CN1091372C - Medicine for curing brain dysfunction and epilepsy - Google Patents
Medicine for curing brain dysfunction and epilepsy Download PDFInfo
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- CN1091372C CN1091372C CN99108234A CN99108234A CN1091372C CN 1091372 C CN1091372 C CN 1091372C CN 99108234 A CN99108234 A CN 99108234A CN 99108234 A CN99108234 A CN 99108234A CN 1091372 C CN1091372 C CN 1091372C
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- 206010015037 epilepsy Diseases 0.000 title claims abstract description 11
- 230000005978 brain dysfunction Effects 0.000 title claims abstract 3
- 229940079593 drug Drugs 0.000 title claims description 5
- 150000002338 glycosides Chemical class 0.000 claims abstract description 67
- 229930182470 glycoside Natural products 0.000 claims abstract description 66
- 238000000034 method Methods 0.000 claims abstract description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 64
- 210000001595 mastoid Anatomy 0.000 claims description 46
- 235000013399 edible fruits Nutrition 0.000 claims description 44
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 42
- 239000003208 petroleum Substances 0.000 claims description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 27
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- 239000000047 product Substances 0.000 claims description 18
- 239000000284 extract Substances 0.000 claims description 9
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- FJPYVLNWWICYDW-UHFFFAOYSA-M sodium;5,5-diphenylimidazolidin-1-ide-2,4-dione Chemical compound [Na+].O=C1[N-]C(=O)NC1(C=1C=CC=CC=1)C1=CC=CC=C1 FJPYVLNWWICYDW-UHFFFAOYSA-M 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
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- WURBVZBTWMNKQT-UHFFFAOYSA-N 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1,2,4-triazol-1-yl)butan-2-one Chemical compound C1=NC=NN1C(C(=O)C(C)(C)C)OC1=CC=C(Cl)C=C1 WURBVZBTWMNKQT-UHFFFAOYSA-N 0.000 description 1
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 1
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- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention relates to medicine for curing brain dysfunction and epilepsy, which is prepared from adelostemma general glycoside used as effective ingredients according to conventional medicine preparing methods.
Description
Technical field
The present invention relates to a kind of medicine for the treatment of disordered brain function and leprosy epilepsy.Particularly, relate to one
Kind with mastoid process fruit (Adekistemma gracillimum) (AG) the extract general glycoside partly serve as effective
The medicine that composition is made.
Background technology
Mastoid process fruit (Adekistemma gracillimum) (AG) only be distributed in southwest China and
Burma, on the ground that distributes normal and Cynanchum otophvllum (Cynanchum otophyllum) (CO) mix living.The people
usually think AG by mistake CO, as tonic, Mental Subnormality (not being schizophrenia)
Sick treatment, calmness and stomachic.So far, yet there are no with mastoid process fruit general glycoside as having
The effect composition is developed as the report of disordered brain function and epilepsy medicine.The present invention is first to this plant root
Pharmacological action study, find epilepsy and little disordered brain function (Mininal Brain
Dysrunction, medical value MBD).The physiologically active position of AG is the root chloroform extraction
General glycoside, general glycoside can activate central nervous system (CNS), improve strychnine excitation (with
Strychnine has synergism), the epilepsy that can cause anti-experimental character; And can improve the benzene crust
Than the appropriate and anticonvulsant action appropriate English sodium of English.It is effective that general glycoside only can resist the pain that hot plate causes,
And invalid to radiation-induced pain, so it mainly acts on the forehead of brain.General glycoside is in the brain
Neurotransmitter also has effect.These results of study show that this general glycoside can be developed to disordered brain function
(MBD) and the treatment of epilepsy medicine.
Summary of the invention
The purpose of this invention is to provide a kind of with mastoid process berry extract general glycoside part as effective ingredient
The treatment disordered brain function and the technical scheme of epileptics.
