CN106474156A - Purposes in preparing medicine for the compositionss - Google Patents

Purposes in preparing medicine for the compositionss Download PDF

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Publication number
CN106474156A
CN106474156A CN201610980007.3A CN201610980007A CN106474156A CN 106474156 A CN106474156 A CN 106474156A CN 201610980007 A CN201610980007 A CN 201610980007A CN 106474156 A CN106474156 A CN 106474156A
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cell
compositionss
chondrocyte
cartilage
cell suspension
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Inventor
裴雪涛
姚海雷
南雪
岳�文
游子娟
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South China Institute Of Biomedicine
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South China Institute Of Biomedicine
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/32—Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
    • A61L27/3817—Cartilage-forming cells, e.g. pre-chondrocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
    • A61L27/3834—Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3839—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by the site of application in the body
    • A61L27/3843—Connective tissue
    • A61L27/3852—Cartilage, e.g. meniscus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/52—Hydrogels or hydrocolloids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/06—Flowable or injectable implant compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Cell Biology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Zoology (AREA)
  • Transplantation (AREA)
  • Developmental Biology & Embryology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Dermatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Botany (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Virology (AREA)
  • Biotechnology (AREA)
  • Dispersion Chemistry (AREA)
  • Rheumatology (AREA)
  • Inorganic Chemistry (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Vascular Medicine (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

The invention discloses purposes in preparing medicine for the compositionss, described medicine is used for repairing cartilage injury, and described compositionss include：Cell suspension and temperature-sensitive hydrogel, wherein cell suspension are by mixing mescenchymal stem cell and chondrocyte and being resuspended in hyaluronic acid solution formation.The compositionss repaired for cartilage injury of the present invention are convenient to be obtained, safe and reliable, and, efficiency high to Chondrocyte Differentiation, cell necessary to tissue repair can be provided for cartilaginous lesion site, and temperature-sensitive hydrogel has the effect of good exogenous cells carrier, the cell in compositionss can be made to be sufficient filling with quickly and efficiently repairing and healing such that it is able to effectively facilitate cartilaginous lesion site at cartilage injury and not to other local migrations.

