CN101468021A - Ceftibuten colon-positioning enteric tablet - Google Patents
Ceftibuten colon-positioning enteric tablet Download PDFInfo
- Publication number
- CN101468021A CN101468021A CNA2007103084352A CN200710308435A CN101468021A CN 101468021 A CN101468021 A CN 101468021A CN A2007103084352 A CNA2007103084352 A CN A2007103084352A CN 200710308435 A CN200710308435 A CN 200710308435A CN 101468021 A CN101468021 A CN 101468021A
- Authority
- CN
- China
- Prior art keywords
- ceftibuten
- weight
- adjuvant
- colon
- mixture
- 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.)
- Pending
Links
Abstract
The invention discloses ceftibuten colon-specific enteric-coated tablets, comprising tablet cores and coating layers. The tablet cores are composed of 10-90 wt.% of ceftibuten, 2-70 wt.% of diluting auxiliary materials, 1-20 wt.% of disintegrating auxiliary materials, 1-20 wt.% of adhering auxiliary materials and 0.1-5 wt.% of lubricant auxiliary materials. The ceftibuten colon-specific enteric-coated tablets can transmit medicament to colons, improve curative effect of colonitis, have low side effect and improve compliance of patients.
Description
Technical field
The invention belongs to the medicine new technical field, specifically, relate to Ceftibuten colon-positioning enteric tablet.Be used for the treatment of colitis.
Background technology
Ceftibuten (Ceftibuten) is the third generation wide spectrum oral cephalosporin of the wild adopted company of Japanese salt initiative, chemical name: (+)-(6R, 7R)-7-((Z)-2-(2-amino-4-thiazole)-4 carboxyls-crotonamide)-8-oxygen-5-sulfur-1-nitrogen dicyclo (4,2,0) oct-2-ene-2-carboxylic acid two water things.
Ceftibuten has another name called the cephalo thiophene rises, and ceftibuten is the oral cephalosporins of a kind of semisynthetic third generation, has very strong antibacterial activity.This product is acidproof, can be oral, the tool broad spectrum antibiotic activity has strong antibacterial activity to the Enterobacter antibacterial, and is stable to beta-lactamase.1992 at first in Japan with commodity Seftem listing by name, after worldwide (except that Japan and some other Asian countries) transfer first spirit-Schering-Plough, go on the market trade name Cedax in more than 30 countries so far.The ceftibuten patent expired in 2003, and capsule and dry suspension are introduced China by Schering Plough company.
Cephalo-type antibiotics is the important component part in the anti-infection drug, cephalosporins class industry has developed into and has accounted for the important industry of world's anti-infectives sales volume more than 40% approximately, the growth rate of cephalosporin has surpassed the medical product average speed of growth at home, is about 28%.
The characteristics of third generation cephalosporin are: has a broad antifungal spectrum, mainly can suppress gram-negative bacteria, and comprise bacillus pyocyaneus effective.Stable to beta-lactamase, the concentration height of infection site tissue, the half-life is longer, and nephrotoxicity is little.But the most kinds of the third generation are wanted drug administration by injection, and are very inconvenient.Cefixime that can be oral (cefixime) absorbs less than half.And ceftibuten (ceftibuten, CTB) bioavailability reaches 90%, is worthy to be popularized very much.This product oral absorption is very fast and complete, the bioavailability height, and the peak concentration of single oral ceftibuten 400mg and intramuscular injection cefuroxime 500mg is suitable, and the mean half-life of ceftibuten is 1.5～1.6h, then the about 4h of mean residence time MRT.The effective blood drug concentration of this product is lasting than cefuroxime, if calculate with 〉=2mg/L concentration, ceftibuten can be kept 9h, and cefuroxime 4h only.This product successive administration, with measured value relatively, the blood peak concentration of drug is slightly high during than single-dose, but does not see the drug accumulation phenomenon.Therefore, this result of the test shows that the antibiotic after effect (PAE) of ceftibuten is more lasting, and to some respiratory pathogen, its PAE can reach more than the 10h, to some infectious disease, oral 400mg/ time of every day, once a day, can reach therapeutic purposes.
In sum, ceftibuten absorbs good, short treating period, and side effect is little, and being be evaluated as is present best oral cephalosporin, therefore, is worth pharmaceutical manufacturer's research and development.
