Pharmaceutical composition for preventing or treating arteriosclerosis and application thereof

Abstract

The invention relates to the technical field of medicines, in particular to a pharmaceutical composition for preventing or treating arteriosclerosis and application thereof. The pharmaceutical composition for preventing or treating arteriosclerosis comprises terazosin or a pharmaceutical salt thereof, and an angiotensin II receptor antagonist. According to the pharmaceutical composition for preventing or treating arteriosclerosis and the application of the pharmaceutical composition, the artery hardness can be reduced, and meanwhile adverse effects on blood pressure are avoided.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a pharmaceutical composition for preventing or treating arteriosclerosis and application thereof. Background Art

[0002] Atherosclerosis is the main pathological basis of cardiovascular and cerebrovascular diseases. Its incidence rate increases year by year with age and changes in lifestyle. Atherosclerosis is mainly manifested by thickening, hardening and loss of elasticity of the arterial wall, which in turn leads to stenosis of the vascular lumen, affects blood flow and increases the risk of cardiovascular and cerebrovascular diseases. Age is one of the main risk factors for the occurrence and development of cardiovascular and cerebrovascular diseases in patients, and vascular degenerative changes play a leading role in this. Vascular degenerative changes refer to the physiological and pathological process of functional and structural aging and degeneration of blood vessels with age under the combined action of other factors (Zhang Yucong, Zhang Cuntai attach importance to the assessment and prevention of vascular aging "Chinese Journal of Geriatrics" 2020, 39 (08) 10.3760 / cma.j.issn.0254-9026.2020.08.001). Vascular degenerative diseases vary due to different target organs. When heart damage occurs, due to the aging and degeneration of the aorta, the left ventricular afterload increases, leading to ventricular remodeling, left heart dysfunction, and eventually heart failure; when kidney damage occurs, the small arteries of the kidney are the first to be affected, causing glomerular damage, which subsequently develops into end-stage renal diseases such as chronic renal failure; when brain damage occurs, vascular aging causes vascular sclerosis, aggravates the damage to the microcirculation vessels in the brain, reduces the oxygen supply capacity and oxygen supply, and causes central nervous system diseases such as stroke or cognitive decline and cognitive impairment. Morphologically, aged blood vessels represent increased collagen fiber deposition, increased and disordered elastic fibers, disordered smooth muscle cell arrangement, and intimal depression. Functionally, aged blood vessels show increased stiffness, decreased sensitivity to vasodilators, increased sensitivity to vasoconstrictors, and decreased angiogenesis. Vascular aging increases susceptibility to hypertension and atherosclerosis (Zhang C, Tao J; Cardiovascular Group, Society of Geriatrics, Chinese Medical Association. Expert consensus on clinical assessment and intervention of vascular aging in China (2018). AgingMed (Milton). 2018 Nov 30;1(3):228-237. doi: 10.1002 / agm2.12049. PMID:31942501; PMCID: PMC6880715.).

[0003] Existing treatments mostly focus on controlling blood pressure, blood lipids, etc., but direct treatment drugs for arteriosclerosis (especially vascular aging-type arteriosclerosis) are still rare. Summary of the invention

[0004] In order to solve the above problems in the prior art, the present invention provides a pharmaceutical composition for preventing or treating arteriosclerosis and its application, which provides a new solution for the treatment of arteriosclerosis and improves the quality of life of patients.

[0005] Based on this, the present invention has the following technical solutions: In a first aspect, the present invention first provides a pharmaceutical composition for preventing or treating arteriosclerosis, characterized in that it comprises: terazosin or a pharmaceutically acceptable salt thereof, and an angiotensin II receptor antagonist.

[0006] Terazosin, as an α1-adrenergic receptor blocker, achieves vasodilation and lowers blood pressure by blocking α1-adrenergic receptors, and is therefore widely used in the clinic to treat benign prostatic hyperplasia and hypertension. The present invention unexpectedly found that terazosin and angiotensin II receptor antagonists have a synergistic effect, and their combined use can significantly reduce vascular hardness, which provides a new idea for the treatment of arteriosclerosis.

