CN101897675B - Solid oral medicinal composition containing valsartan or pharmaceutically acceptable salts of valsartan - Google Patents
Solid oral medicinal composition containing valsartan or pharmaceutically acceptable salts of valsartan Download PDFInfo
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Abstract
The invention relates to a solid oral medicinal composition containing valsartan or the pharmaceutically acceptable salts thereof. Particularly, the composition is directly prepared into particles by a wet method according to a new formula.
Description
Technical field
The present invention relates to a kind of medical component, especially relate to a kind of valve husky smooth solid dosage forms oral medicinal composition and manufacturing approach thereof of containing.
Background technology
Valve sand smooth (VALSARTAN) stop angiotensin II (ANGIOTENSIN II) vasoconstriction (VASOCONSTRICTOR) and aldehyde fat ketone (ALDOSTERONE) secretion usefulness, go up angiotensin II combination AT1 receptor (RECEPTOR) by selecting to hinder at a lot of tissues as vascular smooth muscle and adrenal gland (ADRENAL GLAND).This effect is irrelevant mutually with angiotensin II synthesis path.Therefore valve is husky smoothly is known effective treatment congestive heart failure and is regardless of that age, sex and race bring high blood pressure down, favorable durability simultaneously.
Hydrogen chlorobenzene thiophene pyridazine (HYDROCHLOROTHIAZIDE) is a kind of thiophene
type hiazide) diuretic.Thiophene
class influences renal tubules electrolyte mechanism of absorption again, directly increases almost equivalent sodium and chlorine drainage.Indirectly hydrogen chlorobenzene thiazine rattle away reduce blood plasma volume and the secretion of aldehyde fat ketone, increase in the urine that potassium disappears and minimizing blood in potassium.Feritin-aldehyde fat ketone ring (renin-aldosterone link) is regulated by angiotensin II, and is therefore husky smooth during with clothes with valve, is easy to reverse diuretic and causes that potassium disappears.
Amlodipine (AMLODIPINE) is a kind of dihydropyridine (Dihydropyridine) calcium antagonist; Claiming calcium ion antagonist (calcium ion antagonist) or slow pipeline blocker (slow-channelblocker) again, is can be in order to suppress smooth muscle and the cardiac muscle of calcium ion through the cell membrane intravasation.Experimental data shows that Amlodipine can combine with dihydropyridine and non-dihydropyridine junction.Cardiac muscle and vascular smooth muscle contraction process rely on the outer calcium ion of born of the same parents and get into these cells through the specific ion passage.The alternative calcium ion that suppresses of Amlodipine flows into cell membrane, and especially the effect to vascular smooth cell more is far more than myocardial cell.Serum calcium ion concentration can't receive the influence of Amlodipine.In physiological range, Amlodipine is a kind of ionic compound (pKa=8.6), and it interacts with the kinetics of calcium channel receptor is to have the characteristic that combines and separate progressive speed with receptor, and it facilitates progressive effect.Amlodipine is a kind of Peripheral arteries vasodilation, directly acts on vascular smooth muscle, causes that lowering peripheral blood vessel resists and bring high blood pressure down.Amlodipine treatment hypertension, coronary artery disease comprise chronic stable angina pectoris and the angina pectoris of vasospasm property.
United States Patent (USP) (No.6; 294; 197) having disclosed valve sand smooth is a kind of material of absent-mindedness; When processing lozenge, the not boring of simple filler higher dosage ground absent-mindedness material entering borer (punch), and necessity becomes granule, especially mixes with other absent-mindedness material such as micro-crystallization fiber (Microcrystalline Cellulose) more and will go to handle with compression with the dry type compressor compresses.Simultaneously, United States Patent (USP) 6294197 also disclose for process little lozenge, valve husky smooth in lozenge, must contain at least 35% percentage by weight, valve husky smooth in lozenge the best technology contents such as 57%-62% that are weight percentage.
United States Patent (USP) 6294197 still discloses the husky smooth compound recipe that is constituted with hydrogen chlorobenzene thiophene pyridazine of valve.Wherein the husky smooth content of valve also is defined and accounts for the lozenge percentage by weight at least more than 35%, has also disclosed the technology contents that adopts the dry type compression to make simultaneously.In other words, United States Patent (USP) 6294197 is clear presents it and is subject to prior art and limits the husky smooth content of valve and account for the fact of lozenge percentage by weight more than 35% at least.
Taiwan patent of invention (publication number 200740432; The priority U.S. 60/709; 083, priority date on August 17th, 2005) the relevant valve of record husky smooth and the solid dosage forms of Amlodipine and the method for preparation, it is to utilize the dry type compression method to make granule then to break into monolayer or bi-layer troche.
Taiwan patent of invention (publication number 200808379; The priority U.S. 60/805; 883; Priority date on June 27th, 2006) solid dosage forms of smooth, Amlodipine of the relevant valve sand of record and hydrogen chlorobenzene thiophene pyridazine and preparation method thereof also discloses to have and utilizes its composite dry compression method to make the technology contents that granule breaks into monolayer, bilayer and three layers of lozenge.
Disclosed the comprehensive organism medicine and pharmacology characteristic of above-mentioned substance by aforesaid U.S. Patent 6294197, Taiwan patent of invention publication number 200740432 and Taiwan patent of invention publication number 200808379, therefore the value of exploitation arranged with the combination dosage forms of bioequivalent these the three kinds of medicines of its independent assortment.Yet, owing to the husky smooth characteristic that absent-mindedness is difficult for making ingot that has of aforementioned valve, the solid dosage forms oral medicinal composition that causes prior art to develop can according with the demands of the market.
Summary of the invention
For solving above-mentioned at least one technical problem, the object of the present invention is to provide a kind of contain valve sand smooth, contain the husky smooth and hydrogen chlorobenzene thiophene pyridazine of valve, contain the husky smooth and Amlodipine of valve or contain that valve sand is smooth, the solid dosage forms oral medicinal composition and the manufacturing approach thereof of hydrogen chlorobenzene thiophene pyridazine and Amlodipine.
For solving above-mentioned at least one goal of the invention, solid dosage forms oral medicinal composition provided by the invention includes:
Husky smooth or its pharmaceutically acceptable salt of the valve of effective dose; And
Be fit to utilize wet method for making to make the pharmaceutically acceptable additive of solid dosage forms oral medicinal composition.
Solid dosage forms oral medicinal provided by the present invention prescription can overcome the husky smooth absent-mindedness of valve and is difficult for the characteristic of system ingot, so produce form lozenge dosage form or film clothing lozenge type the solid dosage forms oral medicinal composition to realize the object of the invention.
Another technological means that the present invention taked provides a kind of method of production solid dosage forms oral medicinal composition, includes following steps:
The valve husky main constituent and the suitable pharmaceutically acceptable additive that utilizes wet method for making to make the solid dosage forms oral medicinal composition smooth or its pharmaceutically acceptable salt that will comprise effective dose mix to obtain mixture;
With said mixture with wet granulation pelletize, heat drying after to obtain shot-like particle;
Obtain the solid dosage forms oral medicinal composition with suppressing after said shot-like particle and all the other additives mixed.
Method provided by the present invention can overcome the husky smooth absent-mindedness of valve and be difficult for the characteristic of system ingot, realizes the object of the invention to produce the solid dosage forms oral medicinal composition.
Additional aspect of the present invention and advantage part in the following description provide, and part will become obviously from the following description, or recognize through practice of the present invention.
Description of drawings
Above-mentioned and/or additional aspect of the present invention and advantage are from obviously with easily understanding becoming the description of embodiment below in conjunction with accompanying drawing, wherein:
Fig. 1 is solid dosage forms oral medicinal composition provided by the invention and the comparative solubility test result of existing solid dosage forms oral medicinal composition.
The specific embodiment
Below by embodiment concrete technology contents of the present invention is detailed further.This embodiment is in order to illustrative technology contents of the present invention, but not in order to restriction the present invention.The technical field those of ordinary skill of relevant pharmacy is appreciated that the content by following examples under the present invention, will be enough to support the present invention to contain zone of reasonableness more widely.
Embodiment 1
The solid dosage forms oral medicinal composition that present embodiment provided is valve husky smooth or its pharmaceutically acceptable salt and the suitable pharmaceutically acceptable additive that utilizes wet method for making manufacturing solid dosage forms oral medicinal composition that comprises effective dose.Wherein, this solid dosage forms oral medicinal composition includes husky smooth or its medical acceptable salt of valve of single dose 40-320 milligram.And aforementioned single dose is a record method habitual in pharmaceutical field or pharmaceutical industries correlative technology field; Particularly be meant the dosage that for example single lozenge or capsule are provided when being applied to sufferer.
In the present embodiment, be based on the made solid dosage forms oral medicinal composition of table 1 listed prescription I～IV.Its valve sand that includes 40,80,160 and 320 milligrams of single doses respectively is smooth, and promptly the husky smooth shared percentage by weight of valve is respectively 12%, 22%, 32% and 34%.Can know that by containing the husky smooth solid dosage forms oral medicinal composition prescription of valve shown in the present embodiment the husky smooth shared percentage by weight of its valve all is not higher than 35%, also be the technology contents that its composition is different from the disclosed relevant component ratio of prior art.
Table 1
In addition, the present invention except that can adopt valve husky smooth, also can adopt the husky smooth medical acceptable salt of valve.The technical field those of ordinary skill of relevant pharmacy can easily select husky smooth or its medical acceptable salt of valve to come embodiment of the present invention as required under the present invention.Simultaneously, when using solid dosage forms oral medicinal composition provided by the present invention such as doctor's thing personnel such as doctors, the knowledge that it possessed also is enough to make it to understand the property of medicine of husky smooth or its medical acceptable salt of valve and is able to cooperation and need selects for use.Therefore; Though the main in the present embodiment illustration of the present invention is based on the made solid dosage forms oral medicinal composition of aforementioned prescription I～IV; But, rationally contain the scope of the medical acceptable salt that comprises that valve sand is smooth in fact based on the common knowledge of the technical field of relevant pharmacy under the present invention.
In conjunction with accompanying drawing, the comparative solubility test result of solid dosage forms oral medicinal composition more provided by the invention and existing solid dosage forms oral medicinal composition (like products such as
).Adopt the solid dosage forms oral medicinal composition and the existing solid dosage forms oral medicinal composition that respectively contain the smooth lozenge dosage form provided by the present invention of 80mg valve sand to be dissolved in the solubility curve that is appeared in the PBS of pH 6.8 respectively.
Hence one can see that solid dosage forms oral medicinal composition provided by the present invention has as stated the husky smooth shared percentage by weight of valve be no more than 35% technical characterictic, overcome the restriction of prior art prejudice.Can know by the result of the test that above-mentioned accompanying drawing disclosed again; Though it is smooth at the valve sand below 35% that the technological made solid dosage forms oral medicinal composition that overcomes prior art prejudice restriction according to the present invention only has percentage by weight; The husky smooth content of the valve of existing solid dosage forms oral medicinal composition is overweight percentage ratio 35% then; But solid dosage forms oral medicinal composition of the present invention demonstrates very similar solubility curve with existing solid dosage forms oral medicinal composition, suffices to show that solid dosage forms oral medicinal composition of the present invention has almost completely identical effect with existing solid dosage forms oral medicinal composition in clinical practice.Thereby under the present invention in the relevant technical field of pharmacy those of ordinary skill it will be appreciated that based on the technical characterictic of this case and to the general knowledge of the husky smooth property of medicine of valve the solid dosage forms oral medicinal composition that this case provides can properly be used to treat hypertension, congestive heart failure, angina pectoris, myocardial infarction, arteriosclerosis, renal function deficiency, diabetic nephropathy, diabetic cardiomyopathy, apoplexy, peripheral vascular disease, left ventricular hypertrophy, consciousness dysfunction, headache or chronic heart failure.
Present embodiment can form lozenge dosage form or film clothing lozenge type based on the made solid dosage forms oral medicinal composition of prescription I～IV.According to one of embodiment of the present invention, the manufacturing approach that forms the lozenge dosage form based on the made solid dosage forms oral medicinal composition of prescription I～IV is to include following steps:
The valve husky main constituent and the suitable part of utilizing wet method for making to make the pharmaceutically acceptable additive of solid dosage forms oral medicinal composition smooth or its pharmaceutically acceptable salt that (a) will comprise effective dose are mixed to obtain mixture.In the present embodiment, its main constituent promptly includes 40,80,160 or 320 milligrams of single doses, and promptly percentage by weight 12%, 22%, 32% or 34% valve sand are smooth; In addition in the present embodiment, its additive includes avicel cellulose, lactose, polyvinylpolypyrrolidone, silicon dioxide, magnesium stearate.A kind of practical implementation method of this step is that whole avicel celluloses, a part of lactose and a part of polyvinylpolypyrrolidone are told the major part that becomes additive; And all the other lactose, all the other polyvinylpolypyrrolidone, whole silicon dioxide and whole magnesium stearate are told the remainder that becomes additive, more aforementioned main constituent is mixed to obtain this mixture with the major part of additive.Adopt wet granulation for cooperating, earlier additive is divided into major part and remainder, after treating main constituent and the major part of additive being mixed, remix additive remainder, this belongs to techniques well known.Therefore, the ratio of distinguishing additive major part and remainder also is can cooperate actual needs about those of ordinary skill in the technical field of pharmacy under the present invention, and the item need not to decide in its sole discretion under the situation of creative work repeats no more at this.
(b) with aforementioned mixture with wet granulation pelletize, heat drying after to obtain shot-like particle.Aforementioned wet granulation can be taked the technological means of water pelletize, because wet granulation is a prior art, does not repeat them here.In addition aforementioned mixture can further sieved and granulate after with wet granulation pelletize, heat drying.Particularly, in this step, can adopt the temperature of 60 degree approximately Celsius to carry out heat drying.
(c) suppress after the remainder of aforementioned shot-like particle and aforementioned additive is mixed and obtain the solid dosage forms oral medicinal composition.The technological means of the aforementioned shot-like particle of a kind of concrete compacting is with Ingot pressing machine aforementioned shot-like particle to be pressed into lozenge.The concrete size that this lozenge can adopt is can cooperate the item that need decide in its sole discretion about those of ordinary skill in the technical field of pharmacy under the present invention, and according to present embodiment, concrete size is following:
(I) circle, 9.5 millimeters of diameters, high 4.0-4.4 millimeter (330 milligrams).
(II) circle, 9.5 millimeters of diameters, high 4.6-5.0 millimeter (365 milligrams).
(III) round, 12 millimeters of diameters, high 3.8-4.2 millimeter (500 milligrams).
(IV) round, 13 millimeters of diameters, high 5.0-5.4 millimeter (950 milligrams).
As stated, present embodiment can form lozenge type or film clothing lozenge type based on the made solid dosage forms oral medicinal composition of prescription I～IV.As when making solid dosage forms oral medicinal composition of the present invention form film clothing lozenge type, can be after the aforementioned shot-like particle of compacting be the ingot sheet of lozenge type, further implementation will be covered the step that forms film clothing lozenge type with the agent of film clothing through the aforementioned ingot sheet of compacting.
Method making film clothing ingot with a shot-like particle, belongs to prior art with film clothing agent film coating in this ingot sheet outside again.Following illustration is a kind of behind the aforementioned shot-like particle of compacting, will cover with the agent of film clothing through the aforementioned ingot sheet of compacting to form the feasible method of film clothing lozenge type to make solid dosage forms oral medicinal composition of the present invention.Because as the agent of film clothing to become the details of the prior art of grading be can cooperate needs about having common knowledge the knowledgeable in the those of ordinary skill of pharmacy under the present invention; The item of making decision in the situation that need not creative work; Though, also be enough to let the those of ordinary skill of the affiliated relevant pharmacy of the present invention implemented according to the present invention so locate only to describe for example.
At first get all the film clothing agent composition as shown in table 2 ready; This is included the film clothing agent composition mix homogeneously of hydroxyethylmethyl-cellulose, Polyethylene Glycol, titanium dioxide, Talcum, ferrum oxide and pure water, through homogenizer this film clothing agent composition is mixed mould evenly to obtain the agent of film clothing again.Then take the film clothing agent of the about 2-4% weight that is equivalent to aforementioned ingot sheet, and behind the aforementioned shot-like particle of compacting, will cover with this film clothing agent and can make the solid dosage forms oral medicinal composition form film clothing lozenge type through the aforementioned ingot sheet of compacting.
Table 2
| Composition | Recipe quantity (gram) |
| Hydroxyethylmethyl- |
4 |
| Polyethylene Glycol | 0.7 |
| Titanium dioxide | 1 |
| Talcum | 2.5 |
| Ferrum oxide | 0.6 |
| |
100 |
In addition; Can know that by the technology contents of above-mentioned exposure solid dosage forms oral medicinal composition provided by the present invention not only can define it by its composition and recipe quantity and form; More owing to carried out concrete and clear and definite record for the manufacturing approach of the solid dosage forms oral medicinal composition that forms lozenge dosage form or film clothing lozenge type in the present embodiment, solid dosage forms oral medicinal composition provided by the present invention also can be defined by this manufacturing approach.In other words; The those of ordinary skill of relevant pharmacy is based on the technical characterictic of this case under the present invention, it will be appreciated that the solid dosage forms oral medicinal composition that is defined with this manufacturing approach also can provide as above-mentioned effect to be able to properly be used to treat hypertension, congestive heart failure, angina pectoris, myocardial infarction, arteriosclerosis, renal function deficiency, diabetic nephropathy, diabetic cardiomyopathy, apoplexy, peripheral vascular disease, left ventricular hypertrophy, consciousness dysfunction, headache or chronic heart failure.
Embodiment 2
The solid dosage forms oral medicinal composition that present embodiment provided is valve husky smooth or its pharmaceutically acceptable salt, the hydrogen chlorobenzene thiophene pyridazine of effective dose and the pharmaceutically acceptable additive that is fit to utilize wet method for making manufacturing solid dosage forms oral medicinal composition that includes effective dose; Wherein, this solid dosage forms oral medicinal composition includes the hydrogen chlorobenzene thiophene pyridazine of husky smooth or its medical acceptable salt and single dose 10-30 milligram of the valve of single dose 40-320 milligram.
In the present embodiment, be that illustration discloses the made solid dosage forms oral medicinal composition of prescription I～V based on table 3.The hydrogen chlorobenzene thiophene pyridazine that it includes 12.5,12.5,25,12.5 and 25 milligrams of the husky smooth and corresponding single doses of valve of 80,160,160,320 and 320 milligrams of single doses respectively also is that the husky smooth and shared percentage by weight of hydrogen chlorobenzene thiophene pyridazine of valve is respectively 25%, 34%, 34%, 34% and 34%.Can know by containing the husky smooth solid dosage forms oral medicinal composition prescription of valve shown in the present embodiment; The husky smooth and shared percentage by weight of hydrogen chlorobenzene thiophene pyridazine of its valve all is not higher than 35%, is that its composition is the technology contents that relevant component ratio that the prior art of differing from discloses is arranged yet.
Table 3
In addition; Though mainly be the hydrogen chlorobenzene thiophene pyridazine that adopts 12.5,12.5,25,12.5 and 25 milligrams of single doses in this prescription I～V; But, can make an amount of adjustment to the consumption of hydrogen chlorobenzene thiophene pyridazine because the property of medicine of hydrogen chlorobenzene thiophene pyridazine belongs to known item for the relevant those of ordinary skill of pharmacy under the present invention.Therefore the those of ordinary skill of the affiliated relevant pharmacy of the present invention is when embodiment of the present invention; Based on the technology contents that the present invention disclosed, within the scope of the hydrogen chlorobenzene thiophene pyridazine of single dose 10-30 milligram, need not creative work at least and promptly can implement according to the present invention.
Common knowledge based on relevant hydrogen chlorobenzene thiophene pyridazine in the relevant technical field of pharmacy under the present invention; And be the basis with existing solid dosage forms oral medicinal composition has almost completely identical effect in clinical practice the fact with the solid dosage forms oral medicinal composition of previous embodiment shown in the accompanying drawing 1; In clinical practice, also have almost completely identical effect about those of ordinary skill in the technical field of pharmacy it will be appreciated that the solid dosage forms oral medicinal composition of the embodiment of the invention 2 with existing solid dosage forms oral medicinal composition under the present invention, thereby be able to properly be used to treat hypertension, congestive heart failure, angina pectoris, myocardial infarction, arteriosclerosis, renal function deficiency, diabetic nephropathy, diabetic cardiomyopathy, apoplexy, peripheral vascular disease, left ventricular hypertrophy, consciousness dysfunction, headache or chronic heart failure.
Can form lozenge dosage form or film clothing lozenge type based on the made solid dosage forms oral medicinal composition of prescription I～V shown in the present embodiment.A kind of manufacturing approach that present embodiment is formed the lozenge dosage form based on the made solid dosage forms oral medicinal composition of prescription I～V; The main constituent of being adopted includes the hydrogen chlorobenzene thiophene pyridazine of 12.5,12.5,25,12.5 or 25 milligrams of the husky smooth and single doses of the valve of 80,160,160,320 or 320 milligrams of single doses; Also be that the husky smooth and shared percentage by weight of hydrogen chlorobenzene thiophene pyridazine of valve is respectively 25%, 34%, 34%, 34% or 34%, its similar previous embodiment 1 is said: (a) with aforementioned main constituent and a part that is fit to utilize wet method for making to make the pharmaceutically acceptable additive of solid dosage forms oral medicinal composition mix to obtain mixture; (b) with aforementioned mixture with wet granulation pelletize, heat drying after to obtain shot-like particle and (c) to suppress after the remainder of aforementioned shot-like particle and aforementioned additive is mixed and obtain step such as solid dosage forms oral medicinal composition, realize the present invention so that the solid dosage forms oral medicinal composition to be provided.
In addition; In embodiment 2 also can with based on prescription I～V by the made ingot sheet of said method as core; Implement again to be similar to the film clothing lozenge type manufacture method that previous embodiment 1 is detailed, make the solid dosage forms oral medicinal composition of the embodiment of the invention 2 form film clothing lozenge type.
Further; Can know that by above-mentioned technology contents solid dosage forms oral medicinal composition provided by the present invention not only can define it by its composition and recipe quantity and form; More owing to carried out concrete and clear and definite record for the manufacturing approach of the solid dosage forms oral medicinal composition that forms lozenge dosage form or film clothing lozenge type in the present embodiment, solid dosage forms oral medicinal composition provided by the present invention also can be defined by this manufacturing approach.In other words; Under the present invention in the relevant technical field of pharmacy those of ordinary skill it will be appreciated that the solid dosage forms oral medicinal composition that is defined with this manufacturing approach also can provide as above-mentioned effect to be able to be used to treat hypertension, congestive heart failure, angina pectoris, myocardial infarction, arteriosclerosis, renal function deficiency, diabetic nephropathy, diabetic cardiomyopathy, apoplexy, peripheral vascular disease, left ventricular hypertrophy, consciousness dysfunction, headache or chronic heart failure based on the technical characterictic of this case.
Embodiment 3
The solid dosage forms oral medicinal composition that the embodiment of the invention 3 is provided is valve husky smooth or its pharmaceutically acceptable salt, Amlodipine or its pharmaceutically acceptable salt of effective dose and the pharmaceutically acceptable additive that is fit to utilize wet method for making manufacturing solid dosage forms oral medicinal composition that comprises effective dose; Wherein, this solid dosage forms oral medicinal composition includes Amlodipine or its pharmaceutically acceptable salt of husky smooth or its medical acceptable salt and single dose 2.5-20 milligram of the valve of single dose 40-320 milligram.
In the present embodiment, be based on table 4 and disclose the made solid dosage forms oral medicinal composition of prescription I～IV.The Amlodipine that it includes 5,10,5 and 10 milligrams of the husky smooth and corresponding single doses of valve of 160,160,320 and 320 milligrams of single doses respectively also is that the husky smooth and shared percentage by weight of Amlodipine of valve is to be respectively 33%, 34%, 34% and 34%.Can know that by containing the husky smooth solid dosage forms oral medicinal composition prescription of valve shown in the present embodiment the husky smooth shared percentage by weight of its valve all is not higher than 35%, also be that its composition is the technology contents that relevant component ratio that the prior art of differing from discloses is arranged.
Table 4
The present invention is except that adopting the medical acceptable salt that also can adopt Amlodipine the Amlodipine.The technical field those of ordinary skill of relevant pharmacy can easily cooperate needs to select Amlodipine or its medical acceptable salt to come embodiment of the present invention under the present invention.Simultaneously, when using solid dosage forms oral medicinal composition provided by the present invention such as doctor's thing personnel such as doctors, the Professional knowledge that it possessed also is enough to make it to understand the property of medicine of Amlodipine or its medical acceptable salt and is able to cooperation and need select for use.Therefore; Though the main in the present embodiment illustration of the present invention is based on the made solid dosage forms oral medicinal composition of aforementioned prescription I～IV; But, rationally contain the scope of the medical acceptable salt that comprises Amlodipine in fact based on the general knowledge of the technical field of relevant pharmacy under the present invention.
In addition; Though mainly be the Amlodipine that adopts 5,10,5 and 10 milligrams of single doses in this prescription I～IV; But, can make an amount of adjustment to the consumption of Amlodipine or its medical acceptable salt because the property of medicine of Amlodipine belongs to known item for those of ordinary skill in the relevant technical field of pharmacy under the present invention.Therefore under the present invention in the relevant technical field of pharmacy those of ordinary skill when embodiment of the present invention; Based on the technology contents that the present invention disclosed, in the scope of the Amlodipine of single dose 2.5-20 milligram or its medical acceptable salt, need not creative work at least and promptly can implement according to the present invention.
Common knowledge based on relevant Amlodipine in the relevant technical field of pharmacy under the present invention; And be the basis with existing solid dosage forms oral medicinal composition has almost completely identical effect in clinical practice the fact with the solid dosage forms oral medicinal composition of previous embodiment shown in the accompanying drawing; In clinical practice, also have almost completely identical effect about those of ordinary skill in the technical field of pharmacy it will be appreciated that the solid dosage forms oral medicinal composition of the embodiment of the invention 3 with existing solid dosage forms oral medicinal composition under the present invention, thereby be able to properly be used to treat hypertension, congestive heart failure, angina pectoris, myocardial infarction, arteriosclerosis, renal function deficiency, diabetic nephropathy, diabetic cardiomyopathy, apoplexy, peripheral vascular disease, left ventricular hypertrophy, consciousness dysfunction, headache or chronic heart failure.
Can form lozenge dosage form or film clothing lozenge type based on the made solid dosage forms oral medicinal composition of prescription I～IV shown in the present embodiment.According to the manufacturing approach that forms the lozenge dosage form shown in the present embodiment, based on the made solid dosage forms oral medicinal composition of prescription I～IV; The main constituent of being adopted includes the husky smooth Amlodipine that includes 5,10,5 or 10 milligrams of single doses accordingly that reaches of valve of 160,160,320 or 320 milligrams of single doses; Also be that the husky smooth shared percentage by weight of valve is to be respectively 33%, 34%, 34% or 34%; Its similar previous embodiment 1 details: (a) with aforementioned main constituent and a part that is fit to utilize wet method for making to make the pharmaceutically acceptable additive of solid dosage forms oral medicinal composition mixes with obtain mixture, (b) with aforementioned mixture with wet granulation pelletize, heat drying after to obtain shot-like particle and (c) to suppress after the remainder mixing with aforementioned shot-like particle and aforementioned additive and obtain step such as solid dosage forms oral medicinal composition, reach the object of the invention so that the solid dosage forms oral medicinal composition to be provided.
In the embodiment of the invention 3 also can with based on prescription I～IV according to the made shot-like particle ingot sheet of said method as core; Carry out being similar to the film clothing lozenge type manufacture method that has detailed by previous embodiment 1 again, make the solid dosage forms oral medicinal composition of the embodiment of the invention 3 form film clothing lozenge type.
In addition; Can know that by the technology contents of above-mentioned exposure solid dosage forms oral medicinal composition provided by the present invention not only can define it by its composition and recipe quantity and form; More owing to carried out concrete and clear and definite record for the manufacturing approach of the solid dosage forms oral medicinal composition that forms lozenge dosage form or film clothing lozenge type in the present embodiment, solid dosage forms oral medicinal composition provided by the present invention also can be defined by this manufacturing approach.In other words; Under the present invention in the relevant technical field of pharmacy those of ordinary skill it will be appreciated that the solid dosage forms oral medicinal composition that is defined with this manufacturing approach also can provide as above-mentioned effect to be able to properly be used to treat hypertension, congestive heart failure, angina pectoris, myocardial infarction, arteriosclerosis, renal function deficiency, diabetic nephropathy, diabetic cardiomyopathy, apoplexy, peripheral vascular disease, left ventricular hypertrophy, consciousness dysfunction, headache or chronic heart failure based on the technical characterictic of this case.
The solid dosage forms oral medicinal composition that the embodiment of the invention 4 is provided is valve husky smooth or its pharmaceutically acceptable salt, the hydrogen chlorobenzene thiophene pyridazine of effective dose, Amlodipine or its pharmaceutically acceptable salt of effective dose and the pharmaceutically acceptable additive that is fit to utilize wet method for making manufacturing solid dosage forms oral medicinal composition that includes effective dose; Wherein, this solid dosage forms oral medicinal composition includes valve husky smooth or its medical acceptable salt, the hydrogen chlorobenzene thiophene pyridazine of single dose 10-30 milligram and Amlodipine or its pharmaceutically acceptable salt of single dose 2.5-20 milligram of single dose 40-320 milligram.
In the present embodiment, based on the made solid dosage forms oral medicinal composition of the I～IV that writes out a prescription shown in the table 5.It includes the Amlodipine of 5,10,5 and 10 milligrams of hydrogen chlorobenzene thiophene pyridazine and single doses of 12.5,25,12.5 and 25 milligrams of smooth, the corresponding single doses of valve sand of 160,160,320 and 320 milligrams of single doses respectively, and promptly smooth, hydrogen chlorobenzene thiophene pyridazine of valve sand and the shared percentage by weight of Amlodipine are respectively 33%, 34%, 34% and 34%.Contain the husky smooth solid dosage forms oral medicinal composition prescription of valve by present embodiment institute illustration and can know that the husky smooth shared percentage by weight of its valve all is not higher than 35%, promptly its composition is the technology contents that relevant component ratio that the prior art of differing from discloses is arranged.
Table 5
In addition; Because hydrogen chlorobenzene thiophene pyridazine, Amlodipine or Amlodipine belong to known item in the property of medicine of pharmaceutically acceptable salt for those of ordinary skill in the relevant technical field of pharmacy under the present invention; Therefore under the present invention in the relevant technical field of pharmacy those of ordinary skill when embodiment of the present invention; Based on the technology contents that the present invention disclosed; Be appreciated that at least at the Amlodipine of the hydrogen chlorobenzene thiophene pyridazine of single dose 10-30 milligram and single dose 2.5-20 milligram or Amlodipine in the scope of pharmaceutically acceptable salt; Can adopt hydrogen chlorobenzene thiophene pyridazine and Amlodipine or Amlodipine at pharmaceutically acceptable salt jointly, and need not creative work and must implement according to the present invention.
Common knowledge based on relevant hydrogen chlorobenzene thiophene pyridazine and Amlodipine in the relevant technical field of pharmacy under the present invention; And be the basis with existing solid dosage forms oral medicinal composition has almost completely identical effect in clinical practice the fact with the solid dosage forms oral medicinal composition of previous embodiment shown in the accompanying drawing 1; In clinical practice, also have almost completely identical effect about those of ordinary skill in the technical field of pharmacy it will be appreciated that the solid dosage forms oral medicinal composition of the embodiment of the invention 4 with existing solid dosage forms oral medicinal composition under the present invention, thereby be able to properly be used to treat hypertension, congestive heart failure, angina pectoris, myocardial infarction, arteriosclerosis, renal function deficiency, diabetic nephropathy, diabetic cardiomyopathy, apoplexy, peripheral vascular disease, left ventricular hypertrophy, consciousness dysfunction, headache or chronic heart failure.
Can form lozenge dosage form or film clothing lozenge type based on the made solid dosage forms oral medicinal composition of prescription I～IV shown in the present embodiment.It is a kind of that not only to include the valve sand of 160,160,320 or 320 milligrams of single doses according to the main constituent that manufacturing approach adopted that forms the lozenge dosage form based on prescription I～IV made solid dosage forms oral medicinal composition shown in the present embodiment smooth; And include the Amlodipine of 5,10,5 or 10 milligrams of hydrogen chlorobenzene thiophene pyridazine and the single doses of 12.5,25,12.5 or 25 milligrams of single doses respectively accordingly; Be that valve sand is smooth, hydrogen chlorobenzene thiophene pyridazine and the shared percentage by weight of Amlodipine be respectively 33%, 34%, 34% or 34%; Its similar previous embodiment 1 details: (a) with aforementioned main constituent and a part that is fit to utilize wet method for making to make the pharmaceutically acceptable additive of solid dosage forms oral medicinal composition mixes with obtain mixture, (b) with aforementioned mixture with wet granulation pelletize, heat drying after to obtain shot-like particle and (c) to suppress after the remainder mixing with aforementioned shot-like particle and aforementioned additive and obtain step such as solid dosage forms oral medicinal composition, reach the object of the invention so that the solid dosage forms oral medicinal composition to be provided.
In the embodiment of the invention 4 also can with based on prescription I～IV by the made ingot sheet of said method as core; Carry out the film clothing lozenge type manufacture method that similar previous embodiment 1 details again, make the solid dosage forms oral medicinal composition of the embodiment of the invention 4 form film clothing lozenge type.
In addition; Can know that by the technology contents of above-mentioned exposure solid dosage forms oral medicinal composition provided by the present invention not only can define it by its composition and recipe quantity and form; More owing to carried out concrete and clear and definite record already for the manufacturing approach of the solid dosage forms oral medicinal composition that forms lozenge dosage form or film clothing lozenge type in the present embodiment, solid dosage forms oral medicinal composition provided by the present invention also can be defined by this manufacturing approach.In other words; Under the present invention in the relevant technical field of pharmacy those of ordinary skill it will be appreciated that the solid dosage forms oral medicinal composition that is defined with this manufacturing approach also can provide as above-mentioned effect to be able to properly be used to treat hypertension, congestive heart failure, angina pectoris, myocardial infarction, arteriosclerosis, renal function deficiency, diabetic nephropathy, diabetic cardiomyopathy, apoplexy, peripheral vascular disease, left ventricular hypertrophy, consciousness dysfunction, headache or chronic heart failure based on the application's technical characterictic.
The present invention from the above really can overcome the husky smooth absent-mindedness of valve and be difficult for the characteristic of system ingot and the prejudice of prior art; And then provide and form lozenge dosage form or film clothing lozenge type and the effect solid dosage forms oral medicinal composition almost completely identical with existing solid dosage forms oral medicinal composition, also provide concrete manufacturing approach for making solid dosage forms oral medicinal composition of the present invention on the other hand.
Although illustrated and described embodiments of the invention; For those of ordinary skill in the art; Be appreciated that under the situation that does not break away from principle of the present invention and spirit and can carry out multiple variation, modification, replacement and modification to these embodiment, scope of the present invention is limited accompanying claims and equivalent thereof.
Claims (9)
1. solid dosage forms oral medicinal composition includes:
Shared percentage by weight is at husky smooth or its pharmaceutically acceptable salt of the valve below 35%; And
Be fit to utilize wet method for making to make the pharmaceutically acceptable additive of solid dosage forms oral medicinal composition.
2. solid dosage forms oral medicinal composition as claimed in claim 1, it includes husky smooth or its medical acceptable salt of valve of single dose 40-320 milligram.
3. solid dosage forms oral medicinal composition as claimed in claim 1, it further includes the hydrogen chlorobenzene thiophene pyridazine of single dose 10-30 milligram.
4. solid dosage forms oral medicinal composition as claimed in claim 1, it further includes Amlodipine or its pharmaceutically acceptable salt of single dose 2.5-20 milligram.
5. solid dosage forms oral medicinal composition as claimed in claim 1, it further includes Amlodipine or its pharmaceutically acceptable salt of single dose 10-30 milligram hydrogen chlorobenzene thiophene pyridazine and single dose 2.5-20 milligram.
6. like each described solid dosage forms oral medicinal composition in the claim 1 to 5, it forms the lozenge dosage form.
7. method of producing the solid dosage forms oral medicinal composition includes following steps:
Main constituent and major part are mixed to obtain mixture; Wherein said main constituent includes shared percentage by weight at husky smooth or its pharmaceutically acceptable salt of the valve below 35% or include shared percentage by weight at the valve 35% below husky smooth or its pharmaceutically acceptable salt and hydrogen chlorobenzene thiophene pyridazine or include shared percentage by weight at the valve 35% below husky smooth or its pharmaceutically acceptable salt and Amlodipine or include shared percentage by weight at the valve 35% below husky smooth or its pharmaceutically acceptable salt and hydrogen chlorobenzene thiophene pyridazine and Amlodipine, and said major part includes and is fit to the wet pharmaceutically acceptable additive of method for making manufacturing solid dosage forms oral medicinal composition of utilization;
With said mixture with wet granulation pelletize, heat drying after to obtain shot-like particle;
Suppress after the remainder of said shot-like particle and said additive mixed and obtain said solid dosage forms oral medicinal composition.
8. method as claimed in claim 7, it further includes the said ingot sheet through compacting is covered the step that forms film clothing ingot with the agent of film clothing after the said shot-like particle of compacting forms the ingot sheet.
9. like the solid dosage forms oral medicinal composition of the said method preparation of claim 8, it is to be used to treat hypertension, congestive heart failure, angina pectoris, myocardial infarction, arteriosclerosis, renal function deficiency, diabetic nephropathy, diabetic cardiomyopathy, apoplexy, peripheral vascular disease, left ventricular hypertrophy, consciousness dysfunction, headache or chronic heart failure.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2010101123689A CN101897675B (en) | 2010-02-10 | 2010-02-10 | Solid oral medicinal composition containing valsartan or pharmaceutically acceptable salts of valsartan |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2010101123689A CN101897675B (en) | 2010-02-10 | 2010-02-10 | Solid oral medicinal composition containing valsartan or pharmaceutically acceptable salts of valsartan |
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| CN101897675B true CN101897675B (en) | 2012-11-21 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1232394A (en) * | 1996-06-27 | 1999-10-20 | 诺瓦提斯公司 | Solid oral dosage forms of valsartan |
| CN101237859A (en) * | 2005-08-17 | 2008-08-06 | 诺瓦提斯公司 | Solid dosage forms of valsartan and amlo dipine and method of making the same |
| CN101478956A (en) * | 2006-06-27 | 2009-07-08 | 诺瓦提斯公司 | Solid dosage forms of valsartan, amlodipine and hydrochlorothiazide and method of making the same |
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2010
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1232394A (en) * | 1996-06-27 | 1999-10-20 | 诺瓦提斯公司 | Solid oral dosage forms of valsartan |
| CN101237859A (en) * | 2005-08-17 | 2008-08-06 | 诺瓦提斯公司 | Solid dosage forms of valsartan and amlo dipine and method of making the same |
| CN101478956A (en) * | 2006-06-27 | 2009-07-08 | 诺瓦提斯公司 | Solid dosage forms of valsartan, amlodipine and hydrochlorothiazide and method of making the same |
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| CN101897675A (en) | 2010-12-01 |
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