CN101461803B - Use of grape inner ester - Google Patents
Use of grape inner ester Download PDFInfo
- Publication number
- CN101461803B CN101461803B CN 200710305511 CN200710305511A CN101461803B CN 101461803 B CN101461803 B CN 101461803B CN 200710305511 CN200710305511 CN 200710305511 CN 200710305511 A CN200710305511 A CN 200710305511A CN 101461803 B CN101461803 B CN 101461803B
- Authority
- CN
- China
- Prior art keywords
- auraptene
- group
- capsule
- preparation
- medicine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses novel application of auraptene, which is characterized in that the auraptene extracted from a traditional Chinese medicine Citrus aurantium (bitter orange) is taken as an active ingredient and is mixed with a pharmaceutical carrier and an additive to be prepared into an injection, a tablet, a granule, a pill, a capsule, syrup, an ointment, a soft capsule, an emulsion, a microemulsion preparation and other preparations. A preparation method comprises the following steps: Citrus aurantium and bitter orange are extracted by alcohol, extracted by ethyl acetate, separated by a macroporous resin column and a silica gel column, eluted, condensed and repeatedly recrystallized to obtain the auraptene, and then an excipient is added into the mixture to be prepared into the tablet, the capsule, the emulsion and so on. A prepared medicine in the invention is taken as a novel medicine for resisting senile dementia and promoting gastrointestinal movement, which can produce good economic benefit, and also has broad social benefit.
Description
Technical field
The present invention relates to the purposes of auraptene aspect anti-senile dementia and promotion digestive tract power.Specifically senile dementia (Alzhimer ' sdisease; AD), vascular dementia (Vascular dementia; VD) and Combination dull-witted (Multi-dementia) and promote digestive tract power, lack the medicinal usage and the health purpose of property disease like gastric motilitys such as flatulence, anorexia, dyspepsias.
Background technology
Digestive tract power is that the neuromuscular of a kind of complicacy, hight coordinate is movable, is one of most important physiological function of digestive system.In recent years research confirms, each level such as plexus nervorum (ENS), gastrointestinal smooth muscle or its mutual dysfunction are relevant between the generation of gastrointestinal motility disorder property disease and central nervous system (CNS), autonomic nervous system (ANS), myenteron.The function of these organizational structuries depends on the release of various neurotransmitteies, regulatory factor and peptide hormone and sets up contact, and produces different physiological functions through their its corresponding receptors bind.The physiological Foundations that is not both digestive tract power reinforcing medicine performance pharmacological action of acceptor type and distribution in Different Organs and the structure: muscarinic receptor (m receptor) combines on excitatoty neurotransmitter acetylcholine (Ach) and the smooth muscle, impels smooth muscle contraction; 5-hydroxy tryptamine (5-HT) receives the 5-HT receptor of exciting gastrointestinal tract cholinergic relay cell of physical ability and myenteric nerve plexus, impels acetylcholine to discharge, and produces the effect of gastrointestinal tract dynamia; Dopamine (DA) suppresses smooth muscle contraction through excited DA receptor; The release of NANC (NANC) neurotransmitter can produce inhibitory action; The gastrointestinal motor function is also being regulated in the release of some peptide hormone and the opening of ion channel.When above-mentioned neurotransmitter and hormonal readiness and the pathological changes of gastrointestinal smooth muscle own, can cause the gastrointestinal motility dysfunction, show the symptomes complice of gastrointestinal motility disorder.Auraptene (auraptene) can suppress cholinesterase (Ache) and impel acetylcholine to discharge, and produces the effect of gastrointestinal tract dynamia, and the enhance gastrointestinal smooth muscle contraction is coordinated gastrointestinal motility, promotes gastrointestinal emptying and transhipment, thereby reaches the effect of treatment.
