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CN111991444A - Solubilizing carrier composition for cannabis oil and solubilized cannabis oil solid dispersion - Google Patents

Solubilizing carrier composition for cannabis oil and solubilized cannabis oil solid dispersion Download PDF

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CN111991444A
CN111991444A CN201911397835.4A CN201911397835A CN111991444A CN 111991444 A CN111991444 A CN 111991444A CN 201911397835 A CN201911397835 A CN 201911397835A CN 111991444 A CN111991444 A CN 111991444A
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cannabis oil
solid dispersion
cannabis
oil
carrier composition
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代勇
赵丽梅
常坦然
李如彦
李庆中
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Yunnan Hanmeng Pharmaceutical Co ltd
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Yunnan Hanmeng Pharmaceutical Co ltd
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    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
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    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
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Abstract

The present invention provides a solubilizing carrier composition for cannabis oil and a solubilized cannabis oil solid dispersion. The solid dispersion containing hemp oil comprises hemp oil, a surfactant, a polymer adjuvant, and optionally an antioxidant. The solid dispersion of cannabis oil is obtained by combining cannabis oil and a solubilizing carrier composition. The solubilizing carrier composition includes a surfactant, a polymeric excipient, and optionally an antioxidant. The solid dispersion containing the cannabis oil can be dissolved in water, the solubility and the dissolution rate of the cannabis oil are obviously improved, and the solid dispersion containing the cannabis oil is easy to operate and easy to carry out industrial mass production.

Description

Solubilizing carrier composition for cannabis oil and solubilized cannabis oil solid dispersion
Technical Field
The present application relates to cannabis oil compositions, in particular solubilized solid compositions comprising cannabis oil, solubilizing carrier compositions for solubilizing cannabis oil, and the use of the solubilizing carrier compositions for preparing solubilized cannabis oil solid dispersions.
Background
Cannabis oil is an extract from cannabis. Regarding cannabis, there are generally two categories, one is entertainment product cannabis, which refers to a variety with a tetrahydrocannabinol content higher than 0.3%; in another class, commonly referred to as hemp or industrial hemp, the species is characterized by a tetrahydrocannabinol content of less than 0.3%, which is the major psychoactive chemical component of hemp, can be excited and addictive, and is the major cause of the drug recognized by hemp.
Modern detection techniques have shown that the chemical composition of industrial cannabis is very complex, and at least 483 monomeric compounds have been identified, of which over 60 cannabinoid components are characteristic of industrial cannabis plants. Other components include lipids, flavones, terpenes, hydrocarbons, acyclic macrophenol, alkaloids, lignin, etc., and some of these components have been reported to have better pharmacological activity, such as geranylflavone and terpenes, etc. to have antioxidant, anti-inflammatory, and bactericidal effects.
Currently, the extraction of industrial hemp is mainly focused on the fiber of industrial hemp itself or individual monomer components, such as the extraction of cannabinoids, e.g. Cannabidiol (CBD). Cannabidiol has no psychoactive properties and does not produce excitement and addiction. In 2017, the world health organization stated that Cannabidiol (CBD) does not adversely affect human health, whereas cannabidiol may be used in the medical field. The U.S. Food and Drug Administration (FDA) approved the drug Epidiolex with cannabidiol as the first active in 2018.
Besides Cannabidiol (CBD), a plurality of legal, safe and effective other cannabis active substances can be extracted from industrial cannabis plants such as flowers, leaves and seeds of industrial cannabis, and the extraction method has great development and application values. These cannabinoids extracted from industrial cannabis, including other industrial cannabis extracts, are collectively referred to herein as cannabis oil. In addition to cannabinoids, flavonoids, terpenes, and the like are also included. The hemp oil contains various hemp active substances, and the hemp active substances have special physiological effects and have wide application prospects in the fields of foods, health-care products, medicines and the like.
However, most of these cannabis actives are poorly water soluble ingredients, limiting the range of products that can be developed.
In the prior art, techniques for increasing the solubility of industrial cannabis extracts in water include inclusion compound techniques (e.g. patent application US20190030170a1) and microemulsion techniques (e.g. patent application WO2019014631 a 1).
