CN104825464A - Application of CDCA in preparation of drug for treating osteoarthritis - Google Patents
Application of CDCA in preparation of drug for treating osteoarthritis Download PDFInfo
- Publication number
- CN104825464A CN104825464A CN201510121989.6A CN201510121989A CN104825464A CN 104825464 A CN104825464 A CN 104825464A CN 201510121989 A CN201510121989 A CN 201510121989A CN 104825464 A CN104825464 A CN 104825464A
- Authority
- CN
- China
- Prior art keywords
- cdca
- osteoarthritis
- medicine
- drug
- mmp
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- LJUZGCNRBBTDIB-QNXSSYJKSA-N CCC(CCC(CCCC1[C@@](C)(CC[C@H](C2)O)C2C2)C1[C@@H]2O)[C@H](C)CCC(O)=O Chemical compound CCC(CCC(CCCC1[C@@](C)(CC[C@H](C2)O)C2C2)C1[C@@H]2O)[C@H](C)CCC(O)=O LJUZGCNRBBTDIB-QNXSSYJKSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a new application of a monomer compound CDCA, and particularly relates to the application of the CDCA in preparation of a drug for treating osteoarthritis and a drug composition for treating the osteoarthritis. The drug composition can be prepared into an injection, a tablet, a capsule, an electuary, a drop, a granule or an ointment by adding general medicinal auxiliary components to the CDCA being not less than 98% in purity. A pharmacological experiment result proves that the CDCA can significantly improve inflammatory cell infiltration, proliferation of fibrous tissue and cartilage surface damage and the like situations in an osteoarthritic location, can reduce the levels of MMP-1, MMP-3, IL-1[beta] and PGE2 in synovial fluid and has a strong osteoarthritis-resistant effect, so that the CDCA can be used for preparing a drug for treating the osteoarthritis. The invention provides a new drug source to treatment of the osteoarthritis.
Description
Technical field
The present invention relates to medical art, is the application of CDCA in preparation treatment medicine for treating arthritis
Background technology
Osteoarthritis (Osteoarthritis, OA) is a kind of degenerative disease, is articular cartilage generation degeneration, and main manifestations is metabolism of articular cartilage exception and ossa articularia structural failure, causes afunction time serious.During OA is more common in, old people, onset process is mostly slow, and hands, knee joint, hip and joint of vertebral column are easily got involved, and the palm refers to, wrist and other joints are less gets involved, and the state of an illness is usually with movable and increase the weight of or alleviate because of rest.
Osteoarthritis OA has become the major reason of more than 50 years old crowd disability, is only second to ischemic heart desease.Wherein knee joint incidence rate is the highest, and about there are 3.6 hundred million arthritics in the whole world.Along with the process of Chinese aging, OA patient increases year by year, brings great financial burden and stress to society and patient home.
At present mainly based on some nonspecific drugs, clinical symptoms is alleviated to the treatment of osteoarthritis, the symptom of releasing arthritis patient is carried out by oral opium analgesics (acetaminophen, central analgesia medicine) and nonsteroidal antiinflammatory drug, but fundamentally can not cure osteoarthritis, such medicine is more in the untoward reaction of cardiovascular system and gastrointestinal system simultaneously, limit the scope of its application, therefore urgently research and develop novel anti-medicine for treating arthritis.Natural drug is the important rarity of China, and due to its wide material sources, composition is abundant, untoward reaction is few, is developed to new drug and is easy to the feature that human body accepts, more and more receive the concern of domestic and international researcher.The focus that the novelty for the treatment of osteoarthritis is found in current trial from natural drug, effective active pharmaceutical substance has become research.
Chenodeoxycholic acid (CDCA), chemical name is: 3 α, 7 alpha-dihydroxy--5 β-cholanic acids, white powder, and mp:140-142 DEG C, is soluble in methanol, and be the principle active component in animal bile, structural formula is as follows.
CDCA is as a kind of known monomers compound, although have definite molecular formula and structural formula, but the activity of its research is not high, pharmacological action report at present about CDCA is considerably less, its pharmaceutical research report is mainly antitussive, relievings asthma, promotes bile secretion and dissolve the effect of cholelithiasis, clinical be mainly used in control that treatment cholelithiasis demonstrate,proves or liver and gall diseases prevent and treat aspect.So far, CDCA yet there are no research report as the application of monomeric compound in preparation treatment medicine for treating arthritis.
