CN101518521B - New medical application of cedrol - Google Patents
New medical application of cedrol Download PDFInfo
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- CN101518521B CN101518521B CN2009100109018A CN200910010901A CN101518521B CN 101518521 B CN101518521 B CN 101518521B CN 2009100109018 A CN2009100109018 A CN 2009100109018A CN 200910010901 A CN200910010901 A CN 200910010901A CN 101518521 B CN101518521 B CN 101518521B
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Abstract
The invention relates to new medical application of cedrol (CE), in particular to new application thereof in preparing medicaments for relieving pain and treating arthritis. The cedrol is alpha-cedrol, beta-CE or raceme of the two in any proportion, and the total effective dose of the cedrol is between 1 and 100 mg/kg/d. The CE is extracted from natural plants extensive in sources. The invention adopts rat-paw chondrus inflammation-inducing method and adjuvant arthritis to observe the anti-inflammatory effects of the CE, and results show that the CE has obvious effect of inhibiting nonspecificinflammation reaction caused by carrageenin and also has remarkable effect of treating and preventing the adjuvant arthritis. The invention adopts a tail-flick method to observe the analgesic effects of the CE, and results show that the CE has remarkable analgesic effects on the light-heat stimulated tails of rats. The invention provides a raw material for anti-inflammatory and analgesic drugs, w hich is exact in therapeutic effects, safe, convenient and extensive in sources, and can be combined with one or more pharmaceutically acceptable carriers so as to prepare a cedrol pharmaceutical composition or preparation.
Description
Technical field
The invention belongs to medical technical field, relate to the new medical use of cedrol (CE), be specifically related to its new purposes in analgesia and treatment of arthritis medicine.
Background technology
Arthritis is a kind of common chronic disease, is meant the arthritis pathological changes that is caused by inflammation, infection, wound or other factors, belongs to rheumatism subject disease.Its principal character is redness and swelling of joints, heat, pain and dysfunction.The present arthritic of China estimates at more than 100,000,000, and number is also in continuous increase, and modal is two kinds of osteoarthritis and rheumatoid arthritis.According to another statistics, China more than 50 years old among the crowd half suffer from osteoarthritis; 90% women and 80% male suffer from osteoarthritis among the over-65s crowd.Rheumatoid arthritis is 0.34%～0.36% in the prevalence of China, it is introduced, the rheumatoid arthritis person of the being in a bad way life-span shortens 10～15 years approximately.Arthritis can be divided into according to the cause of disease: rheumatic, rheumatoid, traumatic, osteoarthritis and suppurative arthritis etc.
Rheumatic arthritis belongs to allergic disease, is one of main performance of rheumatic fever.How with febris acuta and arthralgia onset, typical case's performance is slight or the moderate heating, migratory polyarthritis; Mostly the joint of getting involved is big joint such as knee joint, ankle, shoulder, elbow, wrist, commonly is transferred to another joint by a joint, and the pathological changes part presents red, swollen, scorching hot, severe pain; Part patient also has several joints to fall ill simultaneously, and atypical patient only has arthralgia and do not have other inflammation performances, and acute inflammation generally disappears in 2-4 week; Do not stay sequela, but the Chang Fanfu outbreak.If active rheumatism influences heart, then myocarditis can take place, even leave over valve disorder.
Rheumatoid arthritis (rheumatoid arthritis) be a kind of be the chronic general LADA autoimmune disease of characteristic with the articular synovitis.Synovitis is outbreak repeatedly lastingly, the destruction that can cause intraarticular cartilage and bone, and joint function disturbance, in addition maimed.The vasculitis pathological changes is involved each organ of whole body, so primary disease is called rheumatoid disease again.
