CN107670020A - Purposes of the four/Wushengtai GEKG (F) in degenerative arthritis is treated - Google Patents
Purposes of the four/Wushengtai GEKG (F) in degenerative arthritis is treated Download PDFInfo
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- CN107670020A CN107670020A CN201610622504.6A CN201610622504A CN107670020A CN 107670020 A CN107670020 A CN 107670020A CN 201610622504 A CN201610622504 A CN 201610622504A CN 107670020 A CN107670020 A CN 107670020A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/07—Tetrapeptides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
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Abstract
The invention discloses purposes of one kind four/Wushengtai GEKG (F) in degenerative arthritis is treated.
Description
Technical field
The present invention relates to new applications of the four/Wushengtai GEKG (F) in degenerative arthritis is treated.
Prior art
Degenerative arthritis (degenerative joint disease) refers to continuation lesion and the companion of articular cartilage
With the hyperplasia for having superfluous raw bone, wherein hyperplasia bone is mostly occurred in below joint margins or cartilage.The original of degenerative arthritis occurs
Because considerably complicated, but it is mainly relevant with the age of patient during morbidity.Degenerative arthritis often occurs in older length
Person.It is to find that articular cartilage abrasion and fibrosis, superfluous raw bone (spur) occur based on detection to confirm degenerative arthritis
And/or soft tissue irritation.Although known change of age can influence cartilage lesion really, degenerative arthritis really causes a disease
Machine turns still not yet to understand so far.
Degenerative arthritis mostly occurs in the joint of carrying body body weight or finger interphalangeal joint, especially end refer to
Section, wherein arthralgia are clinically main sign with limitation of activity.Pathological examination often finds dysarthrasis and joint margins
Swelling and press pain in addition merge joint sound.
Treating the medicine of degenerative arthritis now includes non-steroid anti-inflammatory agent (such as COX2 pharmaceutical preparations), intra-articular
Local injection steroids and intra-articular injection nutrition lubricant (i.e. sodium hyaluronate preparation).
US 4528133, which is disclosed, some includes 2 or 3 alanine (Ala；A) four victory peptides of residue are in treatment of arthritis
Purposes.
US 6034057 discloses some ring victory peptides for including 8 amino acid residues and 2 linking groups in treatment rheumatoid
Purposes in property arthritis.
US 6589750B2 and US 7429448B2, which disclose Wushengtai QHNPR, to be prevented or is treating tissue or organ (such as
Bone) water-mineral imbalance in purposes, wherein Q represent glutamine (Gln)；H represents histidine (His)；N represents day
Winter amic acid (Asn)；P represents proline (Pro)；And R represents that spermine is sour (Arg).
Prior art does not all teach or suggested：It can be used and be rich in Gly (Gly；G four/Wushengtai) is to treat degenerative
Arthritis.
Therefore, the present inventor carries out further investigated for existing issue, and by be engaged in for many years the research and development of related industry with
Manufacturing experience, the improvement through being continually striving to successfully are developed a kind of for treating the four/five of degenerative arthritis finally with studying
Win peptide GEKG (F), the new selection for the treatment of degenerative arthritis can be provided whereby.
The content of the invention
Therefore, the main object of the present invention is to provide one kind four/Wushengtai GEKG (F) in degenerative arthritis is treated
Purposes.
Based on this, the present invention implements foregoing purpose and efficacy mainly through following technological means.
It is to lift the present invention below to enable your juror to further appreciate that composition, feature and the other purposes of the present invention
Preferred embodiment, and coordinate schema to describe in detail as after, while those skilled in the art can be embodied.
Brief description of the drawings
Fig. 1 shows influence of the four victory peptides to cartilage cell's DNA content；
Fig. 2 shows the influence that four victory peptides synthesize to cultured cartilage tissue collagen；
Fig. 3 shows the influence that four victory peptides synthesize to cultured cartilage histone polysaccharide.
Embodiment
The invention discloses purposes of one kind four/Wushengtai GEKG (F) in degenerative arthritis is treated.Below by way of spy
Fixed specific embodiment illustrates the technology contents of the present invention, makes those skilled in the art light by content disclosed in the present specification
Change places and understand advantages of the present invention and effect.However, the present invention can also be implemented by other different embodiments
Or application.Can be on the premise of without departing from the content of the claim of the present invention, according to a particular embodiment of the invention
Design with demand and be changed.
