CN109106699A - A kind of pharmaceutical composition for treating epilepsy, its preparation method and use - Google Patents
A kind of pharmaceutical composition for treating epilepsy, its preparation method and use Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
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Abstract
The invention discloses a pharmaceutical composition containing cannabidiol and cannabidivarin in a specific ratio, a preparation method thereof and application thereof in epilepsy treatment. Specifically, the pharmaceutical composition takes cannabidiol or pharmaceutically acceptable salt thereof and cannabidivarin or pharmaceutically acceptable salt thereof as pharmaceutical active ingredients, wherein the weight ratio of the cannabidiol or pharmaceutically acceptable salt thereof to the cannabidivarin or pharmaceutically acceptable salt thereof is 10: 1-50. The pharmaceutical composition is particularly beneficial in the treatment of epilepsy, particularly partial seizures.
Description
Technical field
The present invention relates to pharmaceutical technology fields, and in particular to a kind of for treating the pharmaceutical composition of epilepsy, preparation side
Method and its purposes in treatment epilepsy, especially partial seizures.
Background technique
Epilepsy (epilepsy) is a kind of brain diseases chronic as caused by Different types of etiopathogenises, is led with brain neuron over-discharge
Cause that repeatability, ictal and transience central nervous system function is not normal is characterized.
Epilepsy has morbidity in the crowd of any age, area and race, but higher with Children and teenager disease incidence.
Recently as China human mortality aging, the disease incidence of cerebrovascular disease, dementia and nervous system degenerative disease increases, the elderly
Has there is the trend risen in epilepsy invasion rate in group.Epilepsy brings serious negative effect, epilepsy for personal, family and society
It breaks out and causes huge physiology and psychological pain to patient, seriously affect the quality of life of patient and family；It takes for a long time
Antiepileptic and other diagnosis and treatment expenses bring heavy financial burden to family.
The partial seizures (partial seizure) of epilepsy are also referred to as focal seizure (focal seizure).Face
Bed and electroencephalogram initially change prompt, and cerebral hemisphere partial nerve member is activated first, then occurs simultaneously and rapidly discharging, fast
Speed is spread to surrounding normal brain area, generates a series of electro physiologies and neurochemistry variation, until neuronal energy is exhausted and metabolism drop
It is low to make the automatic termination that breaks out.According to episode process whether with the disturbance of consciousness, it is divided into simple partial seizure (unconscious barrier when breaking-out
Hinder) and complex partial seizures (having the different degrees of disturbance of consciousness).Almost all of antiepileptic all there may be adverse reaction,
Its severity has very big difference in Different Individual.The adverse reaction of antiepileptic is to lead to another main original for the treatment of failure
Cause.Most of adverse reaction is slight, but also has a small number of meeting threat to life.The most common adverse reaction includes Central nervous
The influence (calm, drowsiness, dizzy, mutual aid obstacle, cognition, memory etc.) of system, to whole body multisystem influence (hematological system,
Digestive system, weight change, fertility Issue, bone health etc.) and idiosyncrasy reaction.
Hemp knows already as the application of medicine, and in 19th century, hemp products is proposed as hypnosis sedative,
It can be used for treating hysteria, amentia, epilepsy, nerve insomnia, migraine and dysmenorrhea.In the 1940s, research
Personnel's isolated cannabidiol (CBD) from hemp, experiment in vivo find that CBD not only can antagonism THC excitement cannboid I type
The psychotropic activity that receptor (CB1R) is caused, and there is anticonvulsion, antianxiety, antipsychotic, tranquilizing soporific, anti-inflammatory and neural
Protective effect.Preclinical and clinical research shows that cannabidiol (CBD) pharmacokinetics are good, can penetrate blood after injection rapidly
Brain barrier, neuroprotection effect are significant.Cannabidiol (CBD) can play neuroprotection, and its by multipath
Toxicity is weak, few side effects.Currently, FDA has authorized three kinds of the drug containing cannabidiol rare sick (the ictal epilepsies of children
LGS, Dravet epileptic syndromes, hypoxic ischemic encephalopathy of newborn (NHIE)) drug qualification.