In contrast to these solubilization methods, it would be desirable to have a method that is easy to industrially mass produce, easy to carry, convenient to handle, and effective in increasing the aqueous solubility of cannabis oil and its bioavailability, and a solubilized solid dispersion form of cannabis oil composition therefrom.
Disclosure of Invention
The present invention is intended to provide a solid dispersion of a hemp oil composition. Solid Dispersion (SD) refers to a solid dispersion system in which a drug, particularly a poorly soluble drug, is highly dispersed in a suitable carrier material in a molecular, colloidal, microcrystalline or amorphous state, and is also called a solid dispersion.
The present inventors have surprisingly found that the selection of a specific surfactant and a high molecular polymer as a solid dispersion vehicle for hemp oil, together with the addition of a suitable antioxidant, enables the production of a hemp oil solid dispersion in which the solubilization characteristics of the hemp oil composition are enhanced, thereby significantly improving its solubility in water and also enhancing the stability of the composition.
Provided herein is a solubilizing carrier composition for solubilizing cannabis oil, comprising a surfactant and a polymeric excipient. The surfactant is easily soluble in organic solvent such as ethanol or acetone, or medicinal nonionic surfactant with melting point of no higher than 65 deg.C and HLB value of 13-23. Exemplary surfactants include: poloxamer, polyethylene glycol 1000 vitamin E succinate (TPGS), polyoxyethylene hydrogenated castor oil derivatives, or mixtures thereof. The high molecular polymer is easily soluble in organic solvent such as ethanol or acetone, has melting point of no higher than 65 deg.C, and can be used as polymer adjuvant of drug carrier. Exemplary polymeric excipients include: povidone, polyethylene glycol, hydroxypropyl cellulose, polyvinyl alcohol-polyethylene glycol copolymer or a mixture thereof.
The active ingredient in cannabis oil, such as cannabidiol, is susceptible to oxidation and it is therefore preferred to add an antioxidant to the solubilising carrier composition. The antioxidant is, for example, a radical terminator, or a metal ion chelating agent, or a combination of both. Exemplary radical terminators are selected from: t-Butylhydroxyanisole (BHA), di-t-Butylhydroxytoluene (BHT), Propyl Gallate (PG), amyl gallate, t-butylhydroquinone (TBHQ), tert-butylhydroquinone (EBHQ), polyphenolic compounds (such as tea polyphenols, tocopherols, etc.), rosemary extract, lycopene, guaiac resin, riboflavin, anthocyanins, etc.; the metal ion chelating agent is selected from: organic acids such as citric acid, phytic acid, tartaric acid, malic acid, succinic acid, fumaric acid, and maleic acid.
According to one embodiment of the present invention, there is provided a solubilizing carrier composition comprising a.3-10 parts by weight of a surfactant; b. less than 5 parts of a high molecular polymer adjuvant, optionally comprising 0.01-0.05 parts by weight of an antioxidant.
The present invention also provides a solubilized cannabis oil solid dispersion comprising cannabis oil and the above solubilizing carrier composition, wherein the cannabis oil comprises cannabinoids, flavonoids or terpenes; cannabinoids are for example Cannabidiol (CBD), Cannabidivarin (CBDV), Cannabigerol (CBG), cannabichromene (CBC), Cannabinol (CBN), Tetrahydrocannabivarin (THCV), Cannabigerol (CBL); flavonoids are for example: geranylflavone a (cfla), geranylflavone b (cflb), geranylflavone c (cflc); terpenes include: phytol, eugenol, caryophyllene, linalool and the like.
The present invention also provides a method of preparing a cannabis oil solid dispersion, comprising the steps of: the cannabis oil and solubilizing carrier composition are dissolved in an organic solvent such as ethanol, acetone, mixed thoroughly, and the solvent is removed by, for example, distillation under reduced pressure, spray-freeze drying, melting, and the like.
The invention uses specific surfactant and polymer auxiliary material as solubilizing carrier composition for solubilizing the hemp oil, and adds proper antioxidant, thereby not only improving the solubilizing characteristic of the hemp oil solid dispersion, obviously improving the solubility of the hemp oil solid dispersion in water, but also keeping the stability of the hemp oil solid dispersion compatible with the carrier.
