CN101199516A - Benzoyl secnidazole dispersant sheet and preparing method thereof - Google Patents
Benzoyl secnidazole dispersant sheet and preparing method thereof Download PDFInfo
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- CN101199516A CN101199516A CNA2007101918631A CN200710191863A CN101199516A CN 101199516 A CN101199516 A CN 101199516A CN A2007101918631 A CNA2007101918631 A CN A2007101918631A CN 200710191863 A CN200710191863 A CN 200710191863A CN 101199516 A CN101199516 A CN 101199516A
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- secnidazole
- benzoyl
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- filler
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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Abstract
The invention belongs to the field of pharmacy, relating to a benzoyl secnidazole dispersible tablet and a preparation method of the benzoyl secnidazole dispersible tablet. The invention provides a benzoyl secnidazole dispersible tablet, which comprises an active component of benzoyl secnidazole, disintegrating agent, adhesive, filler, lubricant, sweetener and surfactant. The invention also provides the preparation method of the dispersible tablet. The dispersible tablet disintegrates fast, strips fast and takes effect fast. At the same time, the dispersible tablet is convenient to be taken, and plural tablets can be taken in several times with water so that the drug can be taken in high dose. As the prodrug of the secnidazole, the benzoyl secnidazole dispersible tablet can fully develop advantages of administration in single dose.
Description
One, technical field
The present invention relates to a kind of pharmaceutical preparation and processing method thereof, exactly is a kind of benzoyl secnidazole dispersant sheet and preparation method thereof.
Two, background technology
Ameba worm and protozoa have had a strong impact on human beings'health, and the whole world is existing carries amoeba histolytica up to 500,000,000 people, and giardia lamblia the infected is about 2.5 hundred million, and trichomonacide person is about more than 200,000,000.The 5-nitroimidazoles medicine can be used for the treatment of above-mentioned infection, and wherein metronidazole has become national essential drugs, by pharmacopeia is included.Benzoic methyl nitroazole is as the prodrug of metronidazole, because the untoward reaction gentleness, and do not have halitosis etc., progressively substituted metronidazole abroad, and in existing oral mixed rotary liquid of China and capsule listing.Chinese patent 1817346A has reported the development of benzoyl metronidazole dispersion tablets, and to go on the market as new drug.
Dispersible tablet is meant rapid disintegrate of energy and homodisperse tablet in water, has the advantage of tablet and liquid system profit concurrently, has overcome both deficiencies.Compare with general tablet, dispersible tablet has good dispersing state, and disintegration time is short, and the medicine stripping is rapid, absorb soon, and the bioavailability height, untoward reaction is few, characteristics such as taking convenience.Dispersible tablet can be chewed also and can swallow, and is fit to old man, child and other particular patients ' and uses, simultaneously owing to available water disperses to take.
Yet benzoic methyl nitroazole is as the prodrug of metronidazole, and reality is brought into play still its parent drug metronidazole of drug effect in vivo, therefore can't fundamentally improve the therapeutic effect of metronidazole.Secnidazole, chemistry is by name: 1-(2-hydroxypropyl)-2-methyl-5-nitro imidazoles also is a kind of in the 5-nitroimidazoles medicine, its tablet in 1998 in China's import listing.Reported secnidazole single dose 2g (or 30mg.kg
-1) administration, all very effective to treatment giardiasis, acute bowel amebiasis and trichomonal vaginitis, secnidazole also has inhibitory action to protozoa capsule regulating liver-QI ameba when taking continuously.Single dose administration not only means and greatly makes things convenient for the patient, and the alleviation of the medicine pressure that brings thus also can reduce chemical sproof probability of occurrence, and the unique recommendation secnidazole of World Health Organization (WHO) is as the medicine of single-dose treatment amebic dysentery.This shows, in above-mentioned treatment of diseases, compare the most frequently used metronidazole at present, secnidazole with the obvious advantage has the prospect that well substitutes.
Secnidazole only has a tablet in China listing at present, its specification is 250mg/ sheet and 500mg/ sheet, bring into play the advantage of single dose administration 2g, just needs being administered once property of heavy dose to take the 4-8 sheet, administration comparatively bothers, and especially is unfavorable for patient's medication of old man, child and dysphagia.Aspect intravenously administrable, because dissolubility is about 3.4mg/mL in the secnidazole water, be not suitable for injectable powder that is prepared as convenient drug administration etc., only can be prepared as high-capacity injection, basic prescription such as the secnidazole glucose injection of domestic development is: every 100ml injection contains secnidazole 400mg, glucose 5g, also can not bring into play the advantage of secnidazole single dose administration 2g far away.Make dispersible tablet and then can make its taking convenience, adopt multi-disc in water, to disperse oral method can effectively bring into play the advantage of single dose administration together simultaneously, yet secnidazole has abnormal flavour, and water solublity is too high, therefore is not suitable for making dispersible tablet.
