CN105963359A - Application of all-cannabinoid in preparation of drugs for treating depression - Google Patents

Application of all-cannabinoid in preparation of drugs for treating depression Download PDF

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CN105963359A
CN105963359A CN201610421906.XA CN201610421906A CN105963359A CN 105963359 A CN105963359 A CN 105963359A CN 201610421906 A CN201610421906 A CN 201610421906A CN 105963359 A CN105963359 A CN 105963359A
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depression
industrial hemp
fructus cannabis
general anesthesia
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陈天睿
胡瀞月
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Yunnan Rui Biotechnology Co Ltd
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Yunnan Rui Biotechnology Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/60Moraceae (Mulberry family), e.g. breadfruit or fig
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/37Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction

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Abstract

The invention discloses application of all-cannabinoid in preparation of drugs for treating depression. 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. The all-cannabinoid has the obvious relieving effect on the symptoms such as secondary learning memory deterioration of the depression and can be used for preparing the drugs for treating various depression symptoms including endogenous depression, reactive depression, latent depression, secondary depression caused by drugs, climacteric or postnatal depression, depression induced by cerebral trauma or stroke, diabetes-complicated depression and depressive neurosis and used for preparing the drugs for treating the symptoms such as secondary learning memory deterioration and anhedonia which are caused by the depression, and the effect of the all-cannabinoid is better than that of cannabidiol. The all-cannabinoid can be prepared into the clinical drugs of various dosage forms through a conventional preparation method and is convenient to use.

Description

The application in the medicine of preparation treatment depression of the general anesthesia element
Technical field
The invention belongs to industrial hemp and utilize technical field, concretely relate to a kind of with industrial hemp as primary raw material The pharmaceutical composition prepared application in the medicine of preparation treatment depression.
Background technology
The plantation of Fructus Cannabis is with a long history, and ancient times, Fructus Cannabis was 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 containing a kind of toxic component (tetrahydrochysene Fructus Cannabis in Fructus Cannabis Phenol) people can be made to cause unreal addiction, American-European many countries once forbade cultivating Fructus Cannabis within considerably long period.Economic use value due to Fructus Cannabis Height, to the eighties in 20th century, low toxicity Hemp Varieties the plantation that puts it over have been cultivated in the research of some European countries.Nineteen ninety Europe Coenosarc takes the lead in Emergency fixes agricultural policy, has abolished the ban of Fructus Cannabis of forbidding cultivating, has started to recover the production of Fructus Cannabis and research.Beautiful subsequently The states such as state, Canada, Australia relieve the ban of Fructus Cannabis plantation, and whole world Fructus Cannabis cultivated area and fiber production have had rapidly Increasing, the exploitation of industrial hemp are started by American-European countries again, and the demand of ecological Fructus Cannabis is also being increased rapidly by international market Long.According to the economic attribution of Fructus Cannabis, servicing for the mankind for making full use of it, within 1988, the United Nations's clear stipulaties does not possess extraction poison Property composition (tetrahydrocannabinol THC) be worth or suck directly as drugs, specialize in the raw material Fructus Cannabis of industrial use, industrial hemp (the tetrahydrocannabinol content in its trophophase Fructus Cannabis floral leaf is less than 0.3%), legal can carry out implantation in large scale and industrialization Develop.
