Application of sinapic acid and derivatives thereof in preparation of withdrawal medicine for preventing and / or treating methylamphetamine addiction

Abstract

The invention belongs to the field of biological medicines, and discloses application of sinapic acid and derivatives of sinapic acid methyl ester and sinapic acid ethyl ester in withdrawal medicines for preventing and / or treating methamphetamine addiction for the first time. The inventor investigates conditional position preference behaviors of mice addicted to methylamphetamine and sinapic acid, methyl sinalate and ethyl sinalate for treating the mice, and proves that the sinapic acid and derivatives of the sinapic acid, methyl sinalate and ethyl sinalate can relieve dependence and desire on methylamphetamine. Therefore, the sinapic acid and the derivatives of the sinapic acid, namely methyl sinalate and ethyl sinalate, can be used as active ingredients for preparing the drug addiction treatment drugs, a new choice is provided for preventing and / or treating methylamphetamine addiction, and a good clinical application prospect is achieved.

Description

Technical Field

[0001] The invention belongs to the field of biomedicine, and specifically relates to the use of sinapinic acid and its derivatives methyl sinapinic acid and ethyl sinapinic acid in the preparation of drugs for preventing and / or treating methamphetamine addiction and withdrawal. Background Art

[0002] The global drug problem continues to spread, and the number of drug users continues to increase, seriously endangering physical and mental health and social stability. Methamphetamine (MA), commonly known as "ice", belongs to the amphetamine class of psychoactive substances and is highly addictive. It often exists in the form of hydrochloride, a bitter white crystalline powder, easily soluble in water and alcohol, and is usually inhaled or injected. The CAS number is 537-46-2, and the molecular formula is C 10 H 15 N, with a molecular weight of 149.236, has the following structure:

[0003]

[0004] Methamphetamine can be taken in a variety of ways, can inhibit dopamine metabolism and uptake, promote dopamine synthesis, improve reward-related brain dopamine levels, stimulate excitement and reward effect changes, and form mental dependence. Under methamphetamine stimulation, a large amount of dopamine in the synaptic cleft is oxidized to quinones or semiquinones, causing reactive oxygen species (ROS) to significantly produce, inhibiting the generation of mitochondrial adenosine triphosphate (ATP), causing mitochondrial dysfunction, destroying the shape or function of nerve cells, and even nerve cell death, producing serious neurotoxicity (Riddle EL, FleckensteinAE, Hanson GR.Mechanisms ofmethamphetamine-induced dopaminergic neurotoxicity.AAPSJ, 2006, 8 (2): E413-E418.). Methamphetamine poisoning will cause delusion, hallucination, hyperactivity, cardiovascular disease, cognitive deficit, mydriasis, loss of appetite, violence and suicide, etc., and withdrawal symptoms such as mental sluggishness, lethargy, irritability, anxiety and suicidal tendency have been produced after discontinuation.

[0005] At present, low-toxic substances such as methadone are used at home and abroad to replace the pharmacological effects of opioids, control the desire for drugs and reduce withdrawal symptoms, but they are addictive and withdrawal symptoms will still occur after discontinuation. L-tetrahydropalmatine (l-THP) belongs to the same class of tetrahydroberberine compounds and is a new type of brain dopamine receptor blocker. Recent studies have shown that it has good prospects in the treatment of addiction, but its clinical application is limited due to its obvious sedative effect. Patents CN106176740A and CN107936008A report addiction treatment drugs based on the optimized structure of tetrahydroberberine. However, it is urgent and necessary to find and develop safer and more efficient new drugs for addiction treatment.

[0006] Sinapic acid (SA) is a natural phenolic acid found in edible, functional and medicinal plants, berries, vegetables, grains and oilseed crops. Its CAS number is 7362-37-0 and its molecular formula is C 11 H 12 O 5 , molecular weight is 224.21. Sinapic acid has antioxidant, anti-cancer, anti-inflammatory, antianxiety, anti-diabetes, heart, liver and kidney protection and antibacterial effects. Sinapic acid exerts antianxiety effects by activating GABA receptors (Yoon BH, Jung JW, Lee JJ, et al. Anxiolytic-like effects of sinapic acid in mice. Life Sci, 2007, 81 (3): 234-240.), and its free radical scavenging function can provide neuroprotection. In addition, sinapic acid can improve the behavioral defects and dopaminergic neuron loss of Parkinson's disease, which is related to inhibiting abnormal mitochondrial fission and improving mitochondrial function. Patent CN110840835A reported that sinapic acid has a neuroprotective effect. Therefore, we speculate that sinapic acid may have a therapeutic effect on methamphetamine addiction, but there is no relevant report at present.