Description

Purposes in preparing medicine for the compositionss
Technical field
The present invention relates to purposes in preparing medicine for the compositionss.
Background technology
It is that osteoarthritis (osteoarthritis, OA) occur that articular cartilage (articular cartilage, AC) is damaged Major Risk Factors, OA is irreversible, to be palliated the agonizing sufferings by joint replacement when PD is to late period and Recover function.Because the repair ability of articular cartilage is limited it is necessary to early intervention is to prevent from developing into OA.Current controls Treatment mode is intended to stimulate by primary treatment, adjacent tissue and transplanting carrys out repairing articular cartilage.Can by rational repairing and treating To obtain comparatively ideal result in short-term to mid-term, but after longer period of time, easily recur.In recent years, based on biological engineering The tissue engineering technique of the cellular level of tissue is widely studied, and this bioengineered tissue can reappear hyaline cartilage Characteristic, and combine together with original tissue, repairing articular cartilage is damaged significant.
However, current bioengineered tissue repair cartilage injury's aspect research still have to be strengthened.
Content of the invention
It is contemplated that at least solving one of technical problem present in prior art.For this reason, one object of the present invention Be to propose a kind of convenient obtain, safe and reliable, can effectively repair the means of cartilage injury.
It should be noted that the present invention is to be completed based on the following discovery of inventor：
One of wide cartilage repair techniques of cellular level of application are Autologous Chondrocyte transplanting at present (Autologous chondrocyte implantation, ACI) technology.This technology comprises internal operative treatment and thin in vitro Born of the same parents' culture technique：First, the non-bearing region in damaged joints carries out operation acquisition cartilage slices, and is transferred into storing And in the sterile nutrient solution of transport；Then, using collagenase digesting cartilaginous tissue in cell culture chamber, obtain chondrocyte, Using monolayer culture, cultured chondrocytes are expanded to the quantity that can be used for transplanting, filling out of cartilage defects is carried out by surgeon Fill.In this operation process, the chondrocyte of amplification in vitro is expelled to fault location.In order that chondrocyte rests on transplanting portion Position, prevents from floating in a large number, further synovial membrane lobe can be sewn to damage location.However, it is found by the inventors that, Autologous Chondrocyte There is following defect in transplanting：1st, Autologous Chondrocyte transplanting needs Two intrusions to perform the operation, larger to damage to patient.2nd, cartilage is thin In vitro during monolayer amplification, these cell masses lose its phenotype to born of the same parents, and the production of collagen protein is (typically transparent by II type Cartilage) to I type and type III (typical fibrous cartilage) transformation.The result of the change of these phenotypes is that have poor biology The generation of the extracellular matrix of mechanical performance.3rd, donor site provides the limited in one's ability of substantial amounts of chondrocyte.4th, donor set Sickness rate be also Autologous Chondrocyte major obstacle.
And autologous bone marrow mesenchymal stem cells transplanting is also the cartilage repair techniques of the wide cellular level of current application. This technology carries out bone marrow aspiration in the ilium of patient, collects bone marrow；Sample is transferred to toilet and carries out cell separation；To bone marrow Add phosphate buffer in puncture fluid, be then transferred in lymphocyte separation medium, be centrifuged and collect mononuclearcell and count Number, is washed with PBS, is then seeded to culture in culture bottle, so that gained cell amplification is cultivated, passes to the second filial generation and prepares to move Plant；Before transplanting using colony forming unit (Colony-forming unit, CFU) and Flow cytometry cell gram Grand Forming ability and the expression of cell surface marker；Then, the MSCs pancreatin of the second filial generation is digested, and be resuspended in life During treating blood disorderss are clear, and it is loaded in asepsis injector, under perspective, at cell infusion to the knee injuries of patient.However, inventor Find, autologous bone marrow mesenchymal stem cells transplanting has following defect：1st, bone marrow aspiration brings misery to patient.2nd, cell is direct It is expelled to injury region, does not do other measures, cell may float in a large number.3rd, brachymedial phase effect is preferable, but long-time after The injury region pain of patient has risen, and ability to act has also declined.
And mescenchymal stem cell (mesenchymal stem cells, MSCs) transplanting is the very promising strategy of one kind, Because MSCs has high proliferation ability and has the potential being divided into chondrocyte, and then form cartilage.MSCs is that fusiformis is thin Born of the same parents, have fast breeding and self-renewal capacity, are present in a large amount of tissues, including bone marrow, synovial tissue, blood, fatty group Knit and periosteal tissue.They have polyphyly differentiation potential, can be divided into various kinds of cell type to create and to repair mesenchyme group Knit.MSCs can be to one-tenth cartilage, skeletonization, fatty development ways differentiation.Regulatory factor can promote the cartilage of MSC to occur, for example Transforming growth factor (TGF-β) and dexamethasone, this is confirmed with simple external model.
