CN113925896A - Pharmaceutical composition containing cannabis extract, preparation and application thereof - Google Patents
Pharmaceutical composition containing cannabis extract, preparation and application thereof Download PDFInfo
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- CN113925896A CN113925896A CN202010611670.2A CN202010611670A CN113925896A CN 113925896 A CN113925896 A CN 113925896A CN 202010611670 A CN202010611670 A CN 202010611670A CN 113925896 A CN113925896 A CN 113925896A
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Abstract
The invention belongs to the field of medicines, and discloses a pharmaceutical composition containing a cannabis extract, a preparation and application thereof. The pharmaceutical composition containing the cannabis extract comprises a cannabis total terpene phenol extract and a cannabis total terpene inclusion compound, and the composition is prepared from cannabis total terpene phenol and cannabis total terpene (300-1): (1-300) mixing uniformly according to the mass ratio to obtain the product; wherein the content of total cannabiterpenoid phenol in the total cannabiterpenoid phenol extract is 80-90%, and the content of total cannabioid terpene in the total cannabioid clathrate is 6-10%. The pharmaceutical composition containing the cannabis extract can be prepared into granules, capsules and tablets by being supplemented with proper pharmaceutical excipients, so that the synergistic effect between the cannabis total terpene phenol extract and the cannabis total terpene inclusion compound is fully exerted, and the clinical application of the cannabis preparation is enhanced.
Description
Technical Field
The invention relates to the field of medicines, in particular to a pharmaceutical composition containing a cannabis extract, a preparation and application thereof, and more particularly relates to a pharmaceutical composition containing cannabis total terpene phenol and cannabis total terpene, a preparation and application thereof.
Background
Cannabiterpene phenol is the most abundant and well studied active ingredient in cannabis, and now the marketed drug for anti-epilepsy, epididex (cannabidiol), has been developed. The cannabigerol mainly comprises cannabinoids such as Cannabidiol (CBD), Cannabidivarin (CBDV), Cannabinol (CBN), Cannabigerol (CBMG), cannabichromene (CBC), Tetrahydrocannabinol (THC), and delta 9-Tetrahydrocannabivarin (THCV). Wherein, except that the toxic component Tetrahydrocannabinol (THC) can cause hallucinogenic addiction, other components have low toxicity or no toxicity. The existing research shows that the cannabinoids have various pharmacological activities, including anticancer, antiemetic, antibacterial, treating neurological diseases, treating cardiovascular diseases, anti-inflammatory, anti-edema, treating brain diseases, treating glaucoma, etc.
The cannabis total terpenes are a group of compounds with unique aroma and flavor found in cannabis, the content of the terpenes is much lower than that of terpene phenolic components, and no related medicine is developed and marketed. Currently, researchers have isolated and identified over 100 terpene components from cannabis, including alpha-pinene, myrcene, limonene, beta-caryophyllene, linalool, lupinene, ocimene, terpinolene, and the like. In recent years, research shows that cannabiterpenes have various pharmacological activities, namely pain relieving, inflammation diminishing, ulcer preventing, immunity enhancing, oxidation resisting, calming, cancer cell proliferation reducing, bacteriostasis, local anesthesia and the like. In addition, studies have also found that cannabigerol, cannabiterpene and other cannabinoids have a certain synergistic effect-also known as "carry-over effects". However, cannabigerol and cannabiterpene have not been reported for clinical treatment of neurological diseases.
Disclosure of Invention
The invention aims to promote the research and development of the cannabis in a deeper level, fully play the role of the synergistic effect of the components of the cannabis in the treatment of nervous system diseases, and provide a pharmaceutical composition and a preparation containing the cannabis extract and application of the pharmaceutical composition and the preparation as antiepileptic drugs.
In order to achieve the purpose of the invention, the pharmaceutical composition containing the hemp extract comprises a hemp total terpene phenol extract and a hemp total terpene clathrate, wherein the composition is prepared by respectively sieving the hemp total terpene phenol extract and the hemp total terpene clathrate (for example, sieving the mixture by a sieve with 50-150 meshes, preferably sieving the mixture by a sieve with 80 meshes), and then sieving the mixture according to the weight ratio of hemp total terpene phenol to hemp total terpene (300-1): (1-300) uniformly mixing the components in a mass ratio to obtain the composite material; wherein the content of total cannabiterpenoid phenol in the total cannabiterpenoid phenol extract is 80-90%, and the content of total cannabioid terpene in the total cannabioid clathrate is 6-10%.
