CN1778292A - Medical use of salvianolic acid - Google Patents
Medical use of salvianolic acid Download PDFInfo
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- CN1778292A CN1778292A CN 200410084620 CN200410084620A CN1778292A CN 1778292 A CN1778292 A CN 1778292A CN 200410084620 CN200410084620 CN 200410084620 CN 200410084620 A CN200410084620 A CN 200410084620A CN 1778292 A CN1778292 A CN 1778292A
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- allopurinol
- xanthine oxidase
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Abstract
An application of danshinolic acid in preparing the medicines for preventing and treating gout is disclosed. Its advantages are high effect to decrease the uric acid value in serum and low poison.
Description
Technical field
The chemical analysis that the present invention relates to extract from Chinese medicine proves that through pharmacological testing it has medical usage, the medical usage of the salviol class of more specifically saying so.
Background technology
Raising in China along with living standards of the people, the variation of dietary structure, the sickness rate of gout is in rising trend, and gout is a metabolic disease, is difficult to radical cure.Gout is shown effect repeatedly and can be produced urate deposition, and joint deformity and renal calculus have higher hazardness, therefore strengthens the research of gout control medicine significant.
The rising of blood uric acid concentration is the main reason that causes gout in the body.Uric acid is to be transformed by hypoxanthine and xanthine under the xanthine oxidase effect.Owing to lack uricase in the human body, so uric acid is metabolic end-product.
Xanthine oxidase is an action target spot of treatment antihyperuricemic disease drug, the activity that suppresses xanthine oxidase can reduce uric acid concentration in the blood, thereby reach the purpose of treatment gout, allopurinol is unique xanthine oxidase inhibitor that uses clinically, but finds that clinically allopurinol has comparatively serious adverse effects as hepatitis, super quick allergy etc.Limited its safe handling to a certain extent.Will seek the active stronger little xanthine oxidase inhibitor of side effect from natural plants is the good problem that the scientific worker captures gout for this reason.
Summary of the invention
Purpose of the present invention is exactly to seek active stronger xanthine oxidase inhibitor from natural plants.
The present invention relates to extract the salvianolic acid chemical compound of gained from Chinese herbal medicine, comprise salvianolic acid B and other salt, rosmarinic acid, alkannic acid and danshensu, their chemical constitution is as follows:
1：M
+＝Mg
2+/2
2：M
+＝NH
4 ++K
+
Salvianolic acid B (lithospermate B)
C
36H
28MgO
16(sample 17)
Rosmarinic acid (rosmarinic acid) alkannic acid (lithospermic acid)
C
18H
16O
8(sample 15) C
27H
22O
12(sample 16)
Danshensu (Danshensu) sodium salt
C
9H
9O
5Na (sample 19)
Acteoside (C
29H
36O
15) (sample XA-1)
Experimental technique:
1. by the external influence of uricopoiesis method working sample to xanthine oxidase activity
Xanthine oxidase activity is measured list of references (Li H.et al.New guaianolides and xathine oxidaseinhibitory flavonols from Ajania fruticulosa.Journal of NaturalProducts, 62:1053-1055,1999) method is carried out, concrete steps are: add the sample or the positive control allopurinol of variable concentrations in the xanthine solution of 1mM, add 0.1muml
-1Xanthine oxidase, 37 ℃ of reaction 5min measure the uricopoiesis amount at automatic clinical chemistry analyzer (Hitachi-7600), with the uricopoiesis amount of 5min as response speed.
2. by the external influence of superoxide ion method of formation working sample to xanthine oxidase activity
In the xanthine solution of 500 μ M, add the sample and the positive control allopurinol of variable concentrations, add 0.1muml then
-1Xanthine oxidase, the NBT that adds 500 μ M be as developer, in the absorbance recruitment of wavelength 560nm per minute as response speed.
Xanthine can generate uric acid and superoxide ion under the effect of xanthine oxidase, so can measure the activity of xanthine oxidase and the inhibitory action of inhibitor by the generation of measuring uric acid and superoxide ion.
By above identical method, measured 15,16,17,19 respectively, the external inhibitory action of XA-1 sample to xanthine oxidase, concrete outcome sees the following form:
| Sample | 50 3nhibitory dose (IC 50)μg·ml -1 | Suppress type | |
| The uricopoiesis method | The superoxide ion method of formation | ||
| 15 | 42 | 25 | Competitive inhibition |
| 16 | 40 | 24 | Competitive inhibition |
| 17 | 46 | 28 | Competitive inhibition |
| 19 | 48 | 29 | Competitive inhibition |
| XA-1 | 30 | 22 | Competitive inhibition |
Two. the interior influence of body to the mice hyperuricemia
(1). utilize the precursor substance hypoxanthine of uricopoiesis to be model drug, preparation mice hyperuricemia model, observation sample is to the influence of hyperuricemia, concrete grammar reference literature (Tang Can, Yang Kui, the pre-test of hyperuricemia animal model, experimental animal model, 11 (5): 292-294,2000)
1. experimental technique:
Male Kunming strain mice, body weight 18-22g is divided into 5 groups, i.e. the normal saline group at random, high, medium and low dosage group of sample and allopurinol group, the high, medium and low dosage group of sample ig every day administration is 1 time in the model experiment, continuous three days, the sample height, in, low dosage is respectively 20,40,60mgkg
-1, allopurinol dosage is 2mgkg
-1, matched group gives the equal volume normal saline, and after the administration 1 hour the last time, all organized equal lumbar injection 1000mgkg
-1Hypoxanthine, the 2hr posterior orbit is got blood, measures uric acid level in the serum with automatic clinical chemistry analyzer Hitachi-7600.
(2). utilize the uricase inhibitor Oteracil Potassium as model drug, preparation mice metabolic arthritis model, observation sample is to the influence of hyperuricemia.Concrete grammar reference literature (Wang Haidong, Ge Fei etc.Herba Lysimachiae extract is to the influence of hyperuricemia mice, CHINA JOURNAL OF CHINESE MATERIA MEDICA, 27 (12): 939-944,2002)
1. test method:
Male Kunming strain mice, body weight 18-22g is divided into 5 groups, i.e. the normal saline group at random, high, medium and low dosage group of sample sets and allopurinol group, the high, medium and low dosage group of sample ig every day administration is 1 time in the model experiment, and continuous three is big, the sample height, in, low dosage is respectively 20,40,60mgkg
-1, allopurinol dosage is 2mgkg
-1, matched group gives the equal volume normal saline, and after the administration 1 hour the last time, all organized equal lumbar injection Oteracil Potassium, and the 2hr posterior orbit is got blood, measures uric acid level in the serum with automatic clinical chemistry analyzer Hitachi-7600.
By above method, measured 15,16,17,19 respectively, in the XA-1 sample body to the influence of uricopoiesis, concrete outcome sees the following form.
15,16,17,19, the influence of XA-1 sample mice hyperuricemia model that hypoxanthine is caused
| Group | Dosage (mgkg -1) | The serum uric acid value |
| Normal value | 0.068±0.012 | |
| Normal saline | 0.893±0.250 | |
| No. 15 | 20 | 0.624±0.138 ** |
| 40 | 0.589±0.045 ** | |
| 60 | 0.407±0.032 ** | |
| No. 16 | 20 | 0.602±0.127 ** |
| 40 | 0.576±0.113 ** | |
| 60 | 0.389±0.092 ** | |
| No. 17 | 20 | 0.635±0.136 ** |
| 40 | 0.597±0.087 ** | |
| 60 | 0.412±0.103 ** | |
| No. 19 | 20 | 0.652±0.107 ** |
| 40 | 0.601±0.123 ** | |
| 60 | 0.452±0.098 ** | |
| XA-1 | 20 | 0.589±0.147 ** |
| 40 | 0.532±0.103 ** | |
| 60 | 0.462±0.087 ** | |
| Allopurinol | 2 | 0.133±0.038 ** |
* P＜0.01 VS normal saline group
15,16,17,19, the influence of XA-1 sample mice hyperuricemia model that Oteracil Potassium is caused
| Group | Dosage (mgkg -1) | The serum uric acid value |
| Normal value | 0.073±0.18 | |
| Normal saline | 0.325±0.117 | |
| No. 15 | 20 | 0.237±0.086 * |
| 40 | 0.179±0.066 ** | |
| 60 | 0.138±0.047 ** | |
| No. 16 | 20 | 0.231±0.077 * |
| 40 | 0.162±0.058 ** | |
| 60 | 0.122±0.037 ** | |
| No. 17 | 20 | 0.241±0.093 * |
| 40 | 0.183±0.072 ** | |
| 60 | 0.147±0.056 ** | |
| No. 19 | 20 | 0.245±0.068 ** |
| 40 | 0.185±0.063 ** | |
| 60 | 0.185±0.063 ** | |
| XA-1 | 20 | 0.216±0.077 * |
| 40 | 0.162±0.068 ** | |
| 60 | 0.140±0.051 ** | |
| Allopurinol | 2 | 0.139±0.037 ** |
* P＜0.05, * * P＜0.01 VS normal saline group
Description of drawings
Fig. 1 is that No. 15 samples pass through the inhibitory action that the uricopoiesis method is measured xanthine oxidase.