In order to realize purpose of the present invention, the invention provides following technical scheme:
A kind of medicine for the treatment of disordered brain function and epilepsy is characterized in that the medicine method for making is formulated routinely as effective ingredient with mastoid process fruit general glycoside, and described mastoid process fruit general glycoside obtains according to one of following method:
(1), A, get mastoid process fruit root, pulverize, the hot extracting of ethanol 2-3 time, the alcoholic extract recovered alcohol, the concentrated solution chloroform, or with dichloromethane or use ethyl acetate extraction, extract is concentrated into to be done or paste, with petroleum ether reflux 0.5-1 hour, petroleum ether insoluble be a mastoid process fruit general glycoside first product; B, the mastoid process fruit general glycoside first product that A is obtained are dissolved in the alcoholic solution of 45%--50% again, the proportionate relationship of used alcoholic solution and mastoid process fruit general glycoside is: per 1 gram general glycoside is dissolved in 10 milliliters of ethanol, remove by filter insoluble matter then, filtrate decompression is concentrated into dried, can get flaxen mastoid process fruit general glycoside;
(2), A, get mastoid process fruit root, pulverize, industrial chloroform, or with dichloromethane or with ethyl acetate warm macerating 2-3 time reclaims behind the chloroform removal of solvent under reduced pressure again, gets really general glycoside first product of mastoid process; B, the mastoid process fruit general glycoside first product that A is obtained are dissolved in the alcoholic solution of 45%--50%, the proportionate relationship of used alcoholic solution and mastoid process fruit general glycoside is: per 1 gram general glycoside is dissolved in 10 milliliters of ethanol, use filter paper filtering then, discard filtering residue, filtrate decompression is concentrated into paste, 60-90 ℃ of reflux of reuse petroleum ether 1 hour gets mastoid process fruit general glycoside behind the petroleum ether insoluble drying under reduced pressure; Or be dissolved in again with petroleum ether insoluble in the ethanol of 45-50%, get mastoid process fruit general glycoside with spray drying then.
In order to understand essentiality content of the present invention better, the result such as pharmacology, drug effect, toxicity of AG is described with the relevant experimental results of mastoid process berry extract general glycoside (AG) below:
1, acute toxicity:
LD50 mice: 327.7mg/kg
Female rat: 241.0mg/kg
White mouse great and mighty or powerful: 289.3mg/kg
2, sound source outbreak (Audiogenic Seizure) (A.S)
The AG general glycoside shows very strong anti-A.S outbreak effect such as table 1, and shows the dose-effect relationship of tangible medicine.
3, phenobarbital and phenytoin Sodium are had potentiation (seeing Table 2), the antagonism of model has proved the drug effect of AG to MES (outbreak of the super electric body gram of mice).
4, to the synergism of strychnine (central stimulant):
The CD of strychnine
50(CD50): 1.18 ± 0.15mg/kg
AG general glycoside+strychnine: 0.48 ± 0.10mg/kg
5, to the active freely influence of mice:
The sedation of AG general glycoside can and prove (seeing Table 3) by movable number of times decline after the mice administration.
6, the master is relevant with nervous physiology for MBD as a result to neurotransmitter and metabolite effect study thereof: the minimizing of the interior DA (dopamine) of rat brain causes disordered brain function (MBD); Can improve DA if inject amfetamine (Amphetamine), the result makes the animal difficulty steady.The content of DA metabolite is also low than matched group in disordered brain function patient's the brain liquid.AG general glycoside dosage is when 200mg/kg, the content of interior neurotransmitter 5-HT of mouse brain and metabolite 5-HTAA thereof is improved, also improve 3 in the mouse brain cortex, the level of 5-CAMP and CGMP, the DA of other neurotransmitter platform NE also increases (see Table 4 and table 5) to some extent.
To sum up can draw the prospect of AG general glycoside as new drug:
1, drug effect:
The antiepileptic action of AG general glycoside is confirmed by the anticonvulsant action effect of three animal models: i.e. sound source outbreak (AS), maximal electroshock convulsions (MES) and KE (KE).In addition, the positive findings of three pharmacological testings: the AG general glycoside can make free movable minimizing of mice; With strychnine (central stimulants) synergism is arranged and, further supported of the application of AG general glycoside MBD to neurohumoral influence.
2, toxicity:
The LD of general glycoside
50Be 327.7mg/kg, and the median effective dose ED of convulsion outbreak
50Be 13.6mg/kg, so AG general glycoside low toxicity is effective and safety.
3, source (medicine source):
Crude drug source rough estimate AG root can supply amount 5000-10000kg now, but the AG plant can artificial culture.
Because having active blending constituent and its antiepileptic is novel substance, AG can be developed into a kind of new disordered brain function disease and treatment of epilepsy medicine.
