CN1768746A - New medical application of matrine alkaloid - Google Patents
New medical application of matrine alkaloid Download PDFInfo
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- CN1768746A CN1768746A CN 200410036218 CN200410036218A CN1768746A CN 1768746 A CN1768746 A CN 1768746A CN 200410036218 CN200410036218 CN 200410036218 CN 200410036218 A CN200410036218 A CN 200410036218A CN 1768746 A CN1768746 A CN 1768746A
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- matrine
- alkaloid
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- ZSBXGIUJOOQZMP-JLNYLFASSA-N Matrine Chemical class C1CC[C@H]2CN3C(=O)CCC[C@@H]3[C@@H]3[C@H]2N1CCC3 ZSBXGIUJOOQZMP-JLNYLFASSA-N 0.000 title claims abstract description 53
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 23
- 206010039966 Senile dementia Diseases 0.000 claims abstract description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
- 201000010099 disease Diseases 0.000 claims abstract description 13
- 230000004118 muscle contraction Effects 0.000 claims abstract description 7
- 206010028417 myasthenia gravis Diseases 0.000 claims abstract 2
- ZSBXGIUJOOQZMP-UHFFFAOYSA-N Isomatrine Natural products C1CCC2CN3C(=O)CCCC3C3C2N1CCC3 ZSBXGIUJOOQZMP-UHFFFAOYSA-N 0.000 claims description 36
- 229930014456 matrine Natural products 0.000 claims description 29
- 229930013930 alkaloid Natural products 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 16
- LTTQKYMNTNISSZ-MWTRTKDXSA-N (2S)-(-)-kurarinone Chemical compound C1([C@H]2OC=3C(C[C@@H](CC=C(C)C)C(C)=C)=C(O)C=C(C=3C(=O)C2)OC)=CC=C(O)C=C1O LTTQKYMNTNISSZ-MWTRTKDXSA-N 0.000 claims description 12
- 150000003797 alkaloid derivatives Chemical class 0.000 claims description 12
- ZSBXGIUJOOQZMP-BHPKHCPMSA-N sophoridine Chemical compound C1CC[C@@H]2CN3C(=O)CCC[C@@H]3[C@@H]3[C@H]2N1CCC3 ZSBXGIUJOOQZMP-BHPKHCPMSA-N 0.000 claims description 12
- 238000002347 injection Methods 0.000 claims description 11
- 239000007924 injection Substances 0.000 claims description 11
- XQVFLLMCNGKXSM-UHFFFAOYSA-N kurarinone Natural products COc1cc(O)c(C(CC=C(C)C)C(=C)C)c2OC(CC(=O)c12)c3ccc(O)cc3O XQVFLLMCNGKXSM-UHFFFAOYSA-N 0.000 claims description 11
- KDADHLPROOOPIC-UHFFFAOYSA-N neokurarinol Natural products COc1cc(O)ccc1C1CC(=O)c2c(OC)cc(O)c(CC(CCC(C)(C)O)C(C)=C)c2O1 KDADHLPROOOPIC-UHFFFAOYSA-N 0.000 claims description 11
- XVPBINOPNYFXID-JARXUMMXSA-N 85u4c366qs Chemical compound C([C@@H]1CCC[N@+]2(CCC[C@H]3[C@@H]21)[O-])N1[C@@H]3CCCC1=O XVPBINOPNYFXID-JARXUMMXSA-N 0.000 claims description 10
- 229930015582 oxymatrine Natural products 0.000 claims description 10
- AAGFPTSOPGCENQ-JLNYLFASSA-N sophocarpine Chemical compound C1CC[C@H]2CN3C(=O)C=CC[C@@H]3[C@@H]3[C@H]2N1CCC3 AAGFPTSOPGCENQ-JLNYLFASSA-N 0.000 claims description 10
- AAGFPTSOPGCENQ-UHFFFAOYSA-N Sophocarpin I Natural products C1CCC2CN3C(=O)C=CCC3C3C2N1CCC3 AAGFPTSOPGCENQ-UHFFFAOYSA-N 0.000 claims description 9
- IGXQFUGORDJEST-UHFFFAOYSA-N Sophocarpine Natural products O=C1C=CCC2C3CCCC4CCCC(CN12)C34 IGXQFUGORDJEST-UHFFFAOYSA-N 0.000 claims description 9
- 239000004615 ingredient Substances 0.000 claims description 8
- 230000007423 decrease Effects 0.000 claims description 7
- QMGGMESMCJCABO-UHFFFAOYSA-N n-oxysophocarpine Chemical compound C12C3CCC[N+]2([O-])CCCC1CN1C3CC=CC1=O QMGGMESMCJCABO-UHFFFAOYSA-N 0.000 claims description 7
- 208000007964 Organophosphate Poisoning Diseases 0.000 claims description 6
- 201000004810 Vascular dementia Diseases 0.000 claims description 6
