Application of disulfide cyclopeptide compound in preparation of hypolipidemic drugs

Abstract

The invention relates to the technical field of blood fat reduction, in particular to application of a disulfide cyclopeptide compound in preparation of a blood fat reducing medicine. The disulfide cyclopeptide compound has the following structure: R2-R1-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-R3-R4, the compound with the structure can significantly reduce the content of TC, TG, HDL and LDL in serum, a new direction is provided for research and development of blood fat reducing drugs, and meanwhile, the application field of the disulfide cyclopeptide compound is widened.

Description

[0001] This application claims priority to: Chinese patent application number 202411230649.2, filed by Wanbangde Pharmaceutical Group Co., Ltd. on September 3, 2024, entitled "A disulfide cyclic peptide compound, its preparation method and application", the entire contents of which are incorporated herein by reference. Technical Field

[0002] The present invention relates to the technical field of lowering blood lipids, and in particular to the application of disulfide cyclic peptide compounds in the preparation of blood lipid-lowering drugs. Background Art

[0003] Cardiovascular disease is one of the main causes of serious harm to human health. Hyperlipidemia, when plasma lipid concentrations exceed the normal range, is a significant risk factor for the development of cardiovascular diseases such as coronary heart disease and myocardial infarction. Its most direct hazard is the development of atherosclerosis. Therefore, research on lipid-lowering drugs is crucial.

[0004] Traditional lipid-lowering drugs include statins, fibrates, niacin, ezetimibe, and bile acid sequestrants. Atorvastatin and rosuvastatin have become blockbuster drugs in the global pharmaceutical market. Furthermore, fibrates (represented by gemfibrozil and ciprofibrate), Niemann-Pick type C1-like protein (NPC1L1) inhibitors (represented by ezetimibe), bile acid sequestrants (represented by cholestyramine and colesevelam hydrochloride), and niacin compounds also play a crucial role in the prevention, control, and treatment of hyperlipidemia and atherosclerotic heart disease.

[0005] However, the limitations of classic lipid-lowering drugs are gradually emerging. For example, as HMG-CoA reductase inhibitors, statins have some adverse reactions, such as rhabdomyolysis, hepatotoxicity, and cognitive impairment. Clinical trials of niacin compounds have shown that niacin does not significantly improve the risk of atherosclerotic heart disease.

[0006] Currently, new small-molecule lipid-lowering drugs are being researched, including inhibitors of microsomal triglyceride transfer protein (MTP), ATP citrate lyase (ACL) inhibitors, plasma cholesterol ester transfer protein (CETP) inhibitors, and novel peroxisome proliferator-activated receptor agonists. For example, Chinese patent CN110305102A discloses 1,3-benzodioxole natural polyphenolate ester compounds and their pharmaceutical applications. These compounds incorporate a natural polyphenolic acid structure into their structure, using sesamol as a functional fragment. These compounds exhibit significant lipid-lowering activity, simultaneously lowering both triglyceride and cholesterol (TG) levels, while also exhibiting significant anti-lipid peroxidation and antioxidant enhancement. These compounds possess a more potent and broad-spectrum lipid-lowering effect, demonstrating their ability to simultaneously lower TG and TC levels, while also exhibiting anti-lipid peroxidation and antioxidant enhancement.

[0007] At present, the research of new and highly effective lipid-lowering drugs is still very necessary. Summary of the Invention

[0008] The purpose of the present invention is to provide the use of a disulfide cyclic peptide compound in the preparation of a lipid-lowering drug, thereby providing a new direction for the research and development of lipid-lowering drugs and broadening the application field of the disulfide cyclic peptide compound.

[0009] In order to achieve the above-mentioned purpose of the invention, the technical solution of the present invention is as follows: In a first aspect, the present invention provides a disulfide cyclic peptide compound for use in preparing a lipid-lowering drug, wherein the disulfide cyclic peptide compound has the following structure: R2-R1-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-R3-R4, wherein R2 and R4 are each independently selected from an amino group, an acetyl group or a palmitoyl group; R1 and R3 are each independently selected from Ile, Arg, D-Phe, Pro or are deleted, R1 and R3 are not deleted at the same time, and when R1 or R3 is deleted, at least one of R2 and R4 is a palmitoyl group.

