CN1378837A - Application of danshinolic acid compounds in preparing medicines - Google Patents
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- CN1378837A CN1378837A CN 01110378 CN01110378A CN1378837A CN 1378837 A CN1378837 A CN 1378837A CN 01110378 CN01110378 CN 01110378 CN 01110378 A CN01110378 A CN 01110378A CN 1378837 A CN1378837 A CN 1378837A
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Abstract
The tan shinolic acid compound can be used to prepare medicines for resisting thrombus, thrombocyte coagulation, neurocyte wither and HIV infection. Its advantages are strong pharmacological action, and high safety.
Description
The present invention relates to the application of danshinolic acid chemical combination in pharmacy.
Danshinolic acid compounds is extraction separation from the conventional Chinese medicine Radix Salviae Miltiorrhizae, and this compounds is water-soluble.The structure of Radix Salviae Miltiorrhizae and congener class pressure differential self is:
4:R
1=Y; R
2=CH
2COOH; R
3=H 6:R
1=Y; R
2=R
3=H14:R
1=Y; R
2=H; R
3=Gluc.
Multiple red sage formulation with the modern technologies development can be used for treating coronary heart disease, chronic hepatic and renal function disease, infectious disease, cutaneous diseases, hematopathy, type ii diabetes etc.; Report in the prior art that danshinolic acid compounds has effects such as the anti-heart, cerebral ischemia effect and inhibition animal cataract, and oneself is widely used in clinical.
The object of the present invention is to provide danshinolic acid compounds, particularly the new purposes of Radix Salviae Miltiorrhizae total salvianolic acid (SAS) and salvianolic acid A wherein (SalA), salvianolic acid B (SalB), i.e. new application in pharmacy.
In order to finish the present invention's goal of the invention, in fact, the present invention relates to the application of Radix Salviae Miltiorrhizae total salvianolic acid (SAS) in preparation antithrombotic class medicine;
The invention still further relates to the application of Radix Salviae Miltiorrhizae total salvianolic acid (SAS) in the preparation medicament for resisting platelet aggregation;
The invention still further relates to the application of danshinolic acid compounds in the anti-neuronal apoptosis medicine of preparation;
The invention still further relates to the application in preparation inhibition mammal HIV (human immunodeficiency virus) SIVmac infection class medicine of salvianolic acid A (SalA), salvianolic acid B (SalB) and synthesis of derivatives thereof.The concentration of salvianolic acid A during application (SalA) or salvianolic acid B (SalB) and synthesis of derivatives thereof should be (10
-6-10
-9Mol/L) between.
Material of the present invention can adopt the method for following bibliographical information to obtain:
：
1. ma Li Lian, Tan Rui, Chen Weiming " salvianolic acid A, a kind of new depside chemical compound that from the Chinese medicine red sage root, extracts ", " medicinal plants " 1984; 50:227-228.
2. Liu Yu, Zhang Juntian " free radical scavenging effect " " Chinese Pharmaceutical Journal " 1994 of salvianolic acid; 3 (1): 43-49.
Through studies show that, the salvianolic acid particularly antioxidation of salvianolic acid A and B obviously is better than VITE, VITC, mannitol and Semen Ginkgo extrac (Egb761), is the strongest natural component of present known antioxidation.
Can be prepared into various medicaments with salvianolic acid of the present invention and pharmaceutically acceptable carrier, it can be injectable powder, liquid oral liquid etc., adopts the conventional medicine preparation method can make above-mentioned medicament.
Experimental result shows that the present invention has the following advantages:
1. the present invention has excavated new medical application to known danshinolic acid compounds, has opened up a new application;
2. be the known natural separation and Extraction thing of conventional Chinese medicine Radix Salviae Miltiorrhizae, the product of extract owing to danshinolic acid compounds used in the present invention, so safety non-toxic, pharmacological action is strong, and good prospect in medicine is arranged;
3. material extractive technique maturation of the present invention, raw material sources are extensive, have no side effect, no special preparation technological requirement, preparation technology is simple;
4. the medicine made from material of the present invention has significant antithrombotic, anti-platelet aggregation effect, and safe and reliable, noly hemorrhagely waits dangerously, and the blood flow of ischemia cortex is also improved significantly;
5. the medicine made from low concentration material of the present invention has the obvious suppression effect to the mammal HIV (human immunodeficiency virus);
6. the medicine made from material of the present invention has good anti-neuronal apoptosis effect, and mitochondrial injury is had significant protective effect.