And then, inventor passes through a series of researchs and finds, using the mescenchymal stem cell (Umbilical in umbilical cord source Cord Mesenchymal stem cells, UCMSC) it is transplanted at the knee joint injury of patient, can damage effectively treatment cartilage Wound.And, existing ripe UCMSC isolated culture method, and umbilical cord at present easily obtains it is not necessary to take invasive to patient Operation, it is not required that extracting cartilage in other positions, can effectively reduce the misery of patient.And MSC can fast breeding and from I updates, and has into the potential of cartilage differentiation, ensure that the vigor of neocartilage cell, and there is not the hidden of sickness rate Suffer from.
Further, inventor before transplantation, carries out into chondrocyte induction differentiation, to promote UCMSC to cartilage to part UCMSC Direction breaks up, and the chondrocyte of UCMSC and induction is combined with hyaluronic acid (HA) and temperature-sensitive hydrogel, and result can Effectively prevent cell extensive migration, reach the effect of long-term treatment.Wherein, temperature sensitive type poly lactic acid hydrogel is below 37 DEG C Liquid, will form gel after reaching 37 DEG C, play a part exogenous cells carrier, can promote cell movement, stick, Propagation and differentiation, and provide structural support so that cell activity at defect, will not large area move.
Thus, in one aspect of the invention, the invention provides purposes in preparing medicine for the compositionss, described medicine For repairing cartilage injury.According to embodiments of the invention, said composition includes：Cell suspension and temperature-sensitive hydrogel, wherein Described cell suspension is by mixing mescenchymal stem cell and chondrocyte and being resuspended in hyaluronic acid solution formation.
It is surprisingly found by the inventors that, the compositionss repaired for cartilage injury of the present invention are convenient to be obtained, safe and reliable, and And, to the efficiency high of Chondrocyte Differentiation, cell necessary to tissue repair can be provided for cartilaginous lesion site, and temperature sensitive type Hydrogel has the effect of good exogenous cells carrier, the cell in compositionss can be made to be sufficient filling with cartilage injury and Quickly and efficiently repair and heal such that it is able to effectively facilitate cartilaginous lesion site not to other local migrations.
According to embodiments of the invention, in described cell suspension, described mescenchymal stem cell and described chondrocyte Mixed proportion is 1:1～4:1.Thus, cartilage differentiation efficiency high, can provide necessary to tissue repair for cartilaginous lesion site Cell.
According to embodiments of the invention, in described cell suspension, the content of hyaluronic acid is 5～30mg/ml.Thus, Cell mixture is good with the composite effect of hyaluronic acid and temperature-sensitive hydrogel, can effectively prevent cell extensive migration, Such that it is able to reach the effect of long-term treatment.
According to embodiments of the invention, the volume ratio of described cell suspension and described temperature-sensitive hydrogel is 1:1～2.By This, temperature-sensitive hydrogel is good to the supporting effect of the mescenchymal stem cell in cell suspension and chondrocyte mixture, Jin Erneng The cell in compositionss is enough made to be sufficient filling with damaging such that it is able to effectively facilitate cartilage at cartilage injury and not to other local migrations Traumatic part position is quickly and efficiently repaired and is healed.
According to embodiments of the invention, described temperature-sensitive hydrogel is temperature sensitive type poly lactic acid hydrogel.Thereby, it is possible to effective Carry mescenchymal stem cell and chondrocyte mixture, and so that it is sufficient filling with cartilage injury and not to other local migrations.
According to embodiments of the invention, described temperature sensitive type poly lactic acid hydrogel is MPEG-PLGA.Thus, it is as external source Making good use of of sexual cell carrier, can make the cell in compositionss be sufficient filling with cartilage injury and not to other local migrations, Quickly and efficiently repair and heal so as to effectively facilitate cartilaginous lesion site.
According to embodiments of the invention, described mescenchymal stem cell is umbilical cord mesenchymal stem cells.Thus, mesenchyme is done carefully Born of the same parents' wide material sources, easily obtain, safe and harmless, and the efficiency high to cartilage differentiation.
According to embodiments of the invention, described chondrocyte is by the preferred umbilical cord mesenchymal stem cells of mescenchymal stem cell Induction obtains.And, the abductive approach of chondrocyte is not particularly limited, as long as can be from the preferred umbilical cord of mescenchymal stem cell Mescenchymal stem cell effectively induces acquisition chondrocyte.Thus, the compositionss repaired for cartilage injury, to chondrocyte The efficiency high of differentiation, can provide cell necessary to tissue repair for cartilaginous lesion site.
In addition it is also necessary to illustrate, the present invention has at least one of following advantages：
1st, the present invention obtains mescenchymal stem cell, wide material sources by garbage umbilical cord, can obtain in a large number, and will not be to patient Damage.
2nd, the present invention carries out the induction differentiation in chondrocyte direction to part UCMSC, promotes UCMSC to cartilage differentiation Efficiency.
3rd, temperature-sensitive hydrogel can play the effect of good exogenous cells carrier so that cell can be sufficient filling with At cartilage injury, and not to other local migrations.
The additional aspect of the present invention and advantage will be set forth in part in the description, and partly will become from the following description Obtain substantially, or recognized by the practice of the present invention.
Specific embodiment
