CN102552108B - Liquid suppository and preparation method thereof - Google Patents
Liquid suppository and preparation method thereof Download PDFInfo
- Publication number
- CN102552108B CN102552108B CN201210028150.4A CN201210028150A CN102552108B CN 102552108 B CN102552108 B CN 102552108B CN 201210028150 A CN201210028150 A CN 201210028150A CN 102552108 B CN102552108 B CN 102552108B
- Authority
- CN
- China
- Prior art keywords
- copolymer
- embolizing agent
- add
- make
- liquid embolizing
- 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.)
- Active
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses a liquid suppository, a purpose thereof, and a preparation method thereof. The liquid suppository is formed by a copolymer of hydroxyethyl methacrylate and methylacrylate, water, absolute alcohol, and a developing agent solution, which are mixed according to a certain ratio. Clinically, the suppository is used in the treatment of various tumor diseases. The preparation method of the suppository mainly comprises steps of polymerization, purification, drying, and auxiliary solvent addition.
Description
Technical field
The present invention relates to medical technical field, specifically relate to a kind of liquid embolizing agent and uses thereof and preparation method.
Background technology
Interventional therapy, through the development of more than 30 years, has been called three large pillar subjects now together with surgery, internal medicine.A kind of medical apparatus and instruments suppository of wherein often using in interventional therapy is also widely applied, and clinical more conventional suppository mainly contains absorbable gelatin sponge particle suppository, embolism agent of granule of polyvinyl alcohol, N-butyl cyanoacrylate, ethanol, spring embolus at present.Above-mentioned suppository all exists sticky conduit and intravasation branch thereof to cause the danger of complication in various degree.
Retrieve current document and patent thereof, not yet find the compound of the copolymer of hydroxyethyl methylacrylate and methacrylate, and for the report of liquid embolizing agent.
Summary of the invention
The object of the invention is to overcome the deficiency of above-mentioned technology, a kind of liquid embolizing agent and uses thereof and preparation method are provided.
The present invention is achieved by the following technical solutions: by hydroxyethyl methylacrylate, methyl methacrylate, dehydrated alcohol, benzyl alcohol is in 10～50%: 0.5～10%: 40～80ml: 0.1～10% ratio adds in there-necked flask, stirs, add 0.02g initiator azodiisobutyronitrile, the post-heating that stirs carries out polyreaction, and reaction temperature is 50～95 DEG C, after having reacted, remove thermal source, room temperature is cooling.Pour cooled copolymer into 100ml distilled water, make its Precipitation, get precipitation and add 5ml ethanol to make it to dissolve again, add 100ml distilled water to make it again to separate out, so repeatedly several times, finally by drying precipitate.Copolymer, water, dehydrated alcohol, developer solution certain proportion are mixed, and stirring and dissolving, obtains liquid embolizing agent of the present invention.
This liquid embolizing agent proves through animal experiment: 1. product of the present invention, as a kind of non-adhesive liquid embolic material, has easy judgement thromboembolism starting point and terminal, easily by carrying microtubular, and can compatible various commercially available microtubulars; 2. the optimal injection flow velocity of embolism materials is 0.083ml/min; 3. low, the good biocompatibility of product viscosity of the present invention, no cytotoxicity, controllability are good; 4. 16% ethanol is safe as product solvent of the present invention, does not cause the untoward reaction such as the inside and outside destruction of blood vessel; 5. product effect of embolization of the present invention is reliable and stable.
Clinical trial proves: product of the present invention is applicable to the embolotherapy for good pernicious substantial viscera tumor and hemorrhage pathological changes.Product of the present invention can directly inject aneurysm tumor intracavity, adapts to difformity and big or small aneurysm cavity completely, makes not stay between tumor wall and embolism materials any space, thereby reaches the object of permanent thromboembolism.
In the present invention, hydroxyethyl methylacrylate proportion in copolymer is 50%～99%, preferably 85～95%.
In the present invention, copolymer shared ratio in liquid embolizing agent is 1%～99%, preferably 60～80%.
Liquid embolizing agent of the present invention, is liquid under normal conditions, after contact blood of human body, is solid.Can be applied to the various tumors for the treatment of.
