CN101239057A - Use of salvianolic acid B and its salt in treating parkinson's disease - Google Patents
Use of salvianolic acid B and its salt in treating parkinson's disease Download PDFInfo
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- CN101239057A CN101239057A CNA2007100033607A CN200710003360A CN101239057A CN 101239057 A CN101239057 A CN 101239057A CN A2007100033607 A CNA2007100033607 A CN A2007100033607A CN 200710003360 A CN200710003360 A CN 200710003360A CN 101239057 A CN101239057 A CN 101239057A
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Abstract
The invention relates to a new usage of Salvianolic acid B and the salt used in curing parkinsonism, the usages of the medicine combined material of the Salvianolic acid B as well as the salt, and the medicine combined material or each unit being jointly used with other current medicines curing parkinsonism used for curing parkinsonism.
Description
Technical field
The present invention relates to salvianolic acid B and its esters purposes in the treatment parkinson disease.
Background technology
Radix Salviae Miltiorrhizae is the medicine commonly used in China's traditional medicine, the clinical treatment heart, cerebrovascular disease and the associated all kinds of diseases of being mainly used in.Salvianolic acid B is the main effective ingredient of Radix Salviae Miltiorrhizae, and content height, strong drug action have carried out extensive studies to its application in the prior art.
The possible medical usage of known salvianolic acid B comprises:
1, cardiovascular and cerebrovascular disease comprises coronary heart disease, angina pectoris, heart failure, arrhythmia, cerebral infarction, cerebral ischemia etc.See Chinese patent 99112300.X, 02155004.2,200410026913.7,200410048799.8.
2, antitumor.See Chinese patent 02136970.4,200510028311.X.
3, fibrosis disease.See Chinese patent 200410067903.8,200510115662.4.
4, anti-peptic ulcer.See Chinese patent 02144771.3.
5, antiviral.See Chinese patent 01110378.7.
6, anti-senile dementia.See Chinese patent 200610035481.5.
In ZL02160771.0, ZL03151476.6 patent, provide the process of from Radix Salviae Miltiorrhizae, extracting salvianolic acid B.
Parkinson disease are to serve as the central nervous system degenerative disease of main performance with carrying out property dyskinesia, and present medicine mainly comprises Dopaminergics preparation, dopamine-receptor stimulant or promotes dopamine to discharge, suppress the medicine of its degraded.These medicines still can not reach desirable therapeutic because side effect or use are inconvenient, seek and develop new treatment or prevent Parkinsonian medicine to have important social and economic benefit.
Summary of the invention
The object of the present invention is to provide salvianolic acid B and its esters new purposes in the Parkinsonian medicine of preparation treatment.
This laboratory process is to the various monomeric repeated screenings of Radix Salviae Miltiorrhizae, and the checking repeatedly by cell, animal level, the proof salvianolic acid B can suppress the SH-SY5Y cell viability forfeiture that never poison 6-hydroxy dopamine causes, and can suppress the reduction of parkinson rat model striatum DOPAMINE CONTENT IN RABBIT, thereby finished the present invention.
" salvianolic acid B " described in the present invention comprises salvianolic acid B and salvianolic acid B salt.Salvianolic acid B can be the monomeric compound that extracts in the plant, also can be the salvianolic acid B of chemosynthesis, can also be the extract that contains salvianolic acid B.
Salvianolic acid B salt mainly refers to water soluble salt, and its cation can be alkali metal or alkaline-earth metal, as sodium, potassium, magnesium etc., is preferably magnesium ion.
Salvianolic acid B can be prepared into various pharmaceutical compositions by means known in the art with pharmaceutically acceptable carrier, as tablet, capsule, granule, injection etc.; Or and the combination of other Chinese medicine monomer make various dosage form, be used for the parkinson disease treatment by different route of administration.
The present invention has the following advantages:
1, found the new medical application of salvianolic acid B.
2, salvianolic acid B is as the known extract of conventional Chinese medicine Radix Salviae Miltiorrhizae, and the source is wide, and raw material is easy to get, and safety is big, and prospect in medicine is wide.
3, salvianolic acid B also has and pretends usefulness improving brain blood flow, neuroprotective cell, and these characteristics help Parkinsonian treatment, improve patient's life quality.