Below in conjunction with embodiment, the solution of the present invention is explained.It will be understood to those of skill in the art that it is following Embodiment is merely to illustrate the present invention, and should not be taken as limiting the scope of the invention.Unreceipted particular technique or bar in embodiment Part, carry out according to the technology described by document in the art or condition or according to product description.Agents useful for same or instrument The unreceipted production firm person of device, be can by city available from conventional products.
Embodiment 1
Prepare, according to following steps, the compositionss repaired for cartilage injury, and transplanting is carried out to patient cartilage injury and repair Multiple：
1st, the separation and Culture of UCMSC
The fresh umbilical cord got is sent into GMP workshop, separates and obtain UCMSC.UCMSC is cultivated amplification；And take out Part cell carries out chondroblast induction, expands, prepare transplanting after obtaining a number of chondrocyte.
2nd, prepare before transplanting
The chondrocyte that UCMSC obtained above is obtained with induction differentiation, is digested with 0.25% pancreatin, is used in combination Brine, then by UCMSC and chondrocyte according to 1:1～4:1 ratio mixes and is resuspended in hyaluronic acid solution In, to obtain cell suspension, wherein in cell suspension, the content of hyaluronic acid is 5～30mg/ml.By this cell suspension and temperature Quick type polylactic acid hydrogel MPEG-PLGA is mixed with 1: 1～2 volume ratio, and being placed in shaking table makes it fully mix for a period of time, with Just the compositionss repaired for cartilage injury of the present invention are obtained.
Then, the cell sampling in the compositionss present invention repaired for cartilage injury carries out microorganism, virus five Item, mycoplasma, endotoxin and cell function detection, to guarantee safety.
3rd, transplant
Using joint cavity injection method.Wherein, patient carries out arthroscopy before accepting injection, determines at joint injury Size, thickness etc., with every square centimeter 5 × 106The density of cell is injected.
4th, effect observation after transplanting
After treatment, periodically adopt the improvement situation of nuclear magnetic resonance image check knee joint function.
It was found that the cell in the compositionss repaired for cartilage injury of the present invention can be sufficient filling with cartilage injury Place and not to other local migrations, cartilaginous lesion site healing is quick, effectively.
Comparative example 1
Method according to embodiment 1 prepares the compositionss repaired for cartilage injury, and patient cartilage injury is moved Plant and repair, differ only in：
Chondrocyte induction is not carried out to UCMSC, that is, the cell in cell suspension is all using UCMSC.
Observe after transplanting, patient's cartilaginous lesion site chondroid tissue, Principle of Pain is alleviated, damage to have and to a certain degree heal Close.
Comparative example 2
Method according to embodiment 1 prepares the compositionss repaired for cartilage injury, and patient cartilage injury is moved Plant and repair, differ only in：
The ratio of the UCMSC in cell suspension and chondrocyte is 1：3.
Observe after transplanting, patient's cartilaginous lesion site healing speed is slow.
Comparative example 3
Method according to embodiment 1 prepares the compositionss repaired for cartilage injury, and patient cartilage injury is moved Plant and repair, differ only in：
The ratio of cell suspension and temperature sensitive type poly lactic acid hydrogel MPEG-PLGA is 1: 3.
Observe after transplanting, patient's cartilaginous lesion site chondrocyte formation efficiency is relatively low, thus healing speed is slow.
Comparative example 4
Method according to embodiment 1 prepares the compositionss repaired for cartilage injury, and patient cartilage injury is moved Plant and repair, differ only in：
The ratio of cell suspension and temperature sensitive type poly lactic acid hydrogel MPEG-PLGA is 1：3.
Observe after transplanting, patient's cartilaginous lesion site chondrocyte formation efficiency is relatively low, and healing speed is slow.
Comparative example 5
Method according to embodiment 1 prepares the compositionss repaired for cartilage injury, and patient cartilage injury is moved Plant and repair, differ only in：
Do not adopt temperature sensitive type poly lactic acid hydrogel MPEG-PLGA (carrying out injection transplantation only with cell suspension).
Observe after transplanting, a large amount of drift of the cell in compositionss is walked, patient's cartilaginous lesion site chondrocyte formation efficiency Relatively low, healing speed is slow.
Comparative example 6
Method according to embodiment 1 prepares the compositionss repaired for cartilage injury, and patient cartilage injury is moved Plant and repair, differ only in：
Hyaluronic acid solution is substituted using normal saline.
Observe after transplanting, a large amount of drift of the cell in compositionss is walked, patient's cartilaginous lesion site chondrocyte formation efficiency Relatively low, healing speed is slow.
In the description of this specification, reference term " embodiment ", " some embodiments ", " example ", " specifically show The description of example " or " some examples " etc. means specific features, structure, material or the spy describing with reference to this embodiment or example Point is contained at least one embodiment or the example of the present invention.In this manual, to the schematic representation of above-mentioned term not Necessarily refer to identical embodiment or example.And, the specific features of description, structure, material or feature can be any One or more embodiments or example in combine in an appropriate manner.
Although an embodiment of the present invention has been shown and described, it will be understood by those skilled in the art that：Not Multiple changes, modification, replacement and modification can be carried out to these embodiments in the case of the principle of the disengaging present invention and objective, this The scope of invention is limited by claim and its equivalent.