[0010] Preferably, R1 is Arg; R2 is an acetyl group or a palmitoyl group; R3 is Ile, Arg, D-Phe, Pro or missing; R4 is an amino group; Furthermore, when R3 is absent, R2 is a palmitoyl group.

[0011] Further preferably, the disulfide cyclic peptide compound has the following structural formula:

[0012] Wherein, R1, R2, R3 and R4 are as defined above.

[0013] Further preferably, R3 is selected from Ile, D-Phe, Pro or deletion, and R1 is Arg.

[0014] Further preferably, R2 is selected from an acetyl group or a palmitoyl group, and R4 is an amino group.

[0015] Further preferably, when R3 is absent, R4 is a palmitoyl group.

[0016] Further preferably, the disulfide cyclic peptide compound is selected from at least one of the following compounds:

[0017] .

[0018] Further preferably, the disulfide cyclic peptide compound is selected from at least one of the following compounds: 、 、 、 .

[0019] Further preferably, the disulfide cyclic peptide compound is selected from at least one of the following compounds: .

[0020] Preferably, the preparation method of the disulfide cyclic peptide compound comprises the following steps: Step 1: Select a resin and remove the Fmoc protecting group to obtain a resin from which the Fmoc protecting group has been removed; Step 2: Weigh Fmoc-R3-OH or Fmoc-Cys(Trt)-OH and PyBop, and perform a coupling reaction on the resin with the Fmoc protecting group removed to obtain a coupled resin; Step 3: According to the peptide sequence, the coupling resin is coupled from the C-terminus to the N-terminus to obtain a linear peptide resin; Step 4: reacting the cleavage solution with the linear peptide resin to remove the protecting group and obtain a polypeptide; Step 5: dissolving the polypeptide in water, adjusting the pH and adding H2O2 to react to obtain the disulfide cyclic peptide compound.

[0021] Preferably, the lipid-lowering comprises reducing the content of at least one of TC (total cholesterol), TG (triglycerides), HDL (high-density lipoprotein), and LDL (low-density lipoprotein) in the serum of individuals with hyperlipidemia.

[0022] In a second aspect, the present invention provides a lipid-lowering drug, the active ingredient of which is a disulfide cyclic peptide compound.

[0023] Preferably, the lipid-lowering drug further comprises a pharmaceutically acceptable carrier or excipient, wherein the disulfide cyclic peptide compound has the following structure: R2-R1-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-R3-R4, wherein R2 and R4 are each independently selected from an amino group, an acetyl group or a palmitoyl group; R1 and R3 are each independently selected from Ile, Arg, D-Phe, Pro or are deleted, R1 and R3 are not deleted at the same time, and when R1 or R3 is deleted, at least one of R2 and R4 is a palmitoyl group.

[0024] Preferably, R1 is Arg; R2 is an acetyl group or a palmitoyl group; R3 is Ile, Arg, D-Phe, Pro or missing; R4 is an amino group; Furthermore, when R3 is absent, R2 is a palmitoyl group.

[0025] Further preferably, the disulfide cyclic peptide compound has the following structural formula:

[0026] Wherein, R1, R2, R3 and R4 are as defined above.

[0027] Further preferably, R3 is selected from Ile, D-Phe, Pro or deletion, and R1 is Arg.

[0028] Further preferably, R2 is selected from an acetyl group or a palmitoyl group, and R4 is an amino group.

[0029] Further preferably, when R3 is absent, R4 is a palmitoyl group.

[0030] Further preferably, the disulfide cyclic peptide compound is selected from at least one of the following compounds:

[0031] .

[0032] Further preferably, the disulfide cyclic peptide compound is selected from at least one of the following compounds: 、 、 、 .

[0033] Further preferably, the disulfide cyclic peptide compound is selected from at least one of the following compounds: .

