CN110464878A - A kind of application of VEGF - Google Patents

A kind of application of VEGF Download PDF

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Publication number
CN110464878A
CN110464878A CN201910850399.5A CN201910850399A CN110464878A CN 110464878 A CN110464878 A CN 110464878A CN 201910850399 A CN201910850399 A CN 201910850399A CN 110464878 A CN110464878 A CN 110464878A
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fat
vegf
graft preparation
preparation
moist
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CN201910850399.5A
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杨涛
杨鸣谦
王静
贾仕贤
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Shenzhen To Bo Biology Technology Co Ltd
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Shenzhen To Bo Biology Technology Co Ltd
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Priority to CN201910850399.5A priority Critical patent/CN110464878A/en
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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
    • A61L27/36Materials 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
    • A61L27/3604Materials 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 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • 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
    • A61L27/36Materials 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
    • A61L27/38Materials 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
    • A61L27/3804Materials 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
    • A61L27/3834Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
    • 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
    • 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
    • A61L27/54Biologically active materials, e.g. therapeutic substances
    • 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412Tissue-regenerating or healing or proliferative agents
    • A61L2300/414Growth factors

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Transplantation (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Cell Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Botany (AREA)
  • Urology & Nephrology (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Hematology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Materials For Medical Uses (AREA)

Abstract

The invention discloses the application of the application of VEGF a kind of, especially VEGF in the graft preparation that preparation is used for moist CAL.The present invention promotes blood vessel synthesis and endothelial cell proliferation using moist CAL joint VEGF, extends the time-to-live of transplant fat, reduces adiponecrosis, significantly improves the survival rate and quality of transplant fat tissue;Fat absorption rate is reduced, filler is made to tend towards stability, further promotes the treatment level in terms of domestic medical and beauty treatment.