Summary of the invention
The technical problem that the present invention will solve first aspect is, provides the novelty teabag of CDCA, i.e. the application of CDCA in preparation treatment medicine for treating arthritis.
For solving the problem, the technical scheme that first aspect present invention provides is: the application of CDCA in preparation treatment medicine for treating arthritis.
In the preferred technical solution of the present invention, described medicine comprises inertia, the excipient that nontoxic, pharmacology is suitable.
Second aspect present invention provides a kind of medicine for the treatment of osteoarthritis, and this medicine contains the CDCA active component for the treatment of effective dose.
Preferably, described medicine also comprises the medicine of one or more inertia, nontoxic, that pharmacology is suitable excipient.
Preferably, described excipient is carrier, solvent, emulsifying agent, dispersant, wetting agent, binding agent, stabilizing agent, coloring agent, spice.
Preferably, described medicine is tablet, capsule, electuary, drop, lyophilized products, granule, ointment or injection.
In technique scheme, described treatment medicine for treating arthritis compositions adds general medicinal auxiliary element by CDCA more than purity 98% (mass percent), makes tablet, capsule, electuary, drop, lyophilized products, granule, ointment or injection.
Can whole body and/or work partly according to pharmaceutical composition of the present invention, for this reason, can in an appropriate manner, such as, be taken by the approach of mouth, parenteral, lung or nose, the form of taking that can be suitable for these route of administration according to compositions of the present invention is taken.
Being suitable for oral is to work according to prior art level and promptly and/or discharge the form of medication of pharmaceutical composition of the present invention with improved procedure, and comprise with crystallization and/or unbodied and/or dissolved form, such as tablet is (without coating or cated tablet, it such as has and resists gastric juice or delayed dissolved or undissolved coating, compositions according to the present invention discharges), tablet broken rapidly in mouth, or diaphragm, film/lyophilized products, capsule (such as hard or soft capsule), coated tablet, granule, piller, powder, Emulsion, suspension, aerosol or solution according to pharmaceutical composition of the present invention.
Parenteral admistration can avoid absorption step (such as intravenous, intra-arterial, intracardiac, in spinal column or in waist or intraarticular) or comprise absorption (such as intramuscular, subcutaneous, Intradermal, percutaneous or intraperitoneal) simultaneously and carry out.Be suitable for the suitable form of taking of parenteral admistration method in particular for injecting and injecting with solution, suspension, Emulsion, the preparation of lyophilized products or sterilized powder form.
What be suitable for another route of administration is medicament forms such as sucking, and such as powder sucks seven or nebulizer, or can the medicament forms taken of nose, typing drop, solution or spray.
Can be converted into according to pharmaceutical composition of the present invention and described take form.This can in a way known by carrying out with inertia, nontoxic, that pharmacology is suitable mixed with excipients.These excipient comprise carrier (such as microcrystalline Cellulose, lactose, mannitol especially, starch), solvent (such as liquid macrogol), emulsifying agent and dispersant or wetting agent (such as sodium lauryl sulphate, oleic acid polyoxy sorbitan esters, propylene glycol), binding agent (such as polyvinylpyrrolidone), synthesis and natural polymer (such as albumin), stabilizing agent (such as antioxidant, as ascorbic acid), coloring agent (such as inorganic pigment, as iron oxides) and masking property spice and abnormal smells from the patient.
The effective dosage of CDCA can change according to the age body weight of administering mode, patient, coincident with severity degree of condition and other relevant factor, and during oral administration, recommended dose is 500-1000mg/ time, every day 1-2 time; Parenteral recommended dose is 15-45mg/ time, every day 1 time.
Technical scheme of the present invention is: by cutting off anterior cruciate ligament method establishment rabbit knee osteoarthritis model, select CDCA as medicine first, by the mode administration of joint cavity injection, study the impact that it changes the indexs such as the inflammatory cytokine of rabbit knee osteoarthritis model and arthropathology, observe CDCA to the preventive and therapeutic effect of rabbit knee osteoarthritis animal model, thus provide experimental basis for CDCA prevents and treats osteoarthritis.
The invention has the advantages that: (1) the invention has the advantages that: (1) provides CDCA to have the purposes of Effective Anti osteoarthritis: obviously can improve the situations such as osteoarthritis position cell infiltration, proliferation of fibrous tissue and cartilage surface damage, reduce MMP-1 in joint fluid, MMP-3, IL-1 β and PGE
2level, display CDCA has the effect of potent anti-osteoarthritis.
