CN113694049B - Cannabinoid compounds and their use in treating parkinson's disease - Google Patents
Cannabinoid compounds and their use in treating parkinson's disease Download PDFInfo
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Abstract
The invention discloses an application of cannabis full-spectrum oil in treating Parkinson. The cannabis whole lineage oil contains Cannabidivarin (CBDV), cannabigerol (CBG), cannabidiol (CBD) and Tetrahydrocannabidivarin (THCV), and is free of addictive Tetrahydrocannabinol (THC). The cannabis whole-lineage oil has remarkable (0.01P & lt 0.05) Parkinson treatment effect, particularly the composition containing the sub-Cannabidiol (CBDV), the Cannabigerol (CBG), the Cannabidiol (CBD) and the tetrahydrosub-cannabinol (THCV) in the preferable proportion is remarkably superior to the effect when the composition is applied without the THCV or applied according to the proportion not provided by the invention, and the composition has important application value in preparation of Parkinson treatment drugs, has no toxic or side effect and can be used for a long time.
Description
Technical Field
The invention relates to the field of biological medicines, in particular to application of cannabis whole lineage oil in treating Parkinson.
Background
Parkinson's Disease (PD) is a degenerative disorder of the central nervous system, the second most common neurodegenerative disease after alzheimer's disease. PD is generally classified as a movement disorder, primarily characterized by resting tremor, stiffness, bradykinesia, and postural instability, with resting tremor being the most common and often the earliest developing symptom, with dementia usually occurring in the later stages of the disease. Motor symptoms of PD arise from the death of dopamine-producing cells in the substantia nigra (a region of the midbrain), the cause of which is unknown. Although dopamine is effective in treating motor symptoms in the early stages of the disease, dopamine's efficacy is lost in the later stages of the disease and its long-term use can lead to motor complications.
Cannabis is belonging to Cannabis family and genus Cannabis, and has important agricultural and medicinal value. Cannabinoids are a class of chemical substances known to activate cannabinoid receptors in cells, and pharmacological studies have shown that the main active ingredient in cannabis is a cannabinoid (cannabinoids). The phyto-cannabinoids are cannabinoids extracted from cannabis plant, and may also be artificially synthesized. At least 85 different cannabinoids can be isolated from the cannabis plant, differing in their structure depending on where the precursor Cannabinoid (CBG) is cyclized. The main cannabinoids in the hemp plant include Tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD), cannabidivarin (CBDV), tetrahydrocannabidivarin (THCV) and Cannabigerol (CBG), wherein the three components account for more than 90% of the cannabinoids.
It is well known that different cannabinoids have different properties. For example, CBDV is a non-addictive component in marijuana, can block the influence of the main addictive substance THC in marijuana on the human nervous system, and has pharmacological activity of treating epilepsy, neuropathic pain, arthritis, influenza and the like. Thus, it should be appreciated that while cannabinoids are all produced in different lines of the cannabis plant, it cannot be assumed that they all have the same properties. Because of this, research is constantly ongoing on numerous extracts in cannabis, and new breakthroughs are continuing. For example, european patent EP2726069 discloses cannabinoids for use in the prevention or treatment of neurodegenerative diseases or disorders, wherein preferably the cannabinoids are cannabichromene (CBC), cannabinoxide (CBDV) and/or cannabinoid acid (CBDVA) and the neurodegenerative disease or disorder to be prevented or treated is alzheimer's disease. British patent GB2432312 discloses that cannabis plant extract cannabinoids are more effective in preventing neurodegeneration than purified compounds, in particular the extract cannabinoids Tetrahydrocannabinoids (THC) or Cannabinoids (CBD). However, THCV has been rarely reported in the currently published pharmaceutical applications of a range of cannabinoids, and less reported for the treatment of parkinson.
Disclosure of Invention
In view of the blank and the deficiency of the research in the background technology, the invention provides an application of a cannabinoids compound in treating Parkinson, wherein the cannabinoids compound comprises Cannabidiol (CBDV), cannabigerol (CBG), cannabidiol (CBD) and Tetrahydrocannabivarin (THCV), does not contain substance Tetrahydrocannabinol (THC) capable of being addicted to people, has no toxic or side effect, and can safely and effectively treat Parkinson's disease, especially motor complications of Parkinson's disease.
For the purpose of the invention, the cannabinoids comprise CBDV, CBG, CBD and THCV and do not contain THC.
