CN107670021A - Purposes of the five/Argireline KTTKS (F) in degenerative arthritis is treated - Google Patents
Purposes of the five/Argireline KTTKS (F) in degenerative arthritis is treated Download PDFInfo
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- CN107670021A CN107670021A CN201610623696.2A CN201610623696A CN107670021A CN 107670021 A CN107670021 A CN 107670021A CN 201610623696 A CN201610623696 A CN 201610623696A CN 107670021 A CN107670021 A CN 107670021A
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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 five/Argireline KTTKS (F) in degenerative arthritis is treated.
Description
Technical field
The present invention relates to new applications of the five/Argireline KTTKS (F) in degenerative arthritis is treated.
Background technology
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.
It is (all in prevention or treatment tissue or organ that the B2 of the US 6589750 and B2 of US 7429448 disclose Wushengtai QHNPR
Such as bone) water-mineral imbalance in purposes, wherein Q represent glutamine (Gln)；H represents histidine (His)；N is represented
Asparagine 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 from amino acid (Lys；) and Soviet Union amino acid (Thr K；T) five/six
Win peptide 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 studying, successfully develop finally it is a kind of can be used for treatment degenerative arthritis five/
Argireline KTTKS (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 five/Argireline KTTKS (F) in treatment degenerative arthritis
In purposes.
Based on this, the present invention mainly implements foregoing purpose and efficacy by 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 Wushengtai to cartilage cell's DNA content；
Fig. 2 shows the influence that Wushengtai synthesizes to cultured cartilage tissue collagen；
Fig. 3 shows the influence that Wushengtai synthesizes to cultured cartilage histone polysaccharide.
Embodiment
The invention discloses purposes of one kind five/Argireline KTTKS (F) in degenerative arthritis is treated.Below by way of
Particular specific embodiment illustrates the technology contents of the present invention, makes those skilled in the art can be by content disclosed in the present specification
Advantages of the present invention and effect are understood easily.However, the present invention can also be applied by other different embodiments
Row 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 be changed with demand.
Invention also discloses a kind of medical component, and it includes five/Argireline KTTKS (F) of therapeutically effective amount and doctor
Acceptable supporting agent on medicine.The pharmaceutically acceptable supporting agent includes solid carriers, semi-solid supporting agent and liquid carrier, wherein should
It is already known and used for those skilled in the art etc. solid carriers, the species of semi-solid supporting agent and liquid carrier and appropriate dosage
With.The medical component can be in the form of lozenge, tablet, pill, powder or particle.The medical component also can be in gel, paste
Agent or the form of paster.The medical component also can in the form of aqueous buffer, wherein the aqueous buffer include but
It 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)；Revive amino acid (Thr；T)；Silk amine
Acid (Ser；S)；And Phenylalanine (Phe；F).
The invention discloses Wushengtai KTTKS (shown in SEQ ID NO.1) and Argireline KTTKSF (SEQ ID NO.2 institutes
Show) it can be prepared according to prior art, such as A1 of TW 201129368 and the A1 of TW 201333045, 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 250ppm/kg joint cavity injection Wushengtais
KTTKS, 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 | 51.23±2.55 | 6.52±1.29 | 15.56±3.04 |
| B | 120.55±15.28 | 15.19±1.48 | 24.21±3.13 |
| C | 25.11±3.65 | 6.18±2.17 | 15.23±5.62 |
Conclusion
1st, tectology test result indicates that：Injection Wushengtai KTTKS in articular cavity can substantially repair damaged it is soft
Bone tissue, it is very definite for the therapeutic effect of degenerative arthritis.
2nd, Wushengtai KTTKS significantly reduces MDA in synovial membrane, reduces the lipid peroxidation injury degree in articular cavity, thus
Mitigate damage of the free radical to cartilage cell and matrix, have the function that Saving cortilage cartilage.
3rd, Wushengtai KTTKS significantly improves rabbit joint cavity SOD concentration, eliminates free radical caused by inflammation, and then
Protect cartilage and suppress and prevent cartilage lesion.
4th, Wushengtai KTTKS significantly improves rabbit joint cavity NO concentration, thus mitigates destructions of the NO to cartilage.
Embodiment 2
First, experimental method
First, rabbit growth plate chondrocyte is taken, carries out continuing culture, if Wushengtai KTTKS independent roles group, collagen list
Only effect group, Wushengtai KTTKS+ collagen synergy groups, add Wushengtai KTTKS250ppm, collagen (100ng/ml) respectively
And Wushengtai KTTKS (250ppm)+collagen (100ng/ml), and negative control group is set, treat that neocartilage tissue covers with centrifuge tube
Behind bottom, it is transferred in 24 well culture plates and continues to cultivate, example of spatial compartmentalizationis, reaches predetermined incubation time (3,7 and 14 days)
Afterwards, collect sample and carry out every detection.
Then, histology and histochemisty detection is carried out：Make a collection of specimens and carry out HE dyeing, immunohistochemistry (S-P methods)
Detection.
Afterwards, cartilage cell's DNA content is determined using the methods of Hoechst 33258.
Come again, carry out chondrocyte matrix synthesis：Outside moisture removal, in chondrocyte matrix most important composition be collagen and
The proteoglycan being made up of glycosaminoglycan and core protein.By the measure to collagen in cambium and proteoglycan content,
Quantitative analysis matrix content and metabolism status.
Finally, hydroxyl proline method measure cartilage cell's collage synthesis is carried out：Due to ratio phase of the hydroxyl proline in collagen
To constant (account for collagen weight 10%), therefore the yield of cartilage cell's collagen can be analyzed by quantitative hydroxyl proline.
Strictly operated by hydroxyl proline detection kit specification, and calculate the collagen content of each sample.
2nd, experimental result
1st, influences of the Wushengtai KTTKS to the proliferation of chondrocytes：It is notable to the proliferation of chondrocytes to add Wushengtai KTTKS,
Wherein cartilage cell's DNA content shows statistical difference (Fig. 1) with control group, and the result illustrates that Wushengtai KTTKS can be effective
Promote the proliferation of chondrocytes.
2nd, the influence that Wushengtai KTTKS synthesizes to chondrocyte matrix：Addition Wushengtai KTTKS remarkably promotes collagen and egg
The synthesis of white 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 Wushengtai KTTKS 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 the Wushengtai KTTKS 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 Argireline KTTKSF is in the degenerative arthritis for preparing the purposes described in medicine, wherein the drug therapy sufferer.
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 Argireline KTTKSF 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 |
|---|---|---|---|
| CN201610623696.2A CN107670021B (en) | 2016-08-02 | 2016-08-02 | Application of Wushengtai KTTKS in treating degenerative arthritis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610623696.2A CN107670021B (en) | 2016-08-02 | 2016-08-02 | Application of Wushengtai KTTKS in treating degenerative arthritis |
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| Publication Number | Publication Date |
|---|---|
| CN107670021A true CN107670021A (en) | 2018-02-09 |
| CN107670021B CN107670021B (en) | 2020-09-18 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201610623696.2A Active CN107670021B (en) | 2016-08-02 | 2016-08-02 | Application of Wushengtai KTTKS in treating degenerative arthritis |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109833266A (en) * | 2019-03-29 | 2019-06-04 | 深圳市富可迪生物科技有限公司 | Cosmetic composition |
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| WO2005122723A2 (en) * | 2004-06-09 | 2005-12-29 | Beth Israel Deaconess Medical Center | Compositions and methods that enhance articular cartilage repair |
| CN101917959A (en) * | 2006-12-01 | 2010-12-15 | 安特里奥公司 | Peptide nanoparticles and uses therefor |
| CN102076845A (en) * | 2008-04-28 | 2011-05-25 | 特克赛尔公司 | Compositions for treating an arthritic condition |
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| WO2005122723A2 (en) * | 2004-06-09 | 2005-12-29 | Beth Israel Deaconess Medical Center | Compositions and methods that enhance articular cartilage repair |
| CN101917959A (en) * | 2006-12-01 | 2010-12-15 | 安特里奥公司 | Peptide nanoparticles and uses therefor |
| CN102076845A (en) * | 2008-04-28 | 2011-05-25 | 特克赛尔公司 | Compositions for treating an arthritic condition |
| CN102892776A (en) * | 2010-06-30 | 2013-01-23 | 因首太克株式会社 | Novel peptide and use thereof |
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Cited By (1)
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| CN109833266A (en) * | 2019-03-29 | 2019-06-04 | 深圳市富可迪生物科技有限公司 | Cosmetic composition |
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| CN107670021B (en) | 2020-09-18 |
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