CN103070865A - Oral solid preparation taking prucalopride succinate as active ingredient and application of oral solid preparation - Google Patents
Oral solid preparation taking prucalopride succinate as active ingredient and application of oral solid preparation Download PDFInfo
- Publication number
- CN103070865A CN103070865A CN2013100065590A CN201310006559A CN103070865A CN 103070865 A CN103070865 A CN 103070865A CN 2013100065590 A CN2013100065590 A CN 2013100065590A CN 201310006559 A CN201310006559 A CN 201310006559A CN 103070865 A CN103070865 A CN 103070865A
- Authority
- CN
- China
- Prior art keywords
- solid preparation
- succinic acid
- prucalopride
- oral solid
- calcium
- 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
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides oral solid preparation taking prucalopride succinate as an active ingredient, and application of the oral solid preparation. According to the method, the oral solid preparation is prepared by taking prucalopride succinate and pharmaceutically acceptable auxiliary materials and adopting the preparation technology. The solid preparation is stable in quality, controllable, convenient to take, good in compliance, and less in side effects, and is mainly used for chronic constipation in clinic practice.
Description
Technical field
The present invention relates to a kind of oral solid formulation and application thereof of succinic acid prucalopride, belong to medical technical field.
Background technology
The market space for the treatment of constipation medicine is very large.In recent years, along with the impact of the factors such as living standard, life style, dietary structure, in addition increasing sharply of aging population makes the incidence rate of China's constipation be the trend of continuous rising.
The succinic acid prucalopride in October, 2009 after Europe is granted, go on the market in Germany in January, 2010, go on the market in Britain in March, 2010.By Movetis company according to Janssen company (subsidiary under Johnson and the Johnson) authorization.The succinic acid prucalopride is heterocyclic carbamate derivatives, and chemical name is 4-amino-5-chloro-2,3-dihydro-N[1-(3-methoxy-propyl)-4-piperidyl]-the 7-benzofuran carboxamides.It has outstanding intestinal motility stimulation, particularly large intestine and small intestinal is demonstrated significant motility potentiation.The mechanism of action is to strengthen non-epinephrine, the excited feces piece that also passes through of non-cholinergic by the preshoot of large intestine.In addition, their accelerate gastric emptying and small intestinal contraction movement and promotion are to the effect of cholinergic activity.Described chemical compound does not have 5-HT2 or 5-HT3 receptor antagonist performance yet.Can be used for treating the motility obstacle of intestinal system, for example:, gastroparesis, dyspepsia, constipation, pseudo-obstruction, enteroparesis, postoperative enteroparesis, irritable bowel syndrome and drug-induced gastrointestinal smoother are excessively slow.This chemical compound also can be used for promoting large intestine to clean or makes intubate or endoscope operation become easy.
Succinic acid prucalopride and cisapride are all the 5-HT4 receptor stimulating agent.But the succinic acid prucalopride is more effective than cisapride, and selectivity is higher, and external activity is 500 times of cisapride.Colon and stomach 5-HT4 Rd are low, and the medicine that selectivity is high can produce stronger effect.But the gastrointestinal motility of the Canis familiaris L. that succinic acid prucalopride stimulating gastrointestinal function reduces, cisapride then can not.The succinic acid prucalopride is rapid-action in addition, and cisapride is being used a few Zhou Houcai onsets, and succinic acid prucalopride selectivity is high, and untoward reaction is few, is the alternative a kind of novel active drug of patients with chronic constipation.As seen, the listing of succinic acid prucalopride needs Long-term taking medicine treatment chronic constipation and worry because of the patient that the long-term taking cathartic causes various untoward reaction to those, and treatment means safer, more effective, that more suit the medicine to the illness is provided.
Summary of the invention
The purpose of this invention is to provide a kind of oral administration solid preparation for the treatment of chronic constipation, it is take the succinic acid prucalopride as active component, and this preparation is used for the various diseases due to the gastrointestinal peristalsis obstacle.Described preparation is used for the treatment of gastroparesis, dyspepsia, constipation, pseudo-obstruction, enteroparesis, postoperative enteroparesis, irritable bowel syndrome and drug-induced gastrointestinal smoother and crosses the diseases such as slow.And taking convenience, good absorbing, bioavailability is high, compliance good, few side effects.
Described oral administration solid preparation is oral ordinary tablet, freeze-dried instant sheet, Film coated tablets, enteric coatel tablets, hard capsule, granule, oral cavity disintegration tablet, the effervescent tablet of making by preparation technique with succinic acid prucalopride and pharmaceutically acceptable adjuvant.
