Pharmaceutical composition for combined treatment of atherosclerosis

Abstract

The invention belongs to the technical field of medicines, and discloses a pharmaceutical composition for combined treatment of atherosclerosis, and the pharmaceutical composition comprises Asp-Ser-Ser-Ser-Gln-Cys-His-Arg, serine and curcumin. In the mixing process of the targeting peptide R8 and curcumin, a proper amount of serine is added, so that the atherosclerosis treatment effect of the pharmaceutical composition is improved.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology, and particularly relates to a pharmaceutical composition for the combined treatment of atherosclerosis. Background Art

[0002] Atherosclerosis refers to a pathological condition characterized by thickening, hardening, and reduced elasticity of the arterial wall, with the formation of atherosclerotic plaques in the arterial intima. It is the main cause of coronary heart disease, cerebral infarction, and peripheral vascular diseases. Regarding the pathogenesis of this disease, in recent years, most scholars support the "endothelial injury response theory", believing that all 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 artery to intimal injury.

[0003] The damage to the arterial intima can be either functional disorder or anatomical injury. In the case of long-term hyperlipidemia, the increased lipoproteins, mainly oxidized modified low-density lipoproteins (oxLDL) and cholesterol, cause functional damage to the arterial intima, changing the surface characteristics of endothelial cells and white blood cells (monocytes and lymphocytes), and increasing the expression of adhesion factors. The number of monocytes adhering to endothelial cells increases and migrates under the intima between endothelial cells to become macrophages, which phagocytize oxLDL through scavenger receptors and transform into foam cells, forming the earliest atherosclerotic lesion, the lipid streak. Macrophages can oxidize LDL, form peroxides and superoxide ions, and can also synthesize and secrete at least 6 cytokines. Under the action of these cytokines, it promotes the evolution of fatty streaks into fibro-fatty lesions and then develops into fibrous plaques.

[0004] In the case of hemodynamic changes, such as increased blood pressure, turbulence and shear stress changes caused by local vascular stenosis, the continuity between endothelial cells of the arterial intima is interrupted, and endothelial cells retract, thus exposing the tissue under the intima. At this time, platelet-activating factor (PAF) activates platelets in the blood, causing them to adhere and aggregate on the intima, forming an adherent thrombus. Platelets can release many cytokines. These factors enter the arterial wall and also play an important role in promoting the proliferation of smooth muscle cells in atherosclerotic lesions.

[0005] Atherosclerosis is prevalent in the population. Atherosclerosis of different degrees can persist for several years or even decades without any clinical symptoms. Atherosclerosis often affects the aorta, coronary arteries, cerebral arteries, and renal arteries. During the course of the disease, atherosclerotic plaque rupture, thrombosis, vascular lumen stenosis or occlusion can occur, thus disrupting the blood supply to the relevant organs. In certain circumstances, it will suddenly occur in different forms such as myocardial infarction, stroke / TIA, and local tissue ischemia, even endangering life.

[0006] The patent with the authorization announcement number CN119236120B discloses a liposome for actively targeting atherosclerotic plaques and its application in diagnosis. The carrier materials for forming the liposome include a targeting peptide R8-modified methoxypolyethylene glycol phospholipid (R8-DSPE-PEG), polypropylene sulfide-polyethylene glycol (PPS-PEG), and cholesterol (CH). The sequence of the targeting peptide R8 is Asp-Ser-Ser-Ser-Gln-Cys-His-Arg. This liposome can increase the enrichment concentration of fluorescent dyes or drugs at the local lesion site, has the advantages of low toxicity and high efficiency, and the obtained targeted liposome has a good effect on the diagnosis of atherosclerosis. However, if the above-mentioned targeting peptide R8 is used for the treatment of atherosclerosis, it is difficult to directly target drugs with atherosclerotic treatment activity to the lesion site. Through further research, it is found in this application that adding an appropriate amount of serine during the mixing process of the targeting peptide R8 and curcumin helps to improve the effect of the drug composition in treating atherosclerosis. Summary of the Invention

[0007] The present invention provides a drug composition for the combined treatment of atherosclerosis.

[0008] The present invention adopts the following technical solutions: On the one hand, the present invention relates to a drug composition for the combined treatment of atherosclerosis, and the drug composition includes Asp-Ser-Ser-Ser-Gln-Cys-His-Arg, serine, and curcumin.

[0009] Further, the weight ratio of Asp-Ser-Ser-Ser-Gln-Cys-His-Arg, serine, and curcumin is (1 - 2):(1 - 2):(6 - 10).

[0010] Further, the weight ratio of Asp-Ser-Ser-Ser-Gln-Cys-His-Arg, serine, and curcumin is 1:1:8.

[0011] Further, the drug composition further includes pharmaceutically acceptable excipients.

[0012] Further, the drug composition does not include other active ingredients.

