CN107714706A - The application of momordica grosvenori alcohol anti-senile dementia - Google Patents
The application of momordica grosvenori alcohol anti-senile dementia Download PDFInfo
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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Abstract
The invention belongs to natural medicine technical field, is related to the application of momordica grosvenori alcohol and its related compound anti-senile dementia.The present invention proposes the application of momordica grosvenori alcohol and its related compound in prevention and/or treatment medicine for senile dementia and/or health products is prepared.The invention discloses momordica grosvenori alcohol and its new medical use of related compound, i.e. its purposes that can be used for preparing the medicine and/or health products that prevent and/or treat senile dementia.
Description
Technical field
The invention belongs to natural medicine technical field, in particular it relates to which momordica grosvenori alcohol and its related compound are being prepared in advance
Application in anti-or/and treatment senile dementia medicine or/and health products.
Background technology
It is a kind of performance of elderly brain functional disturbance in senile dementia, is to become to turn to intelelectual deterioration and behavior, personality
A kind of illness of feature, including Alzheimer's（AD）, vascular dementia（VD）, mixed dementia and other（Wound, pa
Jin Sen）It is dull-witted.With the aging of China human mortality, this sick number of the infected increases year by year, and senile dementia illness rate is 6%-8%, its
Middle AD patient accounts for more than 60%.This disease is a kind of disease for seriously endangering senior health and fitness, significantly impacts the life of the elderly
Quality, great pain is caused to the elderly's body and mind, while also bring huge burden to family and society.
Senile dementia, the most common are Alzheimer disease (Alzheimer's disease, AD).Alzheimer '
Silent disease is that a kind of primary degenerative encephalopathy in Senectitude and presenium occurs, and refers to a kind of continuation higher nerve work(
Energy moving obstacle, i.e., in the state of no disturbance of consciousness, memory, thinking, analysis judgement, visual space identification, mood etc.
Obstacle.Its characteristic pathological, which becomes, turns to atrophy of cerebral cortex, and is deposited with amyloid-beta, neurofibrillary tangles,
Mass memory nerve member number is reduced, and the formation of senile plaque expelling.Vascular dementia（VD）Refer to by Ischemic Stroke, bleeding
Property palsy and causing remember, recognize and the cranial vascular disease of brain area Low perfusion such as behavior caused by severe cognitive dysfunction synthesis
Sign.China VD illness rate is 1.1%~3.0%, and annual morbidity is in 5-9/1000 people.
At present particularly effective medicine, the curative that in the market has or will emerged are had no for senile dementia
Thing is mainly cholinergic drug, and common is exactly anticholinesterase.Such as Tacrine is first and is approved for old age
The medicine of dementia treatment, but because hepatotoxicity wind agitation is larger, Clinical practice is had logged out at present.Other similar medicines more how piperazine
Although together, the security such as rivastigmine-hydrogentartrate has a further lifting, side effect is still many.In addition Chinese medicine is come from
Huperzine in Huperzine Serrate P.E is also a kind of high selectivity anticholinesterase, and having preferably improves memory and recognize
Know the effect of function, there is anti-senile dementia effect.
The pathogenesis of senile dementia is not still fully aware of at present, and the foundation of the animal model of senile dementia and medicine are ground
It is also ripe not enough to study carefully method.Animal research models used at present are predominantly following several：1. naturally-aged animal model；
2. brain aging animal model caused by suction high-concentrated ozone for a long time；3. aging model caused by long term injections D- galactolipins；4. plus
Fast aging mice model, damage the experimental AD animal models of cholinergic nerve of centrum unit；5. remember caused by chemicals overall applicability
Recall Disorder Model；6. transgenic mice simulation SDAT type Model of Dementia etc..Observational technique is mainly：Darkness avoidance test, shuttle method, diving tower
Method, water maze, electric maze method etc. can the preferably learning abilities of evaluation experimental animal and space exploration ability.