Chinese patent application CN201280004572.6 discloses a kind of cannabidiol (CBD) to be higher than agent in 300mg/ days
The purposes combined with the standard anti-epileptic drug by sodium or calcium channel effect for epilepsy is measured, and is disclosed in embodiment
The combination of the combination of CBD and valproate, phenobarbital, CBD and valproate can increase the incubation period that epileptic attack starts,
Reduce the percentage of tonic-clonic seizures, but the combination of CBD and phenobarbital is almost without obvious synergistic action effect,
Combination is meaningless for the treatment of epilepsy.
U.S. Patent Application Publication No. US2015359756A1 discloses cannabidiol (CBD) and one or more anti-epileptics
The combination of drug (AEDs), wherein the antiepileptic (AEDs) can be selected from: Clobazam, Clorazepate, goes first at Clonazepam
Clobazam, diazepam, ethymal, Felbamate, Gabapentin, high fat diet, drawing section amine, Lamotrigine, Levetiracetam, labor
West is dissolved, midazolam, N- remove first Clobazam, nordazepam, phenytoinum naticum, Stiripentol, Topiramate Trazodone, valproic acid, ammonia for drawing
Hexenoic acid, Zonisamide.However, the patent application does not disclose or implies cannabidiol (CBD) and cannabidivarin
(cannabidivarin) combination and its purposes in treatment epilepsy, especially partial seizures.
The present inventor is by experiment it was unexpectedly observed that when the cannabidiol (CBD) that will be matched containing specified weight
The treatment of epilepsy, especially partial seizures is used for the pharmaceutical composition of cannabidivarin (cannabidivarin)
When, it can produce unexpected synergy between two kinds of active components, two kinds of active components can also be mitigated at the same time
Side effect when exclusive use improves the compliance of patient.
Summary of the invention
It is a kind of with synergistic treatment effect the technical problem to be solved by the present invention is to overcome the deficiencies of the prior art and provide
Fruit also has the treatment epilepsy for mitigating side effect, the especially pharmaceutical composition of partial seizures, preparation at the same time
Method and its purposes in treatment epilepsy, especially partial seizures.
For this purpose, the present invention provides a kind of pharmaceutical composition, described pharmaceutical composition is comprising active pharmaceutical ingredient and pharmaceutically
Acceptable carrier or excipient, wherein the active pharmaceutical ingredient is: a) cannabidiol or its pharmaceutically acceptable salt, and
B) cannabidivarin or its pharmaceutically acceptable salt, and active pharmaceutical ingredient a) and b) between weight proportion be 10:1-
50。
Present inventor it was unexpectedly observed that in the pharmaceutical composition with specified weight match existing cannabidiol and
Cannabidivarin especially can produce unexpected collaboration effect in epilepsy in the therapeutic process of partial seizures
Fruit can also mitigate side effect when two kinds of active components are used alone at the same time, improve the compliance of patient.
In one embodiment of the invention, described two active pharmaceutical ingredient a) in described pharmaceutical composition and b)
Between weight proportion be 10:10.
In another embodiment of the present invention, described two active pharmaceutical ingredient a) in described pharmaceutical composition and
B) weight proportion between is 10:20.
In another embodiment of the present invention, described two active pharmaceutical ingredient a) in described pharmaceutical composition and
B) weight proportion between is 10:30.
In another embodiment of the present invention, described two active pharmaceutical ingredient a) in described pharmaceutical composition and
B) weight proportion between is 10:40.
Preferably, the active pharmaceutical ingredient a) in described pharmaceutical composition is cannabidiol.
Preferably, the active pharmaceutical ingredient b) in described pharmaceutical composition is cannabidivarin.
Cannabidiol and cannabidivarin used in the present invention can be chemosynthesis product, biosynthetic products, from
Plant extracts separation is prepared using other way.For example, cannabidiol of the present invention is from plant extracts
Separation, the extractable shell from the stalk core of hemp Cannabis sativa L., flower, leaf, root or seed of the plant extracts.
