CN1827112A

CN1827112A - Dispersion tablet for treating cardiovascular diseases and its preparation method

Info

Publication number: CN1827112A
Application number: CN 200510095636
Authority: CN
Inventors: 曹明成
Original assignee: Individual
Current assignee: Individual
Priority date: 2005-11-12
Filing date: 2005-11-12
Publication date: 2006-09-06

Abstract

This invention discloses a disperse tablet for cardiovascular disease therapy and its preparing method. Firstly dry raw materials separately and pass them through 100 orders screen; then adopting equivalent incensement method, mix D with micro-crystal cellulose, gelatinized starch, hydropropyl cellulose, acepaten and crosslinked polyketone, execute it to soft material by 2% hydropropyl methylcellulose, pass the soft material through20 orders screen to produce grains, dry the grains in bake oven at 60deg C, treat the grains, add micronized powder silica gel and stearate, mix, tablet and package is ok. This invention has the characteristics of disintegration rapid, absorption quick, biology availability high, adverse affects few and taking convenient. It has efficacies of promoting Qi and blood, and activate collaterals to relieve pain, it can be used to cure thorax paralysis, heartache and intermittent pulse caused by qi stagnation and blood silt, and coronary disease, arrhythmia with above symptoms. It is especially available to old people and patients difficult to swallow solid.

Description

A kind of dispersible tablet for the treatment of cardiovascular disease and preparation method thereof

Technical field

The invention belongs to a kind of new Chinese medicine, more specifically, the present invention relates to a kind of dispersible tablet for the treatment of cardiovascular disease and preparation method thereof.

Background technology

Cardiovascular disease such as coronary heart disease, myocardial ischemia, it is one of main disease that influences human health, become the lethal the first reason of China resident gradually, aged tendency of population in addition, to be called " cardiovascular diseases's century " 21 century is not to exaggerate, and therefore, exploitation effectively prevents and treat the medicine of cardiovascular disease, to improving patient's quality of life, prolonging life has significance.

The cardiovascular drugs of research mostly is chemical synthetic drug at present, side effect is big, by the purified Buxine Tablet of Chinese medicine proved recipe, evident in efficacy, side effect is low, and its main constituent cyclovirobuxinum D is a kind of product of pure natural, is to form by the alkaloid monomer that extracts in the Ramulus Buxi Sinicae is refining, be after ephedrine and arteannuin, another excavates the monomeric compound that is with historically new significance equally that comes out from China's Chinese medicine treasure-house.

Nearly more than ten years, the new drug of treatment coronary heart disease, myocardial ischemia constantly comes out, the similar drug that external production or Chinese-foreign joint venture produce China is continuously seized the beach point, in this case, Buxine (cyclovirobuxinum D) still is subjected to many doctors and patient's welcome, prove that its tool possesses exuberant vitality, but existingly also have only the Buxine tablet a kind of, clinical efficacy significant with it is incompatible; For this reason, we have researched and developed " Huangyangning dispersion tablets " in conjunction with the physicochemical property of Buxine (cyclovirobuxinum D), and it has the effect of promoting flow of QI and blood, removing obstruction in the collateral to relieve pain; The obstruction of qi in the chest and cardialgia that is used for caused by energy stagnation and blood stasis, irregularly intermittent and regularly intermittent pulse; Coronary heart disease, arrhythmia are seen above-mentioned patient; Be intended to further bring into play conventional medicament, especially natural drug enlarges the clinical use of Buxine in the prevention of cardiovascular and cerebrovascular disease and the effect in the treatment, satisfies different demands, for clinical application provides another quick-acting novel medicine.

The dispersible tablet disintegrate is (whole disintegrates in 3 minutes in 20 ℃ ± 1 ℃ water) rapidly, absorb soon the bioavailability height, untoward reaction is few, taking convenience, can swallow, chew contain suck or water in disperse after can with or do not take simultaneously with fruit juice, milk, especially be fit to old, the children and the patient of solid difficulty that swallows; In addition, the same conventional tablet of the preparation technology of dispersible tablet does not have specific (special) requirements to working condition; The research and development of medicine dispersible tablet have become one of country " 95 ", " 15 " and tablet technological development direction project in 2010.

Summary of the invention

The objective of the invention is to: a kind of dispersible tablet for the treatment of cardiovascular disease is provided, has enlarged the clinical scope of application of Buxine (cyclovirobuxinum D), satisfy different demands, for clinical application provides another quick-acting novel medicine.