The invention has the advantages that:
1. liquid embolizing agent of the present invention is liquid before not contacting blood, not sticky conduit in course of conveying.
2. liquid embolizing agent of the present invention is solidified into rapidly solid block after contact blood, and directly vascular embolization, is difficult for intravasation branch, thereby avoids the generation of complication.
3. the tool developing function of product of the present invention own, therefore easily judges thromboembolism starting point and terminal, makes thromboembolism position more accurate.
4. carry without organic solvent (DMSO).
5. product of the present invention and various microtubular are compatible good, for interventional therapy operation provides larger selection space.
6. product of the present invention has good biocompatibility, can not cause chemistry or immunization, application safety after thromboembolism.
Detailed description of the invention
Detailed description of the invention below in conjunction with specific embodiment is described in further detail foregoing of the present invention:
Embodiment 1
By hydroxyethyl methylacrylate, methyl methacrylate, dehydrated alcohol, benzyl alcohol was in 50%: 50%: 40ml: 10% ratio adds in there-necked flask, stirred, add 0.02g initiator azodiisobutyronitrile, the post-heating that stirs carries out polyreaction, and reaction temperature is 85 DEG C, after having reacted, remove thermal source, room temperature is cooling.Pour cooled copolymer into 100ml distilled water, make its Precipitation, get precipitation and add 5ml ethanol to make it to dissolve again, add 100ml distilled water to make it again to separate out, so repeatedly several times, finally by drying precipitate.Copolymer, water, dehydrated alcohol, developer solution certain proportion are mixed, and stirring and dissolving, to obtain final product.
Embodiment 2
By hydroxyethyl methylacrylate, methyl methacrylate, dehydrated alcohol, benzyl alcohol was in 50%: 0.5%: 40ml: 10% ratio adds in there-necked flask, stirred, add 0.02g initiator azodiisobutyronitrile, the post-heating that stirs carries out polyreaction, and reaction temperature is 95 DEG C, after having reacted, remove thermal source, room temperature is cooling.Pour cooled copolymer into 100ml distilled water, make its Precipitation, get precipitation and add 5ml ethanol to make it to dissolve again, add 100ml distilled water to make it again to separate out, so repeatedly several times, finally by drying precipitate.Copolymer, water, dehydrated alcohol, developer solution certain proportion are mixed, and stirring and dissolving, to obtain final product.
Embodiment 3
By hydroxyethyl methylacrylate, methyl methacrylate, dehydrated alcohol, benzyl alcohol was in 50%: 0.5%: 80ml: 0.1% ratio adds in there-necked flask, stirred, add 0.02g initiator azodiisobutyronitrile, the post-heating that stirs carries out polyreaction, and reaction temperature is 50 DEG C, after having reacted, remove thermal source, room temperature is cooling.Pour cooled copolymer into 100ml distilled water, make its Precipitation, get precipitation and add 5ml ethanol to make it to dissolve again, add 100ml distilled water to make it again to separate out, so repeatedly several times, finally by drying precipitate.Copolymer, water, dehydrated alcohol, developer solution certain proportion are mixed, and stirring and dissolving, to obtain final product.
Embodiment 4
By hydroxyethyl methylacrylate, methyl methacrylate, dehydrated alcohol, benzyl alcohol was in 10%: 0.5%: 80ml: 0.1% ratio adds in there-necked flask, stirred, add 0.02g initiator azodiisobutyronitrile, the post-heating that stirs carries out polyreaction, and reaction temperature is 50 DEG C, after having reacted, remove thermal source, room temperature is cooling.Pour cooled copolymer into 100ml distilled water, make its Precipitation, get precipitation and add 5ml ethanol to make it to dissolve again, add 100ml distilled water to make it again to separate out, so repeatedly several times, finally by drying precipitate.Copolymer, water, dehydrated alcohol, developer solution certain proportion are mixed, and stirring and dissolving, to obtain final product.