Detailed description of the preferred embodiments
The present invention provides a water-soluble cannabis oil solid dispersion comprising a solubilizing carrier composition and cannabis oil. The solubilizing carrier composition includes a surfactant and a polymeric excipient and optionally an antioxidant.
The surfactant in the solubilizing carrier composition is selected from the group consisting of pharmaceutically acceptable surfactants having a hydrophilic-lipophilic balance (HLB) value of between 13 and 23, preferably nonionic surfactants. Without being limited to theory, it is required that the surfactant is easily soluble in an organic solvent capable of dissolving hemp oil, preferably ethanol or acetone, etc., or preferably that the surfactant has a melting point of not higher than 65 ℃. Preferred surfactants include: poloxamer, polyethylene glycol 1000 vitamin E succinate (TPGS), polyoxyethylene hydrogenated castor oil derivatives, or mixtures thereof. The surfactant is used in an amount of 3 to 10 parts by weight, preferably 4 to 8 parts by weight, and further preferably 5 to 6 parts by weight based on 1 part by weight of hemp oil.
The polymeric excipients in the solubilizing carrier composition are preferably those that can be used in pharmaceuticals and that can provide sufficient steric hindrance or electrostatic repulsion to the cannabis active in cannabis oil to maintain stability of the cannabis active in the industrial setting. Meanwhile, the polymer auxiliary material is required to be capable of being dissolved in an organic solvent which is easy to dissolve the hemp oil, preferably ethanol or acetone and the like, or the melting point of the polymer auxiliary material is preferably not higher than 65 ℃. Examples of the high molecular polymer include povidone, polyethylene glycol, hydroxypropyl cellulose, polyvinyl alcohol-polyethylene glycol copolymer, and the like. The polymeric excipient is used in an amount of less than 5 parts by weight, preferably 1 to 5 parts by weight, more preferably 2 to 4 parts by weight or 2 to 3 parts by weight based on 1 part by weight of hemp oil.
The active substance contained in cannabis oil, such as cannabidiol, is easily oxidized under air environment conditions. To avoid oxidation of the active, it is preferred to add an antioxidant to the solubilizing carrier composition. The choice of antioxidant is preferably one that is capable of inhibiting the oxidation of phenolics. Preferably, the antioxidant is any one or more of tert-Butyl Hydroxyanisole (BHA), di-tert-Butyl Hydroxytoluene (BHT), Propyl Gallate (PG), amyl gallate, tert-butyl hydroquinone (TBHQ), tert-butyl hydroquinone (EBHQ), ascorbic acid and its derivatives, polyphenolic compounds (such as tea polyphenol, tocopherol, etc.), rosemary extract, lycopene, guaiac resin, riboflavin, anthocyanin, organic acids (such as citric acid, phytic acid, tartaric acid, malic acid, succinic acid, fumaric acid, maleic acid, etc.), etc., in any combination ratio. The antioxidant is used in an amount of 0.01 to 0.05 parts by weight, preferably 0.02 to 0.04 parts by weight, based on 1 part by weight of hemp oil.
The present invention provides a solubilizing carrier composition comprising a pharmaceutically acceptable surfactant selected from the group consisting of surfactants having a hydrophilic-lipophilic balance (HLB) value between 13 and 23; a polymeric excipient useful in medicine capable of providing sufficient steric hindrance or electrostatic repulsion to industrial cannabis actives in cannabis oil to maintain stability of the industrial cannabis actives, and optionally an antioxidant.
According to one embodiment of the present invention, there is provided a solubilizing carrier composition comprising 3 to 10 parts by weight of a pharmaceutically acceptable surfactant selected from the group consisting of surfactants having a hydrophilic-lipophilic balance (HLB) value of between 13 and 23, less than 5 parts by weight of a polymeric excipient useful in pharmaceuticals capable of providing sufficient steric or electrostatic repulsion to industrial cannabis actives in cannabis oil to maintain stability of the industrial cannabis actives, and optionally an antioxidant.