When using medicine of the present invention, the suggestion consumption is 50～150mg/ man day, and preferable amount is the 100mg/ man day.
In order to understand essence of the present invention better, will use the The pharmacological results of Radix Salviae Miltiorrhizae total salvianolic acid (SAS), salvianolic acid A, phenolic acid B and synthesis of derivatives thereof and relevant pharmacology result's accompanying drawing respectively below, its new purposes in pharmaceutical field is described.
Brief Description Of Drawings:
Fig. 1 is among the embodiment 1, and 8 groups of subjects rats are behind the medicine of, various dose not of the same race by injecting, and medicine is to the action diagram of its cerebral thrombosis, i.e. pathologic finding figure; Wherein A:Sham organizes, B: model group, C Sal 3 mg/kg, D:Sal 6 mg/kg, E:Sal 10 mg/kg, F:FD 50 mg/kg, G:FD 200 mg/kg, H:FD 2000mg/kg.
Fig. 2 Hut-78 cell infection positive rate that to be SalA, SalB and SalAA cause simian acquired immunodeficiency syndrome poison SIVmac in vitro influence the result, among the figure zero---zero represents Sal A; ●---● represent Sal B; △---△ represents Sal AA; ▲---▲: contrast;
*,
*With
* *Represent p＜0.05 respectively, p＜0.01 and p＜0.001 (n=4)
Fig. 3 is Sal A, SalB and Sal AA to the result that influences of the generation of virus in the Hut-78 cell conditioned medium liquid of taint with SIV mac, wherein
*,
*With
* *Represent PC0.05 and 0.01 (n=4) respectively;
Fig. 4 suppresses the design sketch of the influence of the PC12-Bax cell line cell apoptosis number that 6-OHDA causes, wherein A for SalB: normal; B: solvent; When handling, C, D6-OHDA add SalB0.1 and 1.0mg/mml.
The test of antithrombotic pharmacology and the result of embodiment 1 Radix Salviae Miltiorrhizae total salvianolic acid
The Wista rat, body weight 240-260 gram, totally 64, after 12% chloral hydrate anesthesia, open one 1cm * 1cm bone window in basis cranii, expose one section middle cerebral artery, suction is had the small pieces quantitative filter paper of 50% liquor ferri trichloridi 10ul, and (2 * 2cm) apply in this section middle cerebral artery, take off filter paper after 30 minutes, use the normal saline flushing local organization, layer-by-layer suture steams again and raises, and the postoperative room temperature is strict controlled in 24-25 ℃ in the art, be administered once by sublingual vein in 30 minutes in postoperative, judge neural disappearance symptom after 24 hours, broken end is got brain then, measures cerebral infarct size and carries out pathological examination to understand thrombosis situation in the blood vessel.
More than test divides 8 groups, i.e. A: sham operated rats; B: model group; C:Sal 3mg/kg group; The D:Sal6mg/kg group; E:Sal 10mg/kg group; F:FD 50mg/kg group; G:FD 200mg/kg group; H:FD2000mg/kg group, concrete administration kind, dosage and experimental result of each group see Table 1, table 2 and pathological examination results are seen Fig. 2.
