CN1833652A - Sustained release composns preparation of Fudosteine and clarithromycin - Google Patents
Sustained release composns preparation of Fudosteine and clarithromycin Download PDFInfo
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- CN1833652A CN1833652A CN 200610035075 CN200610035075A CN1833652A CN 1833652 A CN1833652 A CN 1833652A CN 200610035075 CN200610035075 CN 200610035075 CN 200610035075 A CN200610035075 A CN 200610035075A CN 1833652 A CN1833652 A CN 1833652A
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Abstract
A slowly-releasing composite medicine for treating the diseases in respiratory system is prepared from Fuduositan (15-30 Wt %), clarithromycin (10-40), and auxiliary (rest) including paralyser.
Description
Technical field
The present invention relates to a kind of medicine, more particularly, the present invention relates to the slow release combination preparation of a kind of Fudosteine and clarithromycin.
Background technology
The chemical name of Fudosteine is (-)-(R)-2-amino-3-(3-hydroxypropyl sulfydryl) propanoic acid, is by the exploitation of Japanese SS drugmaker, and permission gives Japan lucky rich (Yoshitomi) drugmaker.This medicine was in official listing in 2002, and commodity are called Cleanal (SS company), Spelear (Ji Fu company).Fudosteine is new cysteine derivative, and stronger expectorant effect is arranged.The import preparation that these class medicines such as ethyl cystein, carbonyl methyl cysteine are arranged on the China market at present.The curative effect of these medicines is not really satisfactory, and particularly their toxic and side effects is very strong, and unstable chemcial property.The expectorant effect of Fudosteine is 3 times of carbonyl methyl cysteine, and toxic and side effects is minimum, chemical property is stable, infects eliminating the phlegm of chronic respiratory system diseasess such as disease, casual property bronchitis applicable to bronchial asthma, chronic bronchitis, bronchiectasis, pulmonary tuberculosis, pneumoconiosis disease, emphysema, atypia acid-fast bacillus.
Chinese patent application 02121468.9 discloses a kind of oral preparation composition, and it contains as the Fudosteine of active component and excipient, and wherein excipient is a carboxymethyl starch sodium.Weight in Fudosteine is 1 part, and the consumption of carboxymethyl starch sodium is 0.01～5 weight portion.The disclosed dosage form of this application is tablet or hard capsule.
Clarithromycin is the semi-synthetic new Macrolide of 14 yuan of rings, also claims clarithromycin, and its interior metabolism product 14-hydroxyl clarithromycin performance antibacterial action can reach high concentration at gastric, and the ability of permeating gastric mucosa is preferably arranged.
Chinese patent application 03147713.5 discloses the medical ophthalmic preparation of a kind of clarithromycin, and wherein the effective dose of clarithromycin and its acceptable soluble-salt is 0.1%～3%, and all the other are that eye pasting substrate is or/and the other medicines acceptable carrier; Eye pasting substrate can be selected from vaseline, liquid paraffin, anhydrous lanolin, and pharmaceutically acceptable salt can be Lactobionate, citrate, hydrochlorate, lactate.
Chinese patent application CN03141742.6 a kind of slowly released clamycin capsule disclosed; it is made up of capsule shell and slow-release micro-pill; slow-release micro-pill is made up of pastille micropill and coatings; particle diameter≤the 2.5mm of slow-release micro-pill; its preparation method is at first with the formula mixture of pastille micropill; place ball-type micropill comminutor to make the pastille micropill, then the pastille micropill is made slow-release micro-pill with coating material, again slow-release micro-pill is filled in capsule shell and obtains slow releasing capsule promptly.
