CN102139127A - Developable gelatin sponge suppository and preparation process thereof - Google Patents
Developable gelatin sponge suppository and preparation process thereof Download PDFInfo
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- CN102139127A CN102139127A CN2011100688215A CN201110068821A CN102139127A CN 102139127 A CN102139127 A CN 102139127A CN 2011100688215 A CN2011100688215 A CN 2011100688215A CN 201110068821 A CN201110068821 A CN 201110068821A CN 102139127 A CN102139127 A CN 102139127A
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Abstract
The invention discloses a developable gelatin sponge suppository for tumor embolism. The developable gelatin sponge suppository disclosed by the invention is prepared by processing gelatin or other colloid high molecular materials. The suppository is characterized by being prepared from gelatin, expanding agent and developing agent in any proportions. The developable gelatin sponge suppository can be degraded in bodies and has embolism and development functions, and the water absorbing capacity is more than 5 times. The developable gelatin sponge suppository can be directly used for embolism and can also be used for embolism after carrying drugs, wherein the carried drugs are anti-tumor drugs. The preparation method of the developable gelatin sponge suppository comprises the following steps of: adding the mixture of the gelatin and the developing agent into a proper thickening agent solution while continuously stirring for fully dissolving; adding the solution into a proper medium; cross-linking and curing with aldehyde compounds; washing or volatilizing the medium and the cross-linking agent; and freeze-drying to obtain microspheres/particles with various particle sizes.
Description
Technical field
The present invention relates to a kind of agent of developed gelfoam embolization and preparation technology thereof who is used for the interventional therapy tumor disease.
Background knowledge
Along with reaching its maturity of interventional therapy, it obtains more and more widely application in field of medical technology.The principle of interventional therapy is the medical image instrument guiding by fine definition, through little otch conduit is inserted the intravital tumor locus of people, by the blood supply of feeding artery perfusion antitumor drug or blocking-up tumor tissues, make tumor necrosis, atrophy at short notice again, reach the purpose of treatment.The key technology of interventional therapy is to select suitable being used to block the suppository of tumor tissues blood supply.
Still do not have clinically at present and have the suppository that develops with the thromboembolism function simultaneously,, use very inconvenience clinically, and can bring certain iatrogenic infringement owing to do not possess developing function.Therefore caused the interest of vast researcher as a kind of novel embolizing dosage form with the suppository of developing function.
Find through literature search prior art, the Chinese patent publication number is CN101007190, open day to be the patent of invention of 2007.08.01, a kind of Biodegradable imaging microspheres vascular embolization material is proposed, be made up of the biodegradation material that can implant in blood vessel and roentgenopaque developing material, biodegradation material parcel developing material forms grain structure.The product biodegradation time can be regulated; X-ray is visual down good, is convenient to observe the thromboembolism position; Can carry out nuclear magnetic resonance, NMR (MRI) inspection behind the thromboembolism; Proportion is moderate, can suspend in blood, can be convenient to deposition, thromboembolism in blood vessel to end blood vessel drift slightly with the mobile of blood, is difficult for backflowing, and polarization is good; Diameter of micro ball can be controlled; Advantages such as product price is cheap.But foregoing invention does not obtain industrialization always, and after biodegradation material and roentgenopaque developing material are combined in this invention, its water absorbing force and the elasticity in blood vessel all do not reach corresponding clinical requirement, and the solid plug suppository in the clinical practice all requires to possess high water absorbing force, elasticity, and foregoing invention does not embody this point.It is the suppository of being made after processed by gelatin or other colloidal type macromolecular materials that the present invention will provide a kind of gelfoam embolization agent of developing, and this suppository is made up of gelatin, extender, developing agent three part arbitrary proportions.It is degradable in vivo, has thromboembolism simultaneously and the two big functions of developing, and water absorbing force is more than 5 times.Animal experiment has been carried out in this gelfoam embolization agent of can developing and preliminary clinical results shows, can reach thromboembolism fully and the two big functions of developing, and its technology is simple, can realize industrialization.
