CN101919913A - Composition with effect of treating rheumatoid arthritis - Google Patents
Composition with effect of treating rheumatoid arthritis Download PDFInfo
- Publication number
- CN101919913A CN101919913A CN 201010241451 CN201010241451A CN101919913A CN 101919913 A CN101919913 A CN 101919913A CN 201010241451 CN201010241451 CN 201010241451 CN 201010241451 A CN201010241451 A CN 201010241451A CN 101919913 A CN101919913 A CN 101919913A
- Authority
- CN
- China
- Prior art keywords
- sinomenine
- radix paeoniae
- paeoniae alba
- total glucosides
- compositions
- 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
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a composition with the effect of treating rheumatoid arthritis, comprising paeony total glucosides, sinomenine and glycyrrhizic acid. The composition has good effect on treating the rheumatoid arthritis.
Description
Technical field
The present invention relates to medical technical field, be specifically related to the compositions of forming by Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid, the preparation method and the application aspect the treatment rheumatoid arthritis thereof of said composition.
Background technology
(rheumatoid arthritis RA) is a kind of in the rheumatism to rheumatoid arthritis, is a kind of autoimmune disease of refractory, because its pathogenesis be it be unclear that, does not also have gratifying therapy both at home and abroad.Scholar both domestic and external has carried out number of research projects from many aspects, attempts to disclose this sick essential characteristic and mechanism, seeks pharmaceutically-active target spot, develops new medicine, but does not still have important breakthrough.
The main clinical manifestation of RA be joint swelling and pain, morning deadlock, dysfunction and index such as laboratory immunology unusual, think that at present its pathomechanism mainly regulates unbalance relevantly with body's immunity, local joint mainly shows as the similar tumor sample of synovial cell abnormality proliferation.The treatment of RA needs long-term prescription, and at present medicine clinically has NSAID (non-steroidal anti-inflammatory drug), acts on antirheumatic etc. slowly.NSAID (non-steroidal anti-inflammatory drug) (as aspirin, diclofenac etc.) just at the symptom control of RA, can not be improved the state of an illness, because it mainly plays a role by suppressing prostaglandin, untoward reaction such as life-time service gastrointestinal tract, hepatorenal damage are many; Slowly though can partly improve the RA state of an illness, onset is slow, does not have direct antiinflammatory action, and because it mainly plays a role by immunosuppressant and antimetabolic, the untoward reaction of similar antitumor drug can appear in life-time service to act on antirheumatic (as methotrexate etc.).
Data according to World Health Organization (WHO) and American Rheumatism Association shows, the patient that the whole world suffers from rheumatism diseases such as rheumatic fever, rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, gout at present has 3.6 hundred million people approximately, is the huge disease group that generally acknowledges in the medical domain.From number of patients, China also is rheumatismal morbidity big country, and rheumatic, patient with rheumatoid arthritis almost account for 18% of population, and wherein the patient with severe symptoms reaches 80,000,000.In the middle of the ill crowd of China's rheumatism, 50% rheumatism of suffering from is in various degree arranged among the crowd more than 50 years old approximately, at the sickness rate of humid area up to 40%.According to the correlation study data show, from 2000 so far, the medication amount of money in China rheumatisant every year substantially all remains on more than 20,000,000,000 yuan.Undoubtedly, the rheumatism medication will be in the potentiality excavation phase in the medication market of China.
The effective site that Radix Paeoniae Alba total glucosides extracts from the Chinese medicine Radix Paeoniae Alba is the crude drug that the upright magnificent pharmacy in Ningbo is produced without competition.Authentication code is the accurate word H19980146 of traditional Chinese medicines, is domestic initiation, is the Radix Paeoniae Alba class medicine of the treatment rheumatism immune disease in unique Chinese medicine source, does not have similar competing product.Be that a kind of brand-new anti inflammatory immunity is regulated medicine, studies show that to have stronger antiinflammatory and immunoregulation effect through pharmacological toxicology, toxicity is little, does not have obvious ill effect; Existing obvious anti-inflammatory and analgesic effect can play dual regulation to the unusual immunologic function of patient again, makes low or strong excessively immunologic function recover normal.With the medicine of other treatment rheumatoid arthritis visibly differently be, it is humble that Radix Paeoniae Alba total glucosides has toxicity, and safety range is big, few side effects and light, and do not need the characteristics of anti symptom treatment.
Have at Radix Paeoniae Alba total glucosides on the basis of the definite curative effect of treatment rheumatoid arthritis, the exploitation that upright magnificent pharmacy is devoted to improve curative effect always, is improved subsequent products such as technology, on the basis of existing documents and materials, carried out compositions related research, purpose is to improve to this treatment of diseases effect of rheumatoid arthritis, promotes absorption, improves the bioavailability of body to peoniflorin.