Preferably, in some embodiments of the present invention, the mass ratio of CBDV, CBG, CBD and THCV in the cannabinoid is 9 to 12:1 to 5: 60-65: 1 to 2.
More preferably, in some embodiments of the invention, the mass ratio of CBDV, CBG, CBD and THCV in the cannabinoid is 10-11:1-3:62-65:1.5-2.
In another aspect, the invention provides a pharmaceutical composition for treating parkinson comprising CBDV, CBG, CBD and THCV, without THC.
Preferably, in a specific example of the present invention, the mass ratio of CBDV, CBG, CBD and THCV in the pharmaceutical composition is 9-12: 1 to 5: 60-65: 1 to 2.
More preferably, in some embodiments of the invention, the mass ratio of CBDV, CBG, CBD and THCV in the pharmaceutical composition is 10-11:1-3:62-65:1.5-2.
The pharmaceutical composition of the present invention can be prepared into specific dosage forms, which include tablets, sugar-coated tablets, film-coated tablets, enteric-coated tablets, capsules, hard capsules, soft capsules, oral liquids, buccal agents, granules, pills, powders, ointments, pellets, suspensions, powders, solutions, injections, suppositories, ointments, plasters, creams, sprays, drops, patches, etc., preferably oral dosage forms.
Further preferably, when the oral dosage form of the present invention is a tablet, the pharmaceutically acceptable excipient may be an inert diluent or filler (e.g., sucrose, microcrystalline cellulose, starch, calcium carbonate, sodium chloride, calcium phosphate, calcium sulfate, or sodium phosphate); disintegrating agents including starch/starch derivatives, croscarmellose sodium, alginates, alginic acid, polyvinylpyrrolidone or sodium starch glycolate; suitable lubricants, such as magnesium stearate; a binder (e.g., gum arabic, alginic acid, sodium alginate, gelatin, starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl cellulose, methyl cellulose, hypromellose, ethyl cellulose, polyvinylpyrrolidone, or polyethylene glycol); and lubricants, glidants, and anti-adherents (e.g., stearic acid, silicates, or talc). Other pharmaceutically acceptable excipients may also be included, such as coloring agents, flavoring agents, plasticizers, humectants, buffering agents, and wetting agents, and the like.
The tablets may be coated if necessary. The coating may be adapted to release the active drug substance in a predetermined pattern (e.g. to achieve a controlled release formulation) or it may be adapted not to release the active drug substance until after passage through the stomach (enteric coating). The coating may be a sugar coating, a film coating (e.g., methylcellulose, methylhydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, acrylate copolymers, polyethylene glycol, and/or polyvinylpyrrolidone), or an enteric coating (e.g., cellulose acetate phthalate, hypromellose phthalate, hydroxypropyl methylcellulose acetate succinate, polyvinyl acetate phthalate, shellac, and/or ethylcellulose).
Formulations for oral use may also be presented as chewable tablets or as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example potato starch, microcrystalline cellulose, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with a water-miscible oil medium, for example liquid paraffin or olive oil.
Formulations for oral use may also be liquids for oral administration, suitable for the preparation of powders, dispersible powders or granules of aqueous suspensions by the addition of water.
The pharmaceutical compositions of the present invention are formed by admixing a plurality of active ingredients of the present invention with a pharmaceutically acceptable carrier and then may be conveniently administered in a variety of dosage forms suitable for the disclosed routes of administration. Administration may be once to many times per day for several days to several years, or may even last for the life of the patient. The carrier includes inert solid diluents or fillers, sterile aqueous solutions and various organic solvents. The pharmaceutical preparations may conveniently be presented in unit dosage form according to standard procedures for pharmaceutical formulations. Each unit dose containing a therapeutically effective amount of the active compound.
Therapeutically effective amounts of drugs in the combinations of the invention include amounts effective to reduce symptoms of Parkinson's disease, to stop or slow the progression of the disease (once it has become clinically significant), or to prevent or reduce the risk of developing the disease, which may vary depending on the nature of the active compounds and the intended dosage regimen. Generally, it is in the range of 0.1mg to 5000mg per unit dose. It is to be noted that the dosage and method of application of the active ingredients will depend upon a variety of factors including the general condition and age of the patient to be treated, the nature of the condition to be treated and the particular active ingredient or ingredients selected and the subjective judgment of the treating physician.
