CN103142489A - Human alpha-atrial natriuretic peptide sustained release microsphere preparation and preparation method thereof - Google Patents
Human alpha-atrial natriuretic peptide sustained release microsphere preparation and preparation method thereof Download PDFInfo
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- CN103142489A CN103142489A CN2012104947228A CN201210494722A CN103142489A CN 103142489 A CN103142489 A CN 103142489A CN 2012104947228 A CN2012104947228 A CN 2012104947228A CN 201210494722 A CN201210494722 A CN 201210494722A CN 103142489 A CN103142489 A CN 103142489A
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Abstract
The invention discloses a human alpha-atrial natriuretic peptide sustained release microsphere preparation and a preparation method thereof. The sustained release microsphere comprises, calculated by weight of the microspheres, 0.1%-20% (w / W) of human alpha-atrial natriuretic peptide, 80%-99.9% of a biodegradable and biocompatible polymer material and molecular weight of 10000-200000 Dalton, and 0%-10% of other pharmaceutically acceptable accessories. The sustained release microsphere provided by invention has average particle size of 10-50 mum, uniform distribution and encapsulation rate above 80%. The sustained release microsphere has release period up to several days or months, significantly reduces the frequency of medication, improves bioavailability of human alpha-atrial natriuretic peptide, reduces side and toxic effects of drugs and benefits clinical treatment.
Description
Technical field:
The present invention relates to sustained release microsphere agents and preparation method thereof technical field, relate in particular to a kind of slow releasing preparation containing people's α-atrial natriuretic peptide and preparation method thereof.
Background technology:
People's α-atrial natriuretic peptide of the present invention is carperitide, claims again card piperazine profit fourth, Hamp, human brain natriuretic peptide, gene recombinaton atrial natriuretic peptide.Indication is acute heart failure, also comprises that the chronic heart failure acute exacerbation is by stimulating cardiac muscle to stretch.It is synthetic by the ventricle endoparticle, and then, by hat vein distribution whole body, the tissues such as vasoactive smooth muscle and kidney, regulate blood pressure and cylinder electrolyte balance.Hormone is regulated in a kind of circulation that it is comprised of 28 aminoacid.Experimental results show that the intraventricular granule of rat also can synthesize this material, has developed the gene recombinaton synthesis technique now.Clinical trial proves, this product in the tissues such as vascular smooth muscle and kidney with the GC-A receptors bind, the activation guanylate cyclase, increase cyclic guanosine monophosphate, and cause vasodilation and diuresis.
Summary of the invention:
The purpose of this invention is to provide a kind of carperitide sustained release microsphere agents and preparation method thereof, sustained release microsphere agents is compared with ordinary preparation, and administration frequency significantly reduces, and patient's acceptance level improves greatly.In addition, it has also eliminated the vivo medicine concentration peak valley phenomenon that normal injection agent multiple dosing produces, and can obtain steadily valid density for a long time, has reduced toxic and side effects, and total dosage reduces.
The present invention has prepared a kind of sustained release microsphere agents of the injection containing the carperitide medicine, it is characterized in that the carperitide sustained-release micro-spheres in described preparation contains carperitide or its salt that accounts for microsphere weight 0.1%-20% (w/w), the molecular weight that accounts for microsphere weight 80%-99.9% is 10,000-200, the macromolecular material of 000 daltonian biodegradable and tool biocompatibility, and pharmaceutically acceptable other adjuvants that account for microsphere weight 0%-10%, microsphere average grain diameter is 10-50 μ m, be evenly distributed, envelop rate is more than 80%.
