Pinocembrin and aminoglycoside drug synergistic antibacterial composition and application thereof
By leveraging the synergistic effect of geranosin and aminoglycosides, the problems of drug resistance and toxic side effects of aminoglycosides have been solved, providing a highly effective antibacterial treatment regimen against Vibrio parahaemolyticus, applicable to tablets, creams, capsules and other dosage forms.
Patent Information
- Application Number
- CN202511947202.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-23
- Publication Date
- 2026-02-27
AI Technical Summary
Existing antibacterial drugs, such as aminoglycosides, have problems such as drug resistance, toxic side effects, and low therapeutic index during use. They are particularly difficult to treat Vibrio parahaemolyticus infections, and new drug development cycles are long with limited market returns.
Gorhodin is compounded with aminoglycoside drugs such as gentamicin or neomycin sulfate in an appropriate ratio to form an antibacterial composition, which is used to prepare antibacterial drugs, including tablets, creams, capsules and other dosage forms. Gorhodin enhances the antibacterial activity of aminoglycoside drugs and reduces their toxic side effects.
It significantly improves antibacterial activity against Vibrio parahaemolyticus, reduces drug toxicity and side effects, provides an effective treatment option for multidrug-resistant strains, and has good prospects for clinical application.
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Figure CN121570478A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biomedical technology, specifically relating to an antibacterial composition that synergistically enhances the effects of geraniol and aminoglycoside drugs, and its application. Background Technology
[0002] Vibrio parahaemolyticus is one of the leading foodborne pathogens in coastal areas worldwide, widely found in nearshore seawater, seabed sediments, and seafood. It primarily causes acute gastroenteritis, which can lead to systemic infection in severe cases, posing a significant threat to public health. Its pathogenic strains not only harm human health but also impact aquaculture. Acute hepatopancreas necrosis disease (AHPND) in shrimp, caused by specific strains, is widespread and rapidly spreading, resulting in mortality rates exceeding 90% in shrimp. In recent years, with increased demand for seafood, the promotion of cold chain logistics, and changes in the marine environment due to global warming, the incidence of Vibrio parahaemolyticus infection has been on the rise, particularly in coastal areas, becoming a significant issue affecting public health and aquaculture.
[0003] Vibrio parahaemolyticus ( V. parahaemolyticus The drug resistance problem of this bacterium is becoming increasingly serious due to the irrational use of antibiotics in aquaculture. Currently, the detection rate of multidrug-resistant strains of this bacterium is as high as 50% to 70%, leading to a sharp increase in the difficulty of treating infections such as food poisoning and septicemia caused by it. In cases of multidrug-resistant strain infection, commonly used drugs may even become ineffective, seriously threatening the development of aquaculture and public health. If this trend continues, as a representative of foodborne drug-resistant bacteria, it is projected to account for a significant share of the 10 million drug-related deaths worldwide by 2050.
[0004] Currently, the development cycle of newly developed antibacterial drugs is long and the actual market returns are limited. This makes antibacterial synergists with broad-spectrum synergistic activity a better choice than developing new antibacterial drugs. They have a wider range of applications and frequencies, and also have higher market return expectations.
[0005] Aminoglycosides are a class of concentration-dependent bactericidal agents composed of amino sugars and aminocyclic alcohols linked by an oxygen bridge. They exert their bactericidal effect by irreversibly binding to the bacterial 30S ribosomal subunit, interfering with mRNA translation, and disrupting bacterial cell membrane integrity. They primarily target aerobic Gram-negative bacteria, including Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae), non-fermenting bacteria (Pseudomonas aeruginosa, Acinetobacter), and some mycobacteria (Mycobacterium tuberculosis). Clinically used aminoglycosides include gentamicin, neomycin, amikacin, tobramycin, streptomycin, and kanamycin. However, their use is often accompanied by multiple toxic side effects, including ototoxicity and nephrotoxicity, severely limiting their application. Reducing the dosage is an effective way to significantly alleviate these side effects. Therefore, developing effective aminoglycoside potentiators has become an important strategy for treating infections caused by multidrug-resistant Gram-negative bacteria.