Further, the cannabis total terpene phenol extract and cannabis total terpene clathrate are prepared by the following method:
(1) crushing, sieving and baking a hemp flower and leaf medicinal material, adding 70-95% ethanol into a certain amount of the baked hemp flower and leaf medicinal material according to a material-liquid ratio of 1: 6-1: 10(w/v), stirring and extracting for two times at room temperature, filtering, combining extracting solutions, centrifuging and filtering, concentrating a centrifugal filtrate under reduced pressure to obtain an extract, adding purified water with 2-5 times of the equivalent weight of the medicinal material, stirring at the temperature of 70-80 ℃, placing in a liquid separation tank, cooling to room temperature, centrifuging, and separating an upper layer to obtain a hemp crude extract; stirring and dissolving the obtained hemp crude extract with 93-98% ethanol with 2-4 times of the equivalent of the medicinal material, adding active carbon with 0.02-0.06 time of the equivalent of the medicinal material, stirring at room temperature, filtering, uniformly mixing the filtrate, and concentrating to obtain an extract; preserving the heat of the extract at 70-90 ℃, performing molecular distillation under vacuum at 70-90 ℃, and collecting light components to obtain a hemp total terpenoid crude extract; taking the hemp total terpene crude extract, adding purified water of which the amount is 6-10 times that of the hemp total terpene crude extract, carrying out steam distillation, collecting by using a light component collector, standing at room temperature, and collecting the upper layer to obtain a hemp total terpene extract; dissolving a hemp total terpene extract by using a proper amount of 80-98% ethanol, dropwise adding the solution into a saturated aqueous solution of beta-cyclodextrin at 50-70 ℃, preserving heat at 50-70 ℃, stirring and clathrating for 1-3 h, standing at room temperature, refrigerating for 12-36 h, filtering, and vacuum drying a filter cake at low temperature (30-50 ℃) for 8-16 h to obtain a hemp total terpene clathrate compound;
(2) and (2) taking a heavy component obtained by molecular distillation in the step (1), preserving heat at 80-95 ℃, performing molecular distillation under the conditions of vacuum and 180-200 ℃, collecting the light component, dissolving the light component by using 3-5 times of 70-90% ethanol, performing column chromatography on a dissolved solution, performing isocratic elution by using 60-80% ethanol as a mobile phase, collecting fractions, and concentrating under reduced pressure to obtain a thick paste, thus obtaining the hemp total terpene phenol extract.
Preferably, the cannabis total terpene phenolics and cannabis total terpenes are present in a 100:1, and mixing uniformly.
The pharmaceutical composition containing the cannabis extract can be prepared into dosage forms such as granules, capsules, tablets and the like with pharmaceutically acceptable auxiliary materials.
Further, the invention provides granules containing the hemp extract pharmaceutical composition, and the granules contain hemp total terpene inclusion compound, hemp total terpene phenol extract, diluent, adhesive and disintegrant.
Preferably, the diluent is selected from one or more than two of starch, lactose, dextrin, powdered sugar, calcium sulfate, sucrose, mannitol, microcrystalline cellulose and glucose; the adhesive is selected from one or more than two of pulping starch, pregelatinized starch, dextrin, polyvidone, ethyl cellulose and hydroxypropyl cellulose; the disintegrating agent is one or more selected from sodium carboxymethyl starch, cross-linked cellulose, corn starch, polyvidone, pregelatinized starch, and alginic acid.
Further preferably, the diluent is sucrose and dextrin, the binder is pulping starch, and the disintegrant is povidone.
More preferably, the granules of the pharmaceutical composition containing the cannabis extract comprise:
further, the preparation method of the granules containing the cannabis extract pharmaceutical composition comprises the following steps: weighing hemp total terpene inclusion compound, povidone, sucrose and dextrin according to the prescription amount, crushing, sieving and fully mixing for later use; preparing the pulping starch into starch slurry with the mass fraction of 8-12%, slowly dripping the hemp total terpene phenol extract into the starch slurry, uniformly mixing, adding the starch slurry into the mixed standby material under stirring, preparing a soft material, sieving to obtain wet granules, and drying.