[0007] Methyl sinapate (MSA) is a derivative produced by the esterification reaction of sinapic acid and methanol. The CAS number is 20733-94-2 and the molecular formula is C 12 H 14 O 5, with a molecular weight of 238.24. Sinapic acid methyl ester can be hydrolyzed into sinapic acid by ferulic acid esterase (Laguna, O., Odinot, E., Bisotto, A., et al. Release of Phenolic Acids from Sunflower and Rapeseed Meals Using Different Carboxylic Esters Hydrolases from Aspergillus niger. Ind. Crops Prod, 2019, 139: 111579.), which can be used as a sinapic acid prodrug. Therefore, we speculate that sinapic acid methyl ester may have a therapeutic effect on methamphetamine addiction, but there is no relevant report yet.

[0008] Ethyl sinapate (SE) is a derivative produced by the esterification reaction of sinapic acid and ethanol. The molecular formula is C 13 H 16 O 5 , molecular weight is 252.26. Sinapic acid ethyl ester can effectively scavenge free radicals, inhibit lipid peroxidation, and has antioxidant activity ( N, Polak T, Makuc D, Poklar Ulrih N, et al. A Kinetic Approach in the Evaluation of Radical-Scavenging Efficiency of Sinapic Acid and Its Derivatives. Molecules, 2017, 22(3): 375.). Therefore, we speculate that ethyl sinapinic acid may have a therapeutic effect on methamphetamine addiction, but there is no relevant report yet. Summary of the invention

[0009] Purpose of the Invention

[0010] The present invention aims at the problem of lack of safe and efficient therapeutic drugs for drug addiction, and for the first time proposes the potential role of sinapinic acid compounds in preventing and / or treating methamphetamine addiction.

[0011] Technical Solution

[0012] The present invention provides the use of a sinapinic acid compound in the preparation of a drug for preventing and / or treating methamphetamine addiction withdrawal, wherein the structure of the sinapinic acid compound is as follows:

[0013]

[0014] R=CH 3 , CH 2 CH 3, CH 2 CH 2 CH 3 or CH 2 (CH 2 ) 2 CH 3 .

[0015] The application is characterized in that the sinapinic acid compound is a preparation formed by preparing sinapinic acid, methyl sinapinic acid ester or ethyl sinapinic acid and a pharmaceutically acceptable excipient.

[0016] The invention discloses an application of protected sinapinic acid and its derivatives methyl sinapinic acid and ethyl sinapinic acid in the preparation of a drug for preventing and / or treating methamphetamine addiction.

[0017] Specifically, the molecular structure of sinapinic acid is as follows:

[0018]

[0019] Specifically, the molecular structure of methyl sinapinic acid is as follows:

[0020]

[0021] Specifically, the molecular structure of ethyl sinapinic acid is as follows:

[0022]

[0023] Preferably, the effective dose of sinapinic acid, methyl sinapinic acid ester and ethyl sinapinic acid ester is 50 mg / kg.

[0024] Preferably, the methamphetamine addiction treatment drug is prepared into a pharmaceutically approved dosage form with sinapic acid, methyl sinapic acid ester or ethyl sinapic acid ester as the sole active ingredient or the main active ingredient and pharmaceutically acceptable excipients.

[0025] The pharmaceutically acceptable excipients include one or more of fillers, diluents, binders, excipients, penetration enhancers, absorption enhancers, surfactants, pH regulators, antioxidants, stabilizers, chelating agents, pore formers, film formers, solvents, cosolvents, flavoring agents, sweeteners and pigments.

[0026] The dosage form for administration through the gastrointestinal tract can be tablets, capsules, soft capsules, liquid capsules, granules, pills, syrups, dry suspensions, oral solutions, oral suspensions, orally disintegrating tablets, oral fast-dissolving films, sustained-release tablets, controlled-release tablets, sustained-release capsules, controlled-release capsules, enteric-coated tablets, and enteric-coated capsules; the dosage form for administration through the non-gastrointestinal tract can be water injections, lyophilized powder injections, sterile powder injections, infusions, eye drops, nasal drops, nasal sprays, pulmonary inhalers, transdermal patches, liniments, ointments, creams, suppositories, subcutaneous implants, long-acting injections, and microneedle preparations. The present invention does not limit the above dosage forms, and any dosage form recognized medically is within the protection scope of the present invention.