In the present invention, the Cannabidivarin (CBDV), cannabigerol (CBG), cannabidiol (CBD) and Tetrahydrocannabidivarin (THCV) may be chemically synthesized products, biologically synthesized products, plant extracts or prepared in other ways.
Further, the Cannabidiol (CBDV), cannabigerol (CBG), cannabidiol (CBD) and Tetrahydrocannabinol (THCV) can be pure products of each component respectively, and the medicinal composition can be obtained by mixing the components; the CBDV, CBG, CBD and THCV may also be present in the same product at the same time, for example a plant extract comprising the CBDV, CBG, CBD and THCV at the same time, such as industrial cannabis whole lineage oil.
Preferably, the plant extract fraction of the plant extract may be one or more of the stem core, flower, leaf, seed and shell of seed of industrial hemp, in particular flower and/or leaf.
In yet another aspect, the invention provides the use of a cannabis whole lineage oil comprising CBDV, CBG, CBD and THCV in the manufacture of a medicament for the treatment of parkinson's disease, in the absence of THC.
Preferably, in a specific example of the present invention, the mass ratio of CBDV, CBG, CBD and THCV in the cannabis full lineage oil is 9-12: 1 to 5:60 to 65:1 to 2.
More preferably, the mass ratio of CBDV, CBG, CBD and THCV in the cannabis full lineage oil is 10-11:1-3:62-65:1.5-2.
The THC-free component of the cannabinoids or the cannabis whole-spectrum oil is less than 0.3% of THC (mass percentage), preferably less than 0.1%, more preferably less than 0.01%, and particularly preferably no THC is detected according to a conventional method in the field.
The treatment of parkinson in the present invention refers to the treatment and prevention of symptoms or the treatment, prevention, delay and reduction of symptoms comprising symptoms triggered by the etiology of parkinson's disease, preferably parkinson's disease. Including, but not limited to, (1) protection against, or reduction or delay in, toxicity caused by alpha-synuclein, and (2) protection against, or reduction or delay in, toxic dopaminergic neurons resulting from abnormal glutamate accumulation, oxidative stress, mitochondrial dysfunction, or neuroinflammation.
The invention is applicable to the treatment of parkinsonism in any mammalian subject, particularly human subjects, at any stage of the disease, particularly for the treatment of bradykinesia or akinesia.
In another aspect, the present invention also provides a method for preparing the hemp full-spectrum oil, comprising the steps of:
(1) Crushing an industrial hemp flower and leaf medicinal material, sieving, baking at 90-110 ℃ for 150-250 min, adding 65-75% ethanol into a certain amount of baked hemp flower and leaf medicinal material according to a material-liquid ratio of 1;
(2) Measuring a sample loading solution, purifying the sample loading solution by a macroporous resin column at a flow rate of 2-4 BV/h, standing for 55-65 min after sample loading, eluting the sample loading solution by purified water, 45-55% ethanol and 75-85% ethanol in sequence at a flow rate of 7-10 BV/h, determining the end point of water elution, eluting the sample loading solution by 45-55% ethanol for 2.5-3 BV and eluting the sample loading solution by 75-85% ethanol for 4.5-5.5 BV, collecting ethanol eluent, and concentrating the ethanol eluent under reduced pressure until the water content is lower than 5% to obtain a crude product of the full spectrum oil;
(3) Taking the crude product of the full spectrum oil, adding 65-75% ethanol, stirring and dissolving, filtering, purifying the obtained filtrate by a chromatographic packed column at the flow rate of 1.5-2.5 BV/h, eluting by 65-75% ethanol for 4.5-5.5 BV after sample loading, and concentrating the 65-75% ethanol eluent under reduced pressure until the water content is lower than 5% to obtain the hemp full spectrum oil, wherein the total cannabinoid content in the hemp full spectrum oil reaches more than 75%, CBDV 9-12%, CBG 1-5%, CBD 60-65%, THCV 1-2%, and THC is not detected.
The cannabinoids compound, the pharmaceutical composition and the cannabis whole-spectrum oil provided by the invention have remarkable (0.01 straw P straw 0.05) effect of treating Parkinson, particularly the composition comprising the sub-Cannabidiol (CBDV), the Cannabigerol (CBG), the Cannabidiol (CBD) and the tetrahydrosub-cannabinol (THCV) in the preferable proportion is remarkably superior to the effect of the composition without THCV or the composition without the proportion, and the composition has important application value in the preparation of the medicament for treating Parkinson, has no toxic or side effect, and can be used for a long time.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention. It is to be understood that the following description is only illustrative of the present invention and is not to be taken in a limiting sense.
