CN102614230A - Medicinal composition for treating rheumatoid arthritis and preparation method and application thereof - Google Patents

Medicinal composition for treating rheumatoid arthritis and preparation method and application thereof Download PDF

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CN102614230A
CN102614230A CN2012100611631A CN201210061163A CN102614230A CN 102614230 A CN102614230 A CN 102614230A CN 2012100611631 A CN2012100611631 A CN 2012100611631A CN 201210061163 A CN201210061163 A CN 201210061163A CN 102614230 A CN102614230 A CN 102614230A
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herba pterocephali
saponin extracts
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CN102614230B (en
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张艺
孟宪丽
赖先荣
古锐
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Chengdu University of Traditional Chinese Medicine
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Chengdu University of Traditional Chinese Medicine
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Abstract

The invention provides a medicinal composition for treating rheumatoid arthritis. The medicinal composition is the preparation which is prepared from the following active ingredients in parts by weight: 1 to 10 parts of pterocephalus hookeri heck total saponins extract and 1 to 10 parts of total iridoid glycoside extract. The invention also provides a preparation method and the application of the medicinal composition. According to the medicinal composition, the pterocephalus hookeri heck total saponins extract and the total iridoid glycoside extract are combined, so the medicinal composition is higher than each extract in the effects of resisting inflammation and rheumatoid arthritis, has a synergistic effect, is positive in the treatment effect and provides a new selection to clinical medication.

Description

A kind of pharmaceutical composition of treating rheumatoid arthritis and its production and use
Technical field
The present invention relates to a kind of pharmaceutical composition Preparation Method And The Use of treating rheumatoid arthritis, belong to drug world.
Background technology
Rheumatoid arthritis (Rheumatiod Arthritis is called for short RA) be a kind of common serve as the general immune disease that mainly shows with the chronic polyarthritis pathological changes, the whole world has more than one hundred million patients.According to statistics, the external prevalence of RA is 1~2%, and indivedual areas are up to 5%; China's sickness rate is about 0.74%, about existing patient 1,000 ten thousand people.Show that according to investigations in normal population, the sickness rate of rheumatoid arthritis accounts for about 0.35% of normal population.The primary disease disability rate is high, and 50%, three year disability rate of 2 years disability rates of patient with rheumatoid arthritis of diagnosis and treatment does not in time reach 70%.And the patient who has suffered from rheumatoid arthritis, average life shortens 10~15 years, so RA has a strong impact on work capacity; The medicine of development RA for the clinical symptoms of alleviating such disease, improves patient's life quality; Ensure the productivity, have positive meaning.
The Tibetan medicine Herba pterocephali, the dry herb for Dipsacaceae plant spoon leaf Herba pterocephali Pterocephalus hookeri(C.B.Clarke)Hoeck has heat-clearing and toxic substances removing, wind-damp dispelling, pain relieving effect.Herba pterocephali is Tibetan medicine's Tibetan medicine commonly used; Have another name called " list appearance poison crow "; Be the national medicine of Tibetan medicine evident characteristic typical case; Medication is with a long history; The Tibetan medicine always is mainly used in it diseases such as treatment rheumatic; Except that Tibetan medicine and closely-related Mongolian medicine thereof, Chinese medicine and other traditional medicine are not used the history of Herba pterocephali basically.Under the Tibetan medicine and pharmacology theoretical direction; Clinical practice with Herba pterocephali is a foundation; Experimental study has been carried out in resisting rheumatoid arthritis effect of Herba pterocephali extract and mechanism; The result shows: the anti-RA effect of Herba pterocephali extract is sure; For experimental adjuvant arthritis animal model constitutional inflammation and Secondary cases arthritis antiphlogistic effects is preferably arranged all; And can alleviate the pathological change of synovial membrane; Significant analgesia role is also arranged simultaneously, and this matches with Herba pterocephali treatment rheumatism, rheumatoid arthritis application with the Tibetan medicine is clinical.(Shen Peng, resisting rheumatoid arthritis effect of Tibetan medicine Herba pterocephali and mechanism research, Chengdu University of Traditional Chinese Medicine, 2002 .)
Chemical constitution study to Herba pterocephali shows, mainly contains compositions such as oleanane type triterpenes saponin, iridoid glycoside compounds, alkaloid, polysaccharide in the Herba pterocephali.Research to the Herba pterocephali effective ingredient shows; Adopt rat acute foot swelling experiment, the experiment of mice granuloma induced by implantation of cotton pellets, the experiment of chmice acute ear swelling and chmice acute to ooze out methods such as experiment; Proved that Herba pterocephali n-butanol portion total saponin extracts has significant anti-inflammatory activity [Guan Xinlu; Deng. the antiinflammatory action of Herba pterocephali and anxious malicious experimentation. the journal .2004 of Beijing University of Chinese Medicine, 27(2):71~73].The main component meliatin of iridoid glycoside in the Herba pterocephali have tangible antiinflammatory pharmacological action, but its analog has immunological enhancement.[Pang Wei. the research of Tibetan medicine Herba pterocephali and application. Chinese national medicine magazine .2007, (5):63-65].Number of patent application :200910196870.x; Herba pterocephali total saponin extracts effective part extract is provided in this invention; Its main component is the oleanane type pentacyclic triterpene saponin; Total saponin extracts content 50-90%; This total saponin extracts can significantly suppress tumor cell proliferation; Directly adopt macroporous resin to separate in this total saponin extracts and obtain, contain iridoid glycoside in the extract.
Comprehensive existing document can be known; Only have at present that total saponin extracts and meliatin have anti-inflammatory and analgesic effect and total saponin extracts antineoplastic report in the Herba pterocephali, also do not see Herba pterocephali total saponin extracts and iridoid glycoside united and use the report of treating rheumatoid arthritis.
Summary of the invention
The object of the present invention is to provide a kind of pharmaceutical composition of treating rheumatoid arthritis and preparation method thereof.
The invention provides a kind of pharmaceutical composition of treating rheumatoid arthritis; It is to be the preparation that active component is prepared from Herba pterocephali total saponin extracts and total iridoid glucoside extract; Wherein, the weight proportion of described total saponin extracts, total iridoid glucoside extract is:
Total saponin extracts 1-10 part, total iridoid glucoside extract 1-10 part.
Wherein, the weight proportion of described total saponin extracts, total iridoid glucoside extract is:
10 parts of total saponin extracts, 1 part of total iridoid glucoside extract; Or 5 parts of total saponin extracts, 5 parts of total iridoid glucoside extracts.
Further, in the said Herba pterocephali total saponin extracts, saponin content is greater than 50%w/w; In the said Herba pterocephali total iridoid glucoside extract, iridoid glycoside content is greater than 50%w/w.
Further, in the said Herba pterocephali total saponin extracts, saponin content is preferably 80-90%w/w greater than 80%w/w; In the said Herba pterocephali total iridoid glucoside extract, iridoid glycoside content is preferably 80-90%w/w greater than 80%w/w.
Wherein, said Herba pterocephali is the dry herb of Dipsacaceae plant spoon leaf Herba pterocephali Pterocephalus hookeri(C.B.Clarke)Hoeck.
The present invention also provides a kind of method for preparing aforementioned pharmaceutical compositions, and it comprises the steps:
(1) preparation Herba pterocephali total saponin extracts
A, get Herba pterocephali, extracting in water filters, and filtrating is adopted nonpolar or low pole purification with macroreticular resin after concentrating, and with after washing decontamination, discards eluent earlier; With the 60-85% ethanol elution, behind the collection ethanol elution;
B, get the ethanol elution of step a, behind the decompression and solvent recovery, add lead acetate solution, stir, filter, filtrate for later use is got deposition, and behind the deleading, drying promptly gets the Herba pterocephali total saponin extracts;
(2) preparation Herba pterocephali total iridoid glucoside extract
Get the filtrating behind the adding lead acetate solution among the step b, after concentrating, use n-butanol extraction, get n-butyl alcohol liquid, behind the recovery solvent, drying promptly gets Herba pterocephali total iridoid glucoside extract;
(3) preparation of drug combination
Take by weighing Herba pterocephali total saponin extracts and total iridoid glucoside extract by the prescription proportioning, add adjuvant pharmaceutically commonly used and be prepared into preparation.
Wherein, select D101, AB-8 or HPD-300 type macroporous adsorbent resin among the step a for use; With the 65-75%v/v ethanol elution; Among the step b, get the ethanol elution of step a, behind the decompression and solvent recovery; Redissolve in 30-95%v/v ethanol, add saturated neutral lead acetate solution, stir; Filter, filtrate for later use is got deposition; Be suspended in the 30-95%v/v ethanol; With hydrogen sulfide gas or cation exchange resin deleading, filter, get filtrating concentrating; Drying promptly gets the Herba pterocephali total saponin extracts.
Further, select D101 type macroporous adsorbent resin among the step a for use; With the 70%v/v ethanol elution; Among the step b, concentration of alcohol is 60-85%v/v.
Further, among the step b, concentration of alcohol is preferably 65-75%v/v.
Further, the concrete operations step of purification with macroreticular resin is following among the step a:
The concentration of sample solution is formulated as 0.1-0.2g crude drug/ml, adopts D101 type purification with macroreticular resin, last appearance flow velocity is 1-3BV/h; Applied sample amount is counted medical material with medical material: resin=(0.5-1.5): 1w/w; With the-5BV water elution, flow velocity is 1-3BV/h, discards eluent; With 70% ethanol elution of-4BV, elution flow rate is 2-4BV/h.
Further preferably, the concentration with sample solution is formulated as 0.1g crude drug/ml medicinal liquid, purification under the employing D101 type macroporous adsorbent resin room temperature; Last appearance flow velocity is BV/h, and applied sample amount is counted medical material with medical material: resin=1: 1, with the 4BV water elution; Flow velocity is BV/h, discards eluent; With 70% ethanol elution of 3BV, elution flow rate is BV/h.
The present invention also provides the purposes of aforementioned pharmaceutical compositions in the medicine of preparation antiinflammatory, analgesia or treatment rheumatoid arthritis.
Pharmaceutical composition of the present invention; Herba pterocephali total saponin extracts and total iridoid glucoside extract compatibility are used; Its antiinflammatory resisting rheumatoid disease effect is better than each single extract; Has synergistic function; Especially with the Herba pterocephali total saponin extracts: Herba pterocephali total iridoid glucoside extract (10: 1) effect is best; Curative effect is more stable, for clinical application provides new selection.
Obviously, according to foregoing of the present invention,,, can also make modification, replacement or the change of other various ways not breaking away under the above-mentioned basic fundamental thought of the present invention prerequisite according to the ordinary skill knowledge and the customary means of this area.
Below, foregoing of the present invention is remake further detailed description through the specific embodiment of embodiment form.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following instance.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
Description of drawings
Fig. 1 AA rat hindlimb constitutional swelling symptom, a left side is the normal control group, the right side is a model control group;
Fig. 2 AA rat forelimb performance Secondary cases swelling symptom, a left side is the normal control group, the right side is a model control group.
The specific embodiment
The preparation of embodiment 1 Herba pterocephali total saponin extracts of the present invention
Get Herba pterocephali crude drug 1000g cutting, add the 1600ml water-wet, reuse 6000ml water boiling and extraction 2 times; Each 1.5h filters, after filtrating concentrates; The centrifugal deposition of removing; Water extract is diluted to 0.1g crude drug/ml medicinal liquid, adopts under the D101 type macroporous adsorbent resin room temperature and goes up appearance, and last appearance flow velocity is 2BV/h; Applied sample amount is 1 times of (medical material: resin=1: 1) of resin demand; With the 4BV water elution, flow velocity is BV/h, discards eluent; With the 70%v/v ethanol elution of 3BV, elution flow rate is BV/h, the eluent decompression recycling ethanol; Be dissolved in the 60%v/v ethanol, add excessive saturated neutral lead acetate solution, stir; Make the Herba pterocephali total saponin extracts precipitate fully, filter, get deposition and be suspended in the 70%v/v ethanol; Feed excess hydrogen sulfide gas deleading; Filter, get the bubbling air of filtrating again and slough hydrogen sulfide gas, decompression recycling ethanol to thick paste shape; Drying promptly gets total saponin extracts.
With the oleanolic acid is reference substance, adopts total saponin extracts content in the colorimetric method for determining extract, and the result sees table 1.
Table 1
Figure DEST_PATH_GDA0000150543790000041
In the Herba pterocephali total saponin extracts, saponin content should not be lower than 50%w/w in oleanolic acid, selects for use saponin content to be not less than the Herba pterocephali total saponin extracts of 80%w/w among the present invention.Simultaneously; Do not detect in the Herba pterocephali total saponin extracts and contain iridoid glycoside; With the regulation of " blank assay being disturbed permission below 5% " in the study of tcm new drug guide, the total iridoid glycoside extractive content is 0-5%w/w in the setting Herba pterocephali total saponin extracts.
The preparation of embodiment 2 Herba pterocephali total iridoid glucoside extracts of the present invention
Get Herba pterocephali crude drug 1000g cutting, add the 1600ml water-wet, add the 6000ml water boiling and extraction again 2 times; Each 1.5h filters, and filtrating concentrates; The centrifugal deposition of removing; Water extract is diluted to 0.1g crude drug/ml medicinal liquid, adopts under the D101 type macroporous adsorbent resin room temperature and goes up appearance, and last appearance flow velocity is 2BV/h; Applied sample amount is 1 times of (medical material: resin=1: 1) of resin demand; With the 4BV water elution, flow velocity is BV/h, discards eluent; With 70% ethanol elution of 3BV, elution flow rate is BV/h, the eluent decompression recycling ethanol; Be dissolved in the 80%v/v ethanol, add excessive saturated neutral lead acetate solution, stir; Make the Herba pterocephali total saponin extracts precipitate fully, filter, get filtrating; Decompression recycling ethanol to thick paste shape is dissolved in water, n-butanol extraction three times; Get n-butyl alcohol liquid; Decompression and solvent recovery to thick paste shape, drying promptly gets the total iridoid glucoside extract.
With the loganin is reference substance, adopts the content of total iridoid glucoside extract in the colorimetric method for determining extract, and the result sees table 2.
Table 2
Figure DEST_PATH_GDA0000150543790000051
In the Herba pterocephali total iridoid glucoside extract, iridoid glycoside content should not be lower than 50%w/w in loganin, selects for use iridoid glycoside content to be not less than the Herba pterocephali total iridoid glucoside extract of 80%w/w among the present invention.
Among the present invention, utilize lead acetate that the Herba pterocephali triterpene saponin is separated with iridoid glycoside, principle is referring to " Chemistry for Chinese Traditional Medicine ", the Xiao Chonghou chief editor, Shanghai science tech publishing house, 1997 the 1st edition, 389 pages, 440 pages.
Embodiment 3 preparation of drug combination of the present invention
Get the total saponin extracts 100g of embodiment 1 preparation, the total iridoid glucoside extract 10g of embodiment 2 preparations, and add proper starch, behind the wet granulation, drying promptly gets medicament composition granule agent of the present invention.
Embodiment 4 preparation of drug combination of the present invention
Get the total saponin extracts 50g of embodiment 1 preparation, the total iridoid glucoside extract 50g of embodiment 2 preparations, and add suitable microcrystalline Cellulose, and encapsulated behind the mixing, promptly get medicament composition capsule agent of the present invention.
Below prove the beneficial effect of pharmaceutical composition of the present invention through pharmacology, the test of pesticide effectiveness.
The drug efficacy study of Test Example 1 pharmaceutical composition of the present invention and Herba pterocephali total saponin extracts, iridoid glucoside extract
1.1 laboratory animal
Healthy Sprague-Dawley(SD) rat, the cleaning level, complete male, body weight 180~220g; Healthy animal quality certification :SCXK(river)2008-24 provides by the production of Sichuan Academy of Medical Sciences institute of lab animals; Experimental animal feeding is at 24+2 ℃, in night and daytime each 12 hours alternative environment, freely absorbs clean food and drinking-water, and animal experimentized after conforming 3 days; Animal feeding and experimental implementation process strictly observe the dependency rule (NIH guide for the care and use of laboratory animals of laboratory animal ethics and welfare).
1.2 the preparation of test medication
According to the Pharmacopoeia of the People's Republic of China 2010 editions and " Ministry of Health of the People's Republic of China's Tibetan medicine ministry standard " record; Coming-of-Age Day, consumption was that 3g/60kg(is in crude drug); Therefore; With various Herba pterocephali extracts: Herba pterocephali total saponin extracts A(embodiment 1 preparation); Iridoid glycoside B(embodiment 2 preparation); Pharmaceutical composition C(total saponin extracts of the present invention: total iridoid glucoside extract=10: 1; Embodiment 3 preparation); Pharmaceutical composition D(total saponin extracts of the present invention: total iridoid glucoside extract=5: 5, embodiment 4 preparation) rat dosage is adjusted into 1250mg crude drug in whole/kg.
1.3 medicine and reagent
Nimesulide dispersible tablet (Nimesulide); The Nanchang City flies great pharmaceutcal corporation, Ltd; The accurate word :H20020196 of traditional Chinese medicines; Lot number :091010; Specification :0.1g/ sheet; Coming-of-Age Day is used dosage :0.2g/60kg, and dosage :33.33mg/kg use in test, and it is subsequent use that the employing distilled water diluting is mixed with the medicinal liquid of 3.33mg/ml during experiment;
Indometacin enteric-coated tablet (Indomethacin); Chongqing Ke Rui pharmaceutical Co. Ltd; The accurate word :H50020263 of traditional Chinese medicines; Lot number :310001; Specification :25mg/ sheet; Coming-of-Age Day is used dosage :75mg/60kg, and dosage :12.5mg/kg use in test, and the employing distilled water diluting is mixed with 2.5 respectively during experiment, the medicinal liquid of 1.25mg/ml is subsequent use;
Complete Freund's adjuvant (Freund ' s Adjuvant Complete), Sigma Chemical, lot number :016K8900, specification: every milliliter of adjuvant contains 1mg deactivation tubercule bacillus; The bacillus calmette-guerin vaccine lyophilized powder, Beijing Biological Product Inst., lot number :20100413, specification :60mg/ props up; The bacill calmette-guerin that adds the doses deactivation in the complete Freund's adjuvant of 1mg/ml once more is prepared into every milliliter of complete Freund's adjuvant that contains 10mg deactivation tubercule bacillus, and 4 ℃ of stored refrigerated are subsequent use.
Carrageenin (Carrageenin), Sigma Chemical, lot number :073K0051.
1.4 statistical method
Adopt SPSS 11.5 statistical softwares to carry out statistical analysis.Measurement data is with Mean ± SD ecbatic, and relatively, variance then adopted the LSD check together between data were organized with single factor variance analysis, and heterogeneity of variance then adopts Tamhane ' s T2 check; Ranked data employing non parametric tests is compared between organizing; P<0.05 o'clock thinks that its group difference has significance.
2. on Carrageenan causes the influence of rat paw edema
2.1 experimental technique
60 of healthy male SD rats are divided into 5 groups at random by body weight, are respectively model control group, positive controls (indomethacin) and Herba pterocephali extract A, B, C, D group.Each organizes rat every day by setting the continuous gastric infusion of dosage 7 days, and model control group gives the equal-volume solvent.
Mark in right back ankle joint before the test, measure sufficient volume twice, average as normal foot volume before the administration by sufficient volumetric method; 30min after the last administration; The right back sufficient sole of the foot subcutaneous injection 1% carrageenin solution 0.1ml of portion causes inflammation in rat; And when causing scorching back 60,120,180,240min; Respectively organize the right back sufficient volume of rat with method mensuration, with the anti-inflammatory effect of paw swelling (administration metapedes volume-administration front foot volume) expression medicine.
2.2 experimental result
Behind the carrageenin of the right back foot injection 1% of rat, tangible swelling appears in sufficient pawl; Compare with model control group; Herba pterocephali extract A and B and compositions C, D can suppress carrageenin and cause rat paw edema; Point out various Herba pterocephali extracts that acute inflammation is had certain inhibitory action; But it is wherein obvious with the effect of compositions C group especially; Its effect is suitable with indomethacin, and therapeutic effect is more stable.The result sees table 3.
Table 3 Wing first extract on carrageenan-induced rat paw edema effect
Figure DEST_PATH_GDA0000150543790000071
Figure DEST_PATH_GDA0000150543790000072
Annotate: compare with model control group, < > * <> P<0.05, < > * <> P<0.01.
3 Herba pterocephali extracts cause rat assist agent arthritis (AA to complete Freund's adjuvant) influence of model
3.1AA the foundation of rat model and dosage regimen
Get 70 of healthy male SD rats, be divided into 7 groups at random, be respectively normal control group, model control group, positive controls (nimesulide) and Herba pterocephali extract A, B, C, D group, every group of 10 rats by body weight.
The modeling of reference literature method in every the right back toes intradermal injection of rat 0.1ml Freund's complete adjuvant (every milliliter of adjuvant contains 10mg deactivation tubercule bacillus), is set up the adjuvant arthritis rats model; The right back toes intradermal injection of rats in normal control group 0.1ml normal saline.
Behind the rat intradermal injection complete Freund's adjuvant, obvious swelling appears in right back foot, approximately peaks behind the 24h, continues detumescence gradually after 3~5 days, is acute inflammatory reaction; What occur once again after 8~9 days after the modeling causes scorching side joint and pedal swelling; Engender non-joint and the pedal swelling that causes scorching side and two forelimbs after 12 days; Symptoms such as weight loss, color of the leather is unglazed; Be the reaction of Secondary cases immune inflammation; And be considered as the successful index of adjuvant-induced arthritis model modeling, concrete See Figure 1, Fig. 2.
After causing inflammation, each organizes rat according to setting dosage successive administration 30 days, and normal control group and model control group rat give the equal-volume distilled water.
3.2 influence to the arthroncus of AA rat constitutional
3.2.1 experimental technique
Each organizes rat in causing scorching preceding 3 days by setting the dosage gastric infusion, normally reaches model control group and gives the equal-volume distilled water.(ml)2 time gets its meansigma methods as causing scorching preceding normal foot volume to adopt volumetric method mensuration to cause the scorching preceding right back whole volume of rat; Simultaneously in cause scorching back 6,12,24,36,48,72h measurements causes scorching sufficient volume so that difference is represented its swelling degree before and after scorching, observation Herba pterocephali extract is to the influence of AA rat acute constitutional inflammation.
3.2.2. experimental result
Compare with the normal control group, behind the right back foot injection of the rat complete Freund's adjuvant, right back foot produces obvious swelling, and swelling reaches peak value when causing inflammation back 12~36h; Compare with model control group; Herba pterocephali extract A, B and compositions C, D all can obviously suppress AA rat constitutional arthroncus due to the complete Freund's adjuvant; Show that all arthroncus has obvious inhibitory action to constitutional for Herba pterocephali total saponin extracts, total iridoid glucoside extract and both compositionss; But take second place with the most obvious group effect of compositions C group effect, the result sees table 4.
Table 4 wing AA first extract on rat paw edema primary influence
Figure DEST_PATH_GDA0000150543790000081
Figure DEST_PATH_GDA0000150543790000082
Annotate: compare with model control group, < > * <> P<0.05, < > * <> P<0.01.
3.3 influence to the arthroncus of AA rat Secondary cases
3.3.1 experimental technique
(ml)2 time gets its meansigma methods to the sufficient volume of the left back foot of rat (the non-inflammation foot that causes), as causing the preceding normal foot volume of inflammation before adopting volumetric method mensuration to cause inflammation; And respectively at causing the 12nd, 18,24, the 30 day non-sufficient volume-variation that causes scorching foot (left side foot) of mensuration in scorching back, with of the influence of observation Herba pterocephali extract to the arthroncus of AA rat Secondary cases.
3.3.2 experimental result
Compare with the normal control group, behind the right back foot injection of the rat complete Freund's adjuvant 12d, left back foot produces obvious Secondary cases swelling, and swelling reaches peak value when causing inflammation back 24d; Compare with model group; Herba pterocephali extract A, B and compositions C, D all can obviously suppress the foot swelling of AA rat Secondary cases; Show that various Herba pterocephali extracts have stronger inhibitory action to the secondary inflammation due to the complete Freund's adjuvant immune stimulating; Wherein, Best with compositions C group action effect; And curative effect is more stable, and the effect of D group is taken second place, and the result sees table 5.
Table 5 wing first extract on AA rats paw edema secondary effects
Figure DEST_PATH_GDA0000150543790000091
Figure DEST_PATH_GDA0000150543790000092
Annotate: compare with model control group, < > * <> P<0.05, < > * <> P<0.01.
4. conclusion
Herba pterocephali total saponin extracts, Herba pterocephali total iridoid glucoside extract and compositions by a certain percentage thereof can suppress obviously all that carrageenin causes rat paw edema, can obviously reduce AA rat constitutional, Secondary cases swollen joint expansibility.Wherein, After total saponin extracts and the use of total iridoid glucoside extract compatibility; Brought into play synergistic function; Its antiinflammatory resisting rheumatoid disease effect is better than each single extract; Especially with the Herba pterocephali total saponin extracts: Herba pterocephali total iridoid glucoside extract (10: 1) effect is best, and curative effect is more stable.