Description

A kind of application of VEGF
Technical field
The invention belongs to fields of biomedicine, and in particular to prepared by a kind of application of VEGF, in particular to a kind of VEGF For the application in the graft preparation of moist CAL.
Background technique
The fat stem cell (adipose-derived stem cells, ADSCs) in body fat source is Zuk in 2001 Deng a kind of adult stem cell found from the fat that vacuum fat sucking art is extracted out.With other mescenchymal stem cells (mesenchymal Stem cells, MSCs) equally, ADSCs has the potential of self-renewing and Multidirectional Differentiation.
It is in recent years to have moist fat stem cell auxiliary Auto fat granule filling transplantation, referred to as moist CAL (cell more Assisted lipotransfer) development record, directly utilize body fat aspirate stand after syringe inner lipid and Liquid portion is rich in without separating the fresh compound Autologous fat grafting of ADSCs and SVF, improves fat cell survival rate.To the greatest extent Pipe still has filler property unstable when in this way, being directly applied to the fat filling of partes corporis humani position, such as fat survival Time is short, is easy going out for phenomena such as being absorbed (postoperative transplant fat absorptivity may be up to 40%~60%) and adiponecrosis It is existing.
Since fat stem cell culture differentiation mechanism is unknown, the various physiology, pathological change after fat transfer are complicated, fat The reason of necrosis is not yet clear, therefore still lacks effective intervention or treatment means.Co culture system in vitro the study found that by ADSCs with Mature fat cell co-cultures, or using the secretion of adipose tissue or conditioned medium etc., also can promote ADSCs at rouge Differentiation, mechanism may be related with the various growth factors wherein contained.Wang Yong is identical to be had growth factor and fat stem cell Trial (the identical human adipose-derived stem cell of Wang Yong and the VEGF-PLGA nanosphere slow-released system building engineering fat being used in combination Correlative study [J] the medical information of tissue), but be directed to its growth that can promote capilary and fat can be promoted dry Cell differentiation is attempted and is explored in the intracorporal stability of people after not mixing to it with stem cell further, with And whether all growth factors can be used in mixing with stem cell, growth factor and stem cell and other compositions is common After mixing the mixture have without side-effects, growth factor for the other compositions that are mixed with human body whether there is or not the equal nothing such as influence It attempts and discloses.Moreover the VEGF in the prior art need to be made as the form of sustained release VEGF to avoid a large amount of VEGF and rouge The problem of persistently playing a role is difficult to after the mixing of fat stem cell.
Summary of the invention
The technical problem to be solved by the present invention is to effectively can be used for fat filling shaping for shortage in the prior art Preparation, especially for moist CAL graft preparation defect, provide the application of VEGF a kind of, especially a kind of VEGF Application in graft preparation of the preparation for moist CAL.
It is (such as moist for carrying out the mostly mixture of fat stem cell and lipochondrion of fatty filling in the prior art CAL), the fatty time-to-live is short after transplanting, and has serious adiponecrosis phenomenon, and fat absorption rate is high, there has been no one kind Effective method guarantees the stability of the mixture for fat filling.Thus, be badly in need of a kind of stability it is good for carrying out The preparation of fat filling shaping, is especially used for the graft preparation of moist CAL.Present inventors have surprisingly found that can by VEGF with The mixture of fat stem cell and lipochondrion combines the graft preparation used as moist CAL, and has been surprisingly found that a variety of After component synergistic effect, VEGF can continually and steadily play a role, without being made as the form of sustained release VEGF, so that it may Significant the phenomenon that alleviating adiponecrosis, fat absorption rate is greatly reduced, guarantees graft stability, to reach scheduled effect Fruit.
The present invention mainly solves above-mentioned technical problem by the following technical programs.
The present invention provides application of the VEGF in the graft preparation that preparation is used for moist CAL.
Preferably, concentration of the VEGF in the graft preparation is 15~25ng/ml;More preferably, described Concentration of the VEGF in the graft preparation is 20ng/ml.
In a preferred embodiment of the present invention, the graft preparation includes moist Grainy fat tissue and fat stem cell Mixed packing;The mixed packing by the way that in vitro adipose tissue is stood naturally, suspending obtains.
The present invention also provides a kind of graft preparations for moist CAL, and it is dry thin that it includes moist Grainy fat tissues and fat The mixed packing of born of the same parents, the graft preparation also includes VEGF, concentration of the VEGF in the graft preparation For 15~25ng/ml.
Preferably, concentration of the VEGF in the graft preparation is 20ng/ml.
As described above, the mixed packing in the present invention by vitro adipose tissue by standing naturally, suspending It arrives.
In the present invention, the preferred temples of the graft preparation fills graft preparation.
On the basis of common knowledge of the art, above-mentioned each optimum condition, can any combination to get each preferable reality of the present invention Example.
The reagents and materials used in the present invention are commercially available.
The positive effect of the present invention is that:
The present invention promotes blood vessel synthesis and endothelial cell proliferation using moist CAL joint VEGF, extends transplant fat Time-to-live, reduce adiponecrosis, significantly improve the survival rate and quality of transplant fat tissue;Reduce fat absorption Rate makes filler tend towards stability, and further promotes the treatment level in terms of domestic medical and beauty treatment, effect is better than angiogenic growth Hepatocyte growth factor (hepatocyte growth factor, HGF).
Specific embodiment
The present invention is further illustrated below by the mode of embodiment, but does not therefore limit the present invention to the reality It applies among a range.In the following examples, the experimental methods for specific conditions are not specified, according to conventional methods and conditions, or according to quotient The selection of product specification.
