CN103989670A - Application of aristolochic acid in preparation of drugs treating rheumatoid arthritis - Google Patents
Application of aristolochic acid in preparation of drugs treating rheumatoid arthritis Download PDFInfo
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- CN103989670A CN103989670A CN201310054582.7A CN201310054582A CN103989670A CN 103989670 A CN103989670 A CN 103989670A CN 201310054582 A CN201310054582 A CN 201310054582A CN 103989670 A CN103989670 A CN 103989670A
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Abstract
The invention provides application of aristolochic acid in preparation of immunosuppressive drugs, especially application in drugs treating rheumatoid arthritis. The aristolochic acid gel provided by the invention can effectively inhibit rheumatoid arthritis and has no renal toxic reaction, thus providing a new choice for clinical treatment of rheumatoid arthritis.
Description
Technical field
The present invention relates to field of medicaments, specifically the purposes of Aristolochic Acid in treatment medicine for treating rheumatoid arthritis.
Background technology
Rheumatoid arthritis (rheumatoid arthritis) is that a kind of to take joint and periarticular soft tissues nonsuppurative inflammation be main chronic systemic disease.Its course of disease is prolonged and repeated, and disability rate is high.The pathological changes outside chronic, symmetry, polysynovitis arthritis and joint of take is main clinical manifestation, belongs to autoimmune inflammatory diseases.Primary disease is globalization and distributes, and China's prevalence is 0.32%-0.36%, is to cause population of China disability and one of Etiological of disabling, once morbidity has a strong impact on patients ' life quality.Current Therapeutic Method is mainly to adopt hormone and antimetabolite to carry out antiinflammatory and immunization therapy, but the untoward reaction of existing Therapeutic Method is large and be difficult to radical cure.Therefore, find and effectively there is immunoregulation effect and the little medicine of side effect, significant for the treatment of rheumatoid arthritis.
Aristolochic Acid has another name called aristolochic acid, and chemical name is 8-methoxyl group-6-nitro-Fei [3,4-d]-1,3-dioxole-5-formic acid, and Aristolochic Acid structural formula is as follows:
Aristolochic Acid is the luxuriant and rich with fragrance compounds of a kind of nitro, is extensively present in birthwort.Through medical circle research, long-term taking can cause that kidney is poisoning, destroy renal function, renal failure and carcinoma of urethra containing the medicine of Aristolochic Acid, even dead.Except Caulis Aristolochiae Manshuriensis, the medical material that contains Aristolochic Acid also has Radix Aristolochiae Fangchi, Radix Aristolochiae, Herba Aristolochiae, Fructus Aristolochiae, Herba Aristolochiae Mollissimae, Radix Aristolochiae Kaempferi, Herba Asari etc.In view of the toxic action of Aristolochic Acid for kidney, comprise that the multinational Yao Jian department of China has prohibited containing the medicinal plants of Fructus Aristolochiae for oral administration.Therefore Aristolochic Acid and be not suitable for systemic administration containing the medicine of Aristolochic Acid.It is investigated, there is no at present Aristolochic Acid or containing the report of the medicine local application of Aristolochic Acid.The inventor proves by experiment, during the local use of Aristolochic Acid preparation, there is remarkable antiinflammatory and immunosuppressive action, rheumatoid arthritis is had therapeutical effect and animal kidney do not produced to toxic and side effects, thereby complete the present invention, for treating clinically rheumatoid arthritis, provide new medication to select.
Summary of the invention
The invention provides the application of Aristolochic Acid in preparing anti-inflammatory drug, especially the application in the medicine for the treatment of rheumatoid arthritis.
Aristolochic Acid can adopt according to techniques well known and be prepared.Also can adopt method preparation provided by the invention, get 10000 grams of Asarum medicinal materials, add 30000 grams of methanol eddies to extract twice, each 3 hours, filter, merge twice filtrate, by filtrate evaporation, reclaim methanol, residue dissolves with 1% aqueous hydrochloric acid solution, add 2% aqueous sodium carbonate to pH8.5, add appropriate dichloromethane extraction 3 times, aqueous phase discarded, dichloromethane extraction liquid is merged, be evaporated to dryly, reclaim dichloromethane, obtain 0.508g Aristolochic Acid.
Aristolochic Acid external preparation comprises gel, ointment, paster agent, lotion, spray etc., can prepare according to means known in the art.
Beneficial effect
1, Aristolochic Acid causes the antiinflammatory action test after inflammation to SD rat toes
One, Experimental agents
Blank group (the blank gel that does not contain any medicine);
Aristolochic Acid low dose group gel (20mg/kg);
Dosage group gel (25mg/kg) in Aristolochic Acid;
Aristolochic Acid high dose group gel (28.5mg/kg);
Positive controls (Novartis Pharma AG produces for diclofenac emulsion agent, trade name diclofenac).
Two, experimental technique
Get 50 of male SD rats, be divided at random 5 groups, 10 every group.In the left back toes of 0.1ml Freund's complete adjuvant (liquid paraffin/wool grease/inactivated vaccine) intradermal injection.Injection adjuvant causes scorching front 24h percutaneous drug delivery, causes scorching rear continuous use 6 days.Administration adopts capillary tube amplifying method to measure the swelling of toes for 6 days afterwards.Swelling rate (%)=(V
t-V
0)/V
0, V wherein
0for causing scorching front toes volume; V
tfor causing the toes swelling volume of scorching latter 6 days.The results are shown in Table 1.
Table 1 Aristolochic Acid gel causes scorching antiphlogistic effects to rat adjuvant
With the comparison of blank group, * P < 0.05, * P < 0.01
Conclusion: as shown in Table 1, the middle and high dosage group of Aristolochic Acid has significant inhibitory action to toes swelling due to rat Freund's complete adjuvant, its effect compares with blank group that there were significant differences, suitable with the effect of positive controls.Prove thus, Aristolochic Acid has significant antiinflammatory action.
2, the inhibitory action test of Aristolochic Acid to mice rheumatoid arthritis
Experiment material
One, animal
Kunming mouse, 18～23g, male and female half and half, light dark period 12/12h, constant temperature (23 ± 2 ℃), relative humidity 65～75% environment are raised, and free diet conforms 3 days afterwards formally for experiment.
Two, Experimental agents
Normal group (not administration)
Model group (the blank gel that does not contain any medicine);
Aristolochic Acid low dose group gel (20mg/kg);
Dosage group gel (25mg/kg) in Aristolochic Acid;
Aristolochic Acid high dose group gel (28.5mg/kg);
Positive controls (Radix Tripterygii Wilfordii lactone alcohol 12mg/kg).
Three, experimental technique
1, rheumatoid arthritis mouse model preparation: cattle II Collagen Type VI is dissolved in to acetic acid, is mixed with 2mg/ml solution, cryopreservation is standby.Bovine collagen acetum is fully mixed at low temperatures with isopyknic Fo Shi Freund's complete adjuvant, form Emulsion.0.1ml Emulsion is expelled to mouse tail subcutaneous.At the 21st day, then replace Fo Shi Freund's complete adjuvant preparation Emulsion with Freund incomplete adjunvant, at the subcutaneous another location injection 0.1ml the second Emulsion of afterbody.6-8 obtains typical rheumatoid arthritis mouse model after week.
2, grouping and dosage
According to body weight, be divided at random: normal group, model group, positive controls; Each 10 of high, medium and low dosage groups.Except normal group, all the other each groups all first cause after rheumatoid arthritis mouse model, then administration respectively.Every morning is coated on mice posterior joint place once by medicine, model group: the blank gel of the weight such as coating; The basic, normal, high dosage group of Aristolochic Acid is coated with respectively the Aristolochic Acid gel of each dosage group; Positive controls: coating Radix Tripterygii Wilfordii lactone alcohol gel, once a day.From latter continuous 28 days of immunity for the second time.In administration, after 4 weeks, use its arthritic arthritic volume of kind of calliper.With animals administer posterior joint volume, be curative effect index, obtain the suppression ratio after every animal-use drug.Suppression ratio=(model group arthritic volume value added-administration group arthritic volume value added)/(model group arthritic volume value added-normal group arthritic volume value added) * 100%
With t check, carry out statistical analysis, evaluate the significance of medication front and back rheumatoid arthritis cyst volume difference in size.