The present invention is achieved in that a kind of dispersible tablet for the treatment of cardiovascular disease, to prepare 1000, it is to make with the raw material of following consumption: cyclovirobuxinum D 0.5g～3.5g, microcrystalline Cellulose 20g～40g, pregelatinized Starch 7g～27g, hyprolose 3g～15g, polyvinylpolypyrrolidone 2g～12g, aspartame 0.2g～1.2g, micropowder silica gel 0.02g～0.12g, magnesium stearate 0.23g～0.43g.

A kind of preparation method for the treatment of the dispersible tablet of cardiovascular disease, may further comprise the steps: earlier that cyclovirobuxinum D, microcrystalline Cellulose, pregelatinized Starch, hyprolose, polyvinylpolypyrrolidone, aspartame, micropowder silica gel, magnesium stearate is dry respectively, cross 100 mesh sieves; Again cyclovirobuxinum D is adopted the equivalent incremental method, with microcrystalline Cellulose, pregelatinized Starch, hyprolose, aspartame, polyvinylpolypyrrolidone mixing, make soft material with 2% hypromellose (HPMC) solution, cross 20 mesh sieves and granulate 60 ℃ of oven dryings, granulate, add micropowder silica gel, magnesium stearate, mixing, tabletting, packing is promptly.

The present invention compared with prior art, it is rapid to have a disintegrate, absorbs fast, the bioavailability height, untoward reaction is few, taking convenience, can swallow, chew contain suck or water in disperse after can with or do not take simultaneously with fruit juice, milk, especially be fit to the old people and the patient of solid difficulty that swallows; One time 1～2,2～3 times on the one; Every contains cyclovirobuxinum D 1mg.

Toxicological study summary of the present invention:

1. the acute toxicity of cyclovirobuxinum D and LD ₅₀

Gastric infusion LD ₅₀, 120 of white mice, grouping is measured, and calculate with 72 hours mortality rates: the result is: LD ₅₀=293 ± 75mg/kg; The LD of intraperitoneal injection ₅₀=89.0 ± 18.4mg/kg; Intravenous injection LD ₅₀=8.94 ± 1.8mg/kg.

2. the sub-acute toxicity test of cyclovirobuxinum D

24 of rabbit are divided three groups, the first group raise clothes 1.2mg/kg/ day, the second group raise clothes 0.3mg/kg/ day, third group is matched group, raise in advance 10 days then medication raise clothes 60 days, the result:

2.160 weigh weekly in it and check sign once, the body weight gain curve and the zero difference of three treated animals are all found depilation, and diarrhoea suppresses the parerethisis sign.

2.2 before the medication, medication 30 days, 60 days checks electrocardiogram once, three treated animal electrocardiograms are not all found significant change.

2.3 before the medication and get blood examination from jugular vein after 60 days and look into following project: erythrocyte number, white blood cell count, the leukocyte classification, paddy third transaminase, the turbidity test of Moschus moschiferous grass phenol, before and after the CCFT, zinc sulphate turbidity test and non-protein nitrogen medication and find no the difference of remarkable meaning between matched group.

2.460 it dead animal is done the pathology cut sections for microscopic examination, the heart, lung, spleen, adrenal gland do not see special change, and medication group first group has 2, and the second group has 1 animal to find that liver has the point-like necrosis region, and matched group is not found this kind variation, and the prompting liver has certain infringement; In addition, first and second groups respectively have three animals to find xanthopsis at the distal convoluted renal tubule place, and character is not clear, may point out medicine to secrete or heavily absorb in this punishment.

3. the animal chronic toxicity test of cyclovirobuxinum D

3.1 rat toxicity test rat is irritated stomach 2.5mg/kg every day, and 3 totally months, be equivalent to 41 times of clinical dosage 0.06mg/kg, to all obviously influences of index such as the body weight of animal, hemogram, liver, renal functioies, histological examination is no abnormality seen also; And 2.5mg/kg was irritated stomach 6 months, and 10mg/kg and 20mg/kg irritate stomach 3 to the fine tolerance of energy in 6 months, and every hemogram biochemical indicator is measured and is not seen obvious change, but liver Interstitial cell spotty necrosis can appear in histological examination, and its incidence rate is relevant with dosage and equation.

3.2 the toxicity test Canis familiaris L. feeding every day 0.5mg/kg of Canis familiaris L. be equivalent to 8 times of people's clinical dosage 6 totally months, all no abnormal discovery is compared in every index inspection (comprising histological examination) with matched group; 2mg/kg (being equivalent to 33 times of people's clinical dosages) can influence the animal food-intake during week taking medicine 21, and losing weight anemia occurs; 4mg/kg (being equivalent to 66 times of people's clinical dosages) can obviously influence food-intake, refusing to eat, and anemia appears in weight loss, even dead.And histological examination: the dosage group is compared with matched group and is shown no obvious abnormalities.