Description of drawings
Fig. 1 salvianolic acid B is to the value-added influence of SH-SY5Y cell
The protective effect that the SH-SY5Y cell viability that Fig. 2 salvianolic acid B causes never poison 6-hydroxy dopamine is lost
The specific embodiment
Below set forth in the external and body of medicine salvianolic acid B of the present invention neuroprotective by following examples and estimate, but be not limited to following approach.Mainly comprise in these biotic experimenies: 1. chemical compound salvianolic acid B cytotoxicity detects; 2. the influence of chemical compound salvianolic acid B SH-SY5Y cell viability forfeiture that 6-hydroxy dopamine (6-OHDA) is caused; 3. the chemical compound salvianolic acid B is to the detection of parkinson rat model striatum DOPAMINE CONTENT IN RABBIT influence.
[embodiment one] salvianolic acid B cytotoxicity detects
Materials and methods
1.SH-SY5Y cell culture
The SH-SY5Y cell is cultivated in 37 ℃, 5%CO2 incubator in the DMEM culture medium that contains 10% hyclone (Gibco) and 100IU/ml penicillin, 100g/ml streptomycin.The observation of cell growth conditions is good, is cultured to the logarithmic growth after date, with SH-SY5Y cell inoculation 96 orifice plates, and 2 * 105 cells/well, 37 ℃, 5%CO2 was hatched 24 hours, after waiting to grow to 80 ~ 90% cells and converging, carried out the administration experiment.
2. salvianolic acid B is to the value-added influence of SH-SY5Y cell
The SH-SY5Y cell is cultivated in 37 ℃, 5%CO2 incubator in the DMEM culture medium that contains 10% hyclone (Gibco) and 100IU/ml penicillin, 100g/ml.The observation of cell growth conditions is good, is cultured to the logarithmic growth after date, with SH-SY5Y cell inoculation 96 orifice plates, 2 * 105 cells/well, 37 ℃, 5%CO2 was hatched 24 hours, after waiting to grow to 80 ~ 90% cells and converging, the chemical compound salvianolic acid B is distinguished administration with final concentration 0.1 μ M/L, 1 μ M/L, 10 μ M/L, 100 μ M/L, no drug cell contrast and blank are established, 37 ℃ simultaneously in every concentration 3 holes, 5%CO2 cultivates, observed result after 24 hours.It is the MTT of 500 μ g/ml that every hole adds final concentration, 37 ℃ of lucifuges, and 5%CO2 cultivated 3 hours, and (VICTORTM Wallac 1420 Multilabel Counter, TurKu Finland) go up the mensuration 570nm light absorption value A of place at multiple labeling inspection enzyme-linked immunosorbent assay instrument.Simultaneously in inverted microscope following every day of observation of cell form.
3. the processing of salvianolic acid B exercising result and statistics
Salvianolic acid B is represented with the percentage ratio that different group absorbances do not have the drug cell matched group relatively the influence of SH-SY5Y cell proliferation:
=(A570 administration-A570 blank)/(A570 contrast---A570 blank) * 100
The result carries out statistical analysis with Origin Pro 7.5, compares with no medicine matched group: *, P＜0.05; *, P＜0.01.
The result
The chemical compound salvianolic acid B is that every day is the observation of cell form under inverted microscope in 6 concentration treatment S H-SY5Y cell processes of Concentraton gradient with 2 times of dilutions, and dosing group cellular morphology and cellular control unit form do not have obvious variation.Test independent triplicate, the MTT testing result is seen Fig. 1.Salvianolic acid B does not all have toxicity at 2.5 ~ 40mol pair cell.
The influence that the SH-SY5Y cell viability that [embodiment two] salvianolic acid B causes 6-hydroxy dopamine (6-OHDA) is lost
Materials and methods
1.SH-SY5Y cell culture
Method is seen embodiment one
2. salvianolic acid B causes the detection of SH-SY5Y cell viability forfeiture influence to 6-hydroxy dopamine (6-OHDA)
The SH-SY5Y cell is cultivated in 37 ℃, 5%CO2 incubator in the DMEM culture medium that contains 10% hyclone (Gibco) and 100IU/ml penicillin, 100g/ml.The observation of cell growth conditions is good, be cultured to the logarithmic growth after date, with SH-SY5Y cell inoculation 96 orifice plates, 2 * 105 cells/well, 37 ℃, 5%CO2 was hatched 24 hours, after waiting to grow to 80 ~ 90% cells and converging, wherein one group with the chemical compound salvianolic acid B with final concentration 2.5 μ M/L, 5 μ M/L, 10 μ M/L administration respectively, every concentration 3 holes give 6-hydroxy dopamine (final concentration is 100mol/L) then; Other one group with the chemical compound salvianolic acid B with final concentration 2.5 μ M/L, 5 μ M/L, 10 μ M/L administration respectively, every concentration 3 holes, cultivate after 3 hours, it is inferior to give a baby a bath on the third day after its birth with serum-free DMEM culture medium, give 6-hydroxy dopamine (final concentration is 100mol/L) then, establish no drug cell contrast and blank simultaneously, 37 ℃, 5%CO2 cultivates, observed result after 24 hours.It is the MTT of 500 μ g/ml that every hole adds final concentration, 37 ℃ of lucifuges, and 5%CO2 cultivated 3 hours, and (VICTORTM Wallac 1420 MultilabelCounter, TurKu Finland) go up the mensuration 570nm light absorption value A of place at multiple labeling inspection enzyme-linked immunosorbent assay instrument.Simultaneously in inverted microscope following every day of observation of cell form.
