CN108245510A - Cannabidiol and the composition of second propionyl ureas antiepileptic and application thereof - Google Patents
Cannabidiol and the composition of second propionyl ureas antiepileptic and application thereof Download PDFInfo
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- CN108245510A CN108245510A CN201611249138.0A CN201611249138A CN108245510A CN 108245510 A CN108245510 A CN 108245510A CN 201611249138 A CN201611249138 A CN 201611249138A CN 108245510 A CN108245510 A CN 108245510A
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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
- A61K31/05—Phenols
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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Abstract
The invention discloses compositions of a kind of cannabidiol and second propionyl ureas antiepileptic and application thereof, the composition includes cannabidiol and second propionyl ureas antiepileptic or its pharmaceutically acceptable salt, the particularly pharmaceutical composition of cannabidiol and phenytoinum naticum, the composition is used for the treatment of epilepsy particularly partial seizures, unexpected synergistic therapeutic effect can be obtained, the side effect that cannabidiol or phenytoinum naticum are used alone can also be mitigated or eliminated, improve the compliance of patient.
Description
Technical field
The present invention relates to pharmaceutical technology fields, and in particular to a kind of cannabidiol and second propionyl ureas antiepileptic are special
The composition for being phenytoinum naticum and its application in treatment epilepsy particularly partial seizures.
Background technology
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 incidence.
Recently as China human mortality aging, the 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.
Partial seizures (partial seizure) are also referred to as focal seizure (focal seizures), it is clinical and
Electroencephalogram initially changes prompting, and cerebral hemisphere partial nerve member is activated first, then occurs simultaneously and rapidly discharging, rapidly to
Surrounding normal brain area is spread, and generates a series of electro physiologies and neurochemistry variation, until neuronal energy is exhausted and metabolism reduction makes
Breaking-out is automatic to be terminated.According to episode process whether with the disturbance of consciousness, it is divided into simple partial seizure (unconscious obstacle during breaking-out)
With complex partial seizures (having the different degrees of disturbance of consciousness).Clinical common medicine has dilantin sodium, carbamazepine, Oxcarbazepine
Deng.But these adverse drug reactions are obvious, as phenytoinum naticum (phenytoyin, PHT) can cause gingival hyperplasia, fash, altogether
Ji imbalance and slow poisoning encephalopathy etc. bring many unnecessary pains to patient.
Hemp knows, and that in 19th century hemp products is proposed as hypnosis sedative already as the application of medicine,
It can be used for treatment hysteria, amentia, epilepsy, nerve insomnia, migraine and dysmenorrhoea.
In the 1940s, researcher's isolated cannabidiol (CBD) from hemp, experiment in vivo finds CBD not
But the psychotropic activity that energy antagonism THC excitement cannboid I receptors (CB1R) are caused, and with anticonvulsion, antianxiety, anti-essence
Refreshing disease, tranquilizing soporific, anti-inflammatory and neuroprotection.Preclinical and clinical research shows that CBD pharmacokinetics are good, injection
After can penetrate blood-brain barrier rapidly, neuroprotection effect is notable.CBD can play neuroprotection by multipath, and
And its toxicity is weak, few side effects.At present, FDA authorized three kinds of the drug containing cannabidiol it is rare disease (children are ictal insane
Epilepsy LGS, Dravet epileptic syndromes, hypoxic ischemic encephalopathy of newborn (NHIE)) drug qualification.
Patent application CN201280004572.6 disclose a kind of cannabidiol (CBD) be higher than the dosage of 300mg/ days with
The standard anti-epileptic drug combination acted on by sodium or calcium channel for epilepsy purposes, and disclose in embodiment CBD with
The combination of the combination of valproate, phenobarbital, CBD and valproate can increase the incubation period that epileptic attack starts, and reduce
The percentage of tonic-clonic seizures, but the combination of CBD and phenobarbital is almost without apparent synergistic action effect, the two
Combination it is meaningless for the treatment of epilepsy.
The present inventor is found through experiments that second propionyl ureas antiepileptic such as phenytoinum naticum being made with CBD and combine
Object is used for the treatment of epilepsy particularly epilepsy partial seizures, can obtain unexpected synergistic therapeutic effect, it is particularly possible to
The side effect that cannabidiol or phenytoinum naticum are used alone is mitigated or eliminated, is greatly improved the compliance of patient.
Invention content
The present invention provides a kind of pharmaceutical composition, and described pharmaceutical composition includes cannabidiol (CBD) and second propionyl ureas
Antiepileptic or its pharmaceutically acceptable salt.
