Application of amomum tsao-ko essential oil in preparation of medicine for preventing and treating aortic dissection

Abstract

The invention provides application of amomum tsao-ko essential oil in preparation of medicines for preventing and treating aortic dissection, and finds that the amomum tsao-ko essential oil can obviously reduce the death rate of mice with aortic dissection, improve the survival rate of the mice and reduce the aortic arch dilation degree and the blood vessel inner diameter; the occurrence of the aortic dissection and the cavity and rupture of the aortic middle-layer structure are inhibited, and a novel potential therapeutic drug is provided for the treatment of the aortic dissection.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparations, and in particular relates to the application of cardamom essential oil in the preparation of drugs for the prevention and treatment of aortic dissection. Background Technology

[0002] Aortic dissection is a life-threatening condition, typically caused by a tear in the aortic intima or intramural hemorrhage, allowing blood to enter the aortic media and form a false lumen, leading to a degenerative remodeling of the aortic wall. As blood continues to flow into the aortic wall, the intimal flap can extend proximally and distally from the initial tear or hemorrhage site, potentially affecting collateral arteries. The first two weeks after the onset of aortic dissection are considered the acute phase, during which patients are highly susceptible to life-threatening complications and death. Treatment for aortic dissection primarily includes medication and surgery. Although these treatments have made significant progress, the high complexity of aortic dissection surgery, postoperative multi-organ dysfunction, and coagulation disorders cannot be completely avoided. Furthermore, postoperative vascular degeneration can lead to further degenerative changes, increasing the risk of secondary surgery and rupture. Therefore, preventative and therapeutic drugs for acute aortic dissection remain a hot topic in clinical research.

[0003] Cardamom, also known as Amomum tsao-ko, is the dried, mature fruit of a perennial herbaceous plant belonging to the genus Amomum in the ginger family (Zingiberaceae). In my country, it is mainly distributed in Yunnan, Guangxi, Guizhou, and Sichuan provinces. As a major traditional Chinese medicine used both as food and medicine, cardamom is widely used not only as a food flavoring, but its deep-processed product—cardamom essential oil—also has significant application value. Cardamom essential oil is a natural volatile aroma component extracted from cardamom using physical or chemical methods; its chemical composition is a complex mixture. Currently, various active ingredients have been identified from cardamom volatile oil, mainly including six categories: monoterpenes, oxygenated monoterpenes, sesquiterpenes, oxygenated sesquiterpenes, aliphatic compounds, and aromatic compounds. Among them, eucalyptol, citral, 2-decenal, 2-dodecenal, and geraniol acetate are representative components with higher content and playing a dominant role in cardamom essential oil.

[0004] Recent studies have shown that cardamom essential oil possesses multiple biological activities, including antibacterial, anti-inflammatory, and antioxidant effects, leading to its widespread application in food, pharmaceutical, and cosmetic development. Of particular note are its key components, such as citral, eucalyptol, and α-terpineol, which have demonstrated potential effects in cardiovascular protection, including alleviating atherosclerosis, reducing hypertension, and mitigating heart damage.

[0005] However, although there is a certain research foundation for cardamom essential oil in the cardiovascular field, there are currently no research reports on its application in the prevention and treatment of aortic dissection. Therefore, systematically exploring the potential applications of cardamom essential oil in the prevention and treatment of aortic dissection will not only help expand its new uses in the medical field, but also provide new natural product resources for the prevention and treatment of cardiovascular diseases, which has important scientific value and social significance. Summary of the Invention

[0006] In view of this, the present invention aims to propose the application of cardamom essential oil in the preparation of drugs for the prevention and treatment of aortic dissection, and to provide a new potential therapeutic drug for the treatment of aortic dissection.

[0007] To achieve the above objectives, the technical solution of the present invention is implemented as follows: In a first aspect, the present invention provides the use of cardamom essential oil in the preparation of drugs for the prevention and / or treatment of aortic dissection.

[0008] Furthermore, the cardamom essential oil is the sole active ingredient.

