CN1546111A - Application of Naoxinqing Tablet in the preparation of medicine for preventing and treating nerve function retrograde affection - Google Patents
Application of Naoxinqing Tablet in the preparation of medicine for preventing and treating nerve function retrograde affection Download PDFInfo
- Publication number
- CN1546111A CN1546111A CNA2003101124268A CN200310112426A CN1546111A CN 1546111 A CN1546111 A CN 1546111A CN A2003101124268 A CNA2003101124268 A CN A2003101124268A CN 200310112426 A CN200310112426 A CN 200310112426A CN 1546111 A CN1546111 A CN 1546111A
- Authority
- CN
- China
- Prior art keywords
- group
- rat
- treatment
- medicine
- brain heart
- 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.)
- Granted
Links
- 239000003814 drug Substances 0.000 title claims abstract description 36
- 238000002360 preparation method Methods 0.000 title claims description 8
- 210000005036 nerve Anatomy 0.000 title abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 27
- 201000010099 disease Diseases 0.000 claims description 25
- 210000000653 nervous system Anatomy 0.000 claims description 15
- 208000024827 Alzheimer disease Diseases 0.000 claims description 14
- 230000007850 degeneration Effects 0.000 claims description 12
- 206010039966 Senile dementia Diseases 0.000 claims description 7
- 210000004556 brain Anatomy 0.000 abstract description 42
- 244000236655 Diospyros kaki Species 0.000 abstract description 4
- 239000000284 extract Substances 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 abstract 6
- 235000019439 ethyl acetate Nutrition 0.000 abstract 2
- 235000011511 Diospyros Nutrition 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 241000700159 Rattus Species 0.000 description 41
- 230000000694 effects Effects 0.000 description 21
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 19
- 230000006870 function Effects 0.000 description 16
- 208000028867 ischemia Diseases 0.000 description 13
- 229940079593 drug Drugs 0.000 description 11
- 230000001681 protective effect Effects 0.000 description 11
- 208000024891 symptom Diseases 0.000 description 11
- 230000000302 ischemic effect Effects 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 238000011160 research Methods 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 230000000971 hippocampal effect Effects 0.000 description 8
- 210000001320 hippocampus Anatomy 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 230000005779 cell damage Effects 0.000 description 7
- 208000037887 cell injury Diseases 0.000 description 7
- 229960003980 galantamine Drugs 0.000 description 7
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 7
- 210000003061 neural cell Anatomy 0.000 description 7
- 210000004129 prosencephalon Anatomy 0.000 description 7
- 210000002763 pyramidal cell Anatomy 0.000 description 7
- 230000010410 reperfusion Effects 0.000 description 7
- 201000006474 Brain Ischemia Diseases 0.000 description 6
- 206010012289 Dementia Diseases 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 230000002490 cerebral effect Effects 0.000 description 6
- 230000003203 everyday effect Effects 0.000 description 6
- 230000010354 integration Effects 0.000 description 6
- 108700017511 rat Y acceptor Proteins 0.000 description 6
- 210000002784 stomach Anatomy 0.000 description 6
- 206010008120 Cerebral ischaemia Diseases 0.000 description 5
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 5
- 230000006399 behavior Effects 0.000 description 5
- 230000017531 blood circulation Effects 0.000 description 5
- 206010008118 cerebral infarction Diseases 0.000 description 5
- 230000005611 electricity Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 206010022437 insomnia Diseases 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 206010013952 Dysphonia Diseases 0.000 description 4
- 201000004810 Vascular dementia Diseases 0.000 description 4
- 210000003701 histiocyte Anatomy 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 206010034754 petechiae Diseases 0.000 description 4
- 235000008597 Diospyros kaki Nutrition 0.000 description 3
- 206010022998 Irritability Diseases 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 208000026106 cerebrovascular disease Diseases 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 208000037920 primary disease Diseases 0.000 description 3
- 238000012549 training Methods 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 206010001497 Agitation Diseases 0.000 description 2
- 206010008132 Cerebral thrombosis Diseases 0.000 description 2
- 206010008190 Cerebrovascular accident Diseases 0.000 description 2
- 241000218628 Ginkgo Species 0.000 description 2
- 235000011201 Ginkgo Nutrition 0.000 description 2
- 235000008100 Ginkgo biloba Nutrition 0.000 description 2
- 206010019233 Headaches Diseases 0.000 description 2
- 206010062717 Increased upper airway secretion Diseases 0.000 description 2
- 206010021703 Indifference Diseases 0.000 description 2
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 206010056677 Nerve degeneration Diseases 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 208000002173 dizziness Diseases 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 230000009191 jumping Effects 0.000 description 2
- 230000006386 memory function Effects 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 208000026435 phlegm Diseases 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 208000006888 Agnosia Diseases 0.000 description 1
- 241001047040 Agnosia Species 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010003062 Apraxia Diseases 0.000 description 1
- 206010003084 Areflexia Diseases 0.000 description 1
- 206010065559 Cerebral arteriosclerosis Diseases 0.000 description 1
- 206010012218 Delirium Diseases 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
- 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 1
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- ZRJBHWIHUMBLCN-UHFFFAOYSA-N Shuangyiping Natural products N1C(=O)C=CC2=C1CC1C(=CC)C2(N)CC(C)=C1 ZRJBHWIHUMBLCN-UHFFFAOYSA-N 0.000 description 1
- 208000032023 Signs and Symptoms Diseases 0.000 description 1
