Cannabinoid compounds, methods of making and using the same

Abstract

The application provides a cannabinoid compound, a preparation method and application thereof. The cannabinoid compound has a structure shown in formula (I). The application obtains the cannabinoid compound with the novel structure through an artificial synthesis method, and finds that the cannabinoid compound has a selective inhibitory effect on a TRPM8 channel, so that a theoretical basis and a material basis are provided for further development of the cannabinoid compound as a potential drug.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and more specifically, to a cannabinoid compound, its preparation method, and its application. Background Technology

[0002] Cannabis, a plant belonging to the Moraceae family, is also known as fire hemp, thread hemp, white hemp, green hemp, and wild hemp. It is an annual erect herbaceous plant. Cannabis is considered a drug-producing plant under international law and the legal systems of most countries, primarily due to the addictive nature of tetrahydrocannabinol (THC), which has a strong effect on the central nervous system. Cannabinoids are the components that produce hallucinations and euphoria when cannabis is used as a drug. Based on THC content, cannabis can be divided into two categories: industrial hemp (THC < 0.3%, showing no psychoactive activity) and recreational cannabis (THC > 0.5%, exhibiting significant psychoactive activity and a tendency for abuse). Cannabidiol (CBD) is an important compound extracted from industrial hemp. When we talk about industrial hemp, we are usually referring to CBD. It is unrelated to the efficacy of drugs affecting mental state and does not affect motor function, memory, or body temperature. Due to its good safety profile and lack of psychoactive effects, it can be used to treat conditions including inflammation, neurodegenerative diseases, epilepsy, autoimmune diseases such as multiple sclerosis, arthritis, schizophrenia, and cancer.

[0003] Cannabis, a plant in the Moraceae family, contains secondary metabolites of hundreds of chemical entities, each with potentially interesting biological properties. More than 90 cannabinoids are known, and besides THC and CBD, other typical cannabinoids from plant sources include cannabinoids (CBC), cannabinol (CBG), cannabidiol (CBDV), and tetrahydrocannabinol (THCV). Although these compounds have similar chemical structures, they can induce different pharmacological effects, indicating significant potential for development.

[0004] Transient receptor potential (TRP) channels are involved in a wide range of physiological functions, from the transmission of vision, hearing, and taste, to nociception and temperature sensation, and the control of muscle contraction and vasomotor activity. Furthermore, TRP channels are key participants in regulating intestinal motility, mineral absorption, blood circulation, bladder and airway hypersensitivity, fluid homeostasis, and cell growth and survival. This makes the TRP family important therapeutic targets for many major diseases, such as cardiovascular disease, neurodegenerative diseases, pain, and cancer. There are 6 subfamilies and 28 members of TRP channels in mammals, among which TRPV1, TRPA1, and TRPM8 are currently the focus of research.

[0005] TRPM8 channels, cold-activated pathways, are primarily expressed in somatosensory neurons of the dorsal root ganglion and trigeminal ganglion. They can be activated by various chemical and physical stimuli, such as menthol, phosphatidylinositol-4,5-bisphosphate (PIP2), and voltage, thereby activating cellular signaling and participating in a wide range of physiological processes. TRPM8 has been found to play a crucial role as a major mediator of menthol-induced acute and migraine headaches, making it a potential therapeutic target for cold-related pain, chronic pain, and migraines. Furthermore, TRPM8 channels are involved in irritable bowel syndrome, oropharyngeal dysphagia (OD), and chronic cough; therefore, the TRPM8 receptor is considered a valuable therapeutic target for developing related targeted drugs. In addition, there are numerous reports on TRPM8 channels targeting cancer treatment, showing promising therapeutic potential in prostate cancer, breast cancer, colon cancer, lung cancer, and skin cancer.

[0006] CN101678059A discloses plant extracts containing cannabinoids (THC, CBD, CBG, CBC, THCV, THCA, CBDV, CBDA) for the prevention and treatment of diseases that are relieved by blocking one or more TRP channels, such as neuropathic pain, cancer, and inflammation.

