CN101007190A - Biodegradable imaging microspheres vascular embolization material - Google Patents
Biodegradable imaging microspheres vascular embolization material Download PDFInfo
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- CN101007190A CN101007190A CN 200710026274 CN200710026274A CN101007190A CN 101007190 A CN101007190 A CN 101007190A CN 200710026274 CN200710026274 CN 200710026274 CN 200710026274 A CN200710026274 A CN 200710026274A CN 101007190 A CN101007190 A CN 101007190A
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- vascular embolization
- copolymer
- biodegradable
- embolization material
- imaging microspheres
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Abstract
The invention discloses a biological decomposable developing micro sphere typed vascular plug material, which comprises the following parts: biological decomposable material, developing material without permeating X ray and antineoplastic agent. The invention is convenient to adjust time to do biological decomposition, which can do MRI examination after plugging.
Description
Technical field
The present invention relates to a kind of vascular suppository material, particularly a kind of Biodegradable imaging microspheres vascular embolization material.
Background technology
In the prior art, multiple intervention vascular suppository material has been arranged, mainly contain polyvinyl alcohol (Polyvinyl Alcohol, PVA) microsphere, sodium alginate micro ball, gelfoam, surgical thread, stainless steel spring circle, platinum microcoils, taking off property sacculus, alpha-cyanoacrylate (Cyanoacrylates), dewatered ethanol, iodized oil, sodium morrhuate etc.At clinical use medi-spring steel ring, surgical thread, gelfoam good clinical effectiveness is arranged when bolt blocks up trunk, influence long-term efficacy but prop up circulation foundation because of side.The mistake bolt easily takes place in liquid suppository such as alpha-cyanoacrylate (Cyanoacrylates), dewatered ethanol, iodized oil, sodium morrhuate when clinical manipulation, operation easier is big.Polyvinyl alcohol (Polyvinyl Alcohol, PVA), sodium alginate micro ball and gelfoam, surgical thread etc. be invisible under X-ray, is difficult to observe the thromboembolism position.
The objective of the invention is to provide a kind of comparatively ideal intervention vascular suppository material, particularly novel end is vascular occlusive agent or end vascular suppository material slightly slightly, and have the following advantages: X-ray is visual down good, is convenient to observe the thromboembolism position, has avoided the mistake bolt effectively; Have biodegradability, embolus can be degraded in the time of setting, and prevents the excessive damage to organ; Nonferromagnetic can be carried out nuclear magnetic resonance, NMR (MPI) 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; Product price is cheap.
Summary of the invention
The present invention is intended to develop a kind of Biodegradable imaging microspheres vascular embolization material, have visual under biodegradability, the X ray, can flowing with blood to advantages such as end blood vessel drift slightly, low prices.
The object of the present invention is achieved like this:
A kind of Biodegradable imaging microspheres vascular embolization material, described a kind of Biodegradable imaging microspheres vascular embolization material is made up of the biodegradation material that can implant in blood vessel and roentgenopaque developing material, and biodegradation material parcel developing material forms grain structure.
Described biodegradation material refers to: polylactic acid, the poly (lactic acid-glycolic acid) copolymer, polylactic acid-copolyether, polycaprolactone, polycaprolactone-polyether block copolymer, the polycaprolactone copolymer, polycaprolactone-polyethers-polylactide copolymer, poly-(Acetic acid, hydroxy-, bimol. cyclic ester-polylactide) copolymer, Acetic acid, hydroxy-, bimol. cyclic ester-L-lactide-caprolactone copolymer, polycaprolactone-poly-second lactone-poly-glycolide copolymer and other fatty acid polyglycol lactone copolymers, and the blend or derivatives thereof of glue protein, chitin, chitosan, gelatin or alginate natural high molecular substance or above various materials.
Described developing material includes effective development composition of intravascular contrast media.