- 208000032109 Transient ischaemic attack Diseases 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000003035 anti-peroxidant effect Effects 0.000 description 1
- 201000007201 aphasia Diseases 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 210000001841 basilar artery Anatomy 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 210000003792 cranial nerve Anatomy 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 230000003419 expectorant effect Effects 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- ZRJBHWIHUMBLCN-YQEJDHNASA-N huperzine A Chemical compound N1C(=O)C=CC2=C1C[C@H]1\C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-YQEJDHNASA-N 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 201000005851 intracranial arteriosclerosis Diseases 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
- 229960003987 melatonin Drugs 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000029052 metamorphosis Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 239000009335 naoxintong Substances 0.000 description 1
- 230000003961 neuronal insult Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 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 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000028527 righting reflex Effects 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 230000009758 senescence Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 210000002385 vertebral artery Anatomy 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
Images
Abstract
The invention relates to the use of Brain Refreshing Tablet in preparing medicament for prevention and treatment of nerve functional catagenesis, wherein the Brain Refreshing Tablet is prepared from the active component of acetic ester extract from persimmon leaves, each tablet contains acetic ester extract 50mg.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to the application of NAOXINQING PIAN in preparation control function of nervous system degeneration disease medicine.
Background technology
" NAOXINQING PIAN " is that the ethyl acetate extract by Folium Kaki is the Chinese patent medicine that active component is made, and is mainly used in diseases such as treatment cerebral arteriosclerosis, transient ischemic attack, cerebral thrombosis, cerebral thrombosis sequela, angina pectoris.
Function of nervous system's degeneration disease is the mid-aged population commonly encountered diseases, elderly dementia's disease wherein be a kind of be the neurodegenerative disease of feature with intelligence, hypomnesis, comprise AD and VD, the obstacle that the AD disease is the most outstanding is cognitive dysmnesia, and VD then is to be the nerve degeneration disease of main cause with the cerebral ischemia.Be used for function of nervous system's degeneration disease treatment of diseases expense domestic every year up to last 1,000,000,000 yuan, the whole world brings heavy burden for family and society especially up to multi-million dollar.A great medical problem is not only in the control of this disease, also is the social problem of a sternness simultaneously, so we are necessary to develop the new drug of control function of nervous system degeneration disease.
Theory of Chinese medical science think function of nervous system's degeneration disease be kidney qi and the five internal organs gradually void decline on the basis since the stagnation of QI, blood stasis, expectorant turbid due to, promptly deficiency of kidney-essence is this, negative and positive are empty partially for becoming, and stasis of blood stagnation of phlegm key is the key of morbidity, and its morbidity and senescence process are closely related.Folium Kaki bitter in the mouth, cold in nature, have blood circulation promoting and blood stasis dispelling, lung heat clearing, heat-clearing and toxic substances removing, the diuresis that purifies the blood, etc. effect.So supposition is the control that the NAOXINQING PIAN of raw material can be used for function of nervous system's degeneration disease with the Folium Kaki extract.
At present, neurodegenerative disease does not still have good Therapeutic Method and medicine, mainly is at different cause of disease hypothesis, has proposed the method for multiple alternative drugs treatment.As galantamine, huperzine A (Huperzine A-Zhulin Antun), vitamin E, nerve growth factor (NGF), melatonin treatment AD, dopamine is controlled PD.But these clinical applications have again because of its toxic and side effects has limited application, the medicine of therefore developing new treatment nerve degeneration disease is necessary.
NAOXINQING PIAN clinical practice is not seen the report that is useful on control function of nervous system degeneration disease for many years.
Summary of the invention
The range of application that the objective of the invention is further expansion " the brain heart is clear " sheet is for control function of nervous system degeneration disease provides a kind of new product.
The present invention confirms by effect experiment and clinical trial: " NAOXINQING PIAN " can be used for preparing the medicine of control function of nervous system degeneration disease, in particular for preparation control medicine for senile dementia.
In order to understand essence of the present invention better, test in animal body and human clinical trial result with " the brain heart is clear " sheet below, its new purposes in pharmaceutical field is described.
Animal vivo test
One, NAOXINQING PIAN is to AlCl
3Cause the influence of AD disease model rat learning and memory function
1. experiment material: NAOXINQING PIAN (every contains dried cream 50mg) is made into the suspension of suitable concn with normal saline; Experimental animal is used 90 of Healthy female SD rats, body weight 340g～360g, rat is divided into normal group (N group), model group (M group), the brain heart clear low dose of (NXQ1 group), the clear middle dosage (NXQ2 group) of the brain heart, the aloof from politics and material pursuits dosage group of the brain heart (NXQ3 group), matched group (galantamine 30mg), 15 every group at random.