(Alzheimer ' s disease AD), has become a social problem that becomes increasingly conspicuous of aging society to Alzheimer, and people's health and lives safety in serious threat.The reduction of levels of acetylcholine possibly be one of mechanism of AD generation in the body, stimulates the acetylcholine system possibly improve patient's cognition, learning and memory.The anticholinergic medicine is used to treat patient AD and has obtained good curative effect.Discover that the nmda receptor minimizing possibly make patient's AD memory defects worsen.And opened cationic channel after the activation of nmda receptor, can cause sodium ion and flow of calcium ions.The intracellular calcium ion increase will start cascade reaction, cause the reinforcement of synaptic activity.This activity dependent enzymes synapse booster action is called as the long time journey and strengthens (long-term potentiation), is counted as the pattern of learning and memory.Auraptene can suppress activity (the INHIBITION OFACETYLCHOLINESTERASE ACTIVITY BY ESSENTIAL OIL FROM CITRUS PARADISl.M.MIYAZAWA et al. of Ache; NuturalProduct Letters; 2001; 15 (3): 205-210), and can well see through blood brain barrier, this has brought new hope for the treatment Alzheimer.
Fructus Aurantii Immaturus (Fructus aurantii immaturus) is the dry young fruit of rutaceae Citrus aurantium Linn. (Citrus aurantium L.) and mutation or Fructus Citri sinensis (Citrus sinensis Osbeck).Have the dispelling the stagnated QI removing food stagnancy, the effect of painful abdominal mass of loosing of reducing phlegm.
Fructus Aurantii (Fructus aurantii) is the dry immature fruit of rutaceae Citrus aurantium Linn. (Citrus aurantium L.) and mutation thereof.Effect with regulating the flow of QI to ease the stomach, the stagnant relieving distension of row.
Auraptene (auraptene) is a kind of chemical compound with anti-senile dementia and the effect of promotion digestive tract power that extraction separation comes out from Fructus Aurantii Immaturus (shell).Colourless needle, 52～54 ℃ of mp; (n-hexane/acetone), uviol lamp (365nm) is apparent blue-fluorescence down.Chemical molecular formula: C
19H
22O
3Molecular weight: 298.38.Structural formula is following:
Summary of the invention
The present invention relates to the purposes of auraptene in preparation anti-senile dementia and promotion digestive tract power medicine; It is characterized in that the auraptene that will from Chinese medicine Fructus Aurantii Immaturus (shell), extract mixes with pharmaceutical carrier and additive as active component; Process injection, tablet, granule, pill, capsule, effervescent tablet, syrup, the agent of cream magnetic, soft capsule, Emulsion, microemulsion formulation, powder, slow releasing agent, controlled release agent or targeting preparation; As the treatment senile dementia (Alzhimer ' s disease; AD), (Vascular dementia is VD) with Combination dull-witted (Multi-dementia) for vascular dementia; Promote the medicinal usage of gastrointestinal motility for gastric motility shortage property diseases such as treatment flatulence, anorexia, dyspepsias.
The preparation method of described auraptene is following:
Get Fructus Aurantii Immaturus, Fructus Aurantii and pulverize and be coarse powder, with 10 times of amounts of 95% ethanol reflux, extract, 4 times, each 2.5 hours, merge extractive liquid,, being evaporated to does not have alcohol and distinguishes the flavor of.In water, disperse the back to use ethyl acetate extraction the extractum of said extracted, extract 5 times, after the reclaim under reduced pressure acetic acid ethyl acetate extract gets extractum; Process aqueous solution, last D-101 type, AB-8 type macroporous resin column are behind the deionized water eluting; Use 20%, 40%, 70% ethanol elution respectively, reuse 95% ethanol elution is collected 95% ethanol elution; Reclaim under reduced pressure is to not having the alcohol flavor after silica gel column chromatography; Use the petroleum ether-ethyl acetate gradient elution, concentrating under reduced pressure, with petroleum ether-ethyl acetate repeatedly recrystallization obtain the auraptene pure compound.
Pharmacological evaluation of the present invention is following:
1, auraptene is to the influence (anti-senile dementia purposes) of Alzheimer's Disease Rats cognitive function
Laboratory animal is a healthy male SD rat, and body weight 200～250g is provided by the Jiangxi College of Traditional Chinese Medicine Experimental Animal Center.The animal via screening is divided into each 10 of sham operated rats, model group, 15 of auraptene groups with grouping with 35 of qualified rats at random.Sham operated rats (Sham): intracerebroventricular injection citric acid balance liquid.Streptozotocin group (STZ): after the STZ modeling without medicine.Auraptene group (Aur): the 13rd day begins to give auraptene 3mg/kg after the STZ modeling, and medicine is dissolved in the normal saline, oral (filling stomach) administration, once a day, totally 6 weeks.