[0006] Pinocemrin, also known as pine resin or pinocemrin, is a class of widely used dihydroflavanone compounds with the molecular formula C1. 15 H 12 O4, with a molecular weight of 256.26, is characterized by a hydroxyl substitution pattern in the C-ring of the flavonoid skeleton to form specific functional groups, as shown in the following structure:
[0007] This component can be isolated from various plants such as propolis, ginkgo leaves, and cardamom, and possesses multiple biological activities including antibacterial, antiviral, anti-inflammatory, antioxidant, and immunomodulatory effects. Studies have reported that jugalin exhibits antibacterial activity against Campylobacter and Aeromonas. However, there are currently no reports on the antibacterial activity of jugalin as an adjuvant to enhance the efficacy of antibacterial drugs. Summary of the Invention
[0008] In view of the deficiencies in the prior art, this invention proposes an antibacterial composition and its application that synergistically enhances the effects of the natural product arbutin and aminoglycoside drugs. By combining arbutin and aminoglycoside drugs in an appropriate ratio, the resulting composition exhibits superior antibacterial activity. In the current environment where various bacteria are gradually developing resistance to common antibacterial drugs, this has extremely important practical significance and clinical research needs.
[0009] The technical solution adopted in this invention: An antibacterial composition comprising geraniol and an aminoglycoside drug.
[0010] In one optional embodiment, the aminoglycoside drug is specifically gentamicin, neomycin, or a pharmaceutically acceptable salt thereof.
[0011] The antibacterial composition is geraniol and gentamicin or their pharmaceutically acceptable salts, in a mass ratio of 1:(2~4), specifically 1:2 or 1:4.
[0012] The antibacterial composition is geraniol and neomycin sulfate or their pharmaceutically acceptable salts, in a mass ratio of 1:(2~4), specifically 1:2 or 1:4.
[0013] The present invention also provides the use of the antibacterial composition in the preparation of drugs against Vibrio parahaemolyticus.
[0014] In one optional embodiment, the antibacterial drug has an inhibitory / killing effect on bacteria, wherein the bacteria are Vibrio parahaemolyticus.
[0015] In one optional embodiment, the bactericidal composition is prepared into a pharmaceutically acceptable dosage form with a pharmaceutically acceptable adjuvant or carrier.
[0016] The additives or carriers include, but are not limited to, water-soluble carrier materials (such as polyethylene glycol, polyvinylpyrrolidone, organic acids, etc.), poorly soluble carrier materials (such as ethyl cellulose, cholesterol stearate, etc.), and enteric carrier materials (such as cellulose acetate phthalate and carboxymethyl ethyl cellulose, etc.).
[0017] The dosage forms include: tablets, creams, capsules, sustained-release and controlled-release preparations, oral liquids, syrups, pellets, injections, lyophilized powder injections, and nano-preparations.
[0018] Compared with the prior art, the present invention has the following beneficial effects: 1. This invention provides a novel use of galactosin in enhancing the antibacterial activity of aminoglycoside drugs, which can solve technical problems such as drug resistance, low therapeutic index and drug toxicity of aminoglycoside drugs.
[0019] 2. The antibacterial composition provided by this invention differs from existing compounds combined with aminoglycoside drugs. The compound can restore the sensitivity of aminoglycoside drugs and significantly reduce the toxic side effects of antibacterial drugs. The combination of the two exhibits strong anti-Vibrio parahaemolyticus activity, demonstrating a better antibacterial effect. This contributes to the development of a new type of antibacterial drug synergist, alleviating the increasingly serious problem of bacterial resistance. Attached Figure Description
[0020] Figure 1 Checkerboard thermogram of the combination of geraniol and neomycin sulfate against Vibrio parahaemolyticus ATCC17082; Figure 2 Checkerboard thermogram of the combination of gentamicin and gentamicin against Vibrio parahaemolyticus ATCC17082; Figure 3Checkerboard thermogram of the combination of geraniol and gentamicin against Vibrio parahaemolyticus CICC24174; Figure 4 The in vitro bactericidal curve of the combination of geraniol and neomycin sulfate against Vibrio parahaemolyticus ATCC17082 is shown. Figure 5 The in vitro bactericidal curve of the combination of geraniol and gentamicin against Vibrio parahaemolyticus ATCC17082 is shown. Figure 6 The in vitro bactericidal curve of the combination of geraniol and gentamicin against Vibrio parahaemolyticus CICC24174 is shown. Detailed Implementation
[0021] The technical solutions of the embodiments of this application will be further described clearly and completely below with reference to the accompanying drawings. It should be noted that the described embodiments are only some embodiments of this application, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of this application without creative effort are within the scope of protection of this application.