2. main agents and instrument AlCl
3(Sigma company); Galantamine (Sigma company); MG2 type Y electricity labyrinth instrument.
3. experimental technique
3.1 the making of AD model
M group, NXQ1,2,3 groups, galantamine group rat lumbar injection every day 1ml concentration are the sterilization AlCl of 9mg/ml
3TSolution, every injection continuously 3 days 1 day at interval, amounts to 72 days.N group rats by intraperitoneal injection 1ml sterile saline, injection cycle and time are the same.
3.2 administration (carrying out simultaneously) with the making of AD model
NXQ1,2,3 groups, galantamine group rat irritate stomach 15ml/kg/ time every day, every day secondary, every continuous irrigation stomach 7 days 1 day at interval, amounts to 72 days.NXQ1 group is each irritates the clear 20mg/kg of the stomach brain heart (dosage of quite being grown up 1/2 times), NXQ2 group is irritated stomach 40mg/kg (dosage of quite being grown up 1 times), NXQ3 group is irritated stomach 80mg/kg (dosage of quite being grown up 2 times), galantamine 60mg/kg (dosage of quite being grown up 2 times), N group and M group rat oral gavage equivalent physiological water, cycle and time are the same.
3.3 memory behavior is measured
After modeling and medication finish, under the condition of night peace and quiet and lucifuge, study with instrument training of Y type electricity labyrinth and mensuration rat obtains and the memory hold facility, voltage 90V, time delay is 1s, train continuously and measure 10 times/only/day, write down the escape latency of rat simultaneously and escape accuracy etc., continuous 4 days.After being subjected to electricity irritation, rat directly escapes to escape for correct to place, safety arm lamp source from energising arm lamp source, and the used time is escape latency.If rat is slack halfway after not escaping or escaping after the electricity irritation, then their escape latency is pressed 2 times of calculating of normal rat average escape latency.
3.4 date processing numerical value is all represented with means standard deviation.With the significance of difference of escape latency between the different variance t check of two samples comparable group, with the significance of difference of escaping accuracy between the rank test comparable group.
4. result
4.1 the brain heart is escaped the influence of accuracy clearly to rat Y labyrinth
In the preceding 3 days test of continuous training, the escape accuracy of M group is minimum, NXQ high dose group the highest.To the 4th day, the escape accuracy of M group did not obviously raise again, and other continuation of 5 groups raise, and the escape accuracy of M group is starkly lower than N group (P＜0.05), NXQ1,2,3 and the galantamine group apparently higher than M group (P＜0.05, or P＜0.001) (seeing Table 1).
Table 1 is respectively organized rat Y labyrinth and is escaped accuracy (x ± s)
| Group | Dosage mg/kg | The 1st day | The 2nd day | The 3rd day | The 4th day |
| N group M group NXQ1 NXQ2 NXQ3 galantamine | ????0 ????0 ????20 ????40 ????80 ????60 | ?0.55±0.23 ?0.50±0.29 ?0.52±0.26 ?0.56±0.27 ?0.55±0.26 ?0.58±0.29 | ?0.73±0.25 ?0.63±0.26 ?0.67±0.24 ?0.70±0.26 ?0.72±0.23 ?0.73±0.25 | ?0.91±0.17 ?0.81±0.19 ?0.86±0.20 ?0.89±0.17 ?0.92±0.09 *?0.90±0.10 | 0.98±0.12 0.85±0.11# 0.95±0.12 *0.98±0.09 **0.99±0.07 **0.98±0.10 ** |
Annotate: compare with the N group: #P＜0.05; Compare with the M group:
*P＜0.05,
*P＜0.0012 time with.
4.2 the brain heart is clearly to the influence of rat Y labyrinth escape latency
Training is after 3 days continuously, and the 4th day mensuration is respectively organized the escape latency of rat.The escape latency of M group is widely different, prolongs (P＜0.05) than N group significance; NXQ1,2,3 groups and galantamine group all shorten (P＜0.05, or P＜0.01) than M group significance, and be more remarkable with the middle and high dosage group of NXQ.(seeing Table 2)
Table 2 is respectively organized rat Y labyrinth escape latency (x ± s)
| Group | Dosage mg/kg | Number of animals n | Incubation period (second) |
| N group M group NXQ1 NXQ2 NXQ3 galantamine | ????0 ????0 ????20 ????40 ????80 ????60 | ????13 ????12 ????13 ????13 ????14 ????13 | ????3.8±2.4 ????7.5±3.9# ????5.2±3.6 ????4.5±2.7* ????3.5±2.6** ????3.8±2.5** |
Annotate: compare with the N group: #P＜0.05; Compare with the M group:
*P＜0.05,
*P＜0.0012
4.3. NAOXINQING PIAN is to the influence of rat Y labyrinth escape behavior's mode
The M group shows as to escape and starts obstacle, and indivedual rats not escape, and escape Halfway Stopping or terminal point mistake.After administration was intervened, escape behavior's mode of middle and high dosage of NAOXINQING PIAN and galantamine group was obviously improved (seeing Table 3).
