CN106075574A - A kind of preparation method of the gel stent of repairing articular cartilage damage - Google Patents

A kind of preparation method of the gel stent of repairing articular cartilage damage Download PDF

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Publication number
CN106075574A
CN106075574A CN201610577602.2A CN201610577602A CN106075574A CN 106075574 A CN106075574 A CN 106075574A CN 201610577602 A CN201610577602 A CN 201610577602A CN 106075574 A CN106075574 A CN 106075574A
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Prior art keywords
sodium
articular cartilage
gel
prepare
hyaluronate
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CN201610577602.2A
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王雅
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/52Hydrogels or hydrocolloids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/26Mixtures of macromolecular compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/06Flowable or injectable implant compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/06Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus

Abstract

The invention discloses the preparation method of the gel stent of a kind of repairing articular cartilage damage, comprise the following steps: S1: preparing weight portion is the hyaluronate sodium of 58 parts and the deionized water of 20 25 parts, hyaluronate sodium and deionized water are mixed, at 10 15 DEG C, react 11 14h, prepare sodium hyaluronate solution;S2: preparing weight portion is the PLGA nano-particle of 69 parts and the azo-bis-isobutyrate hydrochloride of 47 parts, PLGA nano-particle is added in sodium hyaluronate solution, 10 15min are reacted at 15 20 DEG C, it is subsequently adding azo-bis-isobutyrate hydrochloride, at 20 25 DEG C, react 20 30min, prepare hyaluronic acid sodium gel complex solution;S3: be injected into by hyaluronic acid sodium gel complex solution at articular cartilage damage to be repaired, then irradiates through ultraviolet point source, obtains the gel stent of repairing articular cartilage damage.The present invention can the most quickly prepare the gel stent of compound joint cartilage injury, and method is simple, easy to use, low cost.