- VQYBAEAOOJBSTR-QHSBEEBCSA-N Sophoranol Chemical compound C([C@@H]12)CCC(=O)N1C[C@@]1(O)[C@H]3[C@@H]2CCCN3CCC1 VQYBAEAOOJBSTR-QHSBEEBCSA-N 0.000 claims description 4
- VQYBAEAOOJBSTR-AYRXBEOTSA-N Sophoranol Natural products O=C1N2[C@H]([C@@H]3[C@@H]4[C@](O)(C2)CCCN4CCC3)CCC1 VQYBAEAOOJBSTR-AYRXBEOTSA-N 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
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- HVDKSWJHPWCSSC-UHFFFAOYSA-N C=1C=CCN2C=CC=CC12.N1=CC=CC=C1 Chemical compound C=1C=CCN2C=CC=CC12.N1=CC=CC=C1 HVDKSWJHPWCSSC-UHFFFAOYSA-N 0.000 claims description 2
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- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 abstract 1
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- 239000011574 phosphorus Substances 0.000 abstract 1
- 231100000572 poisoning Toxicity 0.000 abstract 1
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- ZRJBHWIHUMBLCN-YQEJDHNASA-N huperzine A Chemical group N1C(=O)C=CC2=C1C[C@H]1\C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-YQEJDHNASA-N 0.000 description 16
- 241000700159 Rattus Species 0.000 description 14
- ZRJBHWIHUMBLCN-SEQYCRGISA-N Huperzine A Natural products N1C(=O)C=CC2=C1C[C@H]1/C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-SEQYCRGISA-N 0.000 description 13
- ZRJBHWIHUMBLCN-UHFFFAOYSA-N Shuangyiping Natural products N1C(=O)C=CC2=C1CC1C(=CC)C2(N)CC(C)=C1 ZRJBHWIHUMBLCN-UHFFFAOYSA-N 0.000 description 13
- ZRJBHWIHUMBLCN-BMIGLBTASA-N rac-huperzine A Natural products N1C(=O)C=CC2=C1C[C@@H]1C(=CC)[C@@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-BMIGLBTASA-N 0.000 description 13
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- 241000219784 Sophora Species 0.000 description 3
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 3
- 229960004373 acetylcholine Drugs 0.000 description 3
- 229940048961 cholinesterase Drugs 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
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- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
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- ADJWEWOIQOTUSH-SWBPCFCJSA-N (+)-Isomatrine Natural products OC[C@@]1(C)[C@@H]2[C@H](O)CC(=C)[C@@H](CCc3cocc3)[C@@]2(C)CCC1 ADJWEWOIQOTUSH-SWBPCFCJSA-N 0.000 description 1
- QVKQQLYSTODTJN-UHFFFAOYSA-N 2-amino-2-(3-oxo-1,2-oxazol-5-yl)acetic acid;hydrate Chemical compound O.OC(=O)C(N)C1=CC(=O)NO1 QVKQQLYSTODTJN-UHFFFAOYSA-N 0.000 description 1
- SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 description 1
- 102100033639 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- 208000024806 Brain atrophy Diseases 0.000 description 1
- 229940122041 Cholinesterase inhibitor Drugs 0.000 description 1
- 208000027691 Conduct disease Diseases 0.000 description 1
- 102100028717 Cytosolic 5'-nucleotidase 3A Human genes 0.000 description 1
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- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- ZQPQGKQTIZYFEF-WCVJEAGWSA-N Huperzine Natural products C1([C@H]2[C@H](O)C(=O)N[C@H]2[C@@H](O)C=2C=CC=CC=2)=CC=CC=C1 ZQPQGKQTIZYFEF-WCVJEAGWSA-N 0.000 description 1
- ZSBXGIUJOOQZMP-QVHKTLOISA-N Isomatrine Chemical compound C1CC[C@@H]2CN3C(=O)CCC[C@@H]3[C@H]3[C@@H]2N1CCC3 ZSBXGIUJOOQZMP-QVHKTLOISA-N 0.000 description 1
- 241000219745 Lupinus Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
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- 241000700157 Rattus norvegicus Species 0.000 description 1
- 101100192365 Rattus norvegicus Ptpn5 gene Proteins 0.000 description 1