Rheumatoid arthritis is claimed rheumatoid (RA) again, is the not clear as yet chronic systemic inflammatory property disease of a kind of cause of disease, is main clinical manifestation with pathological changes outside chronic, symmetry, many synovial jointss inflammation and the joint, belongs to the autoimmune inflammatory diseases.This disease is sent out well in little joints such as hands, wrist, foots, and outbreak is symmetrical distribution repeatedly.Joint red and swollen heat pain and dysfunction are arranged in early days, and late period, stiff deformity in various degree can appear in the joint, and with bone and skeletal muscle atrophy, very easily disabled.From the angle of pathological change, rheumatoid arthritis is a kind of synovium of joint (can feed through to articular cartilage, osseous tissue, articular ligament and flesh key later on) that mainly involves, and is the popularity diseases associated with inflammation of connective tissues such as serous coat, the heart, lung and eye secondly.The general performance of rheumatoid arthritis also has heating, fatigue and weak, pericarditis, subcutaneous nodule, pleuritis, arteritis, peripheral neuropathy etc. except that arthropathy.Generalized rheumatoid arthritis also comprises the popularity pathological changes of whole body except that the inflammatory disorders of joint part.
Traumatic arthritis is many because of wound or lasting chronic strain cause articular cartilage generation degeneration or form bony spur, shows as that diseased joints is swollen, pain and the dyskinesia, is prone to occur in prudent joint, like joints such as shoulder, knee joint, ankles, sees among athlete and the person between twenty and fifty more.
Osteoarthritis is a kind of modal arthropathy, and the title of osteoarthritis is extremely many, like HOA, degenerative osteoarthritis, degeneration property arthritis, hyperplastic osteoarthritis or osteoarthritis, all refers to a kind of disease, the domestic unified osteoarthritis of using.Its prevalence increased along with the age, and the women is more multiple than the male.Osteoarthritis is with the far-end and the PIP of hands, and knee joint, elbow and shoulder joint and joint of vertebral column are got involved easily, the then less morbidity of wrist, ankle joint.Osteoarthritis is caused by tissue degeneratiaon and the strain of accumulation property; Be more common in fat overweight middle-aged and elderly people; The position of regular incidence is that knee joint, finger, neck, lumbar vertebra etc. are located; Symptom is mainly arthralgia, stiff (meeting feel pain relief behind light activity), and arthroncus, amyotrophy etc. can appear in weight person.
Suppurative arthritis is often invaded articular cavity by antibacterial and is caused, is more common in children, often betides hip joint, cardinal symptom be the part red, swollen, bitterly, heat and dysfunction, and whole body poisoning symptom such as hyperpyrexia.
The arthritis no matter which kind of reason causes or the arthritis of which kind of type, diagnosis and treatment early are in order to avoid cause permanent joint function disturbance even disable.
Being used to treat all kinds of arthritis has multiple medicine, and Western medicine has penicillamine, salicylic acid preparation, indometacin, propionate biology, immunosuppressant, levamisole etc.But the side effect of Western medicine is paid close attention to and is estimated by the world day by day, and the sense of self-protection of disease of patient treatment simultaneously makes many pharmacy corporations strengthen the natural drug of dynamics of investment and speed research and development effective and safe in continuous enhancing.
In sum, the present invention has realized the medical application noveltyization of extraction separation gained chemical constituent in the natural plants, has satisfied the demand that arthritic's demand is big, market prospect is good.
CE is a kind of sesquiterpenoid, can from multiple natural plants, extract to obtain.Present purposes is a kind of natural perfume material, is widely used in the Radix Aucklandiae, Xin Xiang and the Eastern perfume, also is used as the fumet of disinfectant and hygienic article in a large number.Sometimes also a small amount of application and pharmaceuticals industry are as a kind of medicine.Have experiment to show, sucking cedrol has sedation to rat and mice; Anti-human lung carcinoma cell NCI-H460 effect is arranged.Its structural formula is as follows.
The structural formula of CE
Summary of the invention
The object of the present invention is to provide the new purposes of CE, i.e. new application in pharmacy.
The present invention relates to CE as the application in the preparation treatment of arthritis medicine.
The present invention relates to CE as the application in the preparation treatment analgesic.
Use with the form of conventional pharmaceutical formulation when the present invention relates to CE and being used to prepare arthritis and analgesic; Described conventional pharmaceutical formulation is contained in the preparation with acceptable carrier pharmaceutically and mixes with the solid or the liquid excipient of the organic or inorganic of parenteral as being suitable in the gastrointestinal; This pharmaceutical formulation science and technology is solid form such as tablet, capsule, powder, pill, granule, also can be liquid form such as injection, Emulsion etc.