[0027] In the present invention, addiction refers to a chronic, relapsing brain disease characterized by compulsive drug seeking and continued drug taking behavior in the knowledge that adverse consequences will occur.

[0028] Beneficial Effects

[0029] The present invention observes the conditioned place preference behavior of mice and finds that sinapinic acid compounds, i.e. compounds having a sinapinic acid nucleus, have a therapeutic effect on the withdrawal reaction of methamphetamine addiction, specifically:

[0030] Sinapic acid, methyl sinapic acid ester and ethyl sinapic acid can improve the conditioned place preference behavior of methamphetamine mice and inhibit the excitement and manic behavior caused by methamphetamine. The experiment proves that sinapic acid, methyl sinapic acid ester and ethyl sinapic acid are potential strategies for preventing and / or treating methamphetamine addiction.

[0031] (1) The present invention proposes for the first time the role of sinapinic acid in preventing and / or treating methamphetamine addiction, discovers a new use of sinapinic acid, expands the application scope of sinapinic acid, and has good clinical application prospects.

[0032] (2) The present invention proposes for the first time the role of sinapinic acid derivatives methyl sinapinic acid ester and ethyl sinapinic acid ester in preventing and / or treating methamphetamine addiction, discovers the potential therapeutic effects of sinapinic acid esters, and provides a new strategy for the treatment of methamphetamine addiction.

[0033] (3) The present invention first observed the behavior of mice through the conditioned place preference (CPP) model and found that sinapic acid and its derivatives methyl sinapic acid and ethyl sinapic acid could alleviate the excitement, restlessness and drug-seeking behavior of mice caused by methamphetamine to varying degrees. This shows that sinapic acid and its derivative sinapic acid esters have a significant effect in improving methamphetamine addiction. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1The present invention is a schematic diagram of the experimental flow chart: wherein: A is an experimental flow chart of the establishment of a methamphetamine conditioned place preference (CPP) model in mice and the intragastric administration during the withdrawal period; wherein, Saline represents saline, MA represents methamphetamine, SA represents sinapinic acid, MSA represents methyl sinapinic acid, and SE represents ethyl sinapinic acid. Withdrawperiod represents that mice are in the withdrawal period after the methamphetamine conditioned place preference model is established, Test1 represents a baseline test, Test2 represents a CPP test after the methamphetamine addiction model is established, and Test3 represents a CPP test after treatment with sinapinic acid, methyl sinapinic acid, and ethyl sinapinic acid, respectively.

[0035] B is a schematic diagram of the CPP test conditions, in which the mouse is first placed in the middle area and allowed to move freely between the black box, the white box, and the middle area for 15 minutes.

[0036] C is a schematic diagram of establishing the methamphetamine conditioned place preference model in mice. When the control group mice were intraperitoneally injected with normal saline and the modeling group mice were intraperitoneally injected with methamphetamine, all mice were placed in a black box for training for 30 minutes.

[0037] D is a schematic diagram of establishing the methamphetamine conditioned place preference model in mice, in which all mice were placed in a white box for training for 30 minutes when physiological saline was injected intraperitoneally.

[0038] Figure 2 is the CPP score of sinapic acid, methyl sinapic acid and ethyl sinapic acid in the treatment of methamphetamine addiction; Control represents the control group, Model represents the methamphetamine model group, SA represents the sinapic acid treatment group (50 mg / kg), MSA represents the methyl sinapic acid treatment group (50 mg / kg), and SE represents the ethyl sinapic acid treatment group (50 mg / kg). Two-way ANOVA was used for statistical analysis, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001, ns represents statistically insignificant difference.

[0039] Figure 3 This is the behavioral trajectory of the control group mice in the CPP test on the 1st, 10th and 23rd days. Their movements in the black box and the white box were similar. The overall results showed that the mice had no obvious preference for the black box and the white box.

[0040] Figure 4The following are the behavioral trajectories of the methamphetamine modeling group mice in the CPP test on the 1st, 10th and 23rd days. The movement of mice in the black box and the white box on the 1st day was similar. After 8 days of methamphetamine modeling, the mice tended to move in the black box on the 10th day, and the movement trajectories in the black box were more chaotic and dense than those in the white box, indicating that the mice had a strong drug-seeking behavior and produced excitement and manic behavior in the black box. After a 12-day withdrawal period, the mice still tended to move in the black box on the 23rd day, and the manic behavior in the black box did not weaken. This shows that the mice have developed a methamphetamine addiction.