Momordica grosvenori alcohol is the aglycon of main chemical compositions triterpene glucoside in Momordica grosvenori, and Momordica grosvenori is Curcurbitaceae
(Cucurbitaceae) ripening fruits of plant Momordica grosvenori, main product are that Guangxi is famous in Guangxi Yongfu, Lingui and Long Shengdeng counties
Special product.Momordica grosvenori is cool in nature, sweet, return lung, large intestine channel, have moisten the lung and relieve the cough, clearing away summerheat, relieving sore-throat open sound, the work(of cool blood laxation
Effect, is the distinctive integration of drinking and medicinal herbs industrial crops in China, while is recorded in Pharmacopoeia of People's Republic of China, as conventional Chinese medicine
Use, it is evident in efficacy in terms for the treatment of sphagitis, pertussis, acute and chronic tracheitis, gastrointestinal disease.The total glycosides of Momordica grosvenori is Momordica grosvenori
In main active ingredient, there is extensive bioactivity and pharmacology value.Modern medicine study proves that the total glycosides of Momordica grosvenori is not only
With antibechic, relieving asthma, eliminating the phlegm, anti-inflammatory, regulation digestive tract function the effect of, moreover it is possible to strengthen immunity, protecting liver, lowering enzymes, treatment it is acute
It is injury of lungs, anti-oxidant and anti-aging.The main component of Fructus Monordicae extract is Momordia grosvenori aglycone, and total glycosides in Momordica grosvenori is cucurbit
Alkane type triterpenoid glycosides compound, including momordica grosvenori glycoside V (Mogroside V);Momordia grosvenori aglycone IVe (Mogroside IVe);Sieve
Chinese fruit glycosides IIIe (Mogroside IIIe);Momordia grosvenori aglycone II A2 (Mogroside II A2);Momordia grosvenori aglycone III A1
(Mogroside III A1);Momordia grosvenori aglycone IVa (Mogroside IVa);Momordica grosvenori glycoside V I (Mogroside VI);Match
Door glycosides I (Siamenoside I);11-O- momordica grosvenori glycoside Vs (11-Oxomogroside V) etc..Momordica grosvenori alcohol is Momordia grosvenori aglycone
The aglycon of class compound, it can be obtained by sour water solution.
Senile dementia has no good prevention or/and medicine at present.The present inventor, which studies, finds that momordica grosvenori alcohol has
Preferably improve the activity of senile dementia symptom, may have in prevention or/and treatment anti senile dementia drug is prepared wide
Prospect.Momordica grosvenori alcohol pharmacological activity itself is extensive, comes from natural plants, securely and reliably, has no that momordica grosvenori alcohol is used to control at present
Treat or/and prevent the relevant report of senile dementia.
The content of the invention
It is an object of the invention to provide a kind of curative for effect, few side effects, the anti-senile dementia disease drug of natural safety, i.e.,
The application of momordica grosvenori alcohol and its related compound in prevention or/and treatment medicine for senile dementia or/and health products is prepared.
It is a further object of the present invention to provide a kind of pharmaceutical composition prevented or/and treat senile dementia, it is at least
Include momordica grosvenori alcohol, and at least one medicinal diluent, carrier or excipient.Further, said composition can also wrap
There are same or like activity, or the other drugs with auxiliary therapeutic action containing at least one.
Momordica grosvenori alcohol and its related compound of the present invention come from cucurbitaceous plant, especially from cucurbitaceous plant
Fruit.Further, above-mentioned plant is exactly Genus Siraitia Merr, and generally above-mentioned fruit refers to Momordica grosvenori.Further, on
It can also be chemical synthesis to state momordica grosvenori alcohol and its related compound, and further can be repaiied according to treatment needs by chemistry
Decorations.
The purity of momordica grosvenori alcohol of the present invention is more than 50%, it is preferred that the purity of momordica grosvenori alcohol is more than 90%.