[0009] Furthermore, the application includes at least one of the following: (1) Application in the preparation of drugs that reduce the incidence and / or mortality of aortic dissection; (2) Application in the preparation of drugs that reduce the degree of aortic arch dilation; (3) Application in the preparation of drugs that reduce the inner diameter of the aorta; (4) Application in the preparation of drugs that inhibit cavitation and / or rupture of the aortic media structure; (5) Application in the preparation of drugs that reduce the breakage of elastic fibers in the neutral membrane of the aorta; (6) Application in the preparation of drugs that reduce collagen deposition in the neutral membrane of the aorta; (7) Application in the preparation of drugs that reduce the accumulation of glycosaminoglycans in the neutral membrane of the aorta; (8) Application in the preparation of drugs that inhibit the expression level of phenotypic transformation genes in aortic smooth muscle cells.

[0010] Furthermore, the daily dosage of the cardamom essential oil can be taken at the conventional dosage; preferably, the daily dosage of the cardamom essential oil is ≤15μL / kg. These dosages can vary depending on the patient's needs, the severity of the condition being treated, and the compounds used. Generally, treatment begins with a smaller dose than the optimal dose of the compound, and then the dose is gradually increased to achieve the best effect. For convenience, if necessary, the total daily dose can be further divided into multiple administrations throughout the day.

[0011] Furthermore, the aortic dissection includes acute aortic dissection or repair aortic dissection.

[0012] Secondly, the present invention provides a pharmaceutical preparation for the prevention and treatment of aortic dissection, wherein the active ingredient of the pharmaceutical preparation includes cardamom essential oil.

[0013] Furthermore, the cardamom essential oil is the sole active ingredient.

[0014] Furthermore, the method for extracting the cardamom essential oil includes the following steps: S1. After crushing the cardamom fruit, put it into a supercritical CO2 extractor and pressurize it to a supercritical state to obtain the initial oil. S2. Centrifuge the initial oil obtained by supercritical CO2 extraction. After centrifugation, separate the upper layer of cardamom oil, which is denoted as cardamom oil 1, and the lower layer is waxy. S3. The wax obtained after centrifugation in step S2 is dissolved in ethanol and then centrifuged again. The upper layer solution is collected and concentrated to obtain cardamom oil 2. S4. Combine the cardamom oil 1 and cardamom oil 2, distill them, and collect the fraction with an evaporation temperature of 60°C to obtain the cardamom essential oil.

[0015] Furthermore, in step S1, the extraction parameters are: 18 MPa / 55℃; the separation parameters are: 6.5 MPa / 60℃; and the time is: 90 min.

[0016] Preferably, in step S1, the cardamom fruit is crushed and then passed through a 20-60 mesh sieve.

[0017] Further, in step S2, the centrifugation speed is 1000~5000 r / min, for example, it can be 1000 r / min, 1500 r / min, 2000 r / min, 2500 r / min, 3000 r / min, 3500 r / min, 4000 r / min, 4500 r / min, or 5000 r / min; the centrifugation temperature is 1~10℃, for example, it can be 1℃, 2℃, 3℃, 4℃, 5℃, 6℃, 7℃, 8℃, 9℃, or 10℃; and the centrifugation time is 5~25 min, for example, it can be 5 min, 10 min, 15 min, 20 min, or 25 min.

[0018] Further, in step S3, the volume ratio of wax to ethanol is 1:5 to 10, for example, it can be 1:5, 1:6, 1:7, 1:8, 1:9, or 1:10; preferably, the ethanol is 95% (volume fraction) ethanol. Further, in step S3, the centrifugation speed is 1000~5000 r / min, for example, it can be 1000 r / min, 1500 r / min, 2000 r / min, 2500 r / min, 3000 r / min, 3500 r / min, 4000 r / min, 4500 r / min, or 5000 r / min; the centrifugation temperature is 1~10℃, for example, it can be 1℃, 2℃, 3℃, 4℃, 5℃, 6℃, 7℃, 8℃, 9℃, or 10℃; and the centrifugation time is 5~25 min, for example, it can be 5 min, 10 min, 15 min, 20 min, or 25 min. Furthermore, in step S3, the concentration temperature is 60~70℃, for example, it can be 60℃, 62℃, 65℃, 68℃, or 70℃.

[0019] Further, in step S4, the feed temperature for distillation is 40~60℃, for example, 40℃, 45℃, 50℃, 55℃, or 60℃, and the flow rate is 300~600mL / h, for example, 300mL / h, 350mL / h, 400mL / h, 450mL / h, 500mL / h, 550mL / h, or 600mL / h. Preferably, in step S4, the distillation is a two-stage distillation, with the first stage evaporation temperature at 120°C and the second stage evaporation temperature at 60°C.