Summary of the invention
It is the suppository of being made after processed by gelatin or other colloidal type macromolecular materials that the present invention will provide a kind of gelfoam embolization agent of developing, and this suppository is made up of gelatin, extender, developing agent three part arbitrary proportions.It is degradable in vivo, has thromboembolism simultaneously and the two big functions of developing, and water absorbing force is more than 5 times.
The present invention also will provide the preparation technology of the above-mentioned gelfoam embolization agent of developing.This preparation technology is simple, and is controlled, and can be by relevant parameter is controlled microsphere or the granule that directly obtains various particle diameters, and microsphere or granule have certain elasticity and dilatancy.
The present invention is achieved by the following technical solutions:
Developed gelfoam embolization agent among the present invention is microsphere or the granule that is formed by gelatin, extender, developing agent crosslinking curing, and suppository of the present invention can be directly used in thromboembolism, also can be used for thromboembolism behind the medicine carrying.This suppository shape is more unified, the surface size homogeneous, and particle size distribution is in the arbitrary narrower scope of 50～1500um.
If the suppository medicine carrying among the present invention can be selected antineoplastic agent for use, as mitomycin, 5-FU, cisplatin etc.
For making suppository have thromboembolism function, high-hydroscopicity and elasticity, other macromolecular materials of employing gelatin, similar gelatin gels character or the compositions of gelatin and other macromolecular materials are as the main material structure, add extender, and become spongy with the aldehyde compound crosslinking curing.Described extender is for meeting the high expansible macromolecular material of water such as sodium polyacrylate, polyacrylic acid etc.Other macromolecular materials such as sodium alginate, the chitosan etc. of other similar gelatin gels character.
For making suppository have developing function, selected developing agent for use, can be two kinds of water solublity developing agent and water-insoluble developing agents.Wherein water solublity developing agent such as iohexol, ioversol, cardiografin, iotrolan etc., water-insoluble developing agent such as barium sulfate etc.
Preparation technology of the present invention comprises the steps:
Do not stopping under the stirring state, with the suitable extender solution of mixture adding of gelatin and developing agent, fully dissolving, this solution is added in the suitable medium, use the aldehyde compound crosslinking curing, flush away or wave cloud medium and cross-linking agent, lyophilization becomes the microsphere/granule of various different-grain diameters.Promptly.
Control gelatin, the mixture of developing agent and the ratio of extender solution, can obtain the microsphere or the granule of different sizes, uniform particle diameter.
The invention has the advantages that its degradable in vivo of gelfoam embolization agent that can develop, have thromboembolism simultaneously and the two big functions of developing, water absorbing force is more than 5 times.These characteristics can improve clinical effect of embolization, save the process of clinical preparation suppository and developing agent, thereby reduce the generation of side effect and the generation of iatrogenic infringement greatly, the clinical manipulation controllability is stronger, but also can in manufacturing process, add antitumor drug, reach the double treatment effect of Drug therapy and thromboembolism.And gelatin has good intermiscibility and degradability, and clinical safety also is guaranteed.
The specific embodiment
Embodiment 1
Sodium polyacrylate is mixed with 0.01～10% solution 100ml, treat fully dissolving after, add the mixture of 10g gelatin, 5g iohexol, water-bath is fully dissolved, drop in the liquid paraffin or vegetable oil of 10 times of amounts, stir 20min, add 1-35% formalin 10ml, continue to stir 3min, ice bath 30min filters, and solid portion alternately washs 3 times with dehydrated alcohol, water, lyophilization, promptly.
Regulate the ratio of gelatin solution concentration, adding aldehyde compound ratio and liquid paraffin or vegetable oil, can obtain the microsphere of different-grain diameter.
Embodiment 2
Sodium polyacrylate is mixed with 0.01～10% solution 100ml, treat fully dissolving after, add the mixture of 10g gelatin, 5g iohexol, 1g mitomycin, water-bath is fully dissolved, drop in the liquid paraffin or vegetable oil of 10 times of amounts, stir 20mm, add 1-35% formalin 10ml, continue to stir 3min, ice bath 30min filters, and solid portion alternately washs 3 times with dehydrated alcohol, water, lyophilization, promptly.