[0022] To better understand the above-mentioned objectives, features, and advantages of the present invention, the advantages of the present invention will be further illustrated below by comparing the embodiments with the accompanying drawings and specific implementation details.
[0023] The standard strain of Vibrio parahaemolyticus, ATCC17802, was purchased from the American Type Culture Collection (ATCC); and the pathogenic strain CICC24174, carrying the AHPND pathogenicity genes PirA and B, was purchased from the China Center of Industrial Culture Collection (CICC). Single colonies of both bacteria were picked and cultured in trypsin-soybean broth (3% NaCl TSB) at 37°C in a shaker until the logarithmic growth phase. The bacterial concentration was then adjusted to 0.5 McFarland turbidity using a McFarland turbidimeter before use.
[0024] Selected Escherichia coli ( E.Coli The standard strain ATCC25922 of Staphylococcus aureus was purchased from the American Type Culture Collection (ATCC); and Staphylococcus aureus (… S.aureusThe standard strain ATCC29213 was purchased from the American Type Culture Collection (ATCC). Single colonies of both bacteria were picked and cultured on MHB medium at 37°C in a shaker until the logarithmic growth phase. The bacterial concentration was then adjusted to 0.5 McFarland turbidity using a McFarland turbidimeter before use.
[0025] Weigh out a certain amount of gentamicin and prepare a stock solution with a concentration of 20 mg / mL using dimethyl sulfoxide (DMSO); prepare stock solutions with a concentration of 20 mg / mL for gentamicin, neomycin sulfate, streptomycin, amikacin, and kanamycin, which are aminoglycoside drugs. The pine resin and aminoglycosides were serially diluted to multiple concentration gradients using TSB medium: the final concentrations of pine resin were 256 μg / mL, 128 μg / mL, 64 μg / mL, 32 μg / mL, 16 μg / mL, 8 μg / mL, 4 μg / mL, 2 μg / mL, 1 μg / mL, 0.5 μg / mL, and 0.25 μg / mL, respectively; the final concentrations of aminoglycosides were 512 μg / mL, 256 μg / mL, 128 μg / mL, 64 μg / mL, 32 μg / mL, 16 μg / mL, 8 μg / mL, 4 μg / mL, 2 μg / mL, 1 μg / mL, and 0.5 μg / mL, respectively, and were reserved for future examples.
[0026] Example 1 This embodiment provides a method for determining the minimum inhibitory concentration (MIC) of ginsenosides and different aminoglycosides against different bacterial strains. The steps are as follows: Take 100 μL of bacterial suspension (the final concentration of bacterial suspension per well is 1.0 × 10⁻⁶). 6 CFUs mL -1 Add the drug to 96-well U-shaped plates, then add 100 μL of different drugs to each well. The negative control group contains only broth medium; the positive control group contains the test bacterial suspension containing 0.2% DMSO. The experimental groups consist of various concentrations of berberine and various concentrations of aminoglycoside single drugs. After adding the drugs, the culture plates were placed in a 37℃ incubator for 18 hours and the results were observed. The drug concentration in the wells that are clear to the naked eye in the 96-well plate is the MIC. The detection results are shown in Table 1.
[0027] Table 1. Single-drug MIC values (μg / mL) of geraniol and different aminoglycosides against different bacterial strains.
[0028] As shown in Table 1, jossin exhibited good antibacterial activity against Vibrio parahaemolyticus ATCC17082 and CICC24174, with a MIC value of 64 μg / mL for both. However, it showed limited inhibitory effects against Escherichia coli ATCC25922 and Staphylococcus aureus ATCC29213, with a MIC value of 256 μg / mL, indicating that its antibacterial spectrum has significant selectivity.
