CN110898017A - Frovatriptan succinate dropping pill and preparation method thereof - Google Patents
Frovatriptan succinate dropping pill and preparation method thereof Download PDFInfo
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- CN110898017A CN110898017A CN201911265065.8A CN201911265065A CN110898017A CN 110898017 A CN110898017 A CN 110898017A CN 201911265065 A CN201911265065 A CN 201911265065A CN 110898017 A CN110898017 A CN 110898017A
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- succinate
- furotriptan
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
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- General Chemical & Material Sciences (AREA)
- Pain & Pain Management (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Medicinal Preparation (AREA)
Abstract
The invention discloses a furotriptan succinate dropping pill and a preparation method thereof. The dripping pill has the advantages of good roundness, rapid medicine dissolution, high bioavailability, simple production process, stable quality of the obtained product and suitability for large-scale production.
Description
Technical Field
The invention relates to a western medicine preparation technology, in particular to a furotriptan succinate dropping pill and a preparation method thereof, belonging to the technical field of medicines.
Background
Migraine is a common chronic neurovascular disease, the most common primary headache type in clinic, the disease is mostly caused in children and adolescence, the peak of the disease occurs in middle and young age, women are common, the prevalence rate is 5% -10% in people, and the genetic background is common. Migraine is primarily caused by dysfunction of the central nervous system, while vascular changes are secondary, with migraine attacks accompanied by numerous neuromediator disturbances in the blood and cerebrospinal fluid. The recent attention paid to the theory of trigeminal vasoreflexion is the combination of nerves, blood vessels and neuromediators, which are integrated into the trigeminal vascular system. This hypothesis suggests that by stimulating certain specific areas in the brain, a series of reactions cause cranial vasodilation and carotid vasodilation, resulting in headache. In this process, 5-HT released by platelets enhances the sensitivity of vascular receptors and plays an important role in pain production. This hypothesis better explains some of the clinical manifestations of migraine, providing a reasonable explanation for the use of drugs acting on both the central and peripheral nervous systems for the treatment of migraine.
Frovatriptan succinate is an isolated cerebral vasoconstrictor, and the activity of Frovatriptan succinate as a vasoconstrictor was observed on isolated arterial vessels and compared with sumatriptan. In the middle cerebral artery of the human brain, furotriptan succinate is a partial agonist (relative to 5-HT) and has at least a 5-fold effect as compared to sumatriptan. Furotriptan succinate is a full agonist for the human basal artery, with about 8.3 times the effect of sumatriptan. Furotriptan succinate had 23 and 3 times greater effect on rabbit basal arteries and cat middle cerebral arteries than sumatriptan, respectively.
The dropping pill has simple using equipment and easily controlled process conditions; the preparation has stable quality and accurate measurement; the matrix has large liquid medicine containing amount, and can solidify the liquid medicine; the dripping pill prepared by solid dispersion technology has the advantages of rapid absorption and high bioavailability. The inclusion compound has the following advantages: covering up bad odor, reducing drug irritation, increasing drug dissolution rate and bioavailability, and improving drug stability.
Disclosure of Invention
In order to solve the defects of poor stability and low bioavailability of the existing furotriptan succinate preparation and research and develop a dripping pill with stable quality, the invention provides a furotriptan succinate dripping pill through screening auxiliary materials and optimizing a process by a large number of tests. Firstly, furotriptan succinate is prepared into inclusion compound, then prepared into dropping pill, and the inclusion and dropping pill technology are combined into a whole, thus exerting the advantages of the two aspects. The dripping pill has stable quality and high bioavailability.
In order to achieve the purpose, the invention adopts the technical scheme that:
a dripping pill of furotriptan succinate comprises furotriptan succinate, an inclusion material, a substrate, a stabilizer and a condensate, and is characterized in that the dripping pill comprises the following components in percentage by weight:
10-20% of furotriptan succinate
10 to 20 percent of inclusion material
65 to 75 percent of matrix
1 percent of stabilizer
And proper amount of condensate.
Preferably, the content of each component is as follows according to weight percentage:
frovatriptan succinate 15%
The inclusion material is 15 percent
70 percent of matrix
1 percent of stabilizer
And proper amount of condensate.
The inclusion material is β -cyclodextrin, the matrix is one or more of sodium carboxymethyl starch, glyceryl monostearate or stearic acid, the stabilizer is sodium dihydrogen phosphate and disodium hydrogen phosphate, and the condensate is liquid paraffin.
