CN106074465A - Cannabinol compounds application in preparation treatment gouty arthritis medicine - Google Patents
Cannabinol compounds application in preparation treatment gouty arthritis medicine Download PDFInfo
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- CN106074465A CN106074465A CN201610421373.5A CN201610421373A CN106074465A CN 106074465 A CN106074465 A CN 106074465A CN 201610421373 A CN201610421373 A CN 201610421373A CN 106074465 A CN106074465 A CN 106074465A
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- cannabinol
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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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic 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
- A61K31/352—Heterocyclic 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
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
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Abstract
The invention discloses cannabinol compounds application in preparation treatment gouty arthritis medicine.Inventor finds that cannabinol compounds has the effect of creatinine, uric acid in hyperuricemia mice serum that significantly reduces 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 cannabinol compounds 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
Technical field
The present invention relates to the cannabinol compounds of extraction new application in medical science from Fructus Cannabis, concretely relate to
Cannabinol compounds application in preparation treatment 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.
Containing multiple cannabinol compounds in Fructus Cannabis.Cannabinol compounds is a terpenoid phenolic compound,
Being separated to more than 70 kinds, the most more important has: cannabinol, cannabidiol, tetrahydrocannabinol, cannabinol, cannabidiolic acid,
Tetrahydro-cannabinolic acid etc..What the most main and content was the highest is cannabidiol, tetrahydrocannabinol and cannabinol, and it has and disappears
Inflammation, analgesia, preventing or arresting vomiting, antitumor, spasmolytic, anxiety etc. act on.
Summary of the invention
It is an object of the invention to provide the new application of cannabinol compounds, i.e. new opplication in pharmacy.
It practice, the present invention relates to cannabinol compounds in the medicine of preparation treatment or prevention gouty arthritis
Application；In described cannabinol compounds, the content of cannabidiol is 0.3%～99.7%, and other compositions are tetrahydrochysene Fructus Cannabis
Phenol, cannabinol, cannabigerol, cannabicyclol, cannabinol, tetrahydro-cannabinolic acid, cannabidiol, acid cannabigerolic acid, hexahydro
One in secondary Fructus Cannabis furan phenolic acid, secondary cannabinol, cannabidivarin CBDV Cannabidivarol, tetrahydrocannabinovarin, Fructus Cannabis chromene and time Fructus Cannabis chromene or
Several mixture.
The invention still further relates to the application in preparation fall blood uric acid medicine of the described cannabinol compounds.
The invention still further relates to the application in preparation treatment or prevention antihyperuricemic disease drug of the described cannabinol compounds.
In order to be more fully understood that the essence of the present invention, pharmacological evaluation and result with cannabinol compounds illustrate below
Its new application in pharmaceutical field.
1, prepare cannabinol compounds, but cannabinol compounds used is 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, precipitation remove impurity
Rear ethanol re-dissolved, lysate is pentane eluting after chromatography, collects eluent, concentrating under reduced pressure, vacuum drying, pulverizes,
Cannabinol compounds.
2, take cannabinol compounds, 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, obtains injection.
3, the cannabinol compounds 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, cannabinol compounds A, B, C group (20mg/kg).A group (cannabidiol content 0.3%), B group (cannabidiol
Content 50%), C group (cannabidiol content 99.7%).
Take the crystallization of 250mg Monosodium urate and add 0.9% chloride injection solution 45ml, then add 5ml Tween 80, heated and stirred, join
Make 50 Monosodium urate injection suspension.In addition to normal group, remaining is respectively organized rat and all anaesthetizes with pentobarbital sodium, and dorsal position is fixed, greatly
Mus right Ankle lateral rear punctures, and injects 0.2ml Monosodium urate suspension, induce gouty arthritis model in articular cavity.
Normal group intraarticular injection equal-volume normal saline.Started to be administered cannabinol compounds injection, continuously the same day in modeling
It is administered 6 days.Within 7th day, stop being administered, adjoin in morning and take blood, centrifuging and taking serum, detects creatinine in serum, uric acid content.With 0.9%
Sodium chloride injection 0.5ml rinses, it is thus achieved that animal suffers from the joint irrigation of knee joint, measures Inflammatory Factors Contents.
(1) take serum, detect creatinine in serum, uric acid content.
Table 1 cannabinol compounds is to creatinine, uric acid content and xanthine oxidase in gouty arthritis rat blood serum
The impact of activity
Note: compared with model group,*P ＜ 0.01.
(2) take flushing liquor, detect flushing liquor IL-1 β, IL-6, PGE2 content.
Table 2 cannabinol compounds shadow to gouty arthritis rat articular flushing liquor IL-1 β, IL-6, PGE2 content
Ring
Note: compared with model group,*P ＜ 0.05.
Experimental result shows: cannabinol compounds can reduce creatinine, uric acid level in hyperuricemia mice serum,
Prevent and treat hyperuricemia to occur.The regulation body cell factor simultaneously, effective antiinflammatory, alleviate gouty arthritis symptom.To gout
Property arthritis has preventive and therapeutic effect.
The invention provides with cannabinol compounds as active component, for treating the medicine system of gouty arthritis
Agent.This pharmaceutical preparation is with above-mentioned cannabinol compounds for effective active composition, and include on pharmaceutics acceptable its
His adjuvant component.Described pharmaceutical preparation includes oral agents and injection, and wherein oral agents includes capsule, oral liquid, tablet, drips
Ball, granule etc., injection type includes injection dosage form and freeze-dried powder injection type etc..When preparing oral formulations optional
Auxiliary type agent can be the conventional filler such as starch, dextrin or cyclodextrin, sucrose, stearate.Lyophilized injectable powder can lead to
Prepared by the methods such as aseptic spray drying, low-temperature vacuum drying, lyophilization of crossing.The later stage preparation technology of each preparation and equipment all belong to
The routine techniques of pharmaceutical 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, cannabinol compounds has been excavated new medical application by the present invention, has opened up a new application.