[0029] Example 2 This embodiment provides a method for determining the MIC of different bacterial strains by combining ginsenosides with different aminoglycoside drugs, and a method for screening the synergistic antibacterial effect of the combination system against different bacterial strains. The steps are as follows: Take 100 μL of bacterial suspension (the final concentration of bacterial suspension per well is 1.0 × 10⁻⁶). 6 CFUs mL -1 Add the drug to a 96-well U-shaped plate, then add 100 μL of different drugs to each well. The negative control group contains only broth medium, the positive control group contains the test bacterial solution containing 0.2% DMSO, and the experimental groups contain 50 μL of each concentration of pineapple and 50 μL of each concentration of aminoglycoside. After adding the drugs, the culture plates are placed in an incubator at 37°C for 18 hours and the results are observed. The drug concentration in the wells that are clear to the naked eye in the 96-well plate is the minimum inhibitory concentration (MIC). Combined with the single-drug MIC values obtained in Example 1, the fractional inhibitory concentration index (FICI) is calculated. The calculation formula is as follows:
[0030] If FICI < 0.5, the effect is synergistic; if 0.5 ≤ FICI ≤ 1, the effect is additive; if FICI > 1, the effect is unrelated or antagonistic. The detection results are shown in Table 2.
[0031] Table 2. MIC values of pine resin combined with different aminoglycoside drugs against different bacterial strains.
[0032] Table 2 shows that, for Vibrio parahaemolyticus ATCC17082, combined with Figure 1 The checkerboard thermogram of the combination of gerbinin and neomycin sulfate against Vibrio parahaemolyticus ATCC17082 showed that the combination of 8 µg / mL gerbinin and 16 µg / mL neomycin sulfate was effective. Figure 1 The combination of the lightest concentrations in the sample exhibits an optimal synergistic effect with a FICI index of 0.375; combined with... Figure 2 Checkerboard thermogram of the combination of gerbinin and gentamicin against Vibrio parahaemolyticus ATCC17082; the combination of 4 µg / mL gerbinin and 16 µg / mL gentamicin is... Figure 2The combination of the lightest colors shows the lowest concentration, with a FICI index of 0.3125, achieving the best synergistic effect.
[0033] Targeting Vibrio parahaemolyticus CICC24174, combined with Figure 3 The checkerboard thermogram of the combination of gerbinin and gentamicin against Vibrio parahaemolyticus CICC24174 showed that the combination of 8 µg / mL gerbinin and 16 µg / mL gentamicin was effective. Figure 3 The combination of the lightest colors shows the lowest concentration, with a FICI index of 0.375, achieving the best synergistic effect.
[0034] When josine is combined with aminoglycosides, it has no effect on Escherichia coli ATCC25922 and Staphylococcus aureus ATCC29213.
[0035] The results showed that the combination of josinolide and neomycin sulfate had a significant synergistic antibacterial effect on Vibrio parahaemolyticus ATCC17082; the combination of josinolide and gentamicin had a significant synergistic antibacterial effect on both Vibrio parahaemolyticus ATCC17082 and CICC24174; and the combination of josinolide with other aminoglycoside drugs had an additive effect on both strains of Vibrio parahaemolyticus.
[0036] Example 3 This embodiment provides a method for determining the minimum bactericidal concentration (MBC) of jojoba extract and different aminoglycoside drugs, used alone and in combination, against different bacterial strains. The steps are as follows: Ten µL of the solution from each well of the 96-well microplate from Examples 1 and 2 that showed no bacterial growth was spotted onto tryptic soy broth (3% NaCl TSA). The plates were then incubated at 37°C for 18 hours. The lowest concentration of MBC in the wells where no bacterial growth was observed was recorded. The experimental results are shown in Table 3.
[0037] Table 3. MBC values of geraniol and aminoglycoside drugs used alone and in combination.
[0038] As shown in Table 3, for Vibrio parahaemolyticus ATCC17082, the MBCs of gentamicin and gentamicin alone were 128 µg / mL and 64 µg / mL, respectively, and the minimum bactericidal combination concentrations (MBCs) of the two combined were 8 µg / mL and 32 µg / mL, respectively. For Vibrio parahaemolyticus CICC24174, the MBCs of gentamicin and gentamicin alone were 128 µg / mL and 64 µg / mL, respectively, and the minimum bactericidal combination concentrations (MBCs) of the two combined were 16 µg / mL and 32 µg / mL, respectively. For Vibrio parahaemolyticus ATCC17082, the MBCs of gentamicin and neomycin sulfate alone were 128 µg / mL and 64 µg / mL, respectively, and the minimum bactericidal combination concentrations (MBCs) of the two combined were 8 µg / mL and 16 µg / mL, respectively.