Wherein, the matrix is preferably sodium carboxymethyl starch and glyceryl monostearate; preferably, the weight ratio of the sodium carboxymethyl starch to the glyceryl monostearate is 1: 1.
the dripping pills of furotriptan succinate can be prepared by the following method:
(1) dissolving furaltriptan succinate and an inclusion material in proportion by using 80% ethanol as a medium, filtering the obtained solution through a microporous filter membrane to be clear, separating a furaltriptan succinate inclusion compound from the mixture, and crushing the inclusion compound and sieving the crushed inclusion compound through a 50-100-mesh sieve;
(2) grinding and uniformly mixing the matrix and the stabilizer, heating and melting the mixture in water, and uniformly mixing the mixture;
(3) adding the prepared furotriptan succinate inclusion compound in the step (1) into the melt prepared in the step (2), uniformly mixing, pouring into an inclined liquid tank, and keeping the temperature at 65-75 ℃ for 10 minutes;
(4) dripping the medicinal liquid into 0-20 deg.C condensate to form dripping pill, adsorbing the condensate, and drying the dripping pill.
The furotriptan succinate dropping pill related by the invention has the following beneficial effects:
(1) the quality is stable, the dissolution rate and bioavailability of the medicine are increased, and the stability of the medicine is improved;
(2) the selected auxiliary materials are common, the production process is simple, the obtained product has good roundness and stable quality, and the method is suitable for large-scale production.
Detailed Description
The following further describes the embodiments of the present invention with reference to examples, but these examples are only illustrative and do not limit the scope of the present invention. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be made without departing from the spirit and scope of the invention.
A preparation method of a dripping pill of furotriptan succinate comprises the following steps:
(1) dissolving furaltriptan succinate and an inclusion material in proportion by using 80% ethanol as a medium, filtering the obtained solution through a microporous filter membrane to be clear, separating a furaltriptan succinate inclusion compound from the mixture, crushing the inclusion compound and sieving the crushed inclusion compound through a 50-100-mesh sieve;
(2) grinding and uniformly mixing the matrix and the stabilizer, heating and melting the mixture in water, and uniformly mixing the mixture;
(3) adding the prepared furotriptan succinate inclusion compound in the step (1) into the melt prepared in the step (2), uniformly mixing, pouring into an inclined liquid tank, and keeping the temperature at 65-75 ℃ for 10 minutes;
(4) dripping the medicinal liquid into 0-20 deg.C condensate to form dripping pill, adsorbing the condensate, and drying the dripping pill.
EXAMPLE 1-6 preparation of furotriptan succinate dropping pills
Preparing the furotriptan succinate dropping pill according to the preparation method and the raw and auxiliary materials in the following formula. Where "/" indicates unused.
Test example 1 measurement of smoothness and roundness and dissolution time limits of Frovatriptan succinate dropping pills obtained in examples 1 to 6
The smooth rounding rate and the dissolution time limit of the prepared dropping pill are detected according to the method specified in 0108 of the general rule of the four departments of the version in 2015 from the Chinese pharmacopoeia, and the measurement results are shown in table 1.
As can be seen from Table 1, the furotriptan succinate dropping pill of example 4 has better smooth rounding rate and better dissolution time limit, which shows that the furotriptan succinate dropping pill prepared by using sodium carboxymethyl starch and glyceryl monostearate as the coating substrate has excellent effect.
EXAMPLE 7-11 preparation of Frovatriptan succinate dropping pills
Preparing the furotriptan succinate dropping pill according to the preparation method and the raw and auxiliary materials in the following formula.
Test example 2 measurement of the rounding rate and the dissolution time limit of furotriptan succinate dropping pills obtained in examples 7 to 11
The measurement method was the same as in test example 1, and the measurement results are shown in Table 2.
As can be seen from table 2, the furotriptan succinate dropping pill of example 9 has better smoothness, roundness and dissolution time, which indicates that when the weight ratio of the matrix sodium carboxymethyl starch to the glyceryl monostearate is 1:1, the prepared furotriptan succinate dropping pill has more excellent effect compared with the dropping pill with other than the specific ratio.
Claims (3)
1. A dripping pill of furotriptan succinate consists of a furotriptan succinate clathrate compound, a matrix and a stabilizer, wherein the clathrate compound comprises furotriptan succinate and an inclusion material, and is characterized in that the dripping pill comprises the following components in percentage by weight:
frovatriptan succinate 15%
The inclusion material is 15 percent
70 percent of matrix
1 percent of stabilizer
And proper amount of condensate.