Regulate the ratio of gelatin solution concentration, adding aldehyde compound ratio and liquid paraffin or vegetable oil, can obtain the microsphere of different-grain diameter.
Embodiment 3
Sodium polyacrylate is mixed with 0.01% solution 100ml, treat fully dissolving after, add the mixture of 10g gelatin, 5g iohexol, 30 ℃ of water-baths are fully dissolved, drop in the liquid paraffin of 10 times of amounts, stir 20min, add 5% formalin 10ml, continue to stir 3min, ice bath 30mm filters, and solid portion alternately washs 3 times with dehydrated alcohol, water, lyophilization, promptly.
Regulate the ratio of gelatin solution concentration, adding aldehyde compound ratio and liquid paraffin or vegetable oil, can obtain the microsphere of different-grain diameter.
Embodiment 4
Sodium polyacrylate is mixed with 10% solution 100ml, treat fully dissolving after, add the mixture of 10g gelatin, 5g iohexol, water-bath is fully dissolved, drop in the liquid paraffin or vegetable oil of 10 times of amounts, stir 20min, add 5% formalin 10ml, continue to stir 3min, ice bath 30min filters, and solid portion alternately washs 3 times with dehydrated alcohol, cold water, lyophilization, promptly.
Regulate the ratio of gelatin solution concentration, adding aldehyde compound ratio and liquid paraffin or vegetable oil, can obtain the microsphere of different-grain diameter.
Embodiment 5
Sodium polyacrylate is mixed with 1% solution 100ml, treat fully dissolving after, add the mixture of 10g gelatin, 5g iohexol, water-bath is fully dissolved, drop in the liquid paraffin or vegetable oil of 10 times of amounts, stir 20min, add 5% formalin 10ml, continue to stir 3min, ice bath 30min filters, and solid portion is handed over battalion's washing 3 times with dehydrated alcohol, cold water, lyophilization, promptly.
Regulate the ratio of gelatin solution concentration, adding aldehyde compound ratio and liquid paraffin or vegetable oil, can obtain the microsphere of different-grain diameter.
Claims (10)
1. the gelfoam embolization agent of can developing is the suppository of being made after processed by gelatin or other colloidal type macromolecular materials, it is characterized in that this suppository is made up of gelatin, extender, developing agent three part arbitrary proportions.It is degradable in vivo, has thromboembolism simultaneously and the two big functions of developing, and water absorbing force is more than 5 times.
2. according to the right 1 described gelfoam embolization agent of developing, it is characterized in that its particle size distribution is in the arbitrary narrower scope of 50～1500um.
3. according to the right 1 described gelfoam embolization agent of developing, it is characterized in that used gelatin answers crosslinking curing to become spongy, have stronger water absorbing force.The gelatin of treated mistake is made microsphere/granule, have certain elasticity and dilatancy.
4. according to the right 1 described gelfoam embolization agent of developing, it is characterized in that this suppository can be directly used in thromboembolism, also can be used for thromboembolism behind the medicine carrying.Contained medicine is an antitumor drug.
5. the gelfoam embolization agent of developing as claimed in claim 1 is characterized in that extender is to meet high expansible macromolecular material of water such as sodium polyacrylate.
6. the gelfoam embolization agent of developing as claimed in claim 1 is characterized in that developing agent can be two kinds of water solublity developing agent and water-insoluble developing agents.
7. the gelfoam embolization agent of developing as claimed in claim 1 is characterized in that gelatin can replace with the compositions of other macromolecular materials or gelatin and other macromolecular materials.
8. technology for preparing as right 1～7 described gelfoam embolization agent of developing may further comprise the steps:
Do not stopping under the stirring state, with the suitable extender solution of mixture adding of gelatin and developing agent, fully dissolving, this solution is added in the suitable straight medium, use the aldehyde compound crosslinking curing, flush away or fling to medium and cross-linking agent, lyophilization becomes the microsphere/granule of various different-grain diameters.Promptly.
