CN1231219C - Huangyangning slow-releasing preparation - Google Patents
Huangyangning slow-releasing preparation Download PDFInfo
- Publication number
- CN1231219C CN1231219C CN 03141370 CN03141370A CN1231219C CN 1231219 C CN1231219 C CN 1231219C CN 03141370 CN03141370 CN 03141370 CN 03141370 A CN03141370 A CN 03141370A CN 1231219 C CN1231219 C CN 1231219C
- Authority
- CN
- China
- Prior art keywords
- preparation
- cyclovirobuxinum
- amount
- tablet
- slow releasing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a medicinal slow-releasing preparation, particularly to a slow-releasing preparation containing cyclobuxine D as a medicinal effective component extracted from traditional Chinese medicine boxwood. The preparation is composed of cyclobuxine D as a medicinal effective component, a medicine slow-releasing stroma and/or other medicinally acceptable carriers.
Description
Technical field:
The present invention relates to a kind of medical slow releasing preparation, particularly contain the slow releasing preparation of the effective ingredient cyclovirobuxinum D that from the Chinese medicine Buxus sinica (Rehd.et Wils.), extracts.
Background technology:
Change has taken place in modern's dietary structure, and fat in the food and heat increase; The living condition is superior relatively, and physical exertion reduces.Some distinctive diseases are also following in the modern life, and the sickness rate of its center, cerebrovascular system disease rises year by year.Since the nineties, coronary heart disease, angina pectoris have become common clinical, frequently-occurring disease from the last century.World Health Organization's prediction, to the year two thousand twenty, the heart, angiopathy will be popular in developing country, wherein mainly be apoplexy and coronary heart disease; The noninfectious sickness rate of China will rise to 79% from present 58%, and its center, angiopathy will account for the first place.
Through making great efforts for many years, clinically intensive researching and analysing carried out in coronary heart disease, the anginal morbidity origin cause of formation, pathologic condition and clinical manifestation, drawing coronary heart disease mainly is because atherosclerotic lesion causes coronary stricture, obturation, influence the coronary circulation blood flow, cause myocardial ischemia, anoxybiotic cardiopathic conclusion.This disease is because position, scope and the degree difference of pathological changes are divided into latent coronary heart disease, angina pectoris, myocardial infarction, myocardial fibrosis, sudden death.Common have latent coronary heart disease, angina pectoris, a myocardial infarction etc.In view of the above, medical worker has explored the above treatment of diseases method of multiple treatment, develops multiple medicine, and removing for extensive patients to a certain extent or alleviating ailing puzzlement provides effective means.
In treatment coronary heart disease, anginal medicine, Chinese medicine is because of its treating both the principal and secondary aspects of a disease, side effect is little to receive publicity especially, " Buxine " (2000 editions kinds of the Pharmacopoeia of the People's Republic of China) are that a kind of effect is good in numerous treatment coronary heart disease, anginal Chinese medicine, well received a kind of medicine is that the preparation of medicinal ingredient has very unique place with the Buxine.It has dissolved in the modern pharmaceutical Technology again when having drawn the traditional clinical efficacy of Chinese medicine.By the contained Buxine of every tablet preparation in Buxine Tablet that records of Pharmacopoeia of the People's Republic of China version in 2000, in cyclovirobuxinum D (C26H46N20), should be the 90.0-110.0% of labelled amount, its purity is quite high.We can say that Buxine is the successful embodiment that motherland's traditional medicine and modern pharmaceutical industrial technology organically combine.
In the last few years, through medical scientific research personnel's continuous exploration, proved further that Buxine was as a kind of monosomic alkali that extracts from Buxus sinica (Rehd.et Wils.) is wooden, has the reduction myocardial oxygen consumption, strengthen myocardial contraction, improve the heart pump function, cardiac muscle is had the pharmacological action of certain protection; And through clinical verification, Buxine not only has the reduction myocardial oxygen consumption, strengthen the effect of myocardial contraction, but also can improve myocardial ischemia, improve coronary circulation, shorten myocardial contraction time interval, make the whenever amount of fighting, cardiac output and ejection fraction increase, illustrate that this medicine can strengthen cardiac pump function and ventricular systolic function under the situation that does not increase myocardial oxygen consumption.In addition, through evidence, found the some other therapeutical effect of Buxine.The Yao Huiqin of Beijing Tongren Hospital of the Capital University of Medical Sciences etc. find that by 100 routine clinical observations Buxine also has the effect that reduces whole blood viscosity and packed cell volume, has certain effect to preventing coronary thrombosis; The Jiang Huamin of Pingyi County, Shandong Province institute of traditional Chinese medicine etc. are by observing discovery to the blood fat of 60 routine hyperlipidemia patients, the detection of hemorheology series, Buxine Tablet truly has and changes hemorheological indexes and reduce TC, TG, the effect of rising HDL, the prompting Buxine has the adjustment blood lipid level, the effect of blood viscosity lowering and microcirculation improvement all has therapeutical effect preferably to hyperlipemia and high blood viscosity patient; The Fang Taihui of Nanjing University of Traditional Chinese Medicine etc. experiment showed, that by pharmacological research cerebral ischemia has obvious protective effect to Buxine to chmice acute, and has tangible antithrombotic effect.