[0007] The present invention also finds that not all α1-adrenergic receptor blockers have the effect of synergizing with angiotensin II receptor antagonists to reduce vascular hardness.

[0008] Preferably, the mass ratio of the terazosin or its pharmaceutically acceptable salt to the angiotensin II receptor antagonist is 1:240-480.

[0009] In the present invention, the mass ratio of the terazosin or its pharmaceutically acceptable salt to the angiotensin II receptor antagonist can be any ratio of 1:240, 1:250, 1:260, 1:270, 1:280, 1:290, 1:300, 1:310, 1:320, 1:330, 1:340, 1:350, 1:360, 1:370, 1:380, 1:390, 1:400, 1:410, 1:420, 1:430, 1:440, 1:450, 1:460, 1:470, and 1:480, or a numerical range in which any two of the above ratios are endpoints.

[0010] The present invention finds that terazosin is used as the main active ingredient to promote the relaxation of vascular smooth muscle and reduce vascular resistance by blocking α1-adrenergic receptors, thereby reducing arterial hardness to a certain extent; angiotensin II receptor antagonists are used as auxiliary ingredients to inhibit excessive activation of sympathetic nerves, reduce myocardial oxygen consumption, improve cardiac function, and further protect the cardiovascular system. The two are used in combination at the above dosage to produce a synergistic effect, effectively reduce arterial hardness, stabilize blood pressure, and improve the prognosis of patients with arteriosclerosis.

[0011] Preferably, the angiotensin II receptor antagonist includes one or more of sartan medoxomil drugs, valsartan or its sustained-release formulation, and irbesartan or its sustained-release formulation; more preferably, the angiotensin II receptor antagonist is a sartan medoxomil drug; further preferably, it is olmesartan medoxomil.

[0012] In the present invention, Alisartan medoxomil selectively binds to angiotensin II receptors, blocks vasoconstriction caused by angiotensin II, promotes aldosterone secretion, and achieves the purpose of lowering blood pressure. Such drugs can steadily and effectively lower blood pressure, reverse or improve myocardial remodeling, improve insulin resistance in hypertensive patients, and promote uric acid excretion, thereby significantly reducing the risk of cardiac and cerebral stroke vascular events.

[0013] As a preferred embodiment of the present invention, the pharmaceutical composition is a mixture of terazosin or a pharmaceutically acceptable salt thereof and allisartan medoxomil.

[0014] Preferably, the pharmaceutically acceptable salt of terazosin includes terazosin hydrochloride and / or terazosin phosphate.

[0015] It is well known to those skilled in the art that the daily dose of terazosin in the treatment of hypertension is more than 2 mg, but the present invention finds that a small dose of terazosin or its pharmaceutical salt can be used to prevent or treat arteriosclerosis, thereby effectively preventing or treating hypertension and other cardiovascular diseases. At the same time, a small dose of terazosin has a small effect on blood pressure, avoiding the side effects that a conventional dose or a large dose may bring.

[0016] Preferably, the daily dose of terazosin or a pharmaceutically acceptable salt thereof is 0.5-1.0 mg, for example, it can be any value among 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, or a numerical range with any two of the above values ​​as endpoints.

[0017] As a preferred embodiment of the present invention, the daily dose of terazosin is 0.5 mg, taken once a day. For a specific patient population, such as the elderly or the weaker physique, it can be taken before going to bed.

[0018] Preferably, the daily dose of the angiotensin II receptor antagonist is 80-240 mg, for example, it can be any value among 80 mg, 90 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, and 240 mg, or a numerical range with any two of the above values ​​as endpoints.

[0019] As a preferred embodiment of the present invention, the daily dose of Alisartan medoxomil is a low dose within the conventional dose range, and the dose can be adjusted according to the specific conditions of the patient, preferably 240 mg per day.

[0020] In the present invention, compared with traditional antihypertensive drugs, low-dose terazosin has less effect on blood pressure, and allisartan medoxomil is used as an auxiliary drug to achieve the effect of lowering blood pressure and reduce the risk of further development of arteriosclerosis. By using a small dose of terazosin in combination with the above-mentioned dose of allisartan medoxomil, arterial hardness and hypertension levels can be reduced at the same time, which helps to improve the prognosis of patients with arteriosclerosis, reduce the risk of cardiovascular and cerebrovascular diseases, and improve the quality of life of patients.