[0007] How to obtain more analogues of these cannabinoids and provide new options for drug development? Currently, apart from extracts from the aforementioned cannabinoid-containing plants, there are no other analogues reported. Summary of the Invention

[0008] The present invention aims to provide a cannabinoid compound, its preparation method and application, so as to explore new cannabinoid compounds and their application in the field of pharmacology.

[0009] To achieve the above objectives, according to one aspect of the present invention, a cannabinoid compound (referred to as cannabinoid A in this application) is provided, the cannabinoid compound having the structure shown in formula (I): Formula (I).

[0010] According to a second aspect of the invention, a medicament is provided comprising an effective amount of a cannabinoid compound of formula (I) above and a pharmaceutically acceptable excipient.

[0011] According to a third aspect of the invention, the use of the cannabinoid compound of formula (I) above in the preparation of a medicament for treating diseases that benefit from TRPM8 channel inhibition is provided.

[0012] Furthermore, diseases that benefit from TRPM8 channel inhibition include chronic pain, migraine, irritable bowel syndrome, dysphagia, chronic cough, and cancer; preferably, cancers include prostate cancer, breast cancer, colon cancer, lung cancer, and skin cancer.

[0013] Furthermore, the drug is administered orally, by injection, or transdermally; preferably, the dosage form of the drug is selected from capsules, tablets, oral liquids, injections, or transdermal absorbents; preferably, the injection is an intravenous injection.

[0014] According to a fourth aspect of the present invention, a method for preparing the cannabinoid compound of formula (I) is provided, the method comprising: dissolving cannabidiol in an organic solvent to obtain a cannabidiol solution; and converting the cannabidiol solution at 50-90°C to generate the cannabinoid compound of formula (I).

[0015] Furthermore, the mass-to-volume ratio of cannabidiol to organic solvent is 10g:5~10L; preferably, the reaction temperature for conversion is 70~90℃; preferably, the reaction time for conversion is 48~96h, more preferably 70~85h.

[0016] Further, the cannabidiol solution is placed at 70-90°C for conversion to generate cannabinoid compounds as shown in formula (I), which includes: converting the cannabidiol solution at 70-90°C to obtain a conversion product; concentrating the conversion product under reduced pressure to dryness to obtain a crude product; and purifying the crude product to obtain cannabinoid compounds.

[0017] Furthermore, the crude product is purified by silica gel column chromatography; preferably, the eluent for silica gel column chromatography is a mixture of petroleum ether and ethyl acetate, more preferably, the volume ratio of petroleum ether to ethyl acetate is 80:1 to 10:1.

[0018] Furthermore, the organic solvent is selected from one or more of the group consisting of methanol, ethanol, isopropanol and acetonitrile.

[0019] By applying the technical solution of this invention, cannabidiol (CBD) is converted into a cannabinoid compound of formula (I) under specific temperature conditions. This novel cannabinoid compound is obtained through artificial synthesis and is found to have a selective inhibitory effect on the TRPM8 channel, providing a theoretical basis and material foundation for its further development into a potential drug. Attached Figure Description

[0020] The accompanying drawings, which form part of this application, 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 The mass spectrum of cannabinoid A in Example 1 is shown; Figure 2 The 1H NMR spectrum of cannabinoid A in Example 1 is shown; Figure 3 The nuclear magnetic resonance HH COSY spectrum of cannabinoid A in Example 1 is shown; Figure 4 The nuclear magnetic resonance HMQC spectrum of cannabinoid A in Example 1 is shown. Detailed Implementation

[0021] It should be noted that, unless otherwise specified, the embodiments and features described in this application can be combined with each other. The present invention will now be described in detail with reference to the embodiments.

[0022] In order to further develop new cannabinoid compounds with potential medicinal value, this application avoids the existing methods of isolating extracts from cannabis plants to obtain cannabinoid compounds, and attempts to improve the synthetic pathways and sources of such compounds through chemical synthesis.