Pharmaceutical composition of the present invention further includes pharmaceutically acceptable carrier or excipient.
Pharmaceutical composition of the present invention can by any administration route appropriate such as oral, rectum, nose, lung,
In part (including oral cavity and sublingual), transdermal, brain pond, intraperitoneal, vagina and parenteral (including subcutaneous, intramuscular, intrathecal, vein
It is interior and intradermal) approach administration.Preferably, pharmaceutical composition of the present invention is administered by oral route.It should be understood that preferred
Administration route depends on ordinary circumstance, age, gender, weight, the property of disease to be treated, severity of patient to be treated
With the active constituent of specific choice.
Specific dosage form can be made according to the conventional formulation technologies of this field in pharmaceutical composition of the present invention.
In one embodiment, pharmaceutical composition of the present invention is the dosage form of oral administration.The oral administration
Dosage form can be selected from solid dosage forms and liquid dosage form.Preferably, the solid dosage forms be tablet, powder agent, granule, pill,
Pastille or capsule；The liquid dosage form is solution, emulsion, suspension, syrup or elixir.
In another embodiment, pharmaceutical composition of the present invention is the dosage form of parenteral.The stomach and intestine
The dosage form of external administration can be selected from sterile Injectable solution, dispersion liquid, suspension, lotion and be redissolved in front of use sterile
Injectable solution or dispersion liquid injection sterile powder.
In another embodiment, pharmaceutical composition of the present invention is the dosage form of skin or mucosa delivery.It is described
The dosage form of skin or mucosa delivery can be selected from suppository, ointment, cream, gelling agent, aerosol, spray, powder spray, skin
Patch, implant etc..
In one embodiment, the present invention also provides a kind of sides for being used to prepare pharmaceutical composition of the present invention
Method, described method includes following steps: 1) the active pharmaceutical ingredient a) cannabidiol or its pharmacy for being 10:1-50 by weight proportion
Upper acceptable salt and b) cannabidivarin or its pharmaceutically acceptable salt and pharmaceutically acceptable carrier or excipient
It is uniformly mixed；2) mixture for optionally obtaining step 1) is prepared into any pharmaceutically acceptable dosage form.
It, can be using usually used any pharmaceutically acceptable load in the art in order to prepare described pharmaceutical composition
Body, diluent, excipient or other additives.
For example, solid carrier known in the art can be used in order to prepare the solid dosage forms of oral administration.Solid carrier
Example have lactose, sucrose, cyclodextrin, agar, pectin, Arabic gum, the lower alkyl ether of cellulose, cornstarch, Ma Ling
Sweet potato starch, talcum powder, magnesium stearate, gelatin etc..In addition, any other the purpose of being commonly used in coloring, flavoring, anti-corrosion can be used
Auxiliary material or additive, as long as they are compatible with active constituent or used ingredient.It, can be with using above-mentioned solid carrier
Pharmaceutical composition of the invention is prepared into the form such as tablet, powder agent, granule, pill, pastille or capsule.
Similarly, in order to prepare the liquid dosage form of oral administration, liquid-carrier known in the art can be used.Liquid carries
The example of body has water, ethyl alcohol, glycerol, propylene glycol, polyethylene glycol, syrup, atoleine, ethyl oleate, isopropyl myristate
And fat oil such as peanut oil, sesame oil, soybean oil, cottonseed oil, olive oil etc..It, can will be of the invention using aforesaid liquid carrier
Pharmaceutical composition be prepared into the form such as solution, emulsion, suspension, syrup or elixir.
In order to prepare the dosage form of parenteral, sterile carrier known in the art can be used.The sterile carrier example
Such as water for injection, oil for injection such as vegetable oil such as sesame oil, soybean oil, peanut oil, castor oil, tea oil, other solvent for injection
Such as ethyl alcohol, glycerol, propylene glycol, polyethylene glycol, Ergol, ethyl oleate, dimethyl acetamide.If desired, may be used also
To use various additives such as solubilizer, wetting agent, emulsifier, buffer, suspending agent, antioxidant, bacteriostatic agent, local analgesia
Agent, isotonic regulator etc..For injection sterile powder, filler and protective agent such as lactose, sucrose, malt can also be used
Sugar, mannitol, glycine and human serum albumins etc..
