CN105175501A - Polypeptide for promoting bone formation, synthesis method and applications thereof - Google Patents
Polypeptide for promoting bone formation, synthesis method and applications thereof Download PDFInfo
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Abstract
The present invention belongs to the technical field of biological medicine, and discloses a polypeptide for promoting bone formation, a synthesis method and applications thereof, wherein the polypeptide has the amino acid residue sequence represented by SEQ ID NO:1 in the sequence table. According to the present invention, the calcined bone targeting binding polypeptide can promote the bone cell generation, the synthesis method is simple, the mass production can be achieved, and the synthesized polypeptide has characteristics of degradation resistance and high activity, and is especially suitable for osteoporosis treatment.
Description
Technical field
The invention belongs to field of biomedicine technology, be specifically related to a kind of promote osteogenetic polypeptide and synthetic method thereof and application.
Background technology
At present, by the research to BMP mechanism of action, the bioactive sequence wherein played a role is selected to carry out external synthesis, and devise there is the active region of target in conjunction with mineral substance support, obtain can be combined with calcining ox bone bracket stable, the BMP-2 functional polypeptide of slowly-releasing, synthesize cost lower than 1% of BMP-2 market value.With the active contrast experiment of BMP-2 albumen, BMP-2 functional polypeptide is all better than BMP-2 albumen for the promoter action of the key indexs such as osteoblastic propagation and alkaline phosphatase activities.Carry out experimental evaluation in animal body at present, in 1-2 month, will main result be obtained.This functional polypeptide also has potential application prospect in the treatment of osteoporosis.
The major issue that current BMP-2 exists can not stablize compound with timbering material, and in body, release is run off fast, therefore needs in production to strengthen consumption, add the side effect such as ectopic osteogenesis and inflammation risk, and cost is high.The eukaryotic expression system somewhat expensive that U.S. BMP-2 product adopts, active better.Domestic prokaryotic expression system cost is lower, poor activity.
There is the base group modification BMP that people will be combined with collagen before, obtain the binding ability with bone, but collagen is the composition that in body, Various Tissues is common, collagen component and the osseous tissue of such as tendon are completely the same, also containing abundant this collagen in muscular fascia, in addition blood vessel and skin even in the tissue such as cartilage, the various fibers of meniscus all containing collagen component.Therefore its security remains a unsettled problem.
How effectively BMP is controlled in osseous tissue local, avoid and the attached combination of other histocyte parent, become an important problem.
Summary of the invention
The object of the present invention is to provide and a kind of promote osteogenetic polypeptide and synthetic method thereof and application.
The osteogenetic polypeptide of a kind of promotion is the polypeptide of one of following amino acid residue sequences:
1) sequence table SEQ IDNO:1 (KIPKASSVPTELSAISTLYL), shown amino acid residue sequence;
2) amino acid residue sequence shown in sequence table SEQ IDNO:1 (KIPKASSVPTELSAISTLYL) had a polypeptide of forging bone target combined function through the replacement of 1 to 3 amino-acid residue, disappearance or interpolation.
Further, present invention also offers the gene of the osteogenetic polypeptide of the above-mentioned promotion of coding, for adopting engineered method to carry out production aforementioned polypeptides, and taking purification process conventional in genetically engineered to be purified.
The synthetic method of the osteogenetic polypeptide of above-mentioned promotion, carry out in accordance with the following steps:
(1) with RinkAmide resin or Fmoc-Gly-WANG resin for starting raw material, with the amino acid of Fmoc protection for monomer, condensing agent is adopted to carry out connecing reactive polypeptide, connect amino acid one by one, last peptide chain uses the thiohydracrylic acid of protection, after obtaining protection resin, synchronously carry out de-side chain protected group and cut peptide;
(2) add and cut peptide reagent and carry out cutting peptide;
(3) be solvent with ether, precipitate and collect and promote osteogenetic polypeptide crude product;
(4) by soluble in water for osteogenetic polypeptide crude product, regulate pH to 7.5-10.0 with ammoniacal liquor, collect and promote osteogenetic polypeptide;
(5) the osteogenetic polypeptide of promotion step (4) collected, by HPLC separation and purification, obtains target product.
Described condensing agent is HBTU/HOBt, TBTU/HOBt, BOP/HOBt, TBTU/HOAt, HBTU/HOA or BOP/HOAt.