Table 1: salvianolic acid is to the influence of the rat nervous symptoms of rat medium-sized artery thrombosis model (n=8, X ± s)
Compare with model group:
*P＜0.01,
* *P＜0.001 table 2: salvianolic acid is to the influence of the rat cerebral infarction area of middle cerebral artery thrombus model (n=8, X ± s)
Compare with model group:
*P＜0.01,
* *P＜0.001
| Group | Dosage (mg/kg) | The nervous symptoms scoring |
| Sham operated rats | ?2.25±1.28 *** | |
| Model group | ?8.50±1.20 | |
| Salvianolic acid | ?3 | ?7.88±1.13 |
| ?6 | ?6.638±1.06 ** | |
| ?10 | ?4.38±0.92 *** | |
| FUFANG DANSHEN ZHUSHEYE | ?50 | ?8.38±0.92 |
| ?200 | ?8.25±1.04 | |
| ?2000 | ?8.38±1.06 |
| Group | Dosage (mg/kg) | The nervous symptoms scoring |
| Sham operated rats | ?0 *** | |
| Model group | ?13.05±1.16 | |
| Salvianolic acid | 3 | ?11.96±0.99 |
| 6 | ?7.95±1.10 ** | |
| 10 | ?4.93±0.64 *** | |
| FUFANG DANSHEN ZHUSHEYE | 50 | ?12.45±0.73 |
| 200 | ?11.90±1.16 | |
| 2000 | ?12.16±1.21 |
30 minutes iv observe in postoperative, and two groups of rats can finding to inject total salvianolic acid 6,10mg/kg obviously dwindle cerebral infarct size and improve behavior disorder; In the cerebral tissue PATHOMORPHOLOGICAL OBSERVATION OF PULLORUM, thrombosis reduces in the two treated animal middle cerebral arterys of injection salvianolic acid 6,10mg/kg, and three groups of all not demonstration effects of injection FUFANG DANSHEN ZHUSHEYE 50,200 and 2000mg/kg.Result of the test shows that Radix Salviae Miltiorrhizae total salvianolic acid injection has tangible anti thrombotic action.
Embodiment 2:
Embodiment 2 is the pharmacological testing of Radix Salviae Miltiorrhizae total salvianolic acid to the blood coagulation system function effect.
Kunming mouse is divided into 6 groups, difference tail vein injection saline, FUFANG DANSHEN ZHUSHEYE 200mg/kg, 2000mg/kg, total salvianolic acid 3mg/kg, 6mg/kg, 10mg/kg, after half an hour mice is got blood with plucking the eyeball method, the back of bleeding is carried on the sheet glass and is surveyed clotting time, and all the other blood are with 3.8% sodium citrate anticoagulant, measure platelet count, thrombinogen and Fibrinogen.
Show to the result of the test shown in 6 that as table 3 total salvianolic acid has obvious antithrombotic and antiplatelet aggregative activity, but the These parameters of blood coagulation system is not all had influence, it is very safe to illustrate that total salvianolic acid is used for antithrombotic, antiplatelet aggregation, the no hemorrhage danger that waits.
Table 3: the intravenous injection salvianolic acid is to the influence (n=10) of clotting time of mice
Table 4: the intravenous injection total salvianolic acid is to the influence (n=5) of mouse platelets counting
| Dosage (mg/kg) | Clotting time (second ± SD) | ????P | |
| Contrast | ????73.4±40.2 | ||
| FUFANG DANSHEN ZHUSHEYE | ????200 | ????50.3±17 | ????＞0.005 |
| ????2000 | ????48.3±13.7 | ????＞0.005 | |
| Red acid acid | ????3 | ????65.8±33.6 | ????＞0.005 |
| ????6 | ????76.2±30.6 | ????＞0.005 | |
| ????10 | ????71.1±30.4???? | ????＞0.005 |
| Dosage (mg/kg) | Platelet (109/L ± SD) | ????P | |
| Contrast | ????562±142 | ||
| FUFANG DANSHEN ZHUSHEYE | ????200 | ????469±91 | ????＞0.005 |
| ????2000 | ????422±153 | ????＞0.005 | |
| Salvianolic acid | ????3 | ????453±38 | ????＞0.005 |
| ????6 | ????518±89 | ????＞0.005 | |
| ????10 | ????496±25 | ????＞0.005 |
Table 5: the intravenous injection salvianolic acid is to the influence (n=5) of mice thrombinogen
Table 6: the intravenous injection total salvianolic acid is to the fibrinogenic influence of mice (n=5)