- 241001145009 Sophora alopecuroides Species 0.000 description 1
- 241000123725 Sophora tonkinensis Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
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- 239000000064 cholinergic agonist Substances 0.000 description 1
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- QMGGMESMCJCABO-JARXUMMXSA-N oxysophocarpine Chemical compound C([C@@H]1CCC[N@+]2(CCC[C@H]3[C@@H]21)[O-])N1[C@@H]3CC=CC1=O QMGGMESMCJCABO-JARXUMMXSA-N 0.000 description 1
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- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention provides the new use of matrine alkaloid in preventing and treating senile dementia, children's mental retardation, myasthenia gravis and other diseases with muscle contraction force and sleep disorder and in relieving organic phosphorus poisoning.
Description
Invention field
The present invention relates to the medical application of matrine alkaloid at the rescue of prevention and treatment senile dementia disease, muscular contraction force decline disease, the infull property disease of children's intelligence and organophosphate poisoning.
Background technology
Matrine alkaloid system is from Radix Sophorae Flavescentis (Sophora flavescent A it), Herba Sophorae alopecuroidis (S.alopecuroides L.), root of subprostrate sophora (S.subprostrata Chunet T.Chen) and Radix Sophorae Viciifoliae sophora plants such as (Sophoraviciifo liahance) separate the lupin Alkaloid that obtains, and comprise matrine (matrine), oxymatrine (oxymatrine), sophocarpine (sophocarine), N-oxysophocarpine (oxysophocarpine), sophoranol (5 α-hydroxy matrine), the isomer sophoridine (sophoridine) of supanine (supanine) and matrine, Iosmatrine (isomatrine) etc.Present discovers that this Alkaloid mainly contains antiviral, and pharmacological actions such as antiinflammatory, antitumor and adjusting immunity are hepatitis and oncotherapy and adjuvant drug.We study the therapeutical effect that this Alkaloid reduces the rescue of the effect of acetylcholinesterase and treatment senile dementia, muscular contraction force decline disease, the full property disease of children's intelligence, sleep disorder and organophosphate poisoning.Find that this medicine can obviously improve senile dementia patients cognitive and self care ability, patient's abalienation states such as sleep disorder obviously improve after the medication, promote the intelligence of intelligence decline model mice, improve the muscular contraction force of mice, can also reduce the organophosphate poisoning mortality of mice in addition.Can be used for the senile dementia disease,, the prevention or the treatment of the rescue of the full property disease of children's intelligence, sleep disorder and organophosphate poisoning.The purposes research of relevant this medical field of matrine alkaloid does not appear in the newspapers both at home and abroad.
Technology contents
The invention provides the medicinal usage of matrine alkaloid in treatment and prevention senile dementia disease.
The invention provides the purposes of matrine alkaloid in the low property of treatment children's intelligence disease.
The invention provides the medicinal usage of matrine alkaloid in treatment muscular contraction force decline disease.
The invention provides the medicinal usage of matrine alkaloid in the sleep disordered disease of treatment.
The invention provides the medicinal usage of matrine alkaloid at the rescue organophosphate poisoning.