(2) CDCA provided by the invention has the purposes of Effective Anti osteoarthritis, has potential great economy effect.Preparation prepared by CDCA or its pharmaceutically acceptable carrier has the application prospect for the treatment of medicine for treating arthritis, develop according to national original new drug drug approval law procedure, be expected to become the country 1 class high-efficiency low-toxicity treatment osteoarthritis new drug with the independent intellectual property of China, industrialization prospect is clear and definite.
Accompanying drawing explanation
Below in conjunction with drawings and Examples, the invention will be further described:
Figure 1A is the cardinal principle picture of each group of rabbit knee joint specimen; Figure 1B is the impact that CDCA marks substantially on rabbit knee joint;
Fig. 2 A is that each group of rabbit knee joint position articular cartilage pathological tissue changes picture; Fig. 2 B is the impact of CDCA on rabbit knee joint position articular cartilage pathological score;
Fig. 3 A is that each group of rabbit knee joint position synovial membrane pathological tissue changes picture; Fig. 3 B is the impact of CDCA on rabbit knee joint position synovial membrane pathological score;
Fig. 4 is each group of kneed micro-CT picture of rabbit;
Fig. 5 A is that CDCA affects contrast figure to MMP-1 level in rabbit joint fluid, Fig. 5 B is that CDCA affects contrast figure to MMP-3 level in rabbit joint fluid, Fig. 5 C is that CDCA affects contrast figure to IL-1 β level in rabbit joint fluid, and Fig. 5 D is that CDCA is to PGE in rabbit joint fluid
2the impact contrast figure of level;
Wherein, Sham is sham operated rats; Model is model group.CDCA is Chenodeoxycholic acid; CDCA-10 is 10mg/kg treatment group; CDCA-50 is 50mg/kg treatment group; Celecoxib-15 is positive control drug Celecoxib15mg/kg matched group.
Detailed description of the invention
According to following embodiment, the present invention may be better understood.But those skilled in the art will readily understand, the content described by embodiment only for illustration of the present invention, and should can not limit the present invention described in detail by claims yet.
One, material
1. laboratory animal
New zealand white rabbit, 40, male, body weight 3.0 ~ 3.5kg, cleaning grade, is provided by Shanghai Slac Experimental Animal Co., Ltd., laboratory animal production licence number (SCXK (Shanghai) 2012-0002).Duration of test receptacle temperature 20 ± 3.2 DEG C, relative humidity is 65 ~ 75%, freely ingests and drinks water.
2, medicine and reagent:
2.1 medicine
Chenodeoxycholic acid (CDCA, content is >=98%) and celecoxib (Celecoxib, content is >=98%) provide by Sigma-Aldrich (Louis, MO, USA) company.4 DEG C of Refrigerator stores, matching while using.0.9% sodium chloride solution, Otsuka Pharmaceutical (China) Co., Ltd. produces, the accurate word of traditional Chinese medicines: H12020025; Penicillin injection (800,000 unit), Huabei Pharmaceutic Co., Ltd produces, the accurate word of traditional Chinese medicines: H13020657; Chloral hydrate solution, First Affiliated Hospital of Soochow University,Suzhou is produced, Soviet Union's medicine word: H04001504.
2.2 reagent
ELISA kit (TSZ Scientific LLC, Framingham, MA, the USA) company of MMP-1, MMP-3 and IL-1 β produces; PGE
2eLISA kit (R & D Systems, Minneapolis, MN, USA) company produce.
2.3 instrument
Electronic balance scale, EL104 type, Shanghai Yue Ping scientific instrument company limited produces; 3K15 type tabletop refrigerated centrifuge, German Sigma company produces; Sunrise microplate reader, is produced by Tecan company of Switzerland; BX41 optical microscope (Japanese OLYMPUS company).