The exploitation report of dosage forms such as the tablet of at present existing Buxine, injection, drop pill.
Because at present the Buxine product of listing all is the dosage form of common release, needs every day and takes 3 times, brought constantly to the patient, the cardiovascular and cerebrovascular disease patient mostly is middle aged the aged, and is the lifelong participation disease, the compliance particular importance of taking medicine.Therefore the present invention through further investigation and exploration, has made a day clothes cyclovirobuxine-D sustained-release preparation once from improving patient's compliance, has solved this problem.
Summary of the invention:
The invention provides a kind of new pharmaceutical preparation of cyclovirobuxinum D, said preparation can provide the slow release of cyclovirobuxinum D in 24 hours.
Cyclovirobuxinum D slow releasing preparation of the present invention comprises the dosage form that tablet, capsule, granule or other can be oral.
The present invention also provides the preparation method of cyclovirobuxinum D slow releasing preparation.
Cyclovirobuxinum D slow releasing preparation of the present invention comprises cyclovirobuxinum D and sustained-release matrix and/or other drug acceptable carrier.
Slow releasing preparation preparation method of the present invention, comprise with cyclovirobuxinum D and composition mix homogeneously such as suitable sustained-release matrix, diluent, add binding agent to granulate that the oven dry of gained wet granular is to a certain degree, add lubricant, be pressed into the tablet of suitable specification and size or encapsulated.
Cyclovirobuxinum D slow releasing preparation of the present invention, every dose of amount that contains cyclovirobuxinum D is 2-10mg.Described every dose refers to the unit of each dosage form such as every of tablet, every capsules of capsule etc.Wherein the amount of cyclovirobuxinum D accounts for the 0.5-9% of amount of formulation.
Cyclovirobuxinum D slow releasing preparation of the present invention, sustained-release matrix wherein are selected from the mixture of a kind of or its composition in hydroxypropyl emthylcellulose, sodium alginate, chitosan, polyvinyl alcohol, stearic acid, glyceryl monostearate, Brazil wax, ethyl cellulose, the polymethyl methacrylate.Its consumption accounts for the 9.5-62% of amount of formulation.
Cyclovirobuxinum D slow releasing preparation of the present invention, the adjuvant component of described necessity is a diluent, can be selected from the mixture of a kind of or its composition in microcrystalline Cellulose, starch, pregelatinized Starch, lactose, the Icing Sugar.
Cyclovirobuxinum D slow releasing preparation of the present invention, the adjuvant component of described necessity is a binding agent, can be selected from the mixture of hydroxypropyl emthylcellulose with adhesion characteristic, polyvinylpyrrolidone, starch, syrupy a kind of or its composition.
Cyclovirobuxinum D slow releasing tablet of the present invention before being pressed into tablet, can add the pharmaceutically acceptable lubricant of effective dose, comprises the mixture of a kind of or its composition in magnesium stearate, the Pulvis Talci etc.
Above supplementary product consumption accounts for the 35-89% of amount of formulation.
Slow releasing preparation of the present invention, its prescription are formed
Cyclovirobuxinum D 2-10g
Hypromellose (K-15M) 30-120g
Pregelatinized Starch 40-150g
Lactose 20-80g
Microcrystalline Cellulose 10-40g
80% ethanol 70-280ml
Magnesium stearate 1-5g
Make 1000 doses
Preparation method can be, the supplementary material pulverize separately is sieved, and takes by weighing supplementary material by recipe quantity, adopts equivalent incremental method mix homogeneously, adds ethanol, granulations of sieving of system soft material, soft material, wet grain drying, dry after granulate, tabletting or encapsulatedly promptly get preparation of the present invention.
Slow releasing preparation of the present invention can be taken 1 every day, each 1 dose.
Slow releasing preparation of the present invention, particularly tablet have following advantage and good effect:
1. the process of cyclovirobuxinum D slow releasing tablet of the present invention is the preparation method of conventional tablet.Simple and easy to do, need not to increase extras and investment, can large batch of suitability for industrialized production.