[0041] Figure 5 The following are the behavioral trajectories of the mice in the sinapinic acid treatment group in the CPP test on the 1st, 10th and 23rd days. The movement of the mice in the black box and the white box on the 1st day was similar. After 8 days of methamphetamine modeling, the mice tended to move in the black box on the 10th day, and the movement trajectories in the black box were more chaotic and dense than those in the white box, indicating that the mice had a strong drug-seeking behavior and produced excitement and manic behavior in the black box. After 12 days of oral administration of sinapinic acid, the movement of the mice in the black box and the white box on the 23rd day was similar, with no obvious preference for the black box. This shows that sinapinic acid can improve the addiction of mice caused by methamphetamine.

[0042] Figure 6 The following are the behavioral trajectories of mice in the methyl sinapinic acid treatment group in the CPP test on the 1st, 10th and 23rd days. The movement of mice in the black box and the white box on the 1st day was similar. After 8 days of methamphetamine modeling, the mice tended to move in the black box on the 10th day, and the movement trajectories in the black box were more chaotic and dense than those in the white box, indicating that the mice had a strong drug-seeking behavior and produced excitement and manic behavior in the black box. After 12 days of oral administration of methyl sinapinic acid, the movement of mice in the black box and the white box on the 23rd day was similar, with no obvious preference for the black box. This shows that methyl sinapinic acid can improve the addiction of mice caused by methamphetamine.

[0043] Figure 7 The following are the behavioral trajectories of the ethyl sinapinic acid mouse treatment group in the CPP test on the 1st, 10th and 23rd days. The movement of mice in the black box and the white box on the 1st day was similar. After 8 days of methamphetamine modeling, the mice tended to move in the black box on the 10th day, and the movement trajectories in the black box were more chaotic and dense than those in the white box, indicating that the mice had a strong drug-seeking behavior and produced excitement and manic behavior in the black box. After 12 days of oral administration of ethyl sinapinic acid, the movement of mice in the black box and the white box on the 23rd day was similar, with no obvious preference for the black box. This shows that ethyl sinapinic acid can improve the addiction of mice caused by methamphetamine. DETAILED DESCRIPTION

[0044] To make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the following is further described in conjunction with the embodiments. Without departing from the concept of the present invention, all similar substitutions and modifications can be regarded as included in the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention.

[0045] Example 1: Synthesis of Sinapic Acid Derivatives Sinapic Acid Methyl Ester and Sinapic Acid Ethyl Ester

[0046] The methyl sinapate and ethyl sinapate used in the present invention are prepared as follows:

[0047]

[0048] Sinapic acid (Formula I) is reacted with an alkyl alcohol in the presence of concentrated sulfuric acid and heating to synthesize sinapic acid ester (Formula II).

[0049] Where R = CH 3 , to prepare methyl sinapinic acid; R = CH 2 CH 3 , to prepare ethyl sinapinic acid.

[0050] Sinapic acid alkyl ester was prepared with reference to previous literature (Gaspar A, Martins M, Silva P, et al. Dietary phenolic acids and derivatives. Evaluation of the antioxidant activity of sinapic acid and its alkyl esters. J Agric Food Chem, 2010, 58(21): 11273-80).

[0051] Example 2: Sinapic acid and its derivatives methyl sinapic acid and ethyl sinapic acid in treating methamphetamine-addicted mice

[0052] 1. Materials and medicines

[0053] 1.1 Experimental animals: C57BL / 6J mice were purchased from Zhejiang Weitonglihua Experimental Animal Technology Co., Ltd., SPF grade, female, weighing 15-18g, and provided with the Jiangsu Provincial Experimental Animal Facility Use Certificate by the Experimental Animal Center of China Pharmaceutical University. The temperature was (23±1)℃, the humidity was (50±10)%, and all experimental operations on animals were in accordance with the requirements of the Medical Ethics Committee of China Pharmaceutical University.

[0054] 1.2 Medicines

[0055] (1) Methamphetamine, provided by the Drug Control Intelligence Technology Center of the Ministry of Public Security of China in Beijing, was dissolved in physiological saline and administered by intraperitoneal injection.

[0056] (2) Sinapic acid, purchased from Nanjing Jingzhu Biotechnology Co., Ltd., dissolved in 0.5% CMC-Na, and administered by oral gavage.

[0057] (3) Sinapic acid methyl ester, dissolved in 0.5% CMC-Na, administered by oral gavage.

[0058] (4) Sinapic acid ethyl ester, dissolved in 0.5% CMC-Na, administered by oral gavage.