Table 1 different times rat Morris water maze test incubation period (
) (s)
| Group | Before the art (n) | Postoperative 10d (n) | Treatment back (n) |
| Sham STZ AUR | 15.21±6.32(10) 19.61±3.54(10) 18.96±8.11(15) | 16.56±3.22(9) 62.1±2.89(10) * 52.71±5.23(13) * | 18.44±5.65(9) 60.11±6.33(8) 27.62±5.62(12) |
* * and sham operated rats compare, P＜0.01; * and STZ group compare P＜0.01
The learning and memory in rats ability is observed respectively at the 6th week carrying out water maze test after the 10th day and the medication after the modeling, observes the learning and memory in rats ability.The result shows: compare difference not statistically significant between each group incubation period between the preceding Sham of art, STZ, each group of AUR; After the STZ modeling the 10th day, the STZ group obviously prolonged with the auraptene group incubation period, obviously reduced and cross the platform number of times, and with sham operated rats comparison, P＜0.01, there were significant differences, shows the STZ intracerebroventricular injection after 10 days, and the cognitive function of rat obviously descends; Give medicine after 6 weeks, the auraptene group obviously shortens incubation period, crosses the platform increased frequency, respectively with the STZ group relatively, P＜0.01, difference has statistical significance (table 1 and table 2).
Table 2 rat crosses platform number of times (
) (S)
| Group | Before the art (n) | Postoperative 10d (n) | Treatment back (n) |
| Sham STZ AUR | 4.21±6.13(10) 4.61±5.42(10) 4.01±7.55(15) | 3.89±6.55(9) 0.96±8.21(10) * 0.88±4.97(13) * | 4.49±3.68(9) 1.35±7.11(8) 3.78±2.85(12) |
* * and sham operated rats compare, P＜0.01; * and STZ group compare P＜0.01
2, auraptene is to the influence (promotion digestive tract power) of mice gastric emptying, intestinal propulsion function
1) to normal mouse gastric emptying, the propulsive influence of intestinal
Get 60 of NIH mices, the male and female dual-purpose, stratified random is divided into 3 groups: distilled water group, auraptene small dose group, the heavy dose of group of auraptene.Adopt the t check to compare the difference of administration group and distilled water group.The result shows that the auraptene small dose group can promote the small intestine movement of mice progradation, and heavy dose of group suppresses the small intestine movement of mice progradation.The result sees table 3.
Table 3 auraptene is to the influence (
) of intestinal propelling rate
| Group | Number of animals (only) | Dosage (g/kg) | The phenol red residual rate of stomach (%) | Intestinal propulsion rate (%) |
| The heavy dose of group of distilled water group auraptene small dose group auraptene | 20 20 20 | Equal-volume distilled water 0.0045 0.0270 | 27.65±7.01 26.51±5.65 27.88±6.97 | 55.82±8.66 77.68±5.52* 26.38±4.55* |
* compare P＜0.01 with the distilled water group
2) influence that atropine induced mice gastric emptying, intestinal propulsion is suppressed
Get 40 of Kunming mouses, the male and female dual-purpose is divided into 4 groups at random: distilled water group, simple atropine group, auraptene low dose add the atropine group, and the auraptene heavy dose adds the atropine group.Adopt t check relatively administration group and simple atropine group, the difference of atropine group and distilled water group.The result shows that all ability antagonism atropine induced mice gastric emptying, intestinal advance the effect that suppresses to the auraptene small dose group with heavy dose of group.The result sees table 4.