Furthermore, the invention also provides a capsule containing the cannabis extract pharmaceutical composition, and the capsule contains cannabis terpene inclusion compound, cannabis total terpene phenol extract, diluent, adhesive, disintegrant, glidant and lubricant.
Preferably, the diluent is selected from one or more than two of mannitol, microcrystalline cellulose, lactose, corn starch and pregelatinized starch; the adhesive is selected from one or more than two of pulping starch, pregelatinized starch, dextrin, polyvidone, ethyl cellulose and hydroxypropyl cellulose; the disintegrating agent is selected from one or more of sodium carboxymethyl starch, cross-linked cellulose, corn starch, polyvidone, pregelatinized starch and alginic acid; the glidant is selected from superfine silica gel powder and talcum powder; the lubricant can be one or more of magnesium stearate, glyceryl monostearate, stearic acid, and pulvis Talci.
Further preferably, the diluent is microcrystalline cellulose; the binder is povidone; the disintegrating agent is sodium carboxymethyl starch; the glidant is talcum powder; the lubricant is magnesium stearate.
More preferably, the capsule containing the hemp extract pharmaceutical composition comprises:
further, the preparation method of the capsule containing the cannabis extract pharmaceutical composition comprises the following steps: weighing hemp total terpene inclusion compound according to the prescription amount, adding sodium carboxymethyl starch and microcrystalline cellulose, and uniformly mixing for later use; preparing povidone into povidone solution with the mass fraction of 0.8-1.2%, slowly dripping the cannabis total terpene phenol extract into the povidone solution, uniformly mixing, adding the povidone solution into the uniformly mixed standby mixture under stirring to prepare soft materials, sieving to obtain wet granules, drying, sieving to size, adding magnesium stearate and talcum powder, uniformly mixing, and filling capsules.
Furthermore, the invention also provides a tablet containing the hemp extract pharmaceutical composition, and the tablet contains hemp total terpene inclusion compound, hemp total terpene phenol extract, diluent, adhesive, disintegrant and lubricant.
Preferably, the diluent is selected from one or more than two of mannitol, microcrystalline cellulose, lactose, corn starch and pregelatinized starch; the adhesive is selected from one or more than two of pulping starch, pregelatinized starch, dextrin, polyvidone, ethyl cellulose and hydroxypropyl cellulose; the disintegrating agent is selected from one or more of sodium carboxymethyl starch, cross-linked cellulose, corn starch, polyvidone, pregelatinized starch and alginic acid; the lubricant is one or more selected from magnesium stearate, glyceryl monostearate, stearic acid, and pulvis Talci.
Further preferably, the diluent is pregelatinized starch, microcrystalline cellulose; the adhesive is povidone K30; the disintegrating agent is sodium carboxymethyl starch; the lubricant is magnesium stearate.
More preferably, the tablets containing the aforementioned cannabis extract pharmaceutical composition comprise:
further, the preparation method of the tablet containing the cannabis extract pharmaceutical composition comprises the following steps: sieving pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, and magnesium stearate respectively; preparing polyvidone K30 into 3% solution with anhydrous ethanol, slowly adding the total terpene phenol extract of Cannabis sativa L, and mixing; weighing hemp total terpene clathrate, pregelatinized starch, microcrystalline cellulose and sodium carboxymethyl starch according to the prescription, mixing uniformly, adding the prepared povidone K30 solution to prepare soft material, sieving to obtain wet granules, drying, sieving, adding magnesium stearate, mixing uniformly and pressing into tablets.
In a further aspect, the invention provides the use of a pharmaceutical composition comprising the aforementioned cannabis extract in the manufacture of a medicament for the treatment of epilepsy.
The inventor finds that the activity of the cannabis total terpene and the cannabis total terpene phenol is low when the cannabis total terpene and the cannabis total terpene phenol are applied independently, researches the influence of different proportions of the cannabis total terpene phenol and the cannabis total terpene on the drug effect through experiments, determines the optimal proportion range of the cannabis total terpene phenol and the cannabis total terpene, prepares the cannabis total terpene phenol and the cannabis total terpene into granules, capsules and tablets by assisting with proper pharmaceutical excipients, gives full play to the synergistic effect of the cannabis total terpene phenol and the cannabis total terpene phenol, and enhances the clinical application of cannabis preparations.