[0059] 1.3 Experimental instruments

[0060] The conditioned place preference box was purchased from Jiangsu Saiangsi Biotechnology Co., Ltd. The conditioned place preference box mainly consists of three areas: a black box, a white box, and a middle part. The black box is a rough floor with fence-like hollows, all-black walls and facades. The middle area is a rough floor with diamond-shaped hollows, white walls and facades, and the white box is a rough floor with circular hollows, black and white striped walls and facades. There are small doors between different areas, and partitions can be used to achieve isolation and connectivity between areas. When there are partitions between the boxes, that is, when the areas are isolated, the mice can only move in a certain area. When the partitions are removed, that is, when the areas are connected, the mice can move freely between the three areas without being restricted to the black box, white box or middle area.

[0061] The animal spontaneous activity video analysis system is used to record the movement behavior of mice. The system consists of an open field (length × width × height: 45 cm × 45 cm × 45 cm) and Any-maze software.

[0062] 2. Experimental Methods

[0063] The behavioral method of conditioned place preference (CPP) was used to explore the effects of sinapinic acid and its derivatives methyl sinapinic acid ester and ethyl sinapinic acid ester on the behavior of methamphetamine-addicted mice.

[0064] 2.1 Experimental Principle

[0065] Conditioned place preference is an experimental conditioning procedure based on Pavlovian learning, usually used to assess positive affective states (rewards) induced by different stimuli. The model uses a two or three compartment apparatus, each with different characteristics. The characteristics of each compartment are described in 1.3 Experimental apparatus.

[0066] Conditioned place preference (CPP) test: When the areas of the conditional place preference box are connected, the mice are not treated with any drugs on the day of the test. The mice are first placed in the middle area and allowed to move freely between the black box, white box and the middle area for 15 minutes. The time and behavioral trajectory of the mice in the black box, white box and middle area are counted by Any-maze software.

[0067] The model consists of three stages: pre-test period, conditioning training period and withdrawal period. In the pre-test period, all mice were subjected to CPP test before any treatment, with the purpose of measuring the baseline preference of mice. In the conditioning training period of this experiment, saline was paired with white box and methamphetamine was paired with black box, so that the white box was set as the non-drug side and the black box was set as the drug side. The specific process is that when the various areas of the conditioned position preference box are isolated, the control group mice are first injected with saline intraperitoneally, and the modeling group mice are injected with methamphetamine intraperitoneally. All mice are restricted to the black box (drug side) for 30 minutes. The next day, all mice are injected with saline intraperitoneally, and the mice are restricted to the white box (non-drug side) for 30 minutes. After 8 days of alternating training, CPP test is performed to determine whether the mouse can evoke happy memory and produce drug-seeking behavior when it comes into contact with the black box (drug side) again, and increase the activity time in the black box, which indicates that the mouse has developed dependence and craving for methamphetamine and formed methamphetamine addiction. During the withdrawal period, after the methamphetamine administration to mice was stopped, sinapinic acid, methyl sinapinic acid ester or ethyl sinapinic acid was gavage-administered for 12 days, and the CPP test was performed again. The purpose was to determine whether the mice's activity time in the black box was reduced when they were exposed to environmental cues related to methamphetamine again after the treatment drugs were administered. This would indicate that sinapinic acid, methyl sinapinic acid and ethyl sinapinic acid could reduce the mice's dependence on and craving for methamphetamine and improve their addiction to methamphetamine.

[0068] 2.2 Experimental process

[0069] Fifty female C57BL / 6J mice (6 weeks old, weighing 15-18 g) were housed in an SPF animal room and adaptively fed for 1 week, and then randomly divided into a control group (10 mice) and a methamphetamine modeling group (40 mice).

[0070] The experimental process is shown in Figure 1 On the following day 1, a baseline measurement (Test 1) was performed: All mice underwent CPP tests, and after each mouse test, each area was wiped with 75% ethanol to remove odor. After the baseline measurement was completed, the natural preference box of the mouse was set as the white box, and the non-natural preference box of the mouse was set as the black box, according to the time the mouse was in the black box and the white box respectively.

[0071] Then, the methamphetamine CPP model was established: the areas of the conditioned place preference box were closed and not connected to each other. On the second day, the mice in the control group were intraperitoneally injected with normal saline, and the mice in the modeling group were intraperitoneally injected with methamphetamine (2 mg / kg / d) and then placed in the black box for training for 30 minutes. On the third day, the mice in the control group and the modeling group were intraperitoneally injected with normal saline and placed in the white box for training for 30 minutes. The methamphetamine addiction model was established for a total of 8 days. After the modeling was completed, all mice were tested for CPP (Test2).