The results are shown in Table 2.
The therapeutic outcome of table 2 Aristolochic Acid gel to mice rheumatoid arthritis
* with model group comparison, P < 0.01
Result of the test shows, the middle and high dosage group of Aristolochic Acid is the same with positive controls, arthritic volume all has obviously and dwindles than model group, has extremely significantly statistical significance (P < 0.01), proves that the Aristolochic Acid of this type of dosage can effectively suppress rheumatoid arthritis change.
The specific embodiment
Below by specific embodiment, further illustrate technical scheme of the present invention, only the invention will be further described for these embodiment with supplementary, the invention is not restricted to these embodiment.
Embodiment 1
Get 10000 grams of Asarum medicinal materials, add 30000 grams of methanol eddies to extract twice, each 3 hours, filter, merge twice filtrate, filtrate is evaporated, reclaim methanol, residue dissolves with 1% aqueous hydrochloric acid solution, adds 2% aqueous sodium carbonate to pH8.5, add appropriate dichloromethane extraction 3 times, aqueous phase discarded, merges dichloromethane extraction liquid, is evaporated to dry, reclaim dichloromethane, obtain 0.508g Aristolochic Acid.
Embodiment 2
Get 2g carbomer-971 and add appropriate distilled water immersion, stir and make it be swelled into even pasty state, then add ethyl hydroxybenzoate, drip triethanolamine, regulate pH to 7.5; Get in the carbomer solution that 5g Aristolochic Acid adds swelling, then add 15.1g laurocapram, adding distil water is to 80g, is stirred to transparently, obtains gel of the present invention.
Claims (3)
1. the application of Aristolochic Acid in preparing immunosuppressive drug.
2. the application of Aristolochic Acid in the medicine of preparation treatment rheumatoid arthritis.
3. purposes as claimed in claim 1 or 2, wherein this pharmaceutical dosage form is gel.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310054582.7A CN103989670A (en) | 2013-02-20 | 2013-02-20 | Application of aristolochic acid in preparation of drugs treating rheumatoid arthritis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310054582.7A CN103989670A (en) | 2013-02-20 | 2013-02-20 | Application of aristolochic acid in preparation of drugs treating rheumatoid arthritis |
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| CN103989670A true CN103989670A (en) | 2014-08-20 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112778264A (en) * | 2021-01-21 | 2021-05-11 | 江西农业大学 | Aristolochiatic acid derivative and application thereof in preparation of anti-inflammatory drugs |
| CN114469930A (en) * | 2022-04-12 | 2022-05-13 | 中国中医科学院中药研究所 | Application of aristolochic acid IVa in preparing antihistaminic or pneumonia treatment medicine |
-
2013
- 2013-02-20 CN CN201310054582.7A patent/CN103989670A/en active Pending
Non-Patent Citations (4)
| Title |
|---|
| 方 芸等: ""中药不良反应的现状与分析对策"", 《江苏药学与临床研究》 * |
| 蔺亚东等: ""类风湿关节炎治疗中顾护脾胃经验的探讨"", 《江西中医药》 * |
| 陈成伟: "《药物与中毒性肝病》", 31 January 2013 * |
| 陈成伟: "《药物与中毒性肝病》", 31 January 2013, article "抗风湿病药物的肝损伤", pages: 596-597 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112778264A (en) * | 2021-01-21 | 2021-05-11 | 江西农业大学 | Aristolochiatic acid derivative and application thereof in preparation of anti-inflammatory drugs |
| CN112778264B (en) * | 2021-01-21 | 2023-09-15 | 江西农业大学 | Aristolochic acid derivative and application thereof in preparing anti-inflammatory drugs |
| CN114469930A (en) * | 2022-04-12 | 2022-05-13 | 中国中医科学院中药研究所 | Application of aristolochic acid IVa in preparing antihistaminic or pneumonia treatment medicine |
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Application publication date: 20140820 |