Without being limited by theory, because the hemp oil is an oily mixture and contains compounds such as cannabinoids, flavonoids, terpenes and the like, the melting point and the boiling point of the hemp oil are lower, and the hemp oil has stronger hydrophobicity and is easily dissolved in organic solvents such as ethanol, acetone and the like, the hemp oil solid dispersion dissolved in water is difficult to prepare. The choice of carrier is particularly important in the preparation of solid dispersions. The melting point of the carrier is not too high, such as not higher than 65 deg.C, and the carrier and hemp oil have the same easily-soluble organic solvent. Meanwhile, both the cannabinoids and the flavonoids in the cannabis oil are very easy to oxidize, and the carrier material for preparing the solid dispersion mostly contains oxidizing substance components, such as polyoxyethylene, polyethylene glycol or polyethylene and other blocks, and the polymer molecules often leave peroxide in the synthesis process, and in order to prevent the components in the cannabis oil from being oxidized, a proper antioxidant is preferably added.
The present invention also provides a solubilized cannabis oil solid dispersion comprising a solubilizing carrier composition and cannabis oil.
The cannabis oil may be a plant extract from industrial cannabis. The cannabis oil may include various cannabinoids, flavonoids from industrial cannabis extracts, terpenoids and other active substances. The hemp oil according to the invention can be the pure substance of these active substances, i.e. the single active substance, or can be a mixture of these active substances.
For example, the invention prepares a full spectrum hemp oil from flowers and leaves of industrial hemp, which contains almost all main effective components of cannabinoid, flavone, terpenes and the like, has clear components and controllable quality, and has the content of toxic component THC less than or equal to 0.1 percent. The hemp oil comprises the following components (in parts by weight): total cannabinoids no less than 70 parts; the total flavone is not less than 2 parts; not less than 0.2 parts total terpenes, wherein the cannabinoids include: cannabidiol (CBD), Cannabinoid (CBDV), Cannabigerol (CBG), cannabichromene (CBC), Cannabinol (CBN), Tetrahydrocannabivarin (THCV); cannabinol (CBL), and the like; the flavone comprises: geranylflavone A (CFLA), geranylflavone B (CFLB), geranylflavone C (CFLC), etc.; terpenes include: phytol, eugenol, caryophyllene, linalool and the like.
According to one embodiment of the present invention, there is provided a cannabis oil solid dispersion comprising 1 part cannabis oil; 3-10 parts by weight of a pharmaceutically acceptable surfactant selected from the group consisting of surfactants having a hydrophilic-lipophilic balance (HLB) value of between 13 and 23; less than 5 parts by weight of a polymeric excipient useful in pharmaceuticals capable of providing sufficient steric or electrostatic repulsion to industrial cannabis actives in cannabis oil to maintain stability of the cannabis actives, and optionally an antioxidant.
The present invention also provides a method for preparing a solid dispersion of cannabis oil comprising dissolving cannabis oil, the solubilizing carrier composition in an organic solvent and removing the solvent at a temperature of less than 65 ℃, preferably less than 50 ℃ to obtain a solid dispersion of cannabis oil.
In this preparation method, the organic solvent is capable of dissolving the surfactant, polymeric excipients, and antioxidant in the solubilizing carrier composition. The organic solvents are particularly preferably those capable of dissolving the active ingredient in hemp oil. Preferably, the organic solvent is an alcohol such as ethanol, acetone.
Because of the low melting point of hemp oil, it is preferable to remove the organic solvent at low temperature, such as a reduced pressure drying method, a spray freeze drying method, a melting method. Wherein the melting method comprises dissolving hemp oil and antioxidant in organic solvent to obtain organic solution, and melting other components except antioxidant in the carrier composition to obtain molten solution; mixing the molten liquid and the organic solution, heating and evaporating to remove the solvent to obtain the hemp oil solid dispersion.
After the solvent is removed, the hemp oil solid dispersion after the solvent is removed is subjected to a post-treatment including drying such as an oven, a silica gel dryer, or the like, as necessary. The dried hemp oil solid can be pulverized and sieved to obtain a solid dispersion with the desired duration.
The hemp oil solid dispersion obtained by the method can exist stably, and the solubility in water is obviously improved.