Further, effective development composition of described intravascular contrast media comprises a kind of in the following material at least: the surplus materials after the ionic contrast agent cardiografin is handled through vacuum freeze-drying method; Surplus materials after non-ionic contrast agent iohexol (Iohexol) or Iopromide (Iopromide) or B-15000 (Iopamidol) are handled through vacuum freeze-drying method; Surplus materials after nonionic dimer iotrolan intravascular contrast media such as (Iotrolan) is handled through vacuum freeze-drying method.
The proportion of described a kind of Biodegradable imaging microspheres vascular embolization material is at 0.8g/cm
3To 1.65g/cm
3Between, its optimum is 1.0g/cm
3To 1.35g/cm
3
The diameter of described a kind of Biodegradable imaging microspheres vascular embolization material is between 10 μ m to 1500 μ m, size according to diameter of micro ball is divided into different brackets, 10 μ m～150 μ m, 100 μ m～350 μ m, 200 μ m～500 μ m, 400 μ m～650 μ m, 500 μ m～750 μ m, 650 μ m～950 μ m, 850 μ m～1100 μ m, 1000 μ m～1350 μ m, 1250 μ m～1500 μ m.
A kind of Biodegradable imaging microspheres vascular embolization material of the present invention, owing to adopted the biodegradation material that in blood vessel, to implant to wrap up the structure that roentgenopaque developing material forms the graininess microsphere, have the following advantages: X-ray is visual down good, be convenient to observe the thromboembolism position, avoided the mistake bolt effectively; Have biodegradability, embolus can be degraded in the time of setting, and prevents the excessive damage to organ; Nonferromagnetic can be carried 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; Product price is cheap; A kind of comparatively ideal intervention vascular suppository material, particularly end vascular suppository material slightly is provided.
Description of drawings
Fig. 1 is the structural representation of a kind of Biodegradable imaging microspheres vascular embolization material of the present invention.
Among the above-mentioned figure: 1 is biodegradation material, and 2 is developing material.
Specific embodiment
Embodiment 1: the present invention's development polylactic acid (PLA) microsphere
Buy intravascular contrast media on the market,, after handling through vacuum freeze-drying method, keep the surplus materials after its lyophilization, as developing material (2) as ionic contrast agent cardiografin (Urografin).
Adopt polylactic acid as biodegradation material (1), can make developing material (2) microsphere easily according to the common processes that polylactic acid is made the pastille microsphere as the lapping of various medicines.
Polylactic acid is made the pastille microsphere as the lapping of various medicines, and many common processes have been arranged.As: set sail etc. and on " China Medicine University's journal,, 35 (3): 207-210 in 2004 ", to have delivered " ciprofloxacin polylactic acid microsphere preparation technology's research ", disclose a kind of preparation technology who contains the lactic acid microspheres of ciprofloxacin medicine in the article; Zhao Ruiling has delivered the article of " preparation of amycin polylactic acid microsphere and release behaviour in vitro research " on " the 24th the 2nd phase of volume of Chinese Hospitals pharmaceutical journal 2004 ", disclose a kind of preparation technology who contains the lactic acid microspheres of amycin medicine in the article; Li Yan etc. have delivered " preparation of polylactic acid, poly (lactic acid-glycolic acid) copolymer microsphere and influence the progress of its qualitative factor " review article on " foreign medical science pharmacy fascicle; June calendar year 2001; the 28th the 3rd phase of volume ", disclose the preparation of various microspheres in the article and influenced the factor of microspheres quality.
The manufacturing of the present invention's product can adopt emulsifying-solvent evaporated method preparation to contain the polylactic acid microsphere of developing material (2), and specific practice is as follows:
An amount of polylactic acid is dissolved in the organic solvent (as dichloromethane), and a certain proportion of developing material (2) is scattered in wherein, under certain mixing speed, slowly be added in the disperse medium (PVA solution), behind the emulsifying certain hour, be poured into volatilization organic solvent in the dispersive medium (low concentration PVA solution) again, centrifugal then, filter, clean, dry, screening, sterilization, promptly get the polylactic acid microsphere that contains developing material (2).