Respiratory system disease is a kind of commonly encountered diseases, frequently-occurring disease, and worldwide its sickness rate is all higher, and the trend of increase is arranged, and it is China human mortality's a second largest factor.World population is just being stepped into senescence at present, and the over-65s old man accounts for sizable ratio because of respiratory system disease death.Breathe heavily, cough, expectorant, scorching four diseases is respiratory system disease common symptons, reciprocal causation simultaneously.Expectorant is the product of respiratory inflammation, can stimulate respiratory mucosa, causes cough and asthma, and can increase the weight of to infect.When acute/chronic bronchitis or patients with chronic obstructive pulmonary diseases respiratory failure, spend height or form the expectorant bolt, can block respiratory tract and cause suffocating as patient's thick sputum.
Up to the present, do not see the combination preparation that uses Fudosteine and clarithromycin in the prior art as yet, therefore be necessary to provide the slow release combination preparation of a kind of Fudosteine and clarithromycin, come the therapeutic alliance respiratory tract disease that disappears, so that satisfy the vast needs of suffering from the respiratory system disease patient, alleviate the medication burden.
Summary of the invention
The object of the present invention is to provide the combination preparation of a kind of Fudosteine and clarithromycin.
Another object of the present invention provides the preparation method of preparation Fudosteine and clarithromycin combination preparation.
A further object of the present invention provides the purposes that the medicine aspect that is combined in preparation treatment respiratory system disease of the Fudosteine of effective dose and the clarithromycin that effective dose is gone up in treatment is gone up in treatment.
For achieving the above object, on the one hand, the invention provides the combination preparation of a kind of Fudosteine and clarithromycin, this combination preparation comprises active component Fudosteine, active component clarithromycin and pharmaceutically acceptable pharmaceutic adjuvant, wherein, with the weight percent meter of each component, Fudosteine can account for 5～30% of this combination preparation, clarithromycin can account for 10～40% of this combination preparation, and all the other are pharmaceutic adjuvant.
In the above-mentioned combination preparation, in the gross weight of combination preparation, can further contain 5～60% blocker, also be that pharmaceutic adjuvant comprises blocker and other pharmaceutic adjuvant; Blocker can be selected from as next group one or more in material: hypromellose, carbopol (carbopol), sodium carboxymethyl cellulose, hydroxyethylmethyl-cellulose, methylcellulose, carboxyethyl cellulose, carboxy-propyl cellulose, mountain Yu's acid glyceride, fatty acid and fatty acid ester.Certainly, also can select other suitable blocker for use.
More preferably, in the above-mentioned combination preparation, the percentage by weight of each component is that Fudosteine 10-15%, clarithromycin 15-20%, blocker are 30-50%, and all the other are other pharmaceutic adjuvant.
Combination preparation of the present invention can be to mix complex tablet, compound adhesive wafer or the composite particles agent of making by Fudosteine and clarithromycin; also can be the hybrid particles capsule that is mixed and made into by Fudosteine granule and clarithromycin granule, can also be the lamination tablet of being made by one or more layers Fudosteine layer and one or more layers clarithromycin layer.
In the combination preparation of the present invention, other pharmaceutic adjuvant can comprise filler, binding agent, lubricant, disintegrating agent, low-density adjuvant, extender or blowing agent etc., wherein:
Filler can be one or more in lactose, fructose, glucose, sucrose, mannitol, sorbitol, xylitol, maltose alcohol, erythritol, starch and the modified starch;
Binding agent can be one or more in gelatin, arabic gum, guar gum, xanthan gum, hydroxypropyl emthylcellulose, polyvinylpyrrolidone, ethyl cellulose, dextrin, starch, Polyethylene Glycol, chitosan, maltodextrin, modified starch, pectin, carrageenan and the poloxamer;
Lubricant can be one or more in hydrophilic gel, magnesium stearate, stearic acid, calcium stearate, sodium stearyl fumarate, colloidality silicon dioxide and the Talcum;
Disintegrating agent can be one or more in corn starch, crospolyvinylpyrrolidone, sodium starch glycolate, hydroxyethyl-cellulose, ethyl cellulose, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, amylum pregelatinisatum, microcrystalline Cellulose, microcrystalline Cellulose sodium, alginic acid, alginic acid sodium salt, compressibility sorbitol and the carboxymethylcellulose calcium;
The low-density adjuvant comprises acrylic resin II number, III number, octadecanol, magnesium stearate etc.;
Extender comprises cross-linked pvp, basic magnesium carbonate, sodium carbonate, calcium carbonate etc.
