CN101049303A - Valsartan pills, and preparation method - Google Patents
Valsartan pills, and preparation method Download PDFInfo
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- CN101049303A CN101049303A CN 200610050156 CN200610050156A CN101049303A CN 101049303 A CN101049303 A CN 101049303A CN 200610050156 CN200610050156 CN 200610050156 CN 200610050156 A CN200610050156 A CN 200610050156A CN 101049303 A CN101049303 A CN 101049303A
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- valsartan
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- coolant
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Abstract
A dripping pill of valsartan for treating hypertension is prepared from the valsartan and the matrix of dripping pill. Its preparing process is also disclosed.
Description
Technical field
The invention belongs to the pharmaceutical technology field, valsartan dripping pill that particularly a kind of medicine valsartan (Valsartan) that is used for hypertension therapeutic and drop pill substrate are formulated and preparation method thereof.
Background technology
Hypertension is one of modal cardiovascular disease in the world today, is the dead and wounded or disabled primary cause of disease of adult.Along with progress and the raising day by day of living standards of the people and the continuous quickening of work rhythm of society, the hypertension number of patients increases greatly.China's hypertension prevalence obviously rises, show according to the China's Statistical data, among Chinese 35 to the 74 years old crowd, hypertensive sickness rate is up to about 27 percent, patient's number is near 100,013,000, and annual with the speed increment more than 300 million peoples, China has become the most serious country of hypertension harm in the world.Hypertension can cause the damage of organs such as the heart, brain, kidney, serious threat human beings'health and life.
Valsartan is the efficient antihypertensive drugs of a new generation that Novartis Co.,Ltd develops, and at first uses in European countries such as Germany in 1996, and 1998 in China's listing, more than 70 country's listings in the world at present.Valsartan another name is for cutting down Sha Tan, Wei Ershatan, and penta is husky smooth, DAIWEN, chemistry is called N (1-oxygen amyl group)-N-[[2 '-(CIII one tetrazole-5-yl) [1,1 ' diphenyl-4-yl] methyl]-the L-valine.Be the angiotensin ii receptor antagonist of second listing, become the hypertensive line medicine of treatment; Except treating the hypertension, can also be used for the treatment of heart failure.Valsartan is more safer than captopril angiotensin I receptor antagonist, amlodipine calcium ion antagonist treatment hypertension.Blood pressure lowering is steady, curative effect is strong, safety is good, side effect is low, took in 1st 1 time, and patient's compliance is good.Be used for all kinds of mild to moderate hyperpietics clinically, especially the patient that ACE inhibitor is not tolerated.
The valsartan oral formulations of using clinically is mainly tablet, capsule at present.Because these conventional formulation fabricating technologies have, make this class oral formulations exist disintegration time long, absorption difference, shortcoming such as onset is slow, and bioavailability is lower, thus influence giving full play to of drug effect.Between the storage life, be easy to sliver, variable color, the moisture absorption etc., the quality instability.Also be difficult to simultaneously adapt to and swallow inconvenient patient.Valsartan dripping pill bioavailability height of the present invention, disintegrate is molten loose fast, the dissolution height, steady quality, release fast, produce effects fast can sublingual administration, also can swallow, and is easy to carry and use, for the patient of dysphagia provides a kind of new medication to select.Valsartan dripping pill can be made into the preparation of 10mg small dimension, can adjust taking dose according to the patient age and the state of an illness easily, and divided dose is accurate.Preparation process of the present invention is simple, and workshop does not have dust, uses supplementary product kind few, and production process is short, and cost is low.
Summary of the invention
The present invention seeks to overcome the defective of prior art, for clinical treatment provides a kind of bioavailability height, disintegrate is molten looses soon, dissolution height, steady quality, release fast, quick produce effects, medicine valsartan dripping pill and preparation technology thereof easy to carry and use.
The invention is characterized in by valsartan and drop pill substrate formulated.
The weight ratio of each composition is:
Valsartan: drop pill substrate=1: 1～1: 9
The present invention can be achieved through the following technical solutions:
Get valsartan, pulverize, sieve.Valsartan and drop pill substrate were by weight 1: 1～1: 9 mix homogeneously, put and be heated to fusion in the heater while stirring, stir, the dropping preparation method pill, the water dropper temperature is 75 ℃-95 ℃, splash in dimethicone or other drop pill coolant, the temperature of coolant is 40 ℃--5 ℃, separate drop pill, and absorb coolant, drying, promptly.
Utilize the drop pill of method preparation of the present invention, its beneficial effect is:
1. the quick stripping of medicine, the dissolution height, rapid-action, the bioavailability height, side effect is little.Valsartan dripping pill is to utilize solid dispersion technology, to after medicine and the fusion of drop pill substrate medicine be dispersed in the substrate, solidify by system of dripping and quenching, medicine is scattered in the substrate with molecularity or superfine crystal state, help absorption of human body, bring into play curative effect rapidly, improve bioavailability, reduce side effect, safety is reliable.
