CN102028974A - Repair material for promoting regeneration of defective nerves - Google Patents
Repair material for promoting regeneration of defective nerves Download PDFInfo
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- CN102028974A CN102028974A CN 200910177405 CN200910177405A CN102028974A CN 102028974 A CN102028974 A CN 102028974A CN 200910177405 CN200910177405 CN 200910177405 CN 200910177405 A CN200910177405 A CN 200910177405A CN 102028974 A CN102028974 A CN 102028974A
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Abstract
The invention relates to a repair material for promoting regeneration of defective nerves, a preparation method thereof and application of a porogen in the preparation of repair materials for promoting the regeneration of the defective nerves.
Description
Technical field
The present invention relates to a kind of repair materials that promotes damaged property neuranagenesis, its preparation method, and porogen is used for promoting the repair materials purposes of damaged property neuranagenesis in preparation.
Background technology
The peripheral nerve defection damage is a class incidence rate and the higher common damage of disability rate, nerve autograft is clinical the most frequently used method, be the goldstandard of repairing neurologic defect, but can cause disappearance and sensory disturbance, traumatic neuroma easily takes place for district function of nervous system, cause local pain, the patient often is difficult to accept, and it is less that allogeneic nerve is implanted in clinical practice, mainly is that immunological rejection is heavy, influence regeneration effect, and it is limited to originate.Silica gel tube is the artificial material that is applied to clinical reparation neurologic defect the earliest, can not carry out mass exchange with the external world; Though it can demonstrate neural sensation, the good recovery effects of motion at short notice, but it has and can not be absorbed by the body, and is stranded in for a long time in the human body to compress nerve, and function affects the nerves, need carry out the defective that second operation takes out conduit, limit clinical application range.
The method of clinical repair neurologic defect all exists inevitable defective at present, the biological example type conduit patient self that generally has drawn from, can cause the patient to organize nonvolatil afunction so undoubtedly for the district, and can cause the inflammation of tissue for the district, simultaneously, also will be the problem that is difficult to overcome in the application for district's material deficiency.Therefore, researcher to using artificial nerve trachea, is chosen attention diversion suitable material the material preferably from some biocompatibility of natural and synthetic and is prepared conduit, the regeneration of guiding injured nerve.Use synthetic material to prepare conduit and have easy to processly, can accurately control specification, character, the advantage of good reproducibility is the direction of present people's research.Biodegradation material is introduced peripheral nerve promote its regenerated conduit, the inconvenience of having avoided second operation to take out has a good application prospect undoubtedly.Chitin pipe, chitosan pipe are to study many absorbability nerve tracheas at present.The problem that this material exists at present is that fragility is higher, easy cracked subsiding when tube wall is thin; Blocked up as the tube wall making, then can prolong soak time, regenerating nerve is produced the local compression effect.The biodegradable synthetic material of other reports has: polylactic acid, poly lactose, polyurethane, dehydrated crosslinking gelatin etc.These materials all have excellent biological compatibility, and can be absorbed by human body, are obtaining progress in various degree aspect the bridge joint peripheral nerve defection experimentation.
Ideal nerve trachea at first will satisfy the needed basic demand of nerve growth, i.e. (1) conduit degraded can be synchronous with nerve recovery, and degraded fully; (2) the favorable tissue compatibility and avirulence; (3) have slick inner surface, avoid influencing the growth of regenerating nerve, and be easy to cell growth and stick; (4) tube wall has the selection permeability, can draw nutrient substance from external world's tissue; (5) good physical and mechanical properties and pliability; (6) be easy to machine-shaping.Putting before this, by transplantation experiments in the animal body, observing, measuring the degree of regenerating nerve functional rehabilitation and the number of neuranagenesis etc.
Summary of the invention
The inventor finds under study for action by the macromolecular material porogen being joined the reparation conduit that is formed for damaged property neuranagenesis in the Biodegradable material, make the reparation conduit have half good permeability, for damaged property nerve provides good regenerative environ-ment, thereby make damaged property nerve be able to better regeneration.
The present invention relates to a kind of repair materials or compositions that promotes damaged property neuranagenesis thus, and it comprises Biodegradable material compatible with human body and macromolecular material porogen.
The invention further relates to the product that is used to promote damaged property neuranagenesis, it is formed by repair materials or compositions, and described repair materials or compositions comprise Biodegradable material compatible with human body and macromolecular material porogen.
According to the present invention, term among the present invention " product " says it can is tube for example, as conduit.The length of this conduit is not particularly limited, and it can be decided according to concrete user demand, and the thickness of pipe does not have special requirement, can be 100-200 μ m, and the internal diameter of pipe is not particularly limited, and can be 1.0-2.0mm.Further, there are some holes in the tube wall of above-mentioned conduit, and the aperture in these holes is not particularly limited, and can be 0＜aperture＜50 μ m, preferred 0＜aperture＜10 μ m.
The invention still further relates to the purposes that the macromolecular material porogen is used for providing the repair materials of damaged property neuranagenesis or compositions or repairs product in preparation.
Further, the content (by weight percentage calculate) of macromolecular material porogen in the present composition or product or conduit is 1～40% among the present invention.