The oral colon-specific drug release system is a kind of novel medicine-releasing system that development in recent years is got up, be utilize one or more technology to make in gastrointestinal tract, not discharge medicine after the preparation oral administration and when preparation arrives colon the drug-supplying system of rapid release, make medicine performance part or whole body therapeutic effect, improve drug safety, reduced toxic and side effects.Compared its superiority with other medicine-releasing system, mainly contained: (1) improves the colon local drug concentration, improves curative effect, helps treating the colon local patholoic change.As: ulcerative colitis, colon cancer and constipation etc.; (2) colon positioning release has guaranteed that medicine do not degraded by gastrointestinal enzyme and destroy in upper gi tract, can make macromole class medicines such as polypeptide, protein realize oral administration; (3) colon administration can be avoided first pass effect; (4) solid preparation is chronic in the transhipment of colon, can reach 20～30 hours, and therefore the research and development to sustained-release preparation have directive significance.
The oral colon-specific drug release system is obtaining very big progress through the research of more than ten years aspect galenic pharmacy and the relevant auxiliary materials, formed the drug-supplying system of multiple release mechanism, as pH control type medicine-releasing system, time control type medicine-releasing system, pressure control type medicine-releasing system, flora flip-over type medicine-releasing system etc.
PH control type medicine-releasing system is the colon positioning feed preparation that utilizes the design of gastrointestinal tract pH difference.The pH difference at each position of gastrointestinal tract is raise to small intestinal gradually by stomach, and the pH of general stomach is 0.9～1.5, and the pH of small intestinal is 6.5～8.0.Therefore the optional pH that is used in〉7 o'clock dissolved pH dependency material parcel labels, can protect label by stomach and small intestinal, make it to discharge medicine at ileum far-end or colon.
The medicine oral administration arrives about 6 hours of colon time, promptly so-called time lag through stomach, small intestinal successively.Can utilize control release technic that medicine is not discharged at stomach, small intestinal, discharge, reach the purpose of conlon targeting and arrive colon.
The human gastrointestinal tract wriggling produces pressure, in the harmonization of the stomach small intestinal, because there is a large amount of Digestive systems to exist, has cushioned the suffered pressure of object.In colon, moisture is by a large amount of absorptions, and enterokinesia produces direct pressure to object, and object is broken, and can utilize this principle to make pressure control type medicine-releasing system.
Stomach and intestinal epimere bacterium enzymatic activity are very low, vegetable polysaccharides such as pectin, alginic acid, carrageenin and azo-compound or glycoside prerequisite material etc. can not absorb in the upper gi tract cracking, and arrive large intestine, if but cracking under the effect of big enteric plexus bacterium enzyme peptization enzyme, azo reductase, glycosidase etc. with original shape.Select skeleton or the coating material of these materials for use as medicine, can be with drug delivery to conlon targeting release.
Summary of the invention
The objective of the invention is to utilize positioning release medicine mechanism, a kind of time control type, pH control type and Cefdinir colon-positioning enteric tablet that the two combines of comprising is provided.
To achieve these goals, the present invention adopts following technical scheme:
A kind of Ceftibuten colon-positioning enteric tablet, comprise label and coatings, label is made up of ceftibuten, dilution adjuvant 2～70 weight %, disintegrate adjuvant 1～20 weight %, bonding adjuvant 1～20 weight % and lubricated adjuvant 0.1～5 weight % of 10～90 weight %.
As preferably, in above-mentioned Ceftibuten colon-positioning enteric tablet, described label is made up of ceftibuten, dilution adjuvant 2～70 weight %, disintegrate adjuvant 1～20 weight %, bonding adjuvant 1～20 weight % and lubricated adjuvant 0.1～5 weight % of 40～70 weight %.
In above-mentioned Ceftibuten colon-positioning enteric tablet, coatings is divided into pH type key-course, time type key-course or both are used in combination;
The pH key-course is made up of acrylic resin, plasticizer, lubricant, and wherein the weight % of acrylic resin is 30～75, the weight % of plasticizer is 10～30, the weight % of lubricant is 20～40;
The time key-course is one or more the mixture in acrylic resin, polyethylene glycol 6000, polyvidone, ethyl cellulose, the hypromellose;
The solvent of coatings is one or more the mixture in water, ethanol, isopropyl alcohol, methanol, the tert-butyl alcohol, the acetone.
As preferably, the aforesaid propylene acid resin is one or more the mixture among acrylic resin L100, acrylic resin S100, Eudragit E 100, acrylic resin RL100, acrylic resin RS100, Eudragit E 30D, the acrylic resin L30D; Plasticizer is one or more the mixture in diethyl phthalate, dibutyl phthalate, triethyl citrate, the last of the ten Heavenly stems two butanoic acid diethylester, Oleum Ricini, oleic acid, silicone oil, span, tween, propylene glycol, glycerol, Macrogol 200, PEG400, the Macrogol 600; Lubricant is one or more the mixture in Pulvis Talci, magnesium stearate, the micropowder silica gel; The coatings solvent is 70%～95% alcoholic solution or acetone.