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 construed as limiting the present invention.
The terms "comprises," "comprising," "includes," "including," "has," "having," "contains," "containing," or any other variation thereof, as used herein, 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.
When an amount, concentration, or other value or parameter is expressed as a range, preferred range, or as a range of upper preferable values and lower preferable values, this is to be understood as specifically disclosing all ranges formed from any pair of any upper range limit or preferred value and any lower range limit or preferred value, regardless of whether ranges are separately disclosed.
The indefinite articles "a" and "an" preceding an element or component of the invention are not intended to limit the number requirement (i.e., the number of occurrences) of the element or component. Thus, "a" or "an" should be read to include one or at least one, and the singular form of an element or component also includes the plural unless the number clearly indicates the singular.
In the present invention, the content of cannabis total terpene phenol in the cannabis total terpene phenol extract is 85% and the content of cannabis total terpene in the cannabis total terpene inclusion compound is 8%, unless otherwise specified.
Example 1
Taking 100.0kg of hemp flower and leaf medicinal material, crushing, sieving by a No. 1 sieve, baking for 200min at 100 ℃, taking the baked hemp flower and leaf medicinal material, adding 95% ethanol according to the feed-liquid ratio of 1:8(w/v), stirring and extracting for two times at room temperature for 1 hour each time, filtering, merging extracting solutions, centrifugally filtering, concentrating the centrifugal filtrate under reduced pressure (65 ℃ to-0.08 to-0.09 Mpa) to obtain an extract, adding purified water with 3 times of the equivalent weight of the medicinal material, stirring for 30 minutes at 75 ℃, cooling to room temperature in a liquid separation tank, carrying out butterfly centrifugation, and separating an upper layer to obtain the hemp crude extract. Dissolving the obtained hemp crude extract with 95% ethanol with 3 times of medicinal material equivalent, adding 0.05 times of active carbon with equivalent of medicinal material, stirring at room temperature for 40 min, filtering, mixing the filtrate, and concentrating to obtain extract. Keeping the temperature of the extract at 80 deg.C, performing molecular distillation at vacuum degree of-0.1 Pa (absolute vacuum) and 85 deg.C, and collecting light components to obtain hemp total terpenoid crude extract. Taking the hemp total terpene crude extract, adding 8 times of purified water, performing steam distillation at 100 ℃, collecting by using a light component collector, standing at room temperature, and collecting the upper layer to obtain 100.8g of hemp total terpene extract. Dissolving cannabis sativa total terpene extract 100.0g in appropriate amount of 95% ethanol, dripping into saturated water solution of beta-cyclodextrin at 60 deg.C, stirring and clathrating at 60 deg.C for 2 hr, standing at room temperature, refrigerating for 24 hr, filtering, and vacuum drying filter cake at low temperature (40 deg.C) for 12 hr to obtain cannabis sativa total terpene clathrate 270.5g, wherein the content of cannabis sativa total terpene is 8.0%.
Secondly, taking heavy components obtained by molecular distillation in the step I, preserving heat at 90 ℃, carrying out molecular distillation under the conditions of vacuum degree of-0.1 to-10 Pa (absolute vacuum) and 190 ℃, collecting light components, dissolving the light components by using 80% ethanol of 4 times, carrying out column chromatography on a dissolved solution, carrying out chromatographic column chromatography on octadecylsilane chemically bonded silica gel with the particle size of 40 mu m as a chromatographic filler, using 75% ethanol as a mobile phase and carrying out isocratic elution at the flow rate of 3BV/h, collecting column volume fractions of 1 st to 2.5 times, and concentrating under reduced pressure to thick paste to obtain the cannabis terpene phenolic components, namely the cannabis total terpene phenolic extract, wherein the content of the cannabis total terpene phenolic is 85.0%.