| Dosage (mg/kg) | Former (the s ± SD) of tranamic acid | ????P | |
| Contrast | ????8.3±0.6 | ||
| FUFANG DANSHEN ZHUSHEYE | ????200 | ????8.2±0.6 | ????＞0.05 |
| ????2000 | ????8.1±0.5 | ????＞0.05 | |
| Salvianolic acid | ????3 | ????8.3±0.5 | ????＞0.05 |
| ????6 | ????8.4±1.0 | ????＞0.05 | |
| ????10 | ????8.3±0.6 | ????＞0.05 |
| Dosage (mg/kg) | Fibrinogen (mg/dl ± SD) | ????P | |
| Contrast | ????88±19.4 | ??＞0.05 | |
| FUFANG DANSHEN ZHUSHEYE | ????200 | ||
| ????2000 | ????80.2±17.7 | ??＞0.05 | |
| Salvianolic acid | ????3 | ????91±14.4 | ??＞0.05 |
| ????6 | ????87±20 | ??＞0.05 | |
| ????10 | ????98.2±7.8 | ??＞0.05 |
Embodiment 3:
Embodiment 3 is the pharmacological testing of Radix Salviae Miltiorrhizae total salvianolic acid anti-platelet aggregation effect.
Adopt external and the interior experiment of body, studied the influence of total salvianolic acid collagen, ADP and arachidonic acid (AA) induced platelet aggregation capability.Treated in vitro test: with 1% silicone oil silication stirring rod, test tube, centrifuge tube etc.
External test tube result of the test sees Table 7, salvianolic acid is concentration 0.123,0.164 in vitro, 0.205,0.256, five groups of 0.320mg/ml all can effectively suppress collagen A DP and the inductive platelet aggregation of AA, FUFANG DANSHEN ZHUSHEYE 12.5,25.0,50.0mg/ml also have the platelet aggregation effect of pressing down.
Vivo medicine-feeding test: Kunming mouse is divided into 6 groups, adopt the method for inspection identical with embodiment 3, each the group administration kind and dosage and the results are shown in Table 8, from the result of table 8 as can be seen, two groups of total salvianolic acid 6,10mg/kg can be suppressed glue unit inductive platelet aggregation (P＜0.01) fully, one group of total salvianolic acid 10mg/kg can significantly be suppressed the inductive platelet aggregation of ADP, and FUFANG DANSHEN ZHUSHEYE 200mg/kg and 2g/kg two groups are to collagen and the inductive platelet aggregation unrestraint of ADP effect.Pharmacological tests shows that the Radix Salviae Miltiorrhizae total salvianolic acid has good anti-platelet aggregation effect.
Table 7: the salvianolic acid treated in vitro to the influence of platelet aggregation (X ± S, N=3-4)
| Group | Dosage mg/m l | Aggregation rate (%) collagen ▲ | Dosage mg/m l | Aggregation rate (%) ADP ▲▲ | Dosage mg/ ml | Aggregation rate (%) AA ▲▲ |
| Matched group | ??NS | ?61.0±2.2 | ??NS | ????66.0±1.6 | ??NS | ????77.0±5.0 |
| Salvianolic acid | ??0.092 | ?56.7±5.5 | ??0.54 | ????62.0±2.8 | ??0.84 | ????85.0±4.0 |
| Salvianolic acid | ??0.123 | ?51.3±2.1 ** | ??0.78 | ????56.3± ????????0.6 *** | ??1.20 | ????77.0±2.0 |
| Salvianolic acid | ??0.164 | ?47.3±6.7 * | ??1.11 | ????55.5± ????????2.9 *** | ??1.72 | ????67.0±1.0 |
| Salvianolic acid | ??0.205 | ?36.7±7.0 ** | ??1.59 | ????50.3± ????????1.9 *** | ??2.45 | ????53.3±3.8 *** |
| Salvianolic acid | ??0.256 | ?28.3± ??9.3 *** | ??2.27 | ????38.3± ????????9.0 *** | ??3.50 | ????37.8±4.9 *** |
| Salvianolic acid | ??0.320 | ?0±0 *** | ??3.27 | ????13.5± ????????5.0 *** | ??5.00 | ????21.3±3.9 *** |
| Compound Salviae Miltiorrhizae | ??12.5 | ?54.3±2.5 * | ??27.0 | ????62.0±1.4 * | ??50.0 | ????76.0±5.1 |
| Compound Salviae Miltiorrhizae | ??25.0 | ?41.5± ??3.5 *** | ??54.0 | ????54.7±5.9 * | ??100 | ????61.0±1.7 ** |
| Compound Salviae Miltiorrhizae | ??50.0 | ?0±0 *** | ??108.0 | ????40.7± ????????6.7 *** |
*P＜0.05,
*P＜0.01,
* *P＜0.001 VS, matched group
▲N=3
▲ ▲N=4 (number of animals) compound Salviae Miltiorrhizae; FUFANG DANSHEN ZHUSHEYE.