As used herein, the terms "comprises," "comprising," "includes," "including," "has," "having," "contains" or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a composition, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, process, method, article, or apparatus.
Furthermore, the description below of the terms "one embodiment," "some embodiments," "an example," "a specific example," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above are not necessarily intended to refer to the same embodiment or example.
In some embodiments, when the oral dosage form of the invention is a tablet, the pharmaceutically acceptable excipient may be an inert diluent or filler (e.g., sucrose, microcrystalline cellulose, starch, including potato starch, calcium carbonate, sodium chloride, calcium phosphate, calcium sulfate, or sodium phosphate); disintegrating agents including starch/starch derivatives, croscarmellose sodium, alginates, alginic acid, polyvinylpyrrolidone or sodium starch glycolate; suitable lubricants, such as magnesium stearate; a binder (e.g., gum arabic, alginic acid, sodium alginate, gelatin, starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl cellulose, methyl cellulose, hypromellose, ethyl cellulose, polyvinylpyrrolidone, or polyethylene glycol); and lubricants, glidants, and anti-adherents (e.g., stearic acid, silicates, or talc). Other pharmaceutically acceptable excipients, such as coloring agents, flavoring agents, plasticizers, humectants, buffering agents, and wetting agents, and the like, may also be present.
The tablets may be coated if necessary. The coating may be adapted to release the active drug substance in a predetermined pattern (e.g. to achieve a controlled release formulation) or it may be adapted not to release the active drug substance until after passage through the stomach (enteric coating). The coating may be a sugar coating, a film coating (e.g., based on hypromellose, methylcellulose, methylhydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, acrylate copolymers, polyethylene glycol, and/or polyvinylpyrrolidone), or an enteric coating (e.g., cellulose acetate phthalate, hypromellose phthalate, hydroxypropyl methylcellulose acetate succinate, polyvinyl acetate phthalate, shellac, and/or ethylcellulose).
Formulations for oral use may also be presented as chewable tablets or as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example potato starch, microcrystalline cellulose, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with a water-miscible oil medium, for example liquid paraffin or olive oil.
In some embodiments of the invention, the formulations for oral use may also be liquids for oral administration, suitable for the preparation of powders, dispersible powders or granules of aqueous suspensions by the addition of water. Suitable suspending agents are, for example, sodium carboxymethylcellulose, methylcellulose or/and sodium alginate, etc.
The technical features of the embodiments of the present invention may be combined with each other as long as they do not conflict with each other.
Example 1
Crushing industrial hemp flowers and leaves, sieving the crushed industrial hemp flowers and leaves by a No. 1 sieve, baking the crushed industrial hemp flowers and leaves at 100 ℃ for 200min, adding 70% ethanol into a certain amount of baked hemp flowers and leaves according to a material-liquid ratio of 1.
Measuring a sample loading solution, purifying by a treated macroporous resin column (the diameter-height ratio is 1.
Taking the crude oil of the whole spectrum system, adding 70% ethanol, stirring and dissolving, filtering, purifying the obtained filtrate by a treated polymeric chromatographic packed column UniPSN 30 (the diameter-height ratio is 1.
The total cannabinoid content in the obtained whole-lineage oil was 78.41%, wherein CBDV 10.52%, CBG1.57%, CBD 64.80%, THCV 1.52%, and THC were not detected.
Example 2 animal experiments
1. Preparation of test drugs, whole lineage oil was prepared as in example 1, and 9:1:60:1 and 12:5:65:2 CBDV, CBG, CBD and THCV, pure cannabinoids were prepared and mixed to prepare test groups numbered 1-3, respectively. In addition, the weight ratio of 10.5:1.5:65 mixing CBDV, CBG and CBD to prepare a test group with the number of 4 groups; according to the mass ratio of 10.5:1.5:65: and 4, mixing CBDV, CBG, CBD and THCV to prepare a test group with the number of 5.