The anti-AS outbreak of table 1 AG general glycoside effect
| Dosage mg/kg | Number of animals n | X ± SE before the administration | X ± SE after the administration | The few rate of audiogenic seizure | Number of animals n | ED50mg/kg |
| 6.25 | 10 | 26.0±5.6 | 20.0±5.6 | 23.0 | 0 | 13.6 (7.3-25.5) |
| 12.50 | 10 | 30.7±3.0 | 8.0±3.3 | 73.0 | ||
| 25.00 | 10 | 33.3±3.8 | 2.0±1.8 | 94.0 | ||
| 50.00 | 10 | 33.3±3.8 | 0 | 100 |
Table 2 AG is to the potentiation of phenobarbital and phenytoin Sodium
| Medicine | ED50 |
| Phenobarbital | 13.0(9.7-17.4) |
| Phenytoin Sodium | 4.8(3.4-6.7) |
| AG general glycoside+phenobarbital | 2.0(1.8-3.4) |
| AG general glycoside+phenytoin Sodium | 2.0(1.1-3.6) |
The sedation of table 3 AG general glycoside
| Drug dose (mg/kg) | The free movable number of times of mice/minute (X ± Sx) | ||
| Before the administration | Reduce after the administration number of times/minute | ||
| Reduced in 1 hour (%) | Reduced in 3 hours (%) | ||
| The AG general glycoside | 109.6+8.7 | 0.1±0.3 99.9 | 0.6±1.5 99.5 |
| Chlorpromazine | 103.4+12.5 | 1.4±1.0 98.7 | 6.3±1.7 93.9 |
Table 4 AG general glycoside is to neurohumoral influence in the mouse brain
| Group | Norepinephrine | DOPA | 5-hydroxy tryptamine | The 5-hydroxy tryptamine metabolite | ||||
| x±SE | P | x±SE | P | x±SE | P | x±SE | P | |
| Matched group | 474±16 | 848±56 | 910±42 | 934±73 | ||||
| The administration group | 444±38 | 0.4 | 840±47 | 0.9 | 924±22 | 0.70 | 864±71 | 0.4 |
| The administration group | 452±31 | 0.5 | 870±86 | 0.8 | 968±30 | 0.25 | 1012±42 | 0.1 |
| The administration group | 467±35 | 0.8 | 910±67 | 0.5 | 977±32 | 0.20 | 1135±105 | 0.1 |
| The administration group | 515±37 | 0.25 | 829±33 | 0.8 | 914±56 | ＞0.9 | 1083±69 | 0.1 |
| The administration group | 472±9 | ＞0.9 | 794±56 | 0.5 | 816±23 | 0.40 | 864±41 | 0.4 |
Table 5 AG general glycoside is to the influence of mouse brain cortex (CN)
| Group | cAMP | cGMP | ||
| x±SE | P | x±SE | P | |
| Matched group | 12.2±0.77 | 0.275±0.049 | ||
| The administration group | 16.21±1.18 | 0.01 | 0.346±0.025 | 0.02 |
The specific embodiment
Provide embodiments of the invention below, but content of the present invention is not limited thereto.
Embodiment 1:
Get mastoid process fruit root powder 1000 grams, with 5 kilograms of hot extractings of ethanol 3 times, the 1st time 3 hours, the 2nd, 3 time each 1 hour.The alcoholic extract recovered alcohol, concentrated solution is with chloroform (or with dichloromethane or ethyl acetate) extraction, extract is concentrated into to be done or paste, with petroleum ether (boiling point 60-90 ℃) reflux 0.5-1 hour, stone does not have the solution that ether can stripping, reclaiming behind the petroleum ether can reuse, and petroleum ether soluble matter discards, and petroleum ether insoluble is mastoid process fruit general glycoside first product; The mastoid process that obtains fruit general glycoside first product is dissolved in 45% the ethanol of ten times of amounts (1 gram general glycoside is dissolved in 10 milliliters of ethanol) again, removes by filter insoluble matter, filtrate decompression is concentrated into dried, can get flaxen mastoid process fruit general glycoside 25 grams.Again with mastoid process fruit general glycoside as effective ingredient routinely the medicine method for making make tablet.
Embodiment 2;
Get mastoid process fruit root powder 1000 grams, with 4 kilograms of industrial chloroforms (or with dichloromethane or ethyl acetate) warm macerating 2 times, each 2 hours.Reclaim behind the chloroform removal of solvent under reduced pressure again, the mastoid process fruit general glycoside first product of brownish black; Mastoid process fruit general glycoside first product is dissolved in 50% the alcoholic solution of ten times of amounts, use filter paper filtering, discard filtering residue (the thick thing of black), filtrate decompression is concentrated into paste, reuse petroleum ether (boiling point 60-90 ℃) reflux 1 hour, petroleum ether soluble matter discards, and the petroleum ether that reclaims gained can reuse.Get yellow mastoid process fruit general glycoside 30 grams of pulverizing behind the petroleum ether insoluble drying under reduced pressure.Again with mastoid process fruit general glycoside as effective ingredient routinely the medicine method for making make tablet.