Embodiment 5
By hydroxyethyl methylacrylate, methyl methacrylate, dehydrated alcohol, benzyl alcohol was in 50%: 1%: 80ml: 1% ratio adds in there-necked flask, stirred, add 0.02g initiator azodiisobutyronitrile, the post-heating that stirs carries out polyreaction, and reaction temperature is 50 DEG C, after having reacted, remove thermal source, room temperature is cooling.Pour cooled copolymer into 100ml distilled water, make its Precipitation, get precipitation and add 5ml ethanol to make it to dissolve again, add 100ml distilled water to make it again to separate out, so repeatedly several times, finally by drying precipitate.Copolymer, water, dehydrated alcohol, developer solution certain proportion are mixed, and stirring and dissolving, to obtain final product.
Embodiment 6
Select 6 of healthy family pigs, body weight 25～30kg, male and female are not limit.Preoperative 12h fasting, preoperative 30min intramuscular injection atropine 1mg, application ketalar in conjunction with Midazolam by family's pig general anesthesia to satisfactory state.Isolate afterwards strand portion's arteria saphena, cut, insert 5F catheter sheath, the capable common carotid artery intubate of application 5F angiography catheter, injection of contrast agent row common carotid artery radiography.Under roadmap guides, select and recommend into ascending pharyngeal artery super microtubular through guiding catheter afterwards, microtubular head end is placed on the far-end of rami pharyngei arteriae pharyngeae ascendentis, row microtubular radiography.Under fluoroscopic monitoring, inject product of the present invention with 1ml syringe through microtubular, till thromboembolism no longer develops to common carotid artery radiography check thromboembolism side RMB.By the follow-up observation of predetermined packet of packets time, the follow-up observation time is respectively: after thromboembolism at once, 1 week, 4 weeks, 8 weeks, 12 weeks, 24 weeks, follow-up observation content is animal survival situation (diet, nervous system), check radiography, observes and has or not revascularization phenomenon, finally put to death animal, open cranium complete taking-up bilateral RMB and brain and carry out histology's pathological examination, observe variation in RMB blood vessel and around, histology's pathological examination divides three groups of acute stages (after thromboembolism at once, after thromboembolism 1 week) 2, 1 of subacute stage (after thromboembolism 4 weeks), (after thromboembolism 8 weeks chronic phase, 12 weeks, 24 weeks) 3. in experiment, 6 of 6 boss pigs one-sided strange nets are carried out to successful thromboembolism, in thromboembolism and follow-up observation process, do not run into technical difficulty, the effect of embolization of 6 pigs is comparatively satisfied, there is not plugging phenomenon in thromboembolism process, tube drawing is smooth.And reconfirm that copolymer is good to dissimilar microtubular compatibility.After thromboembolism, follow-up observation laboratory animal is all survived well, and diet and nerve, moving situation all, less than abnormal, also occur without deformity.At once radiography in plan follow-up observation phase interimage check after thromboembolism, ascending pharyngeal artery/strange the net that shows all pig thromboembolism sides is showed no development, wherein ramus anastomoticus (ramu sanastomoticus) RA and arteriae anastomotica (arterial anastomotica) the AA development of external carotid artery crossed by the strange Netcom of 3 pigs, and compared with angiography before thromboembolism, RA and AA have increasing in various degree thick.After sacrifice of animal, dissect, gross specimen is observed, and cerebral tissue has no abnormal changes, thromboembolism in various degree as seen in RMB blood vessel, and the RMB of institute's thromboembolism is real compared with offside matter.Histological observation shows no obvious abnormalities, and pathology light microscopic finding: acute stage, subacute stage, chronic phase are showed no obvious inflammatory reaction has no blood vessel wall destruction and dysmorphology and changes.
Embodiment 7
Select patient's 20 examples, male's 8 examples, women's 12 examples, wherein primary hepatocarcinoma (HCC) 10 examples, hysteromyoma 9 examples, cervical cancer 1 example.All confirm tumor staining through selective arterial according to shadow, after tumor vessel, inject product of the present invention through tremulous pulse, until blood flow is stagnated.
Observe symptom after clinic operation: all patients shows general performance after thromboembolism in various degree, be pain substantially, and 1 example performance body temperature slightly raises (38 DEG C), within 3 days, recovery is normally afterwards.