The macromolecular material of described biodegradable and tool biocompatibility, optional from polylactide (PLA), PGA (PGA), polylactide-co-glycolide (PLGA), polyalkylcyanoacrylate, polycaprolactone (PCL), poly hydroxybutyric acid (PHB), poly-hydroxyl valeric acid (PVA), poly-capric acid (PDA), poly-anhydride, Polyhydroxybutyrate-co-hydroxyvalerate, polylactic acid-polyglycol, polyglycolic acid-Polyethylene Glycol a kind of or its mixture wherein, preferably polylactide and polylactide-co-glycolide mixture.Described lactide and Acetic acid, hydroxy-, bimol. cyclic ester molecular weight ranges be all at 10,000-20,000 dalton, and in polylactide, the proportion of lactide and Acetic acid, hydroxy-, bimol. cyclic ester is 40: 60-75: 25, polylactide and polylactide-co-glycolide proportion are 0: 10-10: 10.
Described pharmaceutically acceptable other adjuvants refer to emulsion stabilizer, described emulsion stabilizer is selected from polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), sodium polymethacrylate, sodium polyacrylate, sodium carboxymethyl cellulose etc., preferably polyethylene alcohol, its amount ranges is 0.1%-10%.
In addition, the present invention also provides the preparation method of preparation containing the sustained release microsphere agents of carperitide medicine, and its concrete technology is as follows:
The first step, at first that carperitide is water-soluble, obtain interior water; Macromolecular material biodegradable and the tool biocompatibility is dissolved in organic solvent, obtains oil phase; Oil phase and interior water are placed in agitator, and breast is even at a high speed, forms the W/O emulsion; Then the W/O emulsion is joined in the emulsion stabilizer aqueous solution, breast is even at a high speed, forms the W/O/W emulsion;
Second step, move into the W/O/W emulsion in the emulsion stabilizer aqueous solution, and stirring at low speed is centrifugal, collects thus obtained microsphere, with distilled water wash repeatedly after, more centrifugal collection, lyophilization, obtain the carperitide sustained-release micro-spheres.
the accompanying drawing explanation:
Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5 are respectively carperitide sustained release microsphere agents vitro release prepared by each embodiment-release time curve chart.
Fig. 1 is embodiment 1 release in vitro curve chart;
Fig. 2 is embodiment 2 release in vitro curve charts;
Fig. 3 is embodiment 3 release in vitro curve charts;
Fig. 4 is embodiment 4 release in vitro curve charts;
Fig. 5 is embodiment 5 release in vitro curve charts.
the specific embodiment:
Below in conjunction with embodiment, embodiment of the present invention are described in detail, but it will be understood to those of skill in the art that the following example is only for the present invention is described, and should not be considered as limiting scope of the present invention.
Embodiment 1
Take the 1.5mg carperitide and be dissolved in distilled water, obtain interior water; Take 100mgPLA and 900mgPLGA (polymerization ratio=3: 3) and be dissolved in dichloromethane, obtain oil phase.The PVA solution 500ml that the PVA solution 50ml that compound concentration is 5% and concentration are 0.5%.First carperitide solution is moved into and is dissolved with in the dichloromethane solution of PLA and PLGA, be placed on the emulsion dispersion machine at a high speed (30000rpm) breast under room temperature even 30 seconds, then the w/o type Emulsion of gained is transferred in the PVA solution that 20ml concentration is 5%, be placed on the emulsion dispersion machine rotating speed with 5000rpm, even 1 minute of breast, obtain W/O/W type emulsion, move in the PVA solution of 500ml0.5%, be placed on mechanical agitator, with the rotating speed stirring at low speed of 500rpm 2 hours, centrifugal, collect thus obtained microsphere, with distilled water, repeatedly wash, and then centrifugal collection, lyophilization, be distributed into the carperitide sustained release microsphere agents of actual drug loading at 2.5mg dosage, the average 15-40 μ of particle diameter m.
The medicine carrying carperitide sustained-release micro-spheres 5mg that precision takes embodiment 1 preparation is dissolved in the 1mL dichloromethane, gradation adds 3mL and 2mL double distilled water to extract medicine, vortex extraction 1min, the centrifugal 3min of 15000rpm, draw and merge supernatant, pipette supernatant 0.5mL and be settled to 10mL with double distilled water, sample introduction 20 μ l, HPLC measures content, the drawing standard curve, calculate the medicine carrying carperitide sustained-release micro-spheres Chinese medicine content of embodiment 1 preparation according to standard curve, calculated yield and envelop rate drug loading are respectively 84.5% and 85.9% accordingly.
