CN1049117C - Tablet for preventing and curing migraine - Google Patents
Tablet for preventing and curing migraine Download PDFInfo
- Publication number
- CN1049117C CN1049117C CN94116067A CN94116067A CN1049117C CN 1049117 C CN1049117 C CN 1049117C CN 94116067 A CN94116067 A CN 94116067A CN 94116067 A CN94116067 A CN 94116067A CN 1049117 C CN1049117 C CN 1049117C
- Authority
- CN
- China
- Prior art keywords
- migraine
- tablet
- preventing
- caffeine
- present
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 208000019695 Migraine disease Diseases 0.000 title claims abstract description 26
- 206010027599 migraine Diseases 0.000 title claims abstract description 26
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 claims abstract description 22
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol hydrochloride Natural products C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 claims abstract description 14
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229960001948 caffeine Drugs 0.000 claims abstract description 11
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 claims abstract description 11
- MEAPRSDUXBHXGD-UHFFFAOYSA-N 3-chloro-n-(4-propan-2-ylphenyl)propanamide Chemical compound CC(C)C1=CC=C(NC(=O)CCCl)C=C1 MEAPRSDUXBHXGD-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229960002790 phenytoin sodium Drugs 0.000 claims abstract description 10
- 229960004604 propranolol hydrochloride Drugs 0.000 claims abstract description 10
- 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 claims abstract description 10
- 210000001367 artery Anatomy 0.000 abstract description 4
- 238000007917 intracranial administration Methods 0.000 abstract description 3
- 208000005392 Spasm Diseases 0.000 abstract description 2
- 239000007787 solid Substances 0.000 abstract 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 15
- 239000003814 drug Substances 0.000 description 9
- 239000003146 anticoagulant agent Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- OFKDAAIKGIBASY-VFGNJEKYSA-N ergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C3=CC=CC4=NC=C([C]34)C2)=C1)C)C1=CC=CC=C1 OFKDAAIKGIBASY-VFGNJEKYSA-N 0.000 description 3
- 229960004943 ergotamine Drugs 0.000 description 3
- XCGSFFUVFURLIX-UHFFFAOYSA-N ergotaminine Natural products C1=C(C=2C=CC=C3NC=C(C=23)C2)C2N(C)CC1C(=O)NC(C(N12)=O)(C)OC1(O)C1CCCN1C(=O)C2CC1=CC=CC=C1 XCGSFFUVFURLIX-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- FIADGNVRKBPQEU-UHFFFAOYSA-N pizotifen Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CCC2=C1C=CS2 FIADGNVRKBPQEU-UHFFFAOYSA-N 0.000 description 3
- 229960004572 pizotifen Drugs 0.000 description 3
- 239000000902 placebo Substances 0.000 description 3
- 229940068196 placebo Drugs 0.000 description 3
- 206010061623 Adverse drug reaction Diseases 0.000 description 2
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 230000000702 anti-platelet effect Effects 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 206010013663 drug dependence Diseases 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000000936 membranestabilizing effect Effects 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 229940100866 phenytoin sodium 100 mg Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 229960003712 propranolol Drugs 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 208000011117 substance-related disease Diseases 0.000 description 2
- 230000024883 vasodilation Effects 0.000 description 2
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- 102400000967 Bradykinin Human genes 0.000 description 1
- 208000002381 Brain Hypoxia Diseases 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- 102000014630 G protein-coupled serotonin receptor activity proteins Human genes 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 208000005946 Xerostomia Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 206010003549 asthenia Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- 229940124827 caffeine tablet Drugs 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 235000018927 edible plant Nutrition 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- SMANXXCATUTDDT-QPJJXVBHSA-N flunarizine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)N1CCN(C\C=C\C=2C=CC=CC=2)CC1 SMANXXCATUTDDT-QPJJXVBHSA-N 0.000 description 1
- 229960000326 flunarizine Drugs 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 231100000567 intoxicating Toxicity 0.000 description 1
- 230000002673 intoxicating effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- DMDOTRUOIVBPSF-UHFFFAOYSA-N naphthalene;hydrochloride Chemical compound Cl.C1=CC=CC2=CC=CC=C21 DMDOTRUOIVBPSF-UHFFFAOYSA-N 0.000 description 1
- 229960000715 nimodipine Drugs 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000008058 pain sensation Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229940120082 propranolol hydrochloride 10 mg Drugs 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- KAVSMINTEBGDTI-UHFFFAOYSA-N pyridine;thiophene Chemical compound C=1C=CSC=1.C1=CC=NC=C1 KAVSMINTEBGDTI-UHFFFAOYSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 239000007779 soft material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to a tablet for preventing and treating migraine, which mainly comprises caffeine, propranolol hydrochloride and phenytoin sodium, wherein each tablet comprises 60 to 100 mg of caffeine, 8 to 150 mg of propranolol hydrochloride and 80 to 150 mg of phenytoin sodium. The present invention can resist platelet aggregation, prevent intracranial artery spasm, increase extracranial artery resistance and prevent intracranial, and therefore, migraine can be relieved. The results of clinical tests indicate that the total effective rate reaches more than 93%, and the present invention is a solid coated tablet for preventing and treating migraine.