Senile dementia of the present invention includes Alzheimer disease, vascular dementia and mixed dementia.
Momordica grosvenori alcohol related compound of the present invention refer to the analog of momordica grosvenori alcohol, derivative, precursor compound,
Metabolin, pharmaceutically active salt or prodrug.
Other drugs of the present invention are with promoting blood circulation and removing blood stasis or improvement memory or the medicine for improving immunity activity, bag
Include but be not limited to tanshinone, tanshin polyphenolic acid B, Quercetin, Puerarin, ginsenoside, notoginsenoside, huperzine, lentinan, spirit
One or more in the compounds such as sesame polysaccharide, resveratrol, rhodiola essence, ligustrazine, polygalic acid.
Other drugs of the present invention are with promoting blood circulation and removing blood stasis or improvement memory or the medicine for improving immunity activity, bag
Include but be not limited to ginkgo leaf, polygala, pseudo-ginseng, ginseng, safflower, peach kernel, grass-leaved sweetflag, the red sage root, rhodiola root, yncaria stem with hooks, the Radix Astragali, Radix Codonopsis
And the one or more in their extract.
The present composition can be prepared according to known method in pharmaceuticals industry piece agent, capsule, pill, pulvis,
Suppository, solution, supensoid agent etc..Wherein it is preferred that suitable for capsule and tablet through gastrointestinal administration.It is corresponding preparing
During the preparation of oral administration, sucrose, lactose, galactolipin, cornstarch, gelatin, microcrystalline cellulose, micro mist silicon can be used
The common medicinal supplementary materials such as glue, carboxymethyl cellulose are as carrier or excipient.
In addition it is also possible to the present composition is prepared into using any means known in pharmaceuticals industry and complementary composition suitable
In the solution or supensoid agent of parenteral route, distilled water, water for injection, isotonic sodium chlorrde solution or Portugal can be used
Grape sugar juice, either low concentration phosphate buffer solution is as carrier or diluent.Can be in these parenteral administrations
One or more other auxiliary elements or additive are added in preparation, such as ascorbic acid can be used to be used as antioxidant
Sodium benzoate etc. is used as preservative.In these formulations, can also containing other appropriate solubilizer, disintegrant, lubricant,
Toner, dispersant or surfactant.
Following examples are intended to further illustrate the present invention, rather than the limitation present invention.Without prejudice to spirit of the invention and
On the premise of principle, any modifications or changes carried out to inventing indivedual technical steps are fallen within the scope of the present invention.
Embodiment
The momordica grosvenori alcohol of embodiment 1 is observed the therapeutic effect of experimental AD rats
1. experiment material
1.1 experimental animal
SD rats, body weight 180-220g, cleaning grade, provided by believing in West China pharmaceutical college experimental animal.
1.2 medicines and reagent
Momordica grosvenori alcohol（Self-control, purity 95%, lot number：20160721）；D- galactolipins；Goose cream Tan propylhomoserin（IBO）；Huperzine-A Tablets, Tests for Uniformity.
1.3 laboratory apparatus
Rat founds position indicator, dentistry drill carriage, HPLC instrument, high speed refrigerator, counter, keeps away camera bellows, Morris water mazes.
Test method and result
Improvement result of 2.1 momordica grosvenori alcohols to senile dementia rat spatial cognition obstacle
Rat Senlie dementia model is caused using IBO, is randomly divided into rat after modeling success：Model to make group, huperzine group,
Momordica grosvenori alcohol low dose group, momordica grosvenori alcohol middle dose group, momordica grosvenori alcohol high dose group simultaneously set Normal group, every group 12 big
Mouse.Model control group and Normal group gavage physiological saline, remaining experimental group press given dose continuous gavage Experimental agents 2
Month.Morris water maze Behaviors surveys are carried out after 2 months, is carried out continuously 7 days, carries out rat training within 1-6 days, last day enters
The relevant Behaviors survey of row, as a result such as table 1.