9. method as claimed in claim 8, the ratio that it is characterized in that gelatin and developer mixture was 1: 0～1: the 1 arbitrary ratio of scope.
10. method as claimed in claim 8, the concentration that it is characterized in that extender solution are the arbitrary concentration of 0.001%～10% scope.
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| CN2011100688215A CN102139127A (en) | 2011-03-17 | 2011-03-17 | Developable gelatin sponge suppository and preparation process thereof |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103006573A (en) * | 2012-12-28 | 2013-04-03 | 杭州艾力康医药科技有限公司 | Method for preparing gelatin microballoon embolization agent |
| CN103977413A (en) * | 2014-05-19 | 2014-08-13 | 东南大学 | Developable composite microsphere embolization agent and preparation method thereof |
| CN108478849A (en) * | 2018-02-07 | 2018-09-04 | 广州迈普再生医学科技股份有限公司 | One kind is absorbable can to stick styptic sponge and preparation method thereof |
| CN113197866A (en) * | 2021-04-23 | 2021-08-03 | 复旦大学附属华山医院 | Radiopaque drug-loaded embolism microsphere for interventional therapy and preparation method thereof |
| CN114028605A (en) * | 2021-10-29 | 2022-02-11 | 厦门大学 | Preparation method and application of injectable gelatin-iodized oil homogeneous preparation for vascular embolism |
| CN115245592A (en) * | 2022-01-06 | 2022-10-28 | 青岛大学 | Luminous and developing two-in-one gelatin embolism microsphere and preparation method thereof |
| CN115252882A (en) * | 2022-07-23 | 2022-11-01 | 深圳市联科翰微医疗科技有限公司 | Visible gelatin embolism microsphere manufacturing process |
| CN115400266A (en) * | 2022-09-05 | 2022-11-29 | 北京邦塞科技有限公司 | Composite microsphere, bone cement, preparation method and application thereof |
| CN116036353A (en) * | 2022-12-05 | 2023-05-02 | 上海七木医疗器械有限公司 | Absorbable embolic material and preparation method and application thereof |
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Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103006573A (en) * | 2012-12-28 | 2013-04-03 | 杭州艾力康医药科技有限公司 | Method for preparing gelatin microballoon embolization agent |
| CN103977413A (en) * | 2014-05-19 | 2014-08-13 | 东南大学 | Developable composite microsphere embolization agent and preparation method thereof |
| CN103977413B (en) * | 2014-05-19 | 2016-03-02 | 东南大学 | One can be developed complex microsphere suppository and preparation method thereof |
| CN108478849A (en) * | 2018-02-07 | 2018-09-04 | 广州迈普再生医学科技股份有限公司 | One kind is absorbable can to stick styptic sponge and preparation method thereof |
| CN113197866A (en) * | 2021-04-23 | 2021-08-03 | 复旦大学附属华山医院 | Radiopaque drug-loaded embolism microsphere for interventional therapy and preparation method thereof |
| CN114028605A (en) * | 2021-10-29 | 2022-02-11 | 厦门大学 | Preparation method and application of injectable gelatin-iodized oil homogeneous preparation for vascular embolism |
| CN115245592A (en) * | 2022-01-06 | 2022-10-28 | 青岛大学 | Luminous and developing two-in-one gelatin embolism microsphere and preparation method thereof |
| CN115252882A (en) * | 2022-07-23 | 2022-11-01 | 深圳市联科翰微医疗科技有限公司 | Visible gelatin embolism microsphere manufacturing process |
| CN115400266A (en) * | 2022-09-05 | 2022-11-29 | 北京邦塞科技有限公司 | Composite microsphere, bone cement, preparation method and application thereof |
| CN115400266B (en) * | 2022-09-05 | 2024-01-19 | 北京邦塞科技有限公司 | Composite microsphere, bone cement and preparation method and application thereof |
| CN116036353A (en) * | 2022-12-05 | 2023-05-02 | 上海七木医疗器械有限公司 | Absorbable embolic material and preparation method and application thereof |
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Application publication date: 20110803 |