[0023] In this invention, the inventors surprisingly discovered that cannabidiol (CBD) can be converted in one step at a certain temperature to form a compound with a completely new structure, referred to in this application as cannabinoid A. As shown in formula (I), its structure is very similar to that of cannabidiol (CBD), and therefore, it is speculated that it possesses pharmacological activities related to cannabinoid compounds such as CBD.

[0024] Formula (I).

[0025] The cannabinoid A of this invention is obtained through CBD conversion. Since the extraction process of CBD from industrial hemp is relatively mature and readily available on the market, cannabinoid A is easier to obtain compared to some naturally occurring cannabinoids with extremely low content. Furthermore, another advantage of this invention is its preparation method. Cannabinoid A is obtained through a one-step conversion of CBD, which offers significant advantages in terms of lower preparation difficulty and cost compared to multi-step total chemical synthesis methods.

[0026] Furthermore, pharmacological tests have revealed that cannabinoid A of the present invention has a certain selective inhibitory effect on the TRPM8 channel in the TRP channel, and can be used to treat diseases that are relieved by blocking the TRPM8 channel, especially showing promise in chronic pain and migraine, irritable bowel syndrome, dysphagia (OD), chronic cough and various cancers, and is expected to have fewer side effects due to its selectivity.

[0027] Based on the above research results, the applicant has proposed the technical solution of this application. In a first typical embodiment, a cannabinoid compound is provided, having the structure shown in formula (I) above. As described above, the compound has been pharmacologically verified by the present invention to have a certain selective inhibitory effect on the TRPM8 channel in the TRP channel, and can be used to treat diseases that are relieved by blocking the TRPM8 channel, especially showing promise in chronic pain and migraine, irritable bowel syndrome, oropharyngeal dysphagia (OD), chronic cough and various cancers, and is expected to have fewer side effects due to its selectivity.

[0028] In a second typical embodiment, a medicament is provided comprising an effective amount of a cannabinoid compound of the structure shown in formula (I) and pharmaceutically acceptable excipients.

[0029] Based on the pharmacological experimental results of this application, the cannabinoid compounds with the structure shown in formula (I) have a certain selective inhibitory effect on the TRPM8 channel in the TRP channel, and therefore have the potential value to be developed into drugs. The excipients required for the preparation of the relevant drugs can vary depending on the dosage form and / or administration method and route of administration of the drug to be prepared, and can be rationally selected from existing pharmaceutical excipients.

[0030] The term "effective amount" here includes both therapeutically effective and preventatively effective amounts. A "therapeuticly effective amount" refers to the effective amount at the necessary dose and for a specific duration to achieve the desired therapeutic outcome. The therapeutically effective amount of a drug can vary depending on various factors, such as an individual's condition, age, sex, and weight, as well as the drug's ability to elicit the desired response in the individual. A therapeutically effective amount is also the amount at which the beneficial therapeutic effect outweighs any toxic or harmful effects of the drug. A "preventatively effective amount" refers to the amount at the necessary dose and for the necessary duration to effectively achieve the desired preventative outcome. A preventatively effective amount can be determined based on the above description of the therapeutically effective amount. For any specific subject, a specific dose can be adjusted over time according to individual needs and the professional judgment of the administerer.

[0031] Excipients can be selected from existing options depending on the dosage form or route of administration. When preparing a drug, in addition to cannabinoid compounds with the structure shown in formula (I), pharmaceutically acceptable carriers, excipients, or adjuvants are further required. Moreover, the drug can be formulated into different dosage forms to accommodate diverse routes of administration, including oral, injectable, or transdermal administration. Drug dosage forms include capsules, tablets, oral solutions, injections, or transdermal absorption formulations.