Carperitide sustained release microsphere agents to embodiment 1 preparation carries out the tablets in vitro investigation, and method is as follows:
Precision takes the carperitide sustained-release micro-spheres of some parts of embodiment 1 preparation, and every part of 5mg is placed in the cillin bottle of 35 10mL, and every part adds the Na that contains 0.1M
2hPO
4naH with 0.1M
2pO
4the phosphate buffer solution of pH7.4, be placed in 37 ℃ of waters bath with thermostatic control, respectively the 0th, 4, 8, 12, 16, 20, 24, 28, within 32 days, take out, centrifugal, again be dispersed in acetate dichloromethane buffer (1: 1v/v), chromatographic column is C1850 * 2mm, mobile phase is 1: 1 containing 0.1% trifluoracetic acid and containing 1% trifluoroacetic 50% acetonitrile mixed solution, flow velocity 1.0ml/min, at the 240nm place, detect, measure remaining dose in microsphere, calculate accumulative releasing degree according to external standard method, the tablets in vitro measurement result of the carperitide sustained release microsphere agents of embodiment 1 preparation is as shown in table 1:
The tablets in vitro experimental result of the carperitide sustained release microsphere agents of table 1 embodiment 1 preparation
Take drug release time as abscissa, and accumulative releasing degree is vertical coordinate, draws the carperitide sustained release microsphere agents tablets in vitro curve of embodiment 1 preparation, the results are shown in Figure of description 1.
Embodiment 2
Take the 20mg carperitide and be dissolved in distilled water, obtain interior water; Take 100mgPLA and 900mgPLGA (polymerization ratio=4: 3) and be dissolved in dichloromethane, obtain oil phase.The PVA solution 500ml that the PVA solution 50ml that compound concentration is 5% and concentration are 0.5%.First carperitide solution is moved into and is dissolved with in the dichloromethane solution of PLGA, be placed on the emulsion dispersion machine at a high speed (30000rpm) breast under room temperature even 30 seconds, then the w/o type Emulsion of gained is transferred in the PVA solution that 20ml concentration is 5%, be placed on the emulsion dispersion machine rotating speed with 5000rpm, even 1 minute of breast, obtain W/O/W type emulsion, move in the PVA solution of 500ml0.5%, be placed on mechanical agitator, with the rotating speed stirring at low speed of 500rpm 2 hours, centrifugal, collect thus obtained microsphere, with distilled water, repeatedly wash, and then centrifugal collection, lyophilization, be distributed into the carperitide sustained release microsphere agents of actual drug loading at 3.0mg dosage, the average 20-40 μ of particle diameter m.
The medicine carrying carperitide sustained-release micro-spheres 5mg that precision takes embodiment 2 preparations is dissolved in the 1mL dichloromethane, gradation adds 3mL and 2mL double distilled water to extract medicine, vortex extraction 1min, the centrifugal 3min of 15000rpm, draw and merge supernatant, pipette supernatant 0.5mL and be settled to 10mL with double distilled water, sample introduction 20 μ l, HPLC measures content, the drawing standard curve, calculate the medicine carrying carperitide sustained-release micro-spheres Chinese medicine content of embodiment 1 preparation according to standard curve, calculated yield and envelop rate drug loading are respectively 78.4% and 86.7% accordingly.