[0034] The phrase "pharmaceutically acceptable carrier" is art-recognized and includes pharmaceutically acceptable materials, components, or vehicles that are suitable for administering the compounds of the present invention to mammals. Carriers include liquid or solid fillers, diluents, excipients, solvents, or encapsulating materials that participate in carrying or transporting the subject substance from one organ or part of the body to another. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation or not injurious to the subject. Some examples of materials that can serve as pharmaceutically acceptable carriers include: sugars such as lactose, glucose, sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium methyl cellulose, ethyl cellulose, and cellulose acetate; tragacanth, malt, gelatin, talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols such as propylene glycol, polyols such as glycerol, benzyl alcohol, glycerin, maltose, maltose, talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols such as propylene glycol, polyols such as glycerol, benzyl alcohol, glycerin, maltose, maltose, talc; Sorbitol, mannitol, and polyethylene glycol, esters such as ethyl oleate and ethyl laurate, agar, buffers such as magnesium hydroxide and aluminum hydroxide, alginic acid, pyrogenic water, isotonic saline, ethanol, phosphate buffered saline, and other nontoxic compatible substances used in pharmaceutical formulations. Wetting agents, emulsifiers, and lubricants such as sodium lauryl sulfate and stearic acid esters, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives, and antioxidants may also be present in the composition.

[0035] Examples of pharmaceutically acceptable antioxidants include: water-soluble antioxidants, such as ascorbic acid, cysteine ​​hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite, etc.; oil-soluble antioxidants, such as ascorbyl palmitate, butylated benzoic acid (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, α-tocopherol, etc.; and metal complexes, such as citric acid, ethylenediaminetetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, etc.

[0036] Suitable pharmaceutically acceptable carriers include, but are not limited to, water, saline solutions (e.g., NaCl), alcohol, gum arabic, vegetable oils, benzyl alcohol, polyethylene glycol, gelatin, sugars (e.g., lactose, amylose, or starch), polyethylene glycol, magnesium stearate, talc, silicic acid, viscous paraffin, essential oils, fatty acid esters, methylcellulose, polyvinylpyrrolidone, etc. The pharmaceutical composition can be sterilized and, if desired, mixed with auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salt buffers for influencing osmotic pressure, colorants, flavorings, and / or aromatic substances, which do not deleteriously react with the active compounds.

[0037] The lipid-lowering drug may also contain a minor amount of a wetting agent, emulsifier, or pH buffer. The lipid-lowering drug may be a liquid solution, suspension, emulsion, tablet, pill, capsule, sustained-release formulation, or powder. The composition may be formulated into a suppository together with conventional binders and carriers (such as triglycerides). Oral formulations may include standard carriers such as pharmaceutical grade mannitol, lactose, magnesium stearate, polyvinylpyrrolidone, saccharin sodium, cellulose, magnesium carbonate, and the like.

[0038] According to conventional methods, the lipid-lowering drug can be formulated into a pharmaceutical composition suitable for intravenous administration to humans. When necessary, the composition may further include a stabilizer and a local anesthetic to relieve pain at the injection site.

[0039] Typically, ingredients are supplied separately or mixed together in unit dosage form, for example as dry lyophilized powders or anhydrous concentrates in sealed containers such as ampoules or sachets showing the amount of active agent. When the lipid-lowering drug is to be administered by infusion, it can be dispersed with an infusion bottle containing pharmaceutical grade sterile water, saline or dextrose water. When the lipid-lowering drug is administered by injection, an ampoule of sterile water for injection or saline can be provided so that the ingredients can be mixed before administration.

[0040] The lipid-lowering drugs of the present invention may also include agents that control the release of the compounds of the present invention, thereby providing timed or sustained-release compositions.

[0041] The lipid-lowering drugs of the present invention include formulations suitable for oral, rectal, topical, vaginal and parenteral (including subcutaneous, intramuscular and intravenous) administration, although the most appropriate route in any particular case depends on the specific subject, the nature and severity of the condition to which the active ingredient is administered. The pharmaceutical composition can be prepared by any method known in the art of pharmacy.