The preparation of 1 Grainy fat tissue of embodiment and fat stem cell " particle " mixed packing
1.1 lipsuctions: the range for sufficiently marking and needing to fill is linked up with patient by operation doctor.Bilateral Symmetry as far as possible, such as There is bilaterally asymmetrical another planning, calculates the total volume for taking around fat.It takes and makees donor site on the inside or outside of bilateral thigh, Using 0.04% lidocaine swelling anaesthesia of manual injection device (avoiding hypertonia too fast), with the noninvasive fat suction needle of 2mm and 20mL Disposable screw syringe liposuction, liposuction amount are one times of requirement.
1.2 prepare Grainy fat tissue and fat stem cell " particle " mixed packing: after being filled syringe, syringe is upright Naturally Inside Syringe endoparticle fatty underlayer moisture (if moisture content is seldom, can also be not excluded for) after suspending is stood, not by liposuction Aspirate pours into physiology salt basin the rinsing Grainy fat tissue aspirate that suspends by syringe bucket deutostoma, does not remove and injects after standing Device endoparticle fat upper layer lipid (grease) part, rotary-classify technology purified particles fat and stem cell particle, are not centrifuged Liquid portion between mixed packing particle in exhaustjet device obtains injection fillers object (the moist fat stem cell of Liu Naijun, Wang Yan Assist Autologous granular fat graft art clinical observation China aesthetic medicine, 2012,21 (11): 1906-1910).
The mixing of 1.3 mixed packings and growth factor: 1. blank control group is simple mixing filler group;2. HGF pairs It is that mixed packing and HGF (20ng/ml) are mixed rapidly according to group;3. VEGF experimental group is mixed packing and VEGF (20ng/ Ml it) mixes rapidly.
1.4 autologous filler objects transplanting: before injection transplantation, by elder generation, area local swelling infiltration anesthesia (0.125% hydrochloric acid benefit card Because of epinephrine solution containing 1:1000000) make each hierarchical organization hydraulic buckling.After anesthesia, the rouge for being 1.5~2.0mm with needle diameter Fat injection needle selects more covert position inserting needle, the fat filling object amount injection fill area that will be calculated along temples muscle and deep It domain can the injection of the Huan Maning while withdraw of the needle when injection rate is more than need to inject 30%.Injection zone is observed after completing injection The filler distribution situation in domain, position unevenly distributed is lightly adjusted with wet gauze.Injection process follows strictly " three low three It is more " principle (low head injection, low-speed centrifugal, low capacity injection, Multiple tunnel, more planes, multi-point injection).Injection volume be 30~ 60ml/ is unilateral;Because of injection fillers of straightening crooked, there is obvious tumefaction by area's early postoperation, ice compress can be interrupted in postoperative 48h, it can office after 72h Portion's hot packing restores nature in 2 weeks.
The moist CAL of 2 multiple spot of embodiment, Multiple tunnel fills initial clinical experience
2.1 are included in standard
By using the mode of multiple spot, Multiple tunnel, between 2017~2018 years, carried out at many levels using autologous fat transplantation Moist CAL temples filling.Patient body is without other exceptions and agrees to sign informed consent form.
2.2 data and method
2.2.1 blank control group: 15, male 1 is female 14, the age 18~49 years old, 32.3 years old average.Operation is temporo Portion's filling, or merge other position autologous fats and fill, because of facial injury soft tissue depression 3 in patient, face is congenital Recess 2, because aging causes concave temporal area 10.HGF control group: 15, male 2 is female 13, the age 19~48 years old, average 33.5 years old.Operation is temples filling, or merges other position autologous fats and fill, because facial injury soft tissue is recessed in patient 4 are fallen into, facial congenital depression 1, because aging causes concave temporal area 10.VEGF experimental group: 15, male 2, female 13, It is age 20~53 years old, 35.1 years old average.Operation is temples filling, or merges the filling of other position autologous fats, in patient because Facial injury soft tissue depression 1, facial congenital depression 3, because aging causes concave temporal area 11.
2.2.2 operation method
(1) it crosses and links up the range for sufficiently marking and needing to fill, as far as possible Bilateral Symmetry with patient, if any bilaterally asymmetrical Another planning, calculates the total amount for taking around fat.
(2) it uses in embodiment 1 under the transplanting systemic vein general anesthesia of control group and experimental group fat granules, notch position In in hair line, the local anaesthesia of notch is made of 0.5% lidocaine, does the notch of an about 1cm, hemostasis is thorough, with diameter 1mm Short tube is injected at hypodermic layer according to scribe area, it then follows Multiple tunnel, threadiness injection.After injection is satisfied, the shallow muscle of temporo is cut with sharp knife Film layer is thoroughly stopped blooding, is injected with injection-tube, if it is desired, cut deep temporal fascia layer again, and injected, accomplish to inject as far as possible Uniformly, excess is injected, and skin suture layer is suitably massaged, and is kept smooth.
(3) post surgery treatment is postoperative does not wrap up, and keeps notch clean.
2.3 postoperative outcome
Follow-up After 3~36 months, 8.2 months average, control group operation is satisfied with 11, satisfaction rate 73.33%.Operation Dissatisfied predominantly fat is at a specified future date to be absorbed, and tumour is formed.Specific complication has: 2 hand 3 months after operation follow-ups, temples injection Position filling effect is unobvious.It is obvious that oedema occur in 2 postoperative 6~14d.Part is slightly congested, and pain is unobvious, checks blood routine As a result normal, consider that local absorption causes, using improving after vein antibiotic 3d.Experimental group operation is satisfied with 14, and satisfaction rate is 93.33%.The dissatisfied predominantly fat of operation is at a specified future date to be absorbed.Specific complication has: follow-up in 6 months after 1 operation, temples injection Position filling effect is unobvious.
Carry out the temples filling preliminary clinical examination of Grainy fat tissue stem cell mixed packing using multi-level, Multiple tunnel mode It tests.To reduce fat absorption rate, filler is made to tend towards stability.Reduce adiponecrosis, extends the survival of transplant fat Time further promotes the treatment level in terms of domestic medical and beauty treatment.

