CN104523709A - Compound sustained-release preparation containing succinate Frovatriptan - Google Patents
Compound sustained-release preparation containing succinate Frovatriptan Download PDFInfo
- Publication number
- CN104523709A CN104523709A CN201410799651.1A CN201410799651A CN104523709A CN 104523709 A CN104523709 A CN 104523709A CN 201410799651 A CN201410799651 A CN 201410799651A CN 104523709 A CN104523709 A CN 104523709A
- Authority
- CN
- China
- Prior art keywords
- slow
- frova
- succinic acid
- release
- aspirin
- 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.)
- Withdrawn
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
Abstract
The invention relates to the field of medicine preparations, and in particular relates to a sustained-release preparation of a compound medicine containing succinate Frovatriptan and aspirin. The sustained-release preparation is characterized by consisting of two parts namely a quick release part and a sustained release part, wherein after the sustained-release preparation enters a human body, the quick release part is rapidly released to achieve a certain blood medicine concentration, and the sustained release part is slowly released to maintain a certain blood medicine concentration, so that good medicine effects can be achieved, and side effects of the medicine can also be effectively avoided. The sustained-release preparation disclosed by the invention has the advantages of quick dissolution, fast absorption, high biological availability, good stability, convenience in taking and the like. The invention also discloses a preparation method of the compound medicine.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, particularly relate to a kind of compound slow release preparation containing succinic acid Frova, belong to medical art.
Background technology
Migraine is clinical modal primary headache type; clinical with ictal middle severe, sample of beating headache for main manifestations; headache mostly is inclined side; general lasting 4-72 hour; can with Nausea and vomiting; light, Sound stimulat or daily routines all can increase the weight of headache, and quiet environment, rest can alleviate headache.Migraine is a kind of common chronic forms vascular illness, and a lot of disease is in child and adolescence, and the young and middle-aged phase reaches onset peak, and women is common, and in crowd, prevalence is 5%-10%, often has genetic background.
Migraine is primary in central nervous system function disorder, and Vascular change is secondary, disorderly with neurotransmitter numerous in blood and cerebrospinal fluid during migraine.Someone also proposes neurogenic inflammation and causes migraine, thinks that cause the neurogenic inflammation of cerebral dura mater and institute's Supply Organization thereof, its main manifestations is plasma protein extravasation and vasodilation by stimulating nervi trigeminus peripheral vessels fiber to discharge vasoactive peptide.Recent research finds that the NO be present in central nervous system plays an important role to the transmission of pain stimulation at maincenter.But what receive much attention in recent years is trigemino-vascular reflex theory, nerve, blood vessel and neurotransmitter triplicity is got up, and is unified in trigeminal vascular system.This hypothesis is thought by stimulating some specific region in brain, causes the outer vasodilation of cranium and internal carotid artery vasodilation, produce headache through series reaction.In the process, the 5-HT of intra platelet free calcium enhances the sensitivity of vascular receptor, plays an important role to the generation of pain.Some the migrainous clinical manifestations of this hypothesis well explain, were used for the treatment of migraine provided rational explanation for some have both acted on medicine that nervus centralis nervous system also acts on peripheral nervous system.
Succinic acid Frova is the in vitro cerebral vasoconstriction agent of multiple species (comprising people).Arterial Rings In Vitro blood vessel observes the activity of succinic acid Frova as vasoconstrictor, and compares with sumatriptan.On people's middle cerebral artery, succinic acid Frova is a kind of partial agonist (relative to 5-HT), and effect is at least 5 times of sumatriptan.Succinic acid Frova is a kind of full agonists to people's basilar artery, and its effect is about 8.3 times of sumatriptan.The effect of succinic acid Frova to rabbit basilar artery and cat brain medium-sized artery is 23 and 3 times of sumatriptan respectively.Rabbit, compared with 5-HT, succinic acid Frova is a kind of partial agonist, and sumatriptan is a kind of full agonist.Cat, relative to 5-HT, succinic acid Frova and sumatriptan are all partial agonists.
Aspirin is a kind of ancient antipyretic analgesic, and aspirin not only can treat Acute Migraine Attacks, and can be used for the recurrence of prevention of migraine.Migrainous mechanism prevented and treated by aspirin: (l) resists the slow sharp skin of morbid substance in blood vessel wall.(2) block or fill the teleneuron of pain, making pain stimulation not reach teleneuron.(3) inflammatory reaction is alleviated.(4) sedation and myorelaxant effects.(5) suppress Cycloxygenase, thus stop prostaglandin, thromboxane element A2 synthesis, anticoagulant and platelet factor release.(6) play a role in 5-hydroxy tryptamine metabolic process, tryptophan is discharged from sero-abluminous binding site, thus improve the free amino acid concentrations required for the synthesis of 5-hydroxyl coloring agent, improve the function of 5-hydroxyl coloring agent system.
