CN101112386A - Smectite middle gut positioning releasing pellet and method for preparing the same - Google Patents
Smectite middle gut positioning releasing pellet and method for preparing the same Download PDFInfo
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- CN101112386A CN101112386A CNA2007100150992A CN200710015099A CN101112386A CN 101112386 A CN101112386 A CN 101112386A CN A2007100150992 A CNA2007100150992 A CN A2007100150992A CN 200710015099 A CN200710015099 A CN 200710015099A CN 101112386 A CN101112386 A CN 101112386A
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- montmorillonitum
- releasing pellet
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Abstract
The present invention is used for treating various acute and chronic diarrheas with the diseased parts at the colon and rectum, which can be packaged by small packages for oral administration and can be further made into other formulations for oral administration. The drug can not be released in the stomach and the small intestine after the oral administration of the drug, so as to ensure to transfer the drug to the colon quantitatively. The prevention has higher specificity to treat the colitis, which can improve the efficacy and has convenient administration.
Description
Technical field
The present invention relates to a kind of Montmorillonitum pharmaceutical preparation, be specifically related to smectite middle gut positioning releasing pellet and preparation method thereof, belong to field of pharmaceutical technology.
Technical background
Montmorillonitum looses as a kind of mucosa protective agent efficiently, and the adsorbent of pathogenic bacteria, virus and toxin thereof is used for the treatment of various acute and chronic diarrhoeal diseasess, high effect nontoxic, now more than 100 countries and regions listing in the whole world.The Montmorillonitum preparation that has now gone on the market also has tablet, suspensoid, granule, dispersible tablet, and they all are ordinary preparations.When being used for the treatment of site of pathological change in the various acute and chronic diarrhoeal diseases of colon and rectum especially colitis, adopt oral or coloclysis, the coloclysis curative effect is significantly better than oral.
Behind the common Montmorillonitum preparation oral, medicine promptly is adsorbed on upper digestive tract before arriving colon or absorption affinity is saturated substantially, thereby relatively poor to the therapeutic effect of colitis; The retention enema administration, drug effect is more oral good, but medicine is at the colon skewness, individual variation is big, and medicine often only can arrive rectum and sigmoid colon, difficult transverse colon and the ascending colon of arriving, this kind route of administration makes the patient very painful simultaneously, and medical worker's burden is also heavy.
Behind the montmorillonite clone targeting releasing preparation oral administration,, do not discharge in the not disintegrate of upper digestive tract medicine, be transported to the colon position after, discharge medicine, thereby valid density exceeds several times than ordinary preparation in colon position topical remedy.The local drug concentration height helps more pathogenic bacteria, virus and toxin thereof and is adsorbed fixing and excretes, and more helps strengthening the defense function of local mucosa.So can improve the curative effect of site of pathological change in the various acute and chronic diarrhoea of colon and rectum especially colitis etc.Taking convenience again can improve the compliance of extensive patients.
The patent of inventor's application, montmorillonite clone targeting releasing preparation and preparation method thereof, application number: 200610171010.7, smectite middle gut location releasing piece and smectite middle gut targeting release capsule have been narrated, its preparation method is: Montmorillonitum is added or do not add adjuvants such as adhesive, disintegrating agent, lubricant granulate routinely or do not granulate, make label or the Capsules commonly used of packing into, wrap in the molten resin film clothing of all insoluble ph dependent form colon in gastric juice, the intestinal fluid more outward; Or Montmorillonitum added or do not add adjuvants such as adhesive, disintegrating agent, lubricant make granule or do not granulate the molten special-purpose Capsules of ph dependent form colon of packing into.Behind this preparation oral, be transported to colon with preparation integral body, because volume is big, be subjected to digestive tract to carry the food rhythm and pace of moving things to influence greatly (close as pylorus etc.), long in the harmonization of the stomach small intestinal holdup time, it is slow to bring into play curative effect.
The objective of the invention is to propose a kind of new smectite middle gut positioning releasing pellet and preparation method thereof in order to overcome the various acute and chronic diarrheal deficiency of existing Montmorillonitum preparation for treating site of pathological change at colon and rectum.
Summary of the invention
The object of the present invention is achieved like this: Montmorillonitum is added common medicinal supplementary material or is not added adjuvant, make the microspheric granula of diameter in the 0.5-2.5mm scope with common method in the galenic pharmacy after, outsourcing one deck all insoluble film-coat in gastric juice, intestinal fluid again.
The available adjuvant commonly used of the present invention comprises: one or more in microcrystalline Cellulose, sodium carboxymethyl cellulose, micropowder silica gel, polyvidone, starch, magnesium stearate, sucrose and the dextrin.
The present invention available in gastric juice, intestinal fluid all insoluble film-coat dress material, comprising: polyacrylic resin III, dibutyl phthalate (DBP) and ethanol.Using proportioning is polyacrylic resin III40g-60g, dibutyl phthalate (DBP) 1ml-5ml, 95% ethanol 800ml-1200ml.Optimization polypropylene acid resin III50g, 95% ethanol 1000ml, dibutyl phthalate (DBP) 3ml.
Smectite middle gut positioning releasing pellet of the present invention, but it is oral after the packing when the various acute and chronic diarrhoea of colon and rectum to be used for the treatment of site of pathological change, and it is oral also can further to make other dosage form.Oral dose is 2-3 time on the one, 1 clothes Montmorillonitum 1-3g.
Advantage of the present invention is: 1. big at the gastrointestinal tract distribution area, and the bioavailability height, in the various acute and chronic diarrhoea of colon especially colitis, specificity is higher to the treatment site of pathological change; 2. because particle diameter is little, be subjected to digestive tract to carry the food rhythm and pace of moving things to influence little (close as pylorus etc.); 3. good fluidity is evenly big or small, is easy to handle (as divided dose, encapsulated, tabletting); 4. the compatibility that is fit to compound preparation.
Below be to preliminary release in vitro degree of the present invention and in vivo test, with effect and the effect that proves conlon targeting release of the present invention.
Test example one.Smectite middle gut positioning releasing pellet disintegration and drug release rate are measured:
According to of the requirement of Chinese Pharmacopoeia version in 2005 to the colon soluble and intestine soluble preparation, detect its disintegration, be simulated gastric fluid (hydrochloric acid solution 9 → 1000) 2 hours, simulated intestinal fluid (pH6.8 phosphate buffer) 3 hours, medicine all should not discharge or dissolve, and in the phosphate buffer of pH7.8-8.0, the film-coat dissolving, disintegrate also discharges medicine.Measure disintegration time mensuration method and drug release rate algoscopy according to Chinese Pharmacopoeia version in 2005 in view of the above, measure disintegration and drug release rate.
The disintegration time mensuration result: measure according to Chinese Pharmacopoeia version disintegration time mensuration in 2005 method, the result meets the requirement of Chinese Pharmacopoeia version in 2005 to the colon soluble and intestine soluble preparation.
Drug release rate measurement result: measure according to Chinese Pharmacopoeia version drug release rate in 2005 algoscopy first method, 100 rev/mins of rotating speeds, 37 ± 5 ℃ of temperature, weight is sent out the burst size of working sample at each time point, the result is in hydrochloric acid solution (9 → 1000) and pH6.8 phosphate buffer, not disintegrate of micropill, no drug release, and in the phosphate buffer of pH7.8, micropill disintegrate in 30 minutes, medicine accumulative total burst size＞40%, 60 minute medicine accumulative total burst size＞80%, 90 minutes medicines accumulative total burst size＞98% meets the requirement of Chinese Pharmacopoeia version in 2005 to the colon soluble and intestine soluble preparation.
Test example two.The smectite middle gut positioning releasing pellet in vivo test.
Montmorillonitum is added an amount of mixing of barium sulfate, make micropill, select healthy premenopausal volunteers 6 examples, oral 3 grams of every example carried out a human body X-ray trace research every 30 minutes, result of study confirms micropill not disintegrate in 4 hours, begin disintegrate after 4 hours, illustrate that micropill discharges medicine before arriving human body ileocecum position, after arriving human body ileocecum position, the micropill disintegrate begins to discharge medicine.
Specific embodiments
The present invention is described further by the following examples.
Embodiment 1: the preparation one of Montmorillonitum micropill
Micropill prescription: Montmorillonitum 600g, microcrystalline Cellulose 18g, wetting agent an amount of (50% ethanol)
Preparation technology: get micropill recipe quantity supplementary material mixing, add wetting agent, cross 20 mesh sieve system wet granulars, wet granular is placed the coating pan of 60-80r/min, behind the sealed rolling 10-30min, uncap, the pot wall is heated to 40-60 ℃, dry rolling 1-2h. topples over micropill and put in the baking oven dryly, promptly gets the Montmorillonitum micropill.
Embodiment 2: the preparation two of Montmorillonitum micropill
Micropill prescription: Montmorillonitum 600g, sodium carboxymethyl cellulose 10g, micropowder silica gel 3g.
Preparation technology: get micropill recipe quantity supplementary material mixing, sodium carboxymethyl cellulose is added suitable quantity of water make 1% aqueous solution, add in the Montmorillonitum, make suitable soft material, cross 20 mesh sieve system wet granulars, drop in the spherical forming machine (500r/min) rolling balling at a high speed. topple over micropill and put in the baking oven dryly, promptly get the Montmorillonitum micropill.