Invention also discloses a kind of medical component, and it includes the four/Wushengtai GEKG (F) and medicine of therapeutically effective amount
Upper acceptable supporting agent.The pharmaceutically acceptable supporting agent includes solid carriers, semi-solid supporting agent and liquid carrier, wherein such
Solid carriers, the species of semi-solid supporting agent and liquid carrier and appropriate dosage were already known and usual for this technical field.Should
Medical component can be in the form of lozenge, tablet, pill, powder or particle.The medical component also can be in gel, paste or patch
The form of piece.The medical component also can be in the form of aqueous buffer, and wherein the aqueous buffer includes but is not limited to
The aqueous solution of phosphate or citrate.
In addition, the present invention uses the abbreviation defined in biochemical science：Rely amino acid (Lys；K)；Glutamine (Glu；E)；And
Phenylalanine (Phe；F).
The invention discloses four victory peptide GEKG (shown in SEQ ID NO.1) and Wushengtai GEKGF (shown in SEQ ID NO.2)
It can be prepared according to prior art, such as TW 201129368A1 and TW 201333045A1, described method.
What the present invention used measures SOD, NO and MDA method in joint fluid and measures collagen and egg in chondrocyte matrix
The method of white polysaccharide was already known and usual for those skilled in the art.
Embodiment
Embodiment 1
First, animal model
3 groups are randomly divided into 15 healthy adult New Zealand White Rabbits：Normal group (A groups), model control group (B groups)
And victory peptide joint cavity injection group (C groups), every group each 5.Operation consent fasting 4 hours, intramuscular injection Ketamine (10mg/kg) and
Atropine(0.2mg/kg).After anesthesia comes into force, animal is fixed on operating table, 8cm is in patella ligament trailing edge and indulges
To otch and skin is started, capsular ligament and synovial membrane is opened along knee cap trailing edge, by 90 ° of knee joint bending, makes distal part of femur cartilage
Expose to the open air, and do 2 a diameter of 3mm, depth 3mm cylindrical type defect, remove the blood coagulation at defect, it is clear with sterile physiological saline solution
After washing joint cavity, carefully suture is layered.Anti-infective one week of Post operation injection penicillin.Can normal diet and from main website after 5 days
It is vertical.
2nd, experimental method
Post operation starts on the 2nd week, A and B groups are without any processing, and C groups press the victory peptide of 250ppm/kg joint cavity injections four
GEKG, injection in every 7 days once, are administered 12 weeks altogether.Joint cavity injection 0.5ml normal saline solutions, collect 0.2ml joint fluids.Cut
Capsular ligament, synovial membrane and complete taking-up tibial prosthesis face, naked eyes and operation Microscopic observation articular cartilage lesion degree are taken out, and cut into slices
Carry out hematoxylin-eosin (HE Stain, Hematoxylin and Eosin Stain) and the light of Toluidine blue staining respectively afterwards
Learn micro- sem observation.
3rd, experimental result
Visual results
After 12 weeks, A group knee joint surfaces are smooth, flexible, visible a little joint fluid in articular cavity；B group defects group only portion
Divide and repair, but defect center still remains depression and slot；The whole defects of C groups have been repaired completely, cross-section structure and natural joint
It is no different, surface cartilage and its lower cancellous bone have been repaired completely, and have no ossified and repairing mark.
Organizational patterns is observed
A groups joint tissue is identical with the feature of natural joint tissue, and surface is ripe cartilaginous tissue, centre is aligned orderly
Ripe epiphyseal plate and lower section be ossified good cancellous bone, and the thickness of cartilaginous tissue is normal；The repair tissue of B group defect groups with
Based on fiber-like cartilage and fibr tissue, interface is continuous between normal structure, and part sample defective region has more fibroid soft
Bone Void Filler, but formed without obvious epiphyseal plate in defective region and the cancellous bone of lower section ossify it is bad；C groups repair tissue with just
The feature no significant difference of normal joint tissue, surface cartilage tissue, epiphyseal plate and lower section cancellous bone have reached normal histology's shape
State, with normal identical, cartilage and bone intersection cannot be distinguished by neocartilage thickness.
Biochemical indicator detects
Compared with B groups, C group articular cartilage forms are obviously improved and SOD is significantly raised in joint fluid simultaneously, and NO and MDA
It is obvious to reduce, as a result as shown in table 1.