[0021] Preferably, the arteriosclerosis is arteriosclerosis caused by vascular aging.

[0022] Specifically, healthy aortas have a strong buffering capacity, which can still provide stable blood flow to microvessels under the condition of cardiac contraction and intermittent ejection, thereby protecting microvessels from the harmful effects of pressure fluctuations. However, with the increase of age and under the action of various cardiovascular risk factors, blood vessels age, structural remodeling and functional disorders occur, the main feature of which is the increase in the hardness of blood vessels. Compared with atherosclerosis, vascular sclerosis caused by vascular aging is significantly different in mechanism and leads to structural remodeling of the vascular wall more widely. In the absence of atherosclerosis, vascular aging mainly causes thickening of the vascular endothelium, especially a significant increase in the thickness of the vascular intima-media layer (IMT), and also causes damage and dysfunction of endothelial cells, resulting in a significant weakening of the vascular nitric oxide (NO)-dependent vasodilation. Structural remodeling and functional disorders affect each other, ultimately leading to the atherosclerosis described in the present invention.

[0023] In certain embodiments, the administration routes of terazosin or its pharmaceutically acceptable salt, and angiotensin II receptor antagonist include oral administration, injection, etc., and oral administration is the best route.

[0024] In a second aspect, the present invention provides a drug for preventing or treating cardiovascular and cerebrovascular diseases, including the pharmaceutical composition for preventing or treating arteriosclerosis.

[0025] In a third aspect, the present invention provides a drug for preventing or treating hypertension, including the pharmaceutical composition for preventing or treating arteriosclerosis.

[0026] In certain embodiments, the drug for preventing or treating arteriosclerosis, the drug for preventing or treating cardiovascular and cerebrovascular diseases, and the drug for preventing or treating hypertension may contain any pharmaceutically acceptable excipient.

[0027] In certain embodiments, the pharmaceutically acceptable excipients include, but are not limited to, at least one of ultrapure water, physiological saline, non-aqueous solvents, solubilizers, co-solvents, binders, disintegrants, colorants, preservatives, dispersants, plasticizers, isotonicity regulators, pH regulators, antibacterial agents, antioxidants and chelating agents, and are not limited thereto.

[0028] In certain embodiments, the dosage forms of the drug for preventing or treating arteriosclerosis, the drug for preventing or treating cardiovascular and cerebrovascular diseases, and the drug for preventing or treating hypertension include, but are not limited to, injections, oral agents, capsules, tablets, powders or suspensions, etc., and are not limited thereto.

[0029] As one of the methods to verify the effect of the present invention, the change of arterial stiffness can be evaluated by measuring the pulse wave velocity (PWV) of the patient, and the effect on blood pressure can be evaluated by measuring the systolic and diastolic blood pressure of the patient. In addition, the effectiveness of the present invention can be further verified by animal experiments.

[0030] It should be noted that the present invention is not only suitable for patients with arteriosclerosis, but can also be used to prevent the occurrence and development of arteriosclerosis, providing cardiovascular protection for a wider range of people.

[0031] In a fourth aspect, the present invention provides the pharmaceutical composition and the use of the pharmaceutical composition in any of the following aspects: a) Preparation of drugs for preventing or treating arteriosclerosis; b) Preparation of drugs for preventing or treating cardiovascular and cerebrovascular diseases; c) preparing medicines for preventing or treating hypertension.

[0032] The present invention provides a pharmaceutical composition for preventing or treating arteriosclerosis and its application, which can reduce arterial hardness while avoiding adverse effects on blood pressure. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0034] Figure 1 This is a bar graph showing that the long-term intervention of terazosin hydrochloride combined with alisartan medoxomil in Example 1 provided by the present invention in an animal model reduces the pulse wave velocity of experimental animals.

