CN103919776B - A kind of pharmaceutical composition for the treatment of of arthritis - Google Patents
A kind of pharmaceutical composition for the treatment of of arthritis Download PDFInfo
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- CN103919776B CN103919776B CN201410173902.5A CN201410173902A CN103919776B CN 103919776 B CN103919776 B CN 103919776B CN 201410173902 A CN201410173902 A CN 201410173902A CN 103919776 B CN103919776 B CN 103919776B
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- arthritis
- acetaminophen
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- tetrahydropalmatine
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- 206010003246 arthritis Diseases 0.000 title claims abstract description 24
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 15
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims abstract description 56
- 229960005489 paracetamol Drugs 0.000 claims abstract description 26
- 239000003814 drug Substances 0.000 claims abstract description 20
- 239000000203 mixture Substances 0.000 claims description 16
- UELPQYXGRIZTHA-XSEBJXQCSA-N rotundin Chemical compound C1[C@H](O)\C(C)=C/[C@H]2OC(=O)C(=C)[C@@H]2[C@H](OC(=O)C(\C)=C/C)C[C@@]2(COC(C)=O)O[C@@H]21 UELPQYXGRIZTHA-XSEBJXQCSA-N 0.000 claims description 9
- UELPQYXGRIZTHA-UHFFFAOYSA-N Rotundin Natural products CC=C(C)/C(=O)OC1CC2(COC(=O)C)OC2CC(O)C(=C/C3OC(=O)C(=C)C13)C UELPQYXGRIZTHA-UHFFFAOYSA-N 0.000 claims description 7
- 238000009472 formulation Methods 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- AEQDJSLRWYMAQI-UHFFFAOYSA-N Tetrahydropalmatine Natural products C1CN2CC(C(=C(OC)C=C3)OC)=C3CC2C2=C1C=C(OC)C(OC)=C2 AEQDJSLRWYMAQI-UHFFFAOYSA-N 0.000 abstract description 21
- AEQDJSLRWYMAQI-KRWDZBQOSA-N tetrahydropalmatine Chemical compound C1CN2CC(C(=C(OC)C=C3)OC)=C3C[C@H]2C2=C1C=C(OC)C(OC)=C2 AEQDJSLRWYMAQI-KRWDZBQOSA-N 0.000 abstract description 21
- 230000000694 effects Effects 0.000 abstract description 14
- 229940079593 drug Drugs 0.000 abstract description 6
- ADVGKWPZRIDURE-UHFFFAOYSA-N 2'-Hydroxyacetanilide Chemical compound CC(=O)NC1=CC=CC=C1O ADVGKWPZRIDURE-UHFFFAOYSA-N 0.000 abstract description 5
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 3
- 231100000331 toxic Toxicity 0.000 abstract description 3
- 230000002588 toxic effect Effects 0.000 abstract description 3
- 241000700159 Rattus Species 0.000 description 11
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 7
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- 206010061218 Inflammation Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 201000008482 osteoarthritis Diseases 0.000 description 3
- 150000003180 prostaglandins Chemical class 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 208000006820 Arthralgia Diseases 0.000 description 2
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- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 2
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- 230000009471 action Effects 0.000 description 2
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- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 2
- 229960001259 diclofenac Drugs 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000008407 joint function Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- OJLOPKGSLYJEMD-URPKTTJQSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(1e)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-URPKTTJQSA-N 0.000 description 2
- 229960005249 misoprostol Drugs 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- CPJSUEIXXCENMM-UHFFFAOYSA-N phenacetin Chemical compound CCOC1=CC=C(NC(C)=O)C=C1 CPJSUEIXXCENMM-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
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- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 229930189907 rotundine Natural products 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- 102400000967 Bradykinin Human genes 0.000 description 1
- 101100275473 Caenorhabditis elegans ctc-3 gene Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010018634 Gouty Arthritis Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 208000003947 Knee Osteoarthritis Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 101100168274 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cox-3 gene Proteins 0.000 description 1
- 208000033240 Progressive symmetric erythrokeratodermia Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001741 anti-phlogistic effect Effects 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000003907 antipyretic analgesic agent Substances 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
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- 230000006020 chronic inflammation Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
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- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
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- 238000006317 isomerization reaction Methods 0.000 description 1
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- 210000001589 microsome Anatomy 0.000 description 1
- 239000004084 narcotic analgesic agent Substances 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 210000000929 nociceptor Anatomy 0.000 description 1
- 229960000381 omeprazole Drugs 0.000 description 1
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- 229960003893 phenacetin Drugs 0.000 description 1
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- CASUWPDYGGAUQV-UHFFFAOYSA-M potassium;methanol;hydroxide Chemical compound [OH-].[K+].OC CASUWPDYGGAUQV-UHFFFAOYSA-M 0.000 description 1
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Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a kind of pharmaceutical composition for the treatment of of arthritis, belong to medical art.This pharmaceutical composition contains tetrahydropalmatine and acetaminophen, and wherein the weight ratio of tetrahydropalmatine and acetaminophen is 1:0.5-4.The most important advantage of the present invention is collaborative antiinflammatory, decrease the consumption that tetrahydropalmatine and acetaminophen are used alone simultaneously, thus the expense of patient medication is reduced, reduce the toxic and side effects of acetyl aminophenol simultaneously, add the safety of medication and the compliance of patient.