Described peptide reagent of cutting is TFA/EDT/HAc/TIS/EDT.The osteogenetic polypeptide of above-mentioned promotion promotes the application in the medicine of bone synthesis in preparation.
Beneficial effect of the present invention: the osteogenetic polypeptide of promotion of the present invention, can promote the generation of osteocyte, its synthetic method is simple, can mass production, and the polypeptide of synthesis is not easy degraded in vivo, active high, is specially adapted to the treatment of osteoporosis.
Embodiment
Below in conjunction with specific embodiment, the present invention will be further described.
BMP-2 protein sequence used in following embodiment is: SEQIDNO:3QAKHKQRKRLKSSCKRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGEC PFPLADHLNSTNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNY QDMVVEGCGCR.Its gene order is: SEQIDNO:4 (CGCGGATCCCAGGCGAAACATAAACAACGTAAACGCCTGAAAAGTTCCTGCAAACG TCATCCGCTGTATGTTGATTTTAGCGACGTCGGCTGGAACGATTGGATTGTTGCTC CGCCGGGCTATCATGCGTTCTACTGCCACGGTGAATGTCCGTTTCCGCTGGCCGAC CATCTGAACTCTACCAATCACGCAATTGTTCAGACGCTGGTTAACAGTGTCAATTC CAAAATCCCGAAAGCGTGCTGTGTCCCGACCGAACTGTCAGCGATCTCGATGCTGT ACCTGGATGAAAATGAAAAAGTGGTCCTGAAAAACTATCAAGACATGGTGGTGGAA GGCTGTGGCTGCCGCTGACTCGAGCGG).
Embodiment 1
1. the synthesis of the present embodiment induced osteogenesis polypeptide
SEQIDNO：1(KIPKASSVPTELSAISTLYL)。
The synthetic method of the osteogenetic polypeptide of above-mentioned promotion, carry out in accordance with the following steps:
(1) with RinkAmide resin or Fmoc-Gly-WANG resin for starting raw material, with the amino acid of Fmoc protection for monomer, condensing agent (HBTU/HOBt) is adopted to carry out connecing reactive polypeptide, connect amino acid one by one, last peptide chain uses the thiohydracrylic acid of protection, after obtaining protection resin, synchronously carry out de-side chain protected group and cut peptide;
(2) add and cut peptide reagent (TFA/EDT/HAc/TIS/EDT) and carry out cutting peptide;
(3) be solvent with ether, precipitate and collect and promote osteogenetic polypeptide crude product;
(4) by soluble in water for osteogenetic polypeptide crude product, regulate pH to 7.5-10.0 with ammoniacal liquor, collect and promote osteogenetic polypeptide;
(5) the osteogenetic polypeptide of promotion step (4) collected, by HPLC separation and purification, obtains target product.
2. test cell line
(1) related equipment is tested
Instrument designation Model manufacturer
Clean bench NU-126-006Nuaire
Research grade inverted microscope IX41OLYMPUS
Refrigerated centrifuge 5810REPPENDORF
Carbonic acid gas incubator NU4750ENuaire
(2) associated materials is tested
SDMSC mono-strain (RASMX-01001), source: Cyagen
Cell state: cell state is good, and form is homogeneous.
Cell Sterility testing result: negative
(3) related reagent is tested
Human embryonic stem cell medium mTeSR1 (Canadian Stemcell company), 1 × PBS (PBS-10001-100),
Human mesenchymal stem cell Osteoinductive differentiation culture medium C P1202 (Wei Tong biotech firm of Shenzhen), 0.25%Trypsin-0.0,4%EDTA (TEDTA-10001-100), BMP-2 (Beijing Bioisystech Co., Ltd of Yi Qiao divine boat)
Induced osteogenesis polypeptide alkaline phosphatase assay test kit (Science and Technology Ltd. is built up in Nanjing) of the present invention.
(4) testing sequence
I, cell prepare: when SDMSC cytogamy reaches 80%, gone down to posterity by cell, are inoculated in through 0.1% gelatin bag by 24 orifice plates crossed, for osteogenic induction.
A. cell dissociation, inoculation:
A. supernatant discarded, cleans cell 2 times with 1 × PBS, adds 1mlPBS and 1ml0.25%Trypsin-0.04%EDTA peptic cell;
B. digest 1-2 minute, under microscope, visible cell gap increases, cell rounding, claps the wall of culture vessel with have gentle hands, and the SDMSC perfect medium adding 2mL immediately stops digestion.