Best plasticizer is one or more the mixture in diethyl phthalate, Oleum Ricini and tween 80, the last of the ten Heavenly stems two butanoic acid diethylester, the triethyl citrate; Best lubricant is a Pulvis Talci.
In above-mentioned Ceftibuten colon-positioning enteric tablet, described dilution adjuvant refers to one or more the mixture in lactose, microcrystalline Cellulose, starch, dextrin, amylum pregelatinisatum, the calcium sulfate; The disintegrate adjuvant is meant one or more the mixture in carboxymethyl starch sodium, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, starch, the hydroxypropyl starch; Bind adjuvant and be meant one or more mixture in starch slurry, hydroxypropyl methylcellulose, polyvidone, syrup, microcrystalline Cellulose, sodium carboxymethyl cellulose, the methylcellulose; Lubricated adjuvant is meant one or more the mixture in Pulvis Talci, magnesium stearate, the micropowder silica gel.
The key of Ceftibuten colon-positioning enteric tablet is the selection of the composition and the coatings prescription of label.The release principle that pH type key-course and time type key-course are used in combination is that medicine is formed in the label that meets in the colon medium, wraps time key-course (gastric solubleness clothing layer) and pH type key-course (enteric coating layer) again.Enteric coating layer is not dissolved when medicine process stomach, and enteric coating layer begins dissolving when arriving small intestinal, and the time is about 1h, gastric solubleness clothing layer dissolving then, about 3h of time.The dissolving of two-layered coating and small intestinal meet the duration of runs, can be with transport of drug to colon.The time that discharges by the controllable thickness pharmacy thing of regulating pH type key-course or time type key-course.
Compared with prior art, the present invention has following beneficial effect: the Ceftibuten colon-positioning enteric tablet of the present invention's design, medicine accurately can be transported to colon, and improved the therapeutic effect of colitis, and the side effect reduction, improved patient's compliance.
The specific embodiment
Embodiment 1 pH control type Ceftibuten colon location preparation,
Label prescription 1
Ceftibuten 200g
Carboxymethyl starch sodium 6g
Lactose 30g
Polyvidone 2.5g
Pulvis Talci 4.5g
75% ethanol liquid 50ml
Label prescription 2
Ceftibuten 200g
Carboxymethyl starch sodium 6g
Starch 30g
Polyvidone 3.5g
Magnesium stearate 4.5g
75% alcoholic solution 50ml
Label prescription 3
Ceftibuten 200g
Low-substituted hydroxypropyl methylcellulose 15g
Starch 20g
Methylcellulose 3g
Pulvis Talci 7.5
75% alcoholic solution 50ml
Label prescription 4
Ceftibuten 200g
Low-substituted hydroxypropyl methylcellulose 15g
Lactose 20g
Polyvidone 3g
Micropowder silica gel 7.5g
Acetone 50ml
Coating solution prescription 1
Acrylic resin S100 10g
Diethyl phthalate 4g
Polyethylene glycol 6000 2.5g
Pulvis Talci 6g
Ethanol 200ml
Coating solution prescription 2
Eudragit E 30D 10g
The last of the ten Heavenly stems two butanoic acid diethylester 1.5g
Polyethylene glycol 6000 2.5g
Pulvis Talci 3g
Acetone 200ml
Coating solution prescription 3
Acrylic resin RL100 10g
Triethyl citrate 2g
Pulvis Talci 2g
Acetone 150ml
The preparation of label: take by weighing ceftibuten, dilution adjuvant, disintegrate adjuvant and bonding adjuvant and cross 80 mesh sieves, mixing adds solvent system soft material, cross 18 mesh sieves, granulate, put into 60 ℃ of dryings of baking oven, cross 16 mesh sieve granulate, add lubricated auxiliary materials and mixing, tabletting is worth label.
The preparation of PH control type coating solution prescription: acrylic resin is dissolved in the solvent, again other compositions is dissolved in the solvent, with homogenizer homogenize 10 minutes.Suspension is poured in the acrylic resin soln, continued in the coating process to stir.
Prepared Ceftibuten colon location preparation is carried out dissolution in vitro experiment, and the result shows in 37 ℃ of gastric juice 2 hours, and stripping is lower than 1%; Stripping in 3 hours is lower than 4% in the phosphate buffer of 37 ℃ of pH6.8; Hour stripping of the phosphate buffer 1 of 37 ℃ of pH7.6 is more than 85%.