Examples
The following are examples of the present invention for illustrating the technical solutions of the present invention. It will be apparent to those skilled in the art that the present invention is not limited to these embodiments.
Example 1 preparation of a hemp oil composition
Weighing hemp oil 1g, poloxamer P40710 g and herba Rosmarini officinalis extract 0.01g, adding 70mL ethanol, and ultrasonic dissolving. And volatilizing ethanol from the mixed solution at 50 ℃ under reduced pressure, drying the residual solid in a vacuum drying oven at 30 ℃ for 12 hours, taking out, grinding by using a mortar, and sieving by using a 60-mesh sieve to obtain the high-purity high.
Example 2 preparation of a hemp oil composition
Weighing 1g of hemp oil, 5g of TPGS, 3g of hydroxypropyl cellulose, 0.01g of citric acid and 0.02g of BHA, adding 60mL of ethanol, performing ultrasonic dissolution, spray-freeze drying the solution, and then placing the solution in a silica gel dryer to room temperature to obtain the traditional Chinese medicine.
Example 3 preparation of a hemp oil composition
Respectively weighing 1g of hemp oil, 1g of PVP K303 g, 4g of Cremophor RH60 (polyoxyethylene 60 hydrogenated castor oil), 0.01g of tartaric acid and 0.04g of BHT, adding 50mL of ethanol, performing ultrasonic dissolution, performing spray freeze drying on the solution, and then placing the solution in a silica gel dryer to room temperature to obtain the traditional Chinese medicine composition.
Example 4 preparation of a hemp oil composition
Respectively weighing 1g of hemp oil and 0.03g of tea polyphenol, adding 5mL of ethanol, and ultrasonically dissolving for later use. 5g of PEG4000 and 3g of TPGS were weighed into 50mL beakers and heated to a molten state in a water bath at 65 ℃. The ethanol solution was poured into the molten vehicle and the heating continued with continued stirring to allow the ethanol to evaporate. Quickly pouring the eutectic substance onto a stainless steel plate which is cooled in advance, spreading the eutectic substance into a thin layer, quickly placing the thin layer in a low-temperature refrigerator at the temperature of 20 ℃ below zero for solidification for 12 hours, then placing the thin layer in a silica gel drier to room temperature, and grinding the obtained solid dispersion by a mortar and sieving the ground solid dispersion by a 60-mesh sieve to obtain the solid dispersion.
Example 5 solubility determination
50mL of purified water was measured and placed in 150mL conical flasks with stoppers, the temperature was maintained in a water bath at 37. + -. 0.5 ℃ and the mixture was added to the mixture in increments of 0.05g (faster first and slower later) and the hemp oil compositions prepared in examples 1 to 4, and the mixture was magnetically stirred until the precipitate was not dissolved overnight (10-12 hours) to determine the end point. The cannabis oil composition dissolution is shown in table 1.
TABLE 1 dissolution of cannabis oil and cannabis oil compositions
Figure RE-GDA0002487764050000071
Taking supersaturated test solution of each group, placing in a centrifuge tube, centrifuging at 5000rpm for 5min, taking supernatant, filtering with 0.22 μm filter membrane, and taking subsequent filtrate to dilute by 5 times to obtain test solution to be tested.
1) Content determination of cannabinoid and flavone
Chromatographic conditions and system applicability experiments: octadecylsilane chemically bonded silica is used as a filler for the chromatographic column; mixing acetonitrile: performing isocratic elution by using a 0.5% formic acid aqueous solution 70:30 as a mobile phase; the detection wavelength was 210 nm. The theoretical plate number should not be lower than 2500 calculated as Cannabidiol (CBD) peak.
Preparation of mixed control solution: precisely weighing 10mg each of Cannabidiol (CBD), Tetrahydrocannabinol (THC) and geranylflavone A (CFLA) reference substances, placing into a 100mL measuring flask, adding methanol to dissolve, and shaking to desired volume.
Respectively and precisely absorbing 10 mu L of each of the reference solution and the test solution, injecting the solutions into a liquid chromatograph, recording a chromatogram, measuring peak areas, and calculating the content of each component according to retention time and correction factors in the table 2.