Table 4 auraptene advances the influence (
) that suppresses to atropine induced mice gastric emptying, intestinal
| Group | Number of animals (only) | Dosage (g/kg) | The phenol red residual rate of stomach (%) | Intestinal propulsion rate (%) |
| Distilled water group atropine group low dose+atropine group heavy dose+atropine group | 10 10 10 10 | Equal-volume distilled water equal-volume distilled water 0.0045 0.0270 | 28.77±8.36 48.21±8.66** 36.21±7.44 △ 47.87±9.12* | 58.77±2.1142.58±5.43**52.47±6.65 △44.71±9.85* |
* compare with the distilled water group, P＜0.05 * * and distilled water group compare, and P＜0.01 △ and atropic group compare, P＜0.01
3) to neostigmine induced mice gastric emptying, the hyperfunction influence of intestinal propulsion
Get 40 of Kunming mouses, the male and female dual-purpose is divided into 4 groups at random: distilled water group, simple neostigmine group, auraptene low dose add the neostigmine group, and the auraptene heavy dose adds the neostigmine group.Adopt t check relatively administration group and simple neostigmine group, the difference of neostigmine group and distilled water group.The result shows all not hyperfunction effects of mice gastric emptying, intestinal propulsion due to the antagonism neostigmine of auraptene small dose group and heavy dose of group.The result sees table 5.
The influence (
) that table 5 auraptene is hyperfunction to mice gastric emptying, intestinal propulsion due to the neostigmine
| Group | Number of animals (only) | Dosage (g/kg) | The phenol red residual rate of stomach (%) | Intestinal propulsion rate (%) |
| Distilled water group neostigmine low dose+neostigmine heavy dose+neostigmine | 10 10 10 10 | Equal-volume distilled water equal-volume distilled water 0.0045 0.0270 | 32.78±8.99 18.66±5.95** 26.33±9.53 34.81±6.58 △△ | ?54.15±7.19?81.03±6.96**?75.21±8.52?80.68±5.87 △△ |
* and distilled water group compare, and P＜0.01 △ △ and distilled water group compare, P＜0.01
From above result of study, can draw the present invention and have following characteristic:
1, auraptene is a cholinesterase inhibitor, through acetylcholine esterase inhibition, improves levels of acetylcholine in the body; To streptozotocin group (STZ) modeling after 10 days; The rat that the cognitive function of rat obviously descends gives auraptene (Aur) after 6 weeks of treatment, and the learning and memory in rats ability is clearly better.
2, auraptene (auraptene) can suppress cholinesterase (Ache) and impels acetylcholine to discharge; Produce the effect of gastrointestinal tract dynamia, the enhance gastrointestinal smooth muscle contraction is coordinated gastrointestinal motility; Promote gastrointestinal emptying and transhipment, and digestive tract power is had dual regulation.
3, the present invention can be with pharmaceutically acceptable excipient; Adopt the conventional method of pharmaceutical field to be prepared into various dosage forms, like injection, tablet, granule, pill, capsule, effervescent tablet, syrup, the agent of cream magnetic, soft capsule, Emulsion, microemulsion formulation, powder, slow releasing agent, controlled release agent or targeting preparation etc.
Embodiments of the invention are described below, but content of the present invention is not limited to this.
The specific embodiment
Embodiment 1: process the sheet agent method: get auraptene 4g, add mixed with excipients and be pressed into tablet, every contains auraptene 4mg.
Embodiment 2: process the capsule method: get auraptene 4g, add mixed with excipients, incapsulate, every contains auraptene 4mg.