2. The furotriptan succinate dropping pill according to claim 1, wherein the inclusion material is β -cyclodextrin, the matrix is sodium carboxymethyl starch and glyceryl monostearate, the weight ratio is 1:1, the stabilizer is sodium dihydrogen phosphate and disodium hydrogen phosphate, and the condensate is liquid paraffin.
3. A method of preparing furotriptan succinate dropping pills according to claim 1, comprising the steps of:
(1) dissolving furaltriptan succinate and an inclusion material in proportion by using 80% ethanol as a medium, filtering the obtained solution through a microporous filter membrane to be clear, separating a furaltriptan succinate inclusion compound from the mixture, and crushing the inclusion compound and sieving the crushed inclusion compound through a 50-100-mesh sieve;
(2) grinding and uniformly mixing the matrix and the stabilizer, heating and melting the mixture in water, and uniformly mixing the mixture;
(3) adding the prepared furotriptan succinate inclusion compound in the step (1) into the melt prepared in the step (2), uniformly mixing, pouring into an inclined liquid tank, and keeping the temperature at 65-75 ℃ for 10 minutes;
(4) dripping the medicinal liquid into 0-20 deg.C condensate to form dripping pill, adsorbing the condensate, and drying the dripping pill.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911265065.8A CN110898017A (en) | 2019-12-11 | 2019-12-11 | Frovatriptan succinate dropping pill and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911265065.8A CN110898017A (en) | 2019-12-11 | 2019-12-11 | Frovatriptan succinate dropping pill and preparation method thereof |
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| Publication Number | Publication Date |
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| CN110898017A true CN110898017A (en) | 2020-03-24 |
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| CN201911265065.8A Withdrawn CN110898017A (en) | 2019-12-11 | 2019-12-11 | Frovatriptan succinate dropping pill and preparation method thereof |
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105030709A (en) * | 2015-07-29 | 2015-11-11 | 成都科创佳思科技有限公司 | Metroprolol succinate dropping pills and preparation method thereof |
| US20160243045A1 (en) * | 2006-03-06 | 2016-08-25 | Pozen Inc. | Dosage forms for administering combinations of drugs |
| CN107157943A (en) * | 2017-05-18 | 2017-09-15 | 青岛正大海尔制药有限公司 | A kind of Topiroxostat preparation and preparation method thereof |
| CN107375225A (en) * | 2017-08-24 | 2017-11-24 | 青岛正大海尔制药有限公司 | Level release formulations of a kind of butanedioic acid furan Luo Qu and preparation method thereof |
| US20170360772A1 (en) * | 2008-01-09 | 2017-12-21 | Charleston Laboratories, Inc. | Pharmaceutical compositions |
| CN109464408A (en) * | 2018-12-28 | 2019-03-15 | 正大制药（青岛）有限公司 | A kind of succinic acid SB 209509 piece |
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2019
- 2019-12-11 CN CN201911265065.8A patent/CN110898017A/en not_active Withdrawn
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20160243045A1 (en) * | 2006-03-06 | 2016-08-25 | Pozen Inc. | Dosage forms for administering combinations of drugs |
| US20170360772A1 (en) * | 2008-01-09 | 2017-12-21 | Charleston Laboratories, Inc. | Pharmaceutical compositions |
| CN105030709A (en) * | 2015-07-29 | 2015-11-11 | 成都科创佳思科技有限公司 | Metroprolol succinate dropping pills and preparation method thereof |
| CN107157943A (en) * | 2017-05-18 | 2017-09-15 | 青岛正大海尔制药有限公司 | A kind of Topiroxostat preparation and preparation method thereof |
| CN107375225A (en) * | 2017-08-24 | 2017-11-24 | 青岛正大海尔制药有限公司 | Level release formulations of a kind of butanedioic acid furan Luo Qu and preparation method thereof |
| CN109464408A (en) * | 2018-12-28 | 2019-03-15 | 正大制药（青岛）有限公司 | A kind of succinic acid SB 209509 piece |
Non-Patent Citations (4)
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| 刘晓霞等: "琥珀酸呋罗曲坦薄膜衣片的制备及体外溶出行为考察", 《中国药房》 * |
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Application publication date: 20200324 |