2. increased administering mode, can swallow, but also sublingual administration.Sublingual administration has made things convenient for the patient of dysphagia for the patient of dysphagia provides a kind of new medication to select.As adopt the sublingual administration administration, and and after contacting, saliva dissolves rapidly, absorb by oral mucosa, directly enter blood circulation without gastrointestinal tract and liver, not only avoided the liver sausage first-pass effect, and it is rapid to have reached onset, improve bioavailability, reduce the purpose of side effect.
3. medicine stability is good.Dropping pill formulation by medicine and substrate heating and melting after, splash in the immiscible liquid coolant and make, reduce with the air contact area, be difficult for oxidation, substrate is non-water thing, is difficult for causing drug hydrolysis, stability of drug is increased, thereby guaranteed drug quality.
4. valsartan dripping pill can be made into the preparation of 10mg small dimension, can adjust taking dose according to the patient age and the state of an illness easily, and divided dose is accurate.
5. drop pill production technology, production equipment are simple, with short production cycle, the production efficiency height, and cost is low.
6. in the main production process of drop pill, used material all is to carry out under liquid state, has reduced dust pollution, helps labor protection and environmental protection, helps the GMP management.
One. the supplementary material medicine
The valsartan dripping pill crude drug is a valsartan.Its chemical name is N (1-oxygen amyl group)-N-[[2 '-(CIII-tetrazole-5-yl) [1,1 ' diphenyl-4-yl] methyl]-the L-valine.
Molecular formula: C
24H
29N
5O
3
Molecular weight: 435.53
Adjuvant is drop pill substrate polyethylene glycols, carboxymethyl starch sodium, poloxamer, betacyclodextrin, stearic acid, sodium stearate, polyoxyethylene monostearate.
Two. preparation method
Get valsartan, pulverize, sieve.Valsartan and drop pill substrate were by weight 1: 1～1: 9 mix homogeneously, put and be heated to fusion in the heater while stirring, stir, the dropping preparation method pill, the water dropper temperature is 75 ℃-95 ℃, splash in dimethicone or other drop pill coolant, the temperature of coolant is 40 ℃--5 ℃, separate drop pill, and absorb coolant, drying, promptly.
Three. specific embodiment
Further the present invention can be described by the following examples, but not limited by embodiment.
Embodiment 1: present embodiment is by valsartan and single-matrix prescription, operate according to the preparation method in (specific embodiment), coolant is a dimethicone, drip the system drop pill, select that roundness, the ball method of double differences are different, hardness, molten diffusing time etc. are index, observe the influence of the weight ratio of medicine and single-matrix to product involved in the present invention, result of the test sees Table 1.
Table 1 medicine and single-matrix formula test (medicine is 1 part)
| 7 | Polyethylene glycol 6000 (5 parts) | +++ | ＜10 | +++ | ＜15 | +++ |
| 8 | Polyethylene glycol 6000 (9 parts) | +++ | ＜10 | +++ | ＜15 | +++ |
Annotate: 1. coolant is a dimethicone, and chilling temperature is 3～5 ℃; Spice insulation and water dropper temperature are 85～90 ℃; Dripping speed is 30～50/minute.
2. above result shows, it is all good to test every index 2,3,4,6,7, No. 8, and promptly medicine and substrate ratio are can drip system smoothly at 1: 3～1: 9 o'clock.But consider factors such as taking dose, optimum ratio is 2,3,6, No. 7 tests, and promptly medicine and substrate ratio are 1: 3～5.
Embodiment 2: present embodiment is by valsartan and mixed-matrix prescription, operate according to the preparation method in (specific embodiment), coolant is a dimethicone, drip the system drop pill, select that roundness, the ball method of double differences are different, hardness, molten diffusing time etc. are for investigating index, to determine the weight ratio of medicine and mixed-matrix, result of the test sees Table 2.
Table 2 medicine and mixed-matrix formula test (medicine is 1 part)
| 8 | Polyethylene glycol 6000: poloxamer=1: 0.2 (3 parts) | +++ | ＜10 | +++ | ＜15 | +++ |
| 9 | Polyethylene glycol 6000: poloxamer=1: 0.2 (9 parts) | +++ | ＜10 | +++ | ＜15 | +++ |
| 10 | Polyethylene glycol 6000: polyoxyethylene monostearate=1: 0.1 (1 part) | ++ | ＜10 | +++ | ＜15 | ++ |
| 11 | Polyethylene glycol 6000: polyoxyethylene monostearate=1: 0.1 (3 parts) | +++ | ＜10 | +++ | ＜15 | +++ |
| 12 | Polyethylene glycol 6000: polyoxyethylene monostearate=1: 0.1 (9 parts) | +++ | ＜10 | +++ | ＜15 | +++ |
Annotate: 1. coolant is a dimethicone, and chilling temperature is 8～5 ℃; Spice insulation and water dropper temperature are 85～90 ℃; Dripping speed is 30～50/minute.