Description
Technical field
The invention belongs to medical art, be specifically related to a kind of pharmaceutical composition for the treatment of of arthritis.
Background technology
Arthritis refers to the arthritis pathological changes caused by inflammation, infection, wound or other factors, belong to rheumatism subject disease, comparatively common are osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and gouty arthritis, all can cause the obstacle of function of joint to some extent, and longer, the touching difficulty of the course of disease more, common trait is the chronic inflammation processes of Progressive symmetric erythrokeratodermia development.Main clinical manifestation is the symptoms such as arthralgia, arthroncus, joint function disturbance, is one of major reason disabled.According to statistics, global arthritic reaches 3.55 hundred million, and China's arthritis is more than 100,000,000, and number is also in continuous increase.Arthritis has had a strong impact on life, the working and learning of patient, so there is the exploitation of the arthritis treatment medicine of good result to have great importance.
At present for the arthritis cure method that also neither one is satisfied, be generally all symptomatic treatment, namely alleviate arthralgia, improve range of motion, reduce joint function disturbance.Slight arthritis can take conservative treatment, and for most of patients with osteoarthritis, slightly can control by taking analgesic drug product to moderate pain, these drug mains will comprise the NSAID (non-steroidal anti-inflammatory drug) such as acetaminophen, diclofenac.The side effect of nonsteroidal antiinflammatory drug to gastrointestinal tract and kidney is comparatively obvious, and the importance of therefore basic pharmaceutical therapeutic alliance is appeared suddenly.The omeprazole of U.S. Xi Er large pharmaceutical factory development wets the compound recipe be made up of NSAID (non-steroidal anti-inflammatory drug) diclofenac and misoprostol, treatment of arthritis is evident in efficacy, misoprostol in compound recipe has stronger antiulcer action, but due to expensive, its application can not get popularizing.
Dl-tetrahydr-Opalmatine (dl-tetrahydropalmatine, THP), belongs to the former little Rhizoma Nelumbinis base analogue (tetrahydroprotoberberines, THPBs) of tetrahydrochysene.THP divides supination can be divided into levo form (1-THP) and d-isomer (d-THP) through chemistry.Result of study for many years shows, only l-THP has central analgesia, calm, stable effect, and d-THP, then without obvious analgesic activity, is emptying dose of dopamine in brain (DA).L-THP clinical application is called rotundine (rotundine), there is the Clinical practice time reaching 40 years, analgesia effect is reliable, have good therapeutical effect, and its analgesic activity does not belong to narcotic analgesic and anti inflammation and heat resolution analgesic category to chronic, persistence dull pain.
Acetaminophen (Acetaminophen is called for short AP) is called in Britain and flutters heat breath epilepsy, is an antipyretic analgesic.First be found in 19 ends, the world, be an active metabolite of the analgesic phenacetin that a kind of toxicity is larger, belong to phenyl amines.This medicine and nineteen fifty-five are gone on the market by MeNeil laboratory in the U.S., are the analgesic drug product that on market, market is best at present.The Analgesic Mechanism of acetaminophen is not yet very clear, may be produce shock effect by the synthesis (comprise and suppress prostaglandin synthetase) of prostaglandin (PG) in suppression central nervous system and the impulsion of blocking-up pain nerve tip, the latter can may make the synthesis of the material of pain receptor sensitivity (as 5-hydroxy tryptamine, Kallidin I etc.) relevant with suppression prostaglandin or other.The acetaminophen of low concentration stimulates the generation of PGs, and the generation of the acetaminophen of high concentration PGs always.Robak is the reported first two-way activity of this medicine in the research of the COX enzyme (Prostaglandin Cyclooxygenase) of cattle seminal vesicle microsome.There is arguement in the binding mode of acetaminophen, it is generally acknowledged that it passes through to suppress Cycloxygenase-3(COX-3 for many years at present always) work, but also need more research.