Two, experimental technique
1, modeling and administration
Get 40 male healthy new zealand white rabbits, body weight 3.0 ~ 3.5kg, be divided into 5 groups at random, often organize 8, be divided into sham operated rats, model group, CDCA low (10mg/kg), CDCA high (50mg/kg) medicine group and positive control drug Celecoxib (15mg/kg) group.All animal model right knee joint preserved skins the previous day, preoperatively weigh, and press 300mg/kg through intraperitoneal injection of anesthesia, be fixed on operating-table by supine position with 10% chloral hydrate, and sterilization paving is single.Sham operated rats only does skin incision, does not cut off anterior cruciate ligament.The animal of model group and each treatment group all adopts anterior cruciate ligament-transection method to bring out osteoarthritis.Concrete operation step is as follows, gets patella inner incision, appears articular cavity, cuts off anterior cruciate ligament, and excises the broken ends of fractured bone 1 ~ 2mm, prevent tissue adhesion, note Saving cortilage cartilage in art, layer-by-layer suture otch, postoperative 3d intramuscular injection penicillin, 400,000 U/d.Observe after each group of laboratory animal surrounding wound healing good after, then carry out joint cavity injection administration, per injection injection volume is 0.5mL, 1 time weekly, carries out 5 weeks continuously.Medicine CDCA group, joint cavity injection gives low (10mg/kg), high (50mg/kg) two kinds of dosage; Positive drug group, joint cavity injection gives Celecoxib (15mg/kg); Model group only gives blank solvent 0.5ml; Sham operated rats will not normally be raised in any process.All each treated animals adopt air tap inserting method to put to death in 7 days after last administration.
2, gross examination of skeletal muscle
Put to death animal when drawing materials, observe right kneed articular surface whether gloss, with or without softening stove, erosion, ulcer and defect, strip off with or without cartilage, subchondral bone matter exposes, and local joint is formed with or without hyperosteogeny.And assess by cardinal principle code of points: 0 point: articular surface is smooth, color and luster is normal; 1 point: articular surface is coarse, have little crack, color and luster is gloomy; 2 points: articular surface is rotten to the corn, and cartilage defect reaches cartilage top layer or middle level; 3 points: articular surface ulcer, defect reaches cartilage deep layer; 4 points: cartilage strips off, subchondral bone matter exposes.
3, pathological study
After adopting air tap inserting method to put to death each group of laboratory animal, sagittal plain cuts right knee joint, bone weight-bearing portion mark wood inside femur, thick about 0.5cm, comprises articular cartilage and subchondral bone, is placed in 10% neutral formalin solution and fixes 24h, 10%EDTA decalcification, dehydration of alcohol, transparent, waxdip, 5 μm of thickness serial section, roasting sheet 1h, dewaxing, aquation, HE dyes, dehydration, transparent, neutral plastic cement mounting.Whether optical microphotograph Microscopic observation articular cartilage structure is clear, and whether chondrocyte arrangement is neat, with or without the proliferation of chondrocytes, disappearance, with or without pathological change situations such as whether cartilage crack, ulcer and defect, cartilage layers fibre composition increase.Observe synovial tissue with or without plump and hypertrophy, invade, with or without situations such as cell infiltration with or without blood vessel.To score standard according to the pathological changes of articular cartilage and synovial membrane in osteoarthritis tissue classification procedure, the lesion degree of each animal knee joint specimen is scored and compares between organizing.
4, the detection of Micro-CT scanning (micro-CT)
After experiment terminates, be flat in the inspection groove of micro-CT system by each group of right knee joint specimen of test rabbit, binding fixedly prevents specimen from moving.Long axis direction along specimen scans, and has scanned rear NRecon software and has carried out three-dimensional reconstruction, then processed further image with CT analysis software, detects the destructiveness of each animal knee joint specimen bone structure.
5, MMP-1, MMP-3, IL-1 β and PGE in joint fluid
2level determination
After experiment terminates, get the right knee joint of each treated animal, with the capable joint puncture of 1ml physiological saline device is housed after depilation, sterilization, lml normal saline is injected articular cavity from suprapatellar bursa position, extract out after repeatedly rinsing, then immediately by centrifugal at 4 DEG C for joint irrigation specimen (3500r/min) 10min, draw supernatant, after carrying out labelling ,-70 DEG C save backup, to measure MMP-1 in rabbit joint fluid, MMP-3, IL-1 β and PGE
2level, all test experience are tested and are all operated according to ELISA kit operation instructions.
6, statistical method
Adopt SPSS 16.0 statistical software processing system, experimental data with
represent, statistical analysis adopts Mann – WhitneyU inspection, and P<0.05 has statistical significance.