[0035] Figure 2 This is a bar graph showing the effect of the combined use of terazosin hydrochloride and allisartan medoxomil on the long-term intervention blood pressure (systolic pressure) of experimental animals in an animal model in Example 1 provided by the present invention.

[0036] Figure 3 This is a bar graph showing the effect of the combined use of terazosin hydrochloride and allisartan medoxomil on the long-term intervention blood pressure (diastolic pressure) of experimental animals in an animal model in Example 1 provided by the present invention.

[0037] Figure 4 The present invention provides a schematic diagram of the effect of the combined use of terazosin hydrochloride and allisartan medoxomil on the morphological changes of vascular tissues in experimental animals in Example 1 (stained sections); wherein, Figure A represents the SHR group, Figure B represents the WKY group, Figure C represents the SHR Terazosin hydrochloride group, Figure D represents the SHR Allisartan isoproxil group, and Figure E represents the SHR Terazosin hydrochloride + Allisartan isoproxil group. DETAILED DESCRIPTION

[0038] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be clearly and completely described below in conjunction with the drawings of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0039] The term "combination therapy" as used herein means that the two active ingredients defined herein (ie, terazosin and angiotensin II receptor antagonist) are administered to the patient simultaneously.

[0040] The term "treatment" as used herein includes treatment that relieves, alleviates or alleviates at least one symptom of a subject or achieves a delay in disease progression, or means preventing, delaying the onset (i.e., the period prior to clinical manifestation of the disease) and / or reducing the risk of disease development or disease exacerbation.

[0041] As used herein, the term "preventing" includes preventing at least one symptom associated with or caused by the state, disease, or disorder being prevented.

[0042] Term used herein " synergy ", refer to at least 2 kinds of therapeutic agents, i.e. this effect of terazosin hydrochloride as defined herein and alisartan medoxomil as defined herein: this effect should be greater than the effect obtained by simply adding up the effects of each medicine used. This effect can be, for example, the progress of slowing down disease or its symptoms. Synergistic effect can be calculated as shown in the examples.

[0043] The term "subject" or "patient" as used herein includes animals that are at risk of cardiovascular and cerebrovascular diseases or have cardiovascular and cerebrovascular diseases or symptoms, wherein cardiovascular and cerebrovascular diseases include hypertension and arteriosclerosis. Examples of subjects include mammals, such as humans, dogs, pigs, rabbits, rats, mice, and transgenic non-human animals.

[0044] As used herein, the term "pharmaceutically acceptable" or "pharmaceutically acceptable..." is defined herein to refer to compounds, materials, compositions and / or dosage forms that are suitable for use in contact with the tissues of a subject (e.g., a human or non-human mammal) within the scope of sound medical judgment without excessive toxicity, irritation, allergic response and / or other complications, and commensurate with a reasonable benefit / risk ratio.

[0045] Unless otherwise specified, the various raw materials used in the examples and comparative examples are commercially available conventional raw materials, and the technical means used are conventional means well known to those skilled in the art.

[0046] Example 1: Detection of the effect of long-term intervention of terazosin hydrochloride combined with alisartan medoxomil on arteriosclerosis Table 1 Equivalent dose ratios between humans and animals based on body surface area

[0047] Dose conversion between rats and humans: The clinical dose for humans is X mg / kg, which is converted to the dose for rats: Dose for rats = X mg / kg × 70kg × 0.018 / 200g =X mg / kg×70kg×0.018 / 0.2kg =6.3 X mg / kg That is, calculated based on the dose per unit body weight, the equivalent dose for rats is 6.3 times that for humans.

[0048] According to this embodiment, the dosage of terazosin hydrochloride for human use is 0.5 mg / d, which is converted into a rat dosage of 6.3×(0.5 / 70)=0.045 mg / kg / d; similarly, the dosage of ollisartan medoxomil for rats is 6.3×(240 / 70)=21.6 mg / kg / d.