2, by serial experiment prove cannabinol compounds can significantly reduce creatinine in hyperuricemia mice serum,
Uric acid level, prevents and treats hyperuricemia and occurs.The regulation body cell factor simultaneously, effective antiinflammatory, alleviate gouty joint inflammation
Shape.Cannabinol compounds has the effect significantly treating and preventing gouty arthritis.
3, the cannabinol compounds 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, after remove impurity, drying, pulverize, CO2 is super faces extraction, and ethanol re-dissolved after precipitation remove impurity is dissolved
Liquid is pentane eluting after chromatography, collects eluent, concentrating under reduced pressure, vacuum drying, pulverizes, obtain cannabinol compounds.
Take cannabinol compounds 100 grams (crossing 80 mesh sieves), add 60 grams of microcrystalline Cellulose, cross 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, to obtain final product.
Embodiment 2
Taking cannabis, leaf, the mixture of fiber crops bran, after remove impurity, drying, pulverize, CO2 is super faces extraction, second after precipitation remove impurity
Alcohol re-dissolved, lysate is pentane eluting after chromatography, collects eluent, concentrating under reduced pressure, vacuum drying, pulverizes, obtain Fructus Cannabis
Phenolic compound.
Taking cannabinol compounds powder, admixture doses 5～the dried starch of 20% and 1～the magnesium stearate of 5%, through mixed
Close, pelletize, be dried, tabletting, prepare tablet.
Embodiment 3
Repeat embodiment 2, have following difference: take the anti-of cannabinol compounds powder, addition sucrose water and convention amount
Rotten agent, the adjuvant such as stabilizer.Filtration, sterilizing, be distributed in 10mL bottle, make oral liquid.
Embodiment 4
Repeat embodiment 2, have following difference: take cannabinol compounds, 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. cannabinol compounds application in the medicine of preparation treatment or prevention gouty arthritis, described cannabinoids
In compound, the content of cannabidiol is 0.3%～99.7%, and other compositions are tetrahydrocannabinol, cannabinol, cannabigerol, greatly
Fiber crops ring phenol, cannabinol, tetrahydro-cannabinolic acid, cannabidiol, acid cannabigerolic acid, hexahydro time Fructus Cannabis furan phenolic acid, secondary cannabinol,
The mixture of one or more in cannabidivarin CBDV Cannabidivarol, tetrahydrocannabinovarin, Fructus Cannabis chromene and time Fructus Cannabis chromene.
2. cannabinol compounds application in preparation fall blood uric acid medicine, cannabidiol in described cannabinol compounds
Content be 0.3%～99.7%, other compositions are tetrahydrocannabinol, cannabinol, cannabigerol, cannabicyclol, cannabinol,
Tetrahydro-cannabinolic acid, cannabidiol, acid cannabigerolic acid, hexahydro time Fructus Cannabis furan phenolic acid, secondary cannabinol, cannabidivarin CBDV Cannabidivarol, tetrahydrochysene
The mixture of one or more in secondary cannabinol, Fructus Cannabis chromene and time Fructus Cannabis chromene.
3. cannabinol compounds application in preparation treatment or prevention antihyperuricemic disease drug, described cannabinoids chemical combination
In thing, the content of cannabidiol is 0.3%～99.7%, and other compositions are tetrahydrocannabinol, cannabinol, cannabigerol, Fructus Cannabis ring
Phenol, cannabinol, tetrahydro-cannabinolic acid, cannabidiol, acid cannabigerolic acid, hexahydro time Fructus Cannabis furan phenolic acid, secondary cannabinol, secondary greatly
The mixture of one or more in fiber crops diphenol, tetrahydrocannabinovarin, Fructus Cannabis chromene and time Fructus Cannabis chromene.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610421373.5A CN106074465A (en) | 2016-06-14 | 2016-06-14 | Cannabinol compounds application in preparation treatment gouty arthritis medicine |
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| CN201610421373.5A CN106074465A (en) | 2016-06-14 | 2016-06-14 | Cannabinol compounds application in preparation treatment gouty arthritis medicine |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN110923242A (en) * | 2019-12-14 | 2020-03-27 | 厦门梓蔓生物科技有限公司 | Transcription factor CsAPL1 separated from hemp glandular hair and application thereof |
| CN112969452A (en) * | 2018-04-09 | 2021-06-15 | 艾乐文特科学公司 | Cannabis sativa extract for treating animal pain |
| US11040932B2 (en) | 2018-10-10 | 2021-06-22 | Treehouse Biotech, Inc. | Synthesis of cannabigerol |
| 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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Cited By (7)
| 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 |
| CN112969452A (en) * | 2018-04-09 | 2021-06-15 | 艾乐文特科学公司 | Cannabis sativa extract for treating animal pain |
| US11040932B2 (en) | 2018-10-10 | 2021-06-22 | Treehouse Biotech, Inc. | Synthesis of cannabigerol |
| 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 |
| CN110923242A (en) * | 2019-12-14 | 2020-03-27 | 厦门梓蔓生物科技有限公司 | Transcription factor CsAPL1 separated from hemp glandular hair and application thereof |
| CN110923242B (en) * | 2019-12-14 | 2021-04-13 | 厦门梓蔓生物科技有限公司 | Transcription factor CsAPL1 separated from hemp glandular hair and application thereof |
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| CB03 | Change of inventor or designer information |
Inventor after: Xu Chenfeng Inventor after: Hu Chengyue Inventor before: Chen Tianrui Inventor before: Hu Chengyue |
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Application publication date: 20161109 |
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