For example, the sterile Injectable solution of parenteral can be prepared as follows: by one or more active constituents and
Possible additive is dissolved in a part of Injectable sterile liquid-carrier (preferably sterile water), adjustment solution to required volume,
It by solution sterilization and is filled into ampoule or bottle appropriate, to obtain sterile Injectable solution.
Preparation for the dosage form of skin or mucosa delivery can be used for skin or mucosa delivery using known in the art
Carrier.The carrier for skin or mucosa delivery can be selected from for example cocoa butter, fatty glyceride, polyethylene glycol,
Poloxamer, paraffin, vaseline, dimethicone, lanolin, beeswax, carbomer, cellulose derivative, polyvinyl alcohol, poly- second
Alkene pyrrolidone, dichlorodifluoromethan hydrocarbon, compressed gas, reservoir material etc..Skin or mucosa delivery are used for using above-mentioned
Carrier, pharmaceutical composition of the invention can be prepared into such as suppository, ointment, cream, gelling agent, aerosol, spray
The forms such as mist agent, powder spray, dermal patch or implant.For example, suppository can be prepared as follows: by suppository base such as cocoa butter
Heating fusing is added drug and is simultaneously uniformly mixed, then by resulting mixture inject in mold and it is cooling to get.
The preparation of the pharmaceutical composition of invention described above can easily be made according to the standardization program of pharmaceutical formulation
At unit dosage forms.The amount of reactive compound in per unit dosage form may according to the various pharmaceutical activity in pharmaceutical composition at
Point property, the property of the pharmaceutical composition, the property of disease to be treated and the situation of patient and change.With regard to medicine of the invention
For the application of compositions, it should provide a effective amount of active pharmaceutical ingredient, and generate expected technical effect.Preferably,
The pharmaceutical composition include 200mg to the cannabidiol of 600mg or its pharmaceutically acceptable salt and 20mg extremely
The cannabidivarin of 3000mg or its pharmaceutically acceptable salt.It is furthermore preferred that the pharmaceutical composition include 200mg extremely
The cannabidiol of 400mg or its pharmaceutically acceptable salt and 200mg to the cannabidivarin of 800mg or its pharmaceutically may be used
The salt of receiving.Most preferably, the pharmaceutical composition includes 200mg to the cannabidiol of 400mg or its is pharmaceutically acceptable
Salt and 400mg to the cannabidivarin of 800mg or its pharmaceutically acceptable salt.Certainly, it generates needed for useful effect
The final dosage of active pharmaceutical ingredient can change and finally be determined by medical worker.
The present invention also provides a kind of pharmaceutical compositions of the invention to prepare the drug for preventing and/or treating epilepsy
In purposes.
Preferably, the types of epilepsy is partial seizures.In one embodiment, the partial seizures are single
Pure partial seizures (localized episode) or complex partial seizures, more preferably simple partial seizure (localized episode).
The present invention also provides a kind of prevention and/or the method for the treatment of epilepsy, especially partial seizures, this method
Pharmaceutical composition of the present invention including giving from therapeutically effective amount to patient in need.
Cannabidiol (CBD) of the present invention containing special ratios or its pharmaceutically acceptable salt and time hemp two
The pharmaceutical composition of phenol (cannabidivarin) or its pharmaceutically acceptable salt is particularly suitable for treating epilepsy, especially
It is partial seizures.Present inventor it was unexpectedly observed that being matched in the pharmaceutical composition with specified weight existing for
Cannabidiol and cannabidivarin especially can produce in the therapeutic process of partial seizures unexpected in epilepsy
Synergy, can also mitigate at the same time two kinds of active components be used alone when side effect, improve the compliance of patient.
