CN103110582A - Cannabinol compound micro-emulsion and preparation method thereof - Google Patents
Cannabinol compound micro-emulsion and preparation method thereof Download PDFInfo
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- CN103110582A CN103110582A CN201310068002XA CN201310068002A CN103110582A CN 103110582 A CN103110582 A CN 103110582A CN 201310068002X A CN201310068002X A CN 201310068002XA CN 201310068002 A CN201310068002 A CN 201310068002A CN 103110582 A CN103110582 A CN 103110582A
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Abstract
The invention relates to the field of pharmaceutic preparations and in particular relates to micro-emulsion containing a cannabinol compound. The micro-emulsion comprises the following components in percentage by weight: (a), 0.01wt%-30wt% of the cannabinol compound; (b), 0.01wt%-30wt% of oil phase, wherein the oil phase is selected from one or more of vegetable oil, fatty acid ethyl ester, fatty acid isopropyl ester, fatty acid glyceride and fatty acid polyethylene glycol glyceride; (c), 0.01wt%-60wt% of surfactant, wherein the surfactant is selected from one or more of polyoxyethylene ether castor oil, polyoxyethylene hydrogenated castor oil, poloxamer, fatty acid polyethylene glycol glyceride, polyoxyethylene dehrdrated sorbitol aliphatic ester and phospholipid; (d), 0.01wt%-40wt% of cosurfactant, wherein the cosurfactant is selected from one or more of alcohol, propylene glycol, isopropyl alcohol, polyethylene glycol, dimethyl isosorbide, isopropenyl carbonate, diethylene glycol monoethyl ether, tetrahydrofuran polyglycol ether and glycerol; and the balance being water or deionized water.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of microemulsion formulation that contains active components of plants and preparation method thereof.
Background technology
Microemulsion is thermodynamically stable, isotropic, the transparent dispersion that two kinds of immiscible liquid generate under the effect of surfactant molecule interfacial film.Be generally to be formed suitable ratio is spontaneous by oil phase, surfactant, cosurfactant and water, viscosity is low, and particle diameter is generally at 10～100nm.
Due to medicine good dispersion in microemulsion, particle diameter is little, is easy to absorb, so microemulsion can promote the absorption of medicine, improves the bioavailability of medicine.In addition, the viscosity of microemulsion is low, can not cause pain during injection, can not cause allergy and fat embolism.And microemulsion is a kind of thermodynamic stable system, can spontaneous formation, be easy to preparation, good stability.
Studies confirm that, contain multiple cannabinol compounds in Fructus Cannabis.Cannabinol compounds is a terpenoid phenolic compound, now has been separated to more than 70 kinds, and wherein more important have: cannabinol, cannabidiol, tetrahydrocannabinol, cannabinol, cannabidiolic acid, tetrahydro-cannabinolic acid etc.What wherein main and content was the highest is cannabidiol, tetrahydrocannabinol and cannabinol, and it has the effects such as antiinflammatory, analgesia, preventing or arresting vomiting, antitumor, spasmolytic, anxiety.
Summary of the invention
The object of the present invention is to provide a kind of water baseization novel form of cannabinol compounds, replace conventional other dosage forms of using.The water that microemulsion of the present invention enriches to originate and Environmental compatibility is good has replaced expensive organic solvent and has reduced the consumption of surfactant in the formula, thereby avoided patient's unnecessary composition of passive absorption when administration as decentralized photo.
The Key technique problem of microemulsified is the solution of effective ingredient bin stability after the correct application of micro-emulsion technology and microemulsified.The present invention is on the basis in the microstructure of research microemulsion, and the oil phase, surfactant and the cosurfactant that focus on being fit to the cannabinol compounds microemulsified screen.
And then, the invention provides a kind of microemulsion that contains cannabinol compounds, it contains following percentage by weight composition:
(a) 0.01～30wt% cannabinol compounds;
(b) 0.01～30wt% oil phase, described oil phase are selected from one or more in vegetable oil, fatty-acid ethyl ester, isopropyl fatty acid ester, fatty glyceride or fatty acid polyethyleneglycol glyceride;
(c) 0.01～60wt% surfactant, described surfactant are selected from one or more in polyoxyethylene ether Oleum Ricini, polyoxyethylene ether castor oil hydrogenated, poloxamer, fatty acid polyethyleneglycol glyceride, polyoxyethylene sorbitan fatty acid ester or phospholipid;
(d) 0.01～40wt% cosurfactant, described cosurfactant is selected from one or more in ethanol, propylene glycol, isopropyl alcohol, Polyethylene Glycol, Isosorbide dimethyl ether, propylene carbonate, TC, Tetrahydrofurfuryl polyethylene glycol ether or glycerol;
Surplus is water or deionized water.
