CN105963358A - Application of all-cannabinoid in preparation of drug for treating Parkinson's disease - Google Patents
Application of all-cannabinoid in preparation of drug for treating Parkinson's disease Download PDFInfo
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Abstract
The invention discloses application of all-cannabinoid in preparation of a drug for treating a Parkinson's disease (PD). The all-cannabinoid is prepared by uniformly mixing, by weight, 0.3-99.7 parts of an industrial hemp seed extract with 99.7-0.3 parts of industrial cannabinoids. Experiments prove that the prepared all-cannabinoid has the effects of removing free radicals, inhibiting lipid peroxidation and enabling generation and removal of oxygen radicals to be in dynamic balance to slow disease progress of the PD. The all-cannabinoid has a good application prospect on preparation of the drug for treating the Parkinson's disease.
Description
Technical field
The invention belongs to industrial hemp and utilize technical field, concretely relating to one with industrial hemp is
The pharmaceutical composition that primary raw material prepares application in preparation treatment Parkinson's disease medicine.
Background technology
The plantation of Fructus Cannabis is with a long history, ancient times Fructus Cannabis be mainly used in fabrication and processing rope, fishing net, clothing and
Paper making raw material, and oils and fats, food etc..Development and progress along with society, it has been found that contain in Fructus Cannabis
Having a kind of toxic component (tetrahydrocannabinol) that people can be made to cause unreal addiction, American-European many countries are once considerably long
Forbid cultivating in period Fructus Cannabis.Owing to the economic use value of Fructus Cannabis is high, to the eighties in 20th century, some Europe
Low toxicity Hemp Varieties the plantation that puts it over have been cultivated in the research of continent country.Nineteen ninety, the European Community took the lead in promptly
Revision agricultural policy, has abolished the ban of Fructus Cannabis of forbidding cultivating, has started to recover the production of Fructus Cannabis and research.Subsequently
The states such as the U.S., Canada, Australia relieve Fructus Cannabis plantation ban, the whole world Fructus Cannabis cultivated area and
Fiber production has had and has increased rapidly, and the exploitation of industrial hemp are started by American-European countries again, international city
The demand of ecological Fructus Cannabis is also being increased rapidly by field.According to the economic attribution of Fructus Cannabis, for making full use of it it is
The mankind service, and within 1988, the United Nations's clear stipulaties does not possess extraction toxic component (tetrahydrocannabinol THC)
It is worth or sucks directly as drugs, specializing in the raw material Fructus Cannabis of industrial use, industrial hemp (its growth
Tetrahydrocannabinol content in phase Fructus Cannabis floral leaf is less than 0.3%), legal can carry out implantation in large scale and work
Industryization develops.
Industrial hemp be show unique characteristics, living resources that comparative advantages are prominent.Industrial hemp and conventional toxic
Fructus Cannabis has essential distinction, and industrial hemp is the raw material of industry product of a class Non-toxic, has high warp
Ji value.Successively 25 industrial hemp kinds are selected altogether to countries in the world at the end of 2003, and
And seven states such as the method for European Union, moral, English the most all become industrial hemp and mainly plant manufacturing country, with industrial hemp
Fiber and fiber crops seed and flower thereof, leaf, root, stem are that raw material carries out series of products research and development and industrialization comprehensive exploitation,
Industrial hemp primary process major product jute skin fiber, stalk core fibre, hemp seed oil fat and seed cake protein,
On the basis of medicinal standard extract realizes industrialization production, carry out deep processing and utilization further, derive from
Product out has reached more than 25,000 kinds, contain the clothing of the mankind, food, shelter, row, with each greatly
Series products.The research of industrial hemp industry, develop and production is concentrated mainly on Europe, Canada, the U.S.
Etc. technology developed country.The development of industrial hemp industry, is first nontoxic from selection-breeding or the low industry poisoned
Fructus Cannabis new varieties start, and achieve the plantation of scale and combining of hi-tech industrialization based on this
Close and develop, define one " emerging pollution-free industry group " and the quick growth point of infant industry economy.
Fructus Cannabis is Fructus Cannabis dry mature fruit, is generally used as medicine by Fructus Cannabis ancient times, and dietetic therapy is the most on the books.
Fructus Cannabis is included in " being medicine and food " " medicine-food two-purpose " list by health ministry.