NO, SOD and MDA value in each group joint fluid of table 1.
| Group | NO(c/mol.L-1) | SOD(c/mol.L-1) | MDA(c/mol.L-1) |
| A | 49.12±1.26 | 5.67±1.85 | 13.46±2.83 |
| B | 115.39±12.94 | 16.29±1.57 | 23.69±2.78 |
| C | 20.76±2.88 | 6.60±1.37 | 13.12±2.28 |
Conclusion
1st, tectology test result indicates that：The cartilage damaged can substantially be repaired in articular cavity by injecting four victory peptide GEKG
Tissue, it is very definite for the therapeutic effect of degenerative arthritis.
2nd, four victory peptide GEKG significantly reduce MDA in synovial membrane, reduce the lipid peroxidation injury degree in articular cavity, thus subtract
Light damage of the free radical to cartilage cell and matrix, has the function that Saving cortilage cartilage.
3rd, four victory peptide GEKG significantly improve rabbit joint cavity SOD concentration, eliminate free radical caused by inflammation, Jin Erbao
Protect cartilage and suppress and prevent cartilage lesion.
4th, four victory peptide GEKG significantly improve rabbit joint cavity NO concentration, thus mitigate destructions of the NO to cartilage.
Embodiment 2
First, experimental method
1st, rabbit growth plate chondrocyte is taken, carries out continuing culture, if four victory peptide GEKG independent roles groups, collagen are individually made
With group, four victory peptide GEKG+ collagen synergy groups, four victory peptide GEKG (250ppm), collagen (100ng/ml) and four are added respectively
Win peptide GEKG (250ppm)+collagen (100ng/ml), and set negative control group, treat that neocartilage tissue covers with centrifugation bottom of the tube
Afterwards, it is transferred in 24 well culture plates and continues to cultivate, example of spatial compartmentalizationis, after reaching predetermined incubation time (3,7 and 14 days), receives
Sample is taken to carry out every detection.
2nd, histology and histochemisty detects：Make a collection of specimens and carry out HE dyeing, immunohistochemistry (S-P methods) detection.
3rd, cartilage cell's DNA content is determined using the methods of Hoechst 33258.
4th, chondrocyte matrix synthesizes：Outside moisture removal, most important composition is collagen and by osamine in chondrocyte matrix
The proteoglycan that glycan is formed with core protein.By the measure to collagen in cambium and proteoglycan content, quantitative point
Analyse matrix content and metabolism status.
5th, hydroxyl proline method measure cartilage cell's collage synthesis：Due to ratio relative constancy of the hydroxyl proline in collagen
(account for collagen weight 10%), therefore the yield of cartilage cell's collagen can be analyzed by quantitative hydroxyl proline.Strictly press
Hydroxyl proline detection kit specification operates, and calculates the collagen content of each sample.
2nd, experimental result
1st, influences of the four victory peptide GEKG to the proliferation of chondrocytes：It is notable to the proliferation of chondrocytes to add four victory peptide GEKG, its
Middle cartilage cell's DNA content shows statistical difference (Fig. 1) with control group, and the result illustrates that four victory peptide GEKG can be effectively facilitated
The proliferation of chondrocytes.
2nd, the influence that four victory peptide GEKG synthesize to chondrocyte matrix：Add four victory peptide GEKG and remarkably promote collagen and albumen
The synthesis of polysaccharide and the proliferation of chondrocytes is further effectively facilitated, the result has statistical difference (Fig. 2 and figure with control group
3)。
Thereby, it is possible to understand that the present invention is the splendid invention of an intention, except effectively solving existing issue, is more significantly improved
Therapeutic efficiency, and have no identical or approximate product creation in identical technical field or openly use, while there is effect
Enhancement.Therefore the present invention has met important document of the patent of invention about " novelty " Yu " creativeness ", is to file an application to invent in accordance with the law
Patent.
Claims (12)
1. a kind of purposes of four victory peptide GEKG in medicine is prepared, the wherein medicine are used for the degenerative arthritis for treating sufferer.
2. the rise of SOD contents and NO and MDA in purposes as claimed in claim 1, the wherein joint fluid of the sufferer through treatment
Content reduces.