Postoperative January imaging examination: PR8 example in Patients with Primary, NC2 example, total effective rate reaches 100%; Patients with uterine myoma all obtains remission in various degree, and total effective rate is 100%;
Clinical trial certificate product of the present invention is for innocent and malignant tumour interventional embolization determined curative effect, safe and reliable.
Claims (4)
1. a liquid embolizing agent, is characterized in that: in described liquid embolizing agent, containing the copolymer of hydroxyethyl methylacrylate and methyl methacrylate, this liquid embolizing agent is liquid under normal conditions, after contact blood of human body, is solid; Described liquid embolizing agent prepares by the following method: by hydroxyethyl methylacrylate, methyl methacrylate, dehydrated alcohol, benzyl alcohol was in 50%: 0.5%: 40ml: 10% ratio adds in there-necked flask, stirred, add 0.02g initiator azodiisobutyronitrile, the post-heating that stirs carries out polyreaction, and reaction temperature is 95 DEG C, after having reacted, remove thermal source, room temperature is cooling; Pour cooled copolymer into 100ml distilled water, make its Precipitation, get precipitation and add 5m1 ethanol to make it to dissolve again, add 100ml distilled water to make it again to separate out, so repeatedly several times, finally drying precipitate is obtained to copolymer; Copolymer, water, dehydrated alcohol, developer solution certain proportion are mixed, and stirring and dissolving, obtains liquid embolizing agent.
2. liquid embolizing agent according to claim 1, is characterized in that copolymer shared ratio in liquid embolizing agent is 1%～99%.
3. the application of liquid embolizing agent claimed in claim 1 in the suppository of preparation treatment tumor.
4. a preparation method for liquid embolizing agent, is characterized in that: described preparation method step is as follows:
By hydroxyethyl methylacrylate, methyl methacrylate, dehydrated alcohol, benzyl alcohol was in 50%: 0.5%: 40ml: 10% ratio adds in there-necked flask, stirred, add 0.02g initiator azodiisobutyronitrile, the post-heating that stirs carries out polyreaction, and reaction temperature is 95 DEG C, after having reacted, remove thermal source, room temperature is cooling; Pour cooled copolymer into 100ml distilled water, make its Precipitation, get precipitation and add 5ml ethanol to make it to dissolve again, add 100ml distilled water to make it again to separate out, so repeatedly several times, finally drying precipitate is obtained to copolymer; Copolymer, water, dehydrated alcohol, developer solution certain proportion are mixed, and stirring and dissolving, obtains liquid embolizing agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210028150.4A CN102552108B (en) | 2012-01-17 | 2012-01-17 | Liquid suppository and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210028150.4A CN102552108B (en) | 2012-01-17 | 2012-01-17 | Liquid suppository and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102552108A CN102552108A (en) | 2012-07-11 |
| CN102552108B true CN102552108B (en) | 2014-06-04 |
Family
ID=46399580
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210028150.4A Active CN102552108B (en) | 2012-01-17 | 2012-01-17 | Liquid suppository and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102552108B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103315945B (en) * | 2013-06-21 | 2014-12-24 | 清华大学 | Vascular embolic agent as well as injection device and application thereof |
| CN115068665A (en) * | 2022-02-09 | 2022-09-20 | 上海市第十人民医院 | Liquid embolic agent |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1192654A (en) * | 1995-07-27 | 1998-09-09 | 微治疗公司 | Novel embolizing compositions |
-
2012
- 2012-01-17 CN CN201210028150.4A patent/CN102552108B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1192654A (en) * | 1995-07-27 | 1998-09-09 | 微治疗公司 | Novel embolizing compositions |
Non-Patent Citations (6)
| Title |
|---|