Example 2
Respectively sieving a hemp total terpene phenol extract (the content of the hemp total terpene phenol is 85%) and a hemp total terpene inclusion compound (the content of the hemp total terpene is 8%) which are extracted from hemp by a sieve of 80 meshes, and uniformly mixing the large total terpene phenol and the hemp total terpene according to the proportion of 300-1: 1-300 (g/g) (the optimal proportion is 100:1), thus obtaining the hemp extract composition.
Example 3
A granule containing Cannabis sativa extract comprises the following components:
the preparation method comprises the following steps: weighing hemp total terpene clathrate, polyvidone, sucrose and dextrin according to the prescription amount, pulverizing, sieving with 100 mesh sieve, and mixing for 30 min; making pulping starch into 10% starch slurry, slowly adding cannabis total terpene phenol extract dropwise into starch slurry, mixing, adding starch slurry into the above mixed materials under stirring, making into soft material, sieving with 14 mesh sieve to obtain wet granules, drying at 40 deg.C for 6 hr, finishing, and packaging into 1000 bags.
Example 4
A capsule containing Cannabis sativa extract comprises the following components:
the preparation method comprises the following steps: weighing hemp total terpene inclusion compound according to the prescription, adding sodium carboxymethyl starch and microcrystalline cellulose, and uniformly mixing for later use; preparing povidone into 1% povidone solution, slowly adding the total terpene phenol extract of cannabis sativa into the povidone solution dropwise, mixing, adding the povidone solution into the above mixture under stirring to obtain soft material, sieving with 20 mesh sieve to obtain wet granules, drying at 40 deg.C for 4 hr, grading with 18 mesh sieve, adding pulvis Talci and magnesium stearate, mixing, and encapsulating to obtain 1000 granules.
Example 5
A tablet containing Cannabis sativa extract comprises the following components:
the preparation method comprises the following steps: sieving pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, and magnesium stearate with 80 mesh sieve respectively; preparing polyvidone K30 into 3% solution with anhydrous ethanol, slowly adding the total terpene phenol extract of Cannabis sativa L, and mixing; weighing hemp total terpene clathrate, pregelatinized starch, microcrystalline cellulose and sodium carboxymethyl starch according to the formula, mixing uniformly, adding polyvidone K30 solution to prepare soft material, and sieving with 20 mesh sieve to obtain wet granules; drying at 40 deg.C for 4h, sieving with 18 mesh sieve, adding magnesium stearate, mixing, and punching into 1000 pieces with diameter of 8 mm.
Pharmacodynamic preliminary screening test effect
First, experiment purpose
The preliminary pharmacodynamic action of different dose proportions of the cannabis total terpene phenol extract and the cannabis total terpene inclusion compound is researched, and a test basis is provided for the continuous development of tested drugs.
Second, Experimental materials
1. Drugs and reagents
1.1 medicine
Drug group: cannabis total terpene phenol extract (total content 85.0%, prepared in example 1), cannabis total terpene inclusion compound (total content 8.0%, prepared in example 1);
preparing the medicine:
-preparation of 1mg/ml total terpene phenol solution: taking a proper amount of hemp total terpene phenol extract, adding soybean oil, and performing ultrasonic-assisted dissolution to prepare a solution with the total terpene phenol concentration of 1 mg/ml;
-preparation of 0.01mg/ml total terpenes solution: taking a proper amount of cannabiterpene inclusion compound, adding soybean oil, and dissolving with ultrasonic assistance to prepare a solution with total terpene concentration of 0.01 mg/ml;
-a first group: total terpene phenol: total terpenes (1.5 mg/kg: 0);
-a second group: total terpene phenol: total terpenes (1 mg/kg: 0.005 mg/kg);
-a third group: total terpene phenol: total terpenes (0.5 mg/kg: 0.005 mg/kg);
-a fourth group: total terpene phenol: total terpenes (0.005 mg/kg: 1 mg/kg);
-a fifth group: total terpene phenol: total terpenes (0: 1.5 mg/kg);
control drugs: carbamazepine;
1.2 reagents
Soybean oil (Liaoning emerging pharmaceutical Co., Ltd., pure pharmaceutical): a test agent vehicle; pentylenetetrazole (Beijing, a general chemical Co., Ltd.) is a chemical substance used to induce epilepsy models.