Pharmacokinetics test of the present invention:

Mouse tail vein injection ³Behind the H-cyclovirobuxinum D, press two-compartment model according to blood drug level and calculate pharmacokinetic parameter T _1/2Be 3.94 ± 1.93h, distribution phase T _1/2α is 0.06h mutually, eliminates phase T _1/2β is 32h mutually; Cyclovirobuxinum D is shown in mice in-vivo tissue distribution result of study, ³Behind the H-cyclovirobuxinum D iv, very fast by each tissue picked-up, 2～3h reaches the peak; Distribute at most with the lung hepatic tissue during peak, next spleen, kidney, intestinal tissue, flesh and cerebral tissue are lower; The medicine retention is of long duration in organizing, and drains slowly; The experiment of tissue slice autoradiography simultaneously shows, cyclovirobuxinum D is higher liver, kidney, lung, enteral concentration, and concentration is lower in the myocardium skeletal muscle, brain, illustrate that cyclovirobuxinum D penetrates a little less than the blood brain barrier ability, distributes at brain and spinal cord and lacks; Right ³The H-cyclovirobuxinum D shows in rat internal metabolism process study experiment, and cyclovirobuxinum D is at spleen, lung, liver, kidney, 24h reaches the peak in the heart, and except that the 2h group distributed at most with hepatic tissue, all the other were all the highest with spleen, and lung, liver, kidney, the heart take second place; Cyclovirobuxinum D 1～3d reaches the peak in the central nervous system, and it distributes few than spleen, lung, liver, kidney, the heart; Repeatedly the oral administration experiment shows, cyclovirobuxinum D distributes at most at spleen, and repeatedly phenomenon all appears accumulating in each internal organs of oral administration; Drain experiment and show that this medicine is drained slowly, discharge rate and radioactivity are at each internal organs distribution result of experiment basically identical.

The specific embodiment

Embodiments of the invention:

1, prescription

Cyclovirobuxinum D 0.5g～3.5g

Microcrystalline Cellulose 20g～40g

Pregelatinized Starch 7g～27g

Hyprolose 3g～15g

Polyvinylpolypyrrolidone 2g～12g

Aspartame 0.2g～1.2g

Micropowder silica gel 0.02g～0.12g

Magnesium stearate 0.23g～0.43g

2% hypromellose (HPMC) solution Q.S

Make 1000

2, preparation technology

Adjuvant is dry respectively earlier, cross 100 mesh sieves; Cyclovirobuxinum D (crossing 200 mesh sieves) is adopted the equivalent incremental method,, make soft material in right amount with 2%HPMC solution with microcrystalline Cellulose, pregelatinized Starch, hyprolose, aspartame, polyvinylpolypyrrolidone mixing, crossing 20 mesh sieves granulates, 60 ℃ of oven dryings, granulate adds micropowder silica gel, magnesium stearate, mixing, measure content, tabletting is measured content, uniformity of dosage units, dispersing uniformity, after qualified, packing.

3, technological process

Claims

1, a kind of dispersible tablet for the treatment of cardiovascular disease, it is characterized in that: to prepare 1000, it is to make with the raw material of following consumption: cyclovirobuxinum D 0.5g～3.5g, microcrystalline Cellulose 20g～40g, pregelatinized Starch 7g～27g, hyprolose 3g～15g, polyvinylpolypyrrolidone 2g～12g, aspartame 0.2g～1.2g, micropowder silica gel 0.02g～0.12g, magnesium stearate 0.23g～0.43g.

2, a kind of preparation method of dispersible tablet according to claim 1 is characterized in that may further comprise the steps:

Earlier that cyclovirobuxinum D, microcrystalline Cellulose, pregelatinized Starch, hyprolose, polyvinylpolypyrrolidone, aspartame, micropowder silica gel, magnesium stearate is dry respectively, cross 100 mesh sieves; Again cyclovirobuxinum D is adopted the equivalent incremental method, with microcrystalline Cellulose, pregelatinized Starch, hyprolose, aspartame, polyvinylpolypyrrolidone mixing, make soft material with 2% hypromellose (HPMC) solution, cross 20 mesh sieves and granulate 60 ℃ of oven dryings, granulate, add micropowder silica gel, magnesium stearate, mixing, tabletting, packing is promptly.