CN101664558B - Chitosan-collagen-diprospan slow releasing system, preparation method and application thereof - Google Patents
Chitosan-collagen-diprospan slow releasing system, preparation method and application thereof Download PDFInfo
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- CN101664558B CN101664558B CN2008100424713A CN200810042471A CN101664558B CN 101664558 B CN101664558 B CN 101664558B CN 2008100424713 A CN2008100424713 A CN 2008100424713A CN 200810042471 A CN200810042471 A CN 200810042471A CN 101664558 B CN101664558 B CN 101664558B
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Abstract
The invention relates to a chitosan-collagen-diprospan slow releasing system, which belongs to the field of biotechnology and medical materials. The chitosan-collagen-diprospan slow releasing system is prepared from chitosan and collagen serving as medicine carriers and steroid hormone (diprospan) serving as a slow releasing medicine. The chitosan-collagen-diprospan releasing system has good biocompatibility and absorbability, and can play a role in physically blocking and inhibiting the growth of fibroblasts; and the diprospan releases at a constant speed through medicine slow releasing technology so that the diprospan can inhibit the proliferation of capillaries and fibroblasts for long term and prevent the formation of adhesion and scars. The chitosan-collagen-diprospan slow releasing system can be used for repairing peripheral nerves clinically, and can provide meaningful reference for the discussion of promoting nerve regeneration and improving nerve function recovery.
Description
Technical field
The invention belongs to biotechnology and macromolecule field of medical materials, the application in being specifically related to chitosan-collagen-Diprospan Soft Release system and preparation method thereof and nerve being repaired around.
Background technology
Peripheral nerve injury is common clinically wound, because its incidence rate is high, therapeutic effect is poor, is the thorny difficult problem in the traumatology department field always.Clinical practice shows that repairing the further major reason that improves of curative effect behind the obstruction peripheral nerve injury is the partial scar hyperplasia of nerve suture mouth.The local hematoma that produces behind the neural prosthesis; Vacillate and invade hematoma from the fibroblast of different parts; Under inflammatory mediator, somatomedin chemotactic that inflammatory cell discharges stimulated, fibroblast assembled, breeds, synthesizes, secretes collagen fiber and forms scar tissue gradually in wound.Scar tissue is mainly through the affect the nerves recovery of function of dual mode, and the one, with the injured nerve adhesion, directly pressuring nerve, and the blood that affects the nerves supplies; The 2nd, cicatrix is grown into stitching mouth gap, hinders the regenerated nerve fiber of near-end through sewing up mouth.The research proof, behind the repair of peripheral nerve, about 50% aixs cylinder just just ends in the scar tissue through sewing up mouth.Described above-mentioned dual mode all can hinder neuranagenesis, influences its functional rehabilitation.In a single day and form fine and close cicatrix, then will have a strong impact on passing through of regenerating nerve.Simple medicine or other means of using various promotion nerve growths often can not obtain ideal effect.Become present peripheral nerve injury and repaired a difficult problem that needs to be resolved hurrily of research field.Therefore, the scar hyperplasia of research prevention of peripheral neurological postoperative improves peripheral nerve and repairs curative effect, improves functional rehabilitation, is the focus of current Chinese scholars research.
At present, Chinese scholars has been carried out a large amount of research aspect infrastest and clinical practice, main concentrating both ways, and the one, utilize biological preparation obstruct nerve suture mouth and surrounding tissue to reach the physics antiblocking effect; The 2nd, the pharmacological action that utilizes the reaction of steroid hormone inflammation-inhibiting is to reach the effect that prevents scar hyperplasia.But general effect is all unsatisfactory.
Chitosan (Chitosan) claim chitosan again, is the deacetylated derivant of chitin, is a kind of a large amount of cationic glucamine polymers that contain; The shell that extensively is present in shrimp, Eriocheir sinensis; Shellfish, animal cartilage etc. have the better tissues compatibility, extremely strong biological activity; Favorable biological degradability and special physiological function are widely used in fields such as medical treatment, health care, agricultural.Be called the mankind's the 6th vital principle after protein, lipid, saccharide, vitamin and mineral by international academic community.Research shows that chitosan has hemostasis, pain relieving, inhibition growth of microorganism, regulates effects such as macrophage and fibroblast, and therefore, many scholars are with its promoter as wound healing.The chitosan of variable concentrations and derivant thereof promote fibroblasts proliferation and migration on the one hand, and the structure that helps newborn repair tissue is reinvented and made up, and can strengthen or recover the mechanical strength of wound healing; Be suppressed to fibrocellular hyper-proliferative on the other hand, prevent scar hyperplasia, help the recovery of outward appearance and function, make wound obtain high-quality healing.Because of drawing; Can be used as the good carrier of local sustained release medicine; Have research to confirm through zoopery, chitosan gentamycin drug delivery system has the inside and outside slow releasing function of body preferably aspect the treatment infection of bone, use simple, convenient, safely, need not the second phase taking-up.But the chitosan degradation in vivo needs the long period.