[0042] The lipid-lowering drugs of the present invention can be administered orally in solid or liquid dosage forms, such as capsules, tablets, lozenges, troches, granules, and powders, or in liquid dosage forms, such as elixirs, syrups, emulsions, dispersions, and suspensions. The active ingredient can also be administered parenterally in sterile liquid dosage forms, such as dispersions, suspensions, or solutions. Other dosage forms that can be used to administer the active ingredient include ointments, creams, drops, transdermal patches, or powders for topical administration; ophthalmic solutions or suspensions, i.e., eye drops, for administration to the eye; sprays or powder compositions for inhalation or intranasal administration; or creams, ointments, sprays, or suppositories for rectal or vaginal administration. Gelatin capsules contain the active ingredient and a powdered carrier, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, etc. Similar diluents can be used to prepare compressed tablets. Both tablets and capsules can be formulated as sustained-release products to provide sustained release of the drug over several hours. Compressed tablets can be coated with sugar or film to cover any unpleasant taste and protect the tablet from air, or can be enteric-coated for selective disintegration in the gastrointestinal tract. Liquid dosage forms for oral administration can include coloring agents and flavoring agents to increase patient acceptance. Generally speaking, water, suitable oil, saline, dextrose (glucose) aqueous solution and related sugar solution and glycols such as propylene glycol or polyethylene glycol are the carriers of suitable parenteral solutions. The solution for parenteral administration preferably includes a water-soluble salt of active ingredient, a suitable stabilizer and the buffer substance used as required. Antioxidant such as sodium bisulfite, sodium sulfite or ascorbic acid alone or in combination is a suitable stabilizer. Citric acid and its salt and sodium EDTA can also be used. In addition, parenteral solutions can also include preservatives, such as benzalkonium chloride, methylparaben or propylparaben and chlorobutanol.

[0043] For inhalation administration, compound of the present invention can be easily delivered in aerosol form from pressurized packaging or aerosol sprayer.The compound can also be delivered in the powder form prepared, and the powder composition can be sucked with the help of blowing into a powder inhaler device.The preferred delivery system for sucking is metered dose inhalation (MDI) aerosol, which can be formulated into a suspension or a solution of the compound of formula I in a suitable propellant, such as fluorocarbon or hydrocarbon.For eye administration, ophthalmic preparations can be prepared with a solution or a suspension of the appropriate weight percent of the compound of formula I in a suitable eye carrier, thereby keeping the compound in contact with the surface of the eye enough time so that the compound is infiltrated into the cornea and the inner area of ​​the eyes.

[0044] Useful pharmaceutical dosage forms for administering the compounds of the present invention include, but are not limited to, hard and soft gelatin capsules, tablets, parenteral injection solutions, and oral suspensions.

[0045] When the compounds of the present invention are administered stepwise or in combination with other therapeutic agents, the same dosage forms as described above may be used. When the drugs are administered in a physical combination, the dosage form and route of administration should be selected based on the compatibility of the combined drugs. The compounds of the present invention may be administered as the sole active ingredient or in combination with a second active ingredient, including those known to be useful in treating related diseases.

[0046] In a third aspect, the present invention provides a method for lowering blood lipids, comprising administering an effective amount of the above-described blood lipid-lowering drug to an individual. The method can be used in vivo or in vitro. The individual can be a mammal, such as a human.

[0047] The lipid-lowering drug is a unit dosage form suitable for single administration of an exact dose. In other embodiments, the amount of the compound is in the range of about 0.001 mg / kg body weight / day to about 1000 mg / kg body weight / day. In other embodiments, the amount of the compound is in the range of about 0.5 mg / kg body weight / day to about 50 mg / kg body weight / day. In some embodiments, the amount of the compound is about 0.001 g / day to about 7 g / day. In other embodiments, the amount of the compound is about 0.002 g / day to about 6 g / day. In other embodiments, the amount of the compound is about 0.005 g / day to about 5 g / day. In other embodiments, the amount of the compound is about 0.01 g / day to about 5 g / day. In other embodiments, the amount of the compound is about 0.02 g / day to about 5 g / day. In other embodiments, the amount of the compound is about 0.05 g / day to about 2.5 g / day. In other embodiments, the amount of the compound is from about 0.1 g / day to about 1 g / day. In other embodiments, dosage levels below the lower limit of the above range may be sufficient. In other embodiments, dosage levels above the upper limit of the above range may be required. In some embodiments, the compound is administered in a single dose once a day. In other embodiments, the compound is administered in multiple doses more than once a day. In some embodiments, the compound is administered twice a day. In other embodiments, the compound is administered three times a day. In other embodiments, the compound is administered four times a day. In other embodiments, the compound is administered more than four times a day. In some embodiments, the individual to whom the pharmaceutical composition is administered is a mammal. In other embodiments, the mammal is a human.