[0049] Spontaneously Hypertensive Rat (SHR) was selected as an atherosclerosis model animal (SHR group), and Wistar-Kyoto Rat (WKY) was selected as a non-atherosclerosis control model (WKY group). Drugs were used to intervene in SHR, including single-drug terazosin hydrochloride (SHR Terazosinhydrochloride group), single-drug allisartan medoxomil (SHR Allisartan isoproxil group), and terazosin hydrochloride and allisartan medoxomil (SHR Terazosin hydrochloride+Allisartan isoproxil group), with 8 rats in each group. All drugs were dissolved in 0.5% sodium carboxymethylate and then administered by gavage. The dosage was calculated according to the clinical dosage designed by the present invention according to the body surface area coefficient, specifically shown in Table 2 Allisartan medoxomil 21.6 mg / kg / d, and a long-term intervention of 3 months was carried out. After the treatment, the pulse wave velocity (PWV) and blood pressure of the rats were measured and statistically analyzed.

[0050] Table 2

[0051] Jin Zhengjun Q value method to calculate the interaction of composites: Q = E a+b / (E a +E b -E a ×E b ), where E a+b is the average value of the data when components A and B are combined, E a and E b They are the average values ​​of the data when component A and component B are used alone. The numerator represents the "measured combined effect", the denominator represents the "expected combined effect", Q is the ratio of the two, Q < 0.85 is antagonistic, 0.85 ≤ Q < 1.15 is additive, and Q ≥ 1.15 is synergistic. Here, the measured value is converted into an effect that can intuitively reflect the drug's action, and the calculation formula is: E i =(1-P i / P 模型组)×100%,P i is the measured value of each group, P 模型组 It is the measured value of the model group.

[0052] Based on this, the effect of drugs on reducing PWV is calculated as shown in Table 3: Table 3 The therapeutic effect of terazosin hydrochloride combined with arisartan medoxomil on arteriosclerosis

[0053] The results showed that the PWV of rats in the combined drug group was significantly lower than that in other groups (p<0.01), and the systolic and diastolic blood pressures were more stable during long-term treatment. This further verified the effectiveness of the long-term treatment of terazosin combined with olisartan medoxomil in reducing arterial stiffness and controlling blood pressure, and had a synergistic effect in the treatment of arterial stiffness.

[0054] The bar graph of different drugs in animal models that reduce pulse wave velocity after long-term intervention in experimental animals is shown in Figure 1 The bar graph of the effects of different drugs on long-term intervention blood pressure (systolic blood pressure) in animal models is shown in Figure 2 The bar graph of the effects of different drugs on long-term intervention blood pressure (diastolic blood pressure) in animal models is shown in Figure 3 Schematic diagram of the effects of different drugs on the morphological changes of vascular tissue in experimental animals (stained sections) Figure 4 ; Among them, Figure A represents the SHR group, Figure B represents the WKY group, Figure C represents the SHR Terazosin hydrochloride group, Figure D represents the SHR Allisartan isoproxil group, and Figure E represents the SHR Terazosin hydrochloride+Allisartan isoproxil group.

[0055] The present invention finds that when the dosage ratio of terazosin hydrochloride to allisartan medoxomil is 1:240, the effect is equivalent to the effect of the combined use of the two in the ratio of 1:480 in Example 1.

[0056] Example 2 The difference between this example and the SHR Terazosin hydrochloride+Allisartan isoproxil group in Example 1 is that Allisartan medoxomil is replaced with an equivalent dose of perindopril tert-butylamine.

[0057] The results showed that the antihypertensive effect of equivalent dose of perindopril tert-butylamine was weaker than that of olisartan medoxomil; the equivalent dose of perindopril tert-butylamine required a double dose to achieve the same effect in reducing PWV. This proves that the synergistic effect of terazosin hydrochloride and olisartan medoxomil in reducing arteriosclerosis is more significant than that of terazosin hydrochloride and other angiotensin II receptor antagonists.

[0058] Example 3 The only difference between this example and the SHR Terazosin hydrochloride+Allisartan isoproxil group in Example 1 is that the daily dose of Allisartan medoxomil is 3.6 mg / kg / d, and the mass ratio of Allisartan medoxomil to Terazosin hydrochloride is 80:1.

[0059] The results showed that the antihypertensive effect of the composition of this mass ratio was not significant; the PWV-reducing effect of the composition of this mass ratio was not significantly different from that of terazosin hydrochloride alone.

