CN100391459C - Doxazosin mesilate slow releasing preparation - Google Patents
Doxazosin mesilate slow releasing preparation Download PDFInfo
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- CN100391459C CN100391459C CNB031333672A CN03133367A CN100391459C CN 100391459 C CN100391459 C CN 100391459C CN B031333672 A CNB031333672 A CN B031333672A CN 03133367 A CN03133367 A CN 03133367A CN 100391459 C CN100391459 C CN 100391459C
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- slow releasing
- doxazosin
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- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 229960001389 doxazosin Drugs 0.000 title abstract description 4
- RUZYUOTYCVRMRZ-UHFFFAOYSA-N doxazosin Chemical compound C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 RUZYUOTYCVRMRZ-UHFFFAOYSA-N 0.000 title 1
- 239000000463 material Substances 0.000 claims abstract description 15
- VJECBOKJABCYMF-UHFFFAOYSA-N doxazosin mesylate Chemical compound [H+].CS([O-])(=O)=O.C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 VJECBOKJABCYMF-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000001856 Ethyl cellulose Substances 0.000 claims abstract description 10
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims abstract description 10
- 235000019325 ethyl cellulose Nutrition 0.000 claims abstract description 10
- 229920001249 ethyl cellulose Polymers 0.000 claims abstract description 10
- 229960000220 doxazosin mesylate Drugs 0.000 claims abstract description 9
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 9
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 9
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Images
Abstract
The present invention provides a slow releasing doxazosin mesilate medicinal preparation for oral administration. The preparation comprises doxazosin mesylate and a polymer which can be accepted by medicine. The preparation comprises 1 to 10% of doxazosin mesylate, 10 to 70% of auxiliary materials for slow release and other auxiliary materials as the rest, wherein the auxiliary materials for slow release are the dissoluble / insoluble salts of hypromellose and/or ethyl cellulose and/or polyacrylic acid resins and/or polyhydroxy ethyl and/ or alginic acid. Compared with a quick releasing preparation, the slow releasing preparation of the present invention can keep effective and smooth blood and medicine concentration within 24 hours, enhance therapeutic effect, improve taste, decrease the time of oral administration, decrease the incidence rate of side effect and provide convenience for oral administration. The present invention can be widely used for treating the diseases of benign prostate hyperplasia, high blood pressure, etc.
Description
Technical field:
The invention belongs to medical technical field, exactly it is the doxazosin mesylate sustained-release preparation of diseases such as the treatment benign prostatic hyperplasia of a kind of administration every day 1 time and hypertension.
Background technology:
Carclura is selectivity α
1The adrenoceptor blocker.By blocking the effect that the α receptor reaches blood vessel dilating, reduces vascular resistance, brings high blood pressure down; Alpha adrenergic receptor by selective exclusion prostate smooth muscle substrate, tunicle and neck of bladder can improve benign prostatic hyperplasia patient's symptom, is used widely clinically.Carclura is soluble in dimethyl sulfoxine; Be dissolved in dimethylformamide; Be slightly soluble in methanol, second alcohol and water (0.8%, 25 ℃); Be insoluble in acetone and dichloromethane; The utmost point is insoluble in chloroform.
This product is mainly in gastrointestinal absorption, and absorption is rapid, complete, and age and sex are to absorbing no significant difference.Doxazosin mesilate tablets is that Pfizer had obtained this product chemical compound patent right in 1978 by the medicine of Britain Pfizer exploitation listing.1988, the Carclura chemical compound was in Denmark's Initial Public Offering, thereafter again successively in country's listings such as Norway, Holland, Britain, West Germany, Italy, Japan, the U.S..Commercially available Carclura ordinary preparation has tablet, capsule etc. at present.For ordinary preparation, common administering mode is initial dose 1mg, and once a day, 1-2 adjusts dosage according to clinical response and tolerance situation after week, and maintenance dose is 1-8mg, every day 1 time.The mode of this repeatedly medication is not only given patient and doctor the inconvenience of having taken, and in case mistake occurs on dosage, patient's health also can be on the hazard.
The Chinese patent of at present relevant Carclura has: 1, " process for synthesizing doxazosin mesylate " (publication number: CN1285353A, application number: 99117037.7); 2, " medicine that contains doxazosin-mesylate of crystalline modification D " (publication number: CN1352571A, application number: 00805173.9).
Slow releasing preparation be with the curative effect of medicine only relevant with vivo medicine concentration and with the third generation dosage form of irrelevant this conceptual foundation development of administration time, do not need frequent drug administration, medicine can discharge on request lentamente at absorption site, blood drug level is reached and remain on and treat within the concentration range, this can make side effects of pharmaceutical drugs be reduced to minimum degree and reduce administration frequency.In general, this kind preparation is compared with fast dissolving dosage form, and the safety and the advantages such as effectiveness and compliance of patients that improve medication are arranged.
Summary of the invention:
The objective of the invention is for a kind of doxazosin mesylate sustained-release preparation of the blood drug level of remaining valid in 24 hours is provided, it can effectively treat benign prostatic hyperplasia and high blood pressure disease.
The object of the present invention is achieved like this:
Preparation of the present invention contains following component by weight percentage:
Carclura 1-10%
Play the adjuvant 10-70% of slow releasing function
Other adjuvant surplus
This preparation comprises the various preparations of film control, skeleton, gel, porous matrix type, also comprises making the various preparations that microcapsule, microsphere etc. are made preparation more earlier.
Solubility/insoluble salt that the above-mentioned adjuvant that plays slow releasing function is hydroxypropyl methylcellulose and/or ethyl cellulose and/or alginic acid and/or polyacrylic resin class and/or polycarboxy ethene and/or other play the adjuvant of slow releasing function, the hydroxypropyl methylcellulose employing includes the extensive stock of hydroxypropyl methylcellulose (HPMC) such as U.S. many elegant (Methocel) of all size, ethyl cellulose adopts the extensive stock that includes ethyl cellulose (EC), and the polyacrylic resin class adopts and includes polyacrylic resin II, the acrylic resin of III class or analog such as all size (Eudragit).Above-mentioned adjuvant is porogen, filler, binding agent, lubricant, emulsifying agent, membrane material, solvent or other adjuvant, and porogen can adopt sucrose, mannitol, starch, Pulvis Talci, silicon dioxide etc.; Filler can adopt lactose, starch, dextrin etc.; Binding agent can adopt the ethanol-water solution of polyvinylpyrrolidone, hypromellose, dehydrated alcohol, various concentration etc.; Wetting agent can adopt the ethanol-water solution of water, dehydrated alcohol, various concentration; Lubricant can adopt stearic acid, Pulvis Talci, magnesium stearate, starch, paraffin etc.; Solubilizing agent can be adopted tartaric acid, citric acid etc.; Emulsifying agent can adopt span80 span85 etc.; Membrane material can adopt polyvinyl alcohol, hydroxyl methylcellulose, hyetellose, hymetellose, methylcellulose etc.; Foaming agent can adopt basic magnesium carbonate, sodium bicarbonate etc.; Bleach activator can adopt hexadecanol, octadecanol, Cera Flava etc.; Solvent can adopt dehydrated alcohol, ethanol, water etc.
The dosage form of-above-mentioned preparation has sheet type, coating type or other pharmaceutically common dosage form.
-advantage of the present invention is: improved curative effect, improved sense of taste, reduced and to take number of times, reduced the side effect incidence rate, taken, easy to carry.
Description of drawings:
Fig. 1 is the stripping curve figure of doxazosin mesylate sustained-release preparation
The specific embodiment:
Embodiment 1:
Present embodiment 1 tablet that adopts the known method of pharmaceuticals industry to make contains following composition by weight percentage:
Carclura 2.7%
HPMCK4M(Methocel?K15MCR) 45％
Lactose 51.6%
Magnesium stearate 0.7%
HPMCK4M is a hydrophilic polymer, is framework material in said preparation, meets the expansion of water or Digestive system and forms the gel barrier, and the diffusion of control Carclura reaches the slow release purpose.
Wherein HPMCK4M can be replaced by the HPMCK100LV of different amounts or HPMCK15M or HPMCK100M, or is used in combination, to adjust the release curve.
Embodiment 2:
Carclura 3%
Carbopol 45%
Lactose 51%
Magnesium stearate 1%
Hydrophilic polymer carbopol (carbomer) is a framework material, meets the expansion of water or Digestive system and forms the gel barrier, and the diffusion of control Carclura reaches the slow release purpose.
Embodiment 3:
Present embodiment 3 tablets that adopt the known method of pharmaceuticals industry to make contain following composition by weight percentage:
Carclura 3%
Sodium alginate 37%
Calcium alginate 3%
Lactose 56%
Magnesium stearate 1%
The insoluble salt of hydrophilic polymer alginic acid and soluble-salt are framework material, meet the gel barrier that the expansion of water or Digestive system forms commissure, and the diffusion of control Carclura reaches the slow release purpose.
Embodiment 4:
Carclura 3%
Ethyl cellulose and stearic acid 55%
Lactose 41%
Magnesium stearate 1%
Bioerodable material stearic acid in vivo gradually corrosion make principal agent discharge slow releasing function gradually, ethyl cellulose is a not corrosion framework material, treats that drug release excretes after intact.
Embodiment 5:
Present embodiment 5 tablets that adopt the known method of pharmaceuticals industry to make contain following composition by weight percentage:
Polyacrylic resin 20%
Lactose 40%
Microcrystalline Cellulose 21%
10% polyvinylpyrrolidone ethanol liquid 3%
Polyacrylic resin is that the undissolved polymer of gastrointestinal tract is the clothing membrane material, adding a spot of polyvinylpyrrolidone ethanol liquid (PVP) in coating solution is porogen, i.e. solubilized in Digestive system, and making on the clothing film has micropore, medicine discharges from micropore, plays slow releasing function.
Embodiment 6:
Ethyl cellulose 36.25%
Lactose 53%
Magnesium stearate 0.75%
Ethyl cellulose is insoluble framework material, and medicine is dispersed in the insoluble framework material, and drug releasing rate depends on that the dissolution velocity of diffusion velocity and medicine is irrelevant.Medicine is the saturated solution state in skeleton, discharge from insoluble framework material, reaches the slow release purpose.
Embodiment 7:
Adopt the gastric floating tablet of the present embodiment 7 of the known method preparation of pharmaceuticals industry to contain following composition by weight percentage:
HPMCK100LV 48％
Stearic acid 7%
Basic magnesium carbonate 11%
PVPK
30 5％
Lactose 20%
Magnesium stearate 1%
HPMCK100LV is a hydrophilic polymer, meets gastric juice and expands and form the gel barrier, and the density of keeping skeleton is less than gastric content density, and floats on the gastric juice; Stearic acid is a bleach activator, and can reduce the hydration rate of skeleton; Basic magnesium carbonate is a foaming agent, meets gastric acid and produces CO
2, can further alleviate the density of preparation, thereby prolong the doxazosin mesilate tablets holdup time under one's belt, reach the slow release purpose.
Embodiment 8:
Adopt the coating type preparation of the present embodiment 8 of the known method preparation of pharmaceuticals industry to contain following composition by weight percentage:
Carclura 5%
Lactose 53.5%
Polyacrylic resin II 38%
Anhydrous alcohol solution 3%
Magnesium stearate 0.5%
Earlier medicine and adjuvant are pressed into label, wrap enteric coating (being polyacrylic resin II) again, when medicine enters intestinal, the enteric coating dissolving, the release medicine plays the delay release action, i.e. the enteric film sustained release.
Embodiment 9:
Adopt the coating type preparation of the present embodiment 9 of the known method preparation of pharmaceuticals industry to contain following composition by weight percentage:
Polyvinylpyrrolidone 9%
Microcrystalline Cellulose 37%
Icing Sugar 30%
Lubricant 20%
Each component is the core on it.
Hypromellose 12g
Propylene glycol 3g
Titanium dioxide 3g
PEG6000 1g
Sodium lauryl sulphate 0.5g
Pulvis Talci 2g
Water 120ml
More than each medicine be the coating aqueous suspension.
Making piller earlier is core, outsourcing hydrophilic film clothing (HPMC etc.), oral after, meet Digestive system, constitute the hydrophilic polymer water absorption and swelling of film-coat, form the gel barrier, controlled drug release.
Claims (1)
1. doxazosin mesylate sustained-release preparation, it is characterized in that: said preparation contains following composition by weight percentage: principal agent is a Carclura, proportion is 1-10%; The adjuvant that plays slow releasing function is one or more of the solubility/insoluble salt of hydroxypropyl methylcellulose and/or ethyl cellulose and/or alginic acid and/or polyacrylic resin and/or carbopol apoplexy due to endogenous wind, and shared percentage by weight is 10-70%; Other is in adjuvant porogen, filler, solubilizing agent, binding agent, lubricant, wetting agent, emulsifying agent, membrane material, foaming agent, bleach activator, correctives, the solvent one or more, and the dosage form of preparation has matrix tablet and intra-gastric floating tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031333672A CN100391459C (en) | 2003-05-26 | 2003-05-26 | Doxazosin mesilate slow releasing preparation |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031333672A CN100391459C (en) | 2003-05-26 | 2003-05-26 | Doxazosin mesilate slow releasing preparation |
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| Publication Number | Publication Date |
|---|---|
| CN1457785A CN1457785A (en) | 2003-11-26 |
| CN100391459C true CN100391459C (en) | 2008-06-04 |
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| CNB031333672A Expired - Fee Related CN100391459C (en) | 2003-05-26 | 2003-05-26 | Doxazosin mesilate slow releasing preparation |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102188431A (en) * | 2011-05-09 | 2011-09-21 | 浙江九旭药业有限公司 | Doxazosin mesylate sustained-release tablets and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1285353A (en) * | 1999-08-20 | 2001-02-28 | 广东康美药业股份有限公司 | Process for synthesizing doxazosin mesylate |
| CN1342068A (en) * | 1999-02-01 | 2002-03-27 | 阿迪尔公司 | Core tablet for controlled release of gliclazide after oral administration |
| US20030059467A1 (en) * | 2001-09-14 | 2003-03-27 | Pawan Seth | Pharmaceutical composition comprising doxasozin |
-
2003
- 2003-05-26 CN CNB031333672A patent/CN100391459C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1342068A (en) * | 1999-02-01 | 2002-03-27 | 阿迪尔公司 | Core tablet for controlled release of gliclazide after oral administration |
| CN1285353A (en) * | 1999-08-20 | 2001-02-28 | 广东康美药业股份有限公司 | Process for synthesizing doxazosin mesylate |
| US20030059467A1 (en) * | 2001-09-14 | 2003-03-27 | Pawan Seth | Pharmaceutical composition comprising doxasozin |
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| CN1457785A (en) | 2003-11-26 |
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