Embodiment 2 time control type Ceftibuten colon positioning release medicine preparation
The label prescription is with embodiment 1.
The preparation of time control type coating solution: acrylic resin is stirred and gets final product adding other components with dissolution with solvents.
Label is carried out multiple coatings.Internal layer coating liquid consists of hypromellose 8g, and solvent is 70%～90% ethanol 200ml.Inferior outer coating solution consists of ethyl cellulose 3g, hypromellose 0.3g, solvent is 70%～90～ethanol 100ml.By the thickness of controlling diaphragm, regulate time lag.Discharging time lag is 3～4 hours.The alcoholic solution of outermost layer bag acrylic resin L100.By the dissolution experiment, the result shows that coated tablet begins dissolving at small intestinal, and discharging time lag is 3.5 hours.
Embodiment 3 time control type and pH dependency colon location preparation
The label prescription is with embodiment 1.
Time key-course coating solution prescription 1:
Eudragit E 100 50g
Polyvidone 15g
Polyethylene glycol 6000 5g
Ethanol 500ml
PH key-course coating solution prescription 1:
Acrylic resin L100 8g
Acrylic resin S100 2g
Diethyl phthalate 4ml
Oleum Ricini 6ml
Tween 80 2ml
Pulvis Talci 6g
Ethanol 200ml
Time key-course coating solution prescription 2
Ethyl cellulose 25g
Hypromellose 5g
Polyethylene glycol 6000 5g
Ethanol 500ml
PH key-course coating solution prescription 2
Acrylic resin S100 30g
Triethyl citrate 5g
Pulvis Talci 7.5g
Ethanol 500ml
The preparation method of pH control type coating solution prescription is with embodiment 1, and the preparation method of time control type coating solution prescription is with embodiment 2.
Inlet temperature is controlled at 30 ℃～50 ℃ during coating, and atomizing pressure is 0.5～1.5bar.
Claims (6)
1. Ceftibuten colon-positioning enteric tablet, comprise label and coatings, label is made up of ceftibuten, dilution adjuvant 2～70 weight %, disintegrate adjuvant 1～20 weight %, bonding adjuvant 1～20 weight % and lubricated adjuvant 0.1～5 weight % of 10～90 weight %.
2. Ceftibuten colon-positioning enteric tablet as claimed in claim 1, it is characterized in that described label by the ceftibuten of 40～70 weight %, dilution adjuvant 2～70 weight %, disintegrate adjuvant 1～20 weight %, bind adjuvant 1～20 weight % and lubricated adjuvant 0.1～5 weight % forms.
3. Ceftibuten colon-positioning enteric tablet as claimed in claim 1 is characterized in that coatings is divided into pH type key-course, time type key-course or both are used in combination.
The pH key-course is made up of acrylic resin, plasticizer, lubricant, and wherein the weight % of acrylic resin is 30～75, the weight % of plasticizer is 10～30, the weight % of lubricant is 15～40;
The time key-course is one or more the mixture in acrylic resin, polyethylene glycol 6000, polyvidone, ethyl cellulose, the hypromellose;
The solvent of coatings is one or more the mixture in water, ethanol, isopropyl alcohol, methanol, the tert-butyl alcohol, the acetone.
4. Ceftibuten colon-positioning enteric tablet as claimed in claim 3 is characterized in that described acrylic resin is one or more the mixture among acrylic resin L100, acrylic resin S100, Eudragit E 100, acrylic resin RL100, acrylic resin RS100, Eudragit E 30D, the acrylic resin L30D; Plasticizer is one or more the mixture in diethyl phthalate, dibutyl phthalate, triethyl citrate, the last of the ten Heavenly stems two butanoic acid diethylester, Oleum Ricini, oleic acid, silicone oil, span, tween, propylene glycol, glycerol, Macrogol 200, PEG400, the Macrogol 600; Lubricant is one or more the mixture in Pulvis Talci, magnesium stearate, the micropowder silica gel; The coatings solvent is 70%～95% alcoholic solution or acetone.
5. Ceftibuten colon-positioning enteric tablet as claimed in claim 4 is characterized in that described plasticizer is one or more the mixture in diethyl phthalate, Oleum Ricini and tween 80, the last of the ten Heavenly stems two butanoic acid diethylester, the triethyl citrate; Best lubricant is a Pulvis Talci.