Matrine alkaloid provided by the invention comprises isomer sophoridine, Iosmatrine of matrine, oxymatrine, sophocarpine, N-oxysophocarpine, sophoranol, supanine and matrine etc.Its architectural feature is to have tetracyclic quinolizine pyridine, as scheming:
The basic structure of matrine alkaloid
For example matrine, oxymatrine,, N-oxysophocarpine and the isomer sophoridine of matrine, the chemical constitution of Iosmatrine be:
Oxymatrine matrine sophocarpine
N-oxysophocarpine sophoridine Iosmatrine
The matrine alkaloid that the present invention relates to can extract from plant and obtain, also can chemosynthesis.
The senile dementia that the present invention relates to comprises alzheimer disease, vascular dementia, mixing is dull-witted and other are dull-witted.
The muscular contraction force decline disease that the present invention relates to comprises heavily levies myasthenia etc.
The effective dose of matrine alkaloid provided by the invention can be made various types of agents according to the method for pharmaceutics with medical dressing, comprises injection, oral formulations and through the preparation of skin mucosa delivery.
The matrine alkaloid that the present invention relates to can be made medicine as effective ingredient with an alkaloid, also can several alkaloids composition compositionss make medicine and functional food as effective ingredient.For example, the kurarinone sheet is effective ingredient with the oxymatrine; Matrine injection is main component with the matrine; The effective ingredient of Radix Sophorae Flavescentis alkaloid gel then comprises matrine, oxymatrine, sophocarpine and N-oxysophocarpine.
Specific embodiment
Embodiment 1. kurarinones are to the observation of senile dementia therapeutic effect
Senile dementia is a kind of common brain popularity degeneration based on chronic organic brain atrophy, degeneration, shows as the memory of carrying out property, cognition, disturbance of intelligence.Comprising alzheimer disease (Alzheimer ' s Disease, AD accounts for 42%), vascular dementia (VD accounts for 26%), Combination dementia (accounting for 12%) and other dementia (accounting for 20%).The prevalence of external report over-65s old man dementia is 4.6%～8.6%, domesticly is reported as 1.0%～4.6%, every increase of age 5 years old, and prevalence will increase by 1 times.The most outstanding symptom of dull-witted patient is memory, thinking, disturbance of intelligence, personality changes and conduct disorder etc.The Therapeutic Method of senile dementia mainly is cholinesterase inhibitor and cholinergic agonist etc. at present, and the medicine of its representative is that huperzine is first-class, and clinical efficacy obtains certainly.
1. case is selected
Select patient's 64 examples of senile dementia (Chang Gu river intelligence test＜20), male 42 examples, women 20 examples.62 years old～89 years old age, average 68 years old.Alzheimer disease (AD) 45 examples wherein, vascular dementia (VD) 16 examples, Combination dementia (MID) 3 examples.Medical history 1～6 year, average 3 years.Adopt domestic current Chang Gu river intelligence scale and daily life self-care ability scale (ADL) to evaluate to observed case.
2. method and result
Adopt the double blind control method, after Chang Gu river intelligence scale and daily life self-care ability scale (ADL) test, patient is divided into 2 groups at random, its test result of 2 groups is not seen remarkable significant difference.Kurarinone group oral kurarinone sheet every day 600mg, 30 days course of treatment, drug withdrawal continued the next course of treatment after 1 week.Huperzine A group oral huperzine A sheet every day 100ug, 30 days course of treatment, drug withdrawal continued the next course of treatment after 1 week.The 13 routine dull-witted patients that select in addition to treat follow the tracks of and follow up a case by regular visits to (initial intelligent scale and the test of daily life self-care ability scale are not seen remarkable significant difference with above-mentioned 2 groups).Take separate after 3 courses of treatment blind, before medication, finish 1 course of treatment after, finish after 3 courses of treatment and treat after 1 year patient is carried out cognitive competence and viability test, relatively t check between the employing group, with p＜0.05 as the significance,statistical index.The result show patient took medicine 1 month, 3 months after its viability and cognitive competence have clear improvement before than medication (table 1).Through following up a case by regular visits to 1 year, to take medicine for a long time and do not see the overt toxicity effect, patient's cognitive function and self care ability decline degree are obviously slowed down than treating group, and effect is better than huperzine A matched group (table 2).