The property of medicine of Fructus Cannabis and pharmacology be: sweet, flat.Return spleen, stomach, large intestine channel.Function cures mainly: moisturize, sliding
Intestinal, treating stranguria, invigorate blood circulation.Control dryness of the intestine constipation, quench one's thirst, pyretic stranguria, migratory arthralgia, dysentery.Menoxenia, scabies,
Tinea leprosy.Those benefits in detail is had to record in medical book, such as " herbal classic ": " invigorating the spleen and replenishing QI.”；Tang Materia Medica: " main
Five kinds of over strain.”；" Handbook of Prescriptions for Emergencies ": " control extreme thirst, day eclipse number bucket, hot urination person: pockmarks one liter, three liters of water,
Boiling three, four boilings, extracting juice drinks it.”；" Japan hanako materia medica ": " qi-restoratives labor, long muscle, stimulating milk secretion, only disappear
Yearningly, expedite the emergence of.Control perverse and unreasonable manner to produce.”；Supplement to the Herbal: " therapeutic method to keep the adverse QI flowing downwards, diuresis, go migratory arthralgia skin stupid, fries order
Perfume (or spice) is smashed to pieces, urine leaching juice clothes；Married woman's footling presentation gulps down two or seven pieces.”；" Treatise on Dietetic Therapy ": " extracting juice is cooked congee,
Go the five internal organs wind, lung moistening.Control that joint is obstructed, deal with, promoting blood circulation.”.
The equal hyoscine of floral leaf of Fructus Cannabis.The property of medicine of Folium Cannabis and pharmacology be: pungent；Poisonous.Return lung；Bladder；
Large intestine channel.Function cures mainly: pain relieving, and Dingchuan drives ascarid.Cure mainly asthma, fall and flutter pain, ascariasis.Fiber crops
The property of medicine and the pharmacology of flower be: bitter；Pungent；Warm in nature；Poisonous.Function cures mainly: dispel the wind；Invigorate blood circulation；Hair growth promoting.
Main air disease numb limbs and tense tendons；Pruritus all over；Women's amenorrhea.
Along with the increase year by year of average human life, the world is just stepping into the whole world aging epoch.Have with the age
The neurodegenerative disease closed is consequently increased, in terms of central nervous system, mainly show as excited with
Process of inhibition weakens, and brain function reduces, hypomnesis and forfeiture, occurs subsequently identifying entering of function
Row goes down and the increasing the weight of of emotionally disturbed.Parkinson disease (PD) are a kind of neural with nigral dopamine energy
Unit's (NDN) characteristic disappearance is the nervous system degeneration disease of main pathological change, clinically with static
Property is trembled, splinting, bradykinesia and posture insufficiency of accommodation are principal character, and its sickness rate can be with the age
Increase and improve.More than 50 years old is 500 people/100,000, within more than 60 years old, then reaches annual 1000 people/10
Ten thousand, the height of prevalence, make the nervous system common disease being only second to cerebrovascular.Parkinson disease pair
Patient, family and society all bring huge pressure so that the whole world gives numerous concerns, handkerchief to it
The medicine research of the gloomy disease of gold becomes an important topic in geriatrics field.
Cannabidiol (CBD) is that a kind of nontoxic of extraction from Fructus Cannabis floral leaf can be used for medicine, cosmetic
Product, the aldehydes matter of a kind of high added value of health food.At present, Israel, the U.S., Britain etc. are sent out
Reach country done raw material with it and developed multiple special effect medicine and cosmetics.CBD is the non-one-tenth in Fructus Cannabis
Addiction composition, can hinder THC to affect nerve system of human body, and have spasmolytic, antirheumatic joint
The pharmacologically actives such as inflammation, anxiety, also have the report in terms for the treatment of Parkinson's disease, but are used alone Fructus Cannabis
The therapeutic effect of diphenol (CBD) is unsatisfactory.Therefore new activity is developed high, little the controlling of toxic and side effects
Treat medicine and seem the most necessary.
Summary of the invention
It is an object of the invention to provide a kind of pharmaceutical composition prepared with industrial hemp for primary raw material
The application in pharmacy of the general anesthesia element.
It practice, the present invention relates to the application in the medicine of preparation treatment Parkinson's disease of the general anesthesia element；Described
General anesthesia element by 0.3 part～the industrial hemp Fructus Cannabis extract of 99.7 weight portions and 99.7 parts～0.3
The industrial hemp Urtica cannabina L. element mixing of weight portion is made.