TABLE 2 cannabinoid and flavone correction factors and Retention time
Figure RE-GDA0002487764050000072
Figure RE-GDA0002487764050000081
Total cannabinoid content ═ CBD% + CBDV% + CBG% + THCV% + CBN% + CBC% + CBL%;
total flavone ═ CFLA% + CFLB% + CFLC%
The English shorthand in the table explains that:
f is a correction factor.
CBD cannabidiol, CBDV cannabinoid (or cannabidivarin), CBG cannabigerol, CBC cannabichromene, CBN cannabinol, THCV tetrahydrocannabinol, THC tetrahydrocannabinol, CBL cannabinol, CFLA geranylflavone A, CFLB geranylflavone B, CFLC geranylgeranylgeranylflavone C.
2) And (3) terpene determination:
gas chromatography conditions: 30mL of a headspace bottle, heating to 90 ℃, and balancing for 30 min; HP-5MS quartz capillary column: 30 m.times.0.25 mm.times.0.25 μm; FID detector (7820A): 250 ℃; a sample inlet: 200 ℃; the interface is 180 ℃; 1:20 split-flow sample injection; the sample injection amount is 0.8 mL; nitrogen gas: 2 mL/min; tail blowing: 25 mL/min; air 300 mL/min; hydrogen gas: 30 mL/min; the column temperature is 50 ℃ (2min) -20 ℃/min-200 ℃ (10 min).
Preparation of a reference solution: 20mg of caryophyllene was precisely weighed and dissolved in 50mL of methanol: a mixed solvent of chloroform (1:1) was prepared as a 0.4mg/mL mother liquor, which was then diluted in multiple proportions (25, 50, 100, 200, 400 times, respectively) for 5 concentration gradients.
Respectively and precisely sucking 0.8mL of each of the reference solution and the test solution, injecting sample in headspace according to the chromatographic conditions, measuring peak area, and calculating the content of each component according to retention time and correction factor in Table 3.
Total terpenes ═ phytol% + eugenol% + caryophyllene% + linalool%
TABLE 3 terpenoid correction factors and Retention times
Name (R) Phytol Linalool Eugenol Dianthus caryophyllus alkene
F value relative to caryophyllene 1.21 0.65 0.58 1.00
Retention time 4.78 8.52 9.22 9.68
3) And (3) summarizing the measurement results:
TABLE 4 results of cannabis oil testing
Figure RE-GDA0002487764050000091
Example 6 stability study
The solid dispersions obtained in examples 1 to 4 and the solid dispersions prepared in examples 1 to 4 without antioxidant were allowed to stand at room temperature, and the contents of total cannabinoid, total flavone and total terpene were examined for 0 day, 10 days, 20 days and 30 days, respectively. The measurement method was the same as in example 5. The measurement results are shown in Table 5. from the examination results, the content of total cannabinoids, total flavonoids and total terpenes in the solid dispersion is stable within 30 days of standing at room temperature, and the content of the solid dispersion without the antioxidant is reduced to different degrees. The solid dispersion prepared by the invention has better chemical stability.
TABLE 5 table for stability of solid dispersions
Figure RE-GDA0002487764050000092
Figure RE-GDA0002487764050000101
The present invention provides a cannabis oil solid dispersion comprising cannabis oil extracted from cannabis sativa and a solubilizing carrier composition, in solid form. The solid dispersion of cannabis oil can be dissolved in water to obtain an aqueous solution of the active substance in cannabis oil. Meanwhile, the cannabis oil solid dispersion can exist stably through the solubilizing carrier composition, and the solubility of insoluble drugs is greatly increased.
The invention creatively selects the specific surfactant and the high molecular polymer as the hemp oil solid dispersion carrier, and simultaneously adds the proper antioxidant, so that the hemp oil solid dispersion carrier has the solubilization characteristic of the solid dispersion and the solubilization of the surfactant, thereby obviously improving the solubility of the hemp oil solid dispersion carrier in water, and also can keep the stability of compatibility with the carrier by adding the proper antioxidant.