In a preference, the percentage by weight of described each composition is: cannabinol compounds 0.2～15wt%, oil phase 0.2～15wt%, surfactant 0.2～40wt%, cosurfactant 0.2～20wt%, surplus is water or deionized water.
In another preference, described cannabinol compounds is selected from one or more in cannabinol, cannabidiol or tetrahydrocannabinol.
In another preference, described oil phase is selected from one or more in soybean oil, ethyl oleate, isopropyl myristate, caprylic/capric triglyceride or oleic acid polyethyleneglycol glyceride.
In another preference, described surfactant is selected from one or more in Cremophor RH40, PLURONICS F87, caprylic/capric polyethyleneglycol glyceride, Tween80 or phospholipid.
In another preference, described cosurfactant is selected from one or more in ethanol, propylene glycol, TC (Transcutol P) or glycerol.
The present invention also provides a kind of preparation method that contains the microemulsion of cannabinol compounds, comprise the cannabinol compounds that at first dissolves 0.01～30wt% with the oil phase that accounts for preparation preparation total amount 0.01～30wt%, add successively again the surfactant of 0.01～60wt%, cosurfactant and the suitable quantity of water of 0.01～40wt%, be stirred to homogeneous phase.
In a preference, the percentage by weight of described each composition is: cannabinol compounds 0.2～15wt%, oil phase 0.2～15wt%, surfactant 0.2～40wt%, cosurfactant 0.2～20wt%.
The details of various aspects of the present invention will be able to detailed description in chapters and sections subsequently.By hereinafter and the description of claim, characteristics of the present invention, purpose and advantage will be more obvious.
The specific embodiment
The inventor has been surprised to find that a kind of micro-emulsion composition that contains the compositions such as cannabinol compounds, oil phase, surfactant, cosurfactant and water through extensive and deep research.When the content of mentioned component was in a suitable scope, resulting micro-emulsion composition had not only kept the pharmacologically active of cannabinol compounds, and has high stability.This micro-emulsion composition and then can promote the absorption of cannabinol compounds improves the latter's bioavailability.
As used herein, cannabinol compounds are terpenoid phenolic compounds, now have been separated to more than 70 kinds, include but not limited to: cannabinol, cannabidiol, tetrahydrocannabinol, cannabinol, cannabidiolic acid, tetrahydro-cannabinolic acid etc.The preferred cannabinol compounds of the present invention is to be selected from one or more in cannabinol, cannabidiol or tetrahydrocannabinol.The amount ranges of cannabinol compounds of the present invention is 0.01～30wt%, preferred 0.2～15wt%.
Oil phase
Studies show that, oil phase not only can the solubilizing hydrophobic medicine, also can promote medicine transhipment in vivo, strengthens the absorption of human body, improves the bioavailability of medicine.The biphase volume that forms Emulsion differs larger, and this Emulsion is more stable.In certain limit, the oil phase molecule volume is larger, and is stronger to the dissolving power of medicine, can not form microemulsion but the oil phase molecule volume is excessive.In order to increase drug solubility, increase formation of microemulsion regional, should select the short chain oil phase.Oil phase commonly used has glyceryl oleate, triglycerin caprylate and the fatty acid ester etc. of the different saturations such as vegetable oil (as Oleum Ricini, Oleum Glycines, Oleum Arachidis hypogaeae semen, Fructus Canarii albi wet goods), ethyl oleate, MCT Oil (GTCC), oleic acid, isopropyl myristate (IPM) at present.Because fatty acid ester mobility, dissolubility and self emulsifying are good than vegetable oil, thus fatty acid ester usually as the optimum selection of oil phase, commonly used have ethyl oleate, Ethyl linoleate, an isopropyl myristate (IPM); Medium chain fatty acid triacylglycerol is as the caprylic/capric triacylglycerol; The long-chain fatty acid triacylglycerol is as oleic acid/linoleic acid triacylglycerol etc.