The evaluation (n=32) of table 1 kurarinone treatment 30 days and 90 days dull-witted patient's cognitive competence and self-care ability improvement
| Group | Self-care ability | Cognitive competence | Sleep disorder (%) | |||
| 30 days | 90 days | 30 days | 90 days | 30 days | 90 days | |
| Blank kurarinone huperzine A | 53±8.6 34±7.9 * 42±9.2 * | 58±7.3 39±9.9 * 46±10.2 * | 12.5±6.5 16.4±3.9 * 15.9±5.4 * | 9.3±8.3 15.8±4.7 ** 13.2±6.6 * | 68％ 36％ * 54％ * | 72％ 29％ ** 48％ * |
Compare p＜0.05 with the blank group;
*P＜0.01
Table 2 kurarinone is treated the evaluation of 1 dementia patient cognitive competence and self-care ability improvement
| Group | n | Self-care ability | Cognitive competence | Sleep disorder (%) | |||
| Before the administration | After the administration | Before the administration | After the administration | Before the administration | After the administration | ||
| Blank kurarinone huperzine A | 9 27 29 | 51±11.4 57±12.9 54±13.2 | 69±15.6 49±20.8 * 58±19.6 * | 14.2±5.6 13.5±6.4 15.1±7.3 | 7.2±5.6 15.3±6.3 * 11.3±7.1 * | 72％ 66％ 71％ | 68％ 46％ * 59％ * |
*Compare p＜0.05 with the blank group
Embodiment 2. matrine intravenous injections are to the observation of senile dementia therapeutic effect
1. case is selected
Clinical diagnosis meets senile dementia 26 examples, male 14 examples, women 12 examples.60 years old～78 years old age, average 65 years old.Observed case is adopted domestic current Chang Gu river intelligence scale and daily life self-care ability scale (ADL) evaluation.
2. method and result
Adopt the double blind control method, each group patient is divided into 3 groups, matrine group intravenous drip every day matrine injection 600mg, one day 1 time, continuous 14 days at random.Huperzine A group oral huperzine A 100ug every day, one day 1 time, continuous 14 days.Before medication, administration carries out the test of intelligence and viability to patient after 14 days, the result shows have clear improvement before treatment back patient's cognitive competence and sleep disorder are than medication (table 3).Effect is suitable with the huperzine A matched group.
The evaluation of table 3 matrine intravenous injection dull-witted patient's cognitive competence improvement in 14 days
| Group | The example number | Cognitive competence | Sleep disorder | ||
| Before the administration | After the administration | Before the administration | After the administration | ||
| Contrast matrine huperzine A | 9 27 29 | 15.1±4.6 14.6±5.3 15.3±6.8 | 14.6±6.7 17.4±6.5 * 17.1±4.6 * | 67％ 78％ 69％ | 59％ 34％ * 52％ |
Compare with matched group
*P＜0.05
3. 3 kinds of Radix Sophorae Flavescentis alkaloids of embodiment are to the observation of senile dementia rat therapeutic effect
1. medicine and reagent: kurarinone, matrine and sophocarpine are produced by Ningxia Boertaili Pharmaceutical Co., Ltd, and the huperzine A sheet is produced by Shanghai red flag pharmaceutical factory.The D-galactose is that reagent two factories in Shanghai produce, and amino-(3-hydroxy-5-isoxazolyl)acetic acid. (IBO) is analytical pure available from Sigma company.Whole blood and cerebral tissue TChE (TchE) detection kit are built up bio-engineering research by Nanjing to be provided.