Table 3 is respectively organized the difference of rat Y labyrinth escape behavior's mode
| Group | Starting mode | Escape speed | Escape terminal point |
| N M NXQ1 NXQ2 NXQ3 galantamine | Directly vow jump acutely toward the light place that jumping spins for several times and vow again toward light place and M group after a few similar, but jumping spring severe degree, but jump the spring severe degree, the number of times and the number of turns of spinning obviously reduce direct the arrow toward the light place and vow that directly past light place directly vows toward the light place | Trotting sprints sprints | Place, safety arm lamp source safety arm proximal part; Knock the labyrinth instrument and only can order about the minority rat near lamp source place safety arm proximal part, knock the labyrinth instrument after great majority trot at once to place, safety arm lamp source, place, safety arm lamp source, place, safety arm lamp source, place, lamp source |
Conclusion: AlCl
3The rat AD model that duplicates is one of animal model of research AD pathogenesis and control drug screening.Give AlCl
3Test with the Y labyrinth after causing the Alzheimer disease model rat to take NAOXINQING PIAN, mice learning and memory function is improved as a result.Show that NAOXINQING PIAN has therapeutical effect to alzheimer disease.
Two, NAOXINQING PIAN is to the neuronic protective effect of preceding cerebral ischemia
1. experiment material
NAOXINQING PIAN (every contains dried cream 50mg) is made into the suspension of suitable concn with normal saline;
Experimental animal is used 90 of Healthy female SD rats, body weight 180g～220g, rat is divided into normal group (N group), model group (M group), the brain heart clear low dose of (NXQ1 group), the clear middle dosage (NXQ2 group) of the brain heart, 15 every group of the aloof from politics and material pursuits dosage group of the brain heart (NXQ3), matched groups (taponin) at random.Administration: administration 12 days (preceding 4 days of ischemia-reperfusion, back 7 days).Stomach water, every day 2 times are irritated in the abdominal cavity.
2. experimental technique
Ischemical reperfusion injury model preparation: carry out with reference to cerebral ischemic model before " pharmacological experimental methodology " Pulsinelli rat four blood vessel blockings.
Preceding cerebral ischemia re-pouring: electricity consumption was coagulated vertebra basilar artery blocking-up vertebral artery blood flow after 24 hours, closed bilateral carotid with the bulldog clamp folder, and blocking blood flow 15 minutes causes preceding cerebral ischemia.Righting reflex loss, platycoria or the like appear in the rat of preceding cerebral ischemic model success immediately.Remove bulldog clamp after 15 minutes, recover supply of blood flow.Recover behind the supply of blood flow in 30～50 minutes rat and stand up again, recover autonomic activities, global brain ischemia is poured into the moulding success again.Rat put in the withdrawal of currency from circulation raise, by the dosage regimen administration.Observe rat behavior and survival condition every day.Ischemia-reperfusion is kill animals after 7 days, gets cerebral hippocampus fixedly sections observation cranial nerve cell apoptosis and metamorphosis; And the pyramidal cell density of calculating survival (individual/mm).The experimental data statistics: data are represented with x ± s, respectively organize the significance of data difference with variance analysis and the analysis of t method of inspection.
3, experimental result:
1. rat hippocampal organism optical microscopically tissue morphology: under the low power lens, normal rat cerebral hippocampal tissue shows " C " shape, is divided into CA1, CA2, CA3 district, and there are 3～4 floor pyramidal cell, marshalling in the CA1 district; Under the high power lens, pyramidal cell nuclear is big and there is 1～2 kernel in the garden, and pyramidal cell density is 185.5 ± 17.1 (seeing Fig. 1, table 4)
2. ischemia-reperfusion is 7 days, the damage of visible obviously rat hippocampal histiocyte.Normal saline group rat hippocampal CA1 district pyramidal cell is most of dead, cell debris distribution at random (seeing Fig. 2, table 4)
3. the brain heart that gives various dose is clear, and rat hippocampal histiocyte damage due to the ischemia-reperfusion is had doses dependency protective effect (seeing Fig. 3-5, table 4).
The clear group of the brain heart that is equivalent to people's usual amounts obviously alleviates rat hippocampal CA1 district neuronal damage due to the ischemia-reperfusion, and its work pyramidal cell density is than the obvious increase of control rats.The integral animal situation is improved, and the activity of rat outward appearance is normal, and fur is smooth, and it is not obvious to lose weight.The animals survived number is obvious more than matched group behind the ischemia-reperfusion.Show that the brain heart has protective effect to acute ischemia clearly.This treats apoplexy for NAOXINQING PIAN and apoplexy sequela provides experimental basis.