Wherein, ethyl oleate is colourless or the pale yellow oily liquid body, easily flows like olive oil, and 150 ℃ of heating a few hours are not destroyed, Chang Zuowei solvent, plasticizer, lubricant and transdermal enhancer.MCT Oil (GTCC) is based on the glyceride of coco-nut oil fatty acid.Oleic acid, formal name used at school are cis-9-18 (carbon) olefin(e) acid, and oleic acid is present in animal and plant fat with glyceride form together with other fatty acids.Isopropyl myristate (IPM) has fabulous infiltration, moistens and emollescence, is commonly used for emulsifying agent and wetting agent, can replace vegetable oil for the preparation of ointment and emulsifiable paste.
Oil phase of the present invention is selected from one or more in vegetable oil, fatty-acid ethyl ester, isopropyl fatty acid ester, fatty glyceride or fatty acid polyethyleneglycol glyceride, one or more in preferred soybean oil, ethyl oleate, isopropyl myristate (IPM), caprylic/capric triacylglycerol (as Miglycol812), caprylic/capric polyethyleneglycol glyceride (as Labrafil M 1944CS).The amount ranges of oil phase of the present invention is 0.01～30wt%, preferred 0.2～15wt%.
Surfactant
The Main Function of surfactant is to reduce interfacial tension to form interfacial film, impels formation of microemulsion.Having oleophylic and hydrophilic radical is its feature on chemical constitution.During the preparation microemulsion medicament, surfactant commonly used is phospholipid, Triton X-100 (OP) class, poly yamanashi esters, polyoxyethylene castor oil (CEL) and derivant, saponins etc.In addition, mixed surfactant can increase the flexibility of interfacial film, is beneficial to formation of microemulsion, and in microemulsion system, surfactant has directive significance to this rule to selecting.Wherein, phospholipid surfactant commonly used is soybean phospholipid and egg yolk lecithin.Soybean phospholipid is natural product, and it not only has extremely strong emulsification, and has nutritive value and medical function concurrently.Triton X-100 (OP) class is faint yellow to the brown color paste, approximately 85 ℃ of fusing points, soluble in water, 1% water liquid pH5～7, HLB value 15, can tolerate the aqueous sulfuric acid of 30% calcium chloride and 50%, be commonly used for emulsifying agent, wetting agent, solubilizing agent, diffusant etc., preparation emulsifiable paste, Emulsion, suppository and suspensoid etc.Poly yamanashi esters, microemulsion emulsifying agent commonly used is polyoxyethylene sorbitan monoleate, for yellowish extremely orange-yellow thick liquid, is the nonionic hydrophilic surfactant active, is commonly used for the solubilizing agent of injection and surfactant and the dispersant of other dosage forms.Polyoxyethylene castor oil (CEL) and derivant belong to non-ionic surface active agent, increase from weak yellow liquid to faint yellow mastic with relative molecular mass.Commonly used have polyoxyethylene hydrogenated Oleum Ricini, a polyoxyethylene castor oil etc.Polyoxyethylene castor oil has the effects such as emulsifying, solubilising, lubricated, skin moistening, antistatic, decontamination, is used as emulsifying agent, solubilizing agent, lubricant etc. in medicament.Saponin is the oligoglycosides of the similar steroid of spirostane and source of students thereof or the oligoglycosides of triterpenoid compound, be present in most plants, it is a kind of naturally occurring emulsifying agent, saponin has the capillary effect of the aqueous solution of reduction, produce the persistency foam after the aqueous solution vibration of most saponin, and not because heating disappears, this can distinguish with the foam that other material produces.
Surfactant of the present invention is selected from one or more in polyoxyethylene ether Oleum Ricini, polyoxyethylene ether castor oil hydrogenated, poloxamer, fatty acid polyethyleneglycol glyceride, polyoxyethylene sorbitan fatty acid ester or phospholipid, one or more in preferred Cremophor RH40 (polyoxyethylene ether (40) castor oil hydrogenated), PLURONICS F87, caprylic/capric polyethyleneglycol glyceride (Labrasol), Tween 80 (Tween80) or phospholipid.The amount ranges of surfactant of the present invention is 0.01～60wt%, preferred 0.2～40wt%.