Fig. 2 is that No. 15 samples are external by the inhibitory action of superoxide ion method of formation to xanthine oxidase.
The present invention compares with existing only xanthine oxidase inhibitor allopurinol, has the following advantages:
1, without any side effects;
2, the source is sufficient, and is easy to prepare.
The specific embodiment
Embodiment
Add 35,70,105 μ gml respectively in the xanthine solution of No. 15 external inhibitory action of sample (measuring) 1mM by the uricopoiesis method to xanthine oxidase
-1No. 15 samples or positive control allopurinol (2 μ gml
-1), add 0.1muml
-1Xanthine oxidase, 37 ℃ of reaction 5min measure the uricopoiesis amount at automatic clinical chemistry analyzer (Hitachi-7600), with the uricopoiesis amount of 5min as response speed.By experiment, No. 15 external effects that stronger inhibition xanthine oxidase is arranged of sample, its 50 3nhibitory dose (IC
50) be 42mgml
-1, belong to competitive inhibition.Concrete outcome is seen Fig. 1.
No. 15 external inhibitory action of sample (by the superoxide ion method of formation) to xanthine oxidase
In the xanthine solution of 500 μ M, add 12,26,38 μ gml respectively
-1No. 15 samples and positive control allopurinol (2 μ gml
-1), add 0.1muml then
-1Xanthine oxidase, the NBT that adds 500 μ M be as developer, in the absorbance recruitment of wavelength 560nm per minute as response speed.
By experiment, the 50 3nhibitory dose (IC of No. 15 sample vitro inhibition superoxide ion generations
50) be 25 μ gml
-1, belong to competitive inhibition.Concrete outcome is seen Fig. 2:
The influence of the mice hyperuricemia that in No. 15 sample bodies hypoxanthine is caused
50 of kunming mouses, male, about about 20 grams of body weight, available from the big Experimental Animal Center of two armies.To buy mice behind the laboratory and be divided into 5 groups at random, it is the normal saline group, No. 15 high, medium and low dosage groups of sample sets and allopurinol group, No. 15 high, medium and low dosage group of sample ig every day administration is 1 time in the model experiment, continuous three days, No. 15 sample height, in, low dosage is respectively 20,40,60mgkg
-1, allopurinol dosage is 2mgkg
-1Matched group gives the equal volume normal saline, takes a blood sample before the 3rd time is irritated stomach respectively, during blood sampling the capillary blood taking tube is cut into length and is about one centimetre for 5 groups, get one in the preceding canthus of the mice about 50mm of place's inserting needle treat hemorrhage after, it is to be measured as normal control to access about 500 μ ml blood with the EP pipe of 500 μ ml.Taking by weighing hypoxanthine 600mg dissolves with the 15ml sodium carboxymethyl cellulose.Irritate stomach at the 3rd time and only distinguished Intraperitoneal injection of hypoxanthine 0.5ml/ before one hour, take a blood sample after the 45min posterior orbit.
With the 2000 rev/mins of centrifugal 5min of blood sample that adopt, Hitachi's automatic clinical chemistry analyzer (7600) is measured the growing amount of uric acid on the about 100 μ l of taking-up blood sample absorption serum.