2. above result shows, it is all better to test every index 2,3,5,6,8,9,11, No. 12, and promptly medicine and substrate ratio are can drip system smoothly at 1: 1～1: 9 o'clock.But consider factors such as taking dose, optimum ratio is 2,5,8, No. 11 tests, and promptly medicine and substrate ratio are 1: 3.
Embodiment 3: present embodiment is by selecting different coolants for use, and coolant is dimethicone, liquid paraffin, vegetable oil, and single-matrix is selected Polyethylene Glycol for use
6000, mixed-matrix is selected Polyethylene Glycol for use
6000: the prescription of poloxamer=1: 0.2, according to the preparation method in (specific embodiment) operation, drip the system drop pill, select that roundness, the ball method of double differences are different, hardness, molten diffusing time etc. are for investigating index, observe the influence of different coolants to product involved in the present invention, result of the test sees Table 3.
Table 3 is selected the test (medicine: substrate=1: 3) of different coolants for use
Annotate: 1. chilling temperature is 8～5 ℃; Spice insulation and water dropper temperature are 85～90 ℃; Dripping speed is 30～50/minute.
2. above result shows, it is better to test every index 1, No. 2, and when promptly selecting above-mentioned different coolant for use, comparatively preferred coolant is a dimethicone.
Embodiment 4: present embodiment is by selecting different coolant temperatures for use, and the temperature of coolant is respectively 35 ℃, and 25 ℃, 15 ℃, 5 ℃, 0 ℃ ,-5 ℃, temperature error ± 2 ℃, substrate is selected Polyethylene Glycol for use
6000,, be coolant with the dimethicone according to the operation of the preparation method in (specific embodiment), drip the system drop pill, select that roundness, the ball method of double differences are different, hardness, molten diffusing time etc. are for investigating index, observe the influence of different coolant temperatures to product involved in the present invention, result of the test sees Table 4.
Table 4 is selected the test (medicine: substrate=1: 3) of different coolant temperatures for use
Annotate: 1. spice insulation and water dropper temperature are 85～90 ℃; Dripping speed is 30～50/minute.
2. above result shows, it is better to test every index 3,4, No. 5, and when promptly selecting above-mentioned different coolant temperature for use, comparatively preferred coolant temperature is 15 ℃～0 ℃
Embodiment 5: present embodiment is by selecting different water dropper temperature for use, and the temperature of water dropper remains on 75 ℃ respectively, and 85 ℃, 95 ℃, temperature error＜3%, single-matrix is selected Polyethylene Glycol for use
6000, mixed-matrix is selected Polyethylene Glycol for use
6000: the prescription of poloxamer=1: 0.2, operate according to the preparation method in (specific embodiment), coolant is a dimethicone, drip the system drop pill, select that roundness, the ball method of double differences are different, hardness, molten diffusing time etc. are for investigating index, observe the influence of different water dropper agent temperature to product involved in the present invention, result of the test sees Table 5.
Table 5 is selected the test (medicine: substrate=1: 3) of different water dropper temperature for use
Annotate: the 1.. chilling temperature is 8～5 ℃; Dripping speed is 30～50/minute.
2. above result shows, it is better to test every index 3, No. 4, and when promptly selecting above-mentioned different water dropper temperature for use, comparatively preferred water dropper temperature is 85 ℃.
Claims (3)
1. valsartan dripping pill and preparation technology thereof is characterized in that by valsartan (Valsartan) and drop pill substrate formulated.The weight ratio of each composition is:
Valsartan: drop pill substrate=1: 1～1: 9.
2. valsartan dripping pill according to claim 1, it is characterized in that described drop pill substrate is a kind of or several compatibilities in polyethylene glycols, carboxymethyl starch sodium, poloxamer, betacyclodextrin, stearic acid, sodium stearate, the polyoxyethylene monostearate, the content of each compatibility composition all is not equal to zero.
3. according to claim 1 described valsartan dripping pill, it is characterized in that preparation method is as follows:
Get valsartan, pulverize, sieve.Valsartan and drop pill substrate were by weight 1: 1～1: 9 mix homogeneously, put and be heated to fusion in the heater while stirring, stir, the dropping preparation method pill, the water dropper temperature is 75 ℃-95 ℃, splash in dimethicone or other drop pill coolant, the temperature of coolant is 40 ℃--5 ℃, separate drop pill, and absorb coolant, drying, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610050156 CN101049303A (en) | 2006-04-03 | 2006-04-03 | Valsartan pills, and preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610050156 CN101049303A (en) | 2006-04-03 | 2006-04-03 | Valsartan pills, and preparation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101049303A true CN101049303A (en) | 2007-10-10 |
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|---|---|---|---|
| CN 200610050156 Pending CN101049303A (en) | 2006-04-03 | 2006-04-03 | Valsartan pills, and preparation method |
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| CN (1) | CN101049303A (en) |
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2006
- 2006-04-03 CN CN 200610050156 patent/CN101049303A/en active Pending
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