[0032] Specifically, the drug of the present invention can be formulated into tablets, capsules, oral liquids, injections, or transdermal absorption formulations according to methods known in the pharmaceutical industry. Preferably, the injection is an intravenous injection. When preparing capsules, tablets, or oral liquids suitable for oral administration, sucrose, lactose, galactose, corn starch, gelatin, microcrystalline cellulose, carboxymethyl cellulose, etc., can be used as carriers or excipients. Alternatively, the drug of the present invention can be formulated into solutions and suspensions suitable for oral administration using methods and excipients known in the pharmaceutical industry. When preparing solutions and suspensions suitable for parenteral administration, distilled water, water for injection, isotonic sodium chloride or glucose solution, or low-concentration (e.g., 1-100 mg) phosphate buffer (PBS) can be used as carriers or diluents. One or more other excipients or additives can be added to these parenteral formulations; for example, ascorbic acid can be used as an antioxidant, and sodium benzoate as a preservative. These dosage forms may also contain other solubilizers, disintegrants, colorants, dispersants, or surfactants.

[0033] In a third typical embodiment, the use of cannabinoid compounds with the structure shown in formula (I) in the preparation of medicaments for treating diseases that benefit from TRPM8 channel inhibition is provided.

[0034] In a preferred embodiment, diseases that benefit from TRPM8 channel inhibition include chronic pain, migraine, irritable bowel syndrome, dysphagia, chronic cough, and cancer; preferably, cancer includes prostate cancer, breast cancer, colon cancer, lung cancer, and skin cancer.

[0035] In a preferred embodiment, the drug is administered orally, by injection, or by transdermal administration; preferably, the dosage form of the drug is selected from capsules, tablets, oral liquids, injections, or transdermal absorbents; preferably, the injection is an intravenous injection.

[0036] In a fourth typical embodiment, a method for preparing a cannabinoid compound with the structure shown in formula (I) is provided. The method includes: dissolving cannabidiol in an organic solvent to obtain a cannabidiol solution; and converting the cannabidiol solution at 50-90°C to generate the cannabinoid compound shown in formula (I).

[0037] Using an organic solvent helps promote the dissolution of cannabidiol. Conversion at 50–90°C yields relatively high reaction rates and yields, as well as relatively high product purity. More importantly, the synthetic method described in this application is simple and has a high yield.

[0038] In a preferred embodiment, the cannabidiol solution is converted at 70-90°C to generate cannabinoid compounds; preferably, the conversion reaction time is 48-96 h, more preferably 70-85 h. At this temperature, both the reaction efficiency and product yield are relatively high. Under the same reaction conditions, the reaction time affects the product yield; a reaction time within 70-85 h results in a relatively high yield.

[0039] In a preferred embodiment, the cannabidiol solution is converted at 50-80°C to generate the cannabinoid compound shown in formula (I). This process includes: converting the cannabidiol solution at 50-80°C to obtain a converted product; concentrating the converted product under reduced pressure to dryness to obtain a crude product; and purifying the crude product to obtain the cannabinoid compound. Under the above conditions, the purity of the purified product is relatively high.

[0040] In a preferred embodiment, the crude product is purified by silica gel column chromatography; preferably, the eluent for silica gel column chromatography is a mixture of petroleum ether and ethyl acetate, more preferably, the volume ratio of petroleum ether to ethyl acetate is 80:1 to 10:1. The product obtained by the above purification method has higher purity.

[0041] In a preferred embodiment, the organic solvent is selected from one or more of the group consisting of methanol, ethanol, isopropanol, acetonitrile, methyl acetate, ethyl acetate, tetrahydrofuran, dichloromethane, or chloroform.

[0042] The beneficial effects of the present invention will be further illustrated below with reference to embodiments.

[0043] Example 1

[0044] 10g of CBD was dissolved in 10L of acetonitrile, heated to 80℃ and maintained for 72h, concentrated under reduced pressure, and subjected to silica gel column chromatography with elution conditions of PE:EA=80:1~10:1 to obtain 3.2g of product, namely cannabinoid A, with a purity of 97.9%.

