CN101543482A - Nano calcium carbonate enteric-coated bioadhesive tablets and their preparation method - Google Patents
Nano calcium carbonate enteric-coated bioadhesive tablets and their preparation method Download PDFInfo
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- CN101543482A CN101543482A CN200910043312A CN200910043312A CN101543482A CN 101543482 A CN101543482 A CN 101543482A CN 200910043312 A CN200910043312 A CN 200910043312A CN 200910043312 A CN200910043312 A CN 200910043312A CN 101543482 A CN101543482 A CN 101543482A
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- enteric
- calcium carbonate
- biological adhesive
- adhesive tablet
- coated
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Abstract
The present invention pertains to the technical field of pharmaceutical preparations. The present invention provides a kind of nano calcium carbonate enteric-coated bioadhesive tablets and their preparation method. The enteric-coated bioadhesive tablets contain the following ingredients: a) the tablet core made from nano calcium carbonate and usable minor ingredients; b) the enteric coating layer made from polyacrylic resin enteric coating material and the minor ingredients that can be used as pharmaceuticals. There are two types of tablet cores. One is bioadhesive prescription granule and the other is disintegrating granule. The nano calcium carbonate enteric-coated bioadhesive tablets prepared by the present invention possess the features of positioning, fast disintegration and bioadhesion. The main medicine is not released in stomach. After entering duodenum, the coating layer will be quickly removed. The disintegrating granule in tablet core makes the tablet core disintegrated in a short time, and the bioadhesive granule clings to the upper section of small intestine for a long time and plays a role of interrupting the enterohepatic circulation of lead; in addition, this nano calcium carbonate enteric-coated bioadhesive tablet has very good extraneous releasing effect and stability and may be developed into a new-type lead removing pharmaceutical.
Description
Technical field
The invention belongs to technical field of medicine, relate to enteric biological adhesive tablet of a kind of nano-calcium carbonate and preparation method thereof, be used for as treating and prevent saturnine medicine.
Background technology
Chronic lead poisoning is a kind of occupation disease and epidemic diseases present stage in China, and modern cityization and industrialization make people's Pb-B generally higher to the pollution of environment.Epidemiological study shows, Chinese children has 100,000,000 above Pb-Bs to exceed standard, lead exceeds standard and can cause interior a plurality of organs of body and tissue to sustain damage, mainly comprise: central nervous system, hemopoietic system, liver and kidney etc., seriously influence people's physical and mental health, especially even more serious to child's Physique growth, psychological maturity, intelligence development and learning behavior influence.
At present, clinically drive plumbous medicine and mostly be chelating agent class medicine such as DMSA and EDTA etc., promptly utilize chelating agent and lead ion to form water miscible lead complex again by renal excretion, this class medicine is for driving the most frequently used also effective method of lead.Its determined curative effect, but have significant disadvantages: 1 toxic and side effects is big; 2 poor selectivity, chelating agent have also been taken away essential trace element in the body when driving lead; 3 these type of medicines are confined to drug administration by injection more, medication inconvenience, and expense is higher; 4 chronic nephropathys, chronic kidney clearance rate reduction person weak effect.And driving lead, traditional Chinese medicine exist curative effect time long, the shortcoming that mechanism is unclear.
In view of above reason, the objective of the invention is to develop a kind of novel oral plumbous medicine that drives.
The object of the present invention is achieved like this:
According to the body internal dynamics feature of lead, the ability of hepatic secretion lead is strong especially, and plumbous concentration is in the blood tens times in the bile, but heavily is absorbed into blood through intestinal-liver circulation, and the plumbous amount that excretes naturally seldom.Therefore, principle of the present invention is to utilize CO
3 2-The lead that discharges with intestinal carries out displacement reaction and forms the ceruse of utmost point indissoluble, the plumbous enterohepatic circulation of blocking-up at intestinal, can discharge the lead of bile secretion effectively from feces, and the lead in the tissue can enter blood and liver according to homoiostasis, and then discharge from gastrointestinal tract again, finally reach and drive away purpose plumbous in the body.Compare with ordinary calcium carbonate, nano-calcium carbonate has that particle is thin, specific surface area is big, good crystalline, whiteness be than advantages such as height, thus the present invention with nano-calcium carbonate as principal agent, developing it becomes a kind of novel oral medication and the saturnine medicine of prevention.
Common calcium preparation comprises that calcium carbonate has the saturnine function of prevention, and its mechanism of action is Ca
2+With Pb
2+Competitive antagonism, such preparation is by increasing Ca
2+In the absorbtivity of small intestinal upper end and competitive antagonism Pb
2+Absorption, make Pb
2+The amount that absorption enters human body reduces, and finally reaches the saturnine function of prevention, yet it is not significantly driven away and therapeutical effect for the higher patient of Pb-B, and therefore, common calcium preparation comprises that calcium carbonate can not be as saturnine medicine.