Experimental result:
No. 15 samples to the influence of mice serum uric acid level (x ± s, n=10)
| Group | Dosage (mgkg -1) | The serum uric acid value |
| No. 15 sample sets allopurinol of normal value normal | 20 40 60 2 | 0.068±0.012 0.893±0.250 0.624±0.138 ** 0.589±0.045 ** 0.407±0.032 ** 0.133±0.038 ** |
* P＜0.01 VSThe normal saline group
The influence of the mice hyperuricemia that in No. 15 sample bodies Oteracil Potassium is caused
Male Kunming strain mice, body weight 18-22g, be divided into 5 groups at random, be the normal saline group, high, medium and low dosage group of sample sets and allopurinol group, No. 15 high, medium and low dosage group of sample ig every day administration is 1 time in the model experiment, continuous three days, No. 15 sample height, in, low dosage is respectively 20,40,60mgkg
-1, allopurinol dosage is 2mgkg
-1, matched group gives the equal volume normal saline, and after the administration 1 hour the last time, all organized equal lumbar injection Oteracil Potassium, and the 2hr posterior orbit is got blood, measures uric acid level in the serum with automatic clinical chemistry analyzer Hitachi-7600.
Experimental result:
No. 15 samples to the influence of mice serum uric acid level (x ± s, n=10)
| Group | Dosage (mgkg -1) | The serum uric acid value |
| No. 15 sample sets allopurinol of normal value normal | 20 40 60 2 | 0.073±0.018 0.325±0.117 0.237±0.086 * 0.179±0.066 ** 0.138±0.047 ** 0.145±0.044 ** |
*P＜0.05,
*P＜0.01
VSThe normal saline group
Claims (1)
1, the medical usage of the following salvianolic acid of a class formation is used in the medicine of preparation treatment or prevention gout
1：M
+＝Mg
2+/2
2：M
+＝NH
4 ++K
+
Salvianolic acid B (lithospermate B)
C
36H
28MgO
16(sample 17)
Rosmarinic acid (rosmarinic acid) alkannic acid (lithospermic acid)
C
18H
16O
8(sample 15) C
27H
22O
12(sample 16)
Danshensu (Danshensu) sodium salt
C
9H
9O
5Na (sample 19)
Acteoside (C2
9H
36O
15) (sample XA-1).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410084620 CN1778292A (en) | 2004-11-26 | 2004-11-26 | Medical use of salvianolic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410084620 CN1778292A (en) | 2004-11-26 | 2004-11-26 | Medical use of salvianolic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1778292A true CN1778292A (en) | 2006-05-31 |
Family
ID=36768830
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410084620 Pending CN1778292A (en) | 2004-11-26 | 2004-11-26 | Medical use of salvianolic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1778292A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101319220B (en) * | 2007-06-05 | 2010-08-25 | 中国中医科学院中药研究所 | Red sage root diterpene synthase gene, encoding product and application thereof |
| CN102423310A (en) * | 2012-01-04 | 2012-04-25 | 中国药科大学 | Application of salvianolic acid C in preparation of drugs for prevention and treatment of hyperuricemia |
| CN109718230A (en) * | 2017-10-27 | 2019-05-07 | 中国医学科学院药物研究所 | Application of the salviandic acid A in preparation inhibiting hyperuricemia and anti-gout drugs |
| US11021454B2 (en) | 2016-02-03 | 2021-06-01 | China Pharmaceutical University | Type of aryl benzofuran amidated derivative and medical use thereof |
-
2004
- 2004-11-26 CN CN 200410084620 patent/CN1778292A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101319220B (en) * | 2007-06-05 | 2010-08-25 | 中国中医科学院中药研究所 | Red sage root diterpene synthase gene, encoding product and application thereof |
| CN102423310A (en) * | 2012-01-04 | 2012-04-25 | 中国药科大学 | Application of salvianolic acid C in preparation of drugs for prevention and treatment of hyperuricemia |
| CN102423310B (en) * | 2012-01-04 | 2012-12-12 | 中国药科大学 | Application of salvianolic acid C in preparation of drugs for prevention and treatment of hyperuricemia |
| US11021454B2 (en) | 2016-02-03 | 2021-06-01 | China Pharmaceutical University | Type of aryl benzofuran amidated derivative and medical use thereof |
| CN109718230A (en) * | 2017-10-27 | 2019-05-07 | 中国医学科学院药物研究所 | Application of the salviandic acid A in preparation inhibiting hyperuricemia and anti-gout drugs |
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