Can contain auxiliary substance, stabilizing agent, wetting agent and other additives commonly used in the above-mentioned preparation, like lactose, citric acid, tartaric acid, magnesium stearate, Gypsum Fibrosum powder, sucrose, corn starch, Pulvis Talci, gelatin, agar, pectin, Oleum Arachidis hypogaeae semen, olive oil, cocoa butter, ascorbic acid, mannitol etc.
The invention still further relates to the application of drug regimen in antiinflammatory and analgesic as active component with CE.This drug regimen can be according to method preparation well known in the art.Can process any dosage form that is applicable to that the human or animal uses through combining through the pharmaceutically acceptable solid of The compounds of this invention and one or more or liquid excipient and/or adjuvant.The content (weight) of The compounds of this invention in its drug regimen is generally 0.1～95%.
CE of the present invention is the amalgam (racemic modification) of α-CE and β-CE and their any ratios.
Solving the technical scheme that the present technique problem adopts is, CE is isolated in preparation from natural plants, and re-refining reaches more than 95% its purity, is used for analgesia and antiinflammatory action, can be used for preparing treatment of arthritis and analgesic drug.
Above-mentioned preparation can be processed according to the conventional preparation technology of various preparations.
CE of the present invention has analgesia and antiinflammatory action preferably, and total effective dose is 1-100mg/kg/d.
The specific embodiment
Following warp further describes the present invention through embodiment, but these embodiment only are explanation the present invention, and should not be construed as any restriction to the scope of the invention.
Embodiment 1: on Carrageenan causes the influence of rat paw edema inflammation
Method: 60 of SD rats; Body weight: ♀ 140～176g;
150～180g;
♀ half and half; Divide 6 groups, 10 every group.Model group is used the 1%TW-80 gastric infusion, receives reagent thing α-CE to establish 100mg/kg, 50mg/kg, 25mg/kg and 4 dose groups of 10mg/kg respectively, and gastric infusion every day (ig) once amounts to administration 4d.Positive control drug is that only gastric infusion (ig) is once before test for aspirin 0.5g/kg.Behind the d4 ig 1h, the right back vola sc 0.5% carrageenin 0.1ml of rat.1h, 2h, 4h, 6h measure the long-pending variation of sufficient corpus unguis with capillary tube method behind sc.The result handles with microcomputer SigmaStat software statistics, relatively the significant difference between aspirin and the model group (1%TW-80).
Result: α-CE25mg/kg, 50mg/kg, 100mg/kg and aspirin 0.5g/kg on Carrageenan cause scorching back rat paw edema has significant inhibitory effect, sees table 1, shows that α-CE has very strong anti-acute inflammation effect.
The inhibitory action of the rat foot claw swelling that table 1. α-CE on Carrageenan causes (X ± SD, statistical method: Mann-Whitney Rank Sum Test; Compare with matched group
*P＜0.05,
*P＜0.01,
* *P＜0.001)
Embodiment 2: to the influence of rat assist agent arthritis
Method: get 60 of SD rats, be divided into 5 groups: (1) 1%TW-80 (solvent) by weight average; (2) positive control drug dexamethasone phosphate injection 2.5mg/kg; (3) α-CE25mg/kg; (4) α-CE50mg/kg; (5) α-CE100mg/kg.All adopt gastric infusion (ig) mode.Be injected in the right back vola with Freund ' s Freund's complete adjuvant 0.1ml (containing bacillus calmette-guerin vaccine 0.5mg).The 30min gastric infusion once before the injection adjuvant.18h measures once right back pedal swelling situation behind injection adjuvant, observes CE to early stage acutely inflamed preventive effect, drug withdrawal then; Begin gastric infusion after one week, every day 1 time, continuous 7 days, measure once left back pedal swelling situation in d15, observe the preventive effect of CE, drug withdrawal then to secondary affection; Begin to carry out the therapeutic administration from d19, every day 1 time, finish up to the d28 experiment; Primary part observation CE from d21 to d28, measures once left back pedal swelling situation to the therapeutical effect of secondary affection every day; From d22 to d28; Observe incidence rate, tuberosity number or the severity of sufficient pawl swelling degree, forelimb and afterbody pathological changes by " study of tcm new drug guide " relevant adjuvant-induced arthritis Secondary cases pathological changes point system every day, presses 5 grades of point systems: 0: do not have red and swollen; 1: little toe joint is swollen slightly; 2: toe joint and pedal swelling; 3: the following foot swelling of ankle joint; 4: comprise the whole sufficient pawl swelling of ankle joint.Experiment finishes the back and puts to death rat, and immune organ thymus is taken out in dissection and spleen is weighed, and calculates organ coefficient; And the neat knee joint of the left and right sides metapedes of rat is cut off, weighed.