United States Patent (USP) 5574167 discloses serial secnidazole derivant, can effective anti-ameba worm and protozoa, and do not have abnormal flavour, thereby can not cause regurgitation, feel sick, vomiting etc.The preparation method embodiment of benzoyl secnidazole is wherein disclosed, its synthetic method is: secnidazole and Benzenecarbonyl chloride. are in the presence of pyridine, the reflux in toluene reaction, washing back organic facies crystallisation by cooling, filtration, cold toluene are washed the back and are obtained dry crude product, and crude product obtains the pure product of benzoyl secnidazole with recrystallizing methanol.But this patent had not both been carried out the structural characterization of product to each secnidazole derivant, did not also provide the physicochemical property of each product, simultaneously not mentioned its any dosage form.The benzoyl secnidazole is as the prodrug of secnidazole, and is fat-soluble good, and free from extraneous odour, is fit to make dispersible tablet.
Three, summary of the invention
Benzoyl secnidazole dispersant sheet provided by the invention is intended to solve single heavy dose (2g) administration problem to give full play to drug effect, and technical problem to be solved is to select appropriate prescription by orthogonal design.
The alleged benzoyl secnidazole of the present invention has following structural formula:
The applicant prepares with reference to U.S.'s disclosed method, chemical name: 1-(2-the hydroxypropyl)-pure product of 2-methyl-5-nitro imidazoles benzoate (benzoyl secnidazole), and product is the off-white color flaky crystal, fusing point 137-138.5 ℃.
Infrared (KBr) v cm
-1: 3130 (imidazole ring C-H), 3020 (phenyl ring C-H), 1720 (ester carbonyl groups), 1600,1480 (phenyl ring skeletons), 1530 (nitros).
1H NMR (TMS, CDCl
3, 400MH
z), δ ppm:7.91 (s, 1H, imidazoles), 7.90-7.42 (m, 5H, phenyl ring), 5.55 (s, 1H, methines), 4.70-4.44 (d, 2H, methine), 2.48 (s, 3H, methyl), 1.50-1.48 (d, 3H, methyl).
This dispersible tablet comprises active component benzoyl secnidazole and pharmaceutic adjuvant, and described pharmaceutic adjuvant comprises disintegrating agent, binding agent, filler, lubricant, sweeting agent, and each component has following percentage by weight:
Benzoyl secnidazole 50～80%
Disintegrating agent 10～40%
Filler 1～20%
Binding agent 1～5%
Lubricant 0.1～1%
Sweeting agent 0～1%.
Preferably:
Benzoyl secnidazole 60～70%
Disintegrating agent 15～35%
Filler 3～15%
Binding agent 1～5%
Lubricant 0.1～1%
Sweeting agent 0～1%.
Disintegrating agent is selected from one or more mixing disintegrating agents in carboxymethyl starch sodium or cross-linking sodium carboxymethyl cellulose or crospolyvinylpyrrolidone or low-substituted hydroxypropyl cellulose or microcrystalline Cellulose or the starch microgel.Preferably contain 0～10% starch microgel to mixing disintegrating agent.
Filler is selected from one or more mixed fillers in microcrystalline Cellulose or agar or lactose or starch or the dextrin.
Binding agent is selected from one or more binding agents in polyvinylpyrrolidone or hydroxypropyl emthylcellulose or methylcellulose or sodium carboxymethyl cellulose or the starch slurry.
Lubricant is selected from Pulvis Talci or magnesium stearate or micropowder silica gel.
Sweeting agent is selected from aspartame or stevioside or protein sugar.
The preparation method of this dispersible tablet comprises mixing, system soft material, wet grain, drying, granulate and tabletting, difference with the prior art is that the filler that will cross the benzoyl secnidazole of 200 mesh sieves and cross the disintegrating agent of 120 mesh sieves and cross 120 mesh sieves is made soft material after with the binding agent mix homogeneously, and in 50～60 ℃ of dry back granulate, tabletting.
The benzoyl secnidazole is as a kind of derivant of secnidazole, hydrolysis discharges secnidazole performance drug effect in vivo, the benzoyl secnidazole dispersant sheet taking convenience, can chew, can swallow, especially but multi-disc is used with aqueous dispersion simultaneously, but the therefore heavy dose of administration of single, thus give full play to the advantage of secnidazole single dose 2g administration.The starch microgel is as a kind of new type medicinal stuff, and its expansion rate of water absorption is very big, impels the rapid disintegrate of dispersible tablet.Benzoyl secnidazole micronization helps it and is dissolved and absorbs rapid onset and improve bioavailability.