[0060] Example 4 The difference between this example and the SHR Terazosin hydrochloride+Allisartan isoproxil group in Example 1 is that the daily dose of terazosin hydrochloride is 0.45 mg / kg / d.

[0061] The results showed that the combination at this dose had a significant antihypertensive effect; however, the combination at this dose was not as effective in reducing PWV as the combination at the specified dose, and had no synergistic effect.

[0062] Comparative Example 1 The difference between this example and the SHR Terazosin hydrochloride+Allisartan isoproxil group in Example 1 is that terazosin hydrochloride is replaced by an equal amount of tamsulosin.

[0063] The results showed that the combination of the ingredients can lower blood pressure, and the blood pressure reduction level is no different from that of the single-drug use of ollisartan medoxomil; the effect of the combination of the ingredients on reducing PWV is no different from that of the single-drug use of ollisartan medoxomil. This proves that not all α1-adrenergic receptor blockers can synergistically reduce arteriosclerosis with ollisartan medoxomil.

[0064] Experimental Example 1 In the animal experiment, the aorta tissue of the rats in Example 1 was taken for pathological sectioning and EVG staining observation to evaluate the morphological changes of the vascular tissue. The results showed that the collagen fibers of the vascular walls of the rats in the combined medication group were neatly arranged and maintained elasticity, which was significantly improved compared with the SHR group, further proving the protective effect of the combined use of terazosin and arisartan medoxomil on vascular tissue.

[0065] In summary, the combined composition for treating arteriosclerosis provided by the present invention comprises a small dose of terazosin and allisartan medoxomil, which can control blood pressure stability while effectively reducing arterial hardness, and provides a new option for the treatment of arteriosclerosis. The combined composition has significant clinical effects and broad application prospects.

[0066] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A pharmaceutical composition for preventing or treating arteriosclerosis, characterized in that: include: Terazosin or a pharmaceutically acceptable salt thereof, and Angiotensin II receptor antagonists.

2. The pharmaceutical composition for preventing or treating arteriosclerosis according to claim 1, characterized in that: The mass ratio of the terazosin or its pharmaceutically acceptable salt to the angiotensin II receptor antagonist is 1:240-480.

3. The pharmaceutical composition for preventing or treating arteriosclerosis according to claim 1 or 2, characterized in that: The angiotensin II receptor antagonist includes one or more of sartan medoxomil drugs, valsartan or its sustained-release formulation, and irbesartan or its sustained-release formulation; preferably, the angiotensin II receptor antagonist is a sartan medoxomil drug; more preferably, ollisartan medoxomil.

4. The pharmaceutical composition for preventing or treating arteriosclerosis according to any one of claims 1 to 3, characterized in that The pharmaceutically acceptable salt of terazosin includes terazosin hydrochloride and / or terazosin phosphate.

5. The pharmaceutical composition for preventing or treating arteriosclerosis according to any one of claims 1 to 4, characterized in that The daily dosage of terazosin or its pharmaceutically acceptable salt is 0.5-1.0 mg.

6. The pharmaceutical composition for preventing or treating arteriosclerosis according to any one of claims 1 to 5, characterized in that The daily dose of the angiotensin II receptor antagonist is 80-240 mg.

7. The pharmaceutical composition for preventing or treating arteriosclerosis according to any one of claims 1 to 6, characterized in that The arteriosclerosis is arteriosclerosis caused by vascular aging.

8. A drug for preventing or treating cardiovascular and cerebrovascular diseases, characterized in that: A pharmaceutical composition for preventing or treating arteriosclerosis comprising any one of claims 1 to 7.

9. A drug for preventing or treating hypertension, characterized in that: A pharmaceutical composition for preventing or treating arteriosclerosis comprising any one of claims 1 to 7.

10. Use of the pharmaceutical composition according to any one of claims 1 to 7 in any of the following aspects: a) Preparation of drugs for preventing or treating arteriosclerosis; b) Preparation of drugs for preventing or treating cardiovascular and cerebrovascular diseases; c) preparing medicines for preventing or treating hypertension.

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