Embodiment 3: get mastoid process fruit root powder 1000 grams, and with 3 kilograms of industrial chloroforms (or with dichloromethane or ethyl acetate) warm macerating 3 times, each 1.5 hours.Reclaim behind the chloroform removal of solvent under reduced pressure again, the mastoid process fruit general glycoside first product of brownish black; Mastoid process fruit general glycoside first product is dissolved in 45% the alcoholic solution of ten times of amounts, use filter paper filtering, discard filtering residue (the thick thing of black), filtrate decompression is concentrated into paste, reuse petroleum ether (boiling point 60-90 ℃) reflux 1 hour, petroleum ether soluble matter discards, and the petroleum ether that reclaims gained can reuse.Be dissolved in again with petroleum ether insoluble in 50% the ethanol, get mastoid process fruit general glycoside 28 grams with spray drying then.Again with mastoid process fruit general glycoside as effective ingredient routinely the medicine method for making make tablet.
Embodiment 4:
Get mastoid process fruit root powder 1000 grams, with 5 kilograms of hot extractings of ethanol 3 times, the 1st time 3 hours, the 2nd, 3 time each 1 hour.The alcoholic extract recovered alcohol, concentrated solution is with chloroform (or with dichloromethane or ethyl acetate) extraction, extract is concentrated into to be done or paste, with petroleum ether (boiling point 60-90 ℃) reflux 0.5-1 hour, stone does not have the solution that ether can stripping, reclaiming behind the petroleum ether can reuse, and petroleum ether soluble matter discards, and petroleum ether insoluble is mastoid process fruit general glycoside first product; The mastoid process that obtains fruit general glycoside first product is dissolved in 45% the ethanol of ten times of amounts (.1 gram general glycoside is dissolved in 10 milliliters of ethanol) again, removes by filter insoluble matter, filtrate decompression is concentrated into dried, can get flaxen mastoid process fruit general glycoside 25 grams.Again with mastoid process fruit general glycoside as effective ingredient routinely the medicine method for making make capsule.
Embodiment 5:
Get mastoid process fruit root powder 1000 grams, with 4 kilograms of industrial chloroforms (or with dichloromethane or ethyl acetate) warm macerating 2 times, each 2 hours.Reclaim behind the chloroform removal of solvent under reduced pressure again, the mastoid process fruit general glycoside first product of brownish black; Mastoid process fruit general glycoside first product is dissolved in 50% the alcoholic solution of ten times of amounts, use filter paper filtering, discard filtering residue (the thick thing of black), filtrate decompression is concentrated into paste, reuse petroleum ether (boiling point 60-90 ℃) reflux 1 hour, petroleum ether soluble matter discards, and the petroleum ether that reclaims gained can reuse.Get yellow mastoid process fruit general glycoside 30 grams of pulverizing behind the petroleum ether insoluble drying under reduced pressure.Again with mastoid process fruit general glycoside as effective ingredient routinely the medicine method for making make capsule.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN99108234A CN1091372C (en) | 1999-05-31 | 1999-05-31 | Medicine for curing brain dysfunction and epilepsy |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN99108234A CN1091372C (en) | 1999-05-31 | 1999-05-31 | Medicine for curing brain dysfunction and epilepsy |
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| Publication Number | Publication Date |
|---|---|
| CN1235830A CN1235830A (en) | 1999-11-24 |
| CN1091372C true CN1091372C (en) | 2002-09-25 |
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|---|---|---|---|
| CN99108234A Expired - Fee Related CN1091372C (en) | 1999-05-31 | 1999-05-31 | Medicine for curing brain dysfunction and epilepsy |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9150608B2 (en) | 2010-03-18 | 2015-10-06 | Biotechnology Research Corp. Ltd. | Neuro-protective compounds and their use |
Citations (3)
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|---|---|---|---|---|
| CN1108948A (en) * | 1994-08-24 | 1995-09-27 | 王洪图 | Medicine for epilepsy and asomnia |
| CN1120951A (en) * | 1995-05-19 | 1996-04-24 | 王文生 | Chinese patent drug Yuxianzaichundan pellet for treatment of epilepsy |
| CN1124637A (en) * | 1994-12-17 | 1996-06-19 | 王富龙 | Dingxiansan capsule for curing epilepsy |
-
1999
- 1999-05-31 CN CN99108234A patent/CN1091372C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1108948A (en) * | 1994-08-24 | 1995-09-27 | 王洪图 | Medicine for epilepsy and asomnia |
| CN1124637A (en) * | 1994-12-17 | 1996-06-19 | 王富龙 | Dingxiansan capsule for curing epilepsy |
| CN1120951A (en) * | 1995-05-19 | 1996-04-24 | 王文生 | Chinese patent drug Yuxianzaichundan pellet for treatment of epilepsy |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9150608B2 (en) | 2010-03-18 | 2015-10-06 | Biotechnology Research Corp. Ltd. | Neuro-protective compounds and their use |
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| Publication number | Publication date |
|---|---|
| CN1235830A (en) | 1999-11-24 |
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