The raw material composition of described general anesthesia element is preferably industrial hemp Fructus Cannabis extract 40 parts and industry is big
Fiber crops Urtica cannabina L. element 60 parts.
Wherein, described industrial hemp Fructus Cannabis extract is prepared by the following method and forms:
(1) ripe industrial hemp Fructus Cannabis is taken, drying, remove impurity, standby after pulverizing；
(2) under the conditions of 20～85 DEG C, extract pulverizing Fructus Cannabis material with ethanol, concentration of alcohol
Being 95%～100% (V/V), solid-liquid ratio is 1:5～1:20；
(3) leach lixiviating solution, after concentrating under reduced pressure, be industrial hemp Fructus Cannabis extract.
When industrial hemp Fructus Cannabis being extracted with ethanol, following various ways can be used to carry out: as
Extract under room temperature, every batch materials extraction 2 times, each 7～10 days；Under the conditions of 60～85 DEG C, heating
Extract 2 times, each 1～3 hour；Ultrasonic assistant extracts, ultrasonic frequency 30～60kHz, merit
Rate 100～1000W, extraction time 30～60min, extraction temperature 25～50 DEG C；Also microwave can be used
Other prior art such as assisted extraction.
Described industrial hemp Urtica cannabina L. element is prepared by the following method and forms:
(1) flower of industrial hemp, leaf, fiber crops bran or the mixture of three, drying, remove impurity, powder are taken
It is broken to 10～60 mesh；
(2) supercritical carbon dioxide extraction: the above-mentioned industrial hemp raw material crushed is put into supercritical
In carbon dioxide extraction apparatus, control extraction temperature 40～50 DEG C, extraction time 30～90min, extraction
Pressure 25～35Mpa, carbon dioxide flow 40kg/h, extract is collected in separating still outlet；
(3) the extract ethanol elution of 95%～100% (V/V) of 0.2～10 times of volume, eluting
Number of times is 1～3 time；
(4) eluent is collected, concentrating under reduced pressure, vacuum drying, i.e. obtain industrial hemp Urtica cannabina L. element after pulverizing.
The flower of described industrial hemp, leaf, the optimum ratio of fiber crops bran three's mixture are 1:3:2.
Common Folium Cannabis, Flos Cannabis be respectively provided with toxicity (containing tetrahydrocannabinol THC marijuana hemp to the most unreal
Material).For getting rid of the toxicity of crude drug, present invention preferably employs the industrial hemp kind of Yunnan growth
Flower, leaf, fiber crops bran and the Fructus Cannabis of " cloud fiber crops No. 1 " are as raw material.By China's relevant legal documents rule
Fixed, " cloud fiber crops No. 1 " can only be planted within the border in Yunnan, and its flower, leaf, numb bran can only be in border, Yunnan
Interior processing.
The pharmaceutical composition general anesthesia element of the present invention can make different pharmaceutical preparation, further including being administered orally
Agent and injection, wherein oral agents includes capsule, oral liquid, tablet, drop pill, granule etc., injection
Including injection dosage form and freeze-dried powder injection type etc..The available auxiliary type when preparing oral formulations
Agent can be the conventional filler such as starch, dextrin or cyclodextrin, sucrose, stearate.Lyophilized injectable powder
Can be prepared by methods such as aseptic spray drying, low-temperature vacuum drying, lyophilizations.After each preparation
Phase preparation technology and equipment all belong to the routine techniques of pharmaceutical field, and this is not construed as limiting by the present invention, therefore at this
Not describe in detail.
The pharmaceutical composition general anesthesia element of the present invention has the effect of clear and definite treatment Parkinson's disease.Experiment
Finding, general anesthesia element can significantly reduce the number of revolutions of PD rat model prepared by 6-OHDA, and with administration
The prolongation of time, has the trend that certain effect strengthens；The mice PD model of MPTP induction can be obviously improved
The rotarod activity ability of mice, and increase the motion of mice.General anesthesia element can obviously reduce the oxygen of murine brain
Change stress level, make PD model mouse cerebral tissue MDA content significantly reduce, hence it is evident that improve the vigor of SOD,
Show obvious antioxidant activity.The mechanism of action of result prompting general anesthesia element is removed free radical exactly, is pressed down
Lipid peroxidation processed, makes oxygen-derived free radicals produce and removing is in dynamic equilibrium, thus delay the disease of PD
Feelings are in progress.Therefore general anesthesia element of the present invention has clear and definite treatment parkinson effect, effect is better than Fructus Cannabis
Diphenol.
Detailed description of the invention
Below by embodiment, the present invention is described in further detail, but embodiment is not to this
The restriction of bright technical scheme.
Embodiment 1
Use flower, leaf, fiber crops bran and the Urtica cannabina L. of the industrial hemp kind " cloud fiber crops No. 1 " of Yunnan growth
Core is as raw material.Take maturation industrial hemp Fructus Cannabis, drying, remove impurity, standby after pulverizing；Use second
Alcohol to pulverize Fructus Cannabis material extract (under the conditions of 60～85 DEG C, heating extraction 2 times, each 1～
3 hours), concentration of alcohol is 95%～100% (V/V), and solid-liquid ratio is 1:5～1:20；Leach lixiviating solution,
Industrial hemp Fructus Cannabis extract it is after concentrating under reduced pressure.
Take the flower of industrial hemp, leaf, fiber crops bran 1:3:2 mass ratio mixture, drying, remove impurity,
It is crushed to 10～60 mesh；Supercritical carbon dioxide extraction: the above-mentioned industrial hemp raw material crushed is thrown
Enter in supercritical carbon dioxide extraction apparatus, control extraction temperature 40～50 DEG C, extraction time 30～
90min, extracting pressure 25～35Mpa, carbon dioxide flow 40kg/h, extraction is collected in separating still outlet
Thing；The extract ethanol elution of 95%～100% (V/V) of 0.2～10 times of volume, washing steps
It it is 1～3 time；Collect eluent, concentrating under reduced pressure, vacuum drying, after pulverizing, obtain industrial hemp Urtica cannabina L.
Element.
Take industrial hemp Fructus Cannabis extract 40 parts, industrial hemp Urtica cannabina L. element 60 parts, mixing, obtain required
General anesthesia element B.
Embodiment 2
Repeat embodiment 1, have following difference: when industrial hemp Fructus Cannabis being extracted with ethanol,
Extract under room temperature, every batch materials extraction 2 times, each 7～10 days.Take the flower of industrial hemp, leaf, fiber crops
The mixture of bran 1:1:1 mass ratio is as the extraction raw material of industrial hemp Urtica cannabina L. element.
Take industrial hemp Fructus Cannabis extract 0.3 part, industrial hemp Urtica cannabina L. element 99.7 parts, mixing, obtain
Required general anesthesia element A.
Embodiment 3
Repeat embodiment 1, have following difference: when industrial hemp Fructus Cannabis being extracted with ethanol,
Employing ultrasonic assistant extracts, and ultrasonic frequency 30～60kHz, power 100～1000W, during extraction
Between 30～60min, extraction temperature 25～50 DEG C.Take the flower of industrial hemp, leaf, fiber crops bran 3:2:1 matter
The mixture of amount ratio is as the extraction raw material of industrial hemp Urtica cannabina L. element.
Take industrial hemp Fructus Cannabis extract 99.7 parts, industrial hemp Urtica cannabina L. element 0.3 part, mixing, obtain
Required general anesthesia element C.
Embodiment 4
Example 1 gained medicine 100 grams (crosses 80 mesh sieves), adds 60 grams of microcrystalline Cellulose, crosses 80
Mesh sieve three times, mix homogeneously, spray into 95% ethanol solution, soft material processed, cross 40 mesh sieves and pelletize, 60 DEG C
It is dried half an hour, is sub-packed in 3# capsule, aluminium plastic composite packaging, prepare general anesthesia cellulose capsule agent.
Embodiment 5
Example 2 gained medicine, admixture doses 5～the dried starch of 20% and 1～the stearic acid of 5%
Magnesium etc., blended, pelletize, be dried, tabletting, prepare general anesthesia element tablet.
Embodiment 6
The adjuvants such as Example 3 gained medicine, adds sucrose water and the preservative of convention amount, stabilizer.
Filtration, sterilizing, be distributed in 10mL bottle, make general anesthesia element oral liquid.
Embodiment 7
Example 1 gained medicine, adds water for injection and dissolves, add 2.0 ‰ activated carbons, stir,
Filter, continue, with 0.45 μm, 0.22 μm microporous filter membrane classified filtering, to supplement water for injection, subpackage
In cillin bottle, lyophilization, recharge high-purity nitrogen, jump a queue, gland, packaging, prepare general anesthesia element
Injection.
The protection to PD rat model prepared by 6-hydroxyl DOPA (6-OHDA) of the Application Example 1 general anesthesia element
Effect.
1,6-OHDA damage rat substantia nigra makes parkinson disease (PD) model
Choose body weight 200-250g SD male rat, the chloral hydrate 3.5ml/kg lumbar injection of 10%
After anesthesia, rat being fixed on stereotactic apparatus, rack is less than biauricular line level, makes before and after's fontanel be positioned at same
In one level, cut off the Mus hair of calvarium, after iodine tincture wiping, medisection skin, fontanel before and after exposure is pure
Hydrogen peroxide wiping skull surface, makes before and after's fontanel fully show, bores at skull surface injection point by dental burr
The aperture of 1 about 2mm.Adjust the position of microsyringe needle point, with reference to " the rat brain of bag new people etc.
Stereotaxic atlas ", at bregma 4.4mm, sagittal suture (right) 1.3mm, 8.5mm point injection under skull
The 8 μ g/4 μ l 6-OHDA saline solution containing 0.2% ascorbic acid.Injection speed is 0.5 μ L/min, art
With the speed withdraw of the needle of 1mm/min after Bi Liuzhen 10min, sulfa powder closes cranium hole, sews up scalp, iodine tincture
Wiping suture, puts cage and feeds.After radiofrequency ablation 7 days, lumbar injection apomorphine 0.5mg/kg induced
Stable the rotating to damage offside of rat, observes its behavior, records 30min after being administered 10min
Rotational case, number of revolutions per minute more than at least 7 times, be considered to reach PD model needs.
2, Antioxidant Indexes detection SOD activity and MDA assay
Mus broken end opens cranium, takes cerebral tissue specimen, blots the residual blood in surface with filter paper, remove rhinencephalon, brain stem,
Cerebellum.Cerebral tissue specimen is respectively placed in glass homogenizer, is 1 with ice normal saline by quality and volume ratio:
It is prepared as the brain tissue homogenate of 10% under the ratio ice bath of 9, is immediately placed in-30 DEG C of refrigerators preservation, treats
Survey.Cerebral tissue protein quantification is measured with Coomassie Brilliant Blue before test.By test kit description requirement, from
Melt again in tissues following MCAO in rats homogenate and take sample and use 722 type grating spectrophotometers to measure respectively in cerebral tissue
SOD activity, MDA content.
3, the general anesthesia element therapeutical effect to PD model
(1) before rat brain indoor micro-injection 6-OHDA, general anesthesia element A, B, C (20mg/kg), greatly
Fiber crops diphenol (20mg/kg), gavage administration respectively.Respectively at the 7d being administered, 14d, 21d, 28d are respectively
Lumbar injection 0.5mg/kg apomorphine, observes the rat rotary motion to damage offside, and result shows
General anesthesia element can significantly reduce the number of revolutions of PD rat model, and with the prolongation of administration time, has certain
The trend that effect strengthens, and each time point effect is superior to cannabidiol (table 1).
Table 1 general anesthesia element prepared by 6 OHDA PD rat model protective effect (N=10)
Note: compare with model group,*P ＜ 0.05.
(2) after general anesthesia element is administered 14d, put to death 5 groups of rats, take cortex, measure SOD vigor
With MDA content, table 2 show general anesthesia element can substantially reduce 6-OHDA damage rat cerebral tissue oxidation should
Swashing level, general anesthesia element makes PD rat model cerebral tissue MDA content significantly reduce, hence it is evident that improve SOD's
Vigor, is better than cannabidiol, shows antioxidant activity.
The plain impact on 6 OHDA damage rat cerebral tissue's MDA levels and SOD vigor of table 2 general anesthesia (N=10)
| Group | Number of cases | MDA(mol/L) | SOD(mmol/L) |
| Model group | 10 | 11.03±3.39 | 90.12±10.37 |
| Cannabidiol group | 10 | 7.95±2.03* | 134.56±19.86* |
| General anesthesia element A group | 10 | 5.68±1.35*** | 160.18±14.88** |
| General anesthesia element B group | 10 | 4.95±1.12*** | 176.43±18.17*** |
| General anesthesia element C group | 10 | 6.73±1.68** | 150.79±16.56** |
Note: compare with model group,*P ＜ 0.05,**P ＜ 0.01,***P ＜ 0.001.
The protective effect to the PD mouse model of MPTP induction of the Application Example 2 general anesthesia element
1, subcutaneous injection MPTP induces C57/BL mice PD model
Choose body weight 25-27g male C57/BL mice in 8w age and be randomly divided into 5 groups, respectively model group,
General anesthesia element A group (20mg/kg), general anesthesia element B group (20mg/kg), general anesthesia element C group (20mg/kg)
With cannabidiol group (20mg/kg).Matched group and model group give gavage normal saline, administration group in advance
Give the medicine of above-mentioned dosage, 8d model group and each administration group subcutaneous injection MPTP 40mg/kg, give
Medicine capacity 0.1ml/10g, once a day, continuous 7 days, 15d observe mice behavioral indexes and
Carry out biochemical indicator detection.
2, behavioristics's detection
(1) ambulatory activity count is with reference to Kawai H method of testing, self-control 30cm × 30cm × 15cm's
Lucite box, bottom carves the grid of 6cm × 6cm, detects in the environment of quiet, dark.
After mice adapts to environment 10min, the grid number that in counting 5min, mice is moved, survey continuously and make even for 5 times
Average.
(2) Rotarod detection Rotarod experiment needs animal keep balance on roller bearing and transport continuously
Dynamic, it is the experiment of widely used detection sports coordination.C57/BL mice last is administered handle after 1 hour
Mice is placed on the transfer rod instrument of rotation (roller bearing diameter 6cm, rotating speed is 13r/min), is allowed to constantly adjust
Whole extremity, to keep one's balance, are i.e. automatically recorded in the time of bull stick (if dropping down from bull stick
Long detection time 180s, those of exceeding is still designated as 180s).
3, Antioxidant Indexes detection SOD activity and MDA assay
Mus broken end opens cranium, takes cerebral tissue specimen, blots the residual blood in surface with filter paper, remove rhinencephalon, brain stem,
Cerebellum.Cerebral tissue specimen is respectively placed in glass homogenizer, is 1 with ice normal saline by quality and volume ratio:
It is prepared as the brain tissue homogenate of 10% under the ratio ice bath of 9, is immediately placed in-30 DEG C of refrigerators preservation, treats
Survey.Cerebral tissue protein quantification is measured with Coomassie Brilliant Blue before test.By test kit description requirement, from
Melt again in tissues following MCAO in rats homogenate and take sample and use 722 type grating spectrophotometers to measure respectively in cerebral tissue
SOD activity, MDA content.
4, the general anesthesia element protective effect to the PD mouse model of MPTP induction
(1) MPTP makes the bull stick time of mice substantially shorten and the shortening of spontaneous activity time, and general anesthesia is plain
A, B, C (20mg/kg) all can extend the bull stick time of mice after being administered 14d, and increase mice
Assay of spontaneous activity, the display general anesthesia element bull stick that can be obviously improved PD model mice the same with cannabidiol
Mobility, and increase the motion of mice, and effect is better than cannabidiol (table 3,4).
The impact on the PD mice rotarod activity ability of MPTP induction of the table 3 general anesthesia element
| Group | Number of cases | The bull stick time (divides) |
| Model group | 10 | 12.91±3.34 |
| Cannabidiol (20mg/kg) | 10 | 20.74±4.28** |
| General anesthesia element A group (20mg/kg) | 10 | 24.37±3.21** |
| General anesthesia element B group (20mg/kg) | 10 | 25.62±4.25** |
| General anesthesia element C group (20mg/kg) | 10 | 23.48±3.29** |
Note: compare with model group,*P ＜ 0.05,**P ＜ 0.01.
The impact on the PD spontaneous activity in mice of MPTP induction of the table 4 general anesthesia element
Note: compare with model group,**P ＜ 0.01.
(2) after general anesthesia element is administered 14d, put to death 5 groups of mices, take cortex, measure SOD vigor
With MDA content, table 5 shows that general anesthesia element can substantially reduce the oxidative stress of MPTP inducing mouse cerebral tissue
Level, general anesthesia element makes PD model mice cerebral tissue MDA content significantly reduce, hence it is evident that improve the work of SOD
Power, is better than cannabidiol, shows obvious antioxidant activity.
The plain PD model mice cerebral tissue MDA level on MPTP induction of table 5 general anesthesia and the impact of SOD vigor
| Group | Number of cases | MDA(mol/L) | SOD(mmol/L) |
| Model group | 10 | 8.11±1.63 | 70.76±12.85 |
| Cannabidiol group (20mg/kg) | 10 | 5.05±1.96* | 114.87±15.37** |
| General anesthesia element A group (20mg/kg) | 10 | 3.07±0.83** | 143.64±10.04** |
| General anesthesia element B group (20mg/kg) | 10 | 2.57±0.79*** | 154.18±19.69*** |
| General anesthesia element C group (20mg/kg) | 10 | 3.83±1.28** | 134.02±11.54** |
Note: compare with model group,*P ＜ 0.05,**P ＜ 0.01,***P ＜ 0.01.
Claims (6)
1. general anesthesia element application in the medicine of preparation treatment Parkinson's disease；Described general anesthesia element is by 0.3
Part～the industry of the industrial hemp Fructus Cannabis extract of 99.7 weight portions and 99.7 parts～0.3 weight portion big
Fiber crops Urtica cannabina L. element mixing is made.
Application the most according to claim 1, it is characterised in that: the raw material group of described general anesthesia element
Become to be preferably industrial hemp Fructus Cannabis extract 40 parts and industrial hemp Urtica cannabina L. element 60 parts.
Application the most according to claim 1, it is characterised in that: described industrial hemp Fructus Cannabis
Extract is prepared by the following method and forms:
(1) ripe industrial hemp Fructus Cannabis is taken, drying, remove impurity, standby after pulverizing；
(2) under the conditions of 20～85 DEG C, extract pulverizing Fructus Cannabis material with ethanol, concentration of alcohol
Being 95%～100% (V/V), solid-liquid ratio is 1:5～1:20；
(3) leach lixiviating solution, after concentrating under reduced pressure, be industrial hemp Fructus Cannabis extract.
Application the most according to claim 1, it is characterised in that: described industrial hemp Urtica cannabina L. element
It is prepared by the following method and forms:
(1) flower of industrial hemp, leaf, fiber crops bran or the mixture of three, drying, remove impurity, powder are taken
It is broken to 10～60 mesh；
(2) supercritical carbon dioxide extraction: the above-mentioned industrial hemp raw material crushed is put into supercritical
In carbon dioxide extraction apparatus, control extraction temperature 40～50 DEG C, extraction time 30～90min, extraction
Pressure 25～35Mpa, carbon dioxide flow 40kg/h, extract is collected in separating still outlet；
(3) the extract ethanol elution of 95%～100% (V/V) of 0.2～10 times of volume, eluting
Number of times is 1～3 time；
(4) eluent is collected, concentrating under reduced pressure, vacuum drying, i.e. obtain industrial hemp Urtica cannabina L. element after pulverizing.
Application the most according to claim 4, it is characterised in that: the flower of described industrial hemp,
Leaf, the optimum ratio of fiber crops bran three's mixture are 1:3:2.
Application the most according to claim 1, it is characterised in that: the kind of described industrial hemp
It is preferably " cloud fiber crops No. 1 ".
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| CN201610415429.6A CN105963358A (en) | 2016-06-14 | 2016-06-14 | Application of all-cannabinoid in preparation of drug for treating Parkinson's disease |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022058581A1 (en) * | 2020-09-19 | 2022-03-24 | Dmas B.V. | Method for treating hemp and product obtained |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105505565A (en) * | 2015-12-28 | 2016-04-20 | 贵州航天乌江机电设备有限责任公司 | Method for extracting industrial hemp oil rich in cannabidiol |
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2016
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105505565A (en) * | 2015-12-28 | 2016-04-20 | 贵州航天乌江机电设备有限责任公司 | Method for extracting industrial hemp oil rich in cannabidiol |
Non-Patent Citations (1)
| Title |
|---|
| 赵翾等: "响应面法优化火麻仁黄酮提取工艺", 《食品科学》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022058581A1 (en) * | 2020-09-19 | 2022-03-24 | Dmas B.V. | Method for treating hemp and product obtained |
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