And the present invention requires to play a role is CO
3 2-Group, and its sharpest edges just are to absorb and can play expeling and treat saturnine effect by blocking plumbous enterohepatic circulation.Based on CO
3 2-Can produce CO with the gastric acid reaction under one's belt
2, made the CO that blocks plumbous enterohepatic circulation effect
3 2-Can not get protection, so the present invention utilizes enteric-coating material that it is carried out coating can to avoid CO
3 2-Decomposition under one's belt.In addition because medicine is very fast by small intestinal epimere speed, and difficulty soluble salt precipitation displacement reaction speed is slower, therefore the present invention is prepared into the enteric biological adhesive tablet with nano-calcium carbonate, its coatings after entering duodenum is removed rapidly, the quick disintegrate of label, bioadhesion type granule in the prescription can adhere to the small intestinal epimere for a long time, prolong nano-calcium carbonate and plumbous displacement reaction time, bring into play nano-calcium carbonate substantially and block the effect of plumbous enterohepatic circulation, play treatment and prevent saturnine effect.So the invention provides a kind of enteric biologic adhesion preparation of nano-calcium carbonate, and preparation method thereof.
Summary of the invention
The objective of the invention is to prepare that a kind of good effect, price are low, few side effects, preparation method be simple, can and prevent saturnine new oral medicine as treatment.
The pharmaceutical preparation of enteric, the stripping that should make said preparation not produce or seldom produce active component during the stomach by the patient in oral back, and when leaving stomach and enter intestinal, can dissolve and discharge active component quickly.The enteric bioadhesion tablet of the nano-calcium carbonate of a kind of oral administration provided by the invention, the technical scheme that it adopts is:
A. principal agent is a nano-calcium carbonate.
B. the label adjuvant comprises bioadhesive polymer, binding agent, filler, disintegrating agent, lubricant etc.
C. coating material comprises enteric crylic acid resin coating material, plasticizer, lubricant etc.
The key of nano calcium carbonate enteric-coated biological adhesive tablet is the selection of the composition and the coating prescription of label.
The composition of label has two kinds of prescription granulometric composition, is: bioadhesion type granule and disintegration-type granule.Bioadhesion type granule is made up of principal agent, bioadhesive polymer and binding agent, and the disintegration-type granule is made up of principal agent, binding agent and disintegrating agent.
The selected bioadhesive polymer of bioadhesion type granule often selects carbomer, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl-cellulose in the label, with bonding force and release profiles is evaluation index, find that list is too strong with the carbomer adhesion property, release is poor, and single general with other biological adhesive agent adhesion, so the preferred a certain proportion of carbomer of the present invention and hydroxypropyl emthylcellulose are as bioadhesive polymer.
The selected binding agent of bioadhesion type granule often selects polyvinylpyrrolidone, Polyethylene Glycol, hypromellose and Different concentrations of alcohol aqueous solution etc. in the label, complexity and dried particulate fine powder amount with soft material conglobation property, granulation are evaluation index, find that the ethanol water aggregative index is comparatively desirable, therefore preferred alcohol aqueous solution of the present invention, wherein more preferably 50% ethanol water as binding agent.
The selected disintegrating agent of disintegration-type granule often selects carboxymethyl starch sodium, starch, microcrystalline Cellulose, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose etc. in the label, with the release performance is evaluation index, find that carboxymethyl starch sodium, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose disintegrative are strong, consumption is difficult for adjusting, the starch disintegrating property is general, microcrystalline Cellulose disintegrating property comparatively ideal and consumption is easy to adjust, so preferably microcrystalline cellulose of the present invention.
The selected binding agent of disintegration-type granule often selects polyvinylpyrrolidone, Polyethylene Glycol, hypromellose and Different concentrations of alcohol aqueous solution etc. in the label, complexity and dried particulate fine powder amount with soft material conglobation property, granulation are evaluation index, find that hypromellose aqueous solution aggregative index is comparatively desirable, therefore the preferred hypromellose aqueous solution of the present invention, wherein more preferably 3% hypromellose aqueous solution as binding agent.
The particulate weight ratio of bioadhesion type granule and disintegration-type is often selected 4:1 in the label, 3:1,2:1,1:1,1:2,1:3 etc., with release and adhesion is the integrated survey index, and when finding the particle weight ratio for 2:1, release and adhesion are preferable, therefore, the present invention's preferred bioadhesion type granule and the particulate weight ratio of disintegration-type are 2:1.
Lubricant can be selected for use as stearic acid, magnesium stearate, hydrogenated vegetable oil, Pulvis Talci, Polyethylene Glycol etc., the preferred magnesium stearate of the present invention in the label.
Comprise enteric macromolecular material, plasticizer, lubricant, opacifier etc. in the coating prescription.