3. the processing of salvianolic acid B exercising result and statistics
Salvianolic acid B causes the influence of SH-SY5Y cell viability forfeiture to be represented with the percentage ratio that different group absorbances do not have the drug cell matched group relatively to the 6-hydroxy dopamine:
=(A570 administration-A570 blank)/(A570 contrast---A570 blank) * 100
The result carries out statistical analysis with Origin Pro 7.5, compares with no medicine matched group :+, P＜0.05; ++, P＜0.01; Compare with 6-hydroxy dopamine group: *, P＜0.05; *, P＜0.01.
The result
Test independent triplicate, the MTT testing result is seen Fig. 2.Salvianolic acid B causes the forfeiture of SH-SY5Y cell viability to be dose-dependent inhibitory action to the 6-hydroxy dopamine.The protective effect of salvianolic acid B mainly occurs in the born of the same parents.
[embodiment three] salvianolic acid B is to the detection of PD rat model model striatum DOPAMINE CONTENT IN RABBIT influence
Materials and methods
1.SD rat is cultivated
Select 40 of healthy adult SD male rats for use, between body constitution amount 200 ~ 300g, provide by Military Medical Science Institute zoopery center.25 ℃ of rat feeding ambient temperatures.
2. salvianolic acid B is to the detection of PD rat model model striatum DOPAMINE CONTENT IN RABBIT influence
The parkinson rat model is made: the micro-6-OHDA method of directed injection: with pentobarbital sodium (30mg/kg) the intraperitoneal injection of anesthesia rat of 3% (ω), rat head is fixed on the brain solid positioner, the front and back fontanel is equal, exposes skull, the cleaning surface of bone.Determine that with reference to Paxinos and Watson Mus brain stereotaxic atlas the substantia nigra zona compacta coordinate is 5.3mm behind the bregma, sagittal suture is other to the right opens 2.0mm., and the degree of depth is 7.6mm under meninges.The dental burr punching is injected 6-OHDA and the 0.2mg/ml vitamin C injection that 4 μ L mass concentrations are 2 μ g/ μ L with 10 μ L microsyringes, injects speed 1 μ L/min, injection Bi Liuzhen 5min, gelfoam hemostasis, skin suture are inserted in the slowly withdraw of the needle, drill hole.Continuous lumbar injection penicillin 1,000,000 U/ of postoperative (kgd-1) 3d infects with control.Sham-operated control group is then injected Isodose (4 μ L) 0.2mg/ml vitamin C injection in substantia nigra zona compacta.
Animal grouping and processing: therapeutic medication experiment: in 40 rats, select for use 8 to be matched group (irritating stomach equal-volume normal saline).Cause Parkinson disease model, all modeling successes with all the other 32.Be divided into 4 groups at random, every group 8: salvianolic acid B high-dose therapy group (press 100mg/kg dosage and irritate stomach salvianolic acid B solution), dosage treatment group in the salvianolic acid B (press 30mg/kg dosage and irritate stomach salvianolic acid B solution), salvianolic acid B low dose therapy group (press 10mg/kg dosage and irritate stomach salvianolic acid B solution), model group (irritating stomach equal-volume normal saline).Administration 1 time/day, continuous 14 days.
The circling behavior observation index: circling behavior detects, and lumbar injection apomorphine 0.5mg/kg (0.5g/L Sigma) brings out rat and produces to anticlockwise, after the record apomorphine injects, and the rotating cycle in the 30min.Constant turning left, revolution 〉=210r/30min is decided to be the parkinson model of success.