On the other hand, the present invention also provides the preparation method of Fudosteine and clarithromycin combination preparation.For example,, Fudosteine, clarithromycin, blocker and other pharmaceutic adjuvant mix homogeneously can be added finite concentration ethanol water (as 30-70%) again and granulate, add magnesium stearate mix homogeneously tabletting then promptly for tablet; Also Fudosteine, clarithromycin, blocker and pharmaceutic adjuvant mix homogeneously can be added magnesium stearate mix homogeneously direct compression promptly.
The preparation method of Fudosteine and slowly released clamycin capsule can for:
(1) with Fudosteine, clarithromycin, blocker and other pharmaceutic adjuvant mix homogeneously, in coating pan, make fine pellet core with distilled water or ethanol water, dry then, for example dry under 40-50 ℃, make exsiccant ball core;
(2) exsiccant ball core is removed fine powder after, place coating pan to rotate, the blowing hot-air preheating for example is preheated to 30-40 ℃, coating solution is sprayed on above the mobile ball core, the blowing hot-air drying, spraying, drying so reach required weight until coatings repeatedly again.
Again on the one hand, the present invention also provides the purposes of the treatment Fudosteine of going up effective dose and the medicine aspect that is combined in preparation treatment respiratory system disease for the treatment of the clarithromycin of going up effective dose.These respiratory system diseases include but not limited to that bronchial asthma, chronic bronchitis, acute bronchitis, bronchiectasis, pulmonary tuberculosis, pneumoconiosis disease, emphysema, atypia acid-fast bacillus infect disease or diffusivity bronchitis.
The advantage of combination preparation of the present invention is to use conveniently, once take administration Fudosteine and clarithromycin simultaneously, and the effect of this administering drug combinations is better than individually dosedly, and therapeutic effect is better, short treating period, effective percentage height, is particularly suitable for the therapeutic alliance respiratory system disease.Slow release combination preparation drug slow of the present invention discharges, thereby can reduce administration number of times, improves patient's compliance, reduces incidence rate of adverse reaction.
In addition, that combination preparation of the present invention can produce is slower, blood drug level more stably, guarantees that blood drug level in the treatment window, reduces the toxic and side effects of medicine, and improves people's compliance; And, confirmed already that the use in conjunction of Fudosteine and clarithromycin can significantly change pharmacokinetic properties separately, improve the curative effect of treatment respiratory system disease.Ordinary preparation does not contain blocker, and its rate of release is fast, and there is peak valley phenomenon in blood drug level, can't guarantee that blood drug level in the treatment window, when blood drug level is too high, can produce the transport of drug saturated phenomenon, be unfavorable for that medicine shifts to respiratory system, and the side effect effect of medicine is big; Cross when low when blood drug level, medicine can't reach desired effects.
Below, explain the present invention in conjunction with specific embodiments, but these specific embodiment are not to be limitation of the invention.
Specific embodiments
Embodiment 1
The prescription of the Fudosteine of present embodiment and clarithromycin slow-release combination preparation is:
Fudosteine ... ... ... ... 200g
Clarithromycin ... ... ... ... 250g
Lactose ... ... ... ... ... .220g
Low-viscosity hydroxypropylcelluloand ... ... ..30g
The high viscosity hydroxypropyl cellulose ... ... ..200g
Pulvis Talci ... ... ... ... ..40g
Magnesium stearate ... ... ... ... 10g
Film-coat ... ... ... ... ..40g
Make 1000, every contains Fudosteine 200mg, clamycin 2 50mg.