C. use suction pipe imbitition, blow and beat culture vessel surface gently, 3-5 time repeatedly, make cell thoroughly depart from a bottle ware diapire, cell is moved in centrifuge tube, then in culturing bottle, add 1 × PBS wash 1-2 time, and washing lotion is transferred in centrifuge tube in the lump.
D.1100rpm centrifugal 4 minutes are carried out;
E. supernatant discarded adds complete culture solution, fully mixes, and is on average inoculated in 3 bags and is crossed in 12 orifice plates of gelatin, shake up, be positioned in the CO2gas incubator of 37 DEG C and cultivate.
The preparation of II, induced osteogenesis polypeptide: weighed by induced osteogenesis polypeptide and be distributed into 3 parts (1mg/ parts), get a copy of it and dissolve, other are stored in-20 DEG C of refrigerators for for subsequent use.Add the aseptic water dissolution 1mg osteogenin of 1ml in centrifuge tube, filter, be sub-packed in EP pipe, be stored in-80 DEG C of refrigerator-freezers for use.
III, induced osteogenesis:
A. just induction: when cytogamy reaches about 80%, carry out osteogenic induction.Often organize two multiple hole, wherein 2 hole negative controls: use mescenchymal stem cell complete culture solution to cultivate; 2 hole positive controls: use interstital stem cell Osteoinductive differentiation complete culture solution to cultivate; 2 holes are cultivated containing the BMP-2 mescenchymal stem cell complete culture solution of 10ug/ml; 2 holes are containing 30ug/ml's
BMP-2 mescenchymal stem cell complete culture solution is cultivated; 2 holes are cultivated containing the induced osteogenesis polypeptide mescenchymal stem cell complete culture solution of the present invention of 10ug/ml; 2 holes are cultivated containing the induced osteogenesis polypeptide mescenchymal stem cell complete culture solution of the present invention of 30ug/ml.2 plates repeat.
B. within every 3 days, carry out induction and change liquid.
IV. alkaline phosphatase detects:
Get different detection time and put cell, measure test kit (Nanjing is built up) according to alkaline phosphatase (AKP) and each group of AKP content is detected.Concrete operations are as follows:
A. digest each porocyte, after centrifugal, carry out cell counting, adjustment cell quantity, ensure that 50ul cell re-suspension liquid contains and be greater than 5X10
5cell.With 0.05ml damping fluid re-suspended cell, add corresponding solution successively: measure in pipe and add 0.05mL cell suspension, 0.05mL damping fluid, 0.05mL matrix liquid; 0.05mL0.1mg/ml phenol Standard Applying Solution is added, 0.05mL damping fluid, 0.05mL matrix liquid in standard pipe; 0.05mL distilled water is added, 0.05mL damping fluid, 0.05mL matrix liquid in blank tube.Abundant mixing 37 DEG C of water-baths 15 minutes, add 1.5mL nitrite ion, mixing, 520nm, 0.5cm or 1cm optical path colorimetric, and blank tube returns to zero, and surveys each pipe absorbancy.
V. experimental result
A. two weeks alkaline phosphatase assay:
| Measure | Alkaline phosphatase (Jin Shi/100ml) |
| Negative control | 2.57 |
| Positive control | 6.79 |
| 10ug/ml(BMP-2) | 7.52 |
| 30ug/ml(BMP-2) | 13.78 |
| The induced osteogenesis polypeptide of 10ug/ml the present embodiment | 10.16 |
| The induced osteogenesis polypeptide of 30ug/ml the present embodiment | 16.86 |
B. three weeks alkaline phosphatase assay:
Promote the material of bone mass cells growth containing pure natural in above-mentioned Herba Cirsii extract, adopt and extract with the following method: after the dry field thistle leaf powder getting 20 mesh sieves adds petroleum ether degreasing, collect residue, be 5 ~ 35: 1 ethanolic soln adding that volume fraction is 40 ~ 90% by liquid material mass ratio after residue is dried, ultrasonic extraction 3 times under 125 ~ 250W, 55 ~ 80 DEG C of conditions, each 10 ~ 60min, suction filtration, merging filtrate, vacuum-concentrcted, reclaim ethanol, decolouring, obtains field thistle extracting solution with deionized water dissolving, evaporate to dryness, obtains white Herba Cirsii extract.