2. Laboratory apparatus
JTC-1 model electroconvulsive instrument (changdu instrument factory), yles-4C model fatigue rotarod instrument (shanghai atlantoaxi medical instruments ltd.), thousandth balance (mertler-toledo instruments ltd., shanghai) ultrasonic machine (shanghai ning business ultrasonic instruments ltd.).
3. Laboratory animal
The experimental mice were provided by the laboratory animal technology of Beijing Wittiulihua, 35 mice, weighing 190-.
The mice are raised under the conditions of natural light of 12 h/12 h at night, and water and food are freely drunk.
Third, Experimental methods and results
Experimental methods
1. Maximal electric shock experiment (MES)
Experimental animals: mouse
The administration mode comprises the following steps: intraperitoneal injection (i.p.);
the experimental method comprises the following steps: coating 0.9% of physiological saline on two sides of a double-ear tip of a mouse, and clamping the double-ear tip by using an ear electrode; and then, alternating current of 110V and 60Hz is adopted, the electrical stimulation time is 0.2s, and the hind limb of the electrically stimulated mouse with the electrical stimulation can be used for the pharmacological experiment model if the hind limb of the electrically stimulated mouse has a tetanic phenomenon. After 0.5h after the administration of the drug, the test method is used for measuring, if the hind limb of the mouse has the phenomenon of tetany after the electrical stimulation, the drug is considered to have no anti-epileptic activity; otherwise, it has anti-epileptic activity. For the compound with potential activity, the half effective dose ED50 of the compound is further quantitatively evaluated through the pharmacological experimental model.
2. Neurotoxicity Test (TOX)
Experimental animals: mouse
The administration mode comprises the following steps: intraperitoneal injection (i.p.);
the experimental method comprises the following steps: after the test mice are administrated in the abdominal cavity for 0.5h, the test mice are placed on a fatigue bar rotating instrument with the radius of 15mm and the length of 60mm, and the rotating speed is adjusted to 6 rpm. Three tests were performed per mouse, each for 1min, and if the mice did not fall from the test cylinder within 1min, the drug was considered neurotoxic, and vice versa. Half of its toxic dose TD50 was further quantitatively evaluated by this pharmacological experimental model.
3. Convulsion experimental model
Grouping experiments: three groups-blank (soybean oil, 0.5ml/20g), drug group (first group, second group, third group, fourth group, fifth group), control drug group; each group had 5 mice.
The test method of the pentylenetetrazol model comprises the following steps: after 0.5h in the drug group and the control drug group (50mg/kg, i.p.), pentyltetrazole (70mg/kg, i.p.) was subcutaneously administered (s.c), followed by observation for 1 h. A seizure greater than 5s occurs in a mouse within 1h, it is called a clonic seizure, and if the hind limb of the mouse develops a tonic phenomenon, it is called a tonic seizure. And counting the clonus, rigidity and death number of the mice.
Experimental procedures and results: the test drug is dissolved in soybean oil, and two dosage types are injected into the abdominal cavity: 20. 100 mg/kg. Using 5 mice in each group, performing MES and TOX after intraperitoneal injection for half an hour, and recording the phenomenon; blank and control groups were run in the same manner.
PI (TD50/ED50) was calculated and a safe dose was deduced from the PI. The test subjects were then tested according to the convulsion test model method and the results are shown in the following table.
aMaximal electroshock:doses of 30and 100mg/kg were administrated intraperitoneally in mice.
The animals were examined 0.5h after administration.
bn1/n2:the animals protected/the animals tested
As can be seen from the above table, each test subject was overall less toxic at both doses; except for the blank group and the fifth group, the cannabis portion of the test subjects showed anticonvulsant activity at a dose of 100mg/kg, and the anticonvulsant activity of the third group and the control group was comparable and superior to that of the other groups. At a dose of 20mg/kg, the control drug, the second group, the third group, and the first group all exhibited varying degrees of anti-epileptic activity, with the third group being significantly superior to the other groups.
Fourth, conclusion of the experiment
The above results indicate that the third group had comparable efficacy to the control group and was superior to the first, second, fourth, and fifth groups. The antiepileptic pharmacological activity of the composition is higher than that of the composition prepared by independently applying the cannabis total terpene phenol extract and the cannabis total terpene inclusion compound, particularly the ratio is 100:1, and the composition is used at low dose.