Result: α-CE100mg/kg and dexamethasone 2.5mg/kg group treatment back d3 are with regard to onset; Measure 1 left back pedal swelling result every day from d21 to d28 and from d22 to the analysis of d28 Secondary cases pathological changes appraisal result; With matched group significant difference (P＜0.05～0.001) is arranged more all; α-CE50mg/kg group also has notable difference (P＜0.05～0.01), sees table 2 and table 3 in most natural law.Finish the back in the d28 experiment and put to death rat, the neat knee joint of the left and right sides metapedes of rat is cut off weighed, the pedal swelling situation that result and d28 measure matches, and sees table 4.α-CE25mg/kg group organizes with dexamethasone phosphate 2.5mg/kg that the 30min gastric infusion can obviously suppress to cause the early stage acute inflammatory swelling of the sufficient sole of the foot (P＜0.05) after adjuvant is injected before injection adjuvant; α-CE100mg/kg, 50mg/kg and dexamethasone 2.5mg/kg organize administration in continuous 7 days and obviously prevent to cause sufficient sole of the foot Secondary cases swelling reaction after the adjuvant injection, see table 5 for details.Get thymus and spleen is weighed, the result shows that α-CE is dosage to immune organ and relies on inhibitory action.The antiinflammatory action that shows α-CE is relevant with immunosuppressive action, sees table 6.
Table 2, α-CE are to therapeutical effect (X ± SD, the statistical method: T-test of rat assist agent arthritis; Compare with matched group
*P＜0.05,
*P＜0.01,
* *P＜0.001)
Influence (X ± SD, statistical method: Mann-Whitney Rank Sum Test that table 3, α-CE mark to rat assist agent arthritis Secondary cases pathological changes; Compare with matched group
*P＜0.05,
*P＜0.01,
* *P＜0.001)
The weight ratio that table 4, α-CE treat the 10th day (behind the injection adjuvant the 28th day) two metapedes is (X ± SD, statistical method: T-test or Mann-Whitney Rank Sum Test; Compare with matched group
*P＜0.05,
*P＜0.01)
Table 5, α-CE are to preventive effect (X ± SD, the statistical method: Mann-Whitney Rank Sum Test of early stage inflammation of rat assist agent arthritis and secondary affection; Compare with matched group
*P＜0.05)
Table 6, α-CE treat the 10th day (behind the injection adjuvant the 28th day) influence (X ± SD, statistical method: Mann-Whitney Rank Sum Test to rat chest gland and spleen coefficient; Compare P＜0.05 with matched group,
*P＜0.01,
* *P＜0.001)
Embodiment 3: the influence that photo-thermal is stimulated the rat whipping (photo-thermal analgesic model) that causes
Method: 1) dosage is selected and is divided into groups: with the negative contrast of 1%TW-80, and the positive contrast of indomethacin 10mg/kg.α-CE and β-CE amalgam is established 12.5mg/kg, 25mg/kg, three dose groups of 50mg/kg.Every group of 10 rats; ♀
half and half, sub-cage rearing.2) administration: gastric infusion (ig) 1 time, irritating the stomach volume is 1ml/100g.3) observe: 1h behind the ig, photo-thermal stimulation in rats afterbody, the time of whipping appears in the record rat.The result handles with microcomputer SigmaStat software statistics, relatively the significant difference of indomethacin, CE and 1%TW-80 group.