Coating prescription midgut soluble high molecular material selection polyacrylic resin class and cellulose family, with pH responsive type and clothing membrane stability is index, the sensitivity of discovery polyacrylic resin class and good stability are in cellulose family, therefore, optimization polypropylene acid resin class enteric macromolecular material of the present invention: Eudragit L30D-55 and Eudragit L100-55.
Plasticizer often selects diethyl phthalate, dibutyl phthalate, triacetin, triethyl citrate, tributyl citrate etc., optimization citric acid triethyl of the present invention in the coating prescription.
The specific embodiment
(1) by two kinds of prescription granulometric composition label
A bioadhesion type granulometric composition:
B disintegration-type granulometric composition:
Nano calcium carbonate enteric-coated biological adhesive tablet label is formed
(2) enteric layer
Preparation method:
1) preparation of label
Get nano-calcium carbonate, carbomer, the hydroxypropyl emthylcellulose crushing screening of recipe quantity, mixing adds the binding agent ethanol water, mixing granulation, and drying is crossed 16 mesh sieve granulate, gets bioadhesion type granule; Get nano-calcium carbonate, the microcrystalline Cellulose of recipe quantity and pulverize and sieve, mixing adds binding agent hydroxypropyl emthylcellulose aqueous solution, mixing granulation, and drying is crossed 16 mesh sieve granulate, gets the disintegration-type granule; Take by weighing bioadhesion type granule and disintegration-type granule certain proportion, uniform mixing adds 5% carboxymethyl starch sodium and 0.5% magnesium stearate, and tabletting promptly gets nano calcium carbonate enteric-coated biological adhesive tablet label;
2) preparation of enteric layer coating
Eudragit L100-55 is dissolved in the ethanol, triethyl citrate, the micronization Pulvis Talci that adds recipe quantity mix enteric coating liquid;
3) preparation of enteric coatel tablets
Get nano calcium carbonate enteric-coated biological adhesive tablet label, the bag enteric layers makes weightening finish 3%.Promptly get nano calcium carbonate enteric-coated biological adhesive tablet.
Experimental example 1
This experimental example 1 relates to the research of the prepared nano calcium carbonate enteric-coated biological adhesive tablet stability test of the present invention.
The prepared nano calcium carbonate enteric-coated biological adhesive tablet of the present invention was placed 6 months through temperature 40, relative humidity 75%, and accelerated test shows that its appearance character, content and identification check and other inspection items all take place obviously to change; Nano calcium carbonate enteric-coated biological adhesive tablet is placed test in 6 months through room temperature and is investigated, and the result shows that its appearance character, content and identification check and other inspection items all do not take place significantly to change, and illustrates that nano calcium carbonate enteric-coated biological adhesive tablet has good stability.
Experimental example 2
This experimental example 2 relates to the research of the prepared nano calcium carbonate enteric-coated biological adhesive tablet release in vitro degree of the present invention.
[method] carries out according to the relevant basket law regulation of changeing of 2005 editions appendix of Chinese Pharmacopoeia.
The selection of dissolution medium: the condition in the simulated gastric fluid simulated gastric fluid, the condition in the buffer simulation duodenum intestinal juice environment of pH5.8.
Change the basket method by 2005 editions Chinese Pharmacopoeias, with simulated gastric fluid 500ml, rotating speed is 120r.min
-1, temperature is 37 ± 0.5 ℃, and tablet is dropped in the process container, startup rotation immediately also picks up counting, and adds behind the 2h and is preheated to 37 ℃ of Na
2HP0
4Solution is transferred pH to 5.8, continues to stir, and respectively at 0.25,0.5,1,2,3, the 4h 5ml that takes a sample adds 5ml equality of temperature medium simultaneously.Extract at 5ml and to add 10 μ l concentrated hydrochloric acid in the liquid, standardize solution is a 10ml solution behind the ultrasonic 10min, gets subsequent filtrate 30 μ l, adds calcium developer 4ml and mixes, and measures trap at 571nm wavelength place after stablize 2min, according to the Ca with drafting
2+Standard curve Equation for Calculating drug level is drawn the drug release rate curve.
2h in simulated gastric fluid is stable for [result] nano calcium carbonate enteric-coated biological adhesive tablet of the present invention, and all right in the stripping of the buffer of pH5.8, the accumulative total stripping reaches more than 60% in the 2h, and the accumulative total stripping reaches more than 90% in the 4h.
Experimental example 3
This experimental example 3 relates to the research of the prepared nano calcium carbonate enteric-coated biological adhesive tablet external biological adhesion property of the present invention.