6. Ceftibuten colon-positioning enteric tablet as claimed in claim 1 is characterized in that described dilution adjuvant refers to one or more the mixture in lactose, microcrystalline Cellulose, starch, dextrin, amylum pregelatinisatum, the calcium sulfate; The disintegrate adjuvant is meant one or more the mixture in carboxymethyl starch sodium, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, starch, the hydroxypropyl starch; Bind adjuvant and be meant one or more mixture in starch slurry, hydroxypropyl methylcellulose, polyvidone, syrup, microcrystalline Cellulose, sodium carboxymethyl cellulose, the methylcellulose; Lubricated adjuvant is meant one or more the mixture in Pulvis Talci, magnesium stearate, the micropowder silica gel.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007103084352A CN101468021A (en) | 2007-12-29 | 2007-12-29 | Ceftibuten colon-positioning enteric tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007103084352A CN101468021A (en) | 2007-12-29 | 2007-12-29 | Ceftibuten colon-positioning enteric tablet |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101468021A true CN101468021A (en) | 2009-07-01 |
Family
ID=40825983
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007103084352A Pending CN101468021A (en) | 2007-12-29 | 2007-12-29 | Ceftibuten colon-positioning enteric tablet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101468021A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011139253A3 (en) * | 2010-05-04 | 2012-05-31 | Mahmut Bilgic | Pharmaceutical compositions comprising ceftibuten |
| CN107865828A (en) * | 2016-09-24 | 2018-04-03 | 上海中医药大学附属曙光医院 | Prevent and treat oral colon location preparation, the preparation method and applications of colon metastasis of cancer |
| CN111228234A (en) * | 2020-01-07 | 2020-06-05 | 宋凤香 | Coated lidocaine and preparation method and application thereof |
-
2007
- 2007-12-29 CN CNA2007103084352A patent/CN101468021A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011139253A3 (en) * | 2010-05-04 | 2012-05-31 | Mahmut Bilgic | Pharmaceutical compositions comprising ceftibuten |
| CN107865828A (en) * | 2016-09-24 | 2018-04-03 | 上海中医药大学附属曙光医院 | Prevent and treat oral colon location preparation, the preparation method and applications of colon metastasis of cancer |
| CN111228234A (en) * | 2020-01-07 | 2020-06-05 | 宋凤香 | Coated lidocaine and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2490012C2 (en) | Drug delivery systems containing weakly alkaline selective 5-ht3 serotonine antagonist and organic acids | |
| JP6976946B2 (en) | A pharmaceutical composition containing an inhibitor of URAT1 having strong bioactivity. | |
| ES2649063T3 (en) | Pharmaceutical formulations containing rifaximin, procedures for obtaining it and method of treatment of intestinal disease | |
| JPH11508578A (en) | Oral drug with sustained release reversible proton pump inhibitor | |
| KR20050083770A (en) | Gastric acid secretion inhibiting composition | |
| CN101757042A (en) | Probiotic pellet preparation and preparing method thereof | |
| RU2327446C2 (en) | Composition of large intestine release | |
| US4370313A (en) | Nitrofurantoin dosage form | |
| CN103285017B (en) | Compound isosorbide mononitrate aspirin sustained-release capsule preparation and preparation method | |
| CN101716132B (en) | Febuxostat enteric preparation | |
| CN102552256A (en) | Ilaprazole enteric capsule and preparation method thereof | |
| CN101468021A (en) | Ceftibuten colon-positioning enteric tablet | |
| HU184196B (en) | Process for producing preparation containing 7-/d-2-amino-2-phenylacetamino/-3-methyl-3-cephem-4-carboxylic acid monohydrate | |
| CN109044988A (en) | A kind of metformin hydrochloride medicinal composition and its preparation method and application | |
| CN101596162B (en) | Doxycycline hyclate enteric-coated pellet | |
| CN101468022A (en) | Cefdinir colon-positioning enteric tablet | |
| WO2005058282A1 (en) | Double pellet formulation of proton pump inhibitors and clarithromycin for the treatment of gastrointestinal ulcer, and method for producing the same | |
| CN101732280B (en) | Oral preparation of novel colonic positioning release medicine | |
| CN203677566U (en) | Double-layer tablet for treating helicobacter pylori | |
| CN102552214A (en) | Ilaprazole enteric capsule and preparation method thereof | |
| CN101143143A (en) | Medicine for treating gastroesophageal reflux disease and functional dyspepsia | |
| CN100500161C (en) | Azithromycin micro-pill capsule and its preparing method | |
| CN103006611B (en) | Omeprazole enteric bilayer slow-release tablet | |
| CN102018659A (en) | Intestine positioning preparation of glycyrrhetic acid, glycyrrhetinic acid and salts of glycyrrhetic acid and glycyrrhetinic acid, and preparation method and application thereof | |
| CN101011369A (en) | Colon-specific ornidazole tablet |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20090701 |