Further, the Biodegradable material compatible with human body is meant solid-state and the water-insoluble macromolecular material among the present invention, say it to be the polylactic acid or derivatives thereof for example, gelatin and derivant thereof, chitosan, polyurethane, water-insoluble cellulose family and derivant thereof etc.
According to the present invention, the above-mentioned biodegradable product compatible with human body all can be available from market.Polylactic acid derivative is said for example and is polylactic acid-polyglycol copolymer, lactic acid/co-glycolic acid (PLGA), lactic acid/co-glycolic acid-ethylene glycol copolymer.
Porogen is the macromolecular material porogen among the present invention, says to can be the Polyethylene Glycol that comprises PEG400～Macrogol 3000 0 polyamino acid, glucosan, polyvinyl alcohol, water-soluble cellulose class and derivant thereof for example.
PEG400～Macrogol 3000 0 is meant that mean molecule quantity is 400～30000 Polyethylene Glycol.
The invention still further relates to a kind of repair materials or preparation of compositions method that promotes damaged property neuranagenesis, it comprises the Biodegradable material compatible with human body is dissolved in the organic solvent, adds the macromolecular material porogen then, and ultrasonic dispersing is even.
The invention still further relates to the preparation method of the product that is used to promote damaged property neuranagenesis, it comprises the Biodegradable material compatible with human body is dissolved in the organic solvent, adds the macromolecular material porogen then, and ultrasonic dispersing is even; Utilize suitable mold, adopt solvent evaporation method to prepare required product.
Description of drawings
Fig. 1 prepares the reparation conduit that is used to promote neuranagenesis that 1-7 makes for the present invention, and as seen from Figure 1, the nerve trachea of preparation is transparence, and smooth surface has better toughness, and is not yielding.
Fig. 2 prepares the catheter surface sem photograph of 1-7 gained conduit for the present invention.
Fig. 2 A is the dummy pipe inner surface figure that implants.
Fig. 2 B is the dummy pipe outer surface figure that implants.
Fig. 2 C is for implanting conduit inner surface figure back 1 month.
Fig. 2 D is for implanting catheter outer surface figure back 1 month.
Fig. 3 is the regenerating nerve figure in the nerve trachea after three months.
Fig. 4 is art side and strong side triceps surae comparison diagram.
Fig. 5 is the regenerating nerve transmission electron microscope picture, wherein occurs the myelinated nerve fiber that diameter differs in the nerve trachea.
Embodiment:
The preparation 1 of nerve trachea:
(1) take by weighing an amount of polylactic acid (viscosity 0.8), be dissolved in the dichloromethane, be mixed with the solution of 400mg/ml, add 5% Macrogol 3000, ultrasonic dispersing is even.
(2) utilize suitable mold, adopting solvent evaporation method to prepare internal diameter is 1.0～2.0mm, wall thickness 100～200 μ m, the aperture below 10 μ m, the micropore composite conduit of long 14mm.
The preparation 2 of nerve trachea:
(1) take by weighing an amount of polylactic acid (viscosity 0.8), be dissolved in the dichloromethane, be mixed with the solution of 400mg/ml, add 5% cetomacrogol 1000, ultrasonic dispersing is even.
(2) utilize suitable mold, adopting solvent evaporation method to prepare internal diameter is 1.0～2.0mm, wall thickness 100～200 μ m, the aperture below 10 μ m, the micropore composite conduit of long 14mm.
The preparation 3 of nerve trachea:
(1) take by weighing an amount of polylactic acid (viscosity 0.8), be dissolved in the dichloromethane, be mixed with the solution of 400mg/ml, add 5% polyethylene glycol 6000, ultrasonic dispersing is even.
(2) utilize suitable mold, adopting solvent evaporation method to prepare internal diameter is 1.0～2.0mm, wall thickness 100～200 μ m, the aperture below 10 μ m, the micropore composite conduit of long 14mm.
The preparation 4 of nerve trachea:
(1) take by weighing an amount of polylactic acid (viscosity 0.8), be dissolved in the dichloromethane, be mixed with the solution of 400mg/ml, add 15% Macrogol 3000, ultrasonic dispersing is even.
(2) utilize suitable mold, adopting solvent evaporation method to prepare internal diameter is 1.0～2.0mm, wall thickness 100～200 μ m, the aperture below 10 μ m, the micropore composite conduit of long 14mm.
The preparation 5 of nerve trachea:
(1) take by weighing an amount of polylactic acid (viscosity 0.8), be dissolved in the dichloromethane, be mixed with the solution of 400mg/ml, add 15% polyethylene glycol 6000, ultrasonic dispersing is even.
(2) utilize suitable mold, adopting solvent evaporation method to prepare internal diameter is 1.0～2.0mm, wall thickness 100～200 μ m, the aperture below 10 μ m, the micropore composite conduit of long 14mm.
The preparation 6 of nerve trachea:
(1) take by weighing an amount of polylactic acid (viscosity 0.8), be dissolved in the dichloromethane, be mixed with the solution of 400mg/ml, add 30% Macrogol 3000, ultrasonic dispersing is even.
(2) utilize suitable mold, adopting solvent evaporation method to prepare internal diameter is 1.0～2.0mm, wall thickness 100～200 μ m, the aperture below 10 μ m, the micropore composite conduit of long 14mm.
The preparation 7 of nerve trachea:
(1) take by weighing an amount of polylactic acid (viscosity 0.8), be dissolved in the dichloromethane, be mixed with the solution of 400mg/ml, add 30% polyethylene glycol 6000, ultrasonic dispersing is even.
(2) utilize suitable mold, adopting solvent evaporation method to prepare internal diameter is 1.0～2.0mm, wall thickness 100～200 μ m, the aperture below 10 μ m, the micropore composite conduit of long 14mm.
Nerve trachea is repaired the effect assessment of neurologic defect:
12 of Wistar rats, body weight are 250g ± 20g, 6 every group.Anesthesia, the ventricumbent position is fixed, left back lower limb preserved skin, iodophor disinfection, hole, shop towel.Cut skin, muscle fully exposes sciatic nerve, from disconnected neural, forms the neurologic defect of 10mm, and put into respectively at damaged place: A. prepares 4 nerve tracheas, 14mm, and severed nerve 2mm respectively is inserted at two ends; B. allogeneic nerve, 10mm.With conduit or allogeneic nerve socket or directly insert the neural broken ends of fractured bone, sew up.
The gross morphology of postoperative rat is observed appetite, the mental status to experimental rat, and walking situation and post-operative complication situation are observed.Postoperative, the appetite and the mental status of rat are good, and about 10 days, red and swollen or ulcer in various degree appear in art parapodum heel, and the obvious atrophy of two groups of rat art side Calf muscles does not take place but all there is residual foot phenomenon.Observe the microstructure of electric physiology, muscular tension, muscle wet weight and regenerating nerve etc. after 3～4 months, the experiment effect of evaluating combined conduit the results are shown in Table 1.The repairing effect demonstration, in three parameters that neuranagenesis is estimated, the difference not statistically significant between nerve trachea transplantation group and allogeneic nerve transplantation group, so the optic nerve conduit is suitable with the effect of allogeneic nerve bridge joint severed nerve.Nerve trachea can replace clinical allogeneic nerve and transplant reparation.
Observation to implantation catheter shows, the conduit cast that implants in back month is complete, does not subside, and rear tube was degraded fully in three months.
Table 1 nerve conduction velocity, muscular tension and muscle wet weight recovery rate
T assay: three index P＞0.05 between two groups, difference not statistically significant.
Claims (10)
1. a repair materials or compositions that promotes damaged property neuranagenesis, it comprises Biodegradable material compatible with human body and macromolecular material porogen.
2. the material of claim 1 or compositions, wherein by weight percentage, the macromolecular material porogen accounts for the 1-40% of material or compositions.
3. claim 1 or 2 material or compositions, wherein compatible with human body Biodegradable material is selected from the polylactic acid or derivatives thereof, gelatin or derivatives thereof, chitosan, polyurethane, water-insoluble cellulose or derivatives thereof.
4. the material of claim 3 or compositions, wherein the macromolecular material porogen is selected from: comprise the Polyethylene Glycol of PEG400-Polyethylene Glycol 30,000, polyamino acid, glucosan, water-soluble cellulose and derivant thereof.
5. the product that is used for damaged property neuranagenesis, its repair materials or compositions by claim 1 forms.
6. the product of claim 5, wherein this product is a tube.
7. claim 5 or 6 product, wherein by weight, the macromolecular material porogen accounts for the 1-40% of product.
8. the product of claim 7, wherein compatible with human body Biodegradable material is selected from the polylactic acid or derivatives thereof, the gelatin or derivatives thereof, chitosan, polyurethane, the cellulose or derivatives thereof, wherein porogen is selected from: comprise the Polyethylene Glycol of PEG400-Polyethylene Glycol 30,000, polyamino acid, glucosan, water-soluble cellulose and derivant thereof.
9. the macromolecular material porogen is used for promoting the purposes of repair materials or the compositions or the product of damaged property neuranagenesis in preparation.
10. the purposes of claim 9, wherein the macromolecular material porogen is selected from: comprise the Polyethylene Glycol of PEG400-Polyethylene Glycol 30,000, polyamino acid, glucosan, water-soluble cellulose and derivant thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910177405 CN102028974A (en) | 2009-09-28 | 2009-09-28 | Repair material for promoting regeneration of defective nerves |
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| CN 200910177405 CN102028974A (en) | 2009-09-28 | 2009-09-28 | Repair material for promoting regeneration of defective nerves |
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| CN102028974A true CN102028974A (en) | 2011-04-27 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114699560A (en) * | 2021-04-16 | 2022-07-05 | 中国人民解放军总医院 | Double-layer tubular product for promoting defective nerve regeneration |
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- 2009-09-28 CN CN 200910177405 patent/CN102028974A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114699560A (en) * | 2021-04-16 | 2022-07-05 | 中国人民解放军总医院 | Double-layer tubular product for promoting defective nerve regeneration |
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