Claims (8)

1. purposes in preparing medicine for the compositionss, described medicine is used for repairing cartilage injury it is characterised in that described compositionss Including：Cell suspension and temperature-sensitive hydrogel, wherein said cell suspension is by mixing mescenchymal stem cell and chondrocyte Merge and be resuspended in hyaluronic acid solution formation.
2. purposes according to claim 1 is it is characterised in that in described cell suspension, described mescenchymal stem cell and The mixed proportion of described chondrocyte is 1:1～4:1.
3. purposes according to claim 1 is it is characterised in that in described cell suspension, and the content of hyaluronic acid is 5～ 30mg/ml.
4. purposes according to claim 1 is it is characterised in that the volume of described cell suspension and described temperature-sensitive hydrogel Than for 1:1～2.
5. purposes according to claim 1 is it is characterised in that described temperature-sensitive hydrogel is temperature sensitive type poly lactic acid water-setting Glue.
6. purposes according to claim 4 is it is characterised in that described temperature sensitive type poly lactic acid hydrogel is MPEG-PLGA.
7. purposes according to claim 1 is it is characterised in that described mescenchymal stem cell is umbilical cord mesenchymal stem cells.
8. purposes according to claim 1 is it is characterised in that described chondrocyte is by the preferred umbilicuss of mescenchymal stem cell Obtain with mescenchymal stem cell induction.
CN201610980007.3A 2016-11-08 2016-11-08 Purposes in preparing medicine for the compositionss Pending CN106474156A (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108578617A (en) * 2018-04-09 2018-09-28 深圳市莱利赛生物科技有限公司 A kind of application of umbilical cord blood mesenchymal stem cell drug in promoting knee cartilage regeneration
CN109172859A (en) * 2018-09-06 2019-01-11 上海长海医院 Human stem cell source excretion bluk recombination exogenous hyaluronic acid is preparing the application in skin wound defect repair drug or material
CN112336751A (en) * 2020-11-27 2021-02-09 福建华民生物科技有限公司 Medicine for treating cartilage injury and arthritis and matched injection device thereof
CN114931670A (en) * 2022-03-17 2022-08-23 康领泰(上海)生物科技有限公司 Active substance and application of self-healing hydrogel thereof in cartilage repair

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CN114931670B (en) * 2022-03-17 2024-01-16 康领泰(上海)生物科技有限公司 Application of active substance and self-healing hydrogel thereof in cartilage repair

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Application publication date: 20170308