Three, result of implementation
1CDCA is on the impact of rabbit gross examination of skeletal muscle
Sham operated rats shows: cartilage surface is complete smooth, and color and luster is normal, without hydrarthrosis and synovial hyperplasia.Model group shows: cartilage strips off, and subchondral bone exposes, and femoral lateral condyle has obvious hyperosteogeny and ulcer to generate (Figure 1A).Show in CDCA (10mg/kg, 50mg/kg) and Celecoxib (15mg/kg) treatment group: articular cartilage surface owes smooth, be dispersed in ulcer point, cartilaginous edges is formed without hyperosteogeny, have no crackle and softening stove, destructiveness obviously reduces substantially, wherein CDCA (50mg/kg) and Celecoxib (15mg/kg) treatment group compare with model group, and therapeutic effect obviously (P<0.001).Figure 1B is shown in the scoring substantially of each group.
2CDCA is on the impact of rabbit knee joint pathological observation
Articular cartilage HE coloration result: show in sham operated rats: animal cartilage top layer is complete, and cartilage structure is clear and legible, cell arrangement is neat, and damp line structure is complete; Show in model group: cartilage top layer is stripped off, the obvious hypertrophy of cell, arrangement serious diseases, damp line structure destroys (Fig. 2 A).Celecoxib (15mg/kg) treatment group shows: cartilage lesion degree is comparatively light, smooth surface, but still the dyeing intensification of visible cartilage cells of superficial layer and cell arrangement disorder; CDCA (10mg/kg, 50mg/kg) treatment group shows: cartilage top layer little damage, as seen cells of superficial layer hypertrophy to a certain degree, the cartilage lesions such as the dyeing intensification of part cell, but compares with model group and improve significantly.The pathological score of each treated animal articular cartilage is shown in Fig. 2 B.
Synovial membrane HE coloration result: show in sham operated rats: synovial membrane is knitted without plump and hypertrophy, invades, without cell infiltration without blood vessel; Show in model group: synovial lining cell hyperplasia, arrangement is mixed and disorderly, blood capillary and proliferation of fibrous tissue, a large amount of inflammatory cell infiltration (Fig. 3 A).Show in CDCA (10mg/kg, 50mg/kg) treatment group: synovial cell's quantity comparatively model group reduces, slight proliferation of fibrous tissue, a small amount of scorching card cellular infiltration.Wherein CDCA (50mg/kg) and Celecoxib (15mg/kg) treatment group compare with model group, and therapeutic effect obviously (P<0.001).The pathological score of each treated animal synovial membrane is shown in Fig. 3 B.
The impact that 3CDCA treatment detects rabbit knee joint micro-CT
Carry out micro-CT inspection to rabbit knee joint, result shows: in model group, joint part bone structure destruction is serious, and hyperosteogeny is formed and increases; In sham operated rats, boney joint surfaces is smooth, has no bone structure destruction and hyperosteogeny formation; In CDCA (50mg/kg) and Celecoxib (15mg/kg) treatment group, rabbit knee surface is tending towards smooth, and have no obvious hyperosteogeny and formed, bone structure destruction degree obviously reduces, and sees Fig. 4.
4CDCA is to MMP-1, MMP-3, IL-1 β and PGE in joint fluid
2the impact of level
Get the joint fluid of rabbit, adopt ELISA detection method, to MMP-1, MMP-3, IL-1 β and PGE in joint fluid
2level measure.Analysis of test results shows: MMP-1, MMP-3, IL-1 β and PGE in model group joint of animal liquid
2content apparently higher than sham operated rats (P<0.001); CDCA (10mg/kg, 50mg/kg) and Celecoxib (15mg/kg) treatment group compare with model group, all obviously can reduce MMP-1, MMP-3, IL-1 β and PGE in joint fluid
2level, wherein CDCA (50mg/kg) and Celecoxib (15mg/kg) treatment group compare with model group, and inhibitory action significantly (P<0.001), is shown in Fig. 5 A-5D.
Result of implementation brief summary
1. rabbit joint cavity injection CDCA, 1 time weekly, after carrying out treatment in 5 weeks continuously, CDCA (50mg/kg) can reduce the cardinal principle destructiveness of laboratory animal significantly, and knee joint is formed without obvious hyperosteogeny, has no crackle and softening stove.
2. pathologic examination result display, the situations such as the rear rabbit knee joint position cell infiltration of CDCA treatment, proliferation of fibrous tissue and cartilage surface damage all obviously reduce.