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, which is intended to cover any variations, equivalents, or improvements therein, which fall within the spirit and scope of the invention.
Claims (10)
1. A pharmaceutical composition containing a cannabis extract, characterized in that the pharmaceutical composition containing the cannabis extract comprises a cannabis total terpene phenol extract and a cannabis total terpene inclusion compound, and the composition is prepared from cannabis total terpene phenol and cannabis total terpene (300-1): (1-300) uniformly mixing the components in a mass ratio to obtain the composite material; wherein the content of total cannabiterpenoid phenol in the total cannabiterpenoid phenol extract is 80-90%, and the content of total cannabioid terpene in the total cannabioid clathrate is 6-10%.
2. The cannabis extract-containing pharmaceutical composition of claim 1, wherein the cannabis total terpene phenolic extract and cannabis total terpene clathrate are prepared by a method comprising:
(1) crushing, sieving and baking a hemp flower and leaf medicinal material, adding 70-95% ethanol into a certain amount of the baked hemp flower and leaf medicinal material according to the material-liquid ratio of 1: 6-1: 10, stirring and extracting twice at room temperature, filtering, combining extracting solutions, centrifuging and filtering, concentrating a centrifugal filtrate under reduced pressure to obtain an extract, adding purified water with the equivalent of 2-5 times of the medicinal material, preserving heat and stirring at 70-80 ℃, placing in a liquid separation tank, cooling to room temperature, centrifuging, and separating an upper layer to obtain a hemp crude extract; stirring and dissolving the obtained hemp crude extract with 93-98% ethanol with 2-4 times of the equivalent of the medicinal material, adding active carbon with 0.02-0.06 time of the equivalent of the medicinal material, stirring at room temperature, filtering, uniformly mixing the filtrate, and concentrating to obtain an extract; preserving the heat of the extract at 70-90 ℃, performing molecular distillation under vacuum at 70-90 ℃, and collecting light components to obtain a hemp total terpenoid crude extract; taking the hemp total terpene crude extract, adding purified water of which the amount is 6-10 times that of the hemp total terpene crude extract, carrying out steam distillation, collecting by using a light component collector, standing at room temperature, and collecting the upper layer to obtain a hemp total terpene extract; dissolving a hemp total terpene extract by using a proper amount of 80-98% ethanol, dropwise adding the solution into a saturated aqueous solution of beta-cyclodextrin at 50-70 ℃, preserving heat at 50-70 ℃, stirring and clathrating for 1-3 h, standing at room temperature, refrigerating for 12-36 h, filtering, and vacuum drying a filter cake at low temperature (30-50 ℃) for 8-16 h to obtain a hemp total terpene clathrate compound;
(2) and (2) taking a heavy component obtained by molecular distillation in the step (1), preserving heat at 80-95 ℃, performing molecular distillation under the conditions of vacuum and 180-200 ℃, collecting the light component, dissolving the light component by using 3-5 times of 70-90% ethanol, performing column chromatography on a dissolved solution, performing isocratic elution by using 60-80% ethanol as a mobile phase, collecting fractions, and concentrating under reduced pressure to obtain a thick paste, thus obtaining the hemp total terpene phenol extract.
3. The cannabis extract-containing pharmaceutical composition of claim 1, wherein the cannabis total terpene phenolics and cannabis total terpenes are present in a 100:1, and mixing uniformly.
4. A cannabis extract-containing preparation, which is a granule, capsule or tablet prepared from the cannabis extract-containing pharmaceutical composition of any one of claims 1-3 and pharmaceutically acceptable excipients.