At present, in treatment of arthritis, there is not yet using tetrahydropalmatine or by tetrahydropalmatine and the acetaminophen coupling medicine as main active.
Summary of the invention
Acetyl aminophenol can be used for treating knee osteoarthritis, but has larger poison pair effect, because which limit the application in this respect of this medicine due to the acetaminophen of heavy dose.The present inventor finds under study for action unexpectedly, after reducing the dosage of acetyl aminophenol, it is combined with tetrahydropalmatine and can obtain good antiphlogistic effects.
Based on studying discovery above, an object of the present invention is to provide a kind of pharmaceutical composition acting on comprehensive, that toxic and side effects is low and cheap treatment of arthritis.This medicine contains tetrahydropalmatine and the acetaminophen of special ratios, and because two medicine mechanism of action interact, after composition compositions, antiinflammatory action is more comprehensive, and two medicines have share synergism, and its antiinflammatory action is obviously better than the folk prescription of same dose.
In order to realize object of the present invention, inventor is studied by lot of experiments, finally obtains following technical scheme:
A pharmaceutical composition for treatment of arthritis, this pharmaceutical composition contains tetrahydropalmatine and acetaminophen.
Preferably, the pharmaceutical composition for the treatment of of arthritis as above, wherein the weight ratio of tetrahydropalmatine and acetaminophen is 1:0.5-4.
Further preferably, the pharmaceutical composition for the treatment of of arthritis as above, wherein the weight ratio of tetrahydropalmatine and acetaminophen is 1:1.5.
Again further preferably, the pharmaceutical composition for the treatment of of arthritis described above, wherein said tetrahydropalmatine is raceme or the levo form of tetrahydropalmatine.
The pharmaceutical composition for the treatment of of arthritis of the present invention is oral formulations.Preferably, described oral formulations comprises tablet, capsule, granule, oral liquid.Further preferably, the oral formulations described in per unit contains tetrahydropalmatine 20mg, acetaminophen 20-30mg.
By animal experiment study, we find that compositions provided by the present invention can suppress the pedal swelling of model of adjuvant arthritis in rats, effectively regulate PGE in Plasma TNF-α and tissue
2activity.Therefore, two of object of the present invention a kind of new pharmaceutical composition is to provide for the preparation of the purposes in the medicine for the treatment of of arthritis; That is: the compositions that forms of tetrahydropalmatine and acetaminophen is as the application of active component in the medicine preparing treatment of arthritis.Preferably, the compositions that forms of rotundin and acetaminophen is as the application of active component in the medicine preparing treatment of arthritis.
Compared with prior art, the pharmaceutical composition tool that the present invention relates to has the following advantages and progress significantly:
(1) the most important advantage of the present invention is collaborative antiinflammatory, effectively can regulate PGE in Plasma TNF-α and tissue
2activity, thus reach and cure the object of rheumatoid arthritis;
(2) when identical curative effect, decrease the consumption that tetrahydropalmatine and acetaminophen are used alone, especially drastically reduce the area the consumption of acetaminophen, thus the expense of patient medication is reduced, reduce the toxic and side effects of acetyl aminophenol simultaneously, add the safety of medication and the compliance of patient.
Detailed description of the invention
Be below specific embodiments of the invention, technical scheme of the present invention is done to describing further, but protection scope of the present invention be not limited to these embodiments.Every do not deviate from the present invention's design change or equivalent substituting include within protection scope of the present invention.
Embodiment 1 experimental animal model of CFA induced adjuvant arthritis in rats is tested
SD rat 40, body weight 180-220g, after conventional adaptation raises one week, sets up the pathological model of adjuvant-induced arthritis in the sufficient sole of the foot portion intradermal injection Freund's complete adjuvant 0.1mL of rat right hind leg.The successful adjuvant arthritis rats of modeling is divided into four groups at random by body weight, i.e. model control group, rotundin group (20mg/kg/d), acetaminophen group (30mg/kg), compositions group (rotundin 20mg/kg/d+ acetaminophen 30mg/kg/d) totally 4 groups, often organizes 10.After modeling the 4th day, the medicine that gavage gives corresponding dosage is carried out to rotundin group, acetaminophen group, compositions group rat, the isopyknic purified water of model control group gavage, each group every day 1 time, administration three weeks altogether.
