US-12622888-B2 - Pharmaceutical composition and application thereof

Abstract

Provided is a pharmaceutical composition and application thereof, specifically, said pharmaceutical composition comprises: salvianolic acid B as a first active ingredient; and ginsenoside Rg1 as a second active ingredient, and the weight ratio of the first active ingredient to the second active ingredient being 5:(1-4.5). The pharmaceutical composition has a better active-ingredient proportion than the prior art, has a better therapeutic efficacy in preventing and/or treating ischemic diseases, and ischemia-reperfusion tissue or organ damage, and can be used for treating ischemia and/or ischemia-reperfusion damage of different tissues and organs.

Inventors

• Baohong JIANG
• Linlin Wang
• Xiaoyu Wang
• Yao Fu
• Huimiao BIAN
• Rongrong XING

Assignees

• SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES

Dates

Publication Date

20260512

Application Date

20200828

Priority Date

20190829

Claims (19)

1. 1 . A pharmaceutical composition, consisting of: (a) a first active ingredient selected from the group consisting of salvianolic acid B, a stereoisomer thereof, a crystal form thereof, a pharmaceutically acceptable salt, or any combinations thereof; (b) a second active ingredient selected from the group consisting of ginsenoside Rg1, a stereoisomer thereof, a crystal form thereof, a pharmaceutically acceptable salt, or any combinations thereof; and (c) pharmaceutically acceptable carriers; wherein, a weight ratio of the first active ingredient to the second active ingredient is 5: (1.9-3.1), wherein the weight ratio is based on the salvianolic acid B and the ginsenoside Rg1.
2. 2 . The pharmaceutical composition of claim 1 , wherein the weight ratio of the first active ingredient to the second active ingredient is 5:(2-3).
3. 3 . The pharmaceutical composition according to claim 1 , wherein the first active ingredient is the salvianolic acid B and the second active ingredient is the ginsenoside Rg1.
4. 4 . The pharmaceutical composition of claim 1 , wherein a dosage form of the pharmaceutical composition is selected from the group consisting of liquid preparations, solid preparations, gaseous forms, and semi-solid forms.
5. 5 . The pharmaceutical composition of claim 4 , wherein the dosage form is selected from the group consisting of: injections, oral preparations, sublingual preparations, preparations for respiratory administration, preparations for dermal administration, and preparations for mucosal administration.
6. 6 . A combination of active ingredients, wherein the combination of active ingredients consists of: (a) a first active ingredient selected from the group consisting of salvianolic acid B, a stereoisomer thereof, a crystal form thereof, a pharmaceutically acceptable salt, or any combinations thereof; (b) a second active ingredient selected from the group consisting of ginsenoside Rg1, a stereoisomer thereof, a crystal form thereof, a pharmaceutically acceptable salt, or any combinations thereof; wherein, a weight ratio of the first active ingredient to the second active ingredient is 5:(1.9-3.1), wherein the weight ratio is based on the salvianolic acid B and the ginsenoside Rg1.
7. 7 . A kit, wherein the kit consists of: a first pharmaceutical composition, consisting of: (a) a first active ingredient selected from the group consisting of salvianolic acid B, a stereoisomer thereof, a crystalline form thereof, a pharmaceutically acceptable salt, or a combination thereof, and a pharmaceutically acceptable carrier; and a second pharmaceutical composition, consisting of: (b) a second active ingredient selected from the group consisting of ginsenoside Rg1, a stereoisomer thereof, a crystal form thereof, a pharmaceutically acceptable salt, or any combinations thereof; and a pharmaceutically acceptable carrier; wherein, the first pharmaceutical composition and the second pharmaceutical composition are administered in combination and a weight ratio of the first active ingredient to the second active ingredient is 5:(1.9-3.1), wherein the weight ratio is based on the salvianolic acid B and the ginsenoside Rg1.
8. 8 . A method for (i) preventing and/or treating of ischemic diseases; and/or (ii) preventing and/or treating of ischemia-reperfusion injury comprising: administering to a subject in need thereof the pharmaceutical composition according to claim 1 .
9. 9 . The method of claim 8 , wherein the ischemic disease is tissue or organ ischemic injury due to primary lesions of tissues and blood vessels, or at least one ischemic lesions due to secondary causes selected from the group consisting of trauma-induced vascular disconnection, inflammation-induced vascular occlusion, and tumor-induced vascular compression.
10. 10 . The method of claim 9 , wherein the ischemic disease is selected from the group consisting of ischemic heart disease, ischemic stroke, pulmonary embolism, ischemic liver injury, ischemic nephropathy, ischemic nerve injury, and combinations thereof.
11. 11 . The method of claim 10 , wherein the ischemic heart disease comprises coronary heart disease, myocardial infarction, angina, myocardial fibrosis, heart failure, or any combinations thereof.
12. 12 . The method of claim 8 , wherein the ischemia-reperfusion injury is a tissue or organ injury caused by reperfusion.
13. 13 . The method of claim 12 , wherein the tissue or organ is selected from the group consisting of heart, brain, liver, spleen, lung, kidney, muscle, nerve, and combinations thereof.
14. 14 . The method of claim 13 , wherein the tissue or organ injury is at least one injury selected from the group consisting of a reperfusion injury after a surgery and a thrombolytic therapy.
15. 15 . The method of claim 14 , wherein the surgery is selected from the group consisting of: arterial bypass grafting, thrombectomy, percutaneous transluminal coronary angioplasty, cardiac surgery under cardiopulmonary bypass, at least one resuscitation selected from the group consisting of cardiac, pulmonary, and cerebral resuscitation after cardiac arrest, replantation of severed limbs, and organ transplantation.
16. 16 . The pharmaceutical composition of claim 1 , wherein the weight ratio of the first active ingredient to the second active ingredient is 5:2.
17. 17 . The pharmaceutical composition of claim 4 , wherein the dosage form of the pharmaceutical composition is selected from the group consisting of injection liquid, powder injections, capsules, tablets, pills, powders, granules, syrups, oral solutions, and tinctures.
18. 18 . The pharmaceutical composition of claim 5 , wherein the dosage form is injections.
19. 19 . The method of claim 9 , wherein the weight ratio of the first active ingredient to the second active ingredient is 5:2.