Embodiment 3: the preparation three of Montmorillonitum micropill
Micropill prescription: Montmorillonitum 600g, polyvidone 70g.
Preparation technology: the Montmorillonitum " ball mould " of some is dropped in the centrifugal granulator, to the polyvidone liquid of its jet surface atomizing and be sprinkled into montmorillonite powder, granule is increased and circular, topple over micropill and put in the baking oven dryly, promptly get the Montmorillonitum micropill.
Embodiment 4: the preparation four of Montmorillonitum micropill
Micropill prescription: Montmorillonitum 600g preparation technology: add suitable quantity of water in the Montmorillonitum, make suitable soft material, extrude into ball, put drying in the baking oven, promptly get the Montmorillonitum micropill with crowded ball machine.
Embodiment 5: the preparation one of smectite middle gut positioning releasing pellet
Be formulated in the molten resin film coating solution of all insoluble ph dependent form colon in gastric juice, the intestinal fluid: take by weighing polyacrylic resin III50g, pour in the ethanol of 1000ml 95%, stir, add dibutyl phthalate (DBP) 3ml, stir, polyacrylic resin III is all dissolved, standby.
Embodiment 1-embodiment 4 made micropills are put respectively in the coating machine, pressed the film coating method, be used in the molten resin film coating solution of all insoluble ph dependent form colon in gastric juice, the intestinal fluid, the bag film coating.45 ℃ of hot blasts, hydrojet speed 5ml/ minute, 45 rev/mins of rotating speeds in micropill coating weightening finish 10%-20%, can obtain the smectite middle gut positioning releasing pellet of embodiment 1-embodiment 4 correspondences.
Embodiment 6: the preparation two of smectite middle gut positioning releasing pellet
Be formulated in the molten resin film coating solution of all insoluble ph dependent form colon in gastric juice, the intestinal fluid: take by weighing polyacrylic resin III40g, pour in the ethanol of 1000ml 95%, stir, add dibutyl phthalate (DBP) 5ml, stir, polyacrylic resin III is all dissolved, standby.
Micropill prescription: Montmorillonitum 600g, sucrose 60g.
Preparation technology: Montmorillonitum is placed in the fluidising chamber of fluidized coating machine, the hot-air of proper temperature enters fluidising chamber, makes Montmorillonitum floating mixed; Spray into sucrose liquid then, make the Montmorillonitum powder be gathered into micropill, stop sucrose liquid when particle diameter reaches requirement and spray into; The gained micropill directly behind the fluid bed inner drying, sprays into the molten resin film coating solution of all insoluble ph dependent form colon in gastric juice, intestinal fluid, in micropill coating weightening finish 10%-20%, promptly gets smectite middle gut positioning releasing pellet.
Embodiment 7: the preparation three of smectite middle gut positioning releasing pellet
Be formulated in the molten resin film coating solution of all insoluble ph dependent form colon in gastric juice, the intestinal fluid: take by weighing polyacrylic resin III45g, pour in the ethanol of 800ml 95%, stir, add dibutyl phthalate (DBP) 4ml, stir, polyacrylic resin III is all dissolved, standby.
Embodiment 1-embodiment 4 made micropills are put respectively in the coating machine, pressed the film coating method, be used in the molten resin film coating solution of all insoluble ph dependent form colon in gastric juice, the intestinal fluid, the bag film coating.45 ℃ of hot blasts, hydrojet speed 5ml/ minute, 45 rev/mins of rotating speeds in micropill coating weightening finish 10%-20%, can obtain the smectite middle gut positioning releasing pellet of embodiment 1-embodiment 4 correspondences.
Embodiment 8: the preparation four of smectite middle gut positioning releasing pellet
Be formulated in the molten resin film coating solution of all insoluble ph dependent form colon in gastric juice, the intestinal fluid: take by weighing polyacrylic resin III60g, pour in the ethanol of 1200ml 95%, stir, add dibutyl phthalate (DBP) 2ml, stir, polyacrylic resin III is all dissolved, standby.
Embodiment 1-embodiment 4 made micropills are put respectively in the coating machine, pressed the film coating method, be used in the molten resin film coating solution of all insoluble ph dependent form colon in gastric juice, the intestinal fluid, the bag film coating.45 ℃ of hot blasts, hydrojet speed 5ml/ minute, 45 rev/mins of rotating speeds in micropill coating weightening finish 10%-20%, can obtain the smectite middle gut positioning releasing pellet of embodiment 1-embodiment 4 correspondences.
Embodiment 9: the preparation five of smectite middle gut positioning releasing pellet
Be formulated in the molten resin film coating solution of all insoluble ph dependent form colon in gastric juice, the intestinal fluid: take by weighing polyacrylic resin III60g, pour in the ethanol of 1200ml 95%, stir, add dibutyl phthalate (DBP) 3ml, stir, polyacrylic resin III is all dissolved, standby.
Embodiment 1-embodiment 4 made micropills are put respectively in the coating machine, pressed the film coating method, be used in the molten resin film coating solution of all insoluble ph dependent form colon in gastric juice, the intestinal fluid, the bag film coating.45 ℃ of hot blasts, hydrojet speed 5ml/ minute, 45 rev/mins of rotating speeds in micropill coating weightening finish 1C%-20%, can obtain the smectite middle gut positioning releasing pellet of embodiment 1-embodiment 4 correspondences.
Embodiment 10: the preparation of smectite middle gut targeting release capsule
With embodiment 1-embodiment 6 made micropills, add an amount of magnesium stearate, mixing, the Capsules commonly used of packing into can obtain the smectite middle gut targeting release capsule of embodiment 1-embodiment 6 correspondences.
Embodiment 11: the preparation of smectite middle gut location releasing piece
With embodiment 1-embodiment 6 made micropills, add an amount of magnesium stearate, mixing, tabletting, the smectite middle gut that can obtain embodiment 1-embodiment 6 correspondences is located releasing piece.
Claims (8)
1. smectite middle gut positioning releasing pellet is characterized in that containing Montmorillonitum, adjuvant commonly used and all insoluble dress material in gastric juice, intestinal fluid.Wherein dress material comprises: polyacrylic resin III, dibutyl phthalate (DBP) and 95% ethanol.
2. according to the described smectite middle gut positioning releasing pellet preparation method of claim 1, it is characterized in that with Montmorillonitum or with Montmorillonitum and auxiliary materials and mixing commonly used, after making the microspheric granula of diameter in the 0.5-2.5mm scope with common method in the galenic pharmacy, reuse dress material outsourcing thin film clothing.
3. according to the described smectite middle gut positioning releasing pellet of claim 1, it is characterized in that adjuvant commonly used comprises: one or more in microcrystalline Cellulose, sodium carboxymethyl cellulose, micropowder silica gel, polyvidone, starch, magnesium stearate, sucrose and the dextrin.
4. according to the described smectite middle gut positioning releasing pellet of claim 1, it is as follows to it is characterized in that prescription is formed weight ratio:
Montmorillonitum 600g
Adjuvant 18g=200g commonly used
5. according to the described smectite middle gut positioning releasing pellet of claim 1, it is characterized in that the dress material proportioning is as follows:
Polyacrylic resin III40g-60g
Dibutyl phthalate (DBP) 2ml-5ml
95% ethanol 800ml-1200ml.
6. according to the described smectite middle gut positioning releasing pellet of claim 1, it is characterized in that the dress material optimum ratio is as follows:
Polyacrylic resin III50g
95% ethanol 000ml
Dibutyl phthalate (DBP) 3ml.
7. according to the described smectite middle gut positioning releasing pellet of claim 1, but it is oral after the packing when the various acute and chronic diarrhoea of colon and rectum to it is characterized in that being used for the treatment of site of pathological change, and it is oral also can further to make other dosage form.
8. according to the described dosage form of claim 7, it is characterized in that oral dose is 2-3 time on the one, 1 clothes Montmorillonitum 1-3g.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100150992A CN101112386A (en) | 2007-06-29 | 2007-06-29 | Smectite middle gut positioning releasing pellet and method for preparing the same |
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| Application Number | Priority Date | Filing Date | Title |
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| CNA2007100150992A CN101112386A (en) | 2007-06-29 | 2007-06-29 | Smectite middle gut positioning releasing pellet and method for preparing the same |
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| CN101112386A true CN101112386A (en) | 2008-01-30 |
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| CNA2007100150992A Pending CN101112386A (en) | 2007-06-29 | 2007-06-29 | Smectite middle gut positioning releasing pellet and method for preparing the same |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105878584A (en) * | 2016-05-26 | 2016-08-24 | 朱胜利 | Infantile antidiarrheal |
| CN105902625A (en) * | 2016-05-26 | 2016-08-31 | 朱胜利 | Method for taking infantile antidiarrheic |
| CN105998399A (en) * | 2016-05-26 | 2016-10-12 | 朱胜利 | Preparation method of pediatric antidiarrheal |
-
2007
- 2007-06-29 CN CNA2007100150992A patent/CN101112386A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105878584A (en) * | 2016-05-26 | 2016-08-24 | 朱胜利 | Infantile antidiarrheal |
| CN105902625A (en) * | 2016-05-26 | 2016-08-31 | 朱胜利 | Method for taking infantile antidiarrheic |
| CN105998399A (en) * | 2016-05-26 | 2016-10-12 | 朱胜利 | Preparation method of pediatric antidiarrheal |
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