3.micro-CT checks display, rabbit joint cavity injection CDCA, 1 time weekly, and after carrying out treatment in 5 weeks continuously, the rabbit knee surface of CDCA (50mg/kg) treatment group is tending towards smooth, and have no obvious hyperosteogeny and formed, bone structure destruction degree obviously reduces.
MMP-1, MMP-3, IL-1 β and PGE in rabbit joint fluid after 4.CDCA treatment
2level obviously reduce.
In sum, CDCA can reduce MMP-1, MMP-3, IL-1 β and PGE in rabbit joint fluid
2level, alleviates degraded and the infringement of articular cartilage, has certain preventive and therapeutic effect to osteoarthritis.
The present invention is further illustrated by experimental example below.
Prepare the embodiment 1 of medicament:
Get CDCA monomeric compound 20g, add 1,2-PD 100m1, fully dissolve, add sterilized water for injection and be diluted to 1000m1, be dispensed into after mixing in 1000 ampullas, often prop up lml, containing CDCA20mg.
Prepare the embodiment 2 of medicament:
Get CDCA monomeric compound 20g, add medical starch 280g, the two fully mixes, and makes 1000 capsules, and every heavy 0.3g, containing CDCA 20mg.
Prepare the embodiment 3 of medicament:
Get CDCA monomeric compound 100g, add medical starch 200g, the two fully mixes, and makes 1000, and the heavy 0.3g of every sheet, containing CDCA 100mg.
More than show and describe ultimate principle of the present invention, principal character and advantage of the present invention.The technical staff of the industry should understand; the present invention is not by the restriction of above-mentioned example; what describe in above-mentioned example and description just illustrates principle of the present invention; the present invention also has various changes and modifications without departing from the spirit and scope of the present invention, and these changes and improvements all fall in the claimed scope of the invention.Application claims protection domain is defined by appending claims and equivalent thereof.
Claims (7)
- The application of 1.CDCA in preparation treatment medicine for treating arthritis.
- 2. purposes according to claim 1, is characterized in that, described pharmaceutical pack is containing inertia, the excipient that nontoxic, pharmacology is suitable.
- 3. purposes according to claim 1, is characterized in that, described medicine is tablet, capsule, electuary, drop, lyophilized products, granule, ointment or injection.
- 4. treat a medicine for treating arthritis, it is characterized in that, described medicine contains the CDCA active component for the treatment of effective dose.
- 5. medicine according to claim 4, is characterized in that, described medicine also comprises one or more inertia, the excipient that nontoxic, pharmacology is suitable.
- 6. medicine according to claim 5, is characterized in that, described excipient is carrier, solvent, emulsifying agent, dispersant, wetting agent, binding agent, stabilizing agent, coloring agent, spice.
- 7. medicine according to claim 4, is characterized in that, described medicine is injection, tablet, capsule, electuary, drop, granule or ointment.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510121989.6A CN104825464B (en) | 2015-03-19 | 2015-03-19 | CDCA is preparing the application in treating medicine for treating arthritis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510121989.6A CN104825464B (en) | 2015-03-19 | 2015-03-19 | CDCA is preparing the application in treating medicine for treating arthritis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104825464A true CN104825464A (en) | 2015-08-12 |
| CN104825464B CN104825464B (en) | 2018-02-02 |
Family
ID=53803923
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510121989.6A Active CN104825464B (en) | 2015-03-19 | 2015-03-19 | CDCA is preparing the application in treating medicine for treating arthritis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104825464B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113143936A (en) * | 2021-02-10 | 2021-07-23 | 北京蕴汇医药科技有限公司 | Application of chenodeoxycholic acid or derivative thereof in preparation of EGFR and/or STAT3 inhibitor |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101678045A (en) * | 2007-05-14 | 2010-03-24 | 首尔大学校产学协力财团 | Biosurfactant is as the application of antiinflammatory and tissue preservative solution |
| WO2011068927A2 (en) * | 2009-12-04 | 2011-06-09 | Abbott Laboratories | 11-β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 (11B-HSD1) INHIBITORS AND USES THEREOF |