Improvement result of the momordica grosvenori alcohol of table 1 to senile dementia rat spatial cognition obstacle
Note：Compared with model group,*P ＜ 0.05,**P ＜ 0.01.
As can be seen from the above table, momordica grosvenori alcohol improves significantly to the spatial cognition obstacle tool of AD rats, high agent
Amount group and middle dose group effect are more obvious, have significant difference with model group contrast.It is positive to make group huperzine for
AD rat spatial cognitions obstacle also has certain improvement result, but is weaker than momordica grosvenori alcohol.
Improvement result of 2.2 momordica grosvenori alcohols to senile dementia Rats With Memory dysfunction
Experimental animal is grouped and administration as keeping away in camera bellows camera-lucida by experimental rat after being administered 2 months as described above, work as rat
Shocked by electricity 1 second after into camera bellows, then take out animal, after 1 week repeat test, record rat by camera-lucida enter camera bellows time and
Number, number, statistics such as table 2.
Improvement result of the momordica grosvenori alcohol of table 2 to senile dementia Rats With Memory dysfunction
Note：Compared with model group,*P ＜ 0.05,**P ＜ 0.01.
As can be seen from the above results, momordica grosvenori alcohol has the work that improves significantly for the memory dysfunction of AD rats
With, and doses accordance with tolerance is presented.Momordica grosvenori alcohol middle dose group and high dose group and control group comparative effectiveness are notable, positive drug
Thing huperzine also has certain effect.
Influence of 2.3 momordica grosvenori alcohols to senile dementia rat cerebral cortex content of amino acids neurotransmitter
Influence of the momordica grosvenori alcohol of table 3 to senile dementia rat cerebral cortex content of amino acids neurotransmitter
Note：Compared with model group,*P ＜ 0.05,**P ＜ 0.01.
After off-test, take rat cerebral cortex organization ultrasonic to be homogenized, detect content of amino acids neurotransmitter, as a result such as
Table 3.As can be seen from the above table, momordica grosvenori alcohol can suppress the secretion of cerebral cortex glutamic acid, at the same can significantly AD rats it is big
The content of cortex inhibitory aminoacid and γ-aminobutyric acid is notable with model group comparing difference.
2.4 momordica grosvenori alcohols influence on 4 amyloid content in senile dementia Rat hippocampus
The momordica grosvenori alcohol of table 4 influences on 4 amyloid content in senile dementia Rat hippocampus
| Group | Dosage mg/kg | β -AP（pg/ml） |
| Normal group | - | 42.37±15.88 |
| Model group | - | 69.31±13.17 |
| Huperzine | 3x10-5 | 54.46±17.29 |
| Momordica grosvenori alcohol low dose group | 100 | 55.39±14.36 |
| Momordica grosvenori alcohol middle dose group | 200 | 50.23±10.83* |
| Momordica grosvenori alcohol high dose group | 300 | 46.78±8.16** |
Note：Compared with model group,*P ＜ 0.05,**P ＜ 0.01.
The ultrasound homogenate of rat brain hippocampal tissue is taken after off-test, determines 4 amyloid（β-AP）Content, as a result such as table
4. as can be seen from the above table, momordica grosvenori alcohol middle dose group and high dose group dividing to the β-AP in experimental AD rat brains tissue
Secrete with obvious inhibitory action, it is notable with model group comparing difference.