[0045] MS=346, [M+H] + =347.

[0046] 1H-NMR(600 MHz, CDCl3), δ6.31-6.28ppm (s, 2H), δ5.39ppm (s, 1H), δ5.07-5.04ppm (d, 2H), δ4.42-4.41ppm (d, 1H), δ3.30-3.28ppm (dd, 1H), δ2.50-2.48ppm ( t, 2H), δ2.02-1.99ppm (m, 1H), δ1.931.88ppm (dt, 1H), δ1.82ppm, (t, 3H) , δ1.67-1.45ppm (m, 8H), δ1.34-1.25ppm (m, 5H), δ0.89-0.87ppm (t, 3H).

[0047] The mass spectra of cannabinoid A are attached. Figure 1 The proton NMR spectrum is attached. Figure 2 The HH COSY spectrum is attached. Figure 3 The HMQC spectrum is attached. Figure 4 .

[0048] Example 2 10g of CBD was dissolved in 10L of ethanol, heated to 70℃ and maintained for 85h, concentrated under reduced pressure, and subjected to silica gel column chromatography with elution conditions of PE:EA=80:1~10:1 to obtain 3.1g of product, namely cannabinoid A, with a purity of 97.8%.

[0049] Example 3 10g of CBD was dissolved in 10L of acetonitrile, heated to 90℃ and maintained for 70h, concentrated under reduced pressure, and subjected to silica gel column chromatography with elution conditions of PE:EA=80:1~10:1 to obtain 3.0g of product, namely cannabinoid A, with a purity of 98.2%.

[0050] Example 4 10g of CBD was dissolved in 5L of ethanol, heated to 75℃ and maintained for 80h, concentrated under reduced pressure, and subjected to silica gel column chromatography with elution conditions of PE:EA=80:1~10:1 to obtain 2.8g of product, namely cannabinoid A, with a purity of 97.6%.

[0051] Example 5 10g of CBD was dissolved in 5L of ethanol, heated to 50℃ and maintained for 96h, concentrated under reduced pressure, and subjected to silica gel column chromatography with elution conditions of PE:EA = 80:1~10:1 to obtain 0.9g of product, namely cannabinoid A, with a purity of 95.1%.

[0052] Example 6 10g of CBD was dissolved in 5L of ethanol, heated to 85℃ and maintained for 48h, concentrated under reduced pressure, and subjected to silica gel column chromatography with elution conditions of PE:EA = 80:1~10:1 to obtain 0.8g of product, namely cannabinoid A, with a purity of 93.20%.

[0053] Example 7 10g of CBD was dissolved in 3L of ethanol, heated to 70℃ and maintained for 85h, concentrated under reduced pressure, and subjected to silica gel column chromatography with elution conditions of PE:EA = 80:1~10:1 to obtain 0.6g of product, namely cannabinoid A, with a purity of 97.2%.

[0054] Example 8 10g of CBD was dissolved in 5L of ethanol, heated to 70℃ and maintained for 85h, concentrated under reduced pressure, and subjected to silica gel column chromatography with elution conditions of PE:EA = 30:1~5:1 to obtain 3.5g of product, namely cannabinoid A, with a purity of 85.1%.

[0055] Example 9 10g of CBD was dissolved in 5L of ethanol, heated to 70℃ and maintained for 85h, concentrated under reduced pressure, and subjected to silica gel column chromatography with elution conditions of chloroform:methanol = 100:1~30:1 to obtain 2.2g of product, namely cannabinoid A, with a purity of 61.2%.

[0056] Example 10 10g of CBD was dissolved in 10L of methanol, ethanol, isopropanol, acetonitrile, methyl acetate, ethyl acetate, tetrahydrofuran, and chloroform, respectively. The solutions were heated to 70℃ and maintained for 85h. The solutions were then concentrated under reduced pressure and subjected to silica gel column chromatography with elution conditions of PE:EA = 80:1~10:1 to obtain cannabinoid A. The yield and purity of cannabinoid A under different solvents are shown in the table below: Table 1:

[0057] Example 11 (a) Test materials Test sample: Cannabinoid A from Example 1, homemade, with a purity of 97.9%.