Claims (1)
1. auraptene (auraptene) is at the preparation anti-senile dementia and promote the purposes aspect the medicine of digestive tract power; It is characterized in that: the auraptene that will from Chinese medicine Fructus Aurantii Immaturus (shell), extract mixes with pharmaceutical carrier and additive as active component; Process injection, tablet, granule, pill, capsule, effervescent tablet, syrup, the agent of cream magnetic, soft capsule, Emulsion, microemulsion formulation, powder, slow releasing agent, controlled release agent or targeting preparation; As treatment senile dementia (Alzhimer ' s disease; AD), (Vascular dementia is VD) with Combination dull-witted (Multi-dementia) for vascular dementia; Auraptene promotes the medicinal usage of gastrointestinal motility for gastric motility shortage property diseases such as treatment flatulence, anorexia, dyspepsias as unique active component in preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200710305511 CN101461803B (en) | 2007-12-22 | 2007-12-22 | Use of grape inner ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200710305511 CN101461803B (en) | 2007-12-22 | 2007-12-22 | Use of grape inner ester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101461803A CN101461803A (en) | 2009-06-24 |
| CN101461803B true CN101461803B (en) | 2012-01-25 |
Family
ID=40802740
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200710305511 Expired - Fee Related CN101461803B (en) | 2007-12-22 | 2007-12-22 | Use of grape inner ester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101461803B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5945861B2 (en) * | 2011-09-29 | 2016-07-05 | 学校法人松山大学 | Pharmaceutical composition and method for producing the same |
| CN104189346B (en) * | 2014-09-09 | 2016-07-06 | 辽宁华润本溪三药有限公司 | A kind of pharmaceutical composition of short digestive tract power and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4842859A (en) * | 1986-09-08 | 1989-06-27 | Yaguang Liu | Pharmaceutical compositions for reducing hyperlipidemia and platelet-aggregation |
-
2007
- 2007-12-22 CN CN 200710305511 patent/CN101461803B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4842859A (en) * | 1986-09-08 | 1989-06-27 | Yaguang Liu | Pharmaceutical compositions for reducing hyperlipidemia and platelet-aggregation |
Non-Patent Citations (1)
| Title |
|---|
| Hyun-Tai Lee.effect of an aqueous extract of dried immature fruit of Poncirus trifoliate(L.)Raf. on intestinal transit in rodents with experimental gastrointestical motility dysfunctions.《journal of ethnopharmacology》.2005,第102卷(第2期),302-306. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101461803A (en) | 2009-06-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103059043A (en) | Clavatine A-C and preparation method as well as pharmaceutical composition and application thereof | |
| AU2015384083B2 (en) | Use of albiflorin or pharmaceutically acceptable salt for prevention and/or treatment of irritable bowel syndrome | |
| CN106905281B (en) | Inhibit acetyl and the flavone compound of butyrylcholine esterase and application thereof in thick fruit precipice beans rattan | |
| CN102153614B (en) | Method for preparing effective monomer of total alkaloid extract of holarrhena antidysenterica and application thereof | |
| WO2015192758A1 (en) | Anti-tumor pharmaceutical application of pentacyclic triterpene saponin compounds of szechuan melandium root | |
| CN104940479A (en) | TCM composition for treating AD diseases | |
| CN101461803B (en) | Use of grape inner ester | |
| CN102895278A (en) | Application of arctinin and arctigenin in resisting parkinsonism | |
| RU2535019C1 (en) | Sedative and spasmolytic agent | |
| CN101015648B (en) | Use of succinic acid derivative eater compound for treating dementia | |
| CN1733125B (en) | Pharmaceutical purpose of effective parts of immature Bitter orange or trifoliate-orange root-bark | |
| CN102274268B (en) | Traditional Chinese medicine active extract with temperance function, and preparation method and application thereof | |
| CN102188471A (en) | Pharmaceutical composition for treating Alzheimer disease symptom and its preparation method | |
| CN101317867A (en) | Application of standard extract of pseudo-ginseng in preparing medicament for preventing and controlling senile dementia | |
| CN1839855A (en) | Ginsenoside F1 medicinal uses | |
| CN104224796B (en) | Application of oleanane triterpene ester derivative in preparation for anti-neurodegeneration medicine | |
| CN110272407A (en) | A kind of natural isochromanome class compound for blood pressure lowering | |
| CN104415044A (en) | Pharmaceutical composition and preparation thereof for treating stroke and sequelae thereof | |
| CN104857042A (en) | Application of centella selected triterpenes to preparing medicines for preventing or treating senile dementia | |
| CN109223739A (en) | A kind of composition and its preparation method and application | |
| CN102648937A (en) | Application of polygala alkaline hydrolysis product composition in preparation of anti-senile dementia medicine | |
| CN102070700A (en) | Marsdenia tenacissima saponins H and preparation method and application thereof | |
| WO2009149621A1 (en) | Use of icariside ii in manufacture of products for preventing or treating male or female sexual dysfunction | |
| CN101084946A (en) | Active component of levant cotton and preparation method and application thereof | |
| CN106138168A (en) | Cortex Eucommiae extract application in preparation prevention and treatment senile dementia |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120125 Termination date: 20161222 |