2. cyclovirobuxinum D slow releasing tablet of the present invention can increase and reaches the stable state time, helps improving disease-resistant usefulness, reduces administration number of times, reduces toxic and side effects, improves patient's compliance.
Following data declaration beneficial effect of the present invention by experiment.Acute toxicity test, the result shows: cyclovirobuxinum D is to the oral acute toxicity of mice, its LD
50Be 364.75mg/kg, the 95% credible 291.47～456.46mg/kg that is limited to, this dosage are 5137 times of clinical adult dose for oral use, and this provides the pharmacology foundation for clinical disposable heavy dose of medication.Cyclovirobuxinum D is injected acute toxicity to mouse peritoneal, its LD
50Be 73.45mg/kg, the 95% credible 59.84～90.16mg/kg that is limited to.
Long term toxicity test: cyclovirobuxinum D 71.0mg, 35.5mg, three dosage of 17.7mg/kg are equivalent to 1000 times, 500 times, 250 times of clinical medicine dose respectively.Give rat continuous irrigation stomach 4 months, and observed the general state situation of animal behind the medicine, periodic logging body weight, appetite, after administration 2 months, 4 months and the drug withdrawal 15 days, each put to death 1/3 animal, carried out the hematology, histopathological examination is learned and reached substantially to blood biochemical.Every index and matched group relatively there are no significant difference.
Above data show, Buxine Tablet is changed over slow releasing agent, and its toxicity does not increase, for clinical use provides safe assurance.
The test of pesticide effectiveness: by the detection to normal anesthetized open-chest dog hemodynamics and myocardial oxygen consumption figureofmerit, the slow releasing tablet group is compared with ordinary tablet group (positive control drug group), and two groups of pharmacological action intensity are suitable with effect, but the slow releasing tablet group obviously prolongs action time; In mensuration ligation dog anterior descending coronary (LAD) is caused in the influence process of acute myocardial infarction model, the slow releasing tablet group is compared with ordinary tablet group (positive control drug group), be that two medicine pharmacological actions are suitable equally, but the slow releasing tablet group is being used obvious prolongation; Cardiac muscle pathology histological observation result also shows that three dosage of cyclovirobuxine-D sustained-release sheet all can make cardiac muscle fiber edema kitchen range area obviously dwindle, and the edema degree obviously alleviates, and the high dose group effect is the most obvious, is better than positive control drug Buxine Tablet group.
In addition, find that by test the cyclovirobuxine-D sustained-release sheet is prolong rats thrombus in vivo formation time obviously, obviously reduce external blood and form length, reduce wet weight of thrombus and dry weight; Its height, middle dosage group and Buxine Tablet group all can obviously prolong the hemorrhage clotting time of mice, and there are the significant prolongation effect cerebral ischemia time-to-live and hypoxia endurance time; Test group and positive controls all can obviously increase blood stasis Mice Auricle arteriole bore, venule bore and blood capillary opening amount, improve its microcirculation function.
These effects of cyclovirobuxine-D sustained-release sheet, relevant with direct coronary artery dilating, make it myocardial flow and increase.Can reduce cardiac energy and oxygen consumption, oxygen uptake rate is reduced.Prompting cyclovirobuxine-D sustained-release sheet can improve systema cariovasculare functional, regulates heart blood supply oxygen supply balance, has prolonged action time aspect drug effect, and is to preventing and treating cardiovascular disease, significant as commonly encountered diseases such as coronary heart disease, myocardial ischemia.
Stability test: we to three batch samples under the accelerated test condition (40 ℃, RH75%) three months and room temperature keep sample and measured under the condition in three months, every index all meets standards of pharmacopoeia following table 1, table 2 is the pharmacokinetics experimental data, laboratory animal is a Canis familiaris L.:
The concentration of cyclovirobuxinum D (ng/ml) in the different time blood plasma after table 1 administration
| Time | Cyclovirobuxine-D sustained-release sheet (A) | Buxine ordinary tablet (B) |
| 0.25 | 50 | 55 |
| 0.5 | 65 | 95 |
| 0.75 | - | 120 |
| 1 | 80 | 165 |
| 1.5 | - | 180 |
| 2 | 115 | 275 |
| 3 | 170 | - |
| 4 | 220 | 180 |
| 6 | 205 | 150 |
| 8 | 170 | 120 |
| 10 | 140 | - |
| 12 | 115 | 105 |
| 24 | - | 95 |
| 36 | 70 | 90 |
| 48 | 60 | 60 |
Annotate :-data lack
The concentration of cyclovirobuxinum D (ng/ml) in the different time blood plasma after table 2 administration
| Preparation | C max(ng/ml) | Parameter T max(h) | T 1/2(a)(h) |
| Cyclovirobuxine-D sustained-release sheet (A) | 220 | 4 | 1.8 |
| Buxine ordinary tablet (B) | 275 | 2 | 1.1 |
The specific embodiment:
Further specify the present invention by the following examples
The preparation of embodiment 1 slow releasing tablet
Cyclovirobuxinum D 5g
Hypromellose (K-15M) 60g
Pregelatinized Starch 75g
Lactose 40g
Microcrystalline Cellulose 20g
80% ethanol 140ml
Magnesium stearate 2g
Make 1000
The supplementary material pulverize separately is crossed 100 mesh sieves, take by weighing supplementary material, adopt equivalent incremental method mix homogeneously by recipe quantity, add 80% ethanol, the system soft material, soft material is crossed 20 mesh sieves and is granulated, wet granular is in 40 ~ 50 ℃ of dryings, and dry back adds magnesium stearate with 20 mesh sieve granulate, mix homogeneously, semi-finished product are surveyed content, the qualified back circular chamfering punch die tabletting of diameter 8.0mm, sheet shape is circular, sheet heavily is 200mg, and through check, qualified back packing promptly.