[0039] The results showed that the combination of josinosteroids with neomycin sulfate and josinosteroids with gentamicin could both inhibit the growth of Vibrio parahaemolyticus and have a significant bactericidal effect on Vibrio parahaemolyticus, thus significantly reducing the amount of josinosteroids and aminoglycosides used in antibacterial applications.
[0040] Example 4 This embodiment provides an experiment to determine the bactericidal effect of geraniol, when used alone and in combination with neomycin sulfate and gentamicin, against Vibrio parahaemolyticus ATCC17082 and CICC24174. The steps are as follows: 1. Determination of the bactericidal effects of geraniol and neomycin sulfate against Vibrio parahaemolyticus ATCC17082 Vibrio parahaemolyticus was inoculated into TSB (3% NaCl) broth and enriched at 37°C and 200 rpm for 6 hours. The bacterial culture was then analyzed using a McFarland turbidimeter, and the turbidity was adjusted to 0.5, i.e., 1 × 10⁻⁶. 8 CFU / mL, then the bacterial culture was diluted to 1×10⁻⁶. 6 CFU / mL.
[0041] The bacterial culture was divided into four groups, and drug solutions were added to achieve the following final concentrations: 8 µg / mL pine resin group, 16 µg / mL neomycin sulfate group, 8 µg / mL pine resin + 16 µg / mL neomycin sulfate group, and a blank control group without any drug addition. The mixtures were incubated in a 37°C incubator. After 1 h, 3 h, 6 h, 12 h, and 24 h of incubation, 100 µL of each mixture was spread onto 9 cm diameter TSA (3% NaCl) agar medium and incubated overnight for colony counting.
[0042] Figure 4 In vitro bactericidal curves of geraniol and neomycin sulfate as single and combined drugs against Vibrio parahaemolyticus ATCC17082 are shown in the figure. Figure 4As shown, for Vibrio parahaemolyticus ATCC17082, at 24 h of treatment, compared with the control group, treatment with quinacrine and neomycin sulfate alone had no significant effect on bacterial colony count. When quinacrine and neomycin sulfate were used to treat the bacterial culture, at 6 h of treatment, the colony count was significantly lower than that of the control group and the single-drug treatment group. Until 24 h, the colony count in the combined treatment group was significantly lower than that of the control group and the single-drug group. The results indicate that the combined treatment with quinacrine and neomycin sulfate has a significant synergistic bactericidal effect on Vibrio parahaemolyticus ATCC17082.
[0043] 2. Determination of the bactericidal effects of geraniol and gentamicin against Vibrio parahaemolyticus ATCC17082 Vibrio parahaemolyticus was inoculated into TSB (3% NaCl) broth and enriched at 37°C and 200 rpm for 6 hours. The bacterial culture was then analyzed using a McFarland turbidimeter, and the turbidity was adjusted to 0.5, i.e., 1 × 10⁻⁶. 8 CFU / mL, then the bacterial culture was diluted to 1×10⁻⁶. 6 CFU / mL. The bacterial culture was divided into 4 groups and drug solutions were added to achieve the following final concentrations: 8 µg / mL pineapple group, 32 µg / mL gentamicin group, 8 µg / mL pineapple + 32 µg / mL gentamicin group, and a blank control group without any drug addition. The mixtures were incubated in a 37°C incubator. After 1 h, 3 h, 6 h, 12 h, and 24 h of incubation, 100 µL of each mixture was spread onto 9 cm diameter TSA (3% NaCl) agar medium and incubated overnight before colony counting.
[0044] Figure 5 In vitro bactericidal curves of gentamicin and gibberellin alone and in combination against Vibrio parahaemolyticus ATCC17082 are shown in the figures. Figure 5 As shown, for Vibrio parahaemolyticus ATCC17082, at 24 h of treatment, compared with the control group, treatment with gentamicin and pine resin alone had no significant effect on bacterial colony count. When pine resin and gentamicin were used to treat the bacterial culture, at 6 h of treatment, the colony count was significantly lower than that of the control group and the single-drug treatment group. Until 24 h, the colony count in the combined treatment group was significantly lower than that of the control group and the single-drug group. The results indicate that the combined treatment with pine resin and gentamicin has a significant synergistic bactericidal effect on Vibrio parahaemolyticus ATCC17082.