In the present embodiment, developing material (2) can also adopt the surplus materials after non-ionic contrast agent iohexol (Iohexol) or Iopromide (Iopromide) or B-15000 (Iopamidol), nonionic dimer iotrolan intravascular contrast media such as (Iotrolan) are handled through vacuum freeze-drying method.Adopt essentially identical technology also can make the present invention's Biodegradable imaging microspheres vascular embolization material.
Embodiment 2: the present invention's development poly (lactic acid-glycolic acid) copolymer (PLGA) microsphere
The production method of present embodiment product is substantially the same manner as Example 1, difference is biodegradation material (1) is chosen as the poly (lactic acid-glycolic acid) copolymer, and developing material (2) can be selected from a kind of in the following material: the surplus materials after the ionic contrast agent cardiografin is handled through vacuum freeze-drying method; Surplus materials after non-ionic contrast agent iohexol (Iohexol) or Iopromide (Iopromide) or B-15000 (Iopamidol) are handled through vacuum freeze-drying method; Surplus materials after nonionic dimer iotrolan intravascular contrast media such as (Iotrolan) is handled through vacuum freeze-drying method.
The present invention's development PLA microsphere and development PLGA microsphere all adopt the emulsifying dispersion method and are separated the coacervation preparation.In addition, can also adopt supercritical flow new, the solution atomization that will comprise biodegradation material (1) and developing material (2) sprays into and contains compression CO
2Container in because organic solvent is at CO
2In extraction and diffusion cause polymer precipitation and prepared development biodegradation material microspheres such as development PLA, development PLGA, the microsphere flowability, the outward appearance that obtain are all better, and have reduced dosage of surfactant and residual solvent amount.
Embodiment 3: the present invention's development polycaprolactone-poly-second lactone-poly-glycolide copolymer microsphere
The production method of present embodiment product is substantially the same manner as Example 1, difference is biodegradation material (1) is chosen as polycaprolactone-poly-second lactone-poly-glycolide copolymer, and developing material (2) can be selected from a kind of in the following material: the surplus materials after the ionic contrast agent cardiografin is handled through vacuum freeze-drying method; Surplus materials after non-ionic contrast agent iohexol (Iohexol) or Iopromide (Iopromide) or B-15000 (Iopamidol) are handled through vacuum freeze-drying method; Surplus materials after nonionic dimer iotrolan intravascular contrast media such as (Iotrolan) is handled through vacuum freeze-drying method.Adopt the general emulsifying dispersion method and the coacervation that is separated to prepare microsphere or CO
2Supercritical flow new prepares microsphere.
Embodiment 4: the present invention's development chitosan microball
The production method of present embodiment product is substantially the same manner as Example 1, difference is biodegradation material (1) is chosen as chitosan, developing material (2) adopts emulsifying dispersion method or be separated coacervation or CO for the surplus materials of cardiografin after handling through vacuum freeze-drying method
2The supercritical fluid legal system is equipped with cardiografin-chitosan development microsphere of the present invention.
Embodiment 5: the present invention's development gelatine microsphere
The production method of present embodiment product is substantially the same manner as Example 1, difference is biodegradation material (1) is chosen as gelatin, developing material (2) adopts emulsifying dispersion method or be separated coacervation or CO for the surplus materials of cardiografin after handling through vacuum freeze-drying method
2The supercritical fluid legal system is equipped with cardiografin-gelatin development microsphere of the present invention.
In addition, molecular weight that can be by regulating biodegradation material (1) and the chemical group method of grading, the degradation time of control the present invention's development microsphere, convenient clinical needs, as: the microsphere of degraded in 7 days, the microsphere of degraded in 15 days, the microsphere of degraded in 30 days, the microsphere of degraded in 60 days, the microsphere of degraded in 180 days etc.
