Pharmaceutical Compositions for Combined Treatment of Atherosclerosis

Abstract

This invention belongs to the field of pharmaceutical technology and discloses a pharmaceutical composition for the combined treatment of atherosclerosis. The pharmaceutical composition includes Asp-Ser-Ser-Ser-Gln-Cys-His-Arg, serine, and curcumin. In this invention, an appropriate amount of serine is added during the mixing of the targeting peptide R8 and curcumin, which helps to improve the therapeutic effect of the pharmaceutical composition on atherosclerosis.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a pharmaceutical composition for the combined treatment of atherosclerosis. Background Technology

[0002] Atherosclerosis refers to a condition characterized by thickening, hardening, and decreased elasticity of the arterial walls, with the formation of atherosclerotic plaques in the arterial intima. It is a major cause of coronary heart disease, cerebral infarction, and peripheral vascular disease. Regarding the pathogenesis of this disease, most scholars in recent years support the "endothelial injury response theory," which suggests that various major risk factors for this disease ultimately damage the arterial intima, and the formation of atherosclerotic lesions is the result of an inflammatory-fibroproliferative response of the arteries to intimal damage.

[0003] Damage to the arterial intima can manifest as functional disorder or anatomical injury. In cases of long-term hyperlipidemia, elevated lipoproteins, primarily oxidized low-density lipoprotein (oxLDL) and cholesterol, cause functional damage to the arterial intima, altering the surface characteristics of endothelial cells and leukocytes (monocytes and lymphocytes), and increasing the expression of adhesion factors. Monocytes adhere to endothelial cells in greater numbers and migrate from between endothelial cells into the subintimal region, becoming macrophages. These macrophages engulf oxLDL via scavenger receptors, transforming into foam cells and forming the earliest atherosclerotic lipid streaks. Macrophages can oxidize LDL, forming peroxides and superoxide ions, and can also synthesize and secrete at least six cytokines. Under the influence of these cytokines, fatty streaks evolve into fibrolipoles, and further develop into fibrous plaques.

[0004] When hemodynamic changes occur, such as increased blood pressure, turbulence caused by localized vascular stenosis, and changes in shear stress, the continuity between endothelial cells in the arterial intima is disrupted, causing endothelial cell retraction and exposing the underlying tissue. At this time, platelet-activating factor (PAF) activates platelets in the blood, causing them to adhere to and aggregate on the intima, forming a mural thrombus. Platelets can release many cytokines. These factors enter the arterial wall and also play an important role in promoting smooth muscle cell proliferation in atherosclerotic lesions.

[0005] Atherosclerosis is prevalent in the population, and varying degrees of atherosclerosis can persist for years or even decades without any clinical symptoms. Atherosclerosis commonly affects the aorta, coronary arteries, cerebral arteries, and renal arteries. During its course, atherosclerotic plaques can rupture, thrombosis can form, and blood vessels can become narrowed or blocked, thus impairing blood supply to the affected organs. Under certain circumstances, it can suddenly manifest as myocardial infarction, stroke / TIA, or local tissue ischemia, even becoming life-threatening.

[0006] Patent CN119236120B discloses liposomes for actively targeting atherosclerotic plaques and their application in diagnosis. The carrier material forming the liposomes includes a targeting peptide R8 modified with methoxy polyethylene glycol phospholipid (R8-DSPE-PEG), polypropylene sulfur-polyethylene glycol (PPS-PEG), and cholesterol (CH). The sequence of the targeting peptide R8 is Asp-Ser-Ser-Ser-Gln-Cys-His-Arg. These liposomes can increase the concentration of fluorescent dyes or drugs at the lesion site, exhibiting advantages of low toxicity and high efficiency. The resulting targeted liposomes show good efficacy in the diagnosis of atherosclerosis. However, if the aforementioned targeting peptide R8 is used for the treatment of atherosclerosis, it is difficult to directly target drugs with atherosclerotic therapeutic activity to the lesion site. Further research in this application has found that adding an appropriate amount of serine during the mixing of the targeting peptide R8 and curcumin helps improve the therapeutic effect of the drug composition on atherosclerosis. Summary of the Invention

[0007] This invention provides a pharmaceutical composition for combined treatment of atherosclerosis.

[0008] The present invention adopts the following technical solution:

[0009] In one aspect, the present invention relates to a pharmaceutical composition for combined treatment of atherosclerosis, the pharmaceutical composition comprising Asp-Ser-Ser-Ser-Gln-Cys-His-Arg, serine, and curcumin.

[0010] Furthermore, the weight ratio of Asp-Ser-Ser-Ser-Gln-Cys-His-Arg, serine, and curcumin is (1-2):(1-2):(6-10).

[0011] Furthermore, the weight ratio of Asp-Ser-Ser-Ser-Gln-Cys-His-Arg, serine, and curcumin is 1:1:8.

[0012] Furthermore, the pharmaceutical composition also includes pharmaceutically acceptable excipients.

[0013] Furthermore, the pharmaceutical composition does not contain other active ingredients.

[0014] Furthermore, the pharmaceutical composition is an oral formulation.

