CN101057832A - Method for preparing protein or polypeptide medicine slow-releasing microball - Google Patents
Method for preparing protein or polypeptide medicine slow-releasing microball Download PDFInfo
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- CN101057832A CN101057832A CN 200710057357 CN200710057357A CN101057832A CN 101057832 A CN101057832 A CN 101057832A CN 200710057357 CN200710057357 CN 200710057357 CN 200710057357 A CN200710057357 A CN 200710057357A CN 101057832 A CN101057832 A CN 101057832A
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- albumen
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Abstract
The invention discloses a method for preparing slow release micro-balloon for protein or polypeptide medicine, comprising following steps: dissolving one weight unit of protein or polypeptide medicine in 50 -500 weight unit water, stirring and adding 10 -30 weight unit chitose with the degree of deacetylation being 85-90%, and 10 20 weight unit glycine and 10 -20 weight unit manna sugar, spray drying got solution with hypercritical carbon dioxide or spray drying with 80-10bar sub-critical carbon dioxide, getting said product covered with mentioned chitose. The invention is characterized by temperate preparing condition, low temperature, free from influence on medicine activation, no use of organic solvent and environmental-protection.
Description
Technical field
The present invention relates to a kind of preparation method of medicament slow-release microsphere, particularly relate to the preparation method of a kind of albumen or polypeptide medicine slow-releasing microball.
Background technology
Because the characteristic of albumen/polypeptide drug, present administering mode generally all is to adopt drug administration by injection, the advantage that the mode of drug administration by injection has is rapid-action, do not exist " first pass effect ", but, also have some deficiency, the medical worker special as needs carries out in special medical space, in injection process the patient produced stimulation.Therefore,, reduce administration number of times, can improve patient's compliance surely if can prepare a kind of prolongation drug administration by injection at interval.
Have at present albumen or polypeptide class bio-pharmaceutical are made the technology of sustained-release micro-spheres agent, medicine is made slow releasing preparation can reduce administration number of times, prolongs action time, as emulsifying-solvent evaporation method or spray drying method.Emulsifying-solvent evaporation method will be used organic solvent when the preparation medicament slow-release microsphere, organic solvent can pollute environment on the one hand, cause albumen or polypeptide drug degeneration on the other hand easily, though and spray drying method can be not with an organic solvent, but it is higher that one of preparation process condition is exactly a temperature, generally more than 105 ℃, high temperature causes albumen or polypeptide drug degeneration easily.Few because of needing a kind of environmental pollution badly, the preparation method of the impregnable sustained-release micro-spheres of medicine stability.
Summary of the invention
The objective of the invention is to overcome deficiency of the prior art, a kind of environmental protection is provided, drug molecule is difficult for the preparation method of ruined albumen or polypeptide medicine slow-releasing microball.
Technical scheme of the present invention is summarized as follows:
The preparation method of a kind of albumen or polypeptide medicine slow-releasing microball, form by following steps:
The albumen or the polypeptide drug of 1 mass parts are dissolved in the 50-200 mass parts water, the deacetylation that under agitation adds the 10-30 mass parts is chitosan and 10-20 mass parts glycine and the 10-20 mass parts mannitol of 85-90%, gained solution obtains albumen or polypeptide medicine slow-releasing microball by described chitosan parcel through supercritical carbon dioxide auxiliary spray thing drying or the auxiliary spray of the nearly critical carbon dioxide of 80-10bar thing drying.
Described albumen or polypeptide drug are recombinant erythropoietin, epidermal growth factor, transfer factor or insulin, can also be other albumen or polypeptide class medicines.
The mass ratio 1 of described albumen or polypeptide drug and described chitosan: 20-25.
Described supercritical carbon dioxide auxiliary spray thing drying or the auxiliary spray of the nearly critical carbon dioxide of 80-10bar thing drying, nitrogen temperature is 30-65 ℃.
The preparation method of a kind of albumen of the present invention or polypeptide medicine slow-releasing microball is compared with method at present commonly used such as emulsifying-solvent evaporation method, spray drying method, has the outstanding advantage of two aspects.The one, the preparation condition gentleness generally is no more than 60 ℃, and the activity of medicine is affected hardly, and the 2nd, not with an organic solvent, help environmental conservation.
The specific embodiment
The present invention is further illustrated below in conjunction with specific embodiment, but these embodiment can not produce any restriction to the present invention.
Embodiment 1
The recombinant erythropoietin (10000U/ml) of 1 mass parts is dissolved in the 100 mass parts water, the deacetylation that under agitation adds 20 mass parts is 85% chitosan, add 10 mass parts glycine and 10 mass parts mannitol again, then, with the CO under the supercriticality
2Be dissolved in the above-mentioned solution, above-mentioned solution is when spraying in the decompression chamber, and solution sprays in droplet microgranule mode, and is dissolved in the CO in the solution
2Expansion again droplet further is dispersed into thinner droplet, droplet obtains the sustained-release micro-spheres of particle diameter at 1-3 μ m by behind 55 ℃ the nitrogen drying.
Embodiment 2
The insulin (400U/ml) of 1 mass parts is dissolved in the 100 mass parts water, and the deacetylation that adds 25 mass parts is 90% chitosan, adds 10 mass parts glycine and 10 mass parts mannitol again, then, and with the CO under the supercriticality
2Be dissolved in the above-mentioned solution, above-mentioned solution is when spraying in the decompression chamber, and solution sprays in droplet microgranule mode, and droplet obtains the sustained-release micro-spheres of particle diameter at 1-3 μ m by behind 65 ℃ the nitrogen drying.
Embodiment 3
The epidermal growth factor of 1 mass parts is dissolved in 50 parts of water, and the deacetylation that adds 30 mass parts is 90% chitosan, adds 20 mass parts glycine and 20 mass parts mannitol again, then, and with the CO under the nearly critical state of 80bar
2Be dissolved in the above-mentioned solution, above-mentioned solution is when spraying in the decompression chamber, and solution sprays in droplet microgranule mode, and droplet obtains the sustained-release micro-spheres of particle diameter at 1-3 μ m by behind 30 ℃ the nitrogen drying.
Embodiment 4
The transfer factor (100 μ g/3mg) of 1 mass parts is dissolved in 200 parts of water, and the deacetylation that adds 10 mass parts is 90% chitosan, adds 15 mass parts glycine and 15 mass parts mannitol again, then, and with the CO under the nearly critical state of 10bar
2Be dissolved in the above-mentioned solution, above-mentioned solution is when spraying in the decompression chamber, and solution sprays in droplet microgranule mode, and droplet obtains the sustained-release micro-spheres of particle diameter at 1-3 μ m by behind 30 ℃ the nitrogen drying.
Albumen or polypeptide medicine slow-releasing microball with method preparation of the present invention can further be processed into injection (for vein and subcutaneous injection) or oral cavity inhalant.
The advantage of this preparation protide sustained-release micro-spheres shows two aspects, the one, and mild condition, the vapo(u)rizing temperature of use is lower than common spray drying method (generally more than 105 ℃), and drying time is short, only 2-5 second.The activity of medicine can not be affected substantially.The 2nd,, with other prepares the technology of protein medicaments sustained-release micro-spheres at present, compare as emulsifying-solvent evaporation method, used in the present invention is water, CO
2And mannitol and glycine etc., be green material, do not need organic solvent.
Albumen or polypeptide medicine slow-releasing microball experiment in vitro result with method preparation of the present invention show that medicine discharges sustainable 1-2 more than week from microsphere, even can realize administration in every month 1 time.
Claims (4)
1. the preparation method of albumen or polypeptide medicine slow-releasing microball, it is characterized in that forming: the albumen or the polypeptide drug of 1 mass parts are dissolved in the 50-200 mass parts water by following steps, the deacetylation that under agitation adds the 10-30 mass parts is chitosan and 10-20 mass parts glycine and the 10-20 mass parts mannitol of 85-90%, gained solution obtains albumen or polypeptide medicine slow-releasing microball by described chitosan parcel through supercritical carbon dioxide auxiliary spray thing drying or the auxiliary spray of the nearly critical carbon dioxide of 80-10bar thing drying.
2. the preparation method of albumen according to claim 1 or polypeptide medicine slow-releasing microball is characterized in that described albumen or polypeptide drug are recombinant erythropoietin, epidermal growth factor, transfer factor or insulin.
3. the preparation method of albumen according to claim 1 or polypeptide medicine slow-releasing microball is characterized in that the mass ratio 1 of described albumen or polypeptide drug and described chitosan: 20-25.
4. the preparation method of albumen according to claim 1 or polypeptide medicine slow-releasing microball is characterized in that described supercritical carbon dioxide auxiliary spray thing drying or the auxiliary spray of the nearly critical carbon dioxide of 80-10bar thing drying, and nitrogen temperature is 30-65 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100573573A CN100490784C (en) | 2007-05-17 | 2007-05-17 | Method for preparing protein or polypeptide medicine slow-releasing microball |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100573573A CN100490784C (en) | 2007-05-17 | 2007-05-17 | Method for preparing protein or polypeptide medicine slow-releasing microball |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101057832A true CN101057832A (en) | 2007-10-24 |
| CN100490784C CN100490784C (en) | 2009-05-27 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2007100573573A Expired - Fee Related CN100490784C (en) | 2007-05-17 | 2007-05-17 | Method for preparing protein or polypeptide medicine slow-releasing microball |
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| CN (1) | CN100490784C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104840428A (en) * | 2014-02-13 | 2015-08-19 | 山东省生物医药科学院 | Hyaluronic acid-chitosan microsphere carrying epidermal growth factor and preparation method and application of hyaluronic acid-chitosan microsphere |
-
2007
- 2007-05-17 CN CNB2007100573573A patent/CN100490784C/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104840428A (en) * | 2014-02-13 | 2015-08-19 | 山东省生物医药科学院 | Hyaluronic acid-chitosan microsphere carrying epidermal growth factor and preparation method and application of hyaluronic acid-chitosan microsphere |
| CN104840428B (en) * | 2014-02-13 | 2018-07-06 | 山东省药学科学院 | A kind of hyaluronic acid-chitosan microballoon for being loaded with epidermal growth factor and its preparation method and application |
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| Publication number | Publication date |
|---|---|
| CN100490784C (en) | 2009-05-27 |
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Granted publication date: 20090527 Termination date: 20130517 |