Succinic acid prucalopride solid preparation provided by the invention, the specification of succinic acid prucalopride is per unit dosage 0.1-50mg, contain succinic acid prucalopride active ingredient and the excipient substance that is fit to make solid preparation, wherein the percentage by weight of succinic acid prucalopride is 0.1%-95%, and the percentage by weight of adjuvant is 90%-99.9%.Every of described succinic acid prucalopride solid preparation preferably contains succinic acid prucalopride 0.1-50mg.Pharmaceutically acceptable adjuvant can be filler, binding agent, disintegrating agent, lubricant, correctives (necessity) and coating materials.
Wherein filler includes but not limited to lactose, sucrose, glucose, mannitol, sorbitol, calcium sulfate, calcium gluconate, calcium hydrogen phosphate, calcium phosphate, calcium carbonate, calcium bicarbonate, starch, carboxymethyl starch, pregelatinized Starch or microcrystalline Cellulose;
Disintegrating agent includes but not limited to pregelatinized Starch, microcrystalline Cellulose, alginic acid, pure wood fiber element, carboxymethyl starch sodium, guar gum, crospolyvinylpyrrolidone, methylcellulose or cross-linking sodium carboxymethyl cellulose;
Lubricant includes but not limited to magnesium stearate, calcium stearate, Pulvis Talci, glyceryl monostearate, Macrogol 4000, polyethylene glycol 6000, PEG 8000, sodium benzoate, adipic acid, fumaric acid, boric acid, sodium chloride, sodium laurylsulfate or magnesium laurylsulfate;
Correctives includes but not limited to steviosin, sorbitol, maltose alcohol, glycyrrhizin, stem tea element, Sodium Cyclamate, flavoring banana essence, flavoring pineapple essence, Mint Essence, Fructus Foeniculi, vanillin, Fructus Citri Limoniae essence, cherry essence or rose essence;
Coating materials includes but not limited to cellulose and derivant thereof, crylic acid resin, ethene polymers etc.
Pharmaceutical preparation of the present invention also comprises wetting agent, is purified water or ethanol etc.Cucumber can have two kinds of functions concurrently, both can serve as filler such as microcrystalline Cellulose, can serve as disintegrating agent again; Differential silica gel both can serve as disintegrating agent, can serve as lubricant again.
The specific embodiment:
Following examples are used for further specifying the present invention, but the present invention is not limited.
Embodiment 1
Make 1000 succinic acid prucalopride sheets with the raw material of following weight proportion.
Preparation technology:
1. succinic acid prucalopride crude drug was pulverized 80 mesh sieves, and was for subsequent use.
2. lactose is crossed 60 mesh sieves, and is for subsequent use.
3. get succinic acid prucalopride and microcrystalline Cellulose, lactose, the abundant mix homogeneously of cross-linking sodium carboxymethyl cellulose.
4. with water soft material processed, 20 mesh sieves are granulated, 60 ℃ of dryings, 24 mesh sieve granulate.
5. add the abundant mix homogeneously of magnesium stearate, tabletting, and get final product.
Embodiment 2
1. prepare 6% Opadry enteric coating agents alcoholic solution;
2. get embodiment 1 gained element sheet, pour in the coating pan, start coating pan, and blowing hot-air, at 30-40 ℃ of preheating 10min, and blow plain sheet off adhere on the label medicated powder, evenly spray into coating solution, medicinal liquid is evenly coated on the label, namely get succinic acid prucalopride enteric coatel tablets.
Embodiment 3:
Make 1000 succinic acid prucalopride sheets with the raw material of following weight ratio.
Preparation method:
1. succinic acid prucalopride crude drug was pulverized 80 mesh sieves, for subsequent use.
2. get succinic acid prucalopride and sorbitol, microcrystalline Cellulose, cross-linked carboxymethyl fiber sodium, the abundant mix homogeneously of hypromellose E3.
3. with water soft material processed, 24 orders are granulated, 60 ℃ of oven dry, 40 order granulate.
4. add the abundant mix homogeneously of magnesium stearate, tabletting, and get final product.
Embodiment 4:
1. prepare the common gastric solubleness coating solution of Opadry
2. get embodiment 3 gained element sheet, pour in the coating pan, start coating pan, and blowing hot-air, at 30-40 ℃ of preheating 10min, and blow plain sheet off adhere on the label medicated powder, evenly spray into coating solution, medicinal liquid is evenly coated on the label, namely get succinic acid prucalopride general thin garment piece.
Embodiment 5:
Make 1000 succinic acid prucalopride sheets with the raw material of following weight proportion
Preparation method:
1. the succinic acid prucalopride is pulverized, and crosses 80 eye mesh screens, and is for subsequent use.
2. get the succinic acid prucalopride, microcrystalline Cellulose of recipe quantity by equivalent incremental method mix homogeneously; Add again lactose by equivalent incremental method mix homogeneously.
3. the silicon dioxide, the magnesium stearate that add recipe quantity, mix homogeneously.
4. adjustment sheet heavily reaches tabletting behind the pressure, and the punch die model is Ф 8mm scrobicula.
Make 1000 succinic acid prucalopride capsules with the raw material of following weight proportion.
Preparation technology:
1. succinic acid prucalopride raw material and adjuvant are pulverized respectively, crossed 80 mesh sieves.
2. get the succinic acid prucalopride with 5% starch slurry soft material processed, 24 orders are granulated, dry after granulate.
3. add the abundant mix homogeneously of silicon dioxide magnesium, be packed in the capsulae vacuus and get final product.
4. with 5% starch slurry solution soft material processed, 20 mesh sieves are granulated, 60 ℃ of dryings, 24 mesh sieve granulate.
5. add the abundant mix homogeneously of magnesium stearate, be packed in the capsulae vacuus and get final product.
Embodiment 6
Make 1000 bags of succinic acid prucalopride granules with the raw material of following weight proportion
Preparation technology:
Get succinic acid prucalopride and other each adjuvant, pulverize respectively, cross 80 mesh sieves, abundant mixing, with purified water soft material processed, 14 mesh sieves are granulated, drying, granulate, packing, and get final product.
Embodiment 7
Make 1000 succinic acid prucalopride oral cavity disintegration tablets with the raw material of following weight proportion
Preparation technology:
1. succinic acid prucalopride raw material and adjuvant are pulverized respectively, crossed 80 mesh sieves.
2. get succinic acid prucalopride and pregelatinized Starch, microcrystalline Cellulose, the abundant mix homogeneously of carboxymethyl starch sodium, the soft material processed take water as binding agent, 20 mesh sieves are granulated, after the drying, 24 mesh sieve granulate.
3. add cross-linking sodium carboxymethyl cellulose, sucralose, Fructus Citri Limoniae essence and the abundant mix homogeneously of magnesium stearate, tabletting, and get final product.
Embodiment 8
Make 1000 succinic acid prucalopride effervescent tablets with the raw material of following weight proportion
Preparation technology:
Each supplementary material is crossed respectively 60 mesh sieves, and dry in baking oven, moisture control with the abundant mix homogeneously of each adjuvant, is measured intermediate content 2%, calculates sheet heavy, tabletting.
Embodiment 9 succinic acid prucalopride sheets are to the therapeutical effect of constipation
40 of Wistar rats, male and female half and half. cleaning level, body weight 200g ± 10g.
Modeling: normal Wistar rats gavages the Radix Et Rhizoma Rhei powder suspension every day, the Radix Et Rhizoma Rhei consumption is 600mg/ (kgd) during beginning, double on the basis of the day before yesterday every day later on, until the half diarrhea inducing occurs, keep this dosage to disappear to 80% loose stool, and then double on this basis administration, there is again the nearly half rat diarrhoea to occur.So circulation is three times, drug withdrawal after last 80% loose stool disappeared for 1 week.Induce experimental STc rat model.
Grouping and administration: 40 sTC rat models are divided into model control group, succinic acid prucalopride sheet (embodiment 1) group, succinic acid prucalopride sheet (trade name Resolor) group, cisapride sheet group, each 10 at random.Every rats gavaged normal saline of model control group 10mL/ (kgd).Succinic acid prucalopride sheet group gavage every day gives 0.2mg/kg, and cisapride sheet group gavage every day gives 3mg/kg, and gavage is 30 days continuously.
Observation index: the rat fasting be can't help water 24 hours after 1 week of drug withdrawal, put to death with cervical vertebra dislocation behind 10% the carbon suspensioning liquid 2ml gavage 30mjn.Cut open the belly immediately, extract the whole intestinals from the pylorus to the rectum end, under relaxed state, measure the total length of intestinal and the length that the activated carbon suspension advances in intestinal, and calculated activity carbon suspension advances the percentage ratio of length and intestinal total length.
Experimental result: two administration group charcoals end advances length, propelling rate obviously to be better than matched group (P＜0.05), sees Table 1.With respect to the succinic acid prucalopride sheet (trade name Resolor) that has gone on the market, succinic acid prucalopride sheet of the present invention is more remarkable.
Table 1 is respectively organized the charcoal end and is advanced length, propelling rate relatively
Claims (8)
1. solid preparation take the succinic acid prucalopride as active component, it is the solid preparation of making by preparation technique with single dose succinic acid prucalopride and pharmaceutically acceptable adjuvant, includes but not limited to following dosage form: ordinary tablet, freeze-dried instant sheet, Film coated tablets, enteric coatel tablets, effervescent tablet, oral cavity disintegration tablet, hard capsule, granule, be dry mixed outstanding.
2. solid preparation as claimed in claim 1 is characterized in that, the specification of the succinic acid prucalopride in described each prescription is per unit dosage 1-100mg.
3. solid preparation as claimed in claim 1 is characterized in that, its pharmaceutically acceptable adjuvant can be filler, binding agent, disintegrating agent, lubricant, correctives.
4. solid preparation as claimed in claim 3, it is characterized in that, filler includes but not limited to lactose, sucrose, glucose, mannitol, sorbitol, calcium sulfate, calcium gluconate, calcium hydrogen phosphate, calcium phosphate, calcium carbonate, calcium bicarbonate, starch, carboxymethyl starch, pregelatinized Starch, microcrystalline Cellulose, hydroxypropyl cellulose.
5. solid preparation as claimed in claim 3, it is characterized in that, disintegrating agent includes but not limited to pregelatinized Starch, microcrystalline Cellulose, alginic acid, pure wood fiber element, carboxymethyl starch sodium, guar gum, crospolyvinylpyrrolidone, methylcellulose, cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose or gas-producing disintegrant.
6. solid preparation as claimed in claim 3 is characterized in that, lubricant includes but not limited to magnesium stearate, stearic acid, fumaric acid sodium, PEG6000, sodium lauryl sulphate, Glyceryl Behenate, micropowder silica gel, Pulvis Talci.
7. solid preparation as claimed in claim 3 is characterized in that, coating powder includes but not limited to cellulose and derivant thereof, crylic acid resin, ethene polymers etc.
8. preparation according to claim 1 is mainly preparing the purposes for the treatment of in the chronic constipation medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013100065590A CN103070865A (en) | 2012-12-27 | 2013-01-08 | Oral solid preparation taking prucalopride succinate as active ingredient and application of oral solid preparation |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210581791.2 | 2012-12-27 | ||
| CN201210581791 | 2012-12-27 | ||
| CN2013100065590A CN103070865A (en) | 2012-12-27 | 2013-01-08 | Oral solid preparation taking prucalopride succinate as active ingredient and application of oral solid preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103070865A true CN103070865A (en) | 2013-05-01 |
Family
ID=48147712
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2013100065590A Pending CN103070865A (en) | 2012-12-27 | 2013-01-08 | Oral solid preparation taking prucalopride succinate as active ingredient and application of oral solid preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103070865A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104069080A (en) * | 2014-06-26 | 2014-10-01 | 河北创健药业有限公司 | Prucalopride succinate tablet composition |
| CN104352465A (en) * | 2014-11-17 | 2015-02-18 | 成都新恒创药业有限公司 | Prucalopride succinate pharmaceutical composition free of silicon dioxide and preparation method of prucalopride succinate pharmaceutical composition |
| CN104667259A (en) * | 2015-03-26 | 2015-06-03 | 深圳市健元医药科技有限公司 | Medicinal composition capsule for treating chronic constipation and preparation method thereof |
| CN107595798A (en) * | 2017-09-26 | 2018-01-19 | 济川药业集团有限公司 | A kind of general reed Ka Bili tablets of butanedioic acid and preparation method thereof |
| CN108904808A (en) * | 2018-08-15 | 2018-11-30 | 西安力邦医药科技有限责任公司 | A kind of pharmaceutical composition and its application for treating constipation |
| WO2021130684A1 (en) * | 2019-12-23 | 2021-07-01 | Shilpa Medicare Limited | Orally dissolving formulations of prucalopride |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030175336A1 (en) * | 2002-03-13 | 2003-09-18 | Joseph Luber | Soft tablet containing high molecular weight polyethylene oxide |
-
2013
- 2013-01-08 CN CN2013100065590A patent/CN103070865A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030175336A1 (en) * | 2002-03-13 | 2003-09-18 | Joseph Luber | Soft tablet containing high molecular weight polyethylene oxide |
Non-Patent Citations (1)
| Title |
|---|
| J TACK ET AL: "Prucalopride (Resolor) in the treatment of severe chronic constipation in patients dissatisfied with laxatives", 《JOURNAL OF THE BRITISH SOCIETY OF GASTROENTEROLOGY》 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104069080A (en) * | 2014-06-26 | 2014-10-01 | 河北创健药业有限公司 | Prucalopride succinate tablet composition |
| CN104069080B (en) * | 2014-06-26 | 2017-02-22 | 河北创健药业有限公司 | Prucalopride succinate tablet composition |
| CN104352465A (en) * | 2014-11-17 | 2015-02-18 | 成都新恒创药业有限公司 | Prucalopride succinate pharmaceutical composition free of silicon dioxide and preparation method of prucalopride succinate pharmaceutical composition |
| CN104352465B (en) * | 2014-11-17 | 2017-04-12 | 成都新恒创药业有限公司 | Prucalopride succinate pharmaceutical composition free of silicon dioxide and preparation method of prucalopride succinate pharmaceutical composition |
| CN104667259A (en) * | 2015-03-26 | 2015-06-03 | 深圳市健元医药科技有限公司 | Medicinal composition capsule for treating chronic constipation and preparation method thereof |
| CN107595798A (en) * | 2017-09-26 | 2018-01-19 | 济川药业集团有限公司 | A kind of general reed Ka Bili tablets of butanedioic acid and preparation method thereof |
| CN107595798B (en) * | 2017-09-26 | 2020-03-24 | 济川药业集团有限公司 | Prucalopride succinate tablet and preparation method thereof |
| CN108904808A (en) * | 2018-08-15 | 2018-11-30 | 西安力邦医药科技有限责任公司 | A kind of pharmaceutical composition and its application for treating constipation |
| WO2021130684A1 (en) * | 2019-12-23 | 2021-07-01 | Shilpa Medicare Limited | Orally dissolving formulations of prucalopride |
| EP4081218A4 (en) * | 2019-12-23 | 2023-12-06 | Shilpa Medicare Limited | Orally dissolving formulations of prucalopride |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103070865A (en) | Oral solid preparation taking prucalopride succinate as active ingredient and application of oral solid preparation | |
| CN101143135B (en) | Melatonin orally disintegrating tablet and preparation method thereof | |
| CN101229325A (en) | Rhizoma gastrodiae chewable tablet and preparing method thereof | |
| CN107913256A (en) | A kind of macitentan oral disnitegration tablet for treating pulmonary hypertension and preparation method thereof | |
| JP2013533881A (en) | Pharmaceutical composition containing vanoxerin | |
| CN102805746A (en) | Compound pharmaceutical chemical acting on respiratory diseases and preparation process and application thereof | |
| CN102846555B (en) | Solid preparation comprising pirfenidone as active component and application thereof | |
| CN102727456B (en) | Drug port cavity disintegrating tablet and preparation method thereof | |
| CN101015519B (en) | Loratadine oral compound medication composition | |
| CN101642461B (en) | Drug composition of iguratimod and glucosamine, preparation method and drug application thereof | |
| CN101756947A (en) | Compound solid preparation for treating asthma | |
| CN101401796A (en) | Pramipexole orally disintegrating tablets and preparation method thereof | |
| CN101982174A (en) | Formula of compound medicine preparation for relieving cough and preventing asthma and preparation method thereof | |
| CN103720674B (en) | Famotidine floating-adhesive micro-tablet capsule and preparation method thereof | |
| CN101564424B (en) | Common lamiophlomis root chewable tablet and preparation thereof | |
| CN107854671A (en) | A Na series anaesthetic intragastric floating sustained-release preparations and preparation method thereof | |
| CN103156817A (en) | Rizatriptan drug absorbed through mouth mucosa | |
| CN102309480B (en) | Compound antihypertensive pharmaceutical composition and preparation method thereof | |
| CN102973541A (en) | Use of L-citrulline in preparation of anti-gastric ulcer drugs | |
| CN1985807A (en) | Compound Desloratadine-Ambroxol oral disintegrated tablet and its preparing method | |
| CN101756977A (en) | Slow-release preparation of azelnidipine and preparation method thereof | |
| CN102836162A (en) | Oral solid preparation taking tofisopam as active ingredient and application of oral solid preparation | |
| CN101849942A (en) | Medicinal composition for treating hypertension | |
| CN104188930B (en) | Acemetacin three-layer controlled release tablets and preparation method thereof | |
| CN101084898B (en) | Compound chemical medicine with antitussive and phlegm-eliminating action and its preparation technology |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20130501 |
|
| WD01 | Invention patent application deemed withdrawn after publication |