Table 8: the salvianolic acid vivo medicine-feeding to the influence of collagen and the inductive platelet aggregation of ADP (X ± S, n=8)
| Group | Dosage (mg/kg) | Concentration class (%) | |
| Collagen | ????ADP | ||
| Matched group | ????NS | ????57.8±5.0 | ????63.2±5.1 |
| Salvianolic acid | ????3 | ????56.1±3.1 | ????60.6±5.7 |
| Salvianolic acid | ????6 | ????0±0 *** | ????59.3±4.8 |
| Salvianolic acid | ????10 | ????0±0 **** | ????47.4±5.9 *** |
| FUFANG DANSHEN ZHUSHEYE | ????200 | ????61.4±3.8 | ????65.1±5.5 |
| FUFANG DANSHEN ZHUSHEYE | ????2000 | ????55.8±12.4 | ????61.3±8.5 |
* *P＜0.001 VS. matched group
Embodiment 4
Embodiment 4 is pharmacological testing and the result of Radix Salviae Miltiorrhizae total salvianolic acid to the improvement effect of ischemia cortex blood flow.
The Wista rat, male and female half and half, body weight 180-200 gram with 25% urethane ip anesthesia, cuts neck center skin, separates right carotid artery, sunkens cord under tremulous pulse and beats slip-knot, prepares against ligation.Skin is made the long otch of a 1.5cm behind the eye socket of right side, peel off and excise cervical muscle, expose the temporo squamosum, open the bone window of a 1.5cm, expose the middle cerebral artery trunk at temporo squamosum seam crossing, in order to closing with fixed attention, cut calvarium skin 1mm behind calvarium bregma center, right side, the side is opened the 2mm place and is opened a 2.5cm bone window, in order to inserting measurement electrode, skin behind the separation neck is in order to inserting reference electrode.Experiment is divided into 7 groups, it is respectively sham operated rats, model group, FUFANG DANSHEN ZHUSHEYE 0.2g/kg, 2g/kg, salvianolic acid 3mg/kg, 6mg/kg and 10mg/kg, rat is fixed in stereotaxic instrument, reference electrode places cervical region subcutaneous, measurement electrode places 0.8mn under the cortex by the parietal bone window, measures normal blood flow, then with the rat carotid artery ligation, and middle cerebral artery closed with fixed attention, sublingual vein administration after 30 minutes is respectively at 15 minutes and 30 minutes mensuration blood flows after the administration, in addition, get normal mice and measure the influence of cortex blood flow and salvianolic acid normal blood flow by last method, the results are shown in table 9, the result shows that ischemic region cortex blood flow obviously reduced after one-sided middle cerebral artery coagulated closed and one-sided common carotid artery ligation.Salvianolic acid 6mg/kg and 10mg/kg group cortex blood flow obviously recover (p＜0.05), but salvianolic acid does not have influence to normal mice cortex blood flow, illustrates that salvianolic acid has the effect that improves ischemic region cortex blood flow.