Cosurfactant
Cosurfactant is a kind of surface activity and hydrophile-lipophile balance that can change surfactant, participate in forming micelle, adjust the polarity of water and oil, water-soluble alcohol can reduce the polarity of water, oil-soluble alcohol can increase the polarity of oil, thereby affects the phase of system and the activating agent of the microemulsion composition of character mutually.Cosurfactant commonly used has short chain alcohol, organic amino, the acid of alkyl element, single two alkyl acid glyceride and polyoxyethylene fatty acid ester etc.In these cosurfactants, being most widely used of alcohols.Alcohols can improve drug loading, increases drug solubility, and the microemulsion region scope of formation is large, as ethanol, glycerol, PEG400,1,22 propylene glycol etc.
Cosurfactant of the present invention is selected from one or more in ethanol, propylene glycol, isopropyl alcohol, Polyethylene Glycol, Isosorbide dimethyl ether, propylene carbonate, TC (Transcutol), Tetrahydrofurfuryl polyethylene glycol ether (Glycofurol) or glycerol, one or more in preferred alcohol, propylene glycol, TC (Transcutol P) or glycerol.The amount ranges of cosurfactant of the present invention is 0.01～40wt%, preferred 0.2～20wt%.
Except mentioned component, microemulsion of the present invention can also contain one or more other medical additives, as viscosity-control additive, aromatic, correctives, antioxidant, antiseptic etc.
Microemulsion of the present invention can prepare with the conventional method of this area, first with the oil phase dissolving cannabinol phenolic compound that accounts for formula ratio, then adds successively surfactant, cosurfactant and water, is stirred to homogeneous phase and gets final product.
Microemulsion of the present invention has been selected suitable oil, surfactant and cosurfactant, need not with an organic solvent and reduced the consumption of surfactant, has avoided the patient to take in unnecessary composition when administration.And the preparation technology of microemulsion of the present invention is simple, need not to acquire special equipment, has saved research and development and production cost, is suitable for industrialized great production.
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used for explanation the present invention and be not used in and limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example is usually according to normal condition or the condition of advising according to manufacturer.Unless otherwise indicated, otherwise all percent, ratio, ratio or umber by weight.
Unit in percentage by weight in the present invention is well-known to those skilled in the art, for example refers to the weight of contained effective ingredient in the preparation of 100 unit of weights, and symbol is " wt% ".
Unless otherwise defined, the same meaning that all specialties and scientific words and the one skilled in the art who uses in literary composition is familiar with.In addition, any method similar or impartial to described content and material all can be applicable in the inventive method.The use that better implementation method described in literary composition and material only present a demonstration.
The above-mentioned feature that the present invention mentions, or the feature that embodiment mentions can combination in any.All features that patent specification discloses can with any composition forms and use, each feature that discloses in description can anyly provide the alternative characteristics of identical, impartial or similar purpose to replace.Therefore except special instruction is arranged, the feature that discloses is only the general example of equalization or similar features.
Embodiment 1:
Preparation technology
By above-mentioned formula consumption, the raw material cannabidiol is dissolved with soybean oil.
Add successively polyoxyethylene ether (40) castor oil hydrogenated, ethanol, water, stir, fill.
Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 2:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 3:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 4:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 5:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 6:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 7:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 8:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 9:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 10:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 11:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 12:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 13:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 14:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 15:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 16:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 17:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 18:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 19:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 20:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 21:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 22:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 23:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 24:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 25:
Preparation technology is with embodiment 1.Show through study on the stability, before and after the present embodiment gained microemulsion is investigated, outward appearance, particle diameter, content are all without significant difference.
Embodiment 26:
Preparation technology is with embodiment 1.Show through study on the stability, the present embodiment gained microemulsion is investigated front and back content without significant difference, and outward appearance generation significant change, particle diameter enlarges markedly, and the microemulsion quality is unstable.
Embodiment 27:
Preparation technology is with embodiment 1.Show through study on the stability, the present embodiment gained microemulsion is investigated front and back content without significant difference, and outward appearance generation significant change, particle diameter enlarges markedly, and the microemulsion quality is unstable.
Embodiment 28:
Preparation technology is with embodiment 1.Show through study on the stability, the present embodiment gained microemulsion is investigated front and back content without significant difference, and outward appearance generation significant change, particle diameter enlarges markedly, and the microemulsion quality is unstable.
Embodiment 29:
Preparation technology is with embodiment 1.Show through study on the stability, the present embodiment gained microemulsion is investigated front and back content without significant difference, and outward appearance generation significant change, particle diameter enlarges markedly, and the microemulsion quality is unstable.