Summary of the invention
The invention discloses a kind of compound slow release preparation containing succinic acid Frova, can reach that medicine discharges gently, blood drug level steadily, reduce that administration number of times, toxic and side effects are little, patient's compliance improves.The present invention has the advantages such as stripping is rapid, absorption is fast, bioavailability is high, good stability, taking convenience.
Adopt pharmacy common technology; succinic acid Frova and aspirin are pulverized and sieves; again by slow-release material mix homogeneously; pulverize and sieve; then succinic acid Frova is mixed with into immediate-release granules with slow-release material, succinic acid Frova is mixed with into slow-releasing granules with aspirin with slow-release material, more last immediate-release granules to be mixed homogeneously with slow-releasing granules; incapsulate, to obtain final product.
The present invention's preferred slow release succinic acid Frova part is containing other pharmaceutic adjuvant of 40-60% succinic acid Frova, 10-35% slow-release material and surplus; Preferred slow release aspirin part is containing other pharmaceutic adjuvant of 0.1-0.3% aspirin, 50-95% slow-release material and surplus.
Slow releasing preparation of the present invention changes original single delivery form, will discharge fast and organically combine with slow release, produces therapeutic effect rapidly within a certain period of time and maintains the long period.Discharge 15-30% in 1st hour, produce therapeutic effect at once, discharge in remainder 2-24 afterwards hour, thus produce the therapeutic effect continued.
Detailed description of the invention
Embodiment 1
Prescription 1(is by 1000)
A, succinic acid Frova immediate-release granules
Succinic acid Frova 1.0g
Microcrystalline Cellulose 10.0g
Lactose 12.95g
Polyvinylpolypyrrolidone 0.9g
Magnesium stearate 0.15g
B, succinic acid Frova slow-releasing granules
Succinic acid Frova 2.91g
Hydroxypropyl emthylcellulose 12.5g
Carbomer 2.0g
Lactose 8.5g
Magnesium stearate 0.25g
C, aspirin sustained release granule
Aspirin 100g
Hydroxypropyl emthylcellulose 25g
Carbomer 2.5g
Lactose 22.5g
Magnesium stearate 0.25g
Method for making: succinic acid Frova and aspirin were pulverized 80 mesh sieves; again by slow-release material mix homogeneously; pulverized 120 mesh sieves; then succinic acid Frova is mixed with into immediate-release granules with slow-release material; succinic acid Frova is mixed with into slow-releasing granules with aspirin with slow-release material; last again immediate-release granules to be mixed homogeneously with slow-releasing granules, incapsulate, to obtain final product.
Embodiment 2
Prescription 2(is by 1000)
A, succinic acid Frova immediate-release granules
Succinic acid Frova 1.0g
Microcrystalline Cellulose 10.0g
Lactose 12.95g
Polyvinylpolypyrrolidone 0.9g
Magnesium stearate 0.15g
B, succinic acid Frova slow-releasing granules
Succinic acid Frova 2.91g
Hydroxypropyl emthylcellulose 10.5g
Carbomer 6.0g
Lactose 12.5g
Magnesium stearate 0.3g
C, aspirin sustained release granule
Aspirin 100g
Hydroxypropyl emthylcellulose 30g
Carbomer 8.5g
Lactose 12.5g
Magnesium stearate 0.25g
Method for making is with embodiment 1.
Embodiment 3
Prescription 3(is by 1000)
A, succinic acid Frova immediate-release granules
Succinic acid Frova 1.0g
Microcrystalline Cellulose 10.0g
Lactose 12.95g
Polyvinylpolypyrrolidone 0.9g
Magnesium stearate 0.15g
B, succinic acid Frova slow-releasing granules
Succinic acid Frova 2.91g
Hydroxypropyl emthylcellulose 7.5g
Carbomer 1.5g
Lactose 18.5g
Magnesium stearate 0.3g
C, aspirin sustained release granule
Aspirin 100g
Hydroxypropyl emthylcellulose 35g
Carbomer 10.5g
Lactose 8.5g
Magnesium stearate 0.3g
Method for making is with embodiment 1.
Embodiment 4
Prescription 4(is by 1000)
A, succinic acid Frova immediate-release granules
Succinic acid Frova 1.0g
Microcrystalline Cellulose 10.0g
Lactose 12.95g
Polyvinylpolypyrrolidone 0.9g
Magnesium stearate 0.15g
B, succinic acid Frova slow-releasing granules
Succinic acid Frova 2.91g
Hydroxypropyl emthylcellulose 6.5g
Carbomer 4.5g
Lactose 20.5g
Magnesium stearate 0.3g
C, aspirin sustained release granule
Aspirin 100g
Hydroxypropyl emthylcellulose 40g
Carbomer 12g
Ethyl cellulose 6g
Lactose 6g
Magnesium stearate 0.3g
Method for making is with embodiment 1.
Embodiment 5
Prescription 5(is by 1000)
A, succinic acid Frova immediate-release granules
Succinic acid Frova 1.0g
Microcrystalline Cellulose 10.0g
Lactose 12.95g
Polyvinylpolypyrrolidone 0.9g
Magnesium stearate 0.15g
B, succinic acid Frova slow-releasing granules
Succinic acid Frova 2.91g
Hydroxypropyl emthylcellulose 10.5g
Carbomer 2.5g
Lactose 15g
Magnesium stearate 0.3g
C, aspirin sustained release granule
Aspirin 100g
Hydroxypropyl emthylcellulose 30g
Carbomer 12g
Ethyl cellulose 6g
Lactose 6g
Magnesium stearate 0.3g
Method for making is with embodiment 1.
Test example 1 Dissolution Rate Testing
The dissolution of the slow releasing preparation of the compound medicine prepared by embodiment 1-5 is measured according to dissolution determination method (with reference to Chinese Pharmacopoeia 2010 editions two annex XC second methods), with 0.01mol/L hydrochloric acid for dissolution medium, rotating speed is 50 turns per minute, measures drug-eluting amount, result of the test following table:
| 2 minutes | 5 minutes | |
| Embodiment 1 | 81.5 | 87.4 |
| Embodiment 2 | 80.8 | 89.4 |
| Embodiment 3 | 79.3 | 86.7 |
| Embodiment 4 | 81.7 | 89.3 |
| Embodiment 5 | 93.6 | 99.8 |
Result of the test is visible, embodiment 5(prescription 5) result of extraction is best, and the dissolution rate of medicine is the fastest, and this formula preparation technique is simple, and steady quality is reliable, can meet the requirement of industrialized great production.
Claims (10)
1. the compound slow release preparation containing succinic acid Frova, it is characterized in that slow-released part is made up of rapid release and slow release two parts, wherein immediate release section is containing succinic acid Frova 0.5-2mg, and slow-released part is containing succinic acid Frova 1.5-5mg and aspirin 50-150mg.
2. the slow releasing preparation of claim 1, is characterized in that remixing after slow-released part makes slow-releasing granules, slow-release micro-pill or eluting patches respectively by succinic acid Frova and aspirin forming.
3. the slow releasing preparation of claim 2, wherein slow release succinic acid Frova is containing other pharmaceutic adjuvant of 40-60% succinic acid Frova, 10-35% slow-release material and surplus.
4. the slow releasing preparation of claim 2, wherein slow release aspirin is containing other pharmaceutic adjuvant of 0.1-0.3% aspirin, 50-95% slow-release material and surplus.
5. the slow releasing preparation of claim 3 or 4, wherein slow-release material is selected from one or more in carbomer, ethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, stearic acid, glyceryl monostearate, octadecanol, polyethylene, polypropylene, acrylic resin.
6. the slow releasing preparation of claim 1, wherein rapid release succinic acid Frova is containing succinic acid Frova and other pharmaceutic adjuvant.
7. the slow releasing preparation of claim 6, wherein immediate release material is selected from one or more in lactose, sucrose, starch, pregelatinized Starch, cellulose, Icing Sugar, dextrin, glucose, calcium bicarbonate; Disintegrating agent is selected from one or more in carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose; Binding agent is selected from one or more in water, alcohol, polyvinylpyrrolidone, starch slurry; Lubricant is selected from one or more in magnesium stearate, Pulvis Talci, micropowder silica gel, sodium lauryl sulphate or magnesium.
8. the slow releasing preparation of claim 3 or 4 or 6, wherein other pharmaceutic adjuvant is selected from one or more in filler, disintegrating agent, binding agent, lubricant.
9. the slow releasing preparation of claim 8, wherein other pharmaceutic adjuvant is microcrystalline Cellulose, polyvinylpolypyrrolidone, hydroxypropyl emthylcellulose, carbomer, ethyl cellulose, lactose, magnesium stearate.
10. the slow releasing preparation of claim 1, wherein immediate release section is containing succinic acid Frova 1.0mg, and slow-released part is containing succinic acid Frova 2.91mg and aspirin 100mg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410799651.1A CN104523709A (en) | 2014-12-22 | 2014-12-22 | Compound sustained-release preparation containing succinate Frovatriptan |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410799651.1A CN104523709A (en) | 2014-12-22 | 2014-12-22 | Compound sustained-release preparation containing succinate Frovatriptan |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104523709A true CN104523709A (en) | 2015-04-22 |
Family
ID=52839467
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410799651.1A Withdrawn CN104523709A (en) | 2014-12-22 | 2014-12-22 | Compound sustained-release preparation containing succinate Frovatriptan |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104523709A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1522697A (en) * | 1998-07-30 | 2004-08-25 | ������ҩ������˾ | Prevention of migraine recurrence |
| CN101410095A (en) * | 2006-03-06 | 2009-04-15 | 波曾公司 | Dosage forms for administering combinations of drugs |
| CN101890012A (en) * | 2009-09-28 | 2010-11-24 | 江苏亚邦爱普森药业有限公司 | Paracetamol,loratadine and pseudoephedrine sulfate sustained release tablet and preparation method thereof |
| CN101953833A (en) * | 2009-07-13 | 2011-01-26 | 天津药物研究院 | Slowly-controlled release formulation containing rizatriptan benzoate, preparation method and application thereof |
| US20140045801A1 (en) * | 2012-08-09 | 2014-02-13 | Mylan Inc. | Pramipexole transdermal delivery for severe headaches |
-
2014
- 2014-12-22 CN CN201410799651.1A patent/CN104523709A/en not_active Withdrawn
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1522697A (en) * | 1998-07-30 | 2004-08-25 | ������ҩ������˾ | Prevention of migraine recurrence |
| CN101410095A (en) * | 2006-03-06 | 2009-04-15 | 波曾公司 | Dosage forms for administering combinations of drugs |
| CN101953833A (en) * | 2009-07-13 | 2011-01-26 | 天津药物研究院 | Slowly-controlled release formulation containing rizatriptan benzoate, preparation method and application thereof |
| CN101890012A (en) * | 2009-09-28 | 2010-11-24 | 江苏亚邦爱普森药业有限公司 | Paracetamol,loratadine and pseudoephedrine sulfate sustained release tablet and preparation method thereof |
| US20140045801A1 (en) * | 2012-08-09 | 2014-02-13 | Mylan Inc. | Pramipexole transdermal delivery for severe headaches |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103417505B (en) | There is huperzine controlled release preparation of two-phase drug release behavior and preparation method thereof | |
| CN104013592A (en) | Memantine hydrochloride slow-release pill and preparation method thereof | |
| CN101347427A (en) | Compound of losartan compound or its medical salt and calcium channel blocker or its medical salt | |
| WO2021129735A1 (en) | Solid preparation, and preparation method therefor and use thereof | |
| WO2012173581A4 (en) | Thiocolchicoside, etodolac and famotidine combinations | |
| CN1839827A (en) | Strontium ranelate chewing tablet and its preparation process | |
| CN106511312A (en) | Compound sildennafil dapoxetine slow-release capsule and preparation method thereof | |
| CN105412023A (en) | Frovatriptan succinate controlled-release granule and preparation method thereof | |
| CN105213425A (en) | One treats hypertensive compound recipe reserpine oral cavity disintegration tablet and preparation method thereof | |
| WO2005044238A1 (en) | Modified release solid dosage form of amphetamine salts | |
| WO2006000137A1 (en) | Oral disintegrable tablet of notogingseng total sapoin and the preparation process thereof | |
| CN112618554B (en) | Compound tablet for treating hypertension complicated with coronary heart disease and preparation method thereof | |
| CN104523709A (en) | Compound sustained-release preparation containing succinate Frovatriptan | |
| CN104382882B (en) | A kind of Zaleplon dipulse release capsule of non-TCP friendly flow and preparation method thereof | |
| CN105412039A (en) | Frovatriptan succinate controlled-release tablet and preparation method thereof | |
| CN104546817A (en) | Pregabalin sustained release preparation | |
| KR102486126B1 (en) | Pharmaceutical compositions comprising alpelisib | |
| JP2015516446A (en) | (1r, 4r) -6′-fluoro-N, N-dimethyl-4-phenyl-4 ′, 9′-dihydro-3′H-spiro [cyclohexane-1,1′-pyrano [3,4, b] Indole] -4-amine and a pharmaceutical composition comprising gabapentinoid | |
| CN109908162B (en) | Pharmaceutical composition for treating depression, preparation and medical application thereof | |
| CN109010352B (en) | A kind of fatigue-resistant drug composition and its preparation method and application | |
| CN103222966A (en) | Solid pharmaceutical composition containing Fingolimod hydrochloride and preparation method thereof | |
| CN103230594A (en) | Medicine composition of alpha-glucosidase inhibitor and vitamin B | |
| TW200920371A (en) | A combination treatment | |
| CN102552107B (en) | Two-phase release preparation containing zolpidem or salt of zolpidem and preparation method thereof | |
| JP2021534085A (en) | Compositions and Methods for Cancer Treatment |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20150422 |
|
| WW01 | Invention patent application withdrawn after publication |