The experiment of [method] external adhesion: get one of the rabbit of fasting 24h, auricular vein injection air is put to death, and gets small intestinal, content is cleaned up and to soak preservation standby with simulation duodenal juice.Treating excess syndrome is tested medicine, tablet is contacted with mucous membrane of small intestine after simulating duodenum liquid wetting 10min earlier, and apply power 50g, keep 2min, on hook is a plastic bag, adds water by transfusion bag with 5ml/min speed in plastic bag, excessive and separate until Yin Lali, take by weighing the weight of water in plastic bag and the bag, be and organize the adhesion size.
External adhesion time experiment: tablet is contacted with mucous membrane of small intestine after simulating duodenum liquid wetting 10min, do not apply power, it is soaked in the simulation duodenal juice, under the room temperature, observe tablet isolating time from goldbeater's skin, be adhesion time.
Claims (4)
1, a kind of nano calcium carbonate enteric-coated biological adhesive tablet is characterized in that described enteric biological adhesive tablet is made up of following ingredients: a) label of being made up of nano-calcium carbonate and pharmaceutically acceptable auxiliaries; B) enteric coat layer of forming by enteric material and pharmaceutically acceptable auxiliaries.Medicinal adjuvant is a kind of of bioadhesive polymer, filler, disintegrating agent, binding agent, lubricant or several in the described label; Described enteric coating series of strata adopt the pH sensitive high polymer materials.
2, nano calcium carbonate enteric-coated biological adhesive tablet according to claim 1 is characterized in that: the content of nano-calcium carbonate is 100-800mg in this enteric biological adhesive tablet label, and label is by bioadhesion type granule and two kinds of prescriptions of disintegration-type granule granulometric composition; Enteric coat layer accounts for the 1.5-4% of sheet anharmonic ratio example in this enteric biological adhesive tablet, and pH responsive type enteric material is a polyacrylic resin class material in the enteric coat layer, and its content accounts for the 5%-40% of casing liquid gross weight.
3, according to the described nano calcium carbonate enteric-coated biological adhesive tablet of claim 1-2, bioadhesion type granule in this enteric biological adhesive tablet label is made up of nano-calcium carbonate, bioadhesive polymer and binding agent, bioadhesive polymer is a kind of in carbomer, hydroxypropyl emthylcellulose, the chitosan or several, and binding agent is the ethanol water of 30%-70% (v/v); Disintegration-type granule in this enteric biological adhesive tablet label is made up of nano-calcium carbonate, binding agent and disintegrating agent, disintegrating agent is a kind of in polyvinylpolypyrrolidone, microcrystalline Cellulose, the carboxymethyl starch sodium or several, and binding agent is the hydroxypropyl emthylcellulose aqueous solution of 1%-3%; Bioadhesion type granule and the particulate weight ratio of disintegration-type are between the 1:1-3:1 in this enteric biological adhesive tablet label; Also comprise magnesium stearate lubricant in this enteric biological adhesive tablet label and add disintegrating agent carboxymethyl base Starch Sodium.
4, according to the described nano calcium carbonate enteric-coated biological adhesive tablet of claim 1-2, it is characterized in that the used macromolecular material of described polyacrylic resin class coatings is 5.0-5.5 to the sensitivity value of pH, be specially a kind of among Eudragit L30D-55, EudragitL100-55 and the Eudragit RS100 or several; Also comprise plasticizer triethyl citrate and lubricant micronization Pulvis Talci in this enteric biological adhesive tablet enteric coat layer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910043312A CN101543482A (en) | 2009-05-06 | 2009-05-06 | Nano calcium carbonate enteric-coated bioadhesive tablets and their preparation method |
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|---|---|---|---|
| CN200910043312A CN101543482A (en) | 2009-05-06 | 2009-05-06 | Nano calcium carbonate enteric-coated bioadhesive tablets and their preparation method |
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|---|---|
| CN101543482A true CN101543482A (en) | 2009-09-30 |
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|---|---|---|---|
| CN200910043312A Pending CN101543482A (en) | 2009-05-06 | 2009-05-06 | Nano calcium carbonate enteric-coated bioadhesive tablets and their preparation method |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103070844A (en) * | 2013-01-28 | 2013-05-01 | 万平 | Locating quick-release biological adhesive and application thereof |
| CN111035768A (en) * | 2018-10-15 | 2020-04-21 | 北京大学 | Small intestine transporter targeted nano calcium carbonate composition for improving oral absorption of insoluble drugs |
-
2009
- 2009-05-06 CN CN200910043312A patent/CN101543482A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103070844A (en) * | 2013-01-28 | 2013-05-01 | 万平 | Locating quick-release biological adhesive and application thereof |
| CN105560203A (en) * | 2013-01-28 | 2016-05-11 | 万平 | Positioning rapidly-released biological adhesive, preparation method and applications |
| CN111035768A (en) * | 2018-10-15 | 2020-04-21 | 北京大学 | Small intestine transporter targeted nano calcium carbonate composition for improving oral absorption of insoluble drugs |
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Application publication date: 20090930 |