Concrete preparation method:
Quantitatively take by weighing Fudosteine, clarithromycin, hypromellose and lactose by prescription, mix 10min in the quick mixer granulator high speed of KJz one 10 types, with the suitable soft material of distilled water system, 18～20 mesh sieves are granulated, 18 mesh sieve granulate and add Pulvis Talci and the magnesium stearate mixing behind 60 ℃ of hot air dryings, be pressed into every and contain Fudosteine 200, the label of clamycin 2 50mg; Label is pressed well-established law bag film-coat, in order to improve the bitterness of clarithromycin.
Embodiment 2
The prescription of the Fudosteine of present embodiment and clarithromycin slow-release combination preparation is:
Fudosteine ... ... ... ... 400g
Clarithromycin ... ... ... ... 500 grams
Lactose ... ... ... ... ... .220g
Low-viscosity hydroxypropylcelluloand ... ... ..30g
The high viscosity hydroxypropyl cellulose ... ... ..200g
Pulvis Talci ... ... ... ... ..40g
Magnesium stearate ... ... ... ... 10g
Film-coat ... ... ... ... ..40g
Write out a prescription with this, press the preparation method of embodiment 1 substantially, but use 40% the suitable soft material of ethanol water system.Make 1000 of Fudosteine and clarithromycin slow-released tablets altogether, every contains Fudosteine 400mg, clarithromycin 500mg.
Embodiment 3
In the Fudosteine of present embodiment and the clarithromycin slow-release combination preparation, the prescription of medicament pellet is:
Fudosteine ... ... ... ... 200g
Clarithromycin ... ... ... ... 250 grams
Lactose ... ... ... ... ... .220g
Low-viscosity hydroxypropylcelluloand ... ... ..30g
The high viscosity hydroxypropyl cellulose ... ... ..200g
Microcrystalline Cellulose ... ... ... ... .25g
Water ... ... ... ... ... an amount of
The coating solution prescription:
Acrylic resin RS100.................100g
Triethyl citrate ... ... ... ..10g
Polyethylene glycol 6000 ... ... ... ..20g
Ethanol ... ... ... ... ... .850ml
Make 1000 capsules, each contains Fudosteine 200mg, clamycin 2 50mg.
Concrete preparation method:
With the mixture mix homogeneously in the micropill prescription, in coating pan, make fine pellet core with distilled water or ethanol water, dry under 40-50 ℃ then, make exsiccant ball core; Weigh; After exsiccant ball core removed fine powder, place coating pan to rotate, blowing hot-air is preheated to 30-40 ℃, coating solution is sprayed on above the mobile ball core, and the blowing hot-air drying, spraying, drying so reach required weight until coatings repeatedly again.
Fudosteine of the present invention and clarithromycin slow-released tablet are and medicinal fibre ether macromolecular material system The standby sustained release preparation that forms is compared with ordinary preparation, and this medicine sterilizing ability is stronger, takes number of times and subtracts Few (ordinary preparation need take 3-4 time every day, and the sustained release tablets of invention only need are once a day), bad Reacting phase is to reducing, have the characteristics that tolerate preferably, so therapeutic scheme will be easier, for Patient provides a kind of new treatment to select, so development Fudosteine clarithromycin slow-release Preparation is of great significance clinical.
Claims (9)
1, the combination preparation of a kind of Fudosteine and clarithromycin, this combination preparation comprises active component Fudosteine, active component clarithromycin and pharmaceutic adjuvant, wherein, weight percent meter with each component, Fudosteine accounts for 5～30% of described combination preparation, clarithromycin accounts for 10～40% of described combination preparation, and all the other are pharmaceutic adjuvant.
2, combination preparation as claimed in claim 1 is characterized in that, described combination preparation further contains 5～60% blocker; Described blocker is selected from as next group one or more in material: hypromellose, carbopol (carbopol), sodium carboxymethyl cellulose, hydroxyethylmethyl-cellulose, methylcellulose, carboxyethyl cellulose, carboxy-propyl cellulose, mountain Yu's acid glyceride, fatty acid and fatty acid ester.