| Kiyoshi Kazekawa et al.Nontoxic Embolic Liquids for Treatment of Arteriovenous Malformations.《Journal of Biomedical Materials Research》.1998,第38卷(第2期),79页右栏至80页左栏、表1及表2. |
| Nontoxic Embolic Liquids for Treatment of Arteriovenous Malformations;Kiyoshi Kazekawa et al;《Journal of Biomedical Materials Research》;19981206;第38卷(第2期);79页右栏至80页左栏、表1及表3 * |
| 用于肿瘤栓塞术的药用材料研究进展;邹巧根 等;《药学进展》;20081231;第32卷(第1期);第30页左栏 * |
| 甲基丙烯酸-2-羟基乙酯共聚物栓塞脑动静脉畸形的实验研究;盛希忠 等;《中华医学杂志》;20060117;第86卷(第3期);153页左栏及154页左栏 * |
| 盛希忠 等.甲基丙烯酸-2-羟基乙酯共聚物栓塞脑动静脉畸形的实验研究.《中华医学杂志》.2006,第86卷(第3期),153页左栏及154页左栏. |
| 邹巧根 等.用于肿瘤栓塞术的药用材料研究进展.《药学进展》.2008,第32卷(第1期),第30页左栏. |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102552108A (en) | 2012-07-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6789329B2 (en) | Liquid embolic composition | |
| CN105462142B (en) | A kind of temperature sensitive type interpenetration network hydrogel material and its preparation method and application | |
| ES2296607T3 (en) | CYANOACRYLATES THAT INCLUDE INHIBITORS AND AN OPACIFYING AGENT. | |
| AU2019264567B2 (en) | In situ solidifying complex coacervates and methods of making and using thereof | |
| JP5456974B2 (en) | Compositions, systems and methods for treating vascular disorders | |
| JP2001509133A (en) | Compositions for use in occluded vessels | |
| JP5612279B2 (en) | Non-human animal model of myocardial infarction and production method thereof | |
| Akmangit et al. | Preliminary experience with squid: a new liquid embolizing agent for AVM, AV fistulas and tumors | |
| JP2003500114A (en) | Novel high viscosity embolization composition | |
| Owen et al. | A preclinical study of the safety and efficacy of Occlusin™ 500 artificial embolization device in sheep | |
| CN107899064A (en) | A kind of medicine-carried and the preparation method and its usage for having the liquid embolizing agent of developability concurrently | |
| US7374568B2 (en) | Methods for embolizing aneurysmal sites with a high viscosity embolizing composition | |
| Oka et al. | Preoperative superselective embolization of skull-base meningiomas: indications and limitations | |
| Regine et al. | Embolization of traumatic and non-traumatic peripheral vascular lesions with Onyx | |
| CN102552108B (en) | Liquid suppository and preparation method thereof | |
| Vollherbst et al. | Extra-small dual-lumen micro-balloon catheters can improve endovascular embolization: an experimental in vivo and in vitro study | |
| WO2020099190A1 (en) | Polymer for liquid embolic agents and method of obtaining same | |
| WO2018137633A1 (en) | Liquid embolic material and preparation method therefor | |
| JPWO2006030737A1 (en) | Creation of arterial occlusive disease model animals | |
| RU2735500C9 (en) | Method for embolisation of cerebral aneurysms with a liquid adhesive composition | |
| JP2002504406A (en) | Gynecological endovascular embolization treatment | |
| CA3225248A1 (en) | Compositions for embolization | |
| Khan et al. | Embolization for Epistaxis and Cranial Tumors | |
| Wilkinson et al. | 310 Increased Rate of Subarachnoid Hemorrhage in Polycystic Kidney Disease Despite Screening | |
| Mori et al. | Preliminary experiences with near-infrared fluorescence image-guided meningioma removal after embolization with indocyanine green and Eudragit in ethanol solution: Green embolization technique |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170505 Address after: 322200 Zhejiang, Jinhua County, Pujiang Province, No. 133, golden base road Patentee after: Zhejiang better medical instrument Co., Ltd. Address before: 322200 No. 133, golden base road, Pujiang County, Zhejiang Province Patentee before: Tang Xiaoguo |
|
| TR01 | Transfer of patent right | ||
| CP03 | Change of name, title or address |
Address after: 312366 Medical Device Science and Technology Industrial Park No. 1 Yunhai Road, Lihai Town, Binhai New Town, Shaoxing, Zhejiang Province Patentee after: Zhejiang best biological material Co., Ltd. Address before: 322200 Zhejiang, Jinhua County, Pujiang Province, No. 133, golden base road Patentee before: Zhejiang better medical instrument Co., Ltd. |
|
| CP03 | Change of name, title or address |