Table 9: the influence of closed and homonymy common carotid artery ligation rat layer blood flow is coagulated in the salvianolic acid intravenous injection to middle cerebral artery
| Group | Number of animals (N) | Drug dose (mg/kg) | Blood flow (%X ± S | ||
| Before the ligation | After the administration 15 minutes | After the administration 30 minutes | |||
| Sham-operation | ????8 | ????NS | ????100 | ??100.8± ????10.1 ** | ??94.0±12.3 ** |
| Model | ????8 | ????NS | ????100 | ??47.9±12.1 | ??44.2±10.6 |
| Salvianolic acid | ????8 | ????3 | ????100 | ??54.4±12.6 | ??56.4±14.9 |
| Salvianolic acid | ????8 | ????6 | ????100 | ??67.1±14.7 * | ??66.8±16.9 |
| Salvianolic acid | ????8 | ????10 | ????100 | ??63.7±10.0 * | ??61.5±14.4 * |
| Compound Salviae Miltiorrhizae | ????6 | ??0.2g/kg | ????100 | ??50.7±13.1 | ??44.7±12.1 |
| Compound Salviae Miltiorrhizae | ????7 | ??2.0g/kg | ????100 | ??51.2±15.1 | ??48.9±16.9 |
Embodiment 5
Embodiment 5 is the pharmacological testing and the result of salvianolic acid A (SalA), B (SalB) and the anti-Rhesus Macacus HIV (human immunodeficiency virus) of SALAA (SalAA) (SIVmac) pathological changes.
Test is the Hut-78 cell that SIVmac infects with virus, and culture supernatant after three weeks is 1600ccID50 (50% a cell infection dosage) with CEMx-174 titration virus titer, and-20 ℃ frozen standby.Salvianolic acid A has been observed in this research, and B and SALAA infect the output that causes Hut-78 positive cell rate and virus to SIV.Low concentration medicine (10
-6-10
-9Mol/L) can obviously suppress the generation of SIVmac virus, the pair cell pathological changes is improved also certain effect, opposite drug level too high (3 * 10
-6-10-5
Mol/ L) infection has facilitation, concrete condition accompanying drawing 3 and accompanying drawing 4 to SIV.
Result of the test shows that salvianolic acid A, salvianolic acid B and SALAA are at low concentration (10
-6-10
-9Mol/L) pathological changes to Rhesus Macacus HIV (human immunodeficiency virus) (SIVmac) time has the obvious suppression effect.
Embodiment 6
Embodiment 6 is Radix Salviae Miltiorrhizae total salvianolic acid (SAS) and salvianolic acid B (SalB) inhibitory action pharmacological testing and the result to neuronal apoptosis.
The pallasiomy bilateral ligation is caused cerebral ischemia, recover the blood confession after 3.5～4 minutes, took out brain to the 3rd day and fix, embedding, section are with the apoptosis number of TUNEL dyeing counting Hippocampus CAI district pyramidal layer 1mm length under 10 * 20 times of light microscopics.
As shown in table 10, used total salvianolic acid (SAS) 5mg/kg and 10mg/kg Rhizoma Atractylodis Macrocephalae respectively preceding 15 minutes and 10 minutes iv of postoperative once, the result shows that the apoptotic suppression ratio that cerebral ischemia reperfusion injury is caused is 24.4～43.6%; Used salvianolic acid B (SalB) 5mg/kg and 10mg/kg Rhizoma Atractylodis Macrocephalae more respectively preceding 15 minutes and 10 minutes iv of postoperative once, the result shows that the apoptotic suppression ratio that cerebral ischemia reperfusion injury is caused is 29.2～44.8%;
The generation of many factor apoptosis involvements and evolution, Bax wherein, C-jun, p
53Deng being important short apoptogene, bcl-2 and P35 etc. is important anti-apoptotic genes expression.Studies show that it is the startup factor of apoptosis to the change of some molecule permeability that Bax causes mitochondrial membrane.For this reason, we have set up the PC12 cell strain of Bax high expressed first, the Western blotting shows that Bax albumen has high-caliber expression, induce Bax α high expressed can cause the PC12 apoptosis with neurotoxin 6-hydroxyl DOPA, as shown in Figure 5, salvianolic acid B 0.1 and 1.0ng.ml can significantly reduce the apoptotic cell rate of the inductive PC12-Bax α of 6-OHDA, make apoptosis rate drop to 19% and 14.8% from 41%.