[0020] Furthermore, the pharmaceutical preparation also includes pharmaceutically acceptable excipients.

[0021] Furthermore, the excipients include at least one of the following: diluent, binder, wetting agent, lubricant, disintegrant, solvent, emulsifier, cosolvent, preservative, pH adjuster, osmotic pressure adjuster, surfactant, coating material, antioxidant, or buffer.

[0022] Furthermore, the dosage form of the pharmaceutical preparation is a clinically acceptable oral, injectable, or inhaled preparation. For those skilled in the art, the above-mentioned dosage form may contain cardamom essential oil as an active ingredient to prepare the desired pharmaceutical preparation.

[0023] Furthermore, the pharmaceutical preparation is a dosage form including at least one of suspension, granules, capsules, powders, tablets, pills, injections, suppositories, aerosols, or drops.

[0024] Furthermore, the drug preparation is administered via one of the following routes: intravenous injection, intraperitoneal injection, intramuscular injection, subcutaneous injection, oral administration, sublingual administration, nasal administration, or nebulized administration.

[0025] For the preparation of pharmaceutical formulations suitable for this invention, a pharmaceutically acceptable carrier may be a solid or a liquid.

[0026] Solid dosage forms include powders, tablets, tablets, capsules, flat capsules, and dispersible granules. Solid carriers can be one or more substances that also function as diluents, flavoring agents, solubilizers, lubricants, suspending agents, binders, preservatives, tablet disintegrants, or encapsulating materials. In powders, the carrier is a finely divided solid that is mixed with a finely divided active ingredient. In tablets, the active ingredient is mixed with a carrier possessing the necessary binding properties in an appropriate proportion and compressed into the desired shape and size. Suitable carriers include magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth gum, methylcellulose, sodium carboxymethyl cellulose, low-melting-point waxes, cocoa butter, etc.

[0027] Liquid formulations include solutions, suspensions, and emulsions, such as aqueous solutions or water-propylene glycol solutions. For example, parenteral liquid formulations can be formulated as water-polyethylene glycol solutions.

[0028] Therefore, the medicaments used in this invention can be formulated into preparations for parenteral administration (e.g., injection, such as rapid concentration or continuous infusion), and can be present in unit doses in ampoules, pre-filled syringes, small-volume infusion bags, or multi-dose containers together with added preservatives. The composition can be in the form of suspensions, solutions, or emulsions with oily or aqueous carriers, and may contain formulation components such as suspending agents, stabilizers, and / or dispersants. Additionally, the active ingredient can be in powder form, obtained by aseptic separation of sterile solids or by lyophilization of solutions, for reconstitution with a suitable carrier, such as sterile, pyrogen-free water, immediately before use.

[0029] Aqueous solutions suitable for oral administration can be prepared by dissolving the active ingredient in water and adding the desired colorants, flavorings, stabilizers, and thickeners. Aqueous suspensions suitable for oral administration can be prepared by dispersing finely divided active ingredients in water containing a viscous substance, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, or other known suspending agents.

[0030] This also includes solid dosage forms designed to be converted into liquid formulations for oral administration shortly before market launch. These liquid formulations include solutions, suspensions, and emulsions. In addition to the active ingredient, these formulations may contain colorants, flavoring agents, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizers, etc.

[0031] Inhalational administration can also be achieved via aerosols, in which the active ingredient is packaged with a suitable propellant in a pressurized container. Suitable propellants include chlorofluorocarbons (CFCs) such as dichlorodifluoromethane, trichlorofluoromethane, or dichlorotetrafluoroethane, carbon dioxide, or other suitable gases. Aerosols may also contain surfactants, such as lecithin, as appropriate. The dosage of the drug can be controlled via a dispensing valve.

[0032] Alternatively, the active ingredient can be in the form of a dry powder, such as astaxanthin mixed with a suitable powder matrix such as lactose, starch, starch derivatives such as hydroxypropyl methylcellulose, and polyvinylpyrrolidone (PVP). The powder carrier can easily form a gel in the nasal cavity. The powder composition can be present in unit dose form, for example, in capsules or cartridges (such as gelatin sheets or cartridges), or in blister packs in which the powder can be administered via an inhaler.