2. animal grouping, modeling and administration: 57 of 15 monthly age young old female Wistar rats, body weight 300～450g provides by Qingdao City medicine inspecting institute animal center.Conventional sub-cage rearing, natural illumination is arbitrarily drunk water and is got food.Be divided into 6 groups at random, normal control group (abbreviation normal group) wherein, Meynert nuclear injecting normal saline in 6 weeks of intraperitoneal injection of saline and the brain, AD model group (abbreviation model group), bilateral Meynert nuclear injection IBO in lumbar injection D_ galactose (48mg/kg/d) 6 week and the brain, huperzine A matched group (abbreviation huperzine A group) and tried all same model group of thing observation group modeling.Intracerebral injection carries out with reference to relevant document behind lumbar injection
[1]After modeling finished, the huperzine A group was irritated stomach and is given huperzine A 50ug/kg, and kurarinone, matrine and sophocarpine group are irritated stomach medicine 60mg/kg respectively.Normal group, model group give the normal saline with volume.Successive administration 7 days, carries out learning capacity and detects after 1 hour in the last administration, rat is anaesthetized with pentobarbital then, ventral aorta blood sampling 5ml on the ice platform, the rapid taking-up of dissection cerebral cortex as the homogenate medium, is made the homogenate of 10% (W/V) brain cortical tissue with normal saline.According to the mensuration of test kit explanation carrying out acetylcholine esterase active, the mensuration of the acetylcholine esterase active of whole blood is carried out according to literature method
[2]
3. detection index: animal memory behavior test: the passive avoidance step down test, rat is put reaction chamber endoadaptation environment 3min.Pass to the 50V alternating current then.After rat is shocked by electricity.Escape reaction is for jumping onto platform to hide noxious stimulation.Record be subjected in the 5min number of shocks (errors number) as school grade with the response learning ability.Directly rat is placed on the platform behind the 24h.Write down incubation period of jumping off for the 1st time with errors number in reaction memory ability and the 5min, surpass 5min person incubation period in 5min.
Relatively t check between date processing employing group, with p＜0.05 as the statistical significance index.
4. result: 3 kinds of Radix Sophorae Flavescentis alkaloids all can reduce whole blood and cerebral tissue acetylcholine esterase level, improve learning and memory in rats achievement (table 4,5)
3 kinds of Radix Sophorae Flavescentis alkaloids of table 4 are to the influence of TChE level in rat whole blood and the cerebral tissue
| Group | N | Whole blood TchE (mmol/L) | Suppression ratio | Cerebral tissue TchE (umol/g) | Suppression ratio |
| Normal control model contrast huperzine A contrast kurarinone matrine sophocarpine | 10 10 8 10 9 10 | 76±28 84±32 48±35 * 37±29 * 26±35 * 33±27 * | - - 42.86％ 55.95％ 69.05％ 60.71％ | 3.4±0.7 3.8±0.9 2.0±0.6 * 1.4±0.7 ** 1.6±0.8 ** 1.8±0.9 ** | - - 41.18％ 58.82％ 52.94％ 47.06％ |
Compare with model group
*P＜0.05;
*P＜0.01
3 kinds of Radix Sophorae Flavescentis alkaloids of table 5 are to the influence of rat step down test learning and memory ability
| Group | Errors number in the 5min | Incubation period (s) | Errors number in the 5min behind the 24h |
| Normal control model contrast huperzine A contrast kurarinone matrine sophocarpine | 0.9±0.7 16±7.6 4±2.3 * 5±1.9 * 3±2.2 * 4±2.7 * | 237±86 78±27 135±55 * 187±43 * 222±78 * 112±41 * | 0.3±0.2 9±4.2 2±1.6 * 4±2.1 * 3±1.0 * 2±1.5 * |
Compare with model group
*P＜0.05
Embodiment 4 Radix Sophorae Flavescentis alkaloid percutaneous dosings are to the preventive effect of senile dementia rat
1. animal model and 30 of male SD rats of grouping are made Model of Dementia in Rats according to embodiment 3 methods for 20, and 10 is the blank group.Rat model is divided into Radix Sophorae Flavescentis alkaloid paster group and model control group at random, 10 every group.Matrine paster group gives 1/Mus of matrine paster (self-control, and alkaloid meter 500mg) in modeling, change a paster after per 3 days, finishes back 3 days until modeling.Respectively at measuring the learning and memory achievement before the administration and after the administration, put to death rat extracting blood then, measure whole blood cholinesterase activity.
2. before observation index is observed administration, the activity of blood cholinesterase after the administration, and learning and memory achievement.Method is with embodiment 3
3. result: Radix Sophorae Flavescentis alkaloid paster group can obviously be improved the learning and memory achievement (table 6) of dementia rats.