Description

TECHNICAL FIELD The present invention relates to the field of medicine and specifically to a pharmaceutical composition and its application in the prevention and/or treatment of diseases such as ischemic diseases and/or ischemia-reperfusion injury. BACKGROUND The blood vessels are responsible for supplying blood to the tissues and organs of the whole body. If blood vessels blocked, the tissues and organs will cause diseases due to insufficient blood supply, especially the heart, brain and other tissues and organs with high demand for blood oxygen supply; with the dredging of microcirculation during shock, the relief of coronary artery spasm, and the establishment and application of the method such as arterial bypass grafting, thrombolytic therapy, percutaneous transluminal coronary angioplasty, cardiac surgery extracorporeal circulation, cardiopulmonary cerebral resuscitation, replantation of severed limbs and organs transplantation, the blood supply of many tissues and organs may restore (i.e. reperfusion) after ischemia. However, those reperfusions after ischemia sometimes not only fail to restore the function of tissues and organs, but also aggravates the dysfunction and structural damage of the tissues and organs. This phenomenon, in which tissue damage is aggravates or even irreversible after blood flow is restored on the basis of ischemia, is called ischemia-reperfusion injury. Chinese Application No. CN2011102229806 discloses a pharmaceutical composition comprising the compound salvianolic acid B and ginsenoside Rg1, which is effective for cardiac ischemia-reperfusion injury. However, the research on the compatibility of the two is not sufficient, and it is necessary to carry out further in-depth research on the compatibility of the two components to provide pharmaceutical compositions with treatment effects on ischemia-reperfusion injury of different tissues and organs. SUMMARY OF INVENTION The purpose of the present invention is to provide a pharmaceutical composition for preventing and/or treating diseases such as tissue, organ ischemia, and ischemia-reperfusion injury. The first aspect of the invention provides a pharmaceutical composition, comprising: (a) a first active ingredient selected from the group consisting of salvianolic acid B, a stereoisomer thereof, a crystal form thereof, a pharmaceutically acceptable salt or ester thereof, an extract containing salvianolic acid B, and combinations thereof;(b) a second active ingredient selected from the group consisting of ginsenoside Rg1, a stereoisomer thereof, a crystal form thereof, a pharmaceutically acceptable salt or ester thereof, an extract containing ginsenoside Rg1, or combinations thereof; and(c) pharmaceutically acceptable carriers;and the weight ratio of the first active ingredient and the second active ingredient is 5:(1-4.5), wherein the weight ratio is calculated by salvianolic acid B and ginsenoside Rg1. In another preferred embodiment, the first active ingredient comprises a purified product of salvianolic acid B or a pharmaceutically acceptable salt thereof. In another preferred embodiment, the purity of salvianolic acid B in the purified product is ≥90%, preferably ≥95%, more preferably ≥98% or 99%, calculated by the total weight of the purified product. In another preferred embodiment, the first active ingredient comprises salvianolic acid extract with a salvianolic acid B content C1 of ≥30wt %, wherein the content C1 is calculated by the weight of salvianolic acid. In another preferred embodiment, the content C1 of salvianolic acid B in the extract is ≥70%, preferably ≥80%, more preferably ≥90% or ≥95%, calculated by the dry weight of the extract. In another preferred embodiment, the second active ingredient comprises a total saponins extract with a ginsenoside Rg1 content C2 of of ≥30wt %, wherein the content C2 is calculated by the weight of the total saponins. In another preferred embodiment, in the extract, the ginsenoside Rg1 content C2 is ≥70%, preferably ≥80%, more preferably ≥90% or ≥95%, calculated by the dry weight of the extract. In another preferred embodiment, the weight ratio of the first active ingredient to the second active ingredient is 5:(1-4.0), preferably 5:(1.2-3.8), more preferably 5:(1.5-3.5). In another preferred embodiment, the weight ratio of the first active ingredient to the second active ingredient is 5:(1.8-3.2), preferably 5:(1.9-3.1), more preferably 5:(2-3), most preferably 5:2. In another preferred embodiment, the first active ingredient is salvianolic acid B and the second active ingredient is ginsenoside Rg1. In another preferred embodiment, the dosage form of the pharmaceutical composition is selected from the group consisting of liquid dosage forms (e.g., solutions, emulsions, suspensions), solid dosage forms (e. g., lyophilized preparations), gaseous dosage forms, and semi-solid dosage forms. In another preferred embodiment, the dosage form is selected from the group consisting of injec