[0048] The beneficial effects of the present invention are: The present invention provides a disulfide cyclic peptide compound for use in the preparation of lipid-lowering drugs. Animal experiments have shown that the compound with this structure can significantly reduce the levels of TC, TG, HDL, and LDL in serum, providing a new direction for the research and development of lipid-lowering drugs and broadening the application field of the disulfide cyclic peptide compound. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] Figure 1 This is a chart showing the results of the lipid-lowering test. DETAILED DESCRIPTION

[0050] The following non-limiting examples are provided to enable those skilled in the art to more fully understand the present invention, but are not intended to limit the present invention in any way. The following is merely an illustrative description of the scope of the present invention, and those skilled in the art may make various changes and modifications to the present invention based on the disclosed content, which should also fall within the scope of protection claimed in this application.

[0051] The present invention will be further described below by way of specific examples. The various chemical reagents used in the examples of the present invention were obtained through conventional commercial channels unless otherwise specified. Unless otherwise specified, the contents described below are all by weight. Unless otherwise specified, it is understood that the experiments were conducted at room temperature.

[0052] Terms and abbreviations:

[0053] QD: Once a day.

[0054] SC: subcutaneous injection.

[0055] PBS: phosphate-buffered saline.

[0056] Vehicle: control group.

[0057] Compound preparation: The following compounds were synthesized according to the methods described in the priority patent 202411230649.2 or Examples 1 to 7 in CN119462838A, respectively. Their structural characterizations were the same as those described in the priority patent 202411230649.2 or CN119462838A.

[0058] WP302-1: Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-D-Phe-NH2

[0059] WP302-2: Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Pro-NH2

[0060] WP302-3: Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Ile-NH2

[0061] WP302-4: Palm-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2

[0062] WP302-5: Palm-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-D-Phe-NH2

[0063] WP302-6: Palm-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Pro-NH2

[0064] WP302-7: Palm-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-D-Phe-NH2

[0065] The above compounds are used as experimental drugs, and their information is as follows:

[0066] Blood lipid lowering effect test experiment: 1.1 Experimental Animals Experimental animals: DIO model male mice / SPF grade (Changzhou Cavens Laboratory Animal Co., Ltd., license number SYXK(Su)2022-0002), 20-22 weeks old, weighing more than 38 g.

[0067] The DIO mouse (Diet-Induced Obesity) is an animal model used to study obesity and diabetes. By selectively breeding mice with a susceptibility to obesity and diabetes, they develop obesity and diabetes on a high-fat diet. DIO mice are valuable for studying obesity, diabetes, and related metabolic diseases, helping to understand the pathogenesis of these diseases and develop new treatments. The DIO-B6 mouse is an obese mouse model (DIO) induced on a C57BL / 6 background strain using a 60% high-fat diet. These mice exhibit a phenotype characterized by weight gain, elevated random blood glucose levels, increased NK cells and macrophages, and elevated lipid profiles and liver function. They are useful for studying metabolic diseases such as obesity, diabetes, inflammation, and fatty liver disease, as well as for drug screening and preclinical efficacy evaluation.

[0068] Mouse strain: C57BL / 6J; Gender: male; High-fat feeding starting age: 5 weeks; High-fat feed: 60% high-fat feed (D12492).

[0069] The rearing conditions are as follows: Experimental animals were housed in an SPF-grade animal room at Suzhou Fangda Pharmaceutical Development Co., Ltd. The room was equipped with an air-conditioning system for good ventilation, maintaining a temperature between 20 and 26°C and a humidity between 40% and 0%. Artificial lighting was used, with a 12-hour light cycle and a 12-hour dark cycle (except when work lighting was required for experimental procedures or cleaning). Animals had free access to food and water. Animals were acclimated to the laboratory for at least 3 days before dosing. Animals were grouped based on their weight two days prior to dosing.

[0070] 1.2 Preparation of dosing solution: Accurately weigh an appropriate amount of compound, add a calculated volume of 1×PBS to completely dissolve the compound, stir thoroughly, and mix evenly to obtain a dosing solution.

[0071] 1.3 Administration

[0072] Drugs were administered subcutaneously through the skin of the back. After the last dose of the experiment, blood was collected from the inner canthus of the eye. After waiting for more than 30 minutes, whole blood was collected and centrifuged at 3500g for 5 minutes at 4°C to obtain serum. TC (total cholesterol) and TG (triglycerides) were measured using a biochemical analyzer, Hitachi LABOSPECT 006.