Preferably, CBD and second propionyl ureas antiepileptic or its pharmaceutically acceptable salt in described pharmaceutical composition
Mass ratio be 0.4-3:1, preferably 1-3:1, more preferably 3:1.
Preferably, the second propionyl ureas antiepileptic is selected from：Phenytoinum naticum (PHT), Methoin, ethotoin, deoxidation
Benzene is than appropriate.
In a preferred embodiment of the invention, the second propionyl ureas antiepileptic is PHT.
Preferably, the pharmaceutically acceptable salt of the phenytoinum naticum is selected from：Dilantin sodium, calcium diphenylhydantoin, Fosphenytoin
Sodium；
Epilepsy is that the electric discharge of cerebral neuron paroxysmal abnormality leads to the disease of of short duration cerebral disorder, neuronal cell
Impaired, antiepileptic usually controls breaking-out by reducing brain cell excitability, and taking antiepileptic for a long time may
Lead to the missing of some nutriments, it is preferred that neurotrophy class drug is further included in pharmaceutical composition of the present invention, it is special
It is not cranial nerve Amitin object, such as Nerve growth factors drug, B family vitamin such as vitamin B1, B12, oryzanol, Aura
Western smooth, Piracetam, Methycobal, gangliosides, sarcosine peptide aglycone etc..
CBD used in the present invention can be chemosynthesis product, biosynthetic products, plant extracts or using other
Mode is prepared.Preferably, cannabidiol of the present invention is plant extracts, and the plant extract position can be
The stalk core of hemp Cannabis sativa L., flower, leaf, root or seed shell.
Preferably, the pharmaceutical composition further includes pharmaceutically acceptable carrier or excipient.
Composition of the present invention can be made into specific dosage form, for example oral, straight by any appropriate administration route
Intestines, nose, lung, part (including oral cavity and sublingual), in transdermal, brain pond, intraperitoneal, vagina and parenteral (including subcutaneous, flesh
It is interior, intrathecal, intravenous and intradermal) approach administration, preferably oral route.It should be understood that optimization approach depends on patient to be treated
Ordinary circumstance and age, the property of disease to be treated and concrete activity ingredient or selected active constituent.
The composition of oral medication includes solid dosage forms, such as capsule, tablet, sugar coated tablet, pill, pastille, powder agent
And granule.
The composition of oral medication further includes liquid dosage form, such as solution, emulsion, suspension, syrup and elixir.
The composition of parenteral includes sterile aqueous and non-aqueous injectable solutions, dispersion liquid, suspension or breast
Liquid and the aseptic powdery for being redissolved in sterile injectable solution or dispersion liquid before use.
The suitable form of administration of others includes suppository, spray, ointment, cream, gelling agent, inhalant, skin paste
Piece, implants etc..
The composition or composition produced by the invention of the present invention can be given by any appropriate approach, in order to make
For this composition, methods known in the art can be used, and usually used any drug in the art can be used to connect
Carrier, diluent, excipient or the other additives received.
For parenteral, can use the aseptic aqueous solutions of one or more active constituents, aqueous propylene glycol solution,
Aqueous vitamin e solution or sesame oil or peanut oil solution.If it is necessary, this aqueous solution should be buffered appropriately, and liquid
Body diluent is made isotonic of enough salt or glucose first.Aqueous solution be particularly suitable for it is intravenous, intramuscular, subcutaneous and
Intraperitoneal administration.Sterile aqueous media used by being easily made by standard technique well known by persons skilled in the art.
It is (preferably sterile by the way that one or more active constituents and possible additive are dissolved in a part of solvent for injection
Water), to required volume, sterile solution is simultaneously filled into appropriate ampoule or bottle adjustment solution, and it is molten can to prepare injection
Liquid.Common any appropriate additive in the art, such as tonicity agents, preservative, antioxidant etc. can be added in.
Appropriate pharmaceutical carrier includes inert solid diluent or filler, aseptic aqueous solution and various organic solvents.
The example of solid carrier has the low alkyl group of lactose, sucrose, cyclodextrin, agar, pectin, Arabic gum, cellulose
Ether, cornstarch, potato starch, talcum powder, magnesium stearate, gelatin etc..
The auxiliary material or additive of any other the purpose of being commonly used in coloring, flavoring, anti-corrosion can be used, as long as them and work
Property ingredient or used ingredient are compatible.
The example of liquid-carrier has syrup, peanut oil, olive oil, phosphatide, aliphatic acid, fatty acid amine, polyoxyethylene and water.
Similar, carrier or diluent can include any slow-release material known in the art, such as mix individually or with wax
Glycerin monostearate or distearin.
By the way that the active constituent of one or more present invention to be mixed to the composition to be formed with pharmaceutically acceptable carrier,
Then it can easily be given with the various dosage forms of suitable open administration route.It can be facilitated by method known in pharmaceutical field
Ground makes preparation exist with unit dosage forms.
The active constituent of the present invention can be formulated as similar or dissimilar pharmaceutical composition and its unit dosage forms.
If oral medication, using solid carrier, preparation can be tablet, the powder or piller that are placed in hard gelatin capsule
Form can be lozenge or lozenge form.
If using liquid carrier, preparation can be syrup, emulsion, Perle or sterile injection liquid, example
Such as aqueous or non-aqueous liquid suspension or solution.Pharmaceutical preparation can be conveniently fabricated unit according to the standardization program of pharmaceutical formulation
Dosage form.The amount of the reactive compound of per unit dose may change according to the property and expected dosage of reactive compound
Become.
The present invention also provides a kind of preparation methods of aforementioned pharmaceutical compositions, insane the method includes second propionyl ureas is resisted
Epilepsy agent or its pharmaceutically acceptable salt and cannabidiol mixing in proportion, obtain the composition.
The present invention also provides a kind of applications of CBD in the drug for preparing prevention and/or treatment epilepsy, the CBD and second
Propionyl ureas antiepileptic or the combination of its pharmaceutically acceptable salt.
The present invention also provides a kind of application of aforementioned pharmaceutical compositions in the drug for preparing prevention and/or treatment epilepsy.
Preferably, the types of epilepsy is partial seizures, including simple partial seizure (limitation breaking-out), complexity
Partial seizures, more preferably limitation break out；
Preferably, second propionyl ureas antiepileptic or cannabidiol institute is used alone to be mitigated or eliminated in the application
The side effect of generation, it is the cognitive ability damage generated when being used alone such as second propionyl ureas antiepileptic, incoordination, thermophilic
Sleep, have a headache, gingival hyperplasia, the side effects such as crinosity.
The present invention also provides a kind of method prevented and/or treat epilepsy, particularly partial seizures, this method packets
Include the cannabidiol for giving bacterium in need and second propionyl ureas antiepileptic particularly phenytoinum naticum or its
Pharmaceutically acceptable salt combines.
The pharmaceutical composition of the present invention can be by being administered simultaneously or order of administration.Terms used herein " being administered simultaneously " refer to
The time interval for giving cannabidiol and second propionyl ureas antiepileptic such as phenytoinum naticum is no more than 15 minutes, such as most 10 points
Clock, such as most 5 minutes such as 2 minutes most.Cannabidiol and second propionyl ureas antiepileptic such as phenytoinum naticum may be used also
To be included in " same unit dosage forms " or " dosage form of separation ".Terms used herein " same unit dosage forms " refer to both comprising big
Numb diphenol also includes the dosage form of second propionyl ureas antiepileptic such as phenytoinum naticum.Terms used herein " dosage form of separation " refer to
Cannabidiol is contained in a kind of dosage form and second propionyl ureas antiepileptic such as phenytoinum naticum are contained in another dosage form.These combinations
Object is administered with treating the effective quantity of epilepsy particularly partial seizures and dosage regimen to patient.
Pharmaceutical composition provided by the invention includes cannabidiol (CBD) and second propionyl ureas antiepileptic or its pharmacy
The pharmaceutical composition of upper acceptable salt, particularly cannabidiol and phenytoinum naticum, the composition are particularly partial for epilepsy
The treatment of epileptic attack can obtain unexpected synergistic therapeutic effect, it is particularly possible to cannabidiol or benzene be mitigated or eliminated
The side effect that appropriate English is used alone improves the compliance of patient.
Specific embodiment
Compound used in the present invention can be commercially available, can also be prepared according to disclosed preparation method, and unlimited
Make the therapeutic domain of the present invention.
Influence experiment of the combination of 1 CBD of embodiment and second propionyl ureas antiepileptic to epilepsy therapy effect
Experiment material
Experimental animal：Healthy male Wistar rat, weight 75-110g.Before experiment, make animal adequacy test environment, mouse
Cage, infusion protocol and operation.By animal be placed in 21 DEG C, 50% humidity and 12 small time, animal can ad lib and drinking-water.
Experimental method
Rat portions epileptic attack model foundation：Using penicillin-induced rat portions epileptic attack model
(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, it will be intubated the ventriculus dexter cerebri for being implanted into animal under anaesthesia by performing the operation.After administration 1 hour, at 1 minute
It is interior that penicillin (1000IU/kg) injection animal is had into telocoele, and record breaking-out behavior in 2 hours.
Grading system for the partial seizures of penicillin induction is as shown in table 1.
Equation below evaluation can be used in human body equivalent dose (HED)：
HED=animals 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 the people of about 1000mg/ days 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 shows |
| 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 being injected penicillin to there is 1 grade of actuation time in table 1, is calculated as the time started (incubation period),
The time for first appearing partial seizures from animal and once occurring seizure disorder or death to the end is recorded, is calculated 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 are as shown in Table 2-4.
The combination medicine-feeding scheme and experimental result of 2 CBD of table and phenytoinum naticum
The combination medicine-feeding scheme and experimental result of 3 CBD of table and Methoin
The combination medicine-feeding scheme and experimental result of 4 CBD of table and primoline
By table 2-4 results it is found that CBD is applied in combination with second propionyl ureas antiepileptic that animal epileptic model is respectively provided with
Therapeutic effect, but CBD and second propionyl ureas antiepileptic portfolio ratio are 0.4-3:When 1, the combination with other proportional regions
It compares, there is better therapeutic effect, can such as increase the incubation period that epileptic attack starts, reduce seizure duration, drop
Low actual improves the percentage that do not break out.
The zoopery that the combination of 2 CBD of embodiment and second propionyl ureas antiepileptic influences drug side-effect
Experimental animal：Healthy male SD rat, 250-300g.Rearing conditions：22 ± 1 DEG C of room temperature, humidity 50 ± 10%, from
Right illumination, drinking-water of freely ingesting.All animals start to test after adapting in feeding environment 5 days, and fasting 12-16 is small before experiment
When, drinking water is free.Experimental animal is randomly divided into 10 groups, every group 6.
Normal group：Normal experimental animal gives equivalent solvent；
CBD and phenytoinum naticum administering drug combinations group 1：The animal epileptic model that digenic acid is lighted, administration 200mg phenytoinum naticums+
60mgCBD/ days；
CBD and phenytoinum naticum administering drug combinations group 2：The animal epileptic model that digenic acid is lighted, administration 200mg phenytoinum naticums+
800mgCBD/ days；
CBD and phenytoinum naticum administering drug combinations group 3：The animal epileptic model that digenic acid is lighted, administration 200mg phenytoinum naticums+
600mgCBD/ days.
CBD and Methoin administering drug combinations group 1：The animal epileptic model that digenic acid is lighted, administration 100mg Methoins+
30mgCBD/ days；
CBD and Methoin administering drug combinations group 2：The animal epileptic model that digenic acid is lighted, administration 100mg Methoins+
400mgCBD/ days；
CBD and Methoin administering drug combinations group 3：The animal epileptic model that digenic acid is lighted, administration 100mg Methoins+
300mgCBD/ days.
CBD and primoline administering drug combinations group 1：The animal epileptic model that digenic acid is lighted, administration 50mg deoxidation benzene ratios
It is+15mgCBD/ days appropriate；
CBD and primoline administering drug combinations group 2：The animal epileptic model that digenic acid is lighted, administration 50mg deoxidation benzene ratios
It is+200mgCBD/ days appropriate；
CBD and primoline administering drug combinations group 3：The animal epileptic model that digenic acid is lighted, administration 50mg deoxidation benzene ratios
It is+150mgCBD/ days appropriate.
Experimental method：Administration carries out 5 days Morris water maze laboratories after 90 days, and when experiment takes each group experimental animal, daily
Animal is put into towards pool wall in pond, records the time (i.e. escape latency) that platform is searched out in 2min, four quadrants are made even
Mean value is as school grade.Rat does not find platform in 2min, is led on platform by experimenter and stops 30s, then put
In the withdrawal of currency from circulation, make marker around observation, to reach cognition purpose.
Morris water maze laboratories are the research Spatial memory models directly related with hippocampus function, can be accurately anti-
The Spatial learning and memory ability of animal is answered, experimental result is as illustrated in tables 5-7.
5 CBD of table and phenytoinum naticum administering drug combinations group after 90 days each group rat Spatial memory ability search time compare
6 CBD of table and Methoin administering drug combinations group after 90 days each group rat Spatial memory ability search time compare
7 CBD of table and primoline administering drug combinations group each group rat Spatial memory ability search time ratio after 90 days
Compared with
The result shows that, CBD and second propionyl ureas antiepileptic administering drug combinations can play the study for improving rat in table 5-7
With the effect of memory capability, i.e. the two combination improves cognitive ability, and work as CBD while improving and inhibiting epilepsy outbreak
It is 3 with second propionyl ureas antiepileptic administering drug combinations dosage:During 1 proportioning, there is best effect.
The clinical trial that the combination of embodiment 3 CBD and PHT influences drug side-effect
Experimental subjects：60 people of partial seizures volunteer, men and women is unlimited, and stochastic averagina is divided into 2 groups, every group of 20 people,
Respectively control group and experimental group.
Experimental group：200mgPHT+600mgCBD/ days；
Control group：PHT dosages 200mg/ days；
Experimental method：Experimental subjects is administered 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, were compareed by 2 months before treatment based on seizure frequency.
Side effect：Chemical examination blood routine, electrolyte simultaneously monitor blood concentration, record what each point of observation was occurred in 2 months
Side effect；The side effect includes incoordination, drowsiness, headache, involuntary movement such as dystonia (phenytoinum naticum common acute
Adverse reaction)；(the common chronic adverse reactions of phenytoinum naticum) such as gingival hyperplasia, crinosity, facial coarse and acnes；(benzene is appropriate for fash etc.
The adverse reaction of English specificity) etc..
Experimental result is as shown in table 8.
8 side effect of table and recurrence rate experimental result
As seen from the results in Table 8, the combination of CBD and PHT can substantially reduce the side effect and recurrence rate of the two simultaneously, improve and treat
Effect can improve the compliance of patient.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
Within god and principle, any modification for being made, equivalent replacement etc. should all be included in the protection scope of the present invention.
Claims (13)
1. a kind of pharmaceutical composition, described pharmaceutical composition includes cannabidiol, second propionyl ureas antiepileptic or its pharmacy
Upper acceptable salt and pharmaceutically acceptable carrier or excipient.
2. pharmaceutical composition as described in claim 1, which is characterized in that cannabidiol and second propionyl in described pharmaceutical composition
The mass ratio of ureas antiepileptic or its pharmaceutically acceptable salt is 0.4-3:1.
3. pharmaceutical composition as claimed in claim 2, which is characterized in that cannabidiol and second propionyl in described pharmaceutical composition
The mass ratio of ureas antiepileptic or its pharmaceutically acceptable salt is 1-3:1.
4. pharmaceutical composition as claimed in claim 3, which is characterized in that cannabidiol and second propionyl in described pharmaceutical composition
The mass ratio of ureas antiepileptic or its pharmaceutically acceptable salt is 3:1.
5. such as claim 1-4 any one of them pharmaceutical compositions, which is characterized in that the second propionyl ureas antiepileptic
Object is selected from：Phenytoinum naticum, Methoin, ethotoin, primoline.
6. such as claim 1-4 any one of them pharmaceutical compositions, which is characterized in that the pharmaceutical composition includes hemp two
Phenol and phenytoinum naticum or its pharmaceutically acceptable salt.
7. pharmaceutical composition as claimed in claim 6, which is characterized in that the pharmaceutically acceptable salt choosing of the phenytoinum naticum
From：Dilantin sodium, calcium diphenylhydantoin, fosphenytoin sodium.
8. such as claim 1-4 any one of them pharmaceutical compositions, which is characterized in that further included in the pharmaceutical composition
Neurotrophy class drug.
9. pharmaceutical composition as described in claim 1, which is characterized in that the pharmaceutical composition is selected from：Capsule, piece
It is agent, sugar coated tablet, pill, pastille, powder agent, granule, solution, emulsion, suspension, syrup, aseptic injectable solution, sterile
Powder, suppository, spray, ointment, cream, gelling agent, inhalant, dermal patch and implants.
10. a kind of claim 1-9 any one of them pharmaceutical composition is in the drug for preparing prevention and/or treatment epilepsy
Using.
11. application as claimed in claim 10, which is characterized in that the type of the epilepsy is partial seizures, including list
Pure partial seizures, complex partial seizures.
12. the application as described in claim 10 or 11, which is characterized in that is exclusive use second is mitigated or eliminated in the application
Side effect caused by propionyl ureas antiepileptic or cannabidiol.
13. application as claimed in claim 12, which is characterized in that the side effect is damaged for cognitive ability.
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| 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 |
| CN103391775A (en) * | 2011-01-04 | 2013-11-13 | Gw药品有限公司 | Use of the phytocannabinoid cannabidiol (cbd) in combination with a standard anti-epileptic drug (saed) in the treatment of epilepsy |
| CN103826621A (en) * | 2011-09-29 | 2014-05-28 | Gw药品有限公司 | A pharmaceutical composition comprising the phytocannabinoids cannabidivarin (CBDV) and cannabidiol (CBD) |
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