Pd rat model preparation: taking 100 rats to enter an experiment, wherein 10 rats are a sham operation group, injecting physiological saline into the medial forebrain tract, injecting 3% sodium pentobarbital into the abdominal cavity to anaesthetize the rats, strictly horizontally fixing the head of the rat on a brain stereotaxic apparatus, and determining the right lateral forebrain and medial tract (the method refers to a rat brain map compiled by the New Youngi): (1) 3.7mm behind bregma, 1.7mm on the right side of sagittal suture, 7.8mm under skull periosteum and 2.4mm of incisal line; (2) posterior bregma 4.4mm, right side of sagittal suture 1.2mm, inferior skull 7.8mm, and anterior dentition 2.4mm. Drilling holes at the injection sites determined above, extracting 6-OHDA (prepared with 0.2% vitamin C physiological saline solution, concentration 4 μ g/μ l) 6 μ l with 10 μ l microsyringe, injecting 3 μ l each point, withdrawing the needle after leaving the needle for 10min, and suturing the wound surface. After 3 weeks, rats were intraperitoneally injected with apomorphine (0.5 mg/kg), with an average rotation frequency >7 times/min being a successful PD model.
3. Model preparation and behavioral determination: the 60 successful PD models were randomly divided into 6 large groups.
In the experimental groups 1-5, 5 groups of prepared experimental drugs are respectively fed and administrated according to 8.5mg/kg for 4 weeks; group 6 was the PD control group, and the PD model rats were treated in the following manner: levodopa methyl ester + benserazide (50 mg/kg levodopa methyl ester and 25mg/kg benserazide in sterile saline containing 0.2% vitamin C) was injected intraperitoneally for 4 weeks 2 times/day (10 am and 6 pm).
Behavioral observations and scoring of rats were performed on days 8, 15, 22, and 29 morning after drug administration during the course of treatment.
AIM evaluation: AIM was rated in 4 fractions (upper arm AIM, orofacial AIM, axial AIM and rotational AIM), each fraction being further rated on a 5-scale (0-4) by its presence and severity, namely: 0 is none; 1: the duration is less than 30s;2: a duration of 30s to 60s;3: the duration is longer than 60s, and the external stimulation can stop the operation; 4: the duration is longer than 60s, and the external stimulation cannot stop the operation. Evaluation was performed every 20min after dosing, with 1min observation. The total AIM score is counted according to the average value of the total score in the observation time, and theoretically, the maximum AIM score of each component of 1 rat after once administration is 4 scores, and the total AIM score is 16 scores.
4. Statistical analysis method, the experimental data is analyzed by SPSS 13.0 statistical software. The resulting measurements are expressed as means ± standard deviation, and the results are shown in table 1 for comparison of the means of multiple samples using one-way analysis of variance.
TABLE 1 results of animal experiments
5. Analysis of results
The oral-facial AIM scores indicated that the test groups 1-3 had comparable oral-facial scores, and that the mean differences between groups 1-3 and 4-6 were statistically significant (P < 0.05). Group 2 had lower oral facial AIM scores compared to group 4, with statistically significant differences (P < 0.05); group 2 had a lower oral facial AIM score than group 5, with statistically significant differences (P < 0.01).
Upper limb AIM scores showed comparable upper limb scores in groups 1-3, with statistical significance in comparing mean differences between groups 1-3 and groups 4-6 (P < 0.01). Where groups 1-3 had lower upper limb AIM scores than groups 4-5, the differences were statistically significant (P < 0.01).
The axial AIM scores indicated that the test groups 1-3 were comparable in axial score, and that the mean differences between groups 1-3 and 4-6 were statistically significant (P < 0.01). The axial AIM values were reduced by day 22 and day 29 with the groups 1-3 compared to the PD group (group 6), with the differences being statistically significant (P < 0.05), and the axial AIM scores were significantly reduced in the groups 1-3 compared to the groups 4-5 with the differences on day 22 and day 29 being statistically significant (P < 0.01).
The rotating AIM scores showed that the mass ratios of CBDV, CBG, CBD and THCV prepared according to examples 2-4 of the invention were comparable with the rotating scores of test groups 1-3, and the comparative mean differences between groups 1-3 and 4-6 were statistically significant (P < 0.01). Groups 1-3 were administered until day 22, 29 with a statistically significant difference (P < 0.01) compared to the PD group, and groups 1-3 had a statistically significant difference (P < 0.01) compared to groups 4-5 with day 22, 29, with a significantly reduced rolling AIM score.