4. positive control drug taponin capsule (100mg/kg; be equivalent to people's usual amounts): rat hippocampal histiocyte form is normal substantially; pyramidal cell density obviously increases (P＜0.05 than normal saline group; see Fig. 6, table 4), rat hippocampal histiocyte damage due to the ischemia-reperfusion also there is obvious protective effect.
Table 4: NAOXINQING PIAN causes the protective effect of rat hippocampus CA1 cone neural cell injury to the forebrain ischemic reperfusion
| Group | Number of animals | Cone neurocyte density (/mm) |
| Normal control | 6 | 185.5±17.1 |
| Normal saline | ?6 | ?7.1±3.4 ** |
| The clear 10mg/kg of the brain heart | ?6 | ?32.7±22.8 ### |
| The clear 40mg/kg of the brain heart | ?6 | ?74.7±17.7 ### |
| The clear 80mg/kg of the brain heart | ?6 | ?81.7±19.7 ### |
| Taponin 100mg/kg | ?6 | ?47.7±16.0 ### |
Annotate:
*P＞0.05,
*＜0.05,
* *Compare with matched group p＜0.01
#P＞0.05,
##＜0.05,
###Compare with the normal saline group p＜0.01
Conclusion: the NAOXINQING PIAN that studies show that of the present invention is except the drug action of former confirmation; can also remove free radical, anti peroxidation of lipid, anti-acute cerebral ischemia; can suppress the brain tissue apoptosis that ischemia-reperfusion causes; the brain tissue impairment that ischemia-reperfusion is caused has significant protective effect, and can improve the cerebral tissue function of nervous system that ischemia-reperfusion causes.
The clinical verification of control function of nervous system degeneration disease
One, to the preventive and therapeutic effect of vascular dementia:
1 data and method
1.1 case situation: all case all is the department of neurology inpatient, male's 70 examples, women's 20 examples; 58～76 years old age, average 64.9 years old; The course of disease is the shortest 1 year, and is the longest 10 years, average 3.9 years.Do clinical examination, the test of neural scale by the main Neurology Department doctor who grinds cerebrovascular disease, and through head CT or MR prover.
1.2 diagnostic criteria: adopt the diagnostic criteria of DSM-IV medium vessels dementia.
(1) many-sided cognitive defect takes place, show as following the two: memory impairment; At least one of following cognitive disorder: the obstacle of aphasia, apraxia, agnosia, execution managerial function.
(2) above any 1 cognitive disorder has caused tangible society and occupational function defective, and before can finding that these functions obviously are not so good as.
(3) there are limitation nervous system signs and symptom; Or the laboratory evidence of pointing out cerebrovascular disease is arranged, and can think the reason of this obstacle
(4) these defectives are no thanks to due to the delirium.
Concrete reference: new Chinese medicine clinical research guideline; The clinical research guideline of new Chinese medicine treatment senile dementia.
1.3 exclusion standard: primary disease and Hai Jinsiji ischemia index scales (HIS) such as serious nerve, blood, endocrine are arranged, total points 18 minutes, score＜7 are divided into alzheimer disease person.
1.4 scale is selected: 1 U.S.'s simple intelligent scale, total points 30 minutes is if score＜16 minute person is a disturbance of intelligence; 2 Japanese Chang Gu river Dementia scale, total points 30 minutes is if score＜16 minute person is dull-witted the establishment; 3 Hai Jinsiji ischemia index scales (HIS), total points 18 minutes, if score＞7 minute person is a vascular dementia, score＜7 minute person is an alzheimer disease.
1.5 traditional Chinese medical science cardinal symptom: with reference to new Chinese medicine clinical research guideline; The clinical research guideline of new Chinese medicine treatment senile dementia.
In conjunction with clinical experience, with following symptom as observation index: dull expression, dysphonia, or speaking scarcely,taciturn or language perversion, forgetful, be insomnia dizziness, headache, body of the tongue petechia.
1.6 criterion of therapeutical effect: adopt the Comprehensive Assessment method, comment content with the change of aspects such as the intellectual status before and after the patient treatment, traditional Chinese medical science cardinal symptom, sign as combining, and change into emphasis with intelligence.Cured person Chang Gu river Dementia scale test score is increased to normal value, and produce effects person's score increased more than 5 minutes, and responder's score increases less than 5 minutes, and nonresponder's score does not only have increase and descends on the contrary.
1.7 administrated method: morning, noon and afternoon every day are respectively obeyed 4 of NAOXINQING PIAN, and 2 months was 1 course of treatment, and all 3 courses of treatment of medication, other cerebral vasodilators medicine of stopping using therebetween, brain cell metabolic drug, function of nervous system regulate medicine.