Should be noted that herein openly can replace with the identical structure of other effect that the embodiment that the present invention introduced simultaneously realizes unique structure of the present invention with the structure of explanation.Though preferential embodiment of the present invention is introduced in this article and is illustrated; but those skilled in the art know and know that these embodiment illustrate; those skilled in the art can make countless variations, improvement and replacement; and can not break away from the present invention; therefore, should be according to the next qualification protection scope of the present invention of the spirit and scope of appending claims of the present invention.
Claims (6)
1, a kind of Biodegradable imaging microspheres vascular embolization material, it is characterized in that: described a kind of Biodegradable imaging microspheres vascular embolization material is made up of the biodegradation material that can implant in blood vessel (1) and roentgenopaque developing material (2), and biodegradation material (1) parcel developing material (2) forms grain structure.
2, a kind of Biodegradable imaging microspheres vascular embolization material according to claim 1, it is characterized in that described biodegradation material (1) refers to: polylactic acid, the poly (lactic acid-glycolic acid) copolymer, polylactic acid-copolyether, polycaprolactone, polycaprolactone-polyether block copolymer, the polycaprolactone copolymer, polycaprolactone-polyethers-polylactide copolymer, poly-(Acetic acid, hydroxy-, bimol. cyclic ester-polylactide) copolymer, Acetic acid, hydroxy-, bimol. cyclic ester-L-lactide-caprolactone copolymer, polycaprolactone-poly-second lactone-poly-glycolide copolymer and other fatty acid polyglycol lactone copolymers, and glue protein, chitin, chitosan, the blend or derivatives thereof of gelatin or alginate natural high molecular substance or above various materials.
3, a kind of Biodegradable imaging microspheres vascular embolization material according to claim 1 is characterized in that described developing material (2) includes effective development composition of intravascular contrast media.
4, a kind of Biodegradable imaging microspheres vascular embolization material according to claim 3, the effective development composition that it is characterized in that described intravascular contrast media comprise a kind of in the following material at least: the surplus materials after the ionic contrast agent cardiografin is handled through vacuum freeze-drying method; Surplus materials after non-ionic contrast agent iohexol (iohexol) or Iopromide (iopromide) or B-15000 (iopamidol) are handled through vacuum freeze-drying method; Surplus materials after nonionic dimer iotrolan (iotrolan) is handled through vacuum freeze-drying method.
5, a kind of Biodegradable imaging microspheres vascular embolization material according to claim 1, the proportion that it is characterized in that described a kind of Biodegradable imaging microspheres vascular embolization material is at 0.8g/cm
3To 1.65g/cm
3Between, its optimum is 1.0g/cm
3To 1.35g/cm
3
6, a kind of Biodegradable imaging microspheres vascular embolization material according to claim 1, the diameter that it is characterized in that described a kind of Biodegradable imaging microspheres vascular embolization material is between 10 μ m to 1500 μ m, size according to diameter of micro ball, be divided into different brackets, 10 μ m～150 μ m, 100 μ m～350 μ m, 200 μ m～500 μ m, 400 μ m～650 μ m, 500 μ m～750 μ m, 650 μ m～950 μ m, 850 μ m～1100 μ m, 1000 μ m～1350 μ m, 1250 μ m～1500 μ m.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200710026274 CN101007190A (en) | 2007-01-12 | 2007-01-12 | Biodegradable imaging microspheres vascular embolization material |