Industrial hemp be show unique characteristics, living resources that comparative advantages are prominent.Industrial hemp has with conventional toxic Fructus Cannabis Essential distinction, industrial hemp is the raw material of industry product of a class Non-toxic, has high economic use value.At the end of 2003 Countries in the world successively select altogether 25 industrial hemp kinds, and seven states such as the method for European Union, moral, English the most all become industry greatly Fiber crops mainly plant manufacturing country, with industrial hemp fibers and fiber crops seed and flower, leaf, root, stem for raw material carry out series of products research and development with Industrialization comprehensive exploitation, processes major product jute skin fiber, stalk core fibre, hemp seed oil fat and seed dregs of rice egg in industrial hemp primary In vain, medicinal standard extract realize industrialization produce on the basis of, carry out deep processing and utilization, the product derived from further Reached more than 25,000 kinds, contain the clothing of the mankind, food, shelter, row, with each big series products.The research of industrial hemp industry, Exploitation and production are concentrated mainly on the technology developed countries such as Europe, Canada, the U.S..The development of industrial hemp industry, be first Or the low industrial hemp new varieties that poison nontoxic from selection-breeding start, and achieve the plantation of scale and high skill based on this The comprehensive development and utilization of art industrialization, defines 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.Health ministry Fructus Cannabis is included in " being medicine and food " " medicine-food two-purpose " list.The property of medicine of Fructus Cannabis and pharmacology be: sweet, Flat.Return spleen, stomach, large intestine channel.Function cures mainly: moisturize, and laxation is treating stranguria, invigorates blood circulation.Control dryness of the intestine constipation, quench one's thirst, pyretic stranguria, migratory arthralgia, dysentery Disease.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, boil three, four boilings, extracting juice Drink it.”;" Japan hanako materia medica ": " qi-restoratives labor, long muscle, stimulating milk secretion, only quench one's thirst, expedite the emergence of.Control perverse and unreasonable manner to produce.”;Supplement to the Herbal: under " Gas, diuresis, go migratory arthralgia skin stupid, fry and make perfume (or spice) smash 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, and goes 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 master Control: pain relieving, Dingchuan, drive ascarid.Cure mainly asthma, fall and flutter pain, ascariasis.The property of medicine of Flos Cannabis and pharmacology be: bitter;Pungent;Warm in nature;Have Poison.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.
Depression is to endanger the modal mental sickness of human physical and mental health now, and its sickness rate accounts for the 5% of world population Left and right.Severely impact the healthy of the mankind and quality of life.Expecting the year two thousand twenty, depression will be harm human health contracting Short-life second largest disease.
At present, the mechanism of action of antidepressant drug illustrates the most completely.There is the medicine basic role of clear and definite curative effect in nerve Tip synapses, plays therapeutical effect by the level of regulation synaptic space neurotransmitter.Its etiologic etiological Biochemical Research Show that depression is main and maincenter 5-hydroxy tryptamine (5-HT), norepinephrine (NA), dopamine (DA), acetylcholine (Ach) Relevant with 5 kinds of neurotransmitteies such as γ-aminobutyric acid (GABA).
Antidepressants can be divided into non-selective antidepressants in early days and the big class of new selective reuptake inhibitor two. Non-selective antidepressants mainly include oxidase inhibitor (MAOIs) and tricyclic antidepressant (TCAs);Selectivity Reuptake inhibitor mainly has (1) selectivity 5-hydroxy tryptamine (5-HT) reuptake inhibitor (SSRIs), such as fluoxetine (Fluoxetine), paroxetine (Paroxetine).(2) norepinephrine (NA) reuptake inhibitor (NRIs), as auspicious Bo Xiting (Reboxitine).(3) norepinephrine energy and specificity 5-HT reuptake inhibitor (NDRIs), such as mirtazapine (Mirtazapine).(4) 5-HT and NA dual reuptake inhibitor (SNRIs), such as venlafaxine (Venlafaxine) and degree Duloxetine (Duloxetine).(5) 5-HT re-absorption accelerator, such as tianeptine (Tianeptine) etc..
Although existing many antidepressants are for clinic, but some drugs is low because of its response rate, and has potential secondary work With, still there is suitable patient invalid through various Drug therapys, some demands help electro-convulsive therapy.Therefore, the opening of antidepressants Send out and be still the focus of new drug research, in China, for the research and development of antidepressant original new drug also in the starting stage, especially It is the research of the novel antidepressant of triple approach for acting on 5-HT, NA and DA system, more becomes of concern heavy Want problem.
Cannabidiol (CBD) is that a kind of nontoxic of extraction from Fructus Cannabis floral leaf can be used for medicine, cosmetics, health food The aldehydes matter of a kind of high added value.At present, the developed country such as Israel, the U.S., Britain has done raw material with it and has developed Multiple special effect medicine and cosmetics.CBD is the non-additive composition in Fructus Cannabis, and THC can be hindered to affect nerve system of human body, and There is the pharmacologically actives such as spasmolytic, resisting rheumatoid arthritis, anxiety, also have the report in terms for the treatment of mental sickness, but single The therapeutic effect solely using cannabidiol (CBD) is unsatisfactory.Therefore new activity is developed high, the medicine that toxic and side effects is little Seem the most necessary.
Summary of the invention
It is an object of the invention to provide a kind of pharmaceutical composition general anesthesia element prepared with industrial hemp for primary raw material Application in pharmacy.
It practice, the present invention relates to the application in the medicine of preparation treatment depression of the general anesthesia element;Described general anesthesia element by The industrial hemp Urtica cannabina L. element of 0.3 part~the industrial hemp Fructus Cannabis extract of 99.7 weight portions and 99.7 parts~0.3 weight portion mixes Even make.
The invention still further relates to general anesthesia element at preparation treatment endogenous depression, reactive depression, masked depression, medicine Secondary depression, climacteric or postpartum depression, cerebral trauma or the depression of apoplexy induction, diabetes that thing causes merge Application in the medicine of depression and depressive neurosis.
The invention still further relates to general anesthesia element and decline or/and pleasant sensation at the preparation treatment insecondary learning and memory that causes of depression Application in the medicine of deficiency disease.
The raw material composition of described general anesthesia element is preferably industrial hemp Fructus Cannabis extract 40 parts and industrial hemp 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, with ethanol to pulverize Fructus Cannabis material extract, concentration of alcohol be 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 soaked under room temperature Carry, every batch materials extraction 2 times, each 7~10 days;Under the conditions of 60~85 DEG C, heating extraction 2 times, each 1~3 hour;Ultrasonic Ripple assisted extraction, ultrasonic frequency 30~60kHz, power 100~1000W, extraction time 30~60min, extraction temperature 25~ 50℃;Also other prior aries such as microwave radiation exaraction can be used.
Described industrial hemp Urtica cannabina L. element is prepared by the following method and forms:
(1) take the flower of industrial hemp, leaf, fiber crops bran or the mixture of three, drying, remove impurity, be crushed to 10~60 mesh;
(2) supercritical carbon dioxide extraction: the above-mentioned industrial hemp raw material crushed is put into supercritical carbon dioxide extraction During fetching is put, control extraction temperature 40~50 DEG C, extraction time 30~90min, extracting pressure 25~35Mpa, carbon-dioxide flow Amount 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, washing steps is 1~3 Secondary;
(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 are respectively provided with toxicity (containing the extremely unreal material of tetrahydrocannabinol THC marijuana hemp).For row Except the toxicity of crude drug, present invention preferably employs the flower of industrial hemp kind " cloud fiber crops No. 1 " of Yunnan growth, leaf, fiber crops bran With Fructus Cannabis as raw material.By China's relevant legal documents regulation, " cloud fiber crops No. 1 " can only be planted within the border in Yunnan, and its flower, Leaf, fiber crops bran can only be processed within the border in Yunnan.
The pharmaceutical composition general anesthesia element of the present invention can make different pharmaceutical preparation, further including oral agents and pin Agent, wherein oral agents includes capsule, oral liquid, tablet, drop pill, granule etc., and injection includes injection dosage form and injection Freeze-dried powder dosage form etc..When preparing oral formulations, available auxiliary type agent can be starch, dextrin or cyclodextrin, sucrose, hard The conventional filler such as fat acid salt.Lyophilized injectable powder can be by methods such as aseptic spray drying, low-temperature vacuum drying, lyophilizations Preparation.The later stage preparation technology of each preparation and equipment all belong to the routine techniques of pharmaceutical field, and this is not construed as limiting by the present invention, therefore This not describes in detail.
The pharmaceutical composition general anesthesia element of the present invention has the effect of clear and definite treatment depression, and experiment finds, general anesthesia Element can make the mouse tail suspension dead time of behavioral despair depression model all significantly reduce, and the forced swimming dead time significantly drops Low, effect is better than cannabidiol;Reserpine induced mice depression model is had obvious antidepressant effect, and effect is better than Fructus Cannabis Diphenol;Being remarkably improved mice autonomic activities number of times, effect is better than cannabidiol.
General anesthesia of the present invention element has obvious mitigation to degradation under the learning memory of depression secondary.Available In preparation treatment include endogenous depression, reactive depression, masked depression, drug-induced secondary depression, Depression, Patients with Diabetes Accompanied by Depression and the depressibility of climacteric or postpartum depression, cerebral trauma or apoplexy induction are neural Disease is in the application of the medicine of interior various depressive symptoms, and treats, for preparing, the insecondary learning and memory that depression causes Decline, the application in the medicine of the symptoms such as anhedonia.
Detailed description of the invention
Below by embodiment, the present invention is described in further detail, but embodiment is not to the technology of the present invention side The restriction of case.
Embodiment 1
Use flower, leaf, fiber crops bran and the Fructus Cannabis of industrial hemp kind " cloud fiber crops No. 1 " of Yunnan growth as raw material. Take maturation industrial hemp Fructus Cannabis, drying, remove impurity, standby after pulverizing;With ethanol to pulverize Fructus Cannabis material extract ( Under the conditions of 60~85 DEG C, heating extraction 2 times, each 1~3 hour), concentration of alcohol is 95%~100% (V/V), and solid-liquid ratio is 1:5~1:20;Leach lixiviating solution, after concentrating under reduced pressure, be industrial hemp Fructus Cannabis extract.
Take the flower of industrial hemp, leaf, the mixture of fiber crops bran 1:3:2 mass ratio, drying, remove impurity, be crushed to 10~60 mesh; Supercritical carbon dioxide extraction: the above-mentioned industrial hemp raw material crushed is put in supercritical carbon dioxide extraction apparatus, control Extraction temperature 40 processed~50 DEG C, extraction time 30~90min, extracting pressure 25~35Mpa, carbon dioxide flow 40kg/h, point Extract is collected from still outlet;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, soak under room temperature Carry, every batch materials extraction 2 times, each 7~10 days.Take the flower of industrial hemp, leaf, the mixture conduct of fiber crops bran 1:1:1 mass ratio 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, use ultrasonic Ripple assisted extraction, ultrasonic frequency 30~60kHz, power 100~1000W, extraction time 30~60min, extraction temperature 25~ 50℃.Take the flower of industrial hemp, leaf, fiber crops bran 3:2:1 mass ratio mixture as industrial hemp Urtica cannabina L. element extraction raw material.
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, mixing Uniformly, spray into 95% ethanol solution, soft material processed, cross 40 mesh sieves and pelletize, 60 DEG C of dry half an hour, be sub-packed in 3# capsule, plastic-aluminum Composite packaging, prepares general anesthesia cellulose capsule agent.
Embodiment 5
Example 2 gained medicine, admixture doses 5~the dried starch of 20% and 1~the magnesium stearate etc. of 5%, through mixed Close, 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, It is distributed in 10mL bottle, makes general anesthesia element oral liquid.
Embodiment 7
Example 1 gained medicine, add water for injection dissolve, add 2.0 ‰ activated carbons, stirring, filter, continue with 0.45 μm, 0.22 μm microporous filter membrane classified filtering, supplement water for injection, be sub-packed in cillin bottle, lyophilization, recharge high-purity Nitrogen, jumps a queue, gland, packaging, prepares general anesthesia element injection.
The impact of Application Example 1 general anesthesia element desperate depression model test acquired on mouse tail suspension method
Choose body weight 18~22g Kunming mouse 50, male and female half and half, be randomly divided into 5 groups, often group 10, i.e. model group, Cannabidiol group, general anesthesia element A, B, C group.Cannabidiol group and general anesthesia element group are all dissolved with 0.5%CMC-Na or are suspended to required Administration concentration, model group gives the 0.5%CMC-Na of equal volume, each group gastric infusion 7 days all continuously, once a day, last Test after being administered 1h.
Single mice tail end (at the 2cm of tail tip) is sticked at outstanding boot (30cm × 30cm × 25cm) top with adhesive plaster On support so that it is become reversal of the natural order of things state, head, from bottom about 5cm, once hangs 2 mices, and centre dividing plate separates.Mice in order to Overcome abnormal position and struggle activity, but movable a period of time occurs that discontinuity is motionless, the disappointed state of display.The suspension time is 6min, after statistics, in 4min, outstanding tail adds up the dead time (the i.e. mice of motionless state stop struggling motionless or without any activity).Real Test and the results are shown in Table 1:
The impact on rat force swimming test of the table 1 general anesthesia element
Note: compare with model group, * * P < 0.01.
Test result indicate that, compare with model group, general anesthesia element each group mice TST dead time all significantly reduces, and is better than big Fiber crops diphenol.
The impact of Application Example 2 general anesthesia element desperate depression model acquired on mouse forced swimming test method
Choose body weight 18~22g Kunming mouse 50, male and female half and half, be randomly divided into 5 groups, often group 10, i.e. model group, Cannabidiol group, general anesthesia element A, B, C group.Cannabidiol group and general anesthesia element group are all dissolved with 0.5%CMC-Na or are suspended to required Administration concentration, model group gives the 0.5%CMC-Na of equal volume, each group gastric infusion 7 days all continuously, once a day, last Test after being administered 1h.
Mice is placed individually in the cylindrical glass cylinder of high 20cm, diameter 14cm, depth of water 10cm in cylinder, water temperature (25 ± 2) DEG C, timing 6min after mice enters water, swimming accumulative dead time in 4min after record (refer to that mice stops struggle in water, Or aobvious floating state, the most small limb motion is kept afloat keeping head).Experimental result is shown in Table 2:
The impact on Mouse Forced Swim Test of the table 2 general anesthesia element
Group Dosage (mg/Kg) Non-swimming time (second)
Model group 151.2±24.6
Cannabidiol group 10 109.3±13.9**
General anesthesia element A group 20 88.8±16.5**
General anesthesia element B group 20 87.3±12.8***
General anesthesia element C group 20 90.4±18.5**
Note: compare with model group, * * P < 0.01, * * * P < 0.001.
Test result indicate that, compare with model group, the FST dead time of each group of general anesthesia element all significantly reduces, and is better than Fructus Cannabis Diphenol.
The impact on drug-induced depressive state of the Application Example 3 general anesthesia element
The compounds such as reserpine are specifically included that under body temperature by the symptomes complice of monoamine transmitters induction animal in exhaustion brain Fall, blepharoptosis and movable suppression.The generation of these symptoms may be with monoamine transmitters in reserpine reduction brain. especially 5-hydroxyl Tryptamines (5-HT), and the result that supervention 5-HT receptor sensitivity changes.Monoamine transmitters system mainly includes 5-HT system, NE system System and dopamine (DA) system, play an important role in the pathogenesis of depression.5-in Brain of Patients with Depression and cerebrospinal fluid HT, 5-HI-AA, NE equal size is all low than normal person.5-HT relates to the regulation of emotion, sleep, vigilance, memory and appetite etc., NE Deficiency then may result in mental retardation.Monoamine oxidase, MAO (MAO) is the important inactivator of monoamine transmitters (5-HT, NE, DA), if this Enzyme is suppressed, and in making brain, monoamine transmitter contents increases, and this has positive effect to improving depression.In 1950's, People, when observing the curative effect of antihypertensive reserpine, find to there are about this medicine of patient's long-term taking of 10-15% and can produce and press down Strongly fragrant symptom.Pharmaceutical research later shows, the basic pharmacological action of reserpine is to exhaust that the monoamine in teleneuron vesicle is passed Matter, thus proposes the monoamine hypothesis of depression. and thinking that synaptic space monoamine neurotransmitter reduces is the depressed mechanism occurred, and resists and press down Strongly fragrant medicine, by blocking monoamine-reuptake or suppression monoamine oxidase, MAO (MAO), makes mediator metabolism reduce and play antidepressant effect.
Choose body weight 18~22g Kunming mouse 120, male and female half and half, be randomly divided into 6 groups, often group 20, be normal Matched group (distilled water), model group (reserpine 1mg/kg.d), cannabidiol group (20mg/kg.d), general anesthesia element A, B, C group (20mg/kg.d).Each group mice continuous gavage distilled water or relative medicine 6 days, in addition to Normal group, each group gives reserpine Blepharoptosis after 1mg/kg, 60min, temperature decline, movable suppression after 180min.After next day, mice last was administered, 30min puts into In mice open field test case, adapt to 2min, observe the level of mice, Vertical movements number of times in 4min, grid number of i.e. creeping subsequently With number of times of standing.
Mice open field test is creeped grid number and the impact of number of times of standing by each group of table 3
Note: compare with model group, * P < 0.05, * * P < 0.01;Compare with cannabidiol group,P < 0.05.
Test result indicate that, each group of general anesthesia element has obvious antidepressant effect to reserpine induced mice depression model, Effect is better than cannabidiol group.
The impact on mice autonomic activities of the Application Example 4 general anesthesia element
Choose body weight 18~22g Kunming mouse 120, male and female half and half, be randomly divided into 6 groups, often group 20, be normal Matched group (distilled water), model group (reserpine 1mg/kg.d), cannabidiol group (20mg/kg.d), general anesthesia element A, B, C group (20mg/kg.d).Each group mice continuous gavage distilled water or relative medicine 6 days, in addition to normal group, each group is given reserpine 1mg/kg, Blepharoptosis after 60min, temperature decline, movable suppression after 180min.Next day mice last be administered after 30min to put into mice autonomous Movable appearance, the movable number of times in record 5min.
Each group of impact on mice autonomic activities number of times of table 4
Note: compare with model group, * P < 0.05, * * P < 0.01;Compare with cannabidiol group,P < 0.05.
Test result indicate that, each group of general anesthesia element is remarkably improved mice autonomic activities number of times, and effect is better than cannabidiol group.

Claims (8)

1. general anesthesia element application in the medicine of preparation treatment depression;Described general anesthesia element is by 0.3 part~99.7 weight portions The industrial hemp Urtica cannabina L. element mixing of industrial hemp Fructus Cannabis extract and 99.7 parts~0.3 weight portion is made.
2. general anesthesia element is in preparation treatment endogenous depression, reactive depression, masked depression, drug-induced Secondary cases Depression, climacteric or postpartum depression, cerebral trauma or depression, Patients with Diabetes Accompanied by Depression and the depressibility of apoplexy induction Application in neurosal medicine;Described general anesthesia element by 0.3 part~the industrial hemp Fructus Cannabis extract of 99.7 weight portions and The industrial hemp Urtica cannabina L. element mixing of 99.7 parts~0.3 weight portion is made.
3. general anesthesia element declines or/and in the medicine of Anhedonia at the preparation treatment insecondary learning and memory that causes of depression Application;Described general anesthesia element is by 0.3 part~the industrial hemp Fructus Cannabis extract of 99.7 weight portions and 99.7 parts~0.3 weight The industrial hemp Urtica cannabina L. element mixing of part is made.
4. according to the application described in claim 1 or 2 or 3, it is characterised in that: the raw material composition of described general anesthesia element is preferably work Sparetime university's fiber crops Fructus Cannabis extract 40 parts and industrial hemp Urtica cannabina L. element 60 parts.
5. according to the application described in claim 1 or 2 or 3, it is characterised in that: described industrial hemp Fructus Cannabis extract passes through Following methods is prepared from:
(1) ripe industrial hemp Fructus Cannabis is taken, drying, remove impurity, standby after pulverizing;
(2) under the conditions of 20~85 DEG C, extracting pulverizing Fructus Cannabis material with ethanol, concentration of alcohol is 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.
6. according to the application described in claim 1 or 2 or 3, it is characterised in that: described industrial hemp Urtica cannabina L. element is by with lower section Method is prepared from:
(1) take the flower of industrial hemp, leaf, fiber crops bran or the mixture of three, drying, remove impurity, be crushed to 10~60 mesh;
(2) supercritical carbon dioxide extraction: the above-mentioned industrial hemp raw material crushed is put into supercritical carbon dioxide extraction dress In putting, control extraction temperature 40~50 DEG C, extraction time 30~90min, extracting 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, washing steps 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 6, it is characterised in that: the flower of described industrial hemp, leaf, fiber crops bran three's mixture Optimum ratio be 1:3:2.
8. according to the application described in claim 1 or 2 or 3, it is characterised in that: the kind of described industrial hemp is preferably " cloud Fiber crops No. 1 ".
CN201610421906.XA 2016-06-14 2016-06-14 Application of all-cannabinoid in preparation of drugs for treating depression Pending CN105963359A (en)

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US11084770B2 (en) 2016-12-07 2021-08-10 Treehouse Biotech, Inc. Cannabis extracts
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Publication number Priority date Publication date Assignee Title
US11084770B2 (en) 2016-12-07 2021-08-10 Treehouse Biotech, Inc. Cannabis extracts
US11202771B2 (en) 2018-01-31 2021-12-21 Treehouse Biotech, Inc. Hemp powder
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