Embodiment 1～29 preparation of the present invention contains the key technical indexes of microemulsion of cannabinol compounds as shown in table 1:
Many aspects involved in the present invention have been done as above and have been set forth.Yet, it should be understood that before not departing from spirit of the present invention to put, those skilled in the art can be equal to change and modify it, and described change and modification fall into the coverage of the claim of present patent application equally.
Claims (8)
1. microemulsion that contains cannabinol compounds, it contains following percentage by weight composition:
(a) 0.01～30wt% cannabinol compounds;
(b) 0.01～30wt% oil phase, described oil phase are selected from one or more in vegetable oil, fatty-acid ethyl ester, isopropyl fatty acid ester, fatty glyceride or fatty acid polyethyleneglycol glyceride;
(c) 0.01～60wt% surfactant, described surfactant are selected from one or more in polyoxyethylene ether Oleum Ricini, polyoxyethylene ether castor oil hydrogenated, poloxamer, fatty acid polyethyleneglycol glyceride, polyoxyethylene sorbitan fatty acid ester or phospholipid;
(d) 0.01～40wt% cosurfactant, described cosurfactant is selected from one or more in ethanol, propylene glycol, isopropyl alcohol, Polyethylene Glycol, Isosorbide dimethyl ether, propylene carbonate, TC, Tetrahydrofurfuryl polyethylene glycol ether or glycerol;
Surplus is water or deionized water.
2. microemulsion according to claim 1, it is characterized in that, the percentage by weight of described each composition is: cannabinol compounds 0.2～15wt%, oil phase 0.2～15wt%, surfactant 0.2～40wt%, cosurfactant 0.2～20wt%, surplus is water or deionized water.
3. microemulsion according to claim 1, is characterized in that, described cannabinol compounds is selected from one or more in cannabinol, cannabidiol or tetrahydrocannabinol.
4. microemulsion according to claim 1, is characterized in that, described oil phase is selected from one or more in soybean oil, ethyl oleate, isopropyl myristate, caprylic/capric triglyceride or oleic acid polyethyleneglycol glyceride.
5. microemulsion according to claim 1, is characterized in that, described surfactant is selected from one or more in Cremophor RH40, PLURONICS F87, caprylic/capric polyethyleneglycol glyceride, Tween80 or phospholipid.
6. microemulsion according to claim 1, is characterized in that, described cosurfactant is selected from one or more in ethanol, propylene glycol, TC or glycerol.
7. the preparation method that contains the microemulsion of cannabinol compounds claimed in claim 1, comprise the cannabinol compounds that at first dissolves 0.01～30wt% with the oil phase that accounts for preparation preparation total amount 0.01～30wt%, add successively again the surfactant of 0.01～60wt%, cosurfactant and the suitable quantity of water of 0.01～40wt%, be stirred to homogeneous phase.
8. the preparation method of microemulsion according to claim 7, it is characterized in that, the percentage by weight of described each composition is: cannabinol compounds 0.2～15wt%, oil phase 0.2～15wt%, surfactant 0.2～40wt%, cosurfactant 0.2～20wt%.
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| CN112386589B (en) * | 2021-01-21 | 2021-03-23 | 龙麻(上海)医药研发有限责任公司 | Composition for anti-anxiety/anti-depression agent and application thereof |
| CN112715816A (en) * | 2021-02-07 | 2021-04-30 | 澳门德诚生物科技有限公司 | Leisure beverage containing water-soluble nano cannabidiol and preparation method thereof |
| CN113521004A (en) * | 2021-06-24 | 2021-10-22 | 中国农业科学院农产品加工研究所 | Preparation method of high-load cannabidiol oil-in-water macromolecular particle emulsion |
| WO2023278665A1 (en) * | 2021-07-01 | 2023-01-05 | Ananda Scientific Inc. | Methods for treatment of opioid use disorder with cannabinoids |
| CN115364050B (en) * | 2022-08-02 | 2023-07-18 | 无锡诺平医药科技有限公司 | H2CBD emulsion, preparation method and pharmaceutical application thereof |
| CN115364050A (en) * | 2022-08-02 | 2022-11-22 | 无锡诺平医药科技有限公司 | H2CBD emulsion, preparation method and pharmaceutical application thereof |
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