Four, the specific embodiment
1, get benzoyl secnidazole micronization, cross 200 mesh sieves, standby.
2, get disintegrating agent and filler and pulverize, cross 120 mesh sieves, standby.
3, get
Benzoyl secnidazole 625g
Cross-linking sodium carboxymethyl cellulose 110g
Crospolyvinylpyrrolidone 90g
Starch 40g
5% polyvinylpyrrolidone 10g
Micropowder silica gel 0.5%
Aspartame 1%
Make 1000
Formula ratio benzoyl secnidazole, cross-linking sodium carboxymethyl cellulose, crospolyvinylpyrrolidone, starch are fully mixed, add 5% polyvinylpyrrolidone aqueous solution, continue to mix.After making suitable soft material, cross 20 mesh sieve system wet granulars, 50～60 ℃ of dryings, 20 mesh sieve granulate.Press recipe quantity and add micropowder silica gel and aspartame, mixing, tabletting.This dispersible tablet becomes each 3～4 of human oral.
4, get
Benzoyl secnidazole 625g
Starch microgel 50g
Carboxymethyl starch sodium 30g
Microcrystalline Cellulose 80g
Starch 150g
10% starch slurry 20g
Magnesium stearate 0.3%
Make 1000
With formula ratio benzoyl secnidazole, starch microgel, carboxymethyl starch sodium, microcrystalline Cellulose and starch, fully mix, add starch slurry, continue to mix.After making suitable soft material, the wet grain of the 20 mesh sieve systems of crossing, 50～60 ℃ of dryings, 20 mesh sieve granulate.Press recipe quantity and add magnesium stearate, mixing, tabletting.This dispersible tablet becomes each 3～4 of human oral.
Claims (4)
1. a benzoyl secnidazole dispersant sheet comprises active component benzoyl secnidazole and pharmaceutic adjuvant, it is characterized in that: each component has following percentage by weight:
Benzoyl secnidazole 50～80%
Disintegrating agent 10～40%
Filler 1～20%
Binding agent 1～5%
Lubricant 0.1～1%
Sweeting agent 0～1%.
2. dispersible tablet according to claim 1 is characterized in that:
Benzoyl secnidazole 60～70%
Disintegrating agent 15～35%
Filler 3～15%
Binding agent 1～5%
Lubricant 0.1～1%
Sweeting agent 0～1%.
3. dispersible tablet according to claim 1 and 2 is characterized in that: contain 0～10% starch microgel in the disintegrating agent.
4. the preparation method of benzoyl secnidazole dispersant sheet according to claim 1, comprise mixing, system soft material, wet grain, drying, granulate and tabletting, it is characterized in that: will cross 200 mesh sieves the benzoyl secnidazole, cross 120 mesh sieves disintegrating agent, cross 120 mesh sieves filler with the binding agent mix homogeneously after system soft material and wet grain, in 50～60 ℃ of dry back granulate, tabletting.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101918631A CN101199516A (en) | 2007-12-19 | 2007-12-19 | Benzoyl secnidazole dispersant sheet and preparing method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101918631A CN101199516A (en) | 2007-12-19 | 2007-12-19 | Benzoyl secnidazole dispersant sheet and preparing method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101199516A true CN101199516A (en) | 2008-06-18 |
Family
ID=39514996
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007101918631A Pending CN101199516A (en) | 2007-12-19 | 2007-12-19 | Benzoyl secnidazole dispersant sheet and preparing method thereof |
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| Country | Link |
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| CN (1) | CN101199516A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101874799A (en) * | 2010-06-13 | 2010-11-03 | 西安万隆制药有限责任公司 | Composition of secnidazole and lactose and preparation method thereof |
| CN104945386A (en) * | 2015-07-06 | 2015-09-30 | 南京大学 | Pyrazole nitro imidazole derivative containing secnidazole framework and preparation method thereof and application |
-
2007
- 2007-12-19 CN CNA2007101918631A patent/CN101199516A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101874799A (en) * | 2010-06-13 | 2010-11-03 | 西安万隆制药有限责任公司 | Composition of secnidazole and lactose and preparation method thereof |
| CN104945386A (en) * | 2015-07-06 | 2015-09-30 | 南京大学 | Pyrazole nitro imidazole derivative containing secnidazole framework and preparation method thereof and application |
| CN104945386B (en) * | 2015-07-06 | 2017-08-11 | 南京大学 | Pyrazoles nitro imidazole derivatives, its preparation method and the application of one class skeleton containing secnidazole |
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Open date: 20080618 |