[0033] Alternatively, compositions suitable for sustained release of active ingredients can be applied when needed.

[0034] Compared with existing technologies, the application of the cardamom essential oil described in this invention in the preparation of drugs for the prevention and treatment of aortic dissection has the following advantages: (1) The present invention found that cardamom essential oil can significantly reduce the mortality rate of mice with aortic dissection, improve the survival rate of mice, and reduce the degree of aortic arch dilation and vascular diameter; inhibit the occurrence of aortic dissection and the cavity and rupture of the aortic media structure, thus providing a new potential therapeutic drug for the treatment of aortic dissection.

[0035] (2) Through the study of the pharmacological effects of cardamom essential oil, this invention has discovered and verified the use of cardamom essential oil in the prevention and treatment of acute aortic dissection. Cardamom essential oil has a significant effect in improving acute aortic dissection, providing a solid pharmacodynamic basis for new clinical research and application of this drug. After systematic development, it has a broad market prospect and also provides an example for the medicinal route of classic health products and the "new use of old drugs".

[0036] (3) This invention not only establishes a mature animal disease model of acute aortic dissection, providing a solid foundation for subsequent drug development, but also, based on the established animal disease model, discovers and verifies the therapeutic and preventive effects of cardamom essential oil in improving the prognosis of acute aortic dissection. Attached Figure Description

[0037] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an undue limitation of the invention. In the drawings: Figure 1 A schematic diagram illustrating the principle of drug intervention in each group of mice; Figure 2 Survival curves for each group of mice; Figure 3 A schematic diagram showing the incidence of aortic dissection in each group of mice; Figure 4 A representative macroscopic diagram of the aortic tissue of each group of mice; Figure 5Typical ultrasound images of the aorta of mice in each group and schematic diagrams of diameter statistics; Figure 6 Schematic diagram showing Masson staining and collagen content results of aortic tissue from each group of mice; Figure 7 Schematic diagram showing the results of EVG staining and the number of elastic fiber breaks in the aortic tissue of mice in each group; Figure 8 A schematic diagram showing the Alcian Blue staining and glycosaminoglycan content results of aortic tissue from each group of mice. Figure 9 A schematic diagram showing the relative expression levels of genes transforming the smooth muscle phenotype in the aortic tissue of mice in each group. Figure 10 This is a schematic diagram showing the results of detecting the relative expression levels of inflammatory factors and aging-related factors in the aortic tissue of mice in each group. Detailed Implementation

[0038] It should be noted that, unless otherwise specified, the embodiments and features described in the present invention can be combined with each other.

[0039] The present invention will now be described in detail with reference to the accompanying drawings and embodiments.

[0040] This invention establishes a recognized animal model of acute aortic dissection, namely, feeding C57BL / 6J mice with β-aminopropionitrile (BAPN) for 4 weeks to induce the destruction of elastic fiber crosslinking in the aortic wall, leading to aortic dissection formation. This model simulates clinical acute aortic dissection injury. The successful establishment of the model was verified by multiple indicators, including gross pathological morphology of the aorta and pathological staining of lesion sections. It can be used to verify the efficacy of cardamom essential oil. The specific method is as follows: (1) Construction of a mouse model of aortic dissection All animal experiments were conducted in accordance with the guidelines for the use and care of laboratory animals and were approved by the Ethics Committee of China Agricultural University.

[0041] Three-week-old male C57Bl / 6J mice (purchased from Spifort Beijing Biotechnology Co., Ltd.) were randomly divided into three groups: a control group, a BAPN group, and a cardamom essential oil group. The control group was fed a normal diet for 21 consecutive days, while the BAPN group and the cardamom essential oil group were fed a diet containing 0.4% BAPN for 21 consecutive days to establish an aortic dissection model.

[0042] (2) Preparation of cardamom essential oil The cardamom fruit was crushed into appropriate particle size (50 mesh) to increase its surface area and facilitate extraction. The crushed cardamom particles were placed in a supercritical CO2 extractor and pressurized to a supercritical state to obtain the primary oil. Extraction parameters: 18 MPa / 55℃; separation parameters: 6.5 MPa / 60℃; time: 90 min.