[0015] Furthermore, the oral formulation includes liquid formulations, tablets, and capsules.

[0016] Another aspect of the present invention relates to the use of the above-described pharmaceutical composition in the preparation of a medicament for treating atherosclerosis. Preferably, the pharmaceutical composition is used to reduce the impact of atherosclerotic plaques.

[0017] Beneficial effects: In the process of mixing the targeted peptide R8 with curcumin, the present invention adds an appropriate amount of serine, which helps to improve the therapeutic effect of the drug composition on atherosclerosis. Attached Figure Description

[0018] Figure 1 The drug composition for the model group against apoE - / - Photographs showing the effects of plaque buildup on the aortic arch in mice;

[0019] Figure 2 These are experimental photos of the treatment group's drug composition 1;

[0020] Figure 3 These are experimental photos of the treatment group's drug composition group 2;

[0021] Figure 4 These are experimental photos of the control group, drug composition 1.

[0022] Figure 5 These are experimental photos of the control group (Group 2) of the drug composition. Detailed Implementation

[0023] To further understand the present invention, the technical solution of the present invention will be clearly and completely described below with reference to embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0024] Unless otherwise specified, all reagents involved in the embodiments of this invention are commercially available products and can be purchased through commercial channels.

[0025] Example: Preparation of pharmaceutical composition

[0026] Treatment group drug composition 1: 1 part by weight of Asp-Ser-Ser-Ser-Gln-Cys-His-Arg, 1 part by weight of serine and 8 parts by weight of curcumin are dispersed in 100 parts by weight of deionized water and stirred evenly to obtain the drug composition.

[0027] Treatment group drug composition 2: 1 part by weight of Asp-Ser-Ser-Ser-Gln-Cys-His-Arg, 2 parts by weight of serine and 8 parts by weight of curcumin are dispersed in 100 parts by weight of deionized water and stirred evenly to obtain the drug composition.

[0028] Control group drug composition 1: Disperse 1 part by weight of Asp-Ser-Ser-Ser-Gln-Cys-His-Arg and 8 parts by weight of curcumin in 100 parts by weight of deionized water and stir until homogeneous.

[0029] Control group drug composition 2: 1 part by weight of serine and 8 parts by weight of curcumin are dispersed in 100 parts by weight of deionized water and stirred evenly to obtain the drug composition.

[0030] Zoological experiments:

[0031] Laboratory animals:

[0032] Sixty spontaneously atherosclerotic apoE - / - Mice were first given a basic diet and distilled water for one week of acclimatization under the following conditions: 22±1℃, relative humidity 60±10%, and a 12-hour light / dark cycle. After one week of acclimatization, apoE... - / - Mice were fed a high-fat diet (containing 0.25% cholesterol).

[0033] Experimental methods:

[0034] Starting from week 5, mice in each group were administered 1 ml / day of the test sample orally, while the model control group received the same volume of physiological saline by gavage. The administration lasted for 8 weeks. After week 8, the effects of apoE on spontaneous atherosclerosis were observed in each group. - / - The effects of this method on mouse aortic pathology were investigated by performing Oil Red O staining of the aorta and analyzing the percentage of Oil Red O lipid droplets using Image-Pro Plus 6.0 software. The experimental results are as follows: Figures 1-5 As shown in Table 1.

[0035] Table 1: Effects of pharmaceutical compositions on apoE - / - Effect of fatty plaque area in mouse aorta (intracytoplasmic staining, %)

[0036]

[0037] Note: p<0.05, p<0.01 vs. model control group

[0038] The results showed that, due to the presence of curcumin, an active ingredient that can reduce the area of ​​fatty plaques in the aorta, the control group drug composition significantly reduced the area of ​​fatty plaques in the aorta. Compared to the control group drug composition, the treatment group drug composition reduced the area of ​​fatty plaques in the aorta more significantly, especially the treatment group drug composition 1, which showed the greatest reduction in the area of ​​fatty plaques in the aorta. This demonstrates that the drug composition of the present invention, by adding an appropriate amount of serine, significantly improves the therapeutic effect on atherosclerosis.

Claims

1. A pharmaceutical composition for combined treatment of atherosclerosis, characterized in that, The pharmaceutical composition comprises Asp-Ser-Ser-Ser-Gln-Cys-His-Arg, serine, and curcumin; the weight ratio of Asp-Ser-Ser-Ser-Gln-Cys-His-Arg, serine, and curcumin is 1:1:

8.

2. The pharmaceutical composition for combined treatment of atherosclerosis according to claim 1, characterized in that, The pharmaceutical composition also includes pharmaceutically acceptable excipients.

3. The pharmaceutical composition for combined treatment of atherosclerosis according to claim 2, characterized in that, The pharmaceutical composition is an oral preparation.

4. The pharmaceutical composition for combined treatment of atherosclerosis according to claim 3, characterized in that, The oral formulations include liquid formulations, tablets, and capsules.

5. Use of the pharmaceutical composition according to any one of claims 1-4 in the preparation of a medicament for treating atherosclerosis.

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