[0058] Positive controls: cinnamaldehyde (98% purity), ruthenium red (100% purity), capsaicin (100% purity), capsicum (99.3% purity), menthol (97% purity), 2-APB (100% purity).

[0059] (II) Patch-clamp detection of the effects of cannabinoid A on TRPV1, TRPA1, and TRPM8 1) TRPA1 The voltage stimulation protocol for whole-cell patch-clamp recording of TRPA1 currents was as follows: After whole-cell occlusion, the cell membrane voltage was clamped at -80 mV. The recording voltage was stepped from 0 mV to -100 mV and held for 1 ms, followed by a 300 ms ramp stimulation to 100 mV. Data acquisition was repeated every 5 s to observe the effect of the drug on TRPA1 currents. Experimental data were acquired using an EPC-10 amplifier (HEKA) and stored in PatchMaster (HEKA) software.

[0060] 2) TRPV1 The voltage stimulation protocol for whole-cell patch-clamp recording of TRPV1 currents was as follows: After whole-cell occlusion, the cell membrane voltage was clamped at 0 mV. The recording voltage was stepped from 0 mV to -100 mV and held for 1 ms, followed by a 300 ms ramp stimulation to 100 mV. Data was collected every 5 s to observe the effect of the drug on TRPV1 currents. Experimental data were acquired using an EPC-10 amplifier (HEKA Electronics) and stored in PatchMaster (HEKA Electronics) software.

[0061] 3) TRPM8 The voltage stimulation protocol for whole-cell patch-clamp recording of TRPM8 currents was as follows: After whole-cell occlusion, the cell membrane voltage was clamped at -80 mV. The recording voltage was stepped from 0 mV to -100 mV, followed by a 500 ms ramp stimulation to 100 mV. Data was collected every 5 s to observe the effect of the drug on TRPM8 currents. Experimental data were acquired using an EPC-10 amplifier (HEKA Electronics) and stored in PatchMaster (HEKA Electronics) software.

[0062] A capillary glass tube was drawn into a recording electrode using a microelectrode drawing instrument. Under an inverted microscope, the microelectrode manipulator was used to bring the recording electrode into contact with the cell, and negative pressure was applied to aspirate and form a GΩ seal. After forming the GΩ seal, rapid capacitance compensation was performed, and then negative pressure was continued to rupture the cell membrane, establishing a whole-cell recording mode. Slow capacitance compensation was then performed, and the membrane capacitance and series resistance were recorded. No leakage compensation was applied.

[0063] A coverslip containing cells was placed in the recording bath of an inverted microscope. The working solution containing the test compound and the external solution without the compound were perfused through the recording bath by gravity to act on the cells. A vacuum pump was used for fluid exchange during recording. Three cells were independently and repeatedly tested. All electrophysiological experiments were performed at room temperature.

[0064] The agonistic and inhibitory effects of cannabinoid A on TRPA1, TRPV1, and TRPM8 channels were investigated in three independent replicate experiments. The results are summarized below: Table 2: Results of the inhibition of TRPV1 current by cannabinoid A and the inhibition of TRPV1 current by the positive control ruthenium red.

[0065] As can be seen from the table above, cannabinoid A has no stimulatory effect on TRPA1 current, and its inhibitory effect is almost negligible.

[0066] Table 3: Results of the inhibition of TRPV1 current by cannabinoid A and the positive control capsazepine.

[0067] As shown in the table above, cannabinoid A exhibited a weak inhibitory effect compared to the positive control.

[0068] Table 4: Inhibitory effect of cannabinoid A on TRPM8 current and the inhibitory effect of positive control 2-APB on TRPM8 current.