-
2015
- 2015-03-19 CN CN201510121989.6A patent/CN104825464B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101678045A (en) * | 2007-05-14 | 2010-03-24 | 首尔大学校产学协力财团 | Biosurfactant is as the application of antiinflammatory and tissue preservative solution |
| WO2011068927A2 (en) * | 2009-12-04 | 2011-06-09 | Abbott Laboratories | 11-β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 (11B-HSD1) INHIBITORS AND USES THEREOF |
Non-Patent Citations (5)
| Title |
|---|
| HEATHER F BIGG等: "The inhibition of metalloproteinases as a therapeutic target in rheumatoid arthritis and osteoarthritis", 《CURRENT OPINION IN PHARMACOLOGY》 * |
| HIROSHI MITSUI: "Expression of membrane-type matrix metalloproteinases in synovial tissue from patients with rheumatoid arthritis or osteoarthritis", 《MOD RHEUMATOL》 * |
| 姚如愚等: "基质金属蛋白酶与骨关节炎", 《国外医学内科学分册》 * |
| 闫兆威等: "朗德鹅胆汁的化学成分及金属蛋白酶抑制活性研究", 《天然产物研究与开发》 * |
| 阮佳莉等: "金属蛋白酶在骨关节炎表达的研究进展", 《中国骨质疏松杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113143936A (en) * | 2021-02-10 | 2021-07-23 | 北京蕴汇医药科技有限公司 | Application of chenodeoxycholic acid or derivative thereof in preparation of EGFR and/or STAT3 inhibitor |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104825464B (en) | 2018-02-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102548560A (en) | Compositions and methods for prevention and treatment of coronary heart diseases | |
| CN109562281A (en) | The prodrug of phenols TRPV1 agonist is combined with local anesthetic and vasoconstrictor for improving local anaesthesia | |
| Yao et al. | A comparison of lateral fixation versus dual plating for simple bicondylar fractures | |
| Tang et al. | Effect of bioactive peptide of Carapax Trionycis on TGF-β1-induced intracellular events in hepatic stellate cells | |
| CN104825464A (en) | Application of CDCA in preparation of drug for treating osteoarthritis | |
| KR100915124B1 (en) | Preventives or remedies for endometriosis | |
| Chareancholvanich et al. | Efficacy of epinephrine in local infiltration analgesia on pain relief and opioid consumption following total knee arthroplasty: a randomized controlled trial | |
| CN104490908B (en) | A kind of medical composition and its use being derived from the Cortex Eucommiae | |
| CN108686215A (en) | Include the medical composition and its use of chemical ablation agent, bioactive ingredients and vaccine adjuvant | |
| CN104586865A (en) | A pharmaceutical composition for treating cardiovascular diseases | |
| CN111000986A (en) | Application of irisin in preparing medicine for preventing and treating osteoarthritis | |
| CN104257762A (en) | Drug combination and purpose for preventing and curing osteoporosis | |
| CN108159063A (en) | Application of the akebiasaponin D in the drug for promoting cartilage of osteoarthritis reparation is prepared | |
| CN1209116C (en) | Application of akebia saponin D in preparation of medicine for proventing and treating osteo pathic | |
| CN103816172B (en) | The application of eleutheroside E in preparation treatment medicine for treating rheumatoid arthritis | |
| CN106924225A (en) | Application of the magnolol in antineoplastic sensitizer is prepared | |
| CN1827121A (en) | Preparation of safflower and its extract and their medical application in promoting tissue blood vessel regeneration | |
| CN106890189A (en) | Application of the chonglou saponin in antineoplastic sensitizer is prepared | |
| CN100375616C (en) | Bone strengthening dripping pills with Premena fulva craib as raw material and method for preparing the same | |
| CN101396437B (en) | Anti-gout drop pills of pure traditional Chinese medicine | |
| CN1733013A (en) | Novel route for administering hairy holly injection and preparation process thereof | |
| CN108888628A (en) | A kind of ginsenoside GRh2 is preparing application and its drug in resisting toxoplasmosis compound preparation | |
| CN105561310B (en) | A kind of pharmaceutical composition and its preparation method and application containing ginkolide B and Xa factor inhibitor | |
| CN107898828A (en) | Pepper Bi roots of grass compositions dichloromethane extraction position and its preparation method and application | |
| CN102697766A (en) | Application of N-methyl piperonylethylamine and salts of N-methyl piperonylethylamine in preparation of drugs for preventing and/or treating encephalopathy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| EXSB | Decision made by sipo to initiate substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |