CN101057861B - Polycarbophil enteric coated medicinal composition - Google Patents
Polycarbophil enteric coated medicinal composition Download PDFInfo
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- CN101057861B CN101057861B CN2007101106592A CN200710110659A CN101057861B CN 101057861 B CN101057861 B CN 101057861B CN 2007101106592 A CN2007101106592 A CN 2007101106592A CN 200710110659 A CN200710110659 A CN 200710110659A CN 101057861 B CN101057861 B CN 101057861B
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- polycarbophil
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Abstract
The invention relates to a pharmaceutical enteric soluble medicine compound and the method for preparing the same, comprising core of pharmaceutical and shaping for medical use and enteric soluble membrane coating the core. Said enteric soluble medicine compound can be released in intestine quickly, and avoid pharmaceutical swelling in acid gastric.
Description
Technical field
The present invention relates to a kind of be used to prevent and/or treat constipation and diarrheal pharmaceutical composition and preparation method thereof, more particularly, the present invention relates to contain nuclear core that constitutes by Polycarbophil (Polycarbophil) and pharmaceutically acceptable excipient and the pharmaceutical composition that wraps up the coating membrane that contains enteric polymer of this nuclear core.
Background technology
Irritable bowel syndrome is a kind of even without the organic disorderly disease that also can cause abnormal defecation that exists, usually cause by far-end digestive tract function sexual abnormality, generally be divided into following a few subclass: the constipation type that the spastic contraction of DC etc. causes the content transportation lag to cause; Promotion contents such as hyperperistalsis are carried the diarrhea-type that causes; Constipation and the multiple successively alternate type of diarrhoea.Occurrence frequency is higher than the male to the abnormal defecation that irritable bowel syndrome causes (especially constipation) in the women.
Constipation is a kind of common disease, and its sickness rate height, cause of disease complexity can show as not only that defecation frequency reduces, feces is dry and hard, also can show as difficult defecation or sense etc. not to the utmost, often brings many miseries and worry to the patient.The constipation meeting causes habitual anxiety, directly influences the normal of diet or sleep, and quality of life is significantly reduced; Even more serious is that prolonged constipation can increase the risk of suffering from straight colon cancer.
The constipation sickness rate is 3% in youngster, middle age 8%, old people 20% (clinical and The Journal of Experimental Medicine, 2006 (5) 5:601).In the U.S., have every year to account for 1.2% population and see the doctor because of constipation, this ratio is higher relatively at non-white's population risk, accounts for 3.0%～4.0% (Chinese primary health care, 2006 (20) 8:88-90) of total population.Statistics according to the U.S. has the people more than 400 ten thousand that constipation takes place every year approximately, and sickness rate accounts for 2% (Chinese contemporary medical science, 2006 (5) 20:55) of total number of persons.
In China, the sickness rate of constipation also is the gesture of quick growth recent years.Among Beijing, Tianjin and the crowd of area, Xi'an more than 60 years old, chronic constipation patient leads up to 15%～20%.Among the adult of Beijing area, the chronic constipation prevalence is approximately about 6%, and wherein women's prevalence approximately is more than 4 times of male.And the age of constipation patient is just gradually to younger development (the Chinese Hospitals medication is estimated and analyzed 2004 (4) 6:371-373).
For the treatment of constipation, need adopt the operation except that the minority patient with severe symptoms clinically, other all heal with medicine.Generally speaking, can it be divided into according to the different mechanism of medicine: bulk-forming laxative, irritant purgative, permeability cathartic, demulcent cathartics, intestinal motive force medicine, Chinese medicinal formulae six big classes (Shanxi medical education, 2006,1:47-48).Except that the volume medicine, these medicines are often cutting out back constipation meeting recovery, can not take for a long time owing to safety issue.These medicines all can't obtain gratifying clinical efficacy at present.
Polycarbophil is polyacrylic acid and 3,4-glycol-1, the crosslinked resin of 5-hexadiene, the known characteristic with efficient water reservation of this resin.Polycarbophil calcium is the calcium salt of Polycarbophil.Polycarbophil calcium belongs to osmotic laxative.
Behind the oral Polycarbophil calcium tablet, Polycarbophil calcium is sloughed calcium ion and is produced Polycarbophil in acidic gastric juice; Polycarbophil imbibition in the neutral acidity environment of intestinal also mixes with food gradually.During constipation, fully the Polycarbophil after the suction makes feces soften, increase the feces water content, help intestinal to recover wriggling gradually, thereby increases stool and quantity, reaches the effect for the treatment of constipation.When diarrhoea, Polycarbophil then produces anti-diarrhea effect (pharmacotherapy 2 (1), 18-28,1982) by the flowability of moisture content in the suction reduction intestinal.Obviously, the complete disintegrate of Polycarbophil calcium, thoroughly decalcification, abundant imbibition are the prerequisite steps that the performance of Polycarbophil calcium should have pharmacological action.The pharmaceutical composition that contains Polycarbophil calcium is as abnormal defecation (diarrhoea and constipation) and the effective preparation of symptom of digestive tract to irritable bowel syndrome, approval listing abroad.
Yet; the treatment that the Polycarbophil calcium preparation is used for irritable bowel syndrome has following four major defects: 1. disintegrate is not thorough with decalcification: Polycarbophil calcium is with after sour environment contacts; top layer Polycarbophil calcium can quick decalcification form free Polycarbophil; free Polycarbophil and free carboxy have very strong viscosity in Digestive system; form the surface that a kind of gelatinous protective layer is wrapped in internal layer Polycarbophil calcium; stop moisture to enter internal layer, thereby stop the further decalcification of internal layer Polycarbophil calcium.This specific character causes (as gastric juice, pH the is about 1.2) disintegrate fully in acid solution of Polycarbophil calcium, thus reduced actual effective use dosage, and may affect the treatment.Aspect decalcification, when pH4.0 was following, the decalcification of Polycarbophil calcium just can surpass 70% more than 0.5 hour, but still only was 90.5% at 6 hours; When pH4.0 is above, and then obviously decline of decalcification (Biol Pharm Bull.1997,20:275-277).Because people's the stomach emptying time after general the dining is about 4-5 hour, this just mean have the Polycarbophil of considerable part calcium also not decalcification just enter in the intestinal.Almost can't finish the decalcification process under the higher pH environment of Polycarbophil calcium in intestinal, thereby curative effect is reduced.2. water absorbing capacity reduces under one's belt: Polycarbophil calcium under acid condition the water absorbing capacity after (as in gastric juice) decalcification 10 milliliters/below the gram; But when water absorbing capacity when pH4.0 is above increases, can reach 40 milliliters/gram, when water absorbing capacity when pH7.0 is above then sharply increases, when its water absorption is pH4.0 7 of water absorption times (J.Pharm.Pharmacol.1996,48:665-668).Therefore, the suction meeting under one's belt of Polycarbophil calcium is insufficient; The water sorption of Polycarbophil calcium mainly carries out in intestinal.3. high calcium causes untoward reaction: contain the Pharmaceutical composition of Polycarbophil calcium, the calcium ion that discharges in gastrointestinal tract is absorbed by the body easily.Taking the Polycarbophil calcium tablet for a long time can obviously increase calcium absorption in the body, especially when uniting use with active form vitamin D etc., may cause hypercalcemia.Excessive calcium may cause the raising of cardiac contractile force in the human body, and especially when uniting use with cardiac glycoside, its heart condition reaction can be more obvious.In addition, excessive calcium also may cause calcium oxide etc. to be deposited in the tissue such as kidney, forms to contain for example calculus of calcium oxalate etc. of insoluble or slightly soluble calcium salt.4. the preparation specification is difficult for too greatly swallowing: Polycarbophil calcium preparation specification is that 625 milligrams/sheet, sheet heavily are generally 1 gram/sheet at present; Dosage is generally the 1-4 sheet for each person every day.Wherein the actual content of Polycarbophil only is 500 a milligrams/sheet.Therefore to be used for clinical sheet heavy too big for Polycarbophil calcium, is not easy to swallow for old man and child.
For the halfway problem of the disintegrate that solves Polycarbophil calcium, developed Polycarbophil Biocal (trade name: Mitrolan) at present.Can make the imbibition in advance in the oral cavity of Polycarbophil calcium cause dysphagia but chew, and the problem that equally also exists decalcification not thorough (oral cavity acidity is near neutral) and high calcium to bring.EP0273209, US5215754 disclose a kind of Polycarbophil calcium preparation, contain components such as microcrystalline Cellulose, magnesium stearate, crospolyvinylpyrrolidone, polyvinylpyrrolidone, silica gel and stearic acid, and add caramel and carry out coating, developed listing product (trade name: Fibercon) according to above-mentioned patent, but this tablet can not guarantee that disintegrate finishes in 60 minutes, thereby can not guarantee curative effect.EP0488139, US5213806 disclose a kind of can be in gastric juice quickly disintegrated Polycarbophil calcium preparation, contain Polycarbophil calcium and cellulose derivative, though this method has greatly been improved the disintegrate problem, decalcification may be not thoroughly, suction under one's belt the is insufficient and shortcoming of the untoward reaction that high calcium may cause etc. then do not eliminate.Abroad the patent (CN1662247) in China's application discloses a kind of medicinal combination that is used for the Polycarbophil magnesium of same indication, though avoided the problem of the excessive absorption of calcium, the untoward reaction that the same absorption that has also brought excessive magnesium because need could absorb water behind the de-magging under one's belt may bring.In addition, still there is the low problem of water absorbing capacity thoroughly and in acid of disintegrate in Polycarbophil magnesium.
Therefore still solve at the problems referred to above at present without any preparation technique comprehensively.Therefore be necessary to make polycarbophil enteric coated medicinal composition, make it be easy to the disintegrate suction, give full play to the water absorption and swelling character of Polycarbophil and better bring into play its due curative effect, the untoward reaction avoiding causing after the excessive absorption of calcium that prior art occurs or other salt, and can suitably to reduce the preparation sheet heavy and conveniently swallow.
Summary of the invention
The object of the present invention is to provide a kind of make Polycarbophil under one's belt not disintegrate discharge and the enteric-coated medicament combination that discharges in the quick disintegrate of enteral.This pharmaceutical composition has excellent safety and effect, and has brought into play good effectiveness and do not cause for example watery stool, and is too just loose, the side effect of hypercalcemia etc.
The invention provides a kind of Polycarbophil oral enteric pharmaceutical composition, it comprises the nuclear core of a) being made up of Polycarbophil and pharmaceutically acceptable excipient; B) wrap up the coating material that contains a kind of enteric polymer at least of this nuclear core.
Pharmaceutically acceptable excipient of the present invention comprises one or more in filler, disintegrating agent, the lubricant etc.
Coating material of the present invention comprises enteric polymer, it is selected from poly-first ammonium acrylate ester (Methacrylic Acid Copolymers), polyacrylic resin, acrylic resin, hydroxypropylmethyl cellulose phthalate (HPMCP), cellulose acetate phthalate (CAP), acetic acid hydroxypropyl methylcellulose succinyl ester (HPMCPAS), ethyl cellulose (EC), zein, Lac or diketopiperazine polymer, or the combination of above two or more material.The for example commercially available strange L of You Te (the Eudragit L that mainly contains poly-first ammonium acrylate ester, Rhom company) and the strange S of You Te (Eudragit S, Rhom company), mainly contain the Opadry (Opadry, Colorcon company) of hydroxypropylmethyl cellulose phthalate, home-made polyacrylic resin I number, II number and III number.Coating material of the present invention can also substitute with the empty hard capsule that enteric polymer is made.
Preferably, add film property and the film strength of plasticizer to improve the enteric polymer material in coating material of the present invention, plasticizer is selected from Polyethylene Glycol or diethyl phthalate; Also can add some caking inhibiters for example Pulvis Talci, silicon dioxide etc., be beneficial to the carrying out of peplos operation.
Preferably, a kind of Polycarbophil oral enteric pharmaceutical composition of the present invention, by the gross weight of this pharmaceutical composition, it contains the Polycarbophil of 40%-90%, more preferably the Polycarbophil of 50%-80%; 1%-60%, the more preferably filler of 5%-50%; 3%-60%, the more preferably disintegrating agent of 6%-30%; 1%-15%, the more preferably lubricant of 4%-10%; 2%-20%, the more preferably enteric polymer of 3%-15%; 0.1%-10%, the more preferably plasticizer of 0.5%-6%.
Filler of the present invention is selected from microcrystalline Cellulose, starch, amylum pregelatinisatum, lactose, dextrin, mannitol, sucrose or hyprolose, or the combination of above two or more material, preferred lactose or microcrystalline Cellulose.
Disintegrating agent of the present invention is selected from low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, crospolyvinylpyrrolidone or cross-linking sodium carboxymethyl cellulose, or the combination of above two or more material.
Lubricant of the present invention is selected from Pulvis Talci, magnesium stearate or micropowder silica gel, or the combination of above two or more material.
The inventor finds to adopt the coating material that comprises above-mentioned at least a enteric polymer through a large amount of experiments, make this medicine not disintegrate under one's belt, and disintegrate apace under the environment of enteric liquid, thereby reached effect of the present invention well.
The inventor also finds to examine contains these three kinds of disintegrating agents of carboxymethyl starch sodium, crospolyvinylpyrrolidone and low-substituted hydroxypropyl cellulose simultaneously in the core, can make medicine reach better quickly disintegrated effect in the enteric liquid of regulation.Preferred earth's core core contains the carboxymethyl starch sodium of 1%-20% by weight, and more preferably earth's core core contains the carboxymethyl starch sodium of 2%-10% by weight; Preferred earth's core core contains the crospolyvinylpyrrolidone of 1%-20% by weight, and more preferably earth's core core contains the crospolyvinylpyrrolidone of 2%-10% by weight; Preferred earth's core core contains the low-substituted hydroxypropyl cellulose of 1%-20% by weight, and more preferably earth's core core contains the low-substituted hydroxypropyl cellulose of 2%-10% by weight.
The preparation method of polycarbophil enteric coated medicinal composition comprises preparation nuclear core material, preparation coating solution, three steps of preparation enteric-coated medicament combination.
Preparation nuclear core material: adopting dry granulation or direct powder compression, preferably adopt direct powder compression, is crude drug with the Polycarbophil, adds excipient, tabletting behind the mixing.The nuclear core can adopt conventional method, for example round as a ball comminution granulation, extrudes spheronization, and Polycarbophil and excipient are made micropill.Also can make the ball core that contains Polycarbophil with commercially available inertia celphere.
The preparation coating solution: the coating material of enteric polymer that will comprise a kind of or combination in any with dissolve with ethanol after, mix homogeneously is adjusted proper viscosity.
The preparation enteric-coated medicament combination:
By the preparation of above-mentioned nuclear core material, the sheet that presses is weighed in the rearmounted coating pan, spray coating solution and carry out coating, obtain enteric coated tablet.
By the preparation of above-mentioned nuclear core material, the granule for preparing or micropill are weighed in rearmounted coating pan or the fluidized bed coating device, spray coating solution and carry out coating, obtain enteric coated particles, the common hard capsule of packing into promptly gets enteric coated capsule; The hard capsule that the enteric polymer of maybe granule, the micropill that prepare directly being packed into is made gets final product.
The enteric-coated medicament combination of Polycarbophil of the present invention has produced good result, not disintegrate in 2 hours under one's belt enters the rapid disintegrate imbibition of enteral, is formed with the colloid substance of stickiness, thereby the generation curative effect has been avoided prior art decalcification under one's belt, swelling and the generation of the untoward reaction that causes.
As pharmacological active substance, below be described in further detail the present invention with Polycarbophil by embodiment, but and unrestricted the present invention.
Embodiment 1:
| Polycarbophil | 312.5g |
| Lactose | 50g |
| Carboxymethyl starch sodium | 25g |
| Low-substituted hydroxypropyl cellulose | 10g |
| Crospolyvinylpyrrolidone | 10g |
| Magnesium stearate | 2.5g |
| Micropowder silica gel | 20g |
| Make | 1000 |
Take by weighing Polycarbophil, lactose, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium by recipe quantity, silicon dioxide, magnesium stearate mix homogeneously are by the amount tablet machine tabletting of determining.
The plain sheet that makes is weighed in the rearmounted coating pan, and with 50 gram enteric Opadry dissolve with ethanols, sprinkling enteric Opadry ethanol coating solution carries out coating, obtains enteric coated tablet.
Embodiment 2:
| Polycarbophil | 500g |
| Microcrystalline Cellulose | 75g |
| Carboxymethyl starch sodium | 37.5g |
| Low-substituted hydroxypropyl cellulose | 17g |
| Crospolyvinylpyrrolidone | 17g |
| Micropowder silica gel | 35g |
| Make | 1000 |
Take by weighing Polycarbophil, microcrystalline Cellulose, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium by recipe quantity, the silicon dioxide mix homogeneously is by the amount tablet machine tabletting of determining.
The plain sheet that makes is weighed in the rearmounted coating pan, and with polyacrylic resin II numbers and the polyethylene glycol 6000 dissolve with ethanols of 10 grams of 70 grams, sprinkling polyacrylic resin II number carries out coating with polyethylene glycol 6000 ethanol coating solution, obtains enteric coated tablet.
Embodiment 3:
| Polycarbophil | 625g |
| Lactose | 50g |
| Microcrystalline Cellulose | 50g |
| Carboxymethyl starch sodium | 50g |
| Low-substituted hydroxypropyl cellulose | 20g |
| Crospolyvinylpyrrolidone | 20g |
| Magnesium stearate | 5g |
| Micropowder silica gel | 40g |
| Make | 1000 |
Take by weighing Polycarbophil, lactose, microcrystalline Cellulose, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium by recipe quantity, silicon dioxide, magnesium stearate mix homogeneously are by the amount tablet machine tabletting of determining.
The plain sheet that makes is weighed in the rearmounted coating pan, and with the Opadry dissolve with ethanols of 100 grams, sprinkling enteric Opadry ethanol coating solution carries out coating, obtains enteric coated tablet.
Embodiment 4:
Principal agent among the embodiment 1, mixed with excipients is even, place round as a ball coating pelletizing machine to make micropill, after the drying, place in the coating pan or in fluidizing fluid-bed, spray enteric coating liquid and carry out coating, obtain enteric coated micropill, ball footpath scope is between 0.5mm-3mm.Micropill fill capsule is promptly got polycarbophil enteric coated capsule.
Embodiment 5:
Take by weighing principal agent, excipient by embodiment 1 recipe quantity, behind the mix homogeneously, adopt fluid bed or round as a ball coating pelletizing machine that principal agent adjuvant mixture is wrapped on the blank micropill.In fluid bed or round as a ball coating pelletizing machine enteric coating liquid is wrapped on the micropill then, ball footpath scope is between 0.5mm-3mm.Micropill incapsulated promptly get polycarbophil enteric coated capsule.
For the enteric effect of medicine of the present invention is described, we test according to disintegration time mensuration method (two appendix X of Chinese Pharmacopoeia version in 2005 A):
Get the medicine of embodiment 1-5,, continue hanging basket is taken out to check 2 hours in the hydrochloric acid solution (9 → 1000) according to Chinese Pharmacopoeia, after the low amounts of water washing, every pipe adds 1 on baffle plate, checks in phosphate buffer (pH6.8) as stated above again.
Embodiment 1-5 sample testing result disintegration
Result of the test shows, the enteric coated preparation of Polycarbophil, have significant enteric characteristics: in 0.1mol/L HCL solution, there is not disintegrate in 2 hours, and in the solution of phosphate buffer (pH6.8), only need a few minutes with regard to disintegrate rapidly, medicine of the present invention easy disintegrating not in acidic gastric juice is described, and disintegrate rapidly under the intestinal environment.
In order further to verify the curative effect of polycarbophil enteric coated preparation, 6 healthy beagle dogs are divided into three groups, single dose intersection medication, oral administration, give embodiment polycarbophil enteric coated (500mg/ sheet), the commercially available Polycarbophil calcium tablet (625mg/ sheet) and the blank (matched group) of 2 preparations, every day twice, each two.Pour into 100ml water from mouth immediately after the administration.After pouring water, collect the feces of 24 hours Canis familiaris L.s, measure the weight in wet base of feces with a metabolic cage.After the collection, 80 ℃ of dryings of feces 12 to 24 hours are measured the dry weight of feces, calculate the content ratio of water in the feces.
Polycarbophil enteric coated and Polycarbophil calcium tablet are to the influence of beagle dog feces water content
With matched group relatively, polycarbophil enteric coated than the more remarkable weight in wet base that increases feces of Polycarbophil calcium tablet, dry weight and water quantities, dejecta moisture does not change.The result of the test further polycarbophil enteric coated preparation of checking has obtained better therapeutic than Polycarbophil calcium tablet, and can suitably reduce the preparation sheet and heavily conveniently swallow.
Claims (1)
1. Polycarbophil oral enteric tablet, 1000 tablets of medicines are raw materials used is for it:
Polycarbophil 500g
Microcrystalline Cellulose 75g
Carboxymethyl starch sodium 37.5g
Low-substituted hydroxypropyl cellulose 17g
Crospolyvinylpyrrolidone 17g
Micropowder silica gel 35g
Take by weighing Polycarbophil, microcrystalline Cellulose, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium by the said ratio amount, the micropowder silica gel mix homogeneously is by the amount tablet machine tabletting of determining;
The plain sheet that makes is weighed in the rearmounted coating pan, and with polyacrylic resin II numbers and the polyethylene glycol 6000 dissolve with ethanols of 10 grams of 70 grams, sprinkling polyacrylic resin II number carries out coating with polyethylene glycol 6000 ethanol coating solution, obtains enteric coated tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101106592A CN101057861B (en) | 2007-06-08 | 2007-06-08 | Polycarbophil enteric coated medicinal composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101106592A CN101057861B (en) | 2007-06-08 | 2007-06-08 | Polycarbophil enteric coated medicinal composition |
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| Publication Number | Publication Date |
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| CN101057861A CN101057861A (en) | 2007-10-24 |
| CN101057861B true CN101057861B (en) | 2010-07-28 |
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| CN2007101106592A Withdrawn - After Issue CN101057861B (en) | 2007-06-08 | 2007-06-08 | Polycarbophil enteric coated medicinal composition |
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Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104687048B (en) * | 2015-03-09 | 2017-04-19 | 西安交通大学医学院第一附属医院 | Maca tablet and preparation method thereof |
| CN106913552A (en) * | 2017-04-17 | 2017-07-04 | 深圳市泛谷药业股份有限公司 | A kind of polycarbophil Biocal and preparation method thereof |
| CN109010320B (en) * | 2018-09-18 | 2021-09-14 | 浙江汇能生物股份有限公司 | Double-release calcium polycarbophil granules, preparation method and application thereof in livestock and poultry |
| CN112472711A (en) * | 2020-12-22 | 2021-03-12 | 苏州中化药品工业有限公司 | Polycarbophil preparation and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3202577A (en) * | 1962-05-25 | 1965-08-24 | White Lab Inc | Process of treating diarrhea with resins |
| US3297664A (en) * | 1962-08-06 | 1967-01-10 | White Lab Inc | Calcium salts of lightly cross-linked ethylenically unsaturated carboxylic acids anddiethylenically unsaturated aliphatics |
| CN1662247A (en) * | 2002-06-26 | 2005-08-31 | 株式会社富士药品 | Pharmaceutical composition for preventing and/or treating constipation and constipation-induced disorders |
| CN1759844A (en) * | 2005-09-21 | 2006-04-19 | 广州贝氏药业有限公司 | Enteric coated preparation of Clarithromycin |
| CN1923183A (en) * | 2005-09-21 | 2007-03-07 | 广州贝氏药业有限公司 | Clarithromycin enteric medicinal composition |
-
2007
- 2007-06-08 CN CN2007101106592A patent/CN101057861B/en not_active Withdrawn - After Issue
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3202577A (en) * | 1962-05-25 | 1965-08-24 | White Lab Inc | Process of treating diarrhea with resins |
| US3297664A (en) * | 1962-08-06 | 1967-01-10 | White Lab Inc | Calcium salts of lightly cross-linked ethylenically unsaturated carboxylic acids anddiethylenically unsaturated aliphatics |
| CN1662247A (en) * | 2002-06-26 | 2005-08-31 | 株式会社富士药品 | Pharmaceutical composition for preventing and/or treating constipation and constipation-induced disorders |
| CN1759844A (en) * | 2005-09-21 | 2006-04-19 | 广州贝氏药业有限公司 | Enteric coated preparation of Clarithromycin |
| CN1923183A (en) * | 2005-09-21 | 2007-03-07 | 广州贝氏药业有限公司 | Clarithromycin enteric medicinal composition |
Non-Patent Citations (3)
| Title |
|---|
| 说明书第3页第22行至第4页第23行. |
| 说明书第3页第9-17、20-21行 |
| 说明书第4页第4-6行、第10-12行 |
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