Collagen (Collagen) is one type of structural protein that research is more deep, in the formation of animal tissue and organ, plays an important role.Because its wide material sources have biodegradability, biocompatibility and reduced immunogenicity, have been applied to medicament carrier system and field of tissue engineering technology such as artificial blood vessel, valve.The main cause that collagen can be applicable to field of medicaments is it through autohemagglutination and crosslinked, can form the structure with certain intensity and stability, with the medicament carrier system that can be made into various ways behind the weak acid water extraction.The absorption of collagen and the release of active substance receive the used cross-linking agent kind and the influence of quantity.At present, the collagen delivery system comprises that mainly collagen cover, burn and the wound of ophthalmic use collagen sponge, is used for microsphere that gene discharges etc.
Diprospan is a kind of long-acting glucocorticoid, and every ml injection is made up of 5mg BDP and 2mg betamethasone disodium hydrogen phosphate.Betamethasone disodium hydrogen phosphate water soluble, very fast absorption the and onset rapidly in vivo, and BDP is slightly soluble in water can store in vivo and slowly absorb, and keeps the action time in 3-6 weeks.Have the hypertrophy that suppresses blood capillary and fibroblast, delay the granulation tissue growth, and make the collagen fiber dissolving, prevent adhesion and cicatrization, thereby play antiproliferative effect.But, shortcoming such as the side effect of whole body prolonged application is big, and topical application concentration is wayward.
Although the biomembrane and the local sustained release of various different degradation speeds and mechanical property constantly come out medicine; Promoting that also having had some aspect the neuranagenesis tastes; But up to now; Still do not have report both at home and abroad about making that physical barrier and pharmacological action ability is lasting, the ground performance simultaneously that has no side effect, promote the medicament slow release place system of neuranagenesis effect.
Summary of the invention
The purpose of this invention is to provide a kind of chitosan-collagen-Diprospan Soft Release system.Soft Release of the present invention system can be used for clinical peripheral nerve reparation, can promote neuranagenesis for inquiring into chitosan-collagen-Diprospan Soft Release system, improve neurological functional recovery significant reference is provided.
The present invention adopts medical chitose and collagen to process composite membrane as backing material; With this composite membrane is carrier, is slow releasing pharmaceutical with steroid hormone (Diprospan), adopts the medicament slow release technology; Steroid hormone is added in this film, process chitosan-collagen-Diprospan Soft Release system.
Described chitosan-collagen composite membrane degrades it with the preparation of 1:9 degree ratio in vivo fully in the certain hour; Described steroid hormone (Diprospan) adds in this film with the ratio that is fit to, and it is discharged with constant speed.The present invention adopts medicament slow release technology, make steroid hormone in local long term maintenance in valid density, produce synergism with the anti function of composite membrane, suppress scar hyperplasia, improve the effect of neurological functional recovery.
Another object of the present invention provides the method for preparing chitosan-collagen-Diprospan Soft Release system.
Described Soft Release system is through following method and step preparation:
Get 3% solubility in acid chitosan and 1.5% collagen (its victory biomaterial technical research institute of Shanghai provides) and with the mixed of 1:9, add the Diprospan suspension again, the amount of the Diprospan suspension that is added is respectively 0.2ml, 0.4ml, 0.6ml, 0.8ml, 1ml; Preferred 0.6ml fully mixed 60 minutes, under 200 rev/mins of stirrings, splashed into 36% formaldehyde 2ml then gradually; Pour in the mould after 5 minutes, leave standstill the demoulding after 1 hour, the freezing vacuum in distilled water cleaning back is drained machine and was interrupted dry 12 hours; Make chitosan-collagen-Diprospan Soft Release system; Deposit under 4 ℃, the thickness of described film is 0.5mm, and dried film is the tubular structure of a side opening.
Further purpose of the present invention provides the application in the neural around reparation of said chitosan-collagen-Diprospan Soft Release system.
The present invention has carried out peripheral nerve and has repaired zoopery:
60 adult male SD rats (Chinese Academy of Sciences's Experimental Animal Center provides) body weight 250-280g is divided into six groups at random, and 10 every group, A: matched group; B, C, D, E, F: chitosan-collagen-Diprospan group, the amount of the Diprospan suspension of adding is respectively 0.2ml, 0.4ml, 0.6ml, 0.8ml, 1ml, carries out each item monitoring index respectively after surgery in 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks and detects.
The result shows:
1) chitosan-collagen-Diprospan group:
Gross examination of skeletal muscle result: each is organized rat postoperative 2 all interior bilateral lower limb and swelling in various degree all occurs, alleviates gradually after 2 weeks.Skin ulcer appears in totally 42 rat toes or vola, and ulcer heals basically during average about 8 weeks, suffers from limb and does not have obvious swelling, and activity freely.None example infects.
2 weeks of postoperative, the visible local chitosan-collagen of experimental group-Diprospan release membranes and surrounding tissue did not have obvious adhesion when drawing materials, and the neural activity degree can.Wherein, obviously with the E group; F group neural anastomosis mouth suture major part comes off, and only the part filament links to each other, and surrounding tissue is poor.So do not do further to detect.12 when week chitosan-collagen-Diprospan release membranes degraded and absorbed basically forms film appearance tissue, the no clear scar hamartoplasia in part.Wherein, obviously with the D group.In 16 whens week, this release membranes is degraded and absorbed fully, local no clear scar and adhesion, and the neural activity degree is good, and the D group is superior to the E group and is superior to C and organizes and be superior to B and organize.
Histology result: see that nerve suture mouth local scar hamartoplasia is not obvious, clear with the surrounding tissue boundary, the back inflammatory reaction of 2 weeks is not obvious.Postoperative sees on the longitudinal section that the regenerating nerve fiber through sewing up mouth is more straight during 12 weeks, and arrangement architecture is more neat.Wherein, comparatively obvious with the D group.During 16 weeks, chitosan-collagen-Diprospan release membranes degraded and absorbed is complete.AChE dyeing sees through the Motor nerve fibre quantity showed increased of sewing up mouthful, and the D group is superior to the E group and is superior to the C group and is superior to the B group.
Electricity physiology result: postoperative is D, the existing early recovery of E during 3 weeks, and in 12,16 weeks, the recovery rate of wave amplitude that the experimental group sciatic nerve brings out current potential is higher than matched group, and difference has significance meaning (P < 0.05); Preclinical retardation rate is compared with matched group and is decreased, and difference has significance meaning (P < 0.05).The most obvious with the D group.
The computer image analysis result: in 16 weeks of postoperative, the average diameter of aixs cylinder and myelinated nerve fiber regeneration obviously improve.The D group is apparently higher than other experimental group.
2) matched group
Gross examination of skeletal muscle result: skin ulcer appears in totally 9 rat toes or vola, and ulcer heals basically during average about 10 weeks, suffers from limb and does not have obvious swelling, and activity freely.
Postoperative is visible nerve suture mouth local scar hamartoplasia during 2 weeks, and with the surrounding tissue adhesion, neural activity is limited.Sew up a mouthful local adhesion when 4 weeks of postoperative, 8 weeks, 12 weeks, 16 weeks and increase the weight of, nerve does not have mobility basically.
Histology result: see that nerve suture mouth local scar hypertrophy and adhesion are obvious.Seeing on the longitudinal section that nerve suture mouth part is had by cicatrix compressing narrows down in various degree, obvious, misaligned through the regenerating nerve torsion of fibers of sewing up mouthful.AChE dyeing is seen through sewing up the Motor nerve fibre negligible amounts of mouth.
Electricity physiology result: postoperative does not have active electrical potential in early days, and in 12,16 weeks, sciatic nerve brings out at the bottom of the wave amplitude of current potential.
The computer image analysis result: in 16 weeks of postoperative, the regeneration of the myelinated nerve fiber of the average diameter of aixs cylinder is low than experimental group, and significant difference (P < 0.05) is arranged.
3) use the stata8.0 statistical software, non-paired t test between group data and matched group data experimentizes.
The present invention shows through the zoopery result,
(1) chitosan-collagen-Diprospan release membranes can be suppressed to fibrocellular growing multiplication effectively, and can reduce the generation of collagen, and nerve suture mouth cicatrix is reduced, and prevents cicatrix and neural adhesion on the one hand, direct pressuring nerve, and the blood that affects the nerves supplies; Help the regenerating nerve fiber on the other hand through sewing up mouth;
(2) more straight through the regenerating nerve fiber of sewing up mouth, arrangement architecture is more neat, and Motor nerve fibre quantity showed increased;
The recovery rate of (3) repairing the neural wave amplitude that brings out current potential obviously improves; The average diameter of aixs cylinder and myelinated nerve fiber regeneration also obviously improve;
For best, cross hang down then suppress cicatrix effect undesirable during for 0.6ml by the excessive concentration regeneration that affects the nerves for the amount of the Diprospan suspension that (4) adds in described chitosan-collagen-Diprospan slow-released system.
It is medicament carrier system that the present invention adopts chitosan-collagen composite membrane, and chitosan both capable of using and collagen excellent biological compatibility and absorbability in vivo plays physics and deaden and be suppressed to fibroblast growth and promote the endothelial cell growth effect; Collagen capable of using again is one of composition of neural basement membrane, in the neuranagenesis process, participate in to form matrix bridge, and favourable row is in the aixs cylinder progradation of creeping.Simultaneously, can avoid simple chitosan pipe fragility higher, frangible subsiding; The shortcoming that simple collagen tube degradation time is short.Soft Release of the present invention system is novel Biodegradable material, has the advantage of prior art concurrently, has increased the pliability of material, has prolonged degradation time.It is that slow releasing pharmaceutical has utilized it to store in vivo and slowly absorption that the present invention adopts Diprospan; Can keep the action time in 3-6 weeks, discharge, make it have the hypertrophy of long term inhibition blood capillary and fibroblast through constant speed; Can delay the granulation tissue growth; And make the collagen fiber dissolving, and prevented adhesion and cicatrization, play antiproliferative effect.
Chitosan-collagen of the present invention-Diprospan slow-released system is used to repair peripheral nerve, has solved that scar tissue obviously improves the neural axon percent of pass to its compressing and iris action in the neuranagenesis process, and neural the reparation obtains satisfied effect.
The specific embodiment
Embodiment 1
Get 3% solubility in acid chitosan and 1.5% collagen,, gradually add Diprospan suspension 0.2ml again with the mixed of 1:9; Fully mixed 60 minutes, under 200 rev/mins of stirrings, splash into 36% formaldehyde 2ml then gradually, pour in the mould after 5 minutes; Leave standstill the demoulding after 1 hour; Distilled water cleans the freezing vacuum in back and drains machine and be interrupted dry 12 hours, chitosan-collagen-Diprospan release membranes, deposit under 4 ℃.The thickness of described film is 0.5mm, and dried film is the tubular structure of a side opening.
Embodiment 2
Get 3% solubility in acid chitosan and 1.5% collagen,, gradually add Diprospan suspension 0.4ml again with the mixed of 1:9; Fully mixed 60 minutes, under 200 rev/mins of stirrings, splash into 36% formaldehyde 2ml then gradually, pour in the mould after 5 minutes; Leave standstill the demoulding after 1 hour; Distilled water cleans the freezing vacuum in back and drains machine and be interrupted dry 12 hours, chitosan-collagen-Diprospan release membranes, deposit under 4 ℃.The thickness of described film is 0.5mm, and dried film is the tubular structure of a side opening.
Embodiment 3
Get 3% solubility in acid chitosan and 1.5% collagen,, gradually add Diprospan suspension 0.6ml again with the mixed of 1:9; Fully mixed 60 minutes, under 200 rev/mins of stirrings, splash into 36% formaldehyde 2ml then gradually, pour in the mould after 5 minutes; Leave standstill the demoulding after 1 hour; Distilled water cleans the freezing vacuum in back and drains machine and be interrupted dry 12 hours, chitosan-collagen-Diprospan release membranes, deposit under 4 ℃.The thickness of described film is 0.5mm, and dried film is the tubular structure of a side opening.
Embodiment 4
Get 3% solubility in acid chitosan and 1.5% collagen,, gradually add Diprospan suspension 0.8ml again with the mixed of 1:9; Fully mixed 60 minutes, under 200 rev/mins of stirrings, splash into 36% formaldehyde 2ml then gradually, pour in the mould after 5 minutes; Leave standstill the demoulding after 1 hour; Distilled water cleans the freezing vacuum in back and drains machine and be interrupted dry 12 hours, chitosan-collagen-Diprospan release membranes, deposit under 4 ℃.The thickness of described film is 0.5mm, and dried film is the tubular structure of a side opening.
Embodiment 5
Get 3% solubility in acid chitosan and 1.5% collagen,, gradually add Diprospan suspension 1ml again with the mixed of 1:9; Fully mixed 60 minutes, under 200 rev/mins of stirrings, splash into 36% formaldehyde 2ml then gradually, pour in the mould after 5 minutes; Leave standstill the demoulding after 1 hour; Distilled water cleans the freezing vacuum in back and drains machine and be interrupted dry 12 hours, chitosan-collagen-Diprospan release membranes, deposit under 4 ℃.The thickness of described film is 0.5mm, and dried film is the tubular structure of a side opening.
Embodiment 7 zooperies
60 adult male SD rats (available from Chinese Academy of Sciences's Experimental Animal Center) body weight 250-280g is divided into six groups, 10 every group at random.Be divided into matched group; Experimental group: chitosan-collagen-Diprospan group; Numbering: B, C, D, E, F; The amount of the Diprospan suspension that adds is respectively 0.2ml, 0.4ml, 0.6ml, 0.8ml, 1ml, carries out each item monitoring index respectively after surgery in 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks and detects.
1) chitosan-collagen-Diprospan group:
2% pentobarbital sodium intraperitoneal injection of anesthesia; 30-35mg/kg, routine appears right sciatic nerves and cuts off in piriformis lower edge 1.0cm place under the aseptic condition, under operating microscope, is anatomic landmark with neural vascular surface; Adopt the adventitia sewing; Be interrupted 4 pins that coincide with 11-0 nylon wire, all micro suture can guarantee involutory, knotting elasticity unanimity by changeing special messenger's operation.Twine chitosan-collagen-Diprospan biomembrane of implanting above-mentioned variable concentrations around the neural anastomosis mouth, near, the far-end of said film are respectively sewed up a pin and are fixed with near, distal nerve adventitia.Local muscle covers skin suture, sub-cage rearing.
The result shows:
Postoperative 2 in week the bilateral lower limb swelling in various degree all appears, alleviate gradually after 2 weeks, skin ulcer appears in totally 42 rat toes or vola, ulcer heals basically during average about 8 weeks, suffer from limb and do not have obvious swelling, activity freely, none example infects;
2 weeks of postoperative are when drawing materials, and the visible local chitosan-collagen of experimental group-Diprospan release membranes does not have obvious adhesion with surrounding tissue, the neural activity degree can, wherein, obvious with the E group; F group neural anastomosis mouth suture major part comes off, and only the part filament links to each other, and surrounding tissue is poor.12 when week chitosan-collagen-Diprospan release membranes degraded and absorbed basically forms film appearance tissue, and local no clear scar hamartoplasia wherein, is organized obvious with D; In 16 whens week, this release membranes is degraded and absorbed fully, local no clear scar and adhesion, and the neural activity degree is good, and the D group is superior to the E group and is superior to C and organizes and be superior to B and organize in order.
Histology result: nerve suture mouth local scar hamartoplasia is not obvious, and is clear with the surrounding tissue boundary, and the back inflammatory reaction of 2 weeks is not obvious; 12 weeks of postoperative; , see on the longitudinal section that the regenerating nerve fiber through sewing up mouth is more straight, arrangement architecture is more neat, and is wherein, comparatively obvious with the D group; In 16 whens week, chitosan-collagen-Diprospan release membranes degraded and absorbed is complete, and AChE dyeing sees through the Motor nerve fibre quantity showed increased of sewing up mouthful, and the D group is superior to the E group and is superior to the C group and is superior to the B group in order.
Electricity physiology result: postoperative 3 all D, the existing early recovery of E, in 12,16 weeks, the recovery rate of wave amplitude that the experimental group sciatic nerve brings out current potential is higher than matched group, and difference has significance meaning (P < 0.05); Preclinical retardation rate is compared with matched group and decreased, and difference has significance meaning (P < 0.05), and is the most obvious with the D group.
The computer image analysis result: in 16 weeks of postoperative, the average diameter of aixs cylinder and myelinated nerve fiber regeneration obviously improve, and D organizes apparently higher than other experimental group.
2) matched group
2% pentobarbital sodium intraperitoneal injection of anesthesia (30-35mg/kg).Routine appears right sciatic nerves and cuts off in piriformis lower edge 1.0cm place under the aseptic condition; Under operating microscope, be anatomic landmark with neural vascular surface; Adopt the adventitia sewing, be interrupted 4 pins that coincide with 11-0 nylon wire, all micro suture are operated by the special messenger; Guarantee involutory, knotting elasticity unanimity, do not use chitosan-collagen-Diprospan release membranes around the neural anastomosis mouth.
Skin ulcer appears in postoperative totally 9 rat toes or vola, and ulcer heals basically during average about 10 weeks, suffers from limb and does not have obvious swelling, and activity freely.
Postoperative is seen nerve suture mouth local scar hamartoplasia during 2 weeks, and with the surrounding tissue adhesion, neural activity is limited; Sew up a mouthful local adhesion when 4 weeks of postoperative, 8 weeks, 12 weeks, 16 weeks and increase the weight of, nerve does not have mobility basically.
Histology result: see that nerve suture mouth local scar hypertrophy and adhesion are obvious; Seeing on the longitudinal section that nerve suture mouth part is had by cicatrix compressing narrows down in various degree; Regenerating nerve torsion of fibers through sewing up mouth is obvious; Misaligned, AChE dyeing is seen through sewing up the Motor nerve fibre negligible amounts of mouth.
Electricity physiology result: postoperative does not have active electrical potential in early days, and in 12,16 weeks, the wave amplitude that sciatic nerve brings out current potential is low.
The computer image analysis result: in 16 weeks of postoperative, the regeneration of the myelinated nerve fiber of the average diameter of aixs cylinder is low than experimental group, and significant difference (P < 0.05) is arranged.
Claims (4)
1. chitosan-collagen-Diprospan slow-released system is characterized in that by medical chitose and collagen composite membrane be carrier, and adding the steroid hormone Diprospan is slow releasing pharmaceutical, processes chitosan-collagen-Diprospan release membranes; Described chitosan and collagen mixed proportion are 1: 9, and described slow releasing pharmaceutical is processed suspension, and addition is respectively 0.2ml, 0.4ml, 0.6ml, 0.8ml, 1ml;
Described chitosan-collagen-Diprospan release membranes thickness is 0.5mm;
Described film is the tubular structure of a side opening.
2. by the described chitosan-collagen of claim 1-Diprospan release membranes, it is characterized in that described slow releasing pharmaceutical suspension addition is 0.6ml.
3. the method for preparing of the described chitosan-collagen of claim 1-Diprospan slow-released system is characterized in that through following method and step:
Get 3% solubility in acid chitosan and 1.5% collagen,, add Diprospan suspension 0.2ml, 0.4ml, 0.6ml, 0.8ml or 1ml more respectively with 1: 9 mixed; Fully mix after 60 minutes, under 200 rev/mins of stirrings, splash into 36% formaldehyde 2ml, pour in the mould after 5 minutes; Leave standstill the demoulding after 1 hour, distilled water cleans, and is freezing; Vacuum is drained machine and was interrupted dry 12 hours, makes chitosan-collagen-Diprospan Soft Release system, deposits under 4 ℃.
4. repair the application in the peripheral nerve medicine by the chitosan-collagen-Diprospan slow-released system of claim 1 in preparation.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101138656A (en) * | 2007-09-05 | 2008-03-12 | 中国人民解放军第二军医大学 | Preparation method of chitosan composite nerve conduit |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101138656A (en) * | 2007-09-05 | 2008-03-12 | 中国人民解放军第二军医大学 | Preparation method of chitosan composite nerve conduit |
Non-Patent Citations (3)
| Title |
|---|
| 刘强等.《得宝松对周围神经损伤后功能恢复影响的实验研究》.《中国矫形外科杂志》.2003,第11卷(第10期),第692-693页. * |
| 蒋良福等.《几丁糖胶原复合膜及激活态雪旺细胞修复周围神经缺损的实验研究》.《中华手外科杂志》.2005,第21卷(第3期),第172-174页. * |
| 魏欣等.《几丁糖-胶原复合膜促进周围神经再生的实验研究》.《上海医学》.2001,第24卷(第9期),第534-537页. * |
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