Description
The present invention relates to a kind of treatment migraine class medicine, it is a kind ofly to have prevention and treat migrainous sugar cube garment piece.
Migraine is commonly encountered diseases and frequently-occurring disease, average attack rate 5-10%.Particularly in China, along with dwindling of differentials between town and country, the accelerating of people's lives rhythm, prevalence can be growing on and on.Treat migrainous medicine at present, as: Ergotamine and ergotin analog derivative, pizotifen, thiophene pyridine in heptan, Propranolol, aspirin and other NSAID (non-steroidal anti-inflammatory drug), clonidine, nimodipine stable and that occur in recent years and flunarizine etc.These Drug therapy migraine all in various degree to exist effective percentage low or the shortcoming of certain toxic and side effects arranged.But the compound preparation ergotamine and caffeine tablet also is restricted because of the side effect of prolonged application intoxicating and drug dependence or addiction.
The purpose of this invention is to provide a kind of effective percentage height, toxicity is low, and side effect is little, has certain safety and treats migrainous medicine.
Main caffeine, propranolol hydrochloride, the phenytoin Sodium of containing of the present invention is the 90.0-110.0% of labelled amount.
Its prescription: caffeine 60-100mg
Propranolol hydrochloride 8-15mg
Phenytoin Sodium 80-150mg
20% starch slurry 30-55mg
Magnesium stearate 5-10mg
Make 1
Preparation method: adopt the caffeine that meets " Chinese Pharmacopoeia " 8 or five years version regulations, propranolol hydrochloride, phenytoin Sodium take by weighing supplementary material successively, sieve respectively, mix homogeneously is made soft material with 20% starch slurry as binding agent, granulates by 10 nylon mesh, oven dry is 4-6 hour below 60 degree Celsius, natural cooling by 14 mesh sieve granulate, adds the magnesium stearate mix homogeneously again, tabletting, coating is made.
Effect to each component reaches selected being described as follows below:
1, coffee is because central stimulants is share the treatment migraine with Ergotamine for many years, and its migraine effect is relevant to cerebrovascular contraction with it.It can reach the migrainous effect of treatment by anticoagulant.
2, the general bitter edible plant Luo Er of hydrochloric acid is the beta receptor blocker, and its migraine mechanism prevents that with its beta receptor blocking-up the outer vasodilation of cranium is relevant.But heavy dose of Propranolol anticoagulant reduces the 5-HT receptor, and these effects show the migraine effect with preventing intracranial from shrinking relevant.
3, phenytoin Sodium is the sick medicine of epilepsy, also is used for the treatment of migraine, and is relevant with its membrane stabilizing action.
Pathogenesis of migraine mainly is because platelet function abnormality discharges a large amount of 5-HT, cause that entocranial artery shrinks, so that cerebral hypoxia, angiogenic substances such as histamine and Kallidin I are increased, 5-HT is destroyed rapidly simultaneously, thereby makes the outer arteriectasia of cranium cause migraine.Therefore, all energy antagonism 5-HT function of receptors, the medicine that increases outer tremulous pulse resistance of cranium or antiplatelet aggregation all has the effect of alleviation and prevention of migraine outbreak.
Contained caffeine, propranolol hydrochloride, the phenytoin Sodium of the present invention all can influence some link of migraine morbidity, so share " the migraine sheet " of composition, the three aspect treatment, can produce following beneficial effect: 1, antiplatelet aggregative activity, three medicines have synergism, thereby prevent the entocranial artery spasm; 2, prevent the outer arteriectasia aspect of cranium, caffeine and propranolol hydrochloride have synergism, thereby increase the outer tremulous pulse resistance of cranium, alleviate migraine; 3, membrane stabilizing action, propranolol hydrochloride and phenytoin Sodium have synergism, and the pain sensation due to the retardance vasodilation is conducted strong effect; 4, the central inhibitory action of propranolol hydrochloride and phenytoin Sodium can be weakened by caffeine; 5, the used dosage of migraine sheet is significantly less than each prescription dosage, each oral 1 of migraine sheet, every optimum content is caffeine 70mg, hydrochloric acid naphthalene Luo Er 10mg, phenytoin Sodium 100mg, and their common dose is respectively 100mg-300mg, 80mg-120mg and 100mg-200mg, because the used dosage of migraine sheet is little, so side effect is lowered greatly.The present invention shows that through the clinic trial result total effective rate reaches more than 93%.
Migraine sheet and pizotifen sheet and placebo tablet see Table through clinic trial curative effect comparative result
Table one: comparative result is imitated in three medications
Three kinds of drug side effectes relatively see Table two
| Nomenclature of drug | The example number | Cure | Produce effects | Effectively | Invalid | ||||
| The example number | ％ | The example number | ％ | The example number | ％ | The example number | ％ | ||
| The migraine sheet | 32 | 8 | 25 | 13 | 40.62 | 9 | 28.13 | 2 | 8.25 |
| The pizotifen sheet | 30 | 2 | 6.67 | 7 | 23.33 | 11 | 36.67 | 10 | 33.33 |
| Placebo tablet | 31 | 0 | 0 | 3 | 9.68 | 8 | 25.80 | 20 | 64.22 |
Table two: three kinds of drug side effect comparative results
| Nomenclature of drug | The example number | Have no side effect | Dizzy | Xerostomia | Dyskoimesis | Asthenia | Gastrointestinal tract does not relax | Other side effect | |||||||
| The example number | ％ | The example number | ％ | The example number | ％ | The example number | ％ | The example number | ％ | The example number | ％ | The example number | ％ | ||
| The migraine sheet | 32 | 26 | 81.25 | 1 | 3.12 | 0 | 0 | 3 | 9.3 | 0 | 0 | 1 | 3.12 | 1 | 3.12 |
| Benzene miaow pyridine sheet | 30 | 20 | 66.68 | 3 | 10 | 1 | 3.33 | 1 | 3.33 | 3 | 10 | 1 | 3.33 | 1 | 3.33 |
| Placebo tablet | 31 | 28 | 90.31 | 1 | 3.23 | 0 | 3.23 | 1 | 3.23 | 1 | 3.23 | 0 | 0 | 0 | 0 |
Instantiation of the present invention is as follows:
Preferred example is: contain caffeine 70mg in 1, propranolol hydrochloride 10mg, phenytoin Sodium 100mg.
Claims (1)
1, a kind ofly prevent and treat migrainous migraine sheet, it is characterized by: it contains caffeine, propranolol hydrochloride and phenytoin Sodium, and the content of its 1 middle each component is respectively 60-100mg, 8-15mg and 80-150mg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN94116067A CN1049117C (en) | 1994-09-16 | 1994-09-16 | Tablet for preventing and curing migraine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN94116067A CN1049117C (en) | 1994-09-16 | 1994-09-16 | Tablet for preventing and curing migraine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1129105A CN1129105A (en) | 1996-08-21 |
| CN1049117C true CN1049117C (en) | 2000-02-09 |
Family
ID=5037776
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN94116067A Expired - Lifetime CN1049117C (en) | 1994-09-16 | 1994-09-16 | Tablet for preventing and curing migraine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1049117C (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040229901A1 (en) * | 2003-02-24 | 2004-11-18 | Lauren Otsuki | Method of treatment of disease using an adenosine A1 receptor antagonist |
| NZ543109A (en) | 2003-04-25 | 2008-06-30 | Novacardia Inc | Method of improved diuresis in individuals with impaired renal function |
| CN102125522B (en) * | 2010-01-15 | 2013-01-16 | 复旦大学附属华山医院 | P-glycoprotein monoclonal antibody modified phenytoin targeting nanopreparation and preparation method thereof |
| CN103446156A (en) * | 2013-08-20 | 2013-12-18 | 云南农业大学 | Application of caffeine in preparing anticoagulation medicine |
-
1994
- 1994-09-16 CN CN94116067A patent/CN1049117C/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| 《当代结构药物全集》第一版 1993.1.1 王泽民主编，北京科技出版社 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1129105A (en) | 1996-08-21 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: HEBEI TIANCHENG PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: ZHAO MINGYU Effective date: 20070105 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20070105 Address after: Street traffic in Hebei province Cangzhou City Zhiqiang road 061000 Patentee after: Hebei Tiancheng Pharmaceutical Co., Ltd. Address before: 061001 Cangzhou new hospital of Hebei Province Patentee before: Zhao Mingyu |
|
| C17 | Cessation of patent right | ||
| CX01 | Expiry of patent term |
Expiration termination date: 20140916 Granted publication date: 20000209 |