Result: CE12.5mg/kg; 25mg/kg; 50mg/kg and indomethacin 10mg/kg stimulate afterbody that significant analgesic activity is arranged to rat photo-thermal; Rat the time of whipping occurs and postpones 107.8% (p＜0.05), 239.2% (p＜0.01), 243.1% (p＜0.01) and 274.5 (p＜0.001) respectively, sees table 8.
Table 7. α-CE and β-CE amalgam to photo-thermal stimulation in rats afterbody cause whipping reaction influence (x ± SD, statistical method: t-test, with the 1%TW-80 group relatively
*P＜0.05,
*P＜0.01,
* *P＜0.001)
Effective ingredient α-CE and β-CE amalgam among above result of the test explanation the present invention have antiinflammatory and analgesic activity, can in arthritis and analgesic, use.
Claims (6)
1. α-cedrol is as the purposes of unique active component in preparation treatment of arthritis medicine.
2. purposes according to claim 1 is characterized in that: the total effective dose of described α-cedrol is 1-100mg/kg/d.
3. purposes according to claim 1 is characterized in that: described α-cedrol prepares from Cacumen Platycladi, Herba Selaginellae, cypress, Cedrus deoclar (Roxb.) G. Don, Herba Lycopodii, Fructus Viticis, Caulis Mappianthi Iodoidis, Heiguteng exract, Rhizoma Zingiberis Recens, Coleus forskohlii Briq., Ranunculus sieboldii Miq., Flos Bombacis Malabarici, the big Flos Chrysanthemi of red heart, Rhizoma Smilacis Glabrae.
4. purposes according to claim 1 is characterized in that: described arthritis comprises rheumatic, rheumatoid, traumatic, osteoarthritis and suppurative arthritis.
5. purposes according to claim 1 is characterized in that: described α-cedrol can combine to process the cedrol pharmaceutical composition with pharmaceutically acceptable one or more carriers or excipient, and its content in compositions is 0.1～95%.
6. purposes according to claim 1 is characterized in that: described α-cedrol can be prepared into tablet, capsule, powder, pill, granule, injection, Emulsion, plaster, liniment, tincture, oil preparation, press agent, membrane, gel, cataplasma.
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| CN104189818A (en) * | 2014-08-22 | 2014-12-10 | 辽宁新中现代医药有限公司 | Externally applied anti-inflammatory antalgic medicine composition |
| CN106109509A (en) * | 2016-07-14 | 2016-11-16 | 南通香境生物医药科技有限公司 | The application in preparation treatment wound medicine of a kind of Cedrus deoclar (Roxb.) G. Don quintessence oil |
| CN113197904A (en) * | 2021-03-31 | 2021-08-03 | 和田维吾尔药业股份有限公司 | Traditional Chinese medicine active ingredient composition for treating cough and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005048964A1 (en) * | 2003-11-12 | 2005-06-02 | Symrise Gmbh & Co. Kg | Mixture with wintergreen odor and flavor |
| CN101218926A (en) * | 2007-01-08 | 2008-07-16 | 闫双婷 | Chinese medicinal herb made biological pesticide |
-
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005048964A1 (en) * | 2003-11-12 | 2005-06-02 | Symrise Gmbh & Co. Kg | Mixture with wintergreen odor and flavor |
| CN101218926A (en) * | 2007-01-08 | 2008-07-16 | 闫双婷 | Chinese medicinal herb made biological pesticide |
Non-Patent Citations (5)
| Title |
|---|
| 梁玉清.常见针叶行道树化学成分研究进展.《广州化学》.2008,第33卷(第3期),61-66. * |
| 纳智.三种黄皮属植物叶挥发油化学成分的研究.《生物质化学工程》.2006,第40卷(第2期),19-22. * |
| 赵军等.新疆圆柏化学成分研究.《中国药学杂志》.2008,第43卷(第19期),1461-1463. * |
| 陈练等.卷柏属植物化学成分研究进展.《中国民族医药杂志》.2006,(第5期),40-42. * |
| 高静等.柏科药用植物研究进展.《中药材》.2008,第31卷(第11期),1765-1769. * |
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