Description

A kind of preparation method of the gel stent of repairing articular cartilage damage
Technical field
The present invention relates to medicine and technical field of medical instruments, the gel particularly relating to the damage of a kind of repairing articular cartilage props up The preparation method of frame.
Background technology
Along with China enters aging society, knee articular cartilage defect patient gets more and more;At present this type of disease be there is no Good Therapeutic Method;Subchondral bone punching the most conventional, bone cartilage transplantation and native cartilage cell transplantation can only Part relief of symptoms, it is impossible to reach the purpose of cartilage regeneration defect, the repair tissue using this type of method to obtain is mainly composed of I Collagen type, differs greatly compared with the II collagen type of original hyaline cartilage on biological characteristics.
Regeneration and Repair tissue at cartilage defect, the ultimate principle of cartilage regeneration defect is: outside raising self or introducing The stem cell of source property, relatively germinal cell are at cartilage defect, and are divided into cartilaginous tissue under the effects such as relevant growth factors;Close Joint chamber there is polytype mescenchymal stem cell can be enrolled at cartilage defect and carries out injury repairing, such as medulla mesenchyma Synovial Mesenchymal Stem Cells in stem cell, knuckle synovia and the fat mesenchymal stem cell etc. in subpatellar fat pad source;Body Liquid and blood etc. all have inducing mesenchymal stem cell to orient the ability migrated, and the various factors in cartilage microenvironment have and lure Lead the ability of mesenchymal stem cells into chondrocytes directed differentiation;But, due to the office of self Immune inducing in vivo factor stress efficacy The three-dimensional space environment that sex-limited and shortage cell grows, thus, it is impossible to produce the repair tissue similar with original cartilaginous tissue, In order to solve this difficult problem of regenerating bone or cartilage, domestic and international medical circle has carried out substantial amounts of exploration and research between the past few decades;As Study various somatomedin to promote that mesenchymal stem cells into chondrocytes breaks up;Research Gene transfer techniques obtains into cartilage The seed cell that ability is higher;Study novel tissue engineering bracket build organization engineered cartilage in vitro and then implant Deng;But, all there is various limitation in these methods: somatomedin can not internal use due to immunogenicity, gene transfection skill There is safety and oncogenicity problem in art, organization engineered cartilage is implanted and is difficult to integration etc. with original tissue;Thus, at present these Method the most well solves problem;In recent years, at cartilage defect, implantation can raise and induce self mescenchymal stem cell It it is the therapeutic modality having bright prospects to the three-dimensional rack of Chondrocyte Differentiation;Implant three-dimensional porous rack especially to implant and can delay The timbering material of release thing is because recruiting more mescenchymal stem cell and strengthen induction usefulness, thus treatment regenerating bone or cartilage brings Huge hope, has a social and economic significance widely.
At present, research applies more timbering material mostly to be PLGA, PGA, collagen protein, fibrin etc., these supports Material characteristics is the energy inducing cell substantial amounts of I-type collagen of generation, rather than II collagen type, thus it is unfavorable for that mesenchyme is done Cell is to Chondrocyte Differentiation;And in the research field of medicine slow release stent, be used for mostly being somatomedin by the medicine of slow release, this Class drug price is expensive, and has immunogenicity, and vivo applications has the risk bringing zoonosis;Thus, search out Suitable form, timbering material that emiocytosis cartilage cell epimatrix can be promoted and safely and effectively, can internal use Induced drug is the key solving regenerating bone or cartilage problem.
Summary of the invention
The technical problem existed based on background technology, the present invention proposes the gel stent of a kind of repairing articular cartilage damage Preparation method.
The preparation method of the gel stent of a kind of repairing articular cartilage damage that the present invention proposes, comprises the following steps:
S1: prepare hyaluronate sodium and the deionized water of 20-25 part that weight portion is 5-8 part, by hyaluronate sodium and deionization Water mixes, and reacts 11-14h, prepare sodium hyaluronate solution at 10-15 DEG C;
S2: prepare PLGA nano-particle and the azo-bis-isobutyrate hydrochloride of 4-7 part that weight portion is 6-9 part, by PLGA nanometer Granule adds in sodium hyaluronate solution, reacts 10-15min, be subsequently adding azo-bis-isobutyrate hydrochloride at 15-20 DEG C, At 20-25 DEG C, react 20-30min, prepare hyaluronic acid sodium gel complex solution;
S3: hyaluronic acid sodium gel complex solution is injected at articular cartilage damage to be repaired, then through ultraviolet point source Irradiate, obtain the gel stent of repairing articular cartilage damage.
Preferably, in described S1, prepare hyaluronate sodium and the deionized water of 21-24 part that weight portion is 6-7 part, will thoroughly Bright matter acid sodium and deionized water mixing, react 12-13h at 11-14 DEG C, prepare sodium hyaluronate solution.
Preferably, in described S2, prepare PLGA nano-particle and azo two 2,2-Dimethylaziridine of 5-6 part that weight portion is 7-8 part Hydrochlorate, adds PLGA nano-particle in sodium hyaluronate solution, reacts 11-14min, be subsequently adding idol at 16-19 DEG C Nitrogen two 2,2-Dimethylaziridine hydrochlorate, reacts 22-28min at 21-24 DEG C, prepares hyaluronic acid sodium gel complex solution.
Preferably, in described S3, hyaluronic acid sodium gel complex solution is filled to articular cartilage damage to be repaired, Then irradiate through ultraviolet point source, obtain the gel stent of repairing articular cartilage damage.
In the present invention, the injection of the preparation method of the gel stent of described a kind of repairing articular cartilage damage is modified transparent Matter acid sodium gel, for efficient cross-linked gel, dosage of crosslinking agent is few, has stability and the cohesion of enhancing, has the stream of excellence Becoming and learn performance, plasticity is good and is prone to injection, and internal retention time is long, and filling effect is good, and remains to keep biocompatibility, The present invention can the most quickly prepare the gel stent of compound joint cartilage injury, and method is simple, easy to use, low cost.
Accompanying drawing explanation
The present invention will be further described in detail with specific implementation method below in conjunction with the accompanying drawings.
Fig. 1 is the structural representation of the preparation method of the gel stent of a kind of repairing articular cartilage of present invention damage.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is explained orally further.
Embodiment one
The present embodiment proposes the preparation method of the gel stent of a kind of repairing articular cartilage damage, comprises the following steps:
S1: preparing weight portion is the hyaluronate sodium of 5 parts and the deionized water of 20 parts, hyaluronate sodium and deionized water is mixed Close, at 10 DEG C, react 11h, prepare sodium hyaluronate solution;
S2: preparing weight portion is the PLGA nano-particle of 6 parts and the azo-bis-isobutyrate hydrochloride of 4 parts, by PLGA nano-particle Add in sodium hyaluronate solution, at 15 DEG C, react 10min, be subsequently adding azo-bis-isobutyrate hydrochloride, anti-at 20 DEG C Answer 20min, prepare hyaluronic acid sodium gel complex solution;
S3: hyaluronic acid sodium gel complex solution is injected at articular cartilage damage to be repaired, then through ultraviolet point source Irradiate, obtain the gel stent of repairing articular cartilage damage.
Embodiment two
The present embodiment proposes the preparation method of the gel stent of a kind of repairing articular cartilage damage, comprises the following steps:
S1: preparing weight portion is the hyaluronate sodium of 6 parts and the deionized water of 23 parts, hyaluronate sodium and deionized water is mixed Close, at 13 DEG C, react 12h, prepare sodium hyaluronate solution;
S2: preparing weight portion is the PLGA nano-particle of 7 parts and the azo-bis-isobutyrate hydrochloride of 5 parts, by PLGA nano-particle Add in sodium hyaluronate solution, at 18 DEG C, react 13min, be subsequently adding azo-bis-isobutyrate hydrochloride, anti-at 23 DEG C Answer 25min, prepare hyaluronic acid sodium gel complex solution;
S3: hyaluronic acid sodium gel complex solution is injected at articular cartilage damage to be repaired, then through ultraviolet point source Irradiate, obtain the gel stent of repairing articular cartilage damage.
Embodiment three
The present embodiment proposes the preparation method of the gel stent of a kind of repairing articular cartilage damage, comprises the following steps:
S1: preparing weight portion is the hyaluronate sodium of 8 parts and the deionized water of 25 parts, hyaluronate sodium and deionized water is mixed Close, at 15 DEG C, react 14h, prepare sodium hyaluronate solution;
S2: preparing weight portion is the PLGA nano-particle of 9 parts and the azo-bis-isobutyrate hydrochloride of 7 parts, by PLGA nano-particle Add in sodium hyaluronate solution, at 20 DEG C, react 15min, be subsequently adding azo-bis-isobutyrate hydrochloride, anti-at 25 DEG C Answer 30min, prepare hyaluronic acid sodium gel complex solution;
S3: hyaluronic acid sodium gel complex solution is injected at articular cartilage damage to be repaired, then through ultraviolet point source Irradiate, obtain the gel stent of repairing articular cartilage damage.
The above, the only present invention preferably detailed description of the invention, but protection scope of the present invention is not limited thereto, Any those familiar with the art in the technical scope that the invention discloses, according to technical scheme and Inventive concept equivalent or change in addition, all should contain within protection scope of the present invention.

Claims (4)

1. the preparation method of the gel stent of a repairing articular cartilage damage, it is characterised in that comprise the following steps:
S1: prepare hyaluronate sodium and the deionized water of 20-25 part that weight portion is 5-8 part, by hyaluronate sodium and deionization Water mixes, and reacts 11-14h, prepare sodium hyaluronate solution at 10-15 DEG C;
S2: prepare PLGA nano-particle and the azo-bis-isobutyrate hydrochloride of 4-7 part that weight portion is 6-9 part, by PLGA nanometer Granule adds in sodium hyaluronate solution, reacts 10-15min, be subsequently adding azo-bis-isobutyrate hydrochloride at 15-20 DEG C, At 20-25 DEG C, react 20-30min, prepare hyaluronic acid sodium gel complex solution;
S3: hyaluronic acid sodium gel complex solution is injected at articular cartilage damage to be repaired, then through ultraviolet point source Irradiate, obtain the gel stent of repairing articular cartilage damage.
The preparation method of the gel stent of a kind of repairing articular cartilage the most according to claim 1 damage, it is characterised in that In described S1, preparing weight portion is hyaluronate sodium and the deionized water of 21-24 part of 6-7 part, by hyaluronate sodium and go from Sub-water mixes, and reacts 12-13h, prepare sodium hyaluronate solution at 11-14 DEG C.
The preparation method of the gel stent of a kind of repairing articular cartilage the most according to claim 1 damage, it is characterised in that In described S2, prepare PLGA nano-particle and the azo-bis-isobutyrate hydrochloride of 5-6 part that weight portion is 7-8 part, PLGA is received Rice grain adds in sodium hyaluronate solution, reacts 11-14min, be subsequently adding azo two 2,2-Dimethylaziridine hydrochloric acid at 16-19 DEG C Salt, reacts 22-28min at 21-24 DEG C, prepares hyaluronic acid sodium gel complex solution.
The preparation method of the gel stent of a kind of repairing articular cartilage the most according to claim 1 damage, it is characterised in that In described S3, hyaluronic acid sodium gel complex solution is filled to articular cartilage damage to be repaired, then through ultraviolet point light Source is irradiated, and obtains the gel stent of repairing articular cartilage damage.
CN201610577602.2A 2016-07-21 2016-07-21 A kind of preparation method of the gel stent of repairing articular cartilage damage Withdrawn CN106075574A (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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US20070202084A1 (en) * 2005-12-14 2007-08-30 Anika Therapeutics, Inc. Bioabsorbable implant of hyaluronic acid derivative for treatment of osteochondral and chondral defects
CN102727424A (en) * 2012-07-13 2012-10-17 常州药物研究所有限公司 Sodium hyaluronate gel injection for bone joint cavity and preparation method thereof
CN104225677A (en) * 2013-06-13 2014-12-24 山东省生物药物研究院 Cross-linked hyaluronic acid cell-scaffold material and preparation method and application
CN104587531A (en) * 2014-12-25 2015-05-06 南京臻泉医药科技有限公司 Preparation method for gel scaffold for repairing articular cartilage injuries

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070196342A1 (en) * 2005-12-14 2007-08-23 Sadozai Khalid K Meniscal implant of hyaluronic acid derivatives for treatment of meniscal defects
US20070202084A1 (en) * 2005-12-14 2007-08-30 Anika Therapeutics, Inc. Bioabsorbable implant of hyaluronic acid derivative for treatment of osteochondral and chondral defects
CN102727424A (en) * 2012-07-13 2012-10-17 常州药物研究所有限公司 Sodium hyaluronate gel injection for bone joint cavity and preparation method thereof
CN104225677A (en) * 2013-06-13 2014-12-24 山东省生物药物研究院 Cross-linked hyaluronic acid cell-scaffold material and preparation method and application
CN104587531A (en) * 2014-12-25 2015-05-06 南京臻泉医药科技有限公司 Preparation method for gel scaffold for repairing articular cartilage injuries

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Application publication date: 20161109