[0043] The initial oil obtained from supercritical CO2 extraction was centrifuged under the following conditions: 4000 r / min, 5℃, 15 min. After centrifugation, the upper layer of cardamom oil was separated and designated as Cardamom Oil 1, while the lower layer was a waxy substance.

[0044] The lower waxy layer, which is difficult to separate from the cardamom oil after centrifugation in the above steps, is added to 10 times its volume of 95% (volume fraction) ethanol. After thorough dissolution, it is centrifuged at 4000 r / min, 5℃, for 15 min. The upper layer of cardamom oil containing ethanol is separated after centrifugation and concentrated at 65℃; the concentrated liquid is designated as Cardamom Oil 2. Cardamom Oil 1 and Cardamom Oil 2 are combined.

[0045] Finally, the dehydrated cardamom oil was subjected to molecular distillation. The feed temperature was 50℃, the flow rate was 500mL / h, the first stage evaporation temperature was 120℃, and the second stage evaporation temperature was 60℃. The cardamom essential oil obtained from the second stage distillation was collected and used as raw material for subsequent experiments.

[0046] (3) Administration of cardamom essential oil to mice The cardamom essential oil group received an intraperitoneal injection of 60 μL / kg cardamom essential oil per mouse daily. During the administration period, mouse weight and mortality were recorded. After administration, the aortic diameter was measured by ultrasound, and the formation of aortic dissection was observed after dissection. The incidence rate was recorded. Mice (n=12 per group) were sacrificed on day 21. The timeline of model establishment and drug intervention is as follows: Figure 1 As shown.

[0047] Data processing was performed using SPSS 13.0 software. Statistical results are expressed as mean ± standard error (±SEM). Differences between two groups were analyzed using t-tests. When comparing multiple groups, ANOVA was used, and Bonferroni correction was employed for further analysis and validation. A p-value < 0.05 was considered statistically significant. * indicates p < 0.05, ** indicates p < 0.01, and *** indicates p < 0.001.

[0048] Figure 2 The black line represents the control group, the red broken line represents the cardamom essential oil group, and the blue line represents the survival curve of mice in the BAPN group. According to... Figure 2The results showed that compared with the BAPN group, the survival rate of mice in the cardamom essential oil group was significantly improved, proving that cardamom essential oil can reduce the mortality and incidence of aortic dissection in mice. Figure 3 The results showed that on day 21, the mortality rate of mice in the BAPN group was as high as 75%, and the morbidity rate was 25%, while the mortality rate of the cardamom essential oil group was 17%, the morbidity rate was 33%, and the health rate was 50%, proving that cardamom essential oil has a significant effect on the prevention and treatment of aortic dissection.

[0049] Representative macroscopic images of the aorta (e.g.) Figure 4 (as shown), typical aortic ultrasound image and diameter statistics (such as...) Figure 5 As shown in the figure, compared with the control group mice, the BAPN group mice developed severe aortic dissection, while the cardamom essential oil group also developed aortic dissection but with milder symptoms, proving that cardamom essential oil can reduce the degree of aortic arch dilation and the inner diameter of the aorta.

[0050] Further as Figure 6-8 As shown, histological analysis proves that, compared with the BAPN group, cardamom essential oil can reduce the rupture of elastic fibers, collagen deposition, and accumulation of glycosaminoglycans in the aortic neutral lamina, thereby affecting the occurrence and development of aortic dissection.

[0051] Results of smooth muscle phenotype transformation-related gene expression level detection (e.g.) Figure 9 As shown in the figure, compared with the BAPN model group, after intervention with cardamom essential oil, the expression of synthetic marker genes Col1a1, Col3a1, and Mmp2 in mouse aortic smooth muscle cells was upregulated, indicating enhanced activity related to smooth muscle cell proliferation and matrix remodeling; while the expression of contractile marker genes Myh11, Myl9, and Acta2 was downregulated, indicating a decrease in smooth muscle contractile function.

[0052] Results of gene expression level detection for aging and inflammatory factors (e.g.) Figure 10 As shown in the figure, compared with the BAPN model group, after intervention with cardamom essential oil, the expression of aging-related genes p16, p21, and p53 was significantly downregulated, suggesting that cardamom essential oil can alleviate the aging process of aortic tissue in BAPN-induced dissected mice; the expression of inflammation-related factors Cxcl1, Il1a, and Tnf-alpha was reduced, indicating that the local inflammatory response was significantly inhibited.