The striatum DOPAMINE CONTENT IN RABBIT detects: therapeutic administration group breaks end each group rat after 14 days in administration, take out brain rapidly, on ice pan, separate the bilateral striatum,-70 ℃ of preservations, analytical balance claims weight in wet base, press the sucrose solution that 100l/10mg adds 0.32mol/L, make homogenate, add equivalent 0.4mol/L perchloric acid solution, behind the vibration mixing,, get supernatant and place-50 ℃ of refrigerators to take out vacuum after 24 hours and drain with the centrifugal 4min of 12000r/min, add distilled water to the debita spissitudo multiple, adopt the high pressure liquid chromatograph UV-detector to measure dopamine concentration.
3. the processing of salvianolic acid B exercising result and statistics
Influence to rat bilateral striatum DOPAMINE CONTENT IN RABBIT after the administration of PD rat model therapeutic.The result carries out statistical analysis with Origin Pro7.5.
The result
The high pressure liquid chromatograph UV-detector is measured dopamine concentration and be the results are shown in Table 1.The administration of salvianolic acid B therapeutic can dose-dependent inhibition parkinson rat model striatum DOPAMINE CONTENT IN RABBIT reduction.
The administration of table 1 salvianolic acid B therapeutic is to the influence of PD rat model striatum DOPAMINE CONTENT IN RABBIT
Compare *＜0.05, * *＜0.01 with model group; Compare with matched group ++＜0.01
Claims (6)
1. the Parkinsonian pharmaceutical composition of treatment contains medicinal carrier, and be characterized as: its active component is salvianolic acid B and salt thereof.
2. according to the pharmaceutical composition of claim 1, it is characterized by: in the salvianolic acid B salt, cation is selected from alkali metal or alkaline-earth metal.
3. according to the pharmaceutical composition of claim 2, it is characterized by: in the salvianolic acid B salt, cation is selected from potassium ion, sodium ion, calcium ion or magnesium ion.
4. according to the pharmaceutical composition of claim 3, it is characterized by: in the salvianolic acid B salt, cation is selected from magnesium ion.
5. the described pharmaceutical composition of claim 1, wherein said pharmaceutical composition can be formulated into tablet, capsule or injection.
6. salvianolic acid B and salt thereof the application in the Parkinsonian medicine of preparation treatment.
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| Application Number | Priority Date | Filing Date | Title |
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| CNA2007100033607A CN101239057A (en) | 2007-02-06 | 2007-02-06 | Use of salvianolic acid B and its salt in treating parkinson's disease |
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| CNA2007100033607A CN101239057A (en) | 2007-02-06 | 2007-02-06 | Use of salvianolic acid B and its salt in treating parkinson's disease |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103054847A (en) * | 2013-01-04 | 2013-04-24 | 中国药科大学 | Application of salvianolic acid B as catechol-O-methyltransferase inhibitor in treating Parkinson's disease |
| CN106317000A (en) * | 2015-07-06 | 2017-01-11 | 天津天士力之骄药业有限公司 | Salvianolic acid compound as well as preparation method and application thereof |
| JP2018505845A (en) * | 2014-11-14 | 2018-03-01 | ユナイテッド アラブ エミレーツ ユニバーシティＵｎｉｔｅｄ Ａｒａｂ Ｅｍｉｒａｔｅｓ Ｕｎｉｖｅｒｓｉｔｙ | Compounds for contrast agents |
-
2007
- 2007-02-06 CN CNA2007100033607A patent/CN101239057A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103054847A (en) * | 2013-01-04 | 2013-04-24 | 中国药科大学 | Application of salvianolic acid B as catechol-O-methyltransferase inhibitor in treating Parkinson's disease |
| JP2018505845A (en) * | 2014-11-14 | 2018-03-01 | ユナイテッド アラブ エミレーツ ユニバーシティＵｎｉｔｅｄ Ａｒａｂ Ｅｍｉｒａｔｅｓ Ｕｎｉｖｅｒｓｉｔｙ | Compounds for contrast agents |
| EP3218721A4 (en) * | 2014-11-14 | 2018-11-21 | United Arab Emirates University | Compounds for use as imaging agents |
| US10488417B2 (en) | 2014-11-14 | 2019-11-26 | United Arab Emirates University | Compounds for use as imaging agents |
| EP3961216A1 (en) * | 2014-11-14 | 2022-03-02 | United Arab Emirates University | Compounds for use as imaging agents |
| CN106317000A (en) * | 2015-07-06 | 2017-01-11 | 天津天士力之骄药业有限公司 | Salvianolic acid compound as well as preparation method and application thereof |
| CN106317000B (en) * | 2015-07-06 | 2021-02-26 | 天津天士力之骄药业有限公司 | Salvianolic acid compound, preparation method and application thereof |
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Open date: 20080813 |