Claims (9)

  1. Application of the 1.VEGF in the graft preparation that preparation is used for moist CAL.
  2. 2. application as described in claim 1, which is characterized in that concentration of the VEGF in the graft preparation is 15 ~25ng/ml.
  3. 3. application as claimed in claim 2, which is characterized in that concentration of the VEGF in the graft preparation is 20ng/ml。
  4. 4. application as claimed in any one of claims 1 to 3, which is characterized in that the graft preparation includes moist particle The mixed packing of fat and fat stem cell;The mixed packing by the way that in vitro adipose tissue is stood naturally, it is outstanding It is floating to obtain.
  5. 5. such as the described in any item applications of Claims 1 to 4, which is characterized in that the graft preparation is that temples filling moves Galenical.
  6. 6. a kind of graft preparation for moist CAL, it includes moist Grainy fat tissue and the mixed packing of fat stem cell, It is characterized in that, the graft preparation also includes VEGF, concentration of the VEGF in the graft preparation is 15 ~25ng/ml.
  7. 7. graft preparation as claimed in claim 6, which is characterized in that the VEGF is dense in the graft preparation Degree is 20ng/ml.
  8. 8. graft preparation as claimed in claims 6 or 7, which is characterized in that the mixed packing is by will be in vitro Adipose tissue is stood naturally, suspending obtains.
  9. 9. such as the described in any item graft preparations of claim 6~8, which is characterized in that the graft preparation is temples Fill graft preparation.
CN201910850399.5A 2019-09-10 2019-09-10 A kind of application of VEGF Pending CN110464878A (en)

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Citations (5)

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Publication number Priority date Publication date Assignee Title
WO2013003229A1 (en) * 2011-06-28 2013-01-03 Veris Medical, Inc. System and method for collagen isolation
KR20150088374A (en) * 2014-01-23 2015-08-03 주식회사 이에이치엘바이오 Stem cell medium containing cell growth factors from human adipose derived stem cells and cosmetic composition for improvement atopic syndrom prepared therefrom
US20160289641A1 (en) * 2015-04-03 2016-10-06 Industry-Academic Cooperation Foundation, Yonsei University Method for promoting hair growth using composition comprising pdgf-d treated adipose-derived stem cells
CN106421920A (en) * 2016-11-16 2017-02-22 沈阳细胞治疗工程技术研发中心有限公司 Fat filler and preparation method thereof
CN107714727A (en) * 2017-10-24 2018-02-23 成都远山博桥生物科技有限公司 A kind of enriching fat stem cell culture supernatant preparation, its preparation method and application

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013003229A1 (en) * 2011-06-28 2013-01-03 Veris Medical, Inc. System and method for collagen isolation
KR20150088374A (en) * 2014-01-23 2015-08-03 주식회사 이에이치엘바이오 Stem cell medium containing cell growth factors from human adipose derived stem cells and cosmetic composition for improvement atopic syndrom prepared therefrom
US20160289641A1 (en) * 2015-04-03 2016-10-06 Industry-Academic Cooperation Foundation, Yonsei University Method for promoting hair growth using composition comprising pdgf-d treated adipose-derived stem cells
CN106421920A (en) * 2016-11-16 2017-02-22 沈阳细胞治疗工程技术研发中心有限公司 Fat filler and preparation method thereof
CN107714727A (en) * 2017-10-24 2018-02-23 成都远山博桥生物科技有限公司 A kind of enriching fat stem cell culture supernatant preparation, its preparation method and application

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