The momordica grosvenori alcohol of embodiment 2 is to experimental vascular dementia（VD）The influence of learning and memory in rats obstacle
By male Wistar rat, it is placed in and keeps away in camera bellows, after rat enters camera bellows, clicks on 1 second, then take out animal.Next day
Use 10% chloraldurate（0.3ml/100g body weight) intraperitoneal anesthesia, it is fixed on surgical plate, prior to overhead opening, exposure the
One transverse process of cervical vertebra wing aperture, burns bilateral carotid arteries with electric iron, causes permanent occlusion, skin suture.Rat is climbed over, exposure
And free bilateral common carotid arteries, close bilateral common carotid arteries 5 minutes with arteriole folder folder, Reperfu- sion 1 hour, repeatedly for three times, ischemic
Reperfu- sion, causes serious learning memory disorder, postoperative suture muscle skin, and intramuscular injection Benzylpenicillin sodium salt 3 days is anti-infective.Setup Experiments
Operative control group, model are to making group, positive drug group（Ginkgo Leaf Agent）, momordica grosvenori alcohol low dose group, middle dose group and high dose group,
Every group of rat 12, second day after operation start according to dosage to be administered, successive administration 10 days, 1 hour after last time administration, by rat
Once it is put into and keeps away in camera bellows, one every time, record enters camera bellows number, number of elements and latent time in 5 minutes, as a result counts such as
Table 5.
Improvement result of the momordica grosvenori alcohol of table 5 to VD learning and memory function obstacles
| Group | Dosage mg/kg | Incubation period/s | Enter indegree | Into number of elements |
| Operation group | - | 219.8±98.6* | 0.51±0.47** | 3 |
| Model group | - | 51.2±82.4 | 4.21±2.88 | 9 |
| Ginkgo Leaf Agent | 2x10-5 | 195.1±159.6 | 0.72±1.16* | 6 |
| Momordica grosvenori alcohol low dose group | 100 | 193.5±147.3 | 0.78±1.22* | 5 |
| Momordica grosvenori alcohol middle dose group | 200 | 251.8±96.4* | 0.46±0.89** | 4 |
| Momordica grosvenori alcohol high dose group | 300 | 288.2±105.7* | 0.32±0.64** | 4 |
Note：Compared with model group,*P ＜ 0.05,**P ＜ 0.01.
As can be seen from the above table, momordica grosvenori alcohol can significantly improve the learning and memory function barrier of ischemic dementia disease rat
Hinder.
The momordica grosvenori alcohol of embodiment 3 is to NaNO2The influence of caused memory deficits in mice
Take Kunming mouse（ICR mouse, body weight 18-22g）, it is randomly divided into blank control group, model group, positive controls（Gold
Receive more）, momordica grosvenori alcohol low dose group, momordica grosvenori alcohol middle dose group and momordica grosvenori alcohol high dose group, every group of mouse 12.Except blank
Outside group and model group, remaining experimental group presses given dose gastric infusion, and blank group and model group give normal saline, continuously
Administration one week, Jumping test training is carried out before being administered.Before last time is administered, in addition to normal group, remaining each group terminates in training
Subcutaneously note NaNO immediately afterwards2120mg/kg, interval carries out last dose after 24 hours, and is jumped within 1 hour after administration terminates
Platform is tested, the incubation period and errors number that record animal is made a mistake.As a result such as table 6.
The momordica grosvenori alcohol of table 6 is to NaNO2The influence of caused memory deficits in mice
| Group | Dosage mg/kg | Incubation period/s | Errors number |
| Blank group | - | 235.4±95.8** | 0.48±0.62** |
| Model group | - | 76.3±86.2 | 1.26±0.42 |
| Ginkgo Leaf Agent | 2x10-5 | 181.8±82.5** | 0.58±0.71* |
| Momordica grosvenori alcohol low dose group | 100 | 186.4±76.9** | 0.47±0.55** |
| Momordica grosvenori alcohol middle dose group | 200 | 223.7±82.1** | 0.39±0.49** |
| Momordica grosvenori alcohol high dose group | 300 | 276.5±49.3** | 0.28±0.43** |
Note：Compared with model group,*P ＜ 0.05,**P ＜ 0.01.
As can be seen from the above table, momordica grosvenori alcohol is for NaNO2Caused memory deficits in mice tool improves significantly,
Mouse can be substantially reduced to make mistakes number, extend mouse and make a mistake incubation period.