In sum; Pharmaceutical composition of the present invention; Herba pterocephali total saponin extracts and total iridoid glucoside extract compatibility are used; Its antiinflammatory resisting rheumatoid disease effect is better than each single extract; Has synergistic function; Especially with the Herba pterocephali total saponin extracts: Herba pterocephali total iridoid glucoside extract (10: 1) effect is best, and curative effect is more stable, for clinical application provides new selection.

Claims (10)

1. pharmaceutical composition of treating rheumatoid arthritis; It is characterized in that: it is to be the preparation that active component is prepared from Herba pterocephali total saponin extracts and total iridoid glucoside extract; Wherein, the weight proportion of described total saponin extracts, total iridoid glucoside extract is:
Total saponin extracts 1-10 part, total iridoid glucoside extract 1-10 part.
2. pharmaceutical composition according to claim 1 is characterized in that: the weight proportion of described total saponin extracts, total iridoid glucoside extract is:
10 parts of total saponin extracts, 1 part of total iridoid glucoside extract; Or 5 parts of total saponin extracts, 5 parts of total iridoid glucoside extracts.
3. pharmaceutical composition according to claim 1 and 2 is characterized in that: in the said Herba pterocephali total saponin extracts, saponin content is greater than 50%w/w; In the said Herba pterocephali total iridoid glucoside extract, the total iridoid glycoside extractive content is greater than 50%w/w.
4. pharmaceutical composition according to claim 3 is characterized in that: in the said Herba pterocephali total saponin extracts, saponin content is greater than 80%w/w; In the said Herba pterocephali total iridoid glucoside extract, iridoid glycoside content is greater than 80%w/w.
5. according to any described pharmaceutical composition of claim 1-4, it is characterized in that: said Herba pterocephali is the dry herb of Dipsacaceae plant spoon leaf Herba pterocephali Pterocephalus hookeri(C.B.Clarke)Hoeck.
6. method for preparing any described pharmaceutical composition of claim 1-5, it comprises the steps:
(1) preparation Herba pterocephali total saponin extracts
A, get Herba pterocephali, extracting in water filters, and filtrating is adopted nonpolar or low pole purification with macroreticular resin after concentrating, and with after washing decontamination, discards eluent earlier; With the 60-85% ethanol elution, behind the collection ethanol elution;
B, get the ethanol elution of step a, behind the decompression and solvent recovery, add lead acetate solution, stir, filter, filtrate for later use is got deposition, and behind the deleading, drying promptly gets the Herba pterocephali total saponin extracts;
(2) preparation Herba pterocephali total iridoid glucoside extract
Get the filtrating behind the adding lead acetate solution among the step b, after concentrating, use n-butanol extraction, get n-butyl alcohol liquid, behind the recovery solvent, drying promptly gets Herba pterocephali total iridoid glucoside extract;
(3) preparation of drug combination
Take by weighing Herba pterocephali total saponin extracts and total iridoid glucoside extract by the prescription proportioning, add adjuvant pharmaceutically commonly used and be prepared into preparation.
7. method according to claim 6 is characterized in that: select D101, AB-8 or HPD-300 type macroporous adsorbent resin among the step a for use; With the 65-75%v/v ethanol elution; Among the step b, get the ethanol elution of step a, behind the decompression and solvent recovery; Redissolve in 30-95%v/v ethanol, add saturated neutral lead acetate solution, stir; Filter, filtrate for later use is got deposition; Be suspended in the 30-95%v/v ethanol; With hydrogen sulfide gas or cation exchange resin deleading, filter, get filtrating concentrating; Drying promptly gets the Herba pterocephali total saponin extracts.
8. method according to claim 7 is characterized in that: select D101 type macroporous adsorbent resin among the step a for use; With the 70%v/v ethanol elution; Among the step b, concentration of alcohol is 60-85%v/v.
9. according to any described method of claim 6-8, it is characterized in that: the concrete operations step of purification with macroreticular resin is following among the step a:
The concentration of sample solution is formulated as 0.1-0.2g crude drug/ml, adopts D101 type purification with macroreticular resin, last appearance flow velocity is 1-3BV/h; Applied sample amount is counted medical material with medical material: resin=(0.5-1.5): 1w/w; With the-5BV water elution, flow velocity is 1-3BV/h, discards eluent; With 70% ethanol elution of-4BV, elution flow rate is 2-4BV/h.
10. the purposes of any described pharmaceutical composition of claim 1-5 in the medicine of preparation antiinflammatory, analgesia or treatment rheumatoid arthritis.
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