3, combination preparation as claimed in claim 2, it is characterized in that, weight percent meter with each component, described Fudosteine accounts for the 10-15% of described combination preparation, described clarithromycin accounts for the 15-20% of described combination preparation, described blocker accounts for the 30-50% of described combination preparation, and all the other are other pharmaceutic adjuvant.
4, combination preparation as claimed in claim 1 or 2 is characterized in that, described combination preparation is to mix complex tablet, compound adhesive wafer or the composite particles agent of making by Fudosteine and clarithromycin.
5, combination preparation as claimed in claim 1 or 2 is characterized in that, described combination preparation is the hybrid particles capsule that is mixed and made into by Fudosteine granule and clarithromycin granule.
6, combination preparation as claimed in claim 1 or 2 is characterized in that, described combination preparation is the lamination tablet of being made by one or more layers Fudosteine layer and one or more layers clarithromycin layer.
7, a kind of method for preparing Fudosteine and clarithromycin combination preparation, this method comprises:
(1) with Fudosteine, clarithromycin, blocker and other pharmaceutic adjuvant mix homogeneously, in coating pan, make fine pellet core with distilled water or ethanol water, dry then, make exsiccant ball core;
(2) exsiccant ball core is removed fine powder after, place coating pan to rotate, the blowing hot-air preheating is sprayed on coating solution above the mobile ball core, the blowing hot-air drying, spraying, drying so reach required weight until coatings repeatedly again.
8, the purposes of the medicine aspect that is combined in preparation treatment respiratory system disease of the clarithromycin of the Fudosteine of effective dose and the last effective dose of treatment in the treatment.
9, purposes as claimed in claim 8, it is characterized in that described respiratory system disease is bronchial asthma, chronic bronchitis, acute bronchitis, bronchiectasis, pulmonary tuberculosis, pneumoconiosis disease, emphysema, atypia acid-fast bacillus infection disease or diffusivity bronchitis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610035075 CN1833652A (en) | 2006-04-19 | 2006-04-19 | Sustained release composns preparation of Fudosteine and clarithromycin |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610035075 CN1833652A (en) | 2006-04-19 | 2006-04-19 | Sustained release composns preparation of Fudosteine and clarithromycin |
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| CN1833652A true CN1833652A (en) | 2006-09-20 |
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| CN 200610035075 Pending CN1833652A (en) | 2006-04-19 | 2006-04-19 | Sustained release composns preparation of Fudosteine and clarithromycin |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101152172B (en) * | 2006-09-29 | 2010-05-12 | 北京德众万全药物技术开发有限公司 | Fudosteine oral solid composition |
| CN103768011A (en) * | 2012-10-23 | 2014-05-07 | 天津药物研究院 | Fudosteine injection and preparation method thereof |
| CN103893146A (en) * | 2012-12-25 | 2014-07-02 | 天津药物研究院 | Fudosteine-containing sustained-release agent |
| CN106176967A (en) * | 2016-07-19 | 2016-12-07 | 中南民族大学 | A kind of pharmaceutical composition of diastole bronchus smooth muscle |
-
2006
- 2006-04-19 CN CN 200610035075 patent/CN1833652A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101152172B (en) * | 2006-09-29 | 2010-05-12 | 北京德众万全药物技术开发有限公司 | Fudosteine oral solid composition |
| CN103768011A (en) * | 2012-10-23 | 2014-05-07 | 天津药物研究院 | Fudosteine injection and preparation method thereof |
| CN103893146A (en) * | 2012-12-25 | 2014-07-02 | 天津药物研究院 | Fudosteine-containing sustained-release agent |
| CN106176967A (en) * | 2016-07-19 | 2016-12-07 | 中南民族大学 | A kind of pharmaceutical composition of diastole bronchus smooth muscle |
| CN106176967B (en) * | 2016-07-19 | 2017-09-01 | 中南民族大学 | A kind of pharmaceutical composition of diastole bronchus smooth muscle |
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Open date: 20060920 |