Aspect the research of treatment compositions of rheumatoid arthritis and compound recipe, the patent of using with the Radix Paeoniae Alba total glucosides compatibility mainly contains following 2: (Granted publication number is: CN 1218697C) for patent of invention for " be used for the treatment of or improve arthritic pharmaceutical composition and dietary supplement ".Compositions of being made up of sinomenine, peoniflorin, ferulic acid and the effect for the treatment of rheumatoid arthritis are disclosed.(grant number is: CN1200723C), this patent discloses the extract compatibility of the Radix Paeoniae Alba and Radix Glycyrrhizae, is mainly used in relieving spasm to stop pain, treats the viral hepatitis effect for patent of invention of " Radix Paeoniae Alba Radix Glycyrrhizae extract and preparation method thereof " for another.Relevant paper: the paper of Radix Paeoniae Alba total glucosides (peoniflorin) and sinomenine, concentrate on the pharmacokinetic studies aspect, the prompting sinomenine can increase the absorption of peoniflorin.The research aspect of Radix Paeoniae Alba total glucosides (peoniflorin) and Radix Glycyrrhizae extract concentrates on the research aspect of compatibility effect.On existing document basis, the present invention has proved that by a large amount of zooperies and clinical trial the compositions that adopts Radix Paeoniae Alba total glucosides, sinomenine and 3 kinds of medicines of glycyrrhizic acid is better than having wherein 2 kinds of compositionss that compatibility is used of mentioning in the document aspect the pharmacodynamics for the treatment of rheumatoid arthritis, pharmacokinetics, clinical efficacy.
Summary of the invention
The purpose of this invention is to provide a kind of composition and method of making the same that extracts the formation of the effective ingredient glycyrrhizic acid that obtains in the effective site Radix Paeoniae Alba total glucosides that obtains and the effective ingredient sinomenine (or sinomenine hydrochloride) that sinomenine extracts, purification obtains and the Radix Glycyrrhizae that from Radix Paeoniae, extracts.
The purpose of this invention is to provide the application of compositions in treatment rheumatoid arthritis disease that Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid are formed.
Above-mentioned purpose realizes by following technical scheme:
A kind of pharmaceutical composition, its composition comprises Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid.Its mass fraction is: the Radix Paeoniae Alba total glucosides of 30-85 mass fraction; The sinomenine of 5-50 mass fraction; The glycyrrhizic acid of 2-50 mass fraction and this three kinds of compositions are acceptable carrier pharmaceutically.
The acquisition form of Radix Paeoniae Alba total glucosides, sinomenine, glycyrrhizic acid has 2 kinds in the compositions, and is a kind of for adopting the crude drug with the accurate word authentication code of traditional Chinese medicines.A kind of is to adopt the method for extraction separation to obtain required raw material.The preparation method of 3 kinds of raw materials is as follows in the compositions;
The preparation method of Radix Paeoniae Alba total glucosides is: with Radix Paeoniae pulverizing, 40-90% alcohol reflux, extract three times, when merge extractive liquid,, concentrated solution are made a living dose 35%-45%, add saturated NaHCO3 solution in concentrated solution pH value is transferred to 5.9-6.1.Add ethyl acetate extraction 2 times in the above-mentioned medicinal liquid, combining extraction liquid adds n-butyl alcohol in the extract: ethyl acetate mixed liquor (30: 70V/V) extract, merge the n-butyl alcohol acetic acid ethyl acetate extract.With extract concentrate, dry, pulverize, mix, the Radix Paeoniae Alba total glucosides effective part extract.The content of Radix Paeoniae Alba total glucosides in compositions serves as to detect index with peoniflorin and lactone glucoside of Radix Paeoniae, and content of paeoniflorin 40%-90%, the content of lactone glucoside of Radix Paeoniae are 10%-20%.
Sinomenine and sinomenine hydrochloride preparation method are: adopt the Caulis Sinomenii medical material to obtain the Caulis Sinomenii powder through pulverizing, with the Caulis Sinomenii powder through alkalization water reflux, extract, 3 times, merge extractive liquid, concentrates and obtains sinomenine extractum, and macroporous resin enrichment on the Caulis Sinomenii extractum is obtained the sinomenine crude product.The sinomenine crude product is added hydrochloric acid transfer pH value between 2-3.5, activated carbon decolorizing, sucking filtration adds hydrochloric acid again and transfers pH value between 2-3.5, and standing over night stirs, and sucking filtration obtains sinomenine hydrochloride.
The preparation method of glycyrrhizic acid is: glycyrrhizic acid adopts the chemical compound of Radix Glycyrrhizae extract through macroporous adsorbent resin enrichment, washing, dry gained.
Above-mentioned Radix Paeoniae Alba total glucosides, sinomenine (sinomenine hydrochloride) and glycyrrhizic acid preparation of compositions method are: Radix Paeoniae Alba total glucosides dry powder, sinomenine crystal glycyrrhizic acid powder and pharmaceutic adjuvant are prepared into oral formulations and injection or transfusion, oral formulations can be tablet (comprising ordinary tablet, dispersible tablet, slow releasing tablet, controlled release tablet, oral cavity disintegration tablet, buccal tablet), pill, mixture of powders, granule, capsule, coating materials, solution, Emulsion, dispersant, also can use injection, suppository or other suitable form.These preparations prepare according to method well-known to those having ordinary skill in the art.As to make tablet, capsule, the used adjuvant of coating materials be conventional adjuvant, starch for example, and gelatin, arabic gum, Polyethylene Glycol, the used solvent of liquid dosage form is water for example, ethanol, propylene glycol, plant oil such as Semen Maydis oil, Oleum Arachidis hypogaeae semen, Fructus Canarii albi wet goods.Contain the adjuvant that other also can be arranged in Radix Paeoniae Alba total glucosides of the present invention, sinomenine and the glycyrrhizic acid composite preparation, surfactant for example, lubricant, disintegrating agent, antiseptic, correctives, pigments etc. prepare these possible preparations and also belong to application of the present invention.
The present invention has following beneficial effect:
1, the present invention, Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions can be prepared into the various dosage forms on the pharmaceutics, as tablet, capsule, pill etc., and can form multi-component pharmaceutical composition with other active component, provide be convenient to take, the medicine of determined curative effect.
2, the present invention, the compositions that Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid are formed aspect the treatment rheumatoid arthritis, has obtained good effect.
Description of drawings
Fig. 1, blood drug level-time plot in the pharmacokinetic studies process of the present invention
The specific embodiment:
Embodiment 1:
The compositions of a kind of peoniflorin, sinomenine and glycyrrhizic acid, the parts by weight of three kinds of components are: Radix Paeoniae Alba total glucosides 80 parts by weight (800g); Sinomenine 15 parts by weight (150g); Glycyrrhizic acid 5 parts by weight (50g).Its preparation technology is as follows: Radix Paeoniae Alba total glucosides 800g, sinomenine 150g, glycyrrhizic acid 50g, and mix the back and cross 100 mesh sieves, mixing gets Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhetinic acid composition (compositions A).
Embodiment 2:
Get the compositions A of embodiment 1 preparation, add microcrystalline Cellulose 100g, add suitable starch and transfer to 2500g, add magnesium stearate, mix homogeneously, powder directly are pressed into 5000,, make tablet.
Embodiment 3:
Get the compositions A of embodiment 1 preparation, add appropriate amount of starch to 1500g, mix homogeneously, the capsule of packing into No. 0 is made 5000 seed lac wafers.
Embodiment 4:
Get the compositions A2000g of embodiment 1 preparation, add an amount of Icing Sugar, mix homogeneously is a binding agent with ethanol, crosses 40 mesh sieves, and 60 ℃ of oven dry are carried out packing, made granule behind the granulate.
Embodiment 5:
Get the compositions of embodiment 1 preparation, it is an amount of to add the injection water, transfers PH7.3-7.5 with 5%NaOH solution.Filter with No. 3 sintered filter funnels.Embedding is in ampoule, and injection is made in sterilization.
Embodiment 6:
The compositions of a kind of peoniflorin, sinomenine and glycyrrhizic acid, its composition comprises: Radix Paeoniae Alba total glucosides 50 weight fractions (500g); Sinomenine 40 weight fractions (400g); Glycyrrhizic acid 10 weight fractions (10g).Its preparation technology is as follows: get Radix Paeoniae Alba total glucosides 500g, sinomenine 400g, glycyrrhizic acid 10g, mix the back and cross 100 mesh sieves, mixing gets Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhetinic acid composition (compositions B).
Embodiment 7:
Get the compositions B of embodiment 6 preparations, add microcrystalline Cellulose 100g, add suitable starch and transfer 2500g, add magnesium stearate, mix homogeneously, powder directly are pressed into 5000,, make tablet.
Embodiment 8:
Get the compositions B150g of embodiment 6 preparations, add soluble starch 850g, sucrose 1000g, mix homogeneously is made granule and is crossed 24 mesh standard sieve granulate, every packed 1g, promptly.
Set up the rat assist agent arthritis model, counting method is measured the polyarthritis index, weight method is measured body weight, thymus index, index and spleen index, measure secondary side swollen joint expansibility with sufficient volumetric type meter, the ELISA method detects macrophage secretion IL-1 level, 3H-TdR mixes method and measures T, bone-marrow-derived lymphocyte breeder reaction, and HE staining om observation joint pathology morphological change etc. are investigated Radix Paeoniae Alba total glucosides, sinomenine and the glycyrrhizic acid compositions therapeutical effect to rat assist agent arthritis.
1, to the exponential influence of AA rat arthritis:
(bacillus calmette guerin, BCG) 80 ℃ of deactivation 1h are mixed with 10gL with autoclaved liquid paraffin with the bacillus calmette-guerin vaccine of same lot number
-1Emulsion, the mixing of fully milling promptly get Freund's complete adjuvant (Freund ' s completeadjuvant, FCA), cause inflammation in the left back toes intradermal injection of rat FCA 0.1ml.
Afterwards d16, d20, d24 adopt joint mark point system record respectively to organize the generation and the order of severity of rat polyarthritis pathological changes to cause inflammation.Every sufficient pawl is marked by following standard: 0=is normal; 1=ankle joint erythema and slight swelling; The 2=ankle joint is to sole of the foot joint or metacarpal joint erythema and slight swelling; The 3=ankle joint is to metatarsophalangeal joints or metacarpal joint erythema and moderate swelling; The 4=ankle joint is to toe joint erythema and severe swelling.Maximum scores is 12 minutes.
After the rat modeling, it is obvious to cause the arthroncus of scorching parapodum pawl, causes scorching side other sufficient pawl joints in addition after the modeling about d16 and begins swelling, compares with model group, and the d24 medicine all can obviously reduce the arthritis index scoring of AA rat.
Table 1 Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions (compositions) are to the exponential influence in rat assist agent arthritis joint
*p＜0.05，
**p＜0.01
Compare with normal group, other sufficient pawl joints that cause about d16 after the modeling beyond the scorching side begin swelling, swelling appears and after each medication group begin administration.Compare with model group, each medicine of d20, d24 all can obviously reduce the arthritis index scoring of AA rat.
At each medicine of d24 relatively:
Compare in 100mg/kg dosage, the effect of arthritis index scoring that compositions rent to reduce the AA rat is obvious than Radix Paeoniae Alba total glucosides and sinomenine group and Radix Paeoniae Alba total glucosides and glycyrrhizic acid rent effect.
2, to the influence of AA rat paw edema
Respectively cause scorching before and cause inflammation after d0, d16, d20, d24 cause scorching parapodum pawl volume with the measurement of toes volumetric measurement instrument is non-, with rate of increase (d16-d0)/d0, (the d20-d0)/d0 of rat foot claw, (d24-d0)/d0 as the swelling index.
Swelling appears in other sufficient pawls that cause after the rat modeling beyond the scorching side, and d24 compares the reduction rat foot claw swelling that Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions can be in various degree with model group, and effect is better than other matched groups.
Table 2 Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions (the sweet compositions of Chinese herbaceous peony) are to rat assist agent arthritis
The influence of foot pawl swelling degree
##P＜0.01 vs normal group;
*P＜0.05,
*P＜0.01 vs model group.
3, to the influence of thymus index and index and spleen index
Cause and take off neck execution rat after scorching back d28 weighs, peel off thymus and spleen, weigh respectively, compare with the body weight of rat, obtain thymus and index and spleen index with the weight of thymus and spleen.
Index and spleen index raises after the rat modeling, the reduction index and spleen index that Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions can be in various degree, and thymus index reduces after the rat modeling, and Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid composition medicine do not have obvious influence to thymus index.
Table 3 Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions (the sweet compositions of Chinese herbaceous peony) are to the rat assist agent arthritis rat
The influence of index and spleen index and thymus index
##P＜0.01 vs normal group;
*P＜0.05,
*P＜0.01 vs model group;
Index and spleen index raises after the rat modeling, the reduction index and spleen index that individual matched group medicine all can be in various degree.Each medicine compares: compare in 100mg/kg dosage, the effect that compositions reduces index and spleen index is remarkable than other group effects.
4, the influence of inductive T of ConA and LPS and bone-marrow-derived lymphocyte breeder reaction
Aseptic spleen, the thymus got, preparation lymphocyte suspension (1 * 107/ml), on 96 well culture plates, every hole adds 100 μ l cell suspension, and (final concentration is 5 * 106/ml) and LPS (final concentration 4mg/L) or ConA (final concentration 3mg/L), whole volume is 200 μ l, respectively establish 3 multiple holes, put 37oC, 5%CO2 incubator cultivation 42h, induce T, bone-marrow-derived lymphocyte propagation.6h before stop cultivating, every hole adds 25 μ Ci 3H-TdR, cultivate finish after with the cell sucking filtration on glass fiber filter paper, dry back is detected with liquid scintillation counter, the result is with the equal value representation of 3 multiple hole cpm.
Compare with normal group, AA rat T cell proliferation level raises, Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid composition medicine can be in various degree the propagation level of reduction T cell, compare with normal group, AA rat B cell proliferation level raises, the propagation level of the reduction B cell that Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid composition medicine can be in various degree.
5, IL-1's inducing and detecting
Preparation rat abdominal cavity macrophage suspension (1 * 107/ml), add 24 well culture plates, every hole 1ml, put 37oC, 5%CO2 incubator cultivation 2h, abandon or adopt supernatant, wash 3 times with D-Hank`s liquid, remove non-adherent cell, obtain cell monolayer, respectively add 500 μ l DMEM and LPS (final concentration 4mg/L) then, put 37oC, 5%CO2 incubator cultivation 48h, induce and produce IL-1, collect supernatant ,-20oC preserves, and the ELISA method detects IL-1 content.
Compare with normal group, AA rat abdominal cavity macrophage is secreted IL-1 under the stimulation of LPS level raises, Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions can reduction macrophage be in various degree secreted IL-1 under the stimulation of LPS level.
6, Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions are to the effect of rat AA joint pathology variation
Rat ankle joint is fixed with 10% formalin, decalcification, and dehydration, paraffin embedding, section, the pathomorphism of ankle joint is observed in HE dyeing back under optical microscope.
Compare with normal rat, under the light microscopic in the synovial tissue of visible AA model group rat synovial cell proliferation obvious, level increases, arrangement disorder, the proliferation of fibrous tissue of synovial membrane lower floor, inflammatory cell infiltration and pannus form, inflammatory cell infiltration in the cartilage, cartilage destruction.Each medication group all can be improved above pathological change in various degree, mainly shows as synovial cell's layer and does not see showed increased, a small amount of inflammatory cell infiltration.
Compare with model group, each dosage group of Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions is all obviously improved the synovial membrane lower floor inflammatory cell infiltration and the synovial membrane congestion of blood vessel.With Radix Paeoniae Alba total glucosides, sinomenine group and Radix Paeoniae Alba total glucosides and the contrast of glycyrrhizic acid group, from the pathology picture, the compositions group is improved arthritic best results.
Comprehensively show by above-mentioned research experiment, Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions have therapeutical effect to rheumatoid arthritis, and Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions have the index and spleen index that reduces arthritis index, reduction rising, T, B cell proliferation reaction, the inhibition macrophage that downward modulation raises secreted effects such as IL-1.The pathology picture shows that Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions can be improved the pathological change of rheumatoid arthritis in various degree, mainly shows as synovial cell's layer and does not see showed increased, a small amount of inflammatory cell infiltration.Aspect therapeutical effect, be better than Radix Paeoniae Alba total glucosides and sinomenine matched group and Radix Paeoniae Alba total glucosides and glycyrrhizic acid matched group.
The efficacy evaluation test aspect treatment eczema of Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions.
Experimental program:
Adopt open, at random, the contrast clinical trial method, constituent parts is observed qualified case 40 examples.The experimenter is dispensed in following two groups by random digit, the treatment group: Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions (compositions adopts capsule, and each capsule contains the 400mg pharmaceutical composition); Matched group 1: Radix Paeoniae Alba total glucosides, sinomenine group; Matched group 2: Radix Paeoniae Alba total glucosides, glycyrrhizic acid group; Schedule to last the clinical observation in 12-24 week.In 4 week of treatment back observe the curative effect index, 12-24 week end back is observed and is cured number.
Group 550 examples are gone in plan, actually go into to organize case 485 examples, and 65 examples that come off are finally finished qualification test case 456 examples.Wherein Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions group 141 examples; Matched group 1 is 165; Matched group 2 is 150 examples.
Go into to organize the case baseline case and account for 54.58% for man 167, woman 139 accounts for 45.42%.
Experimental result:
The analysis of three groups of case treatments of table 4. back comprehensive therapeutic effect assessment
From treating on the curative effect index after 4 weeks, healing, produce effects, effectively reach on the invalid hierarchical analysis, Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions are better than matched group 1 (Radix Paeoniae Alba total glucosides, sinomenine group) and matched group 2 (Radix Paeoniae Alba total glucosides, glycyrrhizic acid group).Illustrate that Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions can improve the treatment of rheumatoid arthritis effect.
The pharmacokinetic studies experimental result of Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid compositions.
Experimental technique:
New zealand rabbit is male, 2.0Kg, and 12 are divided into four groups, first group of peoniflorin aqueous solution gastric infusion, irritating stomach dosage is 325mg.kg-1, second group gives Radix Paeoniae Alba total glucosides aqueous solution and each 325mg.kg-1 of sinomenine suspension (matched group 1) simultaneously; The 3rd group gives each 325mg.kg-1 of Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid (compositions group) simultaneously; The 4th group give Radix Paeoniae Alba total glucosides and glycyrrhizic acid 325mg.kg-1 (matched group 2) each respectively after administration 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h get blood 0.5ml from auricular vein, place the heparinization test tube, centrifugal, 6000rmin-1,10min gets blood plasma.Press the operation of plasma sample processing method, HPLC analyzes.Content of paeoniflorin in each time point blood plasma of substitution linear regression curve calculation.
The blood drug level analytical method:
The chromatographic system condition
HPLC:Agilent 1100 series; Dikma TechnoiogiesDiamonsil (masonry) C18 chromatographic column (5 μ, 150 * 4.6mm Di Ma company); The C18 pre-column; Mobile phase: methanol-0.01%HAc 40: 60; Column temperature: 25 ℃; Detect wavelength: 230nm; Flow velocity: 1.0mlmin-1.
The plasma sample processing method
Handle plasma sample with perchloric acid precipitation's protein method: get blood plasma 0.1ml, be added in the 1.5ml centrifuge tube, add 6% perchloric acid 0.1ml, vortex oscillation 5min, 12 000rmin-1, centrifugal 10min gets supernatant, and HPLC analyzes.This method is simple to operation, and specificity is good, highly sensitive, and impurity does not disturb Determination on content in the blood plasma,
The relative bioavailability experimental result
Get blood in 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h from auricular vein behind the new zealand rabbit gastric infusion, after plasma sample is handled, after HPLC analyzes.The record peak area, substitution linear regression curve calculates each time point blood drug level, the results are shown in as table 5, and blood drug level-time graph is as shown in Figure 1.
Four groups of experiments of table 5 new zealand rabbit oral administration blood drug level-time data (n=3)
Claims (10)
1. the compositions with the effect of treatment rheumatoid arthritis is characterized in that by the pharmaceutical composition that Radix Paeoniae Alba total glucosides, sinomenine and glycyrrhizic acid are formed, its mass fraction is: the Radix Paeoniae Alba total glucosides of 30-85 mass fraction; The sinomenine of 5-50 mass fraction; The glycyrrhizic acid of 2-50 mass fraction comprises pharmaceutically acceptable carrier of these three kinds of compositions.
2. compositions according to claim 1, described Radix Paeoniae Alba total glucosides is the crude drug that Ningbo LiHua Pharmaceutical Co., Ltd produces without competition, lot number is the accurate word H19980146 of traditional Chinese medicines, the content of Radix Paeoniae Alba total glucosides in compositions serves as to detect index with peoniflorin and lactone glucoside of Radix Paeoniae, content of paeoniflorin 40%-90%, the content of lactone glucoside of Radix Paeoniae are 10%-20%.
3. compositions according to claim 1, the extracting method of described Radix Paeoniae Alba total glucosides is: Radix Paeoniae is pulverized, the 40-90% alcohol reflux, extract three times, merge extractive liquid,, when concentrated solution is made a living dose 35%-45%, in concentrated solution, add saturated NaHCO3 solution pH value is transferred to 5.9-6.1, add ethyl acetate extraction 2 times in the above-mentioned medicinal liquid, combining extraction liquid, add n-butyl alcohol in the extract: ethyl acetate mixed liquor (30: 70V/V) extract, merge the n-butyl alcohol acetic acid ethyl acetate extract, extract is concentrated, dry, pulverize, mix, get the Radix Paeoniae Alba total glucosides effective part extract.
4. compositions according to claim 1, described sinomenine adopts the crude drug sinomenine hydrochloride of existing national certification.
5. compositions according to claim 1, the extracting method of described sinomenine and sinomenine hydrochloride is: adopt the Caulis Sinomenii medical material to obtain the Caulis Sinomenii powder through pulverizing, with the Caulis Sinomenii powder through alkalization water reflux, extract, 3 times, merge extractive liquid,, concentrate and obtain sinomenine extractum, macroporous resin enrichment on the Caulis Sinomenii extractum is obtained the sinomenine crude product, the sinomenine crude product is added hydrochloric acid transfers pH value between 2-3.5, activated carbon decolorizing, sucking filtration adds hydrochloric acid again and transfers pH value between 2-3.5, standing over night, stir, sucking filtration obtains sinomenine hydrochloride.
6. compositions according to claim 1, described glycyrrhizic acid adopts glycyrrhizic acid crude drug or the glycyrrhetate and the glycyrrhizin derivative of existing state approval code.
7. compositions according to claim 1, the extracting method of described glycyrrhizic acid is: glycyrrhizic acid adopts the chemical compound of Radix Glycyrrhizae extract through macroporous adsorbent resin enrichment, washing, dry gained.
8. the described compositions of claim 1, comprise order give with or give Radix Paeoniae Alba total glucosides, sinomenine and the glycyrrhizic acid of pharmaceutically acceptable form simultaneously.
9. compositions according to claim 1, it is characterized in that: Radix Paeoniae Alba total glucosides powder, sinomenine crystal and glycyrrhizic acid powder and pharmaceutic adjuvant are prepared into oral formulations and injection or transfusion, oral formulations can be tablet (comprising ordinary tablet, dispersible tablet, slow releasing tablet, controlled release tablet, oral cavity disintegration tablet, buccal tablet), pill (comprising drop pill, pellet etc.), mixture of powders, granule, capsule, coating materials, solution, Emulsion, dispersant, also can use injection, suppository or other suitable form.
10. compositions according to claim 1 is characterized in that compositions is applied to treat rheumatoid arthritis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010241451 CN101919913B (en) | 2010-07-29 | 2010-07-29 | Composition with effect of treating rheumatoid arthritis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010241451 CN101919913B (en) | 2010-07-29 | 2010-07-29 | Composition with effect of treating rheumatoid arthritis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101919913A true CN101919913A (en) | 2010-12-22 |
| CN101919913B CN101919913B (en) | 2012-12-12 |
Family
ID=43335297
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010241451 Active CN101919913B (en) | 2010-07-29 | 2010-07-29 | Composition with effect of treating rheumatoid arthritis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101919913B (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102600071A (en) * | 2012-03-30 | 2012-07-25 | 湖南正清制药集团股份有限公司 | Method for preparing sinomenine hydrochloride infusion solutions and freeze-dried powder injections |
| CN102614119A (en) * | 2012-03-30 | 2012-08-01 | 湖南正清制药集团股份有限公司 | Method for sinomenine hydrochloride injection by using non-organic solvent |
| CN103285101A (en) * | 2013-05-14 | 2013-09-11 | 亳州千草药业有限公司 | Method for extracting over-ground part of white peony root |
| CN105273015A (en) * | 2015-11-18 | 2016-01-27 | 上海同田生物技术股份有限公司 | Preparation method of high-purity paeoniflorin and albiflorin |
| CN105582104A (en) * | 2015-12-30 | 2016-05-18 | 中国中医科学院中医临床基础医学研究所 | Traditional Chinese medicine composition for treating rheumatoid arthritis |
| CN108689935A (en) * | 2017-04-10 | 2018-10-23 | 南京泽朗生物科技有限公司 | A kind of preparation method of cucoline |
| CN115337318A (en) * | 2022-07-01 | 2022-11-15 | 北京中医药大学 | Traditional Chinese medicine micromolecule self-assembly for treating rheumatoid arthritis |
| WO2023045005A1 (en) * | 2021-09-24 | 2023-03-30 | 宁波立华制药有限公司 | Method for preparing total glucosides of paeonia |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1200723C (en) * | 2002-12-19 | 2005-05-11 | 中国医药研究开发中心有限公司 | White peony and licorice extract and its prepn process |
| CN1218697C (en) * | 2001-03-05 | 2005-09-14 | 杏林科技有限公司 | Pharmaceutical composition for treating or improving arthritis and diet extender |
| CN101264142A (en) * | 2007-03-15 | 2008-09-17 | 宁波立华制药有限公司 | Antiphlogistic, pain relieving, spasmolytic and immunoregulation medicaments and preparation |
-
2010
- 2010-07-29 CN CN 201010241451 patent/CN101919913B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1218697C (en) * | 2001-03-05 | 2005-09-14 | 杏林科技有限公司 | Pharmaceutical composition for treating or improving arthritis and diet extender |
| CN1200723C (en) * | 2002-12-19 | 2005-05-11 | 中国医药研究开发中心有限公司 | White peony and licorice extract and its prepn process |
| CN101264142A (en) * | 2007-03-15 | 2008-09-17 | 宁波立华制药有限公司 | Antiphlogistic, pain relieving, spasmolytic and immunoregulation medicaments and preparation |
Non-Patent Citations (2)
| Title |
|---|
| 《中华中医药学刊》 20080831 刘风云 等 中医药诊治类风湿关节炎的临床及实验研究进展 1768-1771页 1-10 第26卷, 第8期 2 * |
| 《天津药学》 20081231 陈睿 等 中药治疗类风湿关节炎有效成分提取研究进展 71-74页 1-10 第20卷, 第5期 2 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102600071A (en) * | 2012-03-30 | 2012-07-25 | 湖南正清制药集团股份有限公司 | Method for preparing sinomenine hydrochloride infusion solutions and freeze-dried powder injections |
| CN102614119A (en) * | 2012-03-30 | 2012-08-01 | 湖南正清制药集团股份有限公司 | Method for sinomenine hydrochloride injection by using non-organic solvent |
| CN103285101A (en) * | 2013-05-14 | 2013-09-11 | 亳州千草药业有限公司 | Method for extracting over-ground part of white peony root |
| CN105273015A (en) * | 2015-11-18 | 2016-01-27 | 上海同田生物技术股份有限公司 | Preparation method of high-purity paeoniflorin and albiflorin |
| CN105273015B (en) * | 2015-11-18 | 2018-11-30 | 上海同田生物技术股份有限公司 | A kind of preparation method of high-purity Paeoniflorin and albiflorin |
| CN105582104A (en) * | 2015-12-30 | 2016-05-18 | 中国中医科学院中医临床基础医学研究所 | Traditional Chinese medicine composition for treating rheumatoid arthritis |
| CN108689935A (en) * | 2017-04-10 | 2018-10-23 | 南京泽朗生物科技有限公司 | A kind of preparation method of cucoline |
| WO2023045005A1 (en) * | 2021-09-24 | 2023-03-30 | 宁波立华制药有限公司 | Method for preparing total glucosides of paeonia |
| CN115337318A (en) * | 2022-07-01 | 2022-11-15 | 北京中医药大学 | Traditional Chinese medicine micromolecule self-assembly for treating rheumatoid arthritis |
| CN115337318B (en) * | 2022-07-01 | 2023-10-03 | 北京中医药大学 | Traditional Chinese medicine small molecule self-assembly body for treating rheumatoid arthritis |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101919913B (en) | 2012-12-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101919913B (en) | Composition with effect of treating rheumatoid arthritis | |
| CN100488552C (en) | Chinese medicine composition for treating arthritis or gout and preparing method thereof | |
| CN101199683B (en) | Chinese medicine for treating skin disease and preparing method thereof | |
| CN102240372B (en) | Medicine for treating gouty arthritis and hyperuricemia and preparation method thereof | |
| CN100382838C (en) | Chinese medicine for treating blood stagnation disease | |
| CN101810686A (en) | Compatible composition for treating rheumatoid arthritis and preparation method thereof | |
| CN101167937A (en) | Traditional Chinese medicinal composition plaster for curing rheumatism or rheumatoid diseases and preparation method thereof | |
| CN101926815B (en) | Paeoniflorin and glycyrrhetinic acid composition and preparation method and application thereof | |
| CN102698014B (en) | Chinese medicinal composition for treating bone-related diseases and preparation method and application thereof | |
| CN101347605B (en) | Chinese medicinal composition for treating gout and preparation method and application thereof | |
| CN101912577B (en) | Medicament for treating rheumatism and rheumatoid disease and preparation process | |
| CN100477996C (en) | Extract of star of bethlehem and its prepn process, medicinal composition and use | |
| CN101991811B (en) | Traditional Chinese medicine composition for treating rheumatism arthralgia, cold headache, abdominal cavity pain and chilblain and preparation method thereof | |
| CN103405732A (en) | Traditional Chinese medicine patch for treating infant rotavirus enteritis and preparation method thereof | |
| CN100363043C (en) | Chinese traditional medicine composition for treating rheumatic or rheumatoid disease and preparation method thereof | |
| CN1911293B (en) | Gel agent-Guzhining for treating osteoporosis and its preparation method | |
| CN103705812B (en) | A kind of pharmaceutical composition for the treatment of gout and its production and use | |
| CN102614248B (en) | Traditional Chinese herbal composite for treating stroke and chest obstruction | |
| CN101375954B (en) | Medicament composition, preparation method thereof and use | |
| CN101524447A (en) | Pharmaceutical composition for treating constipation and preparation process thereof | |
| CN102188497B (en) | Preparation method of total alkali of corydalis tuber, and corydalis tuber preparation and use thereof | |
| CN101670007B (en) | Drug for preventing and treating kidney diseases and preparation method thereof | |
| CN100998784B (en) | Preparing method of traditional Chinese medicine composition tablet for treating gastrointestinal disease | |
| CN101229334B (en) | Medicine for treating rheumatoid and atrophic arthritis | |
| CN100367997C (en) | Medicine for treating arthrolithiasis and preparing method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |