA be PLGA7525.
6. preparation method as claimed in claim 5, is characterized in that, step 2) PVA concentration of aqueous solution is 0.5%.
7. preparation method as claimed in claim 6, is characterized in that, step 2) in organic mixed solvent be benzyl alcohol and ethyl acetate, the concentration of organic mixed solvent is 1%-2%.
8. preparation method as claimed in claim 7, it is characterized in that, the volume ratio of benzyl alcohol and ethyl acetate is 1: 1.
9. preparation method as claimed in claim 8, is characterized in that, step 3) in emulsion stirring at room temperature be warming up to 45 DEG C after 1 hour and keep 1 hour, then be cooled to 10 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510208322.XA CN104840429B (en) | 2015-04-23 | 2015-04-23 | The preparation method of goserelin acetate microballoon |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510208322.XA CN104840429B (en) | 2015-04-23 | 2015-04-23 | The preparation method of goserelin acetate microballoon |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104840429A true CN104840429A (en) | 2015-08-19 |
| CN104840429B CN104840429B (en) | 2017-12-01 |
Family
ID=53840680
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510208322.XA Active CN104840429B (en) | 2015-04-23 | 2015-04-23 | The preparation method of goserelin acetate microballoon |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104840429B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107335048A (en) * | 2017-06-27 | 2017-11-10 | 中国科学院过程工程研究所 | Carry gonadotropin-releasing hormone (GRH) class compound sustained-release micro-spheres and preparation method thereof |
| CN109692325A (en) * | 2017-10-21 | 2019-04-30 | 齐鲁制药有限公司 | A kind of preparation method of goserelin acetate microballoon |
| CN114569564A (en) * | 2022-03-21 | 2022-06-03 | 浙江圣兆药物科技股份有限公司 | Goserelin sustained release microsphere composition |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1876175A (en) * | 2006-04-18 | 2006-12-13 | 中国人民解放军第二军医大学 | Neurotrophic factor slow release nanometer formulation and its preparation method and uses |
| CN1903365A (en) * | 2005-07-28 | 2007-01-31 | 中国医学科学院生物医学工程研究所 | Drug-carried nanometer particles, and its preparing process for preparing medicien prepn. for anti-restenosis of blood-vessel |
| CN102440964A (en) * | 2011-12-16 | 2012-05-09 | 深圳市健元医药科技有限公司 | Goserelin slow release microsphere preparation and preparation method thereof |
| CN102872450A (en) * | 2012-10-17 | 2013-01-16 | 中国人民解放军总医院 | Composition for composite drug administration |
-
2015
- 2015-04-23 CN CN201510208322.XA patent/CN104840429B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1903365A (en) * | 2005-07-28 | 2007-01-31 | 中国医学科学院生物医学工程研究所 | Drug-carried nanometer particles, and its preparing process for preparing medicien prepn. for anti-restenosis of blood-vessel |
| CN1876175A (en) * | 2006-04-18 | 2006-12-13 | 中国人民解放军第二军医大学 | Neurotrophic factor slow release nanometer formulation and its preparation method and uses |
| CN102440964A (en) * | 2011-12-16 | 2012-05-09 | 深圳市健元医药科技有限公司 | Goserelin slow release microsphere preparation and preparation method thereof |
| CN102872450A (en) * | 2012-10-17 | 2013-01-16 | 中国人民解放军总医院 | Composition for composite drug administration |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107335048A (en) * | 2017-06-27 | 2017-11-10 | 中国科学院过程工程研究所 | Carry gonadotropin-releasing hormone (GRH) class compound sustained-release micro-spheres and preparation method thereof |
| CN107335048B (en) * | 2017-06-27 | 2021-02-19 | 中国科学院过程工程研究所 | Sustained-release microsphere carrying gonadotropin releasing hormone compound and preparation method thereof |
| CN109692325A (en) * | 2017-10-21 | 2019-04-30 | 齐鲁制药有限公司 | A kind of preparation method of goserelin acetate microballoon |
| CN114569564A (en) * | 2022-03-21 | 2022-06-03 | 浙江圣兆药物科技股份有限公司 | Goserelin sustained release microsphere composition |
| CN114569564B (en) * | 2022-03-21 | 2024-02-23 | 浙江圣兆药物科技股份有限公司 | Goserelin sustained-release microsphere composition |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104840429B (en) | 2017-12-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5933025B2 (en) | Microspheres for controlled or sustained release of medication | |
| CN105169366A (en) | Preparation method of triptorelin acetate sustained-release microsphere | |
| CN102271660B (en) | The method for preparing sustained release microparticles | |
| CN103585114B (en) | A kind of method preparing Exenatide release microsphere of improvement | |
| CN102316867A (en) | Amlodipine microsphere preparation, its preparation method and application | |
| ITTO20000963A1 (en) | PROLONGED RELEASE MICROPARTICLE AND METHOD FOR ITS PREPARATION. | |
| CN104840429A (en) | Preparation method of acetic acid goserelin microspheres | |
| CN104887626A (en) | Preparation method of nano suspension | |
| CN102137657A (en) | Method for manufacturing sustained release microsphere by solvent flow evaporation method | |
| CN104382860A (en) | Liraglutide sustained-release microsphere preparation and preparation method thereof | |
| CN104224753A (en) | Small molecule hydrophilic drug-embedded sustained-release capsule and preparation method thereof | |
| CN102258786B (en) | Porous microspheres for medicine carriers, preparation method and medicine loading method | |
| KR20220023951A (en) | Aripiprazole sustained-release microspheres and method for preparing the same | |
| JP2002542184A (en) | Method for microencapsulation of water-soluble substance | |
| CN107441061B (en) | Progesterone sustained-release nanoparticle, preparation method thereof and progesterone sustained-release injection | |
| CN101559038B (en) | Solid lipid nanoparticles of finasteride and preparation method thereof | |
| CN108969751A (en) | A kind of medicament slow-release microsphere and its preparation method and application | |
| Xiao et al. | The effect of polymer blends on initial release regulation and in vitro-in vivo relationship of peptides loaded PLGA-Hydrogel Microspheres | |
| CN105797134A (en) | Insoluble leuprorelin sustained-release preparation | |
| KR101663560B1 (en) | Method for manufacturing uniform delayed-release microspheres | |
| KR20100094227A (en) | Method for manufacturing delayed-release microspheres | |
| CN103462901B (en) | A kind ofly control the residual method of dichloromethane in polymer microsphere formulation | |
| CN103893129A (en) | Paliperidone sustained release microsphere and injection thereof, and preparation method of sustained release microsphere | |
| KR101936040B1 (en) | Preparation of biodegradable microsphere by using stabled monophasic mixture | |
| WO2020047141A1 (en) | Ophthalmic injectable formulation preparing and oculopathy treating and preventing |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| EXSB | Decision made by sipo to initiate substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| DD01 | Delivery of document by public notice |
Addressee: Kuang Lijuan Document name: Notification of Passing Examination on Formalities |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |