CN106074493A - The application in preparation treatment gouty arthritis medicine of a kind of Fructus Cannabis extract - Google Patents

The application in preparation treatment gouty arthritis medicine of a kind of Fructus Cannabis extract Download PDF

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Publication number
CN106074493A
CN106074493A CN201610421303.XA CN201610421303A CN106074493A CN 106074493 A CN106074493 A CN 106074493A CN 201610421303 A CN201610421303 A CN 201610421303A CN 106074493 A CN106074493 A CN 106074493A
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fructus cannabis
cannabis extract
gouty arthritis
medicine
application
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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
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/045Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05Phenols
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N65/00Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
    • A01N65/08Magnoliopsida [dicotyledons]

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses the application in preparation treatment gouty arthritis medicine of a kind of Fructus Cannabis extract.Inventor finds that tetrahydrocannabinol and cannabidiol have the effect of creatinine, uric acid in hyperuricemia mice serum that significantly reduces after mixing in specific proportions first, prevents and treats hyperuricemia and occurs.The regulation body cell factor simultaneously, effective antiinflammatory, alleviate gouty arthritis symptom, gouty arthritis is had treatment and prevention effect.Present invention also offers the pharmaceutical preparation of described Fructus Cannabis extract treatment gouty arthritis and corresponding pharmaceutical dosage form thereof, with conventional preparation method, the medicine of the various different dosage forms used clinically can be formed in, easy to use.

Description

The application in preparation treatment gouty arthritis medicine of a kind of Fructus Cannabis extract
Technical field
The present invention relates to Fructus Cannabis new application in medical science, concretely relate to a kind of Fructus Cannabis extract in preparation treatment Application in gouty arthritis medicine.
Background technology
Gouty arthritis is the class disease that internal purine metabolic disturbance causes.Purine through a series of metabolic alterations, The product ultimately formed is uric acid.Uric acid does not has what physiological function, under normal circumstances, the uric acid of internal generation in human body 2/3 is discharged by kidney, and 1/3 is discharged by large intestine.Internal uric acid is to constantly generate and draining, and therefore it maintains in blood Certain concentration.In the synthesis and catabolic process of purine, there is the participation of multiple enzyme, owing to the birth defect metabolism of enzyme occurs Disorder, makes the synthesis of uric acid increase or discharge and reduces, all can cause hyperuricemia.When serum Uric Acid Concentration is too high, uric acid is i.e. It is deposited in joint, soft tissue, cartilage and kidney with the form of sodium salt.Urate crystals can be gulped down by mononuclear cell in articular cavity Biting, activate NALP3 complex, NALP3 Yu ASC protein binding activates capase1, capase1 therewith is that a kind of IL-1 β converts Enzyme, can shear IL-1 β precursor and be allowed to be formed activated IL-1 β, and then IL-1 β and IL-1 receptor complex is combined, and passes through MyD88 starts the NF κ B insecondary inflammatory cytokine of triggering and transcribes, and ultimately results in inflammatory reaction, forms gouty arthritis. As treatment the most thoroughly can cause arthroncus, deformity, stiff, periarticular ecchymosis, tuberosity.
Its side effect of specific medicament colchicine of clinical treatment acute gouty arthritis is relatively big at present, stomach easily occurs The untoward reaction such as bowel symptoms, bone marrow depression, therefore, needs badly and develops a kind of specially good effect and the relatively small medicine of side effect.
Tetrahydrocannabinol (THC) is the major psychoactive material in Fructus Cannabis.2013, American scientist research found, Tetrahydrocannabinol maybe can infect anti-AIDS.Tetrahydrocannabinol also has alleviating pain, stimulates appetite, and reduces the effect of sense of feeling sick.
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 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, THC can be hindered to affect nerve system of human body, and have The pharmacologically active such as spasmolytic, anxiety, it is known that can serve as treating the diseases such as epilepsy, diabetes, hypoxic ischemic encephalopathy of newborn The active component of sick medicine.
Summary of the invention
It is an object of the invention to provide the new application of Fructus Cannabis, i.e. new opplication in pharmacy.
It practice, the present invention relates to a kind of Fructus Cannabis extract in the medicine of preparation treatment or prevention gouty arthritis Application;Described Fructus Cannabis extract is tetrahydrocannabinol and the cannabidiol mixture according to weight ratio 4 1~1 4.
The invention still further relates to the application in preparation fall blood uric acid medicine of the described Fructus Cannabis extract.
The invention still further relates to the application in preparation treatment or prevention antihyperuricemic disease drug of the described Fructus Cannabis extract.
In order to be more fully understood that the essence of the present invention, pharmacological evaluation and result with described Fructus Cannabis extract illustrate below Its new application in pharmaceutical field.
1, prepare Fructus Cannabis extract, but tetrahydrocannabinol used and cannabidiol are not limited to following preparation method obtains Arrive.
Taking cannabis, leaf, fiber crops bran or three's mixture, after remove impurity, drying, pulverize, CO2 is super faces extraction, first after remove impurity Alcohol re-dissolved, lysate is Hex after chromatographic column separates, and collects eluent, concentrating under reduced pressure, vacuum drying, pulverizes, obtain four Hydrogen cannabinol.Taking cannabis, leaf, fiber crops bran or three's mixture, after remove impurity, drying, pulverize, CO2 is super faces extraction, second after remove impurity Alcohol re-dissolved, lysate is pentane eluting after chromatography, collects eluent, concentrating under reduced pressure, vacuum drying, pulverizes, obtain Fructus Cannabis Diphenol.
Take tetrahydrocannabinol and cannabidiol mixing, obtain A Fructus Cannabis extract (tetrahydrocannabinol and the weight of cannabidiol Amount ratio is 4 1), B Fructus Cannabis extract (weight ratio of tetrahydrocannabinol and cannabidiol is 1 1), C Fructus Cannabis extract (four The weight ratio of hydrogen cannabinol and cannabidiol is 1 4).
2, take Fructus Cannabis extract, add water for injection and dissolve, add 2.0 ‰ activated carbons, stirring, filter, continue to use 0.45 μ M, 0.22 μm microporous filter membrane classified filtering, supplement water for injection, be sub-packed in cillin bottle, lyophilization, recharge high-purity nitrogen, Jump a queue, gland, packaging, obtain Fructus Cannabis extract injection.
3, the Fructus Cannabis extract impact on induced rat gouty arthritis is observed with conventional pharmacological testing.
Choose body weight 180~220gWistar male rat 50, be randomly divided into 5 groups, often group 10, i.e. normal control Group, model group, Fructus Cannabis extract A, B, C group (20mg/kg).Take the crystallization of 250mg Monosodium urate and add 0.9% chloride injection solution 45ml, then add 5ml Tween 80, heated and stirred, it is configured to 50 Monosodium urate injection suspension.In addition to normal group, it is equal that remaining respectively organizes rat Anaesthetizing with pentobarbital sodium, dorsal position is fixed, and Rat Right Ankle lateral rear punctures, and injects 0.2ml uric acid in articular cavity Sodium suspension, induces gouty arthritis model, normal group intraarticular injection equal-volume normal saline.In modeling same day It is administered Fructus Cannabis extract injection, successive administration 6 days.Within 7th day, stop being administered, adjoin in morning and take blood, centrifuging and taking serum, detects blood Creatinine, uric acid content in clear.Rinse with 0.9% sodium chloride injection 0.5ml, it is thus achieved that animal suffers from the joint irrigation of knee joint, measure Inflammatory Factors Contents.
(1) take serum, detect creatinine in serum, uric acid content.
Table 1 Fructus Cannabis extract is to creatinine, uric acid content and xanthine oxidase activity in gouty arthritis rat blood serum Impact
Note: compared with model group,**P < 0.01.
(2) take flushing liquor, detect flushing liquor IL-1 β, IL-6, PGE2 content.
Table 2 Fructus Cannabis extract is on gouty arthritis rat articular flushing liquor IL 1 β, IL 6, the impact of PGE2 content
Note: compared with model group,*P < 0.05.
Experimental result shows: the Fructus Cannabis extract of the present invention can reduce creatinine, uric acid in hyperuricemia mice serum Level, prevents and treats hyperuricemia and occurs.The regulation body cell factor simultaneously, effective antiinflammatory, alleviate gouty arthritis symptom.Right Gouty arthritis has preventive and therapeutic effect.
The invention provides with described Fructus Cannabis extract as active component, for treating the medicine system of gouty arthritis Agent.This pharmaceutical preparation is with described Fructus Cannabis extract for effective active composition, and includes other adjuvants acceptable on pharmaceutics Component.Described pharmaceutical preparation includes oral agents and injection, wherein oral agents include capsule, oral liquid, tablet, drop pill, Granules etc., injection type includes injection dosage form and freeze-dried powder injection type etc..When preparing oral formulations available Auxiliary type agent can be the conventional filler such as starch, dextrin or cyclodextrin, sucrose, stearate.Lyophilized injectable powder can pass through nothing Prepared by the methods such as bacterium spray drying, low-temperature vacuum drying, lyophilization.The later stage preparation technology of each preparation and equipment all belong to pharmacy The routine techniques in field, this is not construed as limiting by the present invention, therefore not describes in detail at this.
Could be aware that from result above, it is an advantage of the current invention that:
1, known compound tetrahydrocannabinol and cannabidiol have been excavated new medical application by the present invention, have opened up one New application.
2, prove that tetrahydrocannabinol and cannabidiol can significantly reduce height after mixing in specific proportions by serial experiment Creatinine, uric acid level in hyperuricemia mice serum, prevent and treat hyperuricemia and occur.The regulation body cell factor simultaneously, effectively Antiinflammatory, alleviates gouty arthritis symptom.The Fructus Cannabis extract of the present invention has and significantly treats and prevents gouty arthritis Effect.
3, the Fructus Cannabis extract safety non-toxic of the present invention, pharmacological action is strong, imply that good prospect in medicine.
4, the present invention products material abundance, inexpensive, have no toxic and side effects, preparation technology is simple, and can make mouth Oral dosage form, injection type, tablet etc., easy to use, injection can make intramuscular injection and intravenous injection.
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
Taking cannabis, leaf and the mixture of fiber crops bran, after remove impurity, drying, pulverize, CO2 is super faces extraction, and after remove impurity, methanol is again Dissolving, lysate is Hex after chromatographic column separates, and collects eluent, concentrating under reduced pressure, vacuum drying, pulverizes, obtain tetrahydrochysene big Fiber crops phenol.Taking cannabis, leaf, after remove impurity, drying, pulverize, CO2 is super faces extraction, and ethanol re-dissolved after remove impurity, lysate is through chromatography Pentane eluting after separation, collects eluent, concentrating under reduced pressure, vacuum drying, pulverizes, obtain cannabidiol.
Tetrahydrocannabinol and cannabidiol are made required Fructus Cannabis extract according to weight ratio 4 1~1 4 mixing.
Take Fructus Cannabis extract 100 grams (80 mesh sieves excessively), add 60 grams of microcrystalline Cellulose, excessively 80 mesh sieve three times, mix homogeneously, 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 combined bag Dress, makes capsule.
Embodiment 2
Taking cannabis, leaf, after remove impurity, drying, pulverize, CO2 is super faces extraction, methanol re-dissolved after remove impurity, lysate warp Hex after chromatographic column separation, collects eluent, concentrating under reduced pressure, vacuum drying, pulverizes, obtain tetrahydrocannabinol.Take cannabis, Leaf, the mixture of fiber crops bran, after remove impurity, drying, pulverize, CO2 is super faces extraction, and ethanol re-dissolved after remove impurity, lysate is through chromatography Pentane eluting after separation, collects eluent, concentrating under reduced pressure, vacuum drying, pulverizes, obtain cannabidiol.
Tetrahydrocannabinol and cannabidiol are made required Fructus Cannabis extract according to weight ratio 4 1~1 4 mixing.
Take Fructus Cannabis extract powder, admixture doses 5~the dried starch of 20% and 1~the magnesium stearate of 5%, blended, Pelletize, be dried, tabletting, prepare tablet.
Embodiment 3
Repeat embodiment 2, have following difference: take Fructus Cannabis extract powder, add sucrose water and the preservative of convention amount, The adjuvants such as stabilizer.Filtration, sterilizing, be distributed in 10mL bottle, make oral liquid.
Embodiment 4
Repeat embodiment 2, have following difference: take Fructus Cannabis extract powder, add water for injection and dissolve, add 2.0 ‰ Activated carbon, stirring, filter, continue, with 0.45 μm, 0.22 μm microporous filter membrane classified filtering, to supplement water for injection, be sub-packed in XiLin In Ping, lyophilization, recharge high-purity nitrogen, jump a queue, gland, packaging, make injection.

Claims (3)

1. Fructus Cannabis extract application in the medicine of preparation treatment or prevention gouty arthritis, described Fructus Cannabis extract is Tetrahydrocannabinol and cannabidiol are according to the mixture of weight ratio 4 1~1 4.
2. Fructus Cannabis extract application in preparation fall blood uric acid medicine, described Fructus Cannabis extract is tetrahydrocannabinol and Fructus Cannabis Diphenol is according to the mixture of weight ratio 4 1~1 4.
3. Fructus Cannabis extract application in preparation treatment or prevention antihyperuricemic disease drug, described Fructus Cannabis extract is tetrahydrochysene Cannabinol and cannabidiol are according to the mixture of weight ratio 4 1~1 4.
CN201610421303.XA 2016-06-14 2016-06-14 The application in preparation treatment gouty arthritis medicine of a kind of Fructus Cannabis extract Pending CN106074493A (en)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107982080A (en) * 2017-12-20 2018-05-04 汉义生物科技(北京)有限公司 The purposes of cannabidiol or Cannador in whitening product is prepared
WO2019119298A1 (en) * 2017-12-20 2019-06-27 汉义生物科技(北京)有限公司 Use of cannabidiol or cannabis extract in preparation of skin whitening products
CN110064030A (en) * 2019-05-30 2019-07-30 厦门梓素生物科技有限公司 One kind extract for treating gouty arthritis medicinal application of CBD containing cannabidiol
CN110270578A (en) * 2019-06-26 2019-09-24 云南绿新生物药业有限公司 A method of utilizing new storage process industrial hemp floral leaf
JP2021527132A (en) * 2018-06-15 2021-10-11 キャンパル アニマル セラピューティクス リミテッド Cannabinoid composition and treatments using it

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107982080A (en) * 2017-12-20 2018-05-04 汉义生物科技(北京)有限公司 The purposes of cannabidiol or Cannador in whitening product is prepared
WO2019119298A1 (en) * 2017-12-20 2019-06-27 汉义生物科技(北京)有限公司 Use of cannabidiol or cannabis extract in preparation of skin whitening products
JP2021506829A (en) * 2017-12-20 2021-02-22 漢義生物科技(北京)有限公司 Use of cannabidiol or cannabis extract in the preparation of whitening products
JP2021527132A (en) * 2018-06-15 2021-10-11 キャンパル アニマル セラピューティクス リミテッド Cannabinoid composition and treatments using it
CN110064030A (en) * 2019-05-30 2019-07-30 厦门梓素生物科技有限公司 One kind extract for treating gouty arthritis medicinal application of CBD containing cannabidiol
CN110270578A (en) * 2019-06-26 2019-09-24 云南绿新生物药业有限公司 A method of utilizing new storage process industrial hemp floral leaf

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Inventor after: Xu Chenfeng

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Application publication date: 20161109

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