Without being limited by theory, the drug in the solid dispersion exists in the carrier material in a molecular state, a colloidal state, a metastable state, a microcrystalline state and an amorphous state, so that the solubility of the drug in water is greatly improved. The presence of the selected surfactant and the high molecular polymer in the carrier material is beneficial to the high dispersibility of the medicament, the increase of the crystal inhibition of the medicament and the improvement of the wettability of the medicament, and meanwhile, the selected surfactant can form micelles in water, the micelles are spheroids formed by oleophilic groups of the surfactant facing inwards and hydrophilic groups facing outwards, the inside of the whole micelle is nonpolar, and the outside of the micelle is polar. As the micelle is a tiny colloidal particle, and the dispersion system belongs to a colloidal solution, the indissolvable substance can be occluded or adsorbed, and the solubility of the indissolvable drug is greatly increased.

Claims (10)

1. A solubilizing carrier composition for cannabis oil comprising
a. A surfactant;
b. high molecular polymer auxiliary materials;
c. optionally an antioxidant;
wherein the surfactant is easily soluble in organic solvent such as ethanol or acetone, or medicinal nonionic surfactant with melting point of no higher than 65 deg.C and HLB value of 13-23;
wherein the high molecular polymer is easily soluble in organic solvent such as ethanol or acetone, or has a melting point of not higher than 65 deg.C, and can be used as medicinal high molecular polymer adjuvant of drug carrier.
2. The solubilizing carrier composition of claim 1, wherein the surfactant is selected from one or more of the following: poloxamer, polyethylene glycol 1000 vitamin E succinate (TPGS), polyoxyethylene hydrogenated castor oil derivatives, or mixtures thereof.
3. The solubilizing carrier composition of claim 1, wherein the pharmaceutically acceptable polymeric excipient is selected from one or more of the following: povidone, polyethylene glycol, hydroxypropyl cellulose, polyvinyl alcohol-polyethylene glycol copolymer or a mixture thereof.
4. The solubilizing carrier composition of claim 1, wherein the antioxidant is selected from the group consisting of a radical terminator, a metal ion chelator, or a combination of both;
the radical terminator is selected from: t-Butylhydroxyanisole (BHA), di-t-Butylhydroxytoluene (BHT), Propyl Gallate (PG), amyl gallate, t-butylhydroquinone (TBHQ), tert-butylhydroquinone (EBHQ), polyphenolic compounds (such as tea polyphenols, tocopherols, etc.), rosemary extract, lycopene, guaiac resin, riboflavin, anthocyanins, etc.;
the metal ion chelating agent is selected from: organic acids such as citric acid, phytic acid, tartaric acid, malic acid, succinic acid, fumaric acid, and maleic acid.
5. The solubilizing carrier composition of any one of claims 1-4, comprising
a.3-10 parts by weight of a surfactant;
b. less than 5 parts by weight of a high molecular polymer adjuvant;
c. optionally 0.01 to 0.05 part by weight of an antioxidant,
based on 1 part by weight of hemp oil.
6. A solubilized cannabis oil solid dispersion comprising cannabis oil and the solubilizing carrier composition of any one of claims 1-5.
7. The cannabis oil solid dispersion of claim 6, wherein the cannabis oil comprises cannabinoids, flavonoids, and terpenes.
8. The cannabis oil solid dispersion of claim 7, wherein
Cannabinoids include: cannabidiol (CBD), Cannabidivarin (CBDV), Cannabigerol (CBG), cannabichromene (CBC), Cannabinol (CBN), Tetrahydrocannabivarin (THCV), Cannabicyclol (CBL);
the flavonoids comprise: geranylflavone a (cfla), geranylflavone b (cflb), geranylflavone c (cflc);
wherein the terpenes include: phytol, eugenol, caryophyllene and linalool.
9. A method of preparing a cannabis oil solid dispersion, comprising the steps of:
i. dissolving the solubilizing composition of any one of claims 1-7 and cannabis oil in an organic solvent;
removing the solvent.
10. The method of claim 9 wherein the organic solvent is selected from the group consisting of solvents capable of dissolving cannabis oil, including ethanol, acetone.
CN201911397835.4A 2019-12-30 2019-12-30 Solubilizing carrier composition for cannabis oil and solubilized cannabis oil solid dispersion Pending CN111991444A (en)

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