For example, can reduce or eliminate individually makes when using medicine composite for curing epileptic attack of the present invention
The side effect caused by cannabidiol or cannabidivarin, it is the drowsiness, diarrhea generated when being used alone such as cannabidiol, tired
Labor, convulsions, vomiting, loss of appetite and weight loss.
In order to be further understood essence and spirit of the invention, combined with specific embodiments below to of the invention excellent
Embodiment and its effect is selected to be described.It is understood, however, that these descriptions are only intended to further illustrate spy of the invention
It seeks peace advantage, and any restrictions is constituted to claim of the invention absolutely not.
Specific embodiment
The source of all raw materials used in the preparation of described pharmaceutical composition is not particularly limited in the present invention, in city
It is being bought on field or according to conventional method well known to those skilled in the art preparation.
Prepare embodiment 1
Pharmaceutical composition 1
The cannabidiol of 600mg micronization and the cannabidivarin of 3000mg micronization are weighed, is sufficiently mixed in mortar
Uniformly to get the pharmaceutical composition 1 of the invention of powder agent (powder) form.
Prepare embodiment 2
Pharmaceutical composition 2
The cannabidiol of 200mg micronization and the cannabidivarin of 20mg micronization are weighed, is sufficiently mixed in mortar
The even pharmaceutical composition 2 of the invention to get powder agent (powder) form.
Prepare embodiment 3
Pharmaceutical composition 3
The cannabidiol of 200mg micronization and the cannabidivarin of 200mg micronization are weighed, is sufficiently mixed in mortar
The even pharmaceutical composition 3 of the invention to get powder agent (powder) form.
Prepare embodiment 4
Pharmaceutical composition 4
The cannabidiol of 200mg micronization and the cannabidivarin of 400mg micronization are weighed, is sufficiently mixed in mortar
The even pharmaceutical composition 4 of the invention to get powder agent (powder) form.
Prepare embodiment 5
Pharmaceutical composition 5
The cannabidiol of 200mg micronization and the cannabidivarin of 600mg micronization are weighed, is sufficiently mixed in mortar
The even pharmaceutical composition 5 of the invention to get powder agent (powder) form.
Prepare embodiment 6
Pharmaceutical composition 6
The cannabidiol of 200mg micronization and the cannabidivarin of 800mg micronization are weighed, is sufficiently mixed in mortar
The even pharmaceutical composition 6 of the invention to get powder agent (powder) form.
Influence experiment of the combination of 1 cannabidiol of experimental example and cannabidivarin to epilepsy therapy effect
Experimental material
Experimental animal: healthy male Wistar rat, weight 75-110g.By animal 21 DEG C, 50% humidity and 12 hours
It is adapted to three days under illumination condition, animal can ad lib and drinking-water.
Experimental method
Rat portions epileptic attack model foundation: penicillin-induced rat portions epileptic attack model is used
(Bostanci and Bagirici, 2006).
Experimental animal is grouped at random, every group 20.Vehicle controls or given the test agent give experimental animal peritoneal injection
Medicine.Herein before one week, operation is passed through under anaesthesia for the ventriculus dexter cerebri of intubation implantation animal.After administration 1 hour, at 1 minute
It is interior that penicillin (1000IU/kg) is injected into animal ventriculus dexter cerebri, and record breaking-out behavior in 2 hours.
The grading system of partial seizures for penicillin induction is as shown in table 1.
Following formula can be used to evaluate for human body equivalent dose (HED):
HED=animal dosage (mg/kg) is multiplied by animal Km/ people Km
The Km of rat is 6, and the Km of people is 37.
Therefore, for the people of 60kg, the dosage of 100mg/kg is equal to the dosage of about 1000mg/ days people in rat, is
It avoids confusion, dosage as described below is the dosage that corresponding people is calculated as according to experimental animal.
Partial seizure scoring and the experimental animal of 1 penicillin of table induction show
| Scoring | Experimental animal performance |
| 0 | Without twitch, behavior is normal |
| 1 | Madness runs/jumps |
| 2 | The myoclonia stage |
| 3 | Unilateral forelimb clonic spasm |
| 4 | Bilateral forelimb clonic spasm |
| 5 | Retain the tonic-clonic seizures of ability of posture control |
| 6 | Tonic-clonic seizures without ability of posture control |
Animal is recorded since injecting penicillin to there is 1 grade of actuation time in table 1, is calculated as time started (incubation period),
It records from animal and first appears the time that seizure disorder or death once occur to the end in partial seizures, calculate insane
Epilepsy is broken out the duration.
Recording laboratory animal The dead quantity calculates the death rate, pays attention to forming the most of dynamic of tonic-clonic seizures
Object is often therefore dead.The quantity that record animal does not break out.
Dosage regimen and experimental result (assessment result of epileptic attack is indicated with the mean+SD of measurement result)
As shown in table 2.
The dosage regimen and experimental result of the pharmaceutical composition of the invention of table 2
As shown in Table 2, for cannabidiol and cannabidivarin, no matter being single use or combining makes
With all having certain therapeutic effect for animal epileptic model.But applicants have unexpectedly found that, when by cannabidiol and
When cannabidivarin is applied in combination with the specific weight proportion of 10:1-50, with positive control phenytoinum naticum and exclusive use
It cannabidiol, cannabidivarin and is compared, is had significant more preferable with cannabidivarin with the cannabidiol that other ratios combine
Synergistic therapeutic effect, such as the incubation period that epileptic attack starts can be dramatically increased, reduce seizure duration, reduced dead
Rate is died, the percentage not broken out is improved.
The combination of 2 cannabidiol of experimental example and cannabidivarin is living in the anti-epileptic of maximal electroshock seizure model
Property test
Experimental animal: this experiment uses 5-7 week old male ICR mouse.By animal feeding temperature be 25 ± 2 DEG C, humidity
It is 60 ± 10%, striation part is 7AM to 7PM photoperiod, under conditions of 7PM to the 7AM dark period.Mouse can arbitrarily feed feed
And drinking public water supply.
Experimental method and experimental result:
Used test compound is positive control phenytoinum naticum and experiment object cannabidiol, cannabidivarin and two
The combination of person in varing proportions.All test compounds are intraperitoneally given, and administered dose is the agent to be scaled corresponding people
Amount indicates.
Experiment the previous day, mouse is weighed and is assigned randomly to several groups, every group 20.Experimental day morning is again
It weighs, to calculate the dosage of every animal.According to dosage shown in the following table 3, it is (insane that mouse physiological saline is given in peritonaeum
Epilepsy model group), phenytoinum naticum, cannabidiol, the combination of cannabidivarin and the two in varing proportions, electric thorn is given after 30 minutes
Swash.By ear-lobe electrode, using the electric current of 30mA, 100Hz pulse frequency is given up to 200mse, by stimulant (UGO BASILE
ECT UNIT 7801, Italia) inducing mouse maximal electroshock seizure, it observes mouse 10 seconds and records tonic hindlimb elongation
Incidence.
Dosage regimen and experimental result are as shown in table 3.
The dosage regimen and experimental result of the pharmaceutical composition of the invention of table 3
By the result in table 3 as it can be seen that nearly all animal in epilepsy model group all show by electro photoluminescence (30mA,
Hind leg elongation 200msec) induced.For cannabidiol and cannabidivarin, no matter being single use or combining makes
With all having certain inhibiting effect for the hind leg elongation induced by electro photoluminescence (30mA, 200msec), but in degree still slightly
It is weaker than positive control phenytoinum naticum.But applicants have unexpectedly found that, when by cannabidiol and cannabidivarin with 200:20-
Hemp when the specific weight proportion of 1000 (i.e. 10:1-50) is applied in combination, with positive control phenytoinum naticum and exclusive use
It diphenol, cannabidivarin and is compared with the cannabidiol that other ratios combine with cannabidivarin, it is significant preferably right to have
In the inhibiting effect of the hind leg elongation induced by electro photoluminescence (30mA, 200 msec).
The clinical trial that the combination of 3 cannabidiol of experimental example and cannabidivarin influences drug side-effect
Experimental subjects: 90 people of partial seizures volunteer, men and women is unlimited, and stochastic averagina is divided into 6 groups, every group of 15 people,
Respectively control group 1-3 and experimental group 1-3.
Control group 1:200mg cannabidiol/day；
Control group 2:200mg cannabidiol+10mg cannabidivarin/day；
Control group 3:200mg cannabidiol+1200mg cannabidivarin/day；
Experimental group 1:200mg cannabidiol+20mg cannabidivarin/day；
Experimental group 2:200mg cannabidiol+100mg cannabidivarin/day；
Experimental group 3:200mg cannabidiol+1000mg cannabidivarin/day.
Experimental method: being administered experimental subjects according to above-mentioned dosage regimen, once a day, successive administration 12 months；Observation
Seizure frequency, side effect during recording the 2nd, 4,6,8,10,12 month, are compareed based on treating preceding 2 months seizure frequencies.
Side effect: chemical examination blood routine, electrolyte simultaneously monitor blood concentration, record and are occurred in each point of observation 2 months
Side effect；The side effect includes drowsiness, diarrhea, fatigue, convulsions, vomiting, loss of appetite and weight loss etc..
Experimental result is as shown in table 4.
4 side effect of table and recurrence rate experimental result
As seen from the results in Table 4, when cannabidiol and cannabidivarin are made with the specific weight proportion combination of 10:1-50
Used time can substantially reduce the side effect main suit incidence of patient and the later six months incidence again that is discontinued, to significantly improve trouble simultaneously
The compliance of person reaches better therapeutic effect.
The above is only a preferred embodiment of the present invention.It should be pointed out that for the ordinary skill people of the art
For member, under the premise of not departing from spirit and principles of the present invention, several improvement, modification and equivalent replacement can also be made
Deng, these improve, modification and equivalent replacement after technical solution also should be regarded as falling within the scope and spirit of the invention.
Claims (12)
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019180706A1 (en) * | 2018-03-19 | 2019-09-26 | Bol Pharma Ltd. | Methods and compositions for treating epilepsy and associated disorders |
| CN113874344A (en) * | 2019-03-08 | 2021-12-31 | 加利福尼亚大学董事会 | Use of 8,9-dihydrocannabidiol compounds |
| CN114746086A (en) * | 2019-11-21 | 2022-07-12 | 吉伟研究有限公司 | Cannabidiol cannabinoid compounds |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103025325A (en) * | 2010-03-30 | 2013-04-03 | Gw药品有限公司 | Use of the phytocannabinoid cannabidivarin (cbdv) in the treatment of epilepsy |
| CN103826621A (en) * | 2011-09-29 | 2014-05-28 | Gw药品有限公司 | Pharmaceutical composition comprising the phytocannabinoids cannabidiol (CBDV) and cannabidiol (CBD) |
-
2017
- 2017-06-23 CN CN201710487740.6A patent/CN109106699A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103025325A (en) * | 2010-03-30 | 2013-04-03 | Gw药品有限公司 | Use of the phytocannabinoid cannabidivarin (cbdv) in the treatment of epilepsy |
| CN103826621A (en) * | 2011-09-29 | 2014-05-28 | Gw药品有限公司 | Pharmaceutical composition comprising the phytocannabinoids cannabidiol (CBDV) and cannabidiol (CBD) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019180706A1 (en) * | 2018-03-19 | 2019-09-26 | Bol Pharma Ltd. | Methods and compositions for treating epilepsy and associated disorders |
| CN113874344A (en) * | 2019-03-08 | 2021-12-31 | 加利福尼亚大学董事会 | Use of 8,9-dihydrocannabidiol compounds |
| CN113874344B (en) * | 2019-03-08 | 2025-05-27 | 加利福尼亚大学董事会 | Uses of 8,9-dihydrocannabidiol compounds |
| CN114746086A (en) * | 2019-11-21 | 2022-07-12 | 吉伟研究有限公司 | Cannabidiol cannabinoid compounds |
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