Carperitide sustained release microsphere agents to embodiment 2 preparations carries out the tablets in vitro investigation, and method is as follows:
Precision takes the carperitide sustained-release micro-spheres of some parts of embodiment 2 preparation, and every part of 5mg is placed in the cillin bottle of 35 10mL, and every part adds the Na that contains 0.1M
2hPO
4naH with 0.1M
2pO
4the phosphate buffer solution of pH7.4, be placed in 37 ℃ of waters bath with thermostatic control, respectively the 0th, 4, 8, 12, 16, 20, 24, 28, within 32 days, take out, centrifugal, again be dispersed in acetate dichloromethane buffer (1: 1v/v), chromatographic column is C1850 * 2mm, mobile phase is 1: 1 containing 0.1% trifluoracetic acid and containing 1% trifluoroacetic 50% acetonitrile mixed solution, flow velocity 1.0ml/min, at the 240nm place, detect, measure remaining dose in microsphere, calculate accumulative releasing degree according to external standard method, the tablets in vitro measurement result of the carperitide sustained release microsphere agents of embodiment 2 preparations is as shown in table 2:
The tablets in vitro experimental result of the carperitide sustained release microsphere agents of table 2 embodiment 2 preparations
Take drug release time as abscissa, and accumulative releasing degree is vertical coordinate, draws the carperitide sustained release microsphere agents tablets in vitro curve of embodiment 2 preparations, the results are shown in Figure of description 2.
Embodiment 3
Take the 100mg carperitide and be dissolved in distilled water, obtain interior water; Take 300mgPLA and 700mgPLGA (polymerization ratio=6: 3) and be dissolved in dichloromethane, obtain oil phase.The PVA solution 1000ml that the PVA solution 100ml that compound concentration is 5% and concentration are 0.5%.First carperitide solution is moved into and is dissolved with in the dichloromethane solution of PLA and PLGA, be placed on the emulsion dispersion machine at a high speed (30000rpm) breast under room temperature even 30 seconds, then the w/o type Emulsion of gained is transferred in the PVA solution that 20ml concentration is 5%, be placed on the emulsion dispersion machine rotating speed with 5000rpm, even 1 minute of breast, obtain W/O/W type emulsion, move in the PVA solution of 500ml0.5%, be placed on mechanical agitator, with the rotating speed stirring at low speed of 500rpm 2 hours, centrifugal, collect thus obtained microsphere, with distilled water, repeatedly wash, and then centrifugal collection, lyophilization, be distributed into the carperitide sustained release microsphere agents of actual drug loading at 3.6mg dosage, the average 5-40 μ of particle diameter m.
The medicine carrying carperitide sustained-release micro-spheres 5mg that precision takes embodiment 3 preparations is dissolved in the 1mL dichloromethane, gradation adds 3mL and 2mL double distilled water to extract medicine, vortex extraction 1min, the centrifugal 3min of 15000rpm, draw and merge supernatant, pipette supernatant 0.5mL and be settled to 10mL with double distilled water, sample introduction 20 μ l, HPLC measures content, the drawing standard curve, calculate the medicine carrying carperitide sustained-release micro-spheres Chinese medicine content of embodiment 3 preparations according to standard curve, calculated yield and envelop rate drug loading are respectively 73.8% and 84.9% accordingly.
Carperitide sustained release microsphere agents to embodiment 3 preparations carries out the tablets in vitro investigation, and method is as follows:
Precision takes the carperitide sustained-release micro-spheres of some parts of embodiment 3 preparation, and every part of 5mg is placed in the cillin bottle of 35 10mL, and every part adds the Na that contains 0.1M
2hPO
4naH with 0.1M
2pO
4the phosphate buffer solution of pH7.4, be placed in 37 ℃ of waters bath with thermostatic control, respectively the 0th, 4, 8, 12, 16, 20, 24, 28, within 32 days, take out, centrifugal, again be dispersed in acetate dichloromethane buffer (1: 1v/v), chromatographic column is C1850 * 2mm, mobile phase is 1: 1 containing 0.1% trifluoracetic acid and containing 1% trifluoroacetic 50% acetonitrile mixed solution, flow velocity 1.0ml/min, at the 240nm place, detect, measure remaining dose in microsphere, calculate accumulative releasing degree according to external standard method, the tablets in vitro measurement result of the carperitide sustained release microsphere agents of embodiment 3 preparations is as shown in table 3:
The tablets in vitro experimental result of the carperitide sustained release microsphere agents of table 3 embodiment 3 preparations
Take drug release time as abscissa, and accumulative releasing degree is vertical coordinate, draws the carperitide sustained release microsphere agents tablets in vitro curve of embodiment 3 preparations, the results are shown in Figure of description 3.
Embodiment 4
Take the 150mg carperitide and be dissolved in distilled water, obtain interior water; Take 500mgPLA and 500mgPLGA (polymerization ratio=8: 3) and be dissolved in dichloromethane, obtain oil phase.The PVA solution 1000ml that the PVA solution 100ml that compound concentration is 5% and concentration are 0.5%.First carperitide solution is moved into and is dissolved with in the dichloromethane solution of PLA and PLGA, be placed on the emulsion dispersion machine at a high speed (30000rpm) breast under room temperature even 30 seconds, then the w/o type Emulsion of gained is transferred in the PVA solution that 20ml concentration is 5%, be placed on the emulsion dispersion machine rotating speed with 5000rpm, even 1 minute of breast, obtain W/O/W type emulsion, move in the PVA solution of 500ml0.5%, be placed on mechanical agitator, with the rotating speed stirring at low speed of 500rpm 2 hours, centrifugal, collect thus obtained microsphere, with distilled water, repeatedly wash, and then centrifugal collection, lyophilization, be distributed into the carperitide sustained release microsphere agents of actual drug loading at 4.6mg dosage, the average 5-40 μ of particle diameter m.
The medicine carrying carperitide sustained-release micro-spheres 5mg that precision takes embodiment 4 preparations is dissolved in the 1mL dichloromethane, gradation adds 3mL and 2mL double distilled water to extract medicine, vortex extraction 1min, the centrifugal 3min of 15000rpm, draw and merge supernatant, pipette supernatant 0.5mL and be settled to 10mL with double distilled water, sample introduction 20 μ l, HPLC measures content, the drawing standard curve, calculate the medicine carrying carperitide sustained-release micro-spheres Chinese medicine content of embodiment 4 preparations according to standard curve, calculated yield and envelop rate drug loading are respectively 80.1% and 90.9% accordingly.
Carperitide sustained release microsphere agents to embodiment 4 preparations carries out the tablets in vitro investigation, and method is as follows:
Precision takes the carperitide sustained-release micro-spheres of some parts of embodiment 4 preparation, and every part of 5mg is placed in the cillin bottle of 35 10mL, and every part adds the Na that contains 0.1M
2hPO
4naH with 0.1M
2pO
4the phosphate buffer solution of pH7.4, be placed in 37 ℃ of waters bath with thermostatic control, respectively the 0th, 4, 8, 12, 16, 20, 24, 28, within 32 days, take out, centrifugal, again be dispersed in acetate dichloromethane buffer (1: 1v/v), chromatographic column is C1850 * 2mm, mobile phase is 1: 1 containing 0.1% trifluoracetic acid and containing 1% trifluoroacetic 50% acetonitrile mixed solution, flow velocity 1.0ml/min, at the 240nm place, detect, measure remaining dose in microsphere, calculate accumulative releasing degree according to external standard method, the tablets in vitro measurement result of the carperitide sustained release microsphere agents of embodiment 4 preparations is as shown in table 4:
The tablets in vitro experimental result of the carperitide sustained release microsphere agents of table 4 embodiment 4 preparations
Take drug release time as abscissa, and accumulative releasing degree is vertical coordinate, draws the carperitide sustained release microsphere agents tablets in vitro curve of embodiment 4 preparations, the results are shown in Figure of description 4.
Take the 200mg carperitide and be dissolved in distilled water, obtain interior water; Take 400mgPLA and 600mgPLGA (polymerization ratio=9: 3) and be dissolved in dichloromethane, obtain oil phase.The PVA solution 1000ml that the PVA solution 100ml that compound concentration is 5% and concentration are 0.5%.First carperitide solution is moved into and is dissolved with in the dichloromethane solution of PLA and PLGA, be placed on the emulsion dispersion machine at a high speed (30000rpm) breast under room temperature even 30 seconds, then the w/o type Emulsion of gained is transferred in the PVA solution that 20ml concentration is 5%, be placed on the emulsion dispersion machine rotating speed with 5000rpm, even 1 minute of breast, obtain W/O/W type emulsion, move in the PVA solution of 500ml0.5%, be placed on mechanical agitator, with the rotating speed stirring at low speed of 500rpm 2 hours, centrifugal, collect thus obtained microsphere, with distilled water, repeatedly wash, and then centrifugal collection, lyophilization, be distributed into the carperitide sustained release microsphere agents of actual drug loading at 5.0mg dosage, the average 5-40 μ of particle diameter m.
The medicine carrying carperitide sustained-release micro-spheres 5mg that precision takes embodiment 5 preparations is dissolved in the 1mL dichloromethane, gradation adds 3mL and 2mL double distilled water to extract medicine, vortex extraction 1min, the centrifugal 3min of 15000rpm, draw and merge supernatant, pipette supernatant 0.5mL and be settled to 10mL with double distilled water, sample introduction 20 μ l, HPLC measures content, the drawing standard curve, calculate the medicine carrying carperitide sustained-release micro-spheres Chinese medicine content of embodiment 5 preparations according to standard curve, calculated yield and envelop rate drug loading are respectively 80.1% and 90.9% accordingly.
Carperitide sustained release microsphere agents to embodiment 5 preparations carries out the tablets in vitro investigation, and method is as follows:
Precision takes the carperitide sustained-release micro-spheres of some parts of embodiment 5 preparation, and every part of 5mg is placed in the cillin bottle of 35 10mL, and every part adds the Na that contains 0.1M
2hPO
4naH with 0.1M
2pO
4the phosphate buffer solution of pH7.4, be placed in 37 ℃ of waters bath with thermostatic control, respectively the 0th, 4, 8, 12, 16, 20, 24, 28, within 32 days, take out, centrifugal, again be dispersed in acetate dichloromethane buffer (1: 1v/v), chromatographic column is C1850 * 2mm, mobile phase is 1: 1 containing 0.1% trifluoracetic acid and containing 1% trifluoroacetic 50% acetonitrile mixed solution, flow velocity 1.0ml/min, at the 240nm place, detect, measure remaining dose in microsphere, calculate accumulative releasing degree according to external standard method, the tablets in vitro measurement result of the carperitide sustained release microsphere agents of embodiment 5 preparations is as shown in table 5:
The tablets in vitro experimental result of the carperitide sustained release microsphere agents of table 5 embodiment 5 preparations
Take drug release time as abscissa, and accumulative releasing degree is vertical coordinate, draws the carperitide sustained release microsphere agents tablets in vitro curve of embodiment 5 preparations, the results are shown in Figure of description 5.
Claims (5)
1. people α-atrial natriuretic peptide sustained release microsphere agents, it is characterized in that: the people α in described preparation-atrial natriuretic peptide sustained-release micro-spheres contains people's α-atrial natriuretic peptide or its salt that accounts for microsphere weight 0.1%-20% (w/w), the molecular weight that accounts for microsphere weight 80%-99.9% is 10, 000-200, the macromolecular material of 000 daltonian biodegradable and tool biocompatibility, and pharmaceutically acceptable other adjuvants that account for microsphere weight 0%-10%, microsphere average grain diameter is 10-50 μ m, be evenly distributed, envelop rate is more than 80%, its preparation method is to adopt emulsion-liquid drying method to prepare in two steps, specific as follows:
The first step, at first that people's α-atrial natriuretic peptide is water-soluble, obtain interior water; Macromolecular material biodegradable and the tool biocompatibility is dissolved in organic solvent, obtains oil phase; Oil phase and interior water are placed in agitator, and breast is even at a high speed, forms the W/O emulsion; Then the W/O emulsion is joined in the emulsion stabilizer aqueous solution, breast is even at a high speed, forms the W/O/W emulsion;
Second step, move into the W/O/W emulsion in the emulsion stabilizer aqueous solution, and stirring at low speed is centrifugal, collects thus obtained microsphere, with distilled water wash repeatedly after, more centrifugal collection, lyophilization, obtain people α-atrial natriuretic peptide sustained-release micro-spheres.
2. people α according to claim 1-atrial natriuretic peptide sustained release microsphere agents, it is characterized in that: the macromolecular material of described biodegradable and tool biocompatibility, optional from polylactide (PLA), PGA (PGA), polylactide-co-glycolide (PLGA), polyalkylcyanoacrylate, polycaprolactone (PCL), poly hydroxybutyric acid (PHB), poly-hydroxyl valeric acid (PVA), poly-capric acid (PDA), poly-anhydride, Polyhydroxybutyrate-co-hydroxyvalerate, polylactic acid-polyglycol, polyglycolic acid-Polyethylene Glycol a kind of or its mixture wherein, preferred polylactide and polylactide-co-glycolide mixture.
3. people α according to claim 3-atrial natriuretic peptide sustained release microsphere agents, it is characterized in that: described lactide and Acetic acid, hydroxy-, bimol. cyclic ester molecular weight ranges are all 10,000-20,000 dalton, in polylactide, the proportion of lactide and Acetic acid, hydroxy-, bimol. cyclic ester is 40: 60-75: 25, and polylactide and polylactide-co-glycolide proportion are 0: 10-10: 10.
4. people α according to claim 1-atrial natriuretic peptide sustained release microsphere agents, it is characterized in that: described pharmaceutically acceptable other adjuvants refer to emulsion stabilizer, described emulsion stabilizer is selected from polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), sodium polymethacrylate, sodium polyacrylate, sodium carboxymethyl cellulose etc., preferably polyethylene alcohol, its amount ranges is 0.1%-10%.
5. people α according to claim 1-atrial natriuretic peptide sustained-release micro-spheres preparation method, it is characterized in that: described organic solvent is selected from dichloromethane, chloroform, ethyl acetate, ether, acetone, dioxane or oxolane etc., preferably dichloromethane.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106309384A (en) * | 2015-06-25 | 2017-01-11 | 深圳翰宇药业股份有限公司 | Injection-use carperitide freeze-dried composition and preparation method thereof |
| CN109608646A (en) * | 2018-11-21 | 2019-04-12 | 深圳市孙逸仙心血管医院（深圳市心血管病研究所） | A kind of nano-carrier of targeted therapy myocardial damage and application |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102198103A (en) * | 2011-05-30 | 2011-09-28 | 深圳翰宇药业股份有限公司 | Stable exenatide sustained-release microsphere preparation and preparation method thereof |
| CN102382188A (en) * | 2011-11-07 | 2012-03-21 | 深圳翰宇药业股份有限公司 | Method for preparing carperitide acetate |
-
2012
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102198103A (en) * | 2011-05-30 | 2011-09-28 | 深圳翰宇药业股份有限公司 | Stable exenatide sustained-release microsphere preparation and preparation method thereof |
| CN102382188A (en) * | 2011-11-07 | 2012-03-21 | 深圳翰宇药业股份有限公司 | Method for preparing carperitide acetate |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106309384A (en) * | 2015-06-25 | 2017-01-11 | 深圳翰宇药业股份有限公司 | Injection-use carperitide freeze-dried composition and preparation method thereof |
| CN106309384B (en) * | 2015-06-25 | 2019-12-03 | 深圳翰宇药业股份有限公司 | A kind of injection Carperitide freeze-dried composition and preparation method thereof |
| CN109608646A (en) * | 2018-11-21 | 2019-04-12 | 深圳市孙逸仙心血管医院（深圳市心血管病研究所） | A kind of nano-carrier of targeted therapy myocardial damage and application |
| CN109608646B (en) * | 2018-11-21 | 2021-03-16 | 深圳市孙逸仙心血管医院（深圳市心血管病研究所） | Nano-carrier for targeted therapy of myocardial injury and application |
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