Table 6. Radix Sophorae Flavescentis alkaloid paster is to the improvement effect of dementia rats learning and memory achievement
| Group | Errors number in the 5min | Incubation period (s) | Errors number in the 5min behind the 24h |
| Normal control model contrast matrine paster | 0.7±0.5 12±3.6 4±2.9 * | 287±121 66±19 175±53 * | 0.5±0.3 11±6.4 2±3.8 * |
Compare with model group:
*P＜0.05
List of references
1 Hu Jingqing, Lai Shilong, Wang Qi waits the .D_ galactose to quicken the preliminary observation [J] of the old and feeble Meynert of merging nuclear damage learning and memory in rats capacity variation. Chinese geriatrics magazine, 2000,19 (2): 5
Before 2 Lee, Liu Wei, Li Fengzhen, etc. there are the two 2 nitrobenzoic acid spectrophotometries of 5,5 ' two sulfur of cholinesterase activity down in hemoglobin. Chinese sanitary inspection magazine, 2001,11:268
Claims (10)
1. the invention provides the medicinal usage of matrine alkaloid in treatment and prevention senile dementia disease.
2. the invention provides the purposes of matrine alkaloid in the low property of treatment children's intelligence disease.
3. the invention provides the medicinal usage of matrine alkaloid in muscular contraction force decline diseases such as treatment myasthenia graviss.
4. the invention provides the medicinal usage of matrine alkaloid in the sleep disordered disease of treatment.
5. the invention provides the medicinal usage of matrine alkaloid at the rescue organophosphate poisoning.
6. comprise isomer sophoridine, Iosmatrine of matrine, oxymatrine, sophocarpine, N-oxysophocarpine, sophoranol, supanine and matrine etc. by the described matrine alkaloid of claim 1-5, its architectural feature is to have tetracyclic quinolizine pyridine, as scheming:
The basic structure of matrine alkaloid
7. can from plant, obtain by extraction separation by the described matrine alkaloid of claim 6, also can chemosynthesis.
8. comprise that by the described senile dementia of claim 1 alzheimer disease, vascular dementia, Combination are dull-witted and other are dull-witted.
9. can make injection by the described matrine alkaloid of claim 6 with different dressing in effective dose, injection powder injection, tablet, capsule, paster, preparations such as gel, with injecting pathway, oral route and mucocutaneous route of administration to patient's administration.
10. can make medicine as effective ingredient with an alkaloid by claim 2 and 3 described matrine alkaloids, also can several alkaloids composition compositionss make the Drug therapy senile dementia as effective ingredient.For example, the kurarinone sheet is effective ingredient with the oxymatrine; Matrine injection is main component with the matrine; The effective ingredient of Radix Sophorae Flavescentis alkaloid gel comprises matrine, oxymatrine, sophocarpine, N-oxysophocarpine and sophoranol.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102657645A (en) * | 2012-05-08 | 2012-09-12 | 吉林大学 | Application of matrine in preparing drug for preventing and treating alzheimer disease |
| CN103301190A (en) * | 2012-06-19 | 2013-09-18 | 中国医学科学院药用植物研究所 | Extracts of vietnamese sophora root and application thereof |
| KR102057440B1 (en) | 2019-02-14 | 2019-12-20 | 경희대학교 산학협력단 | Composition containing sophora flavescens extract or matrine for sedation or sleeping induction |
-
2004
- 2004-11-07 CN CN 200410036218 patent/CN1768746A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102657645A (en) * | 2012-05-08 | 2012-09-12 | 吉林大学 | Application of matrine in preparing drug for preventing and treating alzheimer disease |
| CN103301190A (en) * | 2012-06-19 | 2013-09-18 | 中国医学科学院药用植物研究所 | Extracts of vietnamese sophora root and application thereof |
| CN103301190B (en) * | 2012-06-19 | 2015-10-14 | 中国医学科学院药用植物研究所 | The extract of Radix Sophorae Tonkinensis and application thereof |
| KR102057440B1 (en) | 2019-02-14 | 2019-12-20 | 경희대학교 산학협력단 | Composition containing sophora flavescens extract or matrine for sedation or sleeping induction |
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