Result of the test shows that Radix Salviae Miltiorrhizae total salvianolic acid and salvianolic acid B have the obvious suppression effect to neuronal apoptosis.
Table 10:SAS and SalB influence X ± s, n=5 to gerbil jird cerebral ischemia re-pouring Hippocampus CA1 district pyramidal cell apoptosis number
| Group | Dosage (mg/kg) | An apoptosis cell/m-1 | Suppression ratio/% |
| Matched group | ????- | ??151.8±11.9 | ????- |
| ????SAS | ????5，iv | ??114.8±16.7 ** | ????24.4 |
| ????10，iv | ??85.6±13.5 *** | ????43.6 | |
| ????SalB | ????5，ip | ??107.4±13.6 *** | ????29.2 |
Claims (8)
1. the application of Radix Salviae Miltiorrhizae total salvianolic acid (SAS) in preparation antithrombotic class medicine.
2. the application of Radix Salviae Miltiorrhizae total salvianolic acid (SAS) in preparation anti-platelet aggregation class medicine.
3. salvianolic acid A (SalA) or its synthesis of derivatives suppress to use in the mammal HIV (human immunodeficiency virus) infection class medicine in preparation.
4. application as claimed in claim 3 is characterized in that the concentration of salvianolic acid A (SalA) or its synthesis of derivatives should be 10
-6-10
-9Between the mol/L.
5. salvianolic acid B (SalB) or its synthesis of derivatives suppress to use in the mammal HIV (human immunodeficiency virus) infection class medicine in preparation.
6. application as claimed in claim 5 is characterized in that the concentration of salvianolic acid B (SalB) or its synthesis of derivatives should be 10
-6-10
-9Between the mol/L.
7. the application of salvia miltiorrhiza tanshinoate in the anti-neuronal apoptosis class medicine of preparation.
8. application as claimed in claim 7 is characterized in that salvia miltiorrhiza tanshinoate is meant total salvianolic acid (SAS) or salvianolic acid (BalB).
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|---|---|---|---|
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| CN100531750C (en) * | 2006-01-24 | 2009-08-26 | 山东省医学科学院药物研究所 | Use of red sage root extract in preparing antithrombotic pharmaceutical composition |
| WO2010111935A1 (en) * | 2009-03-30 | 2010-10-07 | 天津天士力制药股份有限公司 | New salvianolic acid compound l, preparation method and use thereof |
| CN102210666A (en) * | 2010-04-06 | 2011-10-12 | 山东靶点药物研究有限公司 | Medical use of salvianolic acid A |
| CN103006582A (en) * | 2012-11-20 | 2013-04-03 | 陆文萍 | Salvianolic acid A lyophilized powder injection and application thereof in preparation of drugs |
| CN103083304A (en) * | 2012-11-20 | 2013-05-08 | 蒋春红 | Application of salvianolic acid A composition for preparing medicines for preventing and/or treating cerebral thrombosis |
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| CN103083302A (en) * | 2012-11-20 | 2013-05-08 | 蒋春红 | Application of salvianolic acid A composition in preparing medicines for protecting ischemic brain tissue damage |
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-
2001
- 2001-04-09 CN CN 01110378 patent/CN1378837A/en active Pending
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| CN103083305B (en) * | 2012-11-20 | 2016-04-27 | 江西青峰药业有限公司 | A kind of salvianolic acid A compositions and prepare medicinal usage |
| CN112516131A (en) * | 2020-05-18 | 2021-03-19 | 南方医科大学 | Application of salvianolic acid B or its pharmaceutically acceptable salt in preparing anti-SARS-CoV-2 medicine |
| CN115364086A (en) * | 2021-05-17 | 2022-11-22 | 中国科学院上海药物研究所 | Application of water-soluble phenolic acid compound or salt of salvia miltiorrhiza bunge in preparation of medicine for treating PRDX 1-related diseases |
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