[0069] As shown in the table above, cannabinoid A exhibited a stronger inhibitory effect compared to the positive control.

[0070] As can be seen from the above description, the embodiments of the present invention achieve the following technical effects: 1. The cannabinoid A of the present invention has a novel structure. Its compound structure is very similar to that of cannabidiol (CBD) and the molecular weight is very similar. Therefore, it may have pharmacological activities similar to those of cannabinoid compounds such as CBD.

[0071] 2. The cannabinoid A of this invention is obtained through CBD conversion. Since the extraction process of CBD from industrial hemp is relatively mature and readily available on the market, cannabinoid A is easier to obtain than some naturally occurring cannabinoids with extremely low content. Furthermore, this invention has advantages in its preparation method; the cannabinoid A of this application is obtained through a one-step conversion of CBD, which is significantly easier and less costly than multi-step total chemical synthesis methods.

[0072] 3. The cannabinoid A of this invention exhibits a certain degree of selective blocking effect on the TRPM8 channel in the TRP channel, almost completely blocking the TRPM8 channel at an experimental concentration of 10 μM, while having almost no effect on the TRPA1 and TRPV1 channels. This is of creative significance for the development of highly selective TRPM8 channel inhibitors, especially in the fields of analgesia and cancer treatment.

[0073] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A cannabinoid compound, characterized in that, The cannabinoid compound has the structure shown in formula (I): Equation (I).

2. A drug, characterized in that, It includes an effective amount of the cannabinoid compound of claim 1 and pharmaceutically acceptable excipients.

3. Use of the cannabinoid compound of claim 1 in the preparation of a medicament for treating diseases that benefit from TRPM8 channel inhibition.

4. The application according to claim 3, characterized in that, The diseases that benefit from TRPM8 channel inhibition include chronic pain, irritable bowel syndrome, chronic cough, and cancer; the cancers include prostate cancer, breast cancer, colon cancer, and lung cancer.

5. The application according to claim 4, characterized in that, The chronic pain includes migraines.

6. The application according to any one of claims 3 to 5, characterized in that, The drug can be administered orally, by injection, or transdermally.

7. The application according to any one of claims 3 to 5, characterized in that, The dosage form of the drug is selected from capsules, tablets, oral liquids, injections, or transdermal absorption agents.

8. The application according to claim 7, characterized in that, The injection is an intravenous injection.

9. The method for preparing the cannabinoid compound according to claim 1, characterized in that, The preparation method includes: Cannabidiol is dissolved in an organic solvent to obtain a cannabidiol solution; The cannabidiol solution was placed at 50-90°C for conversion, and the conversion reaction time was 48-96 h, to generate the cannabinoid compound shown in formula (I); The organic solvent is selected from one or more of the group consisting of methanol, ethanol, isopropanol and acetonitrile.

10. The preparation method according to claim 9, characterized in that, The mass-to-volume ratio of cannabidiol to the organic solvent is 10g:5~10L.

11. The preparation method according to claim 9, characterized in that, The reaction temperature for the transformation is 70~90℃.

12. The preparation method according to claim 9, characterized in that, The reaction time for the transformation is 70-85 hours.

13. The preparation method according to any one of claims 10 to 12, characterized in that, The cannabidiol solution was subjected to conversion at 70-90°C to produce the cannabinoid compound represented by formula (I), comprising: The cannabidiol solution was subjected to conversion at 70-90°C to obtain the conversion product; The conversion product was concentrated to dryness under reduced pressure to obtain a crude product; The crude product was purified to obtain the cannabinoid compounds.

14. The preparation method according to claim 13, characterized in that, The crude product was purified by silica gel column chromatography.

15. The preparation method according to claim 14, characterized in that, The eluent for the silica gel column chromatography is a mixture of petroleum ether and ethyl acetate.

16. The preparation method according to claim 15, characterized in that, The volume ratio of petroleum ether to ethyl acetate is 80:1 to 10:1.

Images