[0073] 1.4 Experimental Results The results are as follows Figure 1The results showed that at a dose of 4 mg / kg, each compound exhibited varying degrees of lipid-lowering efficacy. Compounds WP302-2, WP302-3, WP302-4, and WP302-5 were more effective in lowering total cholesterol (TC), with WP302-4 showing the highest effect. Compounds WP302-2 and WP302-6 were more effective in lowering triglycerides (TG), while WP302-1, WP302-3, WP302-4, WP302-5, and WP302-7 were equally effective and showed the highest efficacy.

[0074] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. The use of a disulfide cyclic peptide compound in the preparation of a lipid-lowering drug, characterized in that: The disulfide cyclic peptide compound has the following structure: R2-R1-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-R3-R4, wherein R2 and R4 are each independently selected from an amino group, an acetyl group or a palmitoyl group; R1 and R3 are each independently selected from Ile, Arg, D-Phe, Pro or are deleted, R1 and R3 are not deleted at the same time, and when R1 or R3 is deleted, at least one of R2 and R4 is a palmitoyl group.

2. The use according to claim 1, characterized in that R1 is Arg; R2 is acetyl or palmitoyl; R3 is Ile, Arg, D-Phe, Pro or missing; R4 is amino; Furthermore, when R3 is absent, R2 is a palmitoyl group.

3. The use according to claim 1 or 2, characterized in that The disulfide cyclic peptide compound has the following structural formula: wherein R1, R2, R3 and R4 are as defined in claim 1 or 2.

4. The use according to claim 1, characterized in that R3 is selected from Ile, D-Phe, Pro or is missing, and R1 is Arg.

5. The use according to claim 1, characterized in that R2 is selected from an acetyl group or a palmitoyl group, and R4 is an amino group.

6. The use according to claim 1, characterized in that When R3 is absent, R4 is a palmitoyl group.

7. The use according to any one of claims 1 to 6, characterized in that The disulfide cyclic peptide compound is selected from at least one of the following compounds: 。 8. The use according to claim 7, characterized in that The disulfide cyclic peptide compound is selected from at least one of the following compounds: 。 9. The use according to claim 8, characterized in that The disulfide cyclic peptide compound is selected from at least one of the following compounds: 。 10. A lipid-lowering drug, characterized in that: It comprises a disulfide cyclic peptide compound and a pharmaceutically acceptable carrier or excipient, wherein the disulfide cyclic peptide compound has the following structure: R2-R1-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-R3-R4, wherein R2 and R4 are each independently selected from an amino group, an acetyl group or a palmitoyl group; R1 and R3 are each independently selected from Ile, Arg, D-Phe, Pro or are deleted, R1 and R3 are not deleted at the same time, and when R1 or R3 is deleted, at least one of R2 and R4 is a palmitoyl group.

11. The lipid-lowering drug according to claim 10 or 11, characterized in that: R1 is Arg; R2 is acetyl or palmitoyl; R3 is Ile, Arg, D-Phe, Pro or missing; R4 is amino; Furthermore, when R3 is absent, R2 is a palmitoyl group.

12. The lipid-lowering drug according to claim 10 or 11, characterized in that: The disulfide cyclic peptide compound has the following structural formula: wherein R1, R2, R3 and R4 are as defined in claim 10 or 11.

13. The lipid-lowering drug according to claim 10 or 11, characterized in that: R3 is selected from Ile, D-Phe, Pro or is missing, and R1 is Arg.

14. The lipid-lowering drug according to claim 10 or 11, characterized in that: R2 is selected from an acetyl group or a palmitoyl group, and R4 is an amino group.

15. The lipid-lowering drug according to claim 10 or 11, characterized in that: When R3 is absent, R4 is a palmitoyl group.

16. The lipid-lowering drug according to claim 10 or 11, characterized in that: The disulfide cyclic peptide compound is selected from at least one of the following compounds: 。 17. The lipid-lowering drug according to claim 10 or 11, characterized in that: The disulfide cyclic peptide compound is selected from at least one of the following compounds: 、 、 、 。 18. The lipid-lowering drug according to claim 10 or 11, characterized in that: The disulfide cyclic peptide compound is selected from at least one of the following compounds: 。

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