By above-mentioned it is demonstrated experimentally that momordica grosvenori alcohol is for spatial cognition caused by senile dementia and ischemic brain dementia
Obstacle and learning and memory function decline tool and improved significantly.Momordica grosvenori alcohol can increase senile dementia rat brain skin
Layer inhibitory aminoacid, glycine, the content of γ-aminobutyric acid, reduce the toxicity of excitability glutamic acid, and can reduce AD rats
β-AP generation in cerebral hippocampus tissue, decline also tool for learning and memory function caused by cerebral ischemia and be significantly improved.
Momordica grosvenori alcohol can also be obviously improved NaNO2Caused memory deficits in mice.It these results suggest that, momordica grosvenori alcohol has obvious anti-
The effect of senile dementia, clinical medicine exploitation can be used as to use.
Claims (10)
1. the application of momordica grosvenori alcohol and related compound in prevention or/and treatment senile dementia medicine or/health products is prepared.
2. application as claimed in claim 1, the momordica grosvenori alcohol come from Genus Siraitia Merr, it is preferable that the momordica grosvenori alcohol
Come from the fruit Momordica grosvenori of Genus Siraitia Merr.
3. application as claimed in claim 2, the momordica grosvenori alcohol could also be from chemical synthesis, and can according to treatment needs
To be further modified by sulphation.
4. application as claimed in claim 1, the purity of the momordica grosvenori alcohol is more than 50%, it is preferable that purity is more than 90%.
5. application as claimed in claim 1, the senile dementia include Alzheimer disease, vascular dementia and mixed type
It is dull-witted.
6. application as claimed in claim 1, the momordica grosvenori alcohol related compound include but is not limited to the similar of momordica grosvenori alcohol
Thing, derivative, precursor compound, metabolin, pharmaceutically active salt or prodrug.
7. the application as described in claim 1-5, the medicine or health products are different purity momordica grosvenori alcohol or its related compounds
Thing forms with pharmaceutically acceptable carrier, diluent or customary adjuvant.
8. momordica grosvenori alcohol with other there is similar Anti-alzheimer's disease drug regimen to prevent or/and treat senile dementia medicine
In application.
9. application as claimed in claim 7, other described Anti-alzheimer's disease medicines are with promoting blood circulation and removing blood stasis or improvement memory
Or improve the medicine of immunity activity, including but not limited to tanshinone, tanshin polyphenolic acid B, Quercetin, Puerarin, ginsenoside, pseudo-ginseng
In the compounds such as saponin(e, huperzine, lentinan, GL-B, resveratrol, rhodiola essence, ligustrazine, polygalic acid
It is one or more.
10. application as claimed in claim 7, other described Anti-alzheimer's disease medicines are with promoting blood circulation and removing blood stasis or improvement memory
Or improve immunity activity medicine, including but not limited to ginkgo leaf, polygala, pseudo-ginseng, ginseng, safflower, peach kernel, grass-leaved sweetflag,
One or more in the red sage root, rhodiola root, yncaria stem with hooks, the Radix Astragali, Radix Codonopsis and their extract.
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| Application Number | Priority Date | Filing Date | Title |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610657939.4A CN107714706A (en) | 2016-08-12 | 2016-08-12 | The application of momordica grosvenori alcohol anti-senile dementia |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101932240A (en) * | 2007-10-10 | 2010-12-29 | 环球有机物有限责任公司 | Anti-glycation methods and compositions |
-
2016
- 2016-08-12 CN CN201610657939.4A patent/CN107714706A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101932240A (en) * | 2007-10-10 | 2010-12-29 | 环球有机物有限责任公司 | Anti-glycation methods and compositions |
Non-Patent Citations (2)
| Title |
|---|
| 刘婧等: "中药治疗老年痴呆的研究进展", 《中国医药科学》 * |
| 司鹏鹏: "罗汉果总苷的微生物转化研究", 《中国优秀硕士学位论文全文数据库农业科技辑》 * |
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