3. the articular chondrocytes hyperplasia of purposes as claimed in claim 1, the wherein sufferer through treatment.
4. a kind of medical component, it includes four victory peptide GEKG of therapeutically effective amount and pharmaceutically acceptable supporting agent.
5. medical component as claimed in claim 4, the wherein medical component in lozenge, tablet, pill, powder, particle,
Gel, paste, the form of paster or aqueous buffer.
6. medical component as claimed in claim 5, the wherein aqueous buffer are the water-soluble of phosphate or citrate
Liquid.
7. a kind of Wushengtai GEKGF is used for the degenerative arthritis for treating sufferer in the purposes for preparing medicine, the wherein medicine.
8. the rise of SOD contents and NO and MDA in purposes as claimed in claim 7, the wherein joint fluid of the sufferer through treatment
Content reduces.
9. the articular chondrocytes hyperplasia of purposes as claimed in claim 7, the wherein sufferer through treatment.
10. a kind of medical component, it includes the Wushengtai GEKGF of therapeutically effective amount and pharmaceutically acceptable supporting agent.
11. medical component as claimed in claim 10, the wherein medical component in lozenge, tablet, pill, powder,
Grain, gel, paste, the form of paster or aqueous buffer.
12. medical component as claimed in claim 11, the wherein aqueous buffer are the water of phosphate or citrate
Solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610622504.6A CN107670020B (en) | 2016-08-02 | 2016-08-02 | Application of tetrapeptide GEKG in treating degenerative arthritis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610622504.6A CN107670020B (en) | 2016-08-02 | 2016-08-02 | Application of tetrapeptide GEKG in treating degenerative arthritis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107670020A true CN107670020A (en) | 2018-02-09 |
| CN107670020B CN107670020B (en) | 2020-09-18 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201610622504.6A Active CN107670020B (en) | 2016-08-02 | 2016-08-02 | Application of tetrapeptide GEKG in treating degenerative arthritis |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005122723A2 (en) * | 2004-06-09 | 2005-12-29 | Beth Israel Deaconess Medical Center | Compositions and methods that enhance articular cartilage repair |
| CN101878019A (en) * | 2007-11-30 | 2010-11-03 | 赢创高施米特有限公司 | Personal care and cosmetic composition containing tetrapeptides with the motifs gx1x2g, px1x2p, or px1x2k |
| CN102076845A (en) * | 2008-04-28 | 2011-05-25 | 特克赛尔公司 | Compositions for treating an arthritic condition |
| CN105377238A (en) * | 2012-07-05 | 2016-03-02 | 台湾微脂体股份有限公司 | Methods of treating arthritis |
-
2016
- 2016-08-02 CN CN201610622504.6A patent/CN107670020B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005122723A2 (en) * | 2004-06-09 | 2005-12-29 | Beth Israel Deaconess Medical Center | Compositions and methods that enhance articular cartilage repair |
| CN101878019A (en) * | 2007-11-30 | 2010-11-03 | 赢创高施米特有限公司 | Personal care and cosmetic composition containing tetrapeptides with the motifs gx1x2g, px1x2p, or px1x2k |
| CN102076845A (en) * | 2008-04-28 | 2011-05-25 | 特克赛尔公司 | Compositions for treating an arthritic condition |
| CN105377238A (en) * | 2012-07-05 | 2016-03-02 | 台湾微脂体股份有限公司 | Methods of treating arthritis |
Non-Patent Citations (6)
| Title |
|---|
| CHUNFEN WANG 等: "Design of gene-activated matrix for the repair of skin and cartilage", 《POLYMER JOURNAL》 * |
| MIKE FARWICK 等: "An ECM-derived Tetrapeptide to Counterbalance ECM Degeneration", 《COSMETICS & TOILETRIES MAGAZINE》 * |
| XD LI 等: "Effects of high intensity exhaustive exercise on SOD, MDA, and NO levels in rats with knee osteoarthritis", 《GENETICS AND MOLECULAR RESEARCH》 * |
| 吴志宏: "骨关节炎的关节软骨细胞外基质的变化", 《实用骨科杂志》 * |
| 白跃宏 等: "《常见疾病三级康复网络体系建设实践》", 31 October 2014, 上海交通大学出版社 * |
| 顾其胜 等: "《胶原蛋白与临床医学》", 31 March 2003, 第二军医大学出版社 * |
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