[0045] 3. Determination of the bactericidal effects of geraniol and gentamicin against Vibrio parahaemolyticus CICC24174 Vibrio parahaemolyticus was inoculated into TSB (3% NaCl) broth and enriched at 37°C and 200 rpm for 6 hours. The bacterial culture was then analyzed using a McFarland turbidimeter, and the turbidity was adjusted to 0.5, i.e., 1 × 10⁻⁶. 8CFU / mL, then the bacterial culture was diluted to 1×10⁻⁶. 6 CFU / mL. The bacterial culture was divided into 4 groups and drug solutions were added to achieve the following final concentrations: 16 µg / mL pineapple group, 32 µg / mL gentamicin group, 16 µg / mL pineapple + 32 µg / mL gentamicin group, and a blank control group without any drug addition. The mixtures were incubated in a 37°C incubator. After 1 h, 3 h, 6 h, 12 h, and 24 h of incubation, 100 µL of each mixture was spread onto 9 cm diameter TSA (3% NaCl) agar medium and incubated overnight before colony counting.
[0046] Figure 6 In vitro bactericidal curves of gentamicin and gibberellin as single and combined agents against Vibrio parahaemolyticus CICC24174 are shown in the figure. Figure 6 As shown, for Vibrio parahaemolyticus CICC24174, at 24 h of treatment, compared with the control group, treatment with gentamicin and ciprofloxacin alone had no significant effect on bacterial colony count. When ciprofloxacin and gentamicin were used to treat the bacterial culture, at 6 h of treatment, the colony count was significantly lower than that of the control group and the single-drug treatment group. Until 24 h, the colony count in the combined treatment group was significantly lower than that of the control group and the single-drug group. The results indicate that the combined treatment with ciprofloxacin and gentamicin has a significant synergistic bactericidal effect on Vibrio parahaemolyticus CICC24174.
[0047] In conclusion, when jossone is combined with aminoglycosides, it can significantly enhance the bactericidal rate and intensity against Vibrio parahaemolyticus, effectively reduce dependence on single drugs and improve antibacterial efficacy. This provides a feasible combination drug regimen for the clinical treatment of Vibrio parahaemolyticus infection and antibacterial control in aquaculture, and has the potential to be further developed into a drug combination against drug-resistant bacteria.
[0048] Although preferred embodiments of this application have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments as well as all changes and modifications falling within the scope of this application.
[0049] Obviously, those skilled in the art can make various modifications and variations to this application without departing from the spirit and scope of this application. Therefore, if such modifications and variations fall within the scope of the claims of this application and their equivalents, this application also intends to include such modifications and variations.
Claims
1. An antibacterial composition, characterized in that, This includes geraniol and aminoglycoside drugs.
2. The antibacterial composition according to claim 1, characterized in that, The aminoglycoside drugs specifically include gentamicin, neomycin, or their pharmaceutically acceptable salts.
3. The antibacterial composition according to claim 2, characterized in that, The antibacterial composition is geraniol and gentamicin or their pharmaceutically acceptable salts, in a mass ratio of 1:(2~4), specifically 1:2 or 1:
4.
4. The antibacterial composition according to claim 2, characterized in that, The antibacterial composition is geraniol and neomycin or their pharmaceutically acceptable salts, in a mass ratio of 1:(2~4), specifically 1:2 or 1:
4.
5. The use of an antibacterial composition as described in any one of claims 1-4 in the preparation of an antibacterial drug.
6. The application according to claim 5, characterized in that, The antibacterial drug has an inhibitory or bactericidal effect on bacteria, and the bacteria are Vibrio parahaemolyticus.
7. The application according to claim 5, characterized in that, The antibacterial composition is prepared into a pharmaceutically acceptable dosage form with a pharmaceutically acceptable adjuvant or carrier.
8. The application according to claim 7, characterized in that, The additives or carriers include, but are not limited to, water-soluble carrier materials, poorly soluble carrier materials, and enteric carrier materials.
9. The application according to claim 7, characterized in that, The dosage forms include tablets, creams, capsules, sustained-release preparations, oral liquids, syrups, pellets, injections, lyophilized powder injections, and nano-preparations.