As can be seen from the above results, the induced osteogenesis polypeptide of the present embodiment and the result of positive control sample are contrasted, can find that the induced osteogenesis polypeptide of the present embodiment completely can induced cell growth.And the result of the induced osteogenesis polypeptide of the present embodiment and the sample of BMP-2 is contrasted, can find that the induced osteogenesis polypeptide of the present embodiment can realize inducing the effect of bone cell growth, and effect is better than BMP-2, adds auxiliary material Herba Cirsii extract, effect is better.
The osteogenetic polypeptide of promotion of the present embodiment, can promote the generation of osteocyte, be specially adapted to the treatment of osteoporosis.
Embodiment 2
1. the synthesis of the present embodiment induced osteogenesis polypeptide
SEQIDNO：2(KIPAASSVPTELSAISTLYL)。
The synthetic method of the osteogenetic polypeptide of above-mentioned promotion, carry out in accordance with the following steps:
(1) with RinkAmide resin or Fmoc-Gly-WANG resin for starting raw material, with the amino acid of Fmoc protection for monomer, condensing agent (TBTU/HOAt) is adopted to carry out connecing reactive polypeptide, connect amino acid one by one, last peptide chain uses the thiohydracrylic acid of protection, after obtaining protection resin, synchronously carry out de-side chain protected group and cut peptide;
(2) add and cut peptide reagent (TFA/EDT/HAc/TIS/EDT) and carry out cutting peptide;
(3) be solvent with ether, precipitate and collect and promote osteogenetic polypeptide crude product;
(4) by soluble in water for osteogenetic polypeptide crude product, regulate pH to 7.5-10.0 with ammoniacal liquor, collect and promote osteogenetic polypeptide;
(5) the osteogenetic polypeptide of promotion step (4) collected, by HPLC separation and purification, obtains target product.
2. test cell line
(1) related equipment is tested
Instrument designation Model manufacturer
Clean bench NU-126-006Nuaire
Research grade inverted microscope IX41OLYMPUS
Refrigerated centrifuge 5810REPPENDORF
Carbonic acid gas incubator NU4750ENuaire
(2) associated materials is tested
SDMSC mono-strain (RASMX-01001), source: Cyagen
Cell state: cell state is good, and form is homogeneous.
Cell Sterility testing result: negative
(3) related reagent is tested
Human embryonic stem cell medium mTeSR1 (Canadian Stemcell company), 1 × PBS (PBS-10001-100),
Human mesenchymal stem cell Osteoinductive differentiation culture medium C P1202 (Wei Tong biotech firm of Shenzhen), 0.25%Trypsin-0.0,4%EDTA (TEDTA-10001-100), BMP-2 (Beijing Bioisystech Co., Ltd of Yi Qiao divine boat)
Induced osteogenesis polypeptide alkaline phosphatase assay test kit (Science and Technology Ltd. is built up in Nanjing) of the present invention.
(4) testing sequence
I, cell prepare: when SDMSC cytogamy reaches 80%, gone down to posterity by cell, are inoculated in through 0.1% gelatin bag by 24 orifice plates crossed, for osteogenic induction.
A. cell dissociation, inoculation:
A. supernatant discarded, cleans cell 2 times with 1 × PBS, adds 1mlPBS and 1ml0.25%Trypsin-0.04%EDTA peptic cell;
B. digest 1-2 minute, under microscope, visible cell gap increases, cell rounding, claps the wall of culture vessel with have gentle hands, and the SDMSC perfect medium adding 2mL immediately stops digestion.
C. use suction pipe imbitition, blow and beat culture vessel surface gently, 3-5 time repeatedly, make cell thoroughly depart from a bottle ware diapire, cell is moved in centrifuge tube, then in culturing bottle, add 1 × PBS wash 1-2 time, and washing lotion is transferred in centrifuge tube in the lump.
D.1100rpm centrifugal 4 minutes are carried out;
E. supernatant discarded adds complete culture solution, fully mixes, and is on average inoculated in 3 bags and is crossed in 12 orifice plates of gelatin, shake up, be positioned in the CO2gas incubator of 37 DEG C and cultivate.