| US12/523,046 US20100021550A1 (en) | 2007-01-12 | 2008-01-14 | Radiopaque biodegradable vascular embolic microspheres |
| PCT/CN2008/070100 WO2008086756A1 (en) | 2007-01-12 | 2008-01-14 | Developable biodegradable microspheric blood vessel embolism materials |
| EP08700770A EP2105150A1 (en) | 2007-01-12 | 2008-01-14 | Developable biodegradable microspheric blood vessel embolism materials |
| JP2009545051A JP2010515493A (en) | 2007-01-12 | 2008-01-14 | Radiopaque biodegradable microsphere type vascular embolization material |
| BRPI0807024-5A BRPI0807024A2 (en) | 2007-01-12 | 2008-01-14 | Biodegradable and radiopaque microspheric material for vascular embulism |
| IL199805A IL199805A0 (en) | 2007-01-12 | 2009-07-12 | Developable biodegradable microspheric blood vessel embolism materials |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200710026274 CN101007190A (en) | 2007-01-12 | 2007-01-12 | Biodegradable imaging microspheres vascular embolization material |
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| Publication Number | Publication Date |
|---|---|
| CN101007190A true CN101007190A (en) | 2007-08-01 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200710026274 Pending CN101007190A (en) | 2007-01-12 | 2007-01-12 | Biodegradable imaging microspheres vascular embolization material |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008086756A1 (en) * | 2007-01-12 | 2008-07-24 | Yanfang Li | Developable biodegradable microspheric blood vessel embolism materials |
| CN102139127A (en) * | 2011-03-17 | 2011-08-03 | 杭州艾力康医药科技有限公司 | Developable gelatin sponge suppository and preparation process thereof |
| CN102139128A (en) * | 2011-03-22 | 2011-08-03 | 杭州艾力康医药科技有限公司 | Developable polyvinyl alcohol microballoon/particle embolic agent and preparation process thereof |
| CN102397590A (en) * | 2010-09-07 | 2012-04-04 | 微创医疗器械(上海)有限公司 | Biodegradable bracket |
| CN103751856A (en) * | 2014-01-22 | 2014-04-30 | 同济大学 | Polylactic acid embolism microsphere with good dispersity |
| CN105214145A (en) * | 2014-06-23 | 2016-01-06 | 李茂全 | The application of polylactic acid microsphere in hemorrhage |
| CN113398320A (en) * | 2021-02-04 | 2021-09-17 | 艾柯医疗器械(北京)有限公司 | Suspended particle contrast liquid embolic agent and preparation method thereof |
| 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 |
-
2007
- 2007-01-12 CN CN 200710026274 patent/CN101007190A/en active Pending
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008086756A1 (en) * | 2007-01-12 | 2008-07-24 | Yanfang Li | Developable biodegradable microspheric blood vessel embolism materials |
| CN102397590A (en) * | 2010-09-07 | 2012-04-04 | 微创医疗器械(上海)有限公司 | Biodegradable bracket |
| CN102139127A (en) * | 2011-03-17 | 2011-08-03 | 杭州艾力康医药科技有限公司 | Developable gelatin sponge suppository and preparation process thereof |
| CN102139128A (en) * | 2011-03-22 | 2011-08-03 | 杭州艾力康医药科技有限公司 | Developable polyvinyl alcohol microballoon/particle embolic agent and preparation process thereof |
| CN103751856A (en) * | 2014-01-22 | 2014-04-30 | 同济大学 | Polylactic acid embolism microsphere with good dispersity |
| CN103751856B (en) * | 2014-01-22 | 2015-07-29 | 同济大学 | A kind of polylactic acid embolism microsphere with good dispersion |
| CN105214145A (en) * | 2014-06-23 | 2016-01-06 | 李茂全 | The application of polylactic acid microsphere in hemorrhage |
| CN113398320A (en) * | 2021-02-04 | 2021-09-17 | 艾柯医疗器械(北京)有限公司 | Suspended particle contrast liquid embolic agent and preparation method thereof |
| CN113398320B (en) * | 2021-02-04 | 2022-05-13 | 艾柯医疗器械(北京)有限公司 | Suspended particle contrast liquid embolic agent and preparation method thereof |
| WO2022166568A1 (en) * | 2021-02-04 | 2022-08-11 | 艾柯医疗器械(北京)有限公司 | Suspended particle contrast liquid embolic agent and preparation method therefor |
| 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 |
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Open date: 20070801 |