[0053] The above results demonstrate that cardamom essential oil can significantly reduce the mortality rate and improve the survival rate of mice with aortic dissection, and reduce the degree of aortic arch dilation and vascular diameter; it also inhibits the occurrence of aortic dissection and the cavity and rupture of the aortic medial structure, providing a new potential therapeutic drug for the treatment of aortic dissection.

[0054] The embodiments described above are only some embodiments of the present invention, not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention.

Claims

1. Application of cardamom essential oil in the preparation of drugs for the prevention and / or treatment of aortic dissection.

2. The application according to claim 1, characterized in that: The cardamom essential oil is the only active ingredient.

3. The application according to claim 1, characterized in that, The application includes at least one of the following: (1) Application in the preparation of drugs that reduce the incidence and / or mortality of aortic dissection; (2) Application in the preparation of drugs that reduce the degree of aortic arch dilation; (3) Application in the preparation of drugs that reduce the inner diameter of the aorta; (4) Application in the preparation of drugs that inhibit cavitation and / or rupture of the aortic media structure; (5) Application in the preparation of drugs that reduce the breakage of elastic fibers in the neutral membrane of the aorta; (6) Application in the preparation of drugs that reduce collagen deposition in the neutral membrane of the aorta; (7) Application in the preparation of drugs that reduce the accumulation of glycosaminoglycans in the neutral membrane of the aorta; (8) Application in the preparation of drugs that inhibit the expression level of phenotypic transformation genes in aortic smooth muscle cells.

4. The application according to claim 1, characterized in that: The daily dosage of the cardamom essential oil is ≤15μL / kg.

5. The application according to claim 1, characterized in that: The aortic dissection includes acute aortic dissection or repair aortic dissection.

6. A pharmaceutical preparation for the prevention and treatment of aortic dissection, characterized in that, The active ingredient of the pharmaceutical preparation includes cardamom essential oil, which is the sole active ingredient.

7. The pharmaceutical preparation according to claim 6, characterized in that, The preparation method of the cardamom essential oil includes the following steps: S1. After crushing the cardamom fruit, put it into a supercritical CO2 extractor and pressurize it to a supercritical state to obtain the initial oil. S2. Centrifuge the initial oil obtained by supercritical CO2 extraction. After centrifugation, separate the upper layer of cardamom oil, which is denoted as cardamom oil 1, and the lower layer is waxy. S3. The wax obtained after centrifugation in step S2 is dissolved in ethanol and then centrifuged again. The upper layer solution is collected and concentrated to obtain cardamom oil 2. S4. Combine the cardamom oil 1 and cardamom oil 2, distill them, and collect the fraction with an evaporation temperature of 60°C to obtain the cardamom essential oil. Preferably, in step S1, the extraction parameters are: 18 MPa / 55℃; the separation parameters are: 6.5 MPa / 60℃; and the time is: 60~120 min. Preferably, in step S2, the centrifugation speed is 1000~5000 r / min, the centrifugation temperature is 1~10℃, and the centrifugation time is 5~25 min; Preferably, in step S3, the volume ratio of wax to ethanol is 1:5~10; Preferably, in step S3, the centrifugation speed is 1000~5000 r / min, the centrifugation temperature is 1~10℃, and the centrifugation time is 5~25 min; Preferably, in step S3, the concentration temperature is 60~70℃; Preferably, in step S4, the feed temperature for distillation is 40~60℃ and the flow rate is 300~600mL / h; Preferably, in step S4, the first-stage evaporation temperature is 120°C, and the second-stage evaporation temperature is 60°C.

8. The pharmaceutical preparation according to claim 6, characterized in that: The pharmaceutical preparation also includes pharmaceutically acceptable excipients.

9. The pharmaceutical preparation according to claim 8, characterized in that, The excipients include at least one of the following: diluent, binder, wetting agent, lubricant, disintegrant, solvent, emulsifier, cosolvent, preservative, pH adjuster, osmotic pressure adjuster, surfactant, coating material, antioxidant, or buffer.

10. The pharmaceutical preparation according to claim 6, characterized in that: The dosage form of the pharmaceutical preparation is a clinically acceptable oral, injectable, or inhaled formulation.

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