Rat respectively at before modeling, before administration, administration three weeks rear fine rules and ruler measure the change of the sufficient sole of the foot Zhou Jing of right hind fixed position.After last administration 5 hours, sterile working under etherization, from heart blood drawing 2-3mL, anticoagulant heparin, isolated blood plasma, is placed in-20 DEG C and preserves test plasma TNF-alpha actives.On the left back ankle joint of every rat, 0.5cm place cuts inflammatory swelling foot, weigh, peeling, shreds, normal saline 5rnl soaks 1 hour, take out Mus pawl, centrifugal soak, Aspirate supernatant 0.1rnl, add the KOH-methanol solution 2ml of 0.5mol/L, isomerization 20 minutes in 50 DEG C of water-baths, with methanol dilution to 20ml, is that 278nm place measures its optical density value (OD) in wavelength.Suitable absorbing light density value is organized to represent PGE with every gram
2activity, as evaluation antiinflammatory index.
Can be found out by the result of the test of table 1, there is height swelling in each modeling rat the 3rd day right back ankle joint after modeling, administration is after three weeks, rotundin or acetyl aminophenol are suppressing the effect on pedal swelling more weak, and after drug combination, the two obtains significant synergism on reduction model of adjuvant arthritis in rats pedal swelling.
The comparison of right hind foot sole of the foot Zhou Jing before and after table 1 administration
Compare with before modeling,
* p< 0.01; Before and after administration, self compares,
# p< 0.05,
## p< 0.01; Compare with model group,
△ p< 0.05,
△ △ p< 0.01; Compare with tetrahydropalmatine group,
★ ★ p< 0.01; Compare with acetaminophen group,
● ● p< 0.01.
Can be found out by the result of the test of table 2, rotundin has the activity of certain reduction model of adjuvant arthritis in rats TNF-α, but to PGE
2not effect; Acetaminophen is to PGE
2there is certain reducing effect, but TNF-α is not affected.Compositions group after two medicine couplings, it is at reduction TNF-α with from PGE
2two indices all achieves good concertedness effect.
PGE in Plasma TNF-α and tissue respectively organized by table 2
2results contrast
Compare with model control group
* p< 0.05,
* p< 0.01;
Compare with tetrahydropalmatine group,
# p< 0.05,
## p< 0.01;
Compare with acetaminophen group,
△ p< 0.05,
△ △ p< 0.01.
Claims (2)
1. the compositions that forms of rotundin and acetaminophen is as the application of active component in the medicine preparing treatment of arthritis, it is characterized in that: described pharmaceutical composition is oral formulations, oral formulations described in per unit contains rotundin 20mg, acetaminophen 30mg.
2. the compositions that forms of rotundin according to claim 1 and acetaminophen is as the application of active component in the medicine preparing treatment of arthritis, it is characterized in that: described oral formulations is tablet, capsule, granule or oral liquid.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410173902.5A CN103919776B (en) | 2014-04-29 | 2014-04-29 | A kind of pharmaceutical composition for the treatment of of arthritis |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410173902.5A CN103919776B (en) | 2014-04-29 | 2014-04-29 | A kind of pharmaceutical composition for the treatment of of arthritis |
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| CN103919776A CN103919776A (en) | 2014-07-16 |
| CN103919776B true CN103919776B (en) | 2016-03-02 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103351308A (en) * | 2006-09-03 | 2013-10-16 | 于崇曦 | Positively charged water-soluble 4-acetamidophenol having rapid skin penetration speed, and related compound prodrug thereof |
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2014
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103351308A (en) * | 2006-09-03 | 2013-10-16 | 于崇曦 | Positively charged water-soluble 4-acetamidophenol having rapid skin penetration speed, and related compound prodrug thereof |
Non-Patent Citations (1)
| Title |
|---|
| 含延胡索乙素成分的药材和制剂含量测定方法研究进展;苏健等;《中国中医药信息杂志》;20101231;第17卷(第12期);110-112 * |
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| CN103919776A (en) | 2014-07-16 |
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