2 curative effects and result
2.1 the scale integration changes before and after the treatment: (seeing Table 5,6)
Simple intelligent scale integration variation before and after table 5 treatment (x ± s)
| The medicine group | ????n | Before the treatment | After the treatment | ????P |
| The clear taponin of the brain heart | ????30 ????30 | ????13.45±5.42 ????13.58±5.38 | ????19.45±6.09 ????19.30±6.06 | ????＜0.05 ????＜0.05 |
Dementia scale integration variation in Chang Gu river before and after table 6 treatment (x ± s)
| The scale name | n | Before the treatment | After the treatment | P |
| The clear taponin of the brain heart | 30 30 | ?12.95±5.62 ?12.98±5.78 | ?18.83±6.19 ?18.72±6.36 | ＜0.05 ＜0.05 |
2.2 traditional Chinese medical science cardinal symptom changes: (seeing Table 7)
Cardinal symptom scoring variation before and after table 7 treatment (x ± s)
| Cardinal symptom | Medicine | ????n | Before the treatment | After the treatment | ??P |
| Dull expression | The clear taponin of the brain heart | ????30 | ??3.35±0.54 ??3.28±0.51 | ??2.31±0.80 ??2.30±0.81 | ??＜0.01 ??＜0.01 |
| Dysphonia | The clear taponin of the brain heart | ????28 | ??3.31±0.65 ??3.31±0.65 | ??2.28±0.93 ??2.31±0.95 | ??＜0.01 ??＜0.01 |
| Forgetful being insomnia | The clear taponin of the brain heart | ????29 | ??3.33±0.56 ??3.31±0.56 | ??1.31±0.95 ??1.33±0.93 | ??＜0.01 ??＜0.01 |
| Dizziness headache | The clear taponin of the brain heart | ????30 | ??3.13±0.85 ??3.16±0.85 | ??1.31±0.85 ??1.30±0.83 | ??＜0.01 ??＜0.01 |
| The body of the tongue petechia | The clear taponin of the brain heart | ????30 | ??2.03±0.42 ??2.05±0.42 | ??1.28±0.64 ??1.29±0.61 | ??＜0.01 ??＜0.01 |
2.3 efficacy analysis: (seeing Table 8)
Two kinds of medicines of table 8 are added up the vascular dementia curative effect
| Name of disease | n | Recovery from illness | Produce effects | Effectively | Invalid | Total effective rate | ||||
| Example | Rate % | Example | Rate % | Example | Rate % | Example | Rate % | ??％ | ||
| The brain heart is clear | 30 | ??0???????0 | ??5???????16.7 | ??18??????60.0 | ??7???????23.3 | ??76.7 | ||||
| Taponin | 30 | ??0???????0 | ??5???????16.3 | ??17??????56.7 | ??8???????26.7 | ??73.3 | ||||
3 conclusions
NAOXINQING PIAN is to the intelligence improvement effect of vascular dementia: can see from 5,6,7 tables, 60 routine patients are through the clothes brain heart cleer and peaceful taponin after 3 courses of treatment, the scale score of two medicines treatment all obviously increases (P＜0.01), illustrates all to regain the strength of memory, improve the intelligence effect.Can know that from 8 tables NAOXINTONG is 76.7% to the total effective rate of primary disease, although cured person is zero, produce effects 5 examples only, effective percentage accounts for half many (60.0%).Both curative effect there was no significant differences of the cleer and peaceful taponin of the brain heart.
Two, to the preventive and therapeutic effect of senile dementia:
1 data and method
1.1 case situation: all case all is the department of neurology inpatient, male's 19 examples, women's 11 examples; 58～76 years old age, average 64.9 years old; The course of disease is the shortest 1 year, and is the longest 10 years, average 3 years.Do clinical examination, the test of neural scale by the main Neurology Department doctor who grinds cerebrovascular disease, and through head CT or MR prover.
1.2 diagnostic criteria: concrete reference: new Chinese medicine clinical research guideline; The clinical research guideline of new Chinese medicine treatment senile dementia.
1.3 exclusion standard: (ditto)
1.4 scale is selected: (ditto)
1.5 traditional Chinese medical science cardinal symptom: (ditto)
1.6 criterion of therapeutical effect: (ditto) above 1.3～1.6 is with reference to new Chinese medicine clinical research guideline; The clinical research guideline of new Chinese medicine treatment senile dementia.