The preparation of II, induced osteogenesis polypeptide: weighed by induced osteogenesis polypeptide and be distributed into 3 parts (1mg/ parts), get a copy of it and dissolve, other are stored in-20 DEG C of refrigerators for for subsequent use.Add the aseptic water dissolution 1mg osteogenin of 1ml in centrifuge tube, filter, be sub-packed in EP pipe, be stored in-80 DEG C of refrigerator-freezers for use.
III, induced osteogenesis:
A. just induction: when cytogamy reaches about 80%, carry out osteogenic induction.Often organize two multiple hole, wherein 2 hole negative controls: use mescenchymal stem cell complete culture solution to cultivate; 2 hole positive controls: use interstital stem cell Osteoinductive differentiation complete culture solution to cultivate; 2 holes are cultivated containing the BMP-2 mescenchymal stem cell complete culture solution of 10ug/ml; 2 holes are containing 30ug/ml's
BMP-2 mescenchymal stem cell complete culture solution is cultivated; 2 holes are cultivated containing the induced osteogenesis polypeptide mescenchymal stem cell complete culture solution of the present invention of 10ug/ml; 2 holes are cultivated containing the induced osteogenesis polypeptide mescenchymal stem cell complete culture solution of the present invention of 30ug/ml.2 plates repeat.
B. within every 3 days, carry out induction and change liquid.
IV. alkaline phosphatase detects:
Get different detection time and put cell, measure test kit (Nanjing is built up) according to alkaline phosphatase (AKP) and each group of AKP content is detected.Concrete operations are as follows:
A. digest each porocyte, after centrifugal, carry out cell counting, adjustment cell quantity, ensure that 50ul cell re-suspension liquid contains and be greater than 5X10
5cell.With 0.05ml damping fluid re-suspended cell, add corresponding solution successively: measure in pipe and add 0.05mL cell suspension, 0.05mL damping fluid, 0.05mL matrix liquid; 0.05mL0.1mg/ml phenol Standard Applying Solution is added, 0.05mL damping fluid, 0.05mL matrix liquid in standard pipe; 0.05mL distilled water is added, 0.05mL damping fluid, 0.05mL matrix liquid in blank tube.Abundant mixing 37 DEG C of water-baths 15 minutes, add 1.5mL nitrite ion, mixing, 520nm, 0.5cm or 1cm optical path colorimetric, and blank tube returns to zero, and surveys each pipe absorbancy.
V. experimental result
A. two weeks alkaline phosphatase assay:
| Measure | Alkaline phosphatase (Jin Shi/100ml) |
| Negative control | 2.57 |
| Positive control | 6.79 |
| 10ug/ml(BMP-2) | 7.52 |
| 30ug/ml(BMP-2) | 13.78 |
| The induced osteogenesis polypeptide of 10ug/ml the present embodiment | 18.16 |
| The induced osteogenesis polypeptide of 30ug/ml the present embodiment | 28.86 |
B. three weeks alkaline phosphatase assay:
| Measure | Alkaline phosphatase (Jin Shi/100ml) |
| Negative control | 6.54 |
| Positive control | 12.86 |
| 10ug/ml(BMP-2) | 15.52 |
| 30ug/ml(BMP-2) | 17.81 |
| The induced osteogenesis polypeptide of 10ug/ml the present embodiment | 25.11 |
| The induced osteogenesis polypeptide of 30ug/ml the present embodiment | 31.81 |
As can be seen from the above results, the induced osteogenesis polypeptide of the present embodiment and the result of positive control sample are contrasted, can find that the induced osteogenesis polypeptide of the present embodiment completely can induced cell growth.And the result of the induced osteogenesis polypeptide of the present embodiment and the sample of BMP-2 is contrasted, can find that the induced osteogenesis polypeptide of the present embodiment can realize the effect of the induced cell growth suitable with BMP-2, and effect is than embodiment 1BMP-2 better effects if.
The osteogenetic polypeptide of promotion of the present embodiment, can promote the generation of osteocyte, be specially adapted to the treatment of osteoporosis.
Claims (6)
1. promote an osteogenetic polypeptide, it is characterized in that, be the polypeptide of one of following amino acid residue sequences:
1) amino acid residue sequence shown in sequence table SEQ IDNO:1;
2) amino acid residue sequence shown in sequence table SEQ IDNO:1 is had through the replacement of 1 to 3 amino-acid residue, disappearance or interpolation a polypeptide promoting that osteocyte generates.