5. The cannabis extract-containing formulation according to claim 4, wherein the formulation is a granule comprising cannabis total terpene clathrate, cannabis total terpene phenol extract, diluent, binder, disintegrant;
preferably, the diluent is selected from one or more than two of starch, lactose, dextrin, powdered sugar, calcium sulfate, sucrose, mannitol, microcrystalline cellulose and glucose; the adhesive is selected from one or more than two of pulping starch, pregelatinized starch, dextrin, polyvidone, ethyl cellulose and hydroxypropyl cellulose; the disintegrating agent is selected from one or more of sodium carboxymethyl starch, cross-linked cellulose, corn starch, polyvidone, pregelatinized starch and alginic acid;
further preferably, the diluent is sucrose and dextrin, the binder is pulping starch, and the disintegrant is povidone;
more preferably, the granules comprise:
6. the cannabis extract-containing formulation according to claim 5, wherein the granules are prepared by a method comprising: weighing hemp total terpene inclusion compound, povidone, sucrose and dextrin according to the prescription amount, crushing, sieving and fully mixing for later use; preparing the pulping starch into starch slurry with the mass fraction of 8-12%, slowly dripping the hemp total terpene phenol extract into the starch slurry, uniformly mixing, adding the starch slurry into the mixed standby material under stirring, preparing a soft material, sieving to obtain wet granules, and drying.
7. The cannabis extract-containing formulation of claim 4, wherein the formulation is a capsule comprising cannabiterpene clathrate, cannabis total terpene phenol extract, diluent, binder, disintegrant, glidant, lubricant;
preferably, the diluent is selected from one or more than two of mannitol, microcrystalline cellulose, lactose, corn starch and pregelatinized starch; the adhesive is selected from one or more than two of pulping starch, pregelatinized starch, dextrin, polyvidone, ethyl cellulose and hydroxypropyl cellulose; the disintegrating agent is selected from one or more of sodium carboxymethyl starch, cross-linked cellulose, corn starch, polyvidone, pregelatinized starch and alginic acid; the glidant is selected from superfine silica gel powder and talcum powder; the lubricant can be one or more of magnesium stearate, glyceryl monostearate, stearic acid, and pulvis Talci;
further preferably, the diluent is microcrystalline cellulose; the binder is povidone; the disintegrating agent is sodium carboxymethyl starch; the glidant is talcum powder; the lubricant is magnesium stearate;
more preferably, the capsule containing the hemp extract pharmaceutical composition comprises:
8. the cannabis extract-containing formulation of claim 7, wherein the capsule is prepared by: weighing hemp total terpene inclusion compound according to the prescription amount, adding sodium carboxymethyl starch and microcrystalline cellulose, and uniformly mixing for later use; preparing povidone into povidone solution with the mass fraction of 0.8-1.2%, slowly dripping the cannabis total terpene phenol extract into the povidone solution, uniformly mixing, adding the povidone solution into the uniformly mixed standby mixture under stirring to prepare soft materials, sieving to obtain wet granules, drying, sieving to size, adding magnesium stearate and talcum powder, uniformly mixing, and filling capsules.
9. The cannabis extract-containing formulation according to claim 4, wherein the formulation is a tablet comprising cannabis total terpene clathrate, cannabis total terpene phenol extract, diluent, binder, disintegrant, lubricant;
preferably, the diluent is selected from one or more than two of mannitol, microcrystalline cellulose, lactose, corn starch and pregelatinized starch; the adhesive is selected from one or more than two of pulping starch, pregelatinized starch, dextrin, polyvidone, ethyl cellulose and hydroxypropyl cellulose; the disintegrating agent is selected from one or more of sodium carboxymethyl starch, cross-linked cellulose, corn starch, polyvidone, pregelatinized starch and alginic acid; the lubricant is one or more than two of magnesium stearate, glyceryl monostearate, stearic acid and talcum powder;
further preferably, the diluent is pregelatinized starch and microcrystalline cellulose; the adhesive is povidone K30; the disintegrating agent is sodium carboxymethyl starch; the lubricant is magnesium stearate;
more preferably, the tablets containing the aforementioned cannabis extract pharmaceutical composition comprise:
still more preferably, the preparation method of the tablet is: sieving pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, and magnesium stearate respectively; preparing polyvidone K30 into 3% solution with anhydrous ethanol, slowly adding the total terpene phenol extract of Cannabis sativa L, and mixing; weighing hemp total terpene clathrate, pregelatinized starch, microcrystalline cellulose and sodium carboxymethyl starch according to the prescription, mixing uniformly, adding the prepared povidone K30 solution to prepare soft material, sieving to obtain wet granules, drying, sieving, adding magnesium stearate, mixing uniformly and pressing into tablets.
10. Use of a cannabis extract-containing pharmaceutical composition according to any of claims 1-3 in the manufacture of a medicament for the treatment of epilepsy.
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