[0072] According to the CPP score, the mice after methamphetamine modeling were randomly divided into methamphetamine model group (Model), sinapinic acid treatment group (SA), methyl sinapinic acid treatment group (MSA), and ethyl sinapinic acid treatment group (SE). There were 10 mice in each group. After stopping the administration of methamphetamine to mice, they entered the withdrawal period. During the withdrawal period, the mice in the sinapinic acid treatment group, methyl sinapinic acid treatment group, and ethyl sinapinic acid treatment group were gavaged, and the dosage was 50 mg / kg / d. The mice in the control group and the methamphetamine model group were given the same volume of 0.5% CMC-Na. After the 12-day withdrawal period, all mice were tested for CPP again (Test3).

[0073] 2.3 Experimental statistical analysis

[0074] (1) Conditioned Place Preference Score (CPP Score): The difference between the time the mouse spends on the drug-treated side and the time the mouse spends on the non-drug-treated side is the conditional place preference score.

[0075] (2) Statistical analysis was performed according to the following method: Data were uniformly expressed as "mean ± standard error", and Graph prism 9.0 software was used for two-way ANOVA to compare the differences among the groups ( Figure 2 ).

[0076] 2.4 Experimental Results

[0077] like Figure 2 As shown in the figure, there was no significant difference in the CPP scores of the control group mice in the CPP test at the baseline, 10th day and 23rd day; the CPP scores of the methamphetamine model group mice on the 10th day were significantly increased compared with the baseline period, indicating that after intraperitoneal injection of methamphetamine, the mice developed a preference for methamphetamine and drug-seeking behavior. The model group mice were not given any drugs, and the CPP scores on the 23rd day did not change significantly compared with the 10th day; after the methamphetamine model mice were gavaged with sinapinic acid, methyl sinapinic acid and ethyl sinapinic acid for 12 days, the CPP scores on the 23rd day were significantly reduced compared with the 10th day, indicating that the preference for methamphetamine and drug-seeking behavior of mice were improved, and the methamphetamine addiction of mice was alleviated.

[0078] The use of sinapinic acid and its derivatives methyl sinapinic acid and ethyl sinapinic acid in preventing and / or treating methamphetamine addiction is the first discovery of the inventors. Whether used alone as an active ingredient or in combination with other ingredients, they are within the protection scope of the present invention.

[0079] The preferred embodiments of the present invention disclosed above are only used to help explain the present invention, and all details are not described in detail, nor are the invention limited to the specific implementation methods described. Many modifications and changes can be made according to the content of this specification. This specification selects and specifically describes these embodiments in order to better explain the principles and practical applications of the present invention, so that those skilled in the art can understand and use the present invention well. The present invention is limited only by the claims and their full scope and equivalents.

Claims

1. Use of a sinapinic acid compound in the preparation of a drug for preventing and / or treating methamphetamine addiction, characterized in that: The structure of the sinapinic acid compound is as follows: R=CH3, CH2CH3, CH2CH2CH3 or CH2(CH2)2CH3.

2. The use according to claim 1, characterized in that: The sinapinic acid compound is a preparation formed by preparing sinapinic acid, methyl sinapinic acid ester or ethyl sinapinic acid ester and a pharmaceutically acceptable excipient.

3. The use according to claim 1, characterized in that: The pharmaceutically acceptable excipients include one or more of fillers, diluents, binders, excipients, penetration enhancers, absorption enhancers, surfactants, pH regulators, antioxidants, stabilizers, chelating agents, pore formers, film formers, solvents, cosolvents, flavoring agents, sweeteners and pigments.

4. The use according to claim 1, characterized in that: The preparation is a dosage form for gastrointestinal administration and non-gastrointestinal administration; The dosage form for administration through the gastrointestinal tract is one or more of tablets, capsules, soft capsules, liquid capsules, granules, dripping pills, syrups, dry suspensions, oral solutions, oral suspensions, orally disintegrating tablets, orally rapidly dissolving films, sustained-release tablets, controlled-release tablets, sustained-release capsules, controlled-release capsules, enteric-coated tablets and enteric-coated capsules; The parenteral dosage form is one or more of aqueous injection, lyophilized powder injection, sterile powder injection, infusion, eye drops, nasal drops, nasal spray, pulmonary inhalation, transdermal patch, liniment, ointment, cream, suppository, subcutaneous implant, long-acting injection and microneedle preparation.

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