1.7 administrated method: (ditto)
2 curative effects and result
2.1 the scale integration changes before and after the treatment: (seeing Table 9,10)
Simple intelligent scale integration variation before and after table 9 treatment (x ± s)
| The medicine group | ????n | Before the treatment | After the treatment | ????P |
| The clear taponin of the brain heart | ????36 ????33 | ??13.45±5.42 ??12.98±5.78 | ??20.35±6.09 ??19.72±6.86 | ????＜0.05 ????＜0.05 |
Dementia scale integration variation in Chang Gu river before and after table 10 treatment (x ± s)
| The scale name | ????n | Before the treatment | After the treatment | ????P |
| The clear taponin of the brain heart | ????36 ????33 | ??12.35±5.42 ??12.18±5.78 | ??19.65±6.19 ??19.32±6.16 | ????＜0.05 ????＜0.05 |
2.2 traditional Chinese medical science cardinal symptom changes: see Table 11
Cardinal symptom variation before and after table 11 treatment (x ± s)
| Cardinal symptom | Medicine | ????n | Before the treatment | After the treatment | ????P |
| Dull expression | The clear taponin of the brain heart | ????33 ????31 | ????3.15±0.54 ????3.13±0.56 | ????2.31±0.85 ????2.32±0.86 | ????＜0.01 ????＜0.01 |
| Dysphonia | The clear taponin of the brain heart | ????28 ????26 | ????3.33±0.66 ????3.32±0.63 | ????2.28±0.91 ????2.29±0.92 | ????＜0.01 ????＜0.01 |
| The contemplative faculty obstacle | The clear taponin of the brain heart | ????33 ????30 | ????3.58±0.64 ????3.56±0.62 | ????2.75±0.88 ????2.74±0.86 | ????＜0.05 ????＜0.05 |
| The judgment obstacle | The clear taponin of the brain heart | ????34 ????32 | ????3.35±0.85 ????3.33±0.83 | ????2.48±0.95 ????2.53±0.89 | ????＜0.05 ????＜0.05 |
| Memory disorder | The clear taponin of the brain heart | ????36 ????33 | ????3.46±0.85 ????3.47±0.87 | ????2.58±0.95 ????2.56±0.98 | ????＜0.05 ????＜0.05 |
| Forgetful being insomnia | The clear taponin of the brain heart | ????35 ????32 | ????3.31±0.54 ????3.32±0.55 | ????1.31±0.95 ????1.46±0.98 | ????＜0.01 ????＜0.01 |
| Irritated, irritability | The clear taponin of the brain heart | ????36 ????33 | ????3.53±0.85 ????3.49±0.85 | ????1.53±0.81 ????1.60±0.85 | ????＜0.01 ????＜0.01 |
| The body of the tongue petechia | The clear taponin of the brain heart | ????36 ????33 | ????2.13±0.40 ????2.15±0.43 | ????1.18±0.62 ????1.23±0.64 | ????＜0.01 ????＜0.01 |
2.3 efficacy analysis: see Table 12
Two kinds of medicines of table 12 are added up the alzheimer disease curative effect
| Name of disease | ??n | Recovery from illness | Produce effects | Effectively | Invalid | Total effective rate | ||||
| Example | Rate % | Example | Rate % | Example | Rate % | Example | Rate % | ???％ | ||
| The brain heart is clear | 36 | ?0????0 | ?6??16.7 | ?21??58.3 | ?9??25.0 | ??75.0 |
| Taponin | 33 | ?0????0 | ?4??10.0 | ?19??57.6 | ?9??27.3 | ??72.3 |
Can know that from 12 tables the brain heart is 75.0% to the total effective rate of primary disease clearly, produce effects 16.7%, slightly higher than 70% total effective rate of present medicine commonly used, and do not observe apparent side effect.
3 conclusions
NAOXINQING PIAN has the improvement effect to the hypophrenia of alzheimer disease, can see from 8,9 tables, 36 routine patients are through obeying the brain heart after clear 2 courses of treatment, the scale score obviously increases (P＜0.01), illustrated and regained the strength of memory, improved the intelligence effect, and doing well,improvings such as dysphonia, insomnia, agitation, irritability, body of the tongue petechia are very obvious, and to turbid phlegm blocking the clear orifices, the alzheimer disease of qi depression to blood stasis (AD disease) 36 routine effective percentage reach more than 75%.Curative effect is suitable with the oral Semen Ginkgo extrac preparation Gin Kgo Plus of taking, but to symptom more remarkable treatment effect such as insomnia, agitation, irritabilities.
Description of drawings
Fig. 1 is normal control causes rat hippocampus CA1 cone neural cell injury to the forebrain ischemic reperfusion a protective effect cell microscopic.
Fig. 2 is normal saline causes rat hippocampus CA1 cone neural cell injury to the forebrain ischemic reperfusion the cell microscopic that influences.
Fig. 3 is the NAOXINQING PIAN low dosage causes rat hippocampus CA1 cone neural cell injury to the forebrain ischemic reperfusion a protective effect cell microscopic.
Fig. 4 is the protective effect cell microscopic that dosage causes rat hippocampus CA1 cone neural cell injury in the NAOXINQING PIAN to the forebrain ischemic reperfusion.
Fig. 5 is the NAOXINQING PIAN high dose causes rat hippocampus CA1 cone neural cell injury to the forebrain ischemic reperfusion a protective effect cell microscopic.
Fig. 6 is taponin causes rat hippocampus CA1 cone neural cell injury to the forebrain ischemic reperfusion a protective effect cell microscopic.
Claims (2)
1, the application of NAOXINQING PIAN in preparation control function of nervous system degeneration disease medicine.
2, according to the application of the said NAOXINQING PIAN of claim 1 in preparation control medicine for senile dementia.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200310112426 CN1250241C (en) | 2003-12-03 | 2003-12-03 | Application of Naoxinqing Tablet in the preparation of medicine for preventing and treating nerve function retrograde affection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200310112426 CN1250241C (en) | 2003-12-03 | 2003-12-03 | Application of Naoxinqing Tablet in the preparation of medicine for preventing and treating nerve function retrograde affection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1546111A true CN1546111A (en) | 2004-11-17 |
| CN1250241C CN1250241C (en) | 2006-04-12 |
Family
ID=34336522
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200310112426 Expired - Lifetime CN1250241C (en) | 2003-12-03 | 2003-12-03 | Application of Naoxinqing Tablet in the preparation of medicine for preventing and treating nerve function retrograde affection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1250241C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101045076B (en) * | 2006-03-27 | 2010-05-12 | 广州白云山和记黄埔中药有限公司 | Extractive of persimmon leaves ethyl acetate used for prevention and/or treatment of glycolipid metabolism related diseases |
| CN106727868A (en) * | 2016-12-26 | 2017-05-31 | 合肥智汇医药科技有限公司 | A kind of application of extractive from leaves of persimmon in the medicine for preparing preventing and treating senile dementia |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101744863B (en) * | 2010-01-29 | 2012-12-12 | 广州白云山和记黄埔中药有限公司 | Persimmon leaf extract preparation, preparing method thereof and application thereof |
-
2003
- 2003-12-03 CN CN 200310112426 patent/CN1250241C/en not_active Expired - Lifetime
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101045076B (en) * | 2006-03-27 | 2010-05-12 | 广州白云山和记黄埔中药有限公司 | Extractive of persimmon leaves ethyl acetate used for prevention and/or treatment of glycolipid metabolism related diseases |
| CN106727868A (en) * | 2016-12-26 | 2017-05-31 | 合肥智汇医药科技有限公司 | A kind of application of extractive from leaves of persimmon in the medicine for preparing preventing and treating senile dementia |
| CN106727868B (en) * | 2016-12-26 | 2020-09-01 | 合肥智汇医药科技有限公司 | Application of persimmon leaf extract in preparation of medicine for preventing and treating senile dementia |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1250241C (en) | 2006-04-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Hakim et al. | Treatment of aseptic diseases of limb distal part joints in Uzbek sport horses. | |
| CN111743934A (en) | Traditional Chinese medicine composition for regulating intestinal flora and application thereof | |
| CN1712054A (en) | Qinchuan Tongbi tablet | |
| JP5856725B2 (en) | Pharmaceutical composition for treating or preventing depression | |
| CN1230161C (en) | Persimmon leaf extract and its preparation and its usage | |
| CN1250241C (en) | Application of Naoxinqing Tablet in the preparation of medicine for preventing and treating nerve function retrograde affection | |
| CN100496482C (en) | Application of ligustilide in preparation of medicine for preventing and treating cerebral ischemia diseases | |
| CN1112424A (en) | Toutongning-medicine for headache | |
| CN104524247B (en) | One treats migrainous medical composition and its use | |
| CN105853479A (en) | Pharmaceutical composition for treating depression | |
| CN1840160A (en) | Powder for resisting hyperosteogeny | |
| CN103156876A (en) | Medicine composition for treating central nervous system diseases and preparation method and application thereof | |
| CN101190315A (en) | Traditional Chinese medicine composition for treating melancholia and preparation method thereof | |
| CN104524188A (en) | Medicament for treating vascular dementia and preparation method of medicament | |
| CN114191422A (en) | Application of phloretin in preparation of antidepressant drugs | |
| CN1872214A (en) | Application of medication composition of containing notoperygium root in preparing medication for treating chronic insufficiency of supplying blood for brain | |
| CN107854620B (en) | Traditional Chinese medicine composition for improving cognitive dysfunction after brain injury and application thereof | |
| CN1081888A (en) | Treatment commonly encountered diseases of internal department, the apoplexy of frequently-occurring disease and the Chinese patent medicine tablet of sequela | |
| CN1380071A (en) | Chinese medicine for curing psychosis and epilepsy | |
| CN1723933A (en) | Traditional Chinese medicine capsule for treating application, and its prodn. method | |
| CN1411861A (en) | Medicine for curing acute injury of muscle and tendon and its preparation method | |
| CN1250278C (en) | Oral medicine for treating dementia and feeblemindedpess | |
| CN1843441A (en) | Rheumatism-eliminating collaterals-dredging externally applied plaster | |
| CN114949086B (en) | Composition for treating cerebral hemorrhage | |
| LU503397B1 (en) | Application of volatile oil of traditional chinese medicine in preparation of antidepressant drug and aromatherapy product |
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 | ||
| CX01 | Expiry of patent term | ||
| CX01 | Expiry of patent term |
Granted publication date: 20060412 |