[0013] Further, the drug composition is an oral preparation.

[0014] Further, the oral preparation includes liquid preparations, tablets, and capsules.

[0015] On the other hand, the present invention relates to the application of the above drug composition in the preparation of a drug for treating atherosclerosis. Preferably, the drug composition is used to reduce the impact of atherosclerotic plaques.

[0016] Beneficial effects: During the mixing process of the targeting peptide R8 and curcumin in the present invention, adding an appropriate amount of serine helps to improve the effect of the pharmaceutical composition in treating atherosclerosis. Description of the drawings

[0017] Figure 1 Photograph of the effect of the pharmaceutical composition of the model group on the aortic arch plaque of apoE - / - mice; Figure 2 Experimental photograph of the first group of the pharmaceutical composition in the treatment group; Figure 3 Experimental photograph of the second group of the pharmaceutical composition in the treatment group; Figure 4 Experimental photograph of the first group of the pharmaceutical composition in the control group; Figure 5 Experimental photograph of the second group of the pharmaceutical composition in the control group. Detailed implementation manners

[0018] To further understand the present invention, the technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts belong to the scope of protection of the present invention.

[0019] Unless otherwise specified, the reagents involved in the embodiments of the present invention are all commercially available products and can be obtained through commercial channels.

[0020] Embodiment: Preparation of the pharmaceutical composition The first pharmaceutical composition in the treatment group: 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 second pharmaceutical composition in the treatment group: 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 first pharmaceutical composition in the control group: 1 part by weight of Asp-Ser-Ser-Ser-Gln-Cys-His-Arg and 8 parts by weight of curcumin are dispersed in 100 parts by weight of deionized water and stirred evenly to obtain; The second pharmaceutical composition in the control group: 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.

[0021] Zoological experiment: Experimental animals: Sixty spontaneous atherosclerotic apoE - / - mice were first freely given a basal diet and distilled water for one week of adaptive feeding. The feeding conditions were: 22 ± 1 °C, relative humidity 60 ± 10%, 12 h light / dark cycle. After 1 week of adaptation, the apoE - / - mice were fed a high-fat diet (containing 0.25% cholesterol).

[0022] Experimental methods: From the 5th week, each group of mice was orally gavaged with 1 ml / d of each test sample, and the model control group was gavaged with the same amount of normal saline. The administration was carried out for 8 weeks. After the administration ended in the 8th week, the effects of each group on the aorta pathology of spontaneous atherosclerotic apoE - / - mice were observed. The aorta was stained with Oil Red O as a whole, and the percentage of the Oil Red O lipid droplet area was analyzed using Image-Pro Plus 6.0 software. The experimental results are as Figures 1-5 shown in Table 1.

[0023] Table 1: Effects of the pharmaceutical composition on the area of fat plaques in the aorta of apoE - / - mice (whole staining, %)

[0024] Note: p < 0.05, p < 0.01 vs the model control group The results showed that due to the active ingredient curcumin that can reduce the area of fat plaques in the aorta, the control group's pharmaceutical composition could significantly reduce the area of fat plaques in the aorta. Compared with the control group's pharmaceutical composition, the treatment group's pharmaceutical composition could more significantly reduce the area of fat plaques in the aorta. In particular, the treatment group's pharmaceutical composition 1 had the largest reduction in the area of fat plaques in the aorta. This indicates that the pharmaceutical composition of the present invention significantly improves the effect of treating atherosclerosis by adding an appropriate amount of serine.

Claims

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

2. The pharmaceutical composition for combined treatment of atherosclerosis according to claim 1, wherein, The weight ratio of Asp-Ser-Ser-Ser-Gln-Cys-His-Arg, serine and curcumin is (1-2):(1-2):(6-10).

3. The pharmaceutical composition for combined treatment of atherosclerosis according to claim 1, characterized in that, The weight ratio of Asp-Ser-Ser-Ser-Gln-Cys-His-Arg, serine and curcumin is 1:1:

8.

4. The pharmaceutical composition for combined treatment of atherosclerosis according to any one of claims 1-3, characterized in that, The pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

5. The pharmaceutical composition for combined treatment of atherosclerosis according to claim 4, wherein, The pharmaceutical composition does not comprise other active ingredients.

6. The pharmaceutical composition for combined treatment of atherosclerosis according to claim 5, characterized in that, The pharmaceutical composition is an oral preparation.

7. The pharmaceutical composition for combined treatment of atherosclerosis according to claim 6, characterized in that, The oral preparation comprises liquid preparation, tablets and capsules.

8. Use of the pharmaceutical composition according to any one of claims 1-7 in the preparation of a medicament for treating atherosclerosis.

9. The application according to claim 8, wherein The pharmaceutical composition is used for reducing the influence of atherosclerotic plaques.

Images