2. the gene of the above-mentioned promotion osteogenesis polypeptide of coding.
3. promote the synthetic method of osteogenetic polypeptide described in claim 1, it is characterized in that, carry out in accordance with the following steps:
(1) with RinkAmide resin or Fmoc-Gly-WANG resin for starting raw material, with the amino acid of Fmoc protection for monomer, condensing agent is adopted to carry out connecing reactive polypeptide, connect amino acid one by one, last peptide chain uses the thiohydracrylic acid of protection, after obtaining protection resin, synchronously carry out de-side chain protected group and cut peptide;
(2) add and cut peptide reagent and carry out cutting peptide;
(3) be solvent with ether, precipitate and collect and promote osteogenetic polypeptide crude product;
(4) by soluble in water for osteogenetic polypeptide crude product, regulate pH to 7.5-10.0 with ammoniacal liquor, collect and promote osteogenetic polypeptide;
(5) the osteogenetic polypeptide of promotion step (4) collected, by HPLC separation and purification, obtains target product.
4. promote the synthetic method of osteogenetic polypeptide according to claim 3, it is characterized in that, described condensing agent is HBTU/HOBt, TBTU/HOBt, BOP/HOBt, TBTU/HOAt, HBTU/HOA or BOP/HOAt.
5. promote the synthetic method of osteogenetic polypeptide according to claim 3, it is characterized in that, described in cut peptide reagent be TFA/EDT/HAc/TIS/EDT.
6. described in claim 1, promote that osteogenetic polypeptide promotes the application in the medicine of bone synthesis in preparation.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111320682A (en) * | 2020-02-27 | 2020-06-23 | 广州领晟医疗科技有限公司 | Application of polypeptide in preparation of medicine for promoting cartilage repair and/or treating osteoarthritis |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1752103A (en) * | 2005-10-27 | 2006-03-29 | 华中科技大学同济医学院附属协和医院 | Delicious peptide 2 bioactive peptides and preparation method and application |
| US8062890B2 (en) * | 2005-08-15 | 2011-11-22 | Wisconsin Alumni Research Foundation | Defined surfaces of self-assembled monolayers and stem cells |
| US8420774B2 (en) * | 2009-12-01 | 2013-04-16 | Wisconsin Alumni Research Foundation | Decorating hydroxyapatite biomaterials with modular biologically active molecules |
| US20130296177A1 (en) * | 2012-05-07 | 2013-11-07 | Wisconsin Alumni Research Foundation | Chemically-defined arrays for screening cell-substrate interactions |
-
2015
- 2015-06-11 CN CN201510317323.8A patent/CN105175501B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8062890B2 (en) * | 2005-08-15 | 2011-11-22 | Wisconsin Alumni Research Foundation | Defined surfaces of self-assembled monolayers and stem cells |
| CN1752103A (en) * | 2005-10-27 | 2006-03-29 | 华中科技大学同济医学院附属协和医院 | Delicious peptide 2 bioactive peptides and preparation method and application |
| US8420774B2 (en) * | 2009-12-01 | 2013-04-16 | Wisconsin Alumni Research Foundation | Decorating hydroxyapatite biomaterials with modular biologically active molecules |
| US20130296177A1 (en) * | 2012-05-07 | 2013-11-07 | Wisconsin Alumni Research Foundation | Chemically-defined arrays for screening cell-substrate interactions |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111320682A (en) * | 2020-02-27 | 2020-06-23 | 广州领晟医疗科技有限公司 | Application of polypeptide in preparation of medicine for promoting cartilage repair and/or treating osteoarthritis |
| CN111320682B (en) * | 2020-02-27 | 2022-07-08 | 广州领晟医疗科技有限公司 | Application of polypeptide in preparation of medicine for promoting cartilage repair and/or treating osteoarthritis |
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Effective date of registration: 20210521 Address after: 100048 51 Fucheng Road, Haidian District, Beijing Patentee after: Fourth Medical Center, General Hospital of the Chinese PLA Patentee after: BEIJING AOSITESAI MEDICAL TECHNOLOGY Co.,Ltd. Address before: 100142 zone 1, 3 / F, No. 160, North West Fourth Ring Road, Haidian District, Beijing Patentee before: BEIJING AOSITESAI MEDICAL TECHNOLOGY Co.,Ltd. |
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