It will be understood by those skilled in the art that the foregoing is only exemplary of the present invention, and is not intended to limit the invention to the particular forms disclosed, since various modifications, substitutions and improvements within the spirit and scope of the invention are possible and within the scope of the appended claims.
Claims (3)
1. The application of a composition of cannabinoids in preparing a medicament for treating Parkinson's disease is characterized in that the composition comprises: cannabidivarin, cannabigerol, cannabidiol and tetrahydrocannabidivarin, free of tetrahydrocannabinol;
the weight ratio of the cannabidiol, the cannabigerol, the cannabidiol and the tetrahydrocannabivarin in the composition is 9:1:60:1; or, the composition comprises 12% of cannabidivarin, cannabigerol, cannabidiol and tetrahydrocannabidivarin by mass: 5:65:2.
2. the use of a combination of cannabinoids as claimed in claim 1, in the manufacture of a medicament for the treatment of parkinson's disease, wherein said treatment of parkinson's disease is the treatment of bradykinesia or akinesia.
3. Use of a cannabis whole lineage oil in the manufacture of a medicament for treating parkinson's disease, wherein the cannabis whole lineage oil comprises cannabidiol, cannabigerol, cannabidiol and tetrahydrocannabivarin, and is free of tetrahydrocannabinol;
the preparation method of the hemp full-spectrum oil comprises the following steps: (1) Crushing industrial hemp flowers and leaves, sieving, baking at 100 ℃ for 200min, adding 70% ethanol into a certain amount of baked hemp flowers and leaves according to a material-liquid ratio of 1;
(2) Measuring a sample loading solution, purifying by a macroporous resin column at a flow rate of 4BV/h, standing for 60min after sample loading, eluting by purified water, 50% ethanol and 80% ethanol sequentially at a flow rate of 9BV/h, determining the end point of water elution, eluting by 50% ethanol for 3BV and 80% ethanol for 5BV, collecting 80% ethanol eluate, and concentrating under reduced pressure until the water content is lower than 5% to obtain a crude product of the full spectrum oil;
(3) Taking the crude product of the hemp full spectrum oil, adding 70% ethanol, stirring and dissolving, filtering, purifying the obtained filtrate by a chromatographic packed column at the flow rate of 2BV/h, eluting with 70% ethanol for 5BV at the flow rate of 2BV/h after sample loading, and concentrating 70% ethanol eluent under reduced pressure until the water content is lower than 5%, thus obtaining the hemp full spectrum oil;
the cannabidiol of the whole hemp spectrum oil comprises 10.52% of cannabidiol, 1.57% of cannabigerol, 64.80% of cannabidiol and 1.52% of tetrahydrocannabivarinol.
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| PCT/CN2021/072758 WO2021232836A1 (en) | 2020-05-21 | 2021-01-19 | Cannabinoid compounds and application thereof in treatment of parkinson's disease |
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| CN115010690B (en) * | 2022-06-06 | 2023-03-21 | 云南翰谷生物科技有限公司 | Preparation method of high-purity cannabinol crystal |
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| CN108366988A (en) * | 2015-09-18 | 2018-08-03 | 普拉提·都纳杜齐有限公司 | Include the combination of oral medication of cannboid, preparation and application |
| CN109568389A (en) * | 2017-09-29 | 2019-04-05 | 汉义生物科技（北京）有限公司 | A kind of preparation method of high-purity cannabinoids extract |
| CN109963595A (en) * | 2016-10-11 | 2019-07-02 | Gbs全球生物制药公司 | For treating the compound mixture containing cannboid of neurodegenerative disease |
| CN110330409A (en) * | 2019-07-24 | 2019-10-15 | 汉义生物科技（北京）有限公司 | A kind of preparation method of industrial hemp extract |
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| CN108366988A (en) * | 2015-09-18 | 2018-08-03 | 普拉提·都纳杜齐有限公司 | Include the combination of oral medication of cannboid, preparation and application |
| CN109963595A (en) * | 2016-10-11 | 2019-07-02 | Gbs全球生物制药公司 | For treating the compound mixture containing cannboid of neurodegenerative disease |
| CN109568389A (en) * | 2017-09-29 | 2019-04-05 | 汉义生物科技（北京）有限公司 | A kind of preparation method of high-purity cannabinoids extract |
| CN110330409A (en) * | 2019-07-24 | 2019-10-15 | 汉义生物科技（北京）有限公司 | A kind of preparation method of industrial hemp extract |
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