CN1981758A - Losartan polassium dropping pills and their preparation - Google Patents

Abstract

A dripping pill of losartan potassium for treating primary hypertension is prepared from losartan potassium and matrix. Its preparing process is also disclosed.

Description

Losartan Potassium drop pill and preparation method thereof

Technical field

The invention belongs to the pharmaceutical technology field, particularly a kind of by Losartan Potassium (Losartan Potassium) and the formulated Losartan Potassium drop pill of drop pill substrate.

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.Because the raising of people's living standard, growing tension is striven in work unexpectedly, and 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.

Losartan Potassium is the oral non-peptide class angiotensin-ii receptor inhibitor of the first generation by Merck ﹠ Co., Inc.'s exploitation listing, and 1994 at first in Sweden's listing, in 1998 at China's official listing, now in the whole world more than 70 countries as the extensive use of clinical treatment medicine.Chemical name is 2-butyl-4-chloro-1-[[2 '-(1H-tetrazolium-5-yl) [1,1 '-xenyl]-4-yl] methyl]-1H-imidazoles-5-methanol monopotassium salt.Be angiotensin-ii receptor (AT1 type) antagonist.Can block the various pharmacological actions (comprise and impel vasoconstriction, effects such as aldosterone release) that endogenous and ectogenic Angiotensin II produce.Optionally act on the AT1 receptor, do not influence the function of ion channel important in other hormone receptors or the cardiovascular, the angiotensin converting enzyme (kininase II) of the Kallidin I that yet do not suppress to degrade does not influence the metabolic process of Angiotensin II and Kallidin I.Being used for the treatment of essential hypertension clinically, is an antihypertensive line medication, its strong drug action, long action time, better tolerance, has the advantage of few generation dry cough untoward reaction, also has the protective effect mechanism to kidney simultaneously.

The Losartan Potassium oral formulations is mainly tablet in the market.Because shortcomings such as these conventional formulation fabricating technologies have, and make this class oral formulations exist disintegration time long, and onset is slow, and bioavailability is lower, thereby influence giving full play to of drug effect.Also be difficult to simultaneously adapt to and swallow inconvenient patient.The research data of having announced shows that just have 1 example that dysphagia may take place in the middle of the per 17 routine patients: this class crowd accounts for 25% in inpatient, then has 40% among the patient who accepts nursing that is in.Losartan Potassium drop 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.The Losartan Potassium drop pill can be made the preparation of 5-12.5mg different size, 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 object of the invention provides a kind of medicine Losartan Potassium drop pill and preparation technology thereof who is used for the treatment of essential hypertension.

The invention is characterized in by Losartan Potassium and drop pill substrate formulated.

The weight ratio of each composition is:

Losartan Potassium: drop pill substrate=1: 1～1: 15

The present invention can be achieved through the following technical solutions:

Get Losartan Potassium, pulverize, sieve.Losartan Potassium mixes by weight 1: 1～1: 15 with drop pill substrate, and heating and melting stirs, and splashes in dimethicone or other drop pill coolant, separates drop pill, absorbs coolant, drying, promptly.

Utilize the drop pill of method preparation of the present invention, its main feature is:

1. the quick stripping of medicine, the dissolution height, rapid-action, the bioavailability height, side effect is little.The Losartan Potassium drop 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.

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. the Losartan Potassium drop pill can be made into the preparation of 5-12.5mg different size, 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.

Losartan Potassium drop pill crude drug is a Losartan Potassium.Its chemical name is 2-butyl-4-chloro-1-[[2 '-(1H-tetrazolium-5-yl) [1,1 '-xenyl]-4-yl] methyl]-1H-imidazoles-5-methanol monopotassium salt.

Molecular formula: C ₂₂H ₂₂ClKN ₆O

Molecular weight: 461.01

The detection method of drop pill and result:

One. detection method:

1. dissolve scattered time limit: check according to inspection technique disintegration (" Chinese Pharmacopoeia 2005 version two ones " appendix XA).

2. dissolution: according to dissolution inspection algoscopy (" Chinese Pharmacopoeia 2005 version two ones " the appendix XC three therapeutic methods of traditional Chinese medicine), be dissolution medium with water 100ml, rotating speed is that per minute 75 changes, and operation in accordance with the law in the time of 45 minutes, is got solution and filtered, and gets subsequent filtrate as need testing solution; It is an amount of that precision takes by weighing losartan in addition, be dissolved in water and quantitatively be diluted to reference substance solution with the need testing solution same concentrations, according to high performance liquid chromatography (" Chinese Pharmacopoeia 2005 version two ones " appendix vD) test, at Kromasil C18 (250mm * 4.6mm, 5 μ m) on the post, with acetonitrile-0.1% phosphoric acid solution (50: 50) is mobile phase, and the detection wavelength is 230nm, flow velocity 1.0mlmin-1.Measure in accordance with the law, calculate every dissolution.

Two. testing result:

Sample number	Dissolve scattered time limit (branch)	Dissolution (being labelled amount %)
			Embodiment 1	＜10	96.1
Embodiment 2	＜10	97.5
			Embodiment 3	＜10	97.0
Embodiment 4	＜10	97.2
			Embodiment 5	＜10	96.8
Embodiment 6	＜10	96.5

The specific embodiment

Further the present invention can be described by the following examples, but not limited by embodiment.

Embodiment: per 1000 Losartan Potassium drop pill supplementary material proportionings

The embodiment sequence number	Losartan Potassium	Polyethylene glycol 6000	Macrogol 4000	Carboxymethyl starch sodium	Poloxamer
						1	10g	35g	5g		2g
2	10g	20g
						3	10g	25g		5g
4	12.5g	30g	5g
						5	12.5g	35g		5g	1g
6	12.5g	25g			5g

Claims (3)

1. Losartan Potassium drop pill and preparation technology thereof is characterized in that by Losartan Potassium (LosartanPotassium) and drop pill substrate formulated.The weight ratio of each composition is:

Losartan Potassium: drop pill substrate=1: 1～1: 15

2. Losartan Potassium drop 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, sodium carboxymethyl cellulose, 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 Losartan Potassium drop pill, it is characterized in that preparation method is as follows: get Losartan Potassium, pulverize, sieve.Losartan Potassium mixes by weight 1: 1～1: 15 with drop pill substrate, and heating and melting stirs, and splashes in dimethicone or other drop pill coolant, separates drop pill, absorbs coolant, drying, promptly.