The preparation of embodiment 2 slow releasing capsulees
Cyclovirobuxinum D 5g
Hypromellose (K-15M) 60g
Pregelatinized Starch 75g
Lactose 40g
Microcrystalline Cellulose 20g
80% ethanol 140ml
Magnesium stearate 2g
Make 1000
The supplementary material pulverize separately is crossed 100 mesh sieves, take by weighing supplementary material, adopt equivalent incremental method mix homogeneously by recipe quantity, add 80% ethanol, the system soft material, soft material is crossed 20 mesh sieves and is granulated, wet granular is in 40 ~ 50 ℃ of dryings, and dry back is with 20 mesh sieve granulate, totally 1000 of No. 1 capsules of packing into.
Claims (5)
1, a kind of cyclovirobuxinum D slow releasing preparation, it is characterized in that, said preparation is by the effective ingredient cyclovirobuxinum D, medicament sustained-release matrix and other drug acceptable carrier are formed, wherein the amount of cyclovirobuxinum D accounts for the 0.5-9% of amount of formulation, the amount of sustained-release matrix accounts for the 9.5-62% of amount of formulation, the amount of medicine acceptable carrier accounts for the 35-89% of amount of formulation, wherein medicament sustained-release matrix is selected from hydroxypropyl emthylcellulose, sodium alginate, chitosan, polyvinyl alcohol, stearic acid, glyceryl monostearate, Brazil wax, ethyl cellulose, polymethyl methacrylate, the other drug acceptable carrier is selected from microcrystalline Cellulose, starch, lactose, Icing Sugar, hydroxypropyl emthylcellulose, polyvinylpyrrolidone, magnesium stearate.
2, preparation according to claim 1, the amount that contains cyclovirobuxinum D in every dose is 2-10mg.
3, preparation according to claim 1 is tablet or capsule.
4, preparation according to claim 1 is a tablet.
5, a kind of preparation method of preparation is characterized in that, the raw material of following composition is made slow releasing preparation,
Cyclovirobuxinum D 2-10g
Hypromellose 30-120g
Pregelatinized Starch 40-150g
Lactose 20-80g
Microcrystalline Cellulose 10-40g
80% ethanol 70-280ml
Magnesium stearate 1-5g
Make 1000 doses
Preparation method is as follows: the raw material pulverize separately is sieved, takes by weighing raw material, adopt equivalent incremental method mix homogeneously, add ethanol by the amount of above-mentioned composition, granulations of sieving of system soft material, soft material, wet grain drying, dry after granulate, tabletting or promptly encapsulated.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03141370 CN1231219C (en) | 2003-06-05 | 2003-06-05 | Huangyangning slow-releasing preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03141370 CN1231219C (en) | 2003-06-05 | 2003-06-05 | Huangyangning slow-releasing preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1460478A CN1460478A (en) | 2003-12-10 |
| CN1231219C true CN1231219C (en) | 2005-12-14 |
Family
ID=29591359
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 03141370 Expired - Fee Related CN1231219C (en) | 2003-06-05 | 2003-06-05 | Huangyangning slow-releasing preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1231219C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101439126B (en) * | 2007-11-22 | 2012-09-05 | 天士力制药集团股份有限公司 | Chinese medicine granule containing Huangyangning and preparation method thereof |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110051633A (en) * | 2018-11-27 | 2019-07-26 | 宁夏医科大学 | A kind of cyclovimbuxine D nanometer formulation and preparation method thereof |
-
2003
- 2003-06-05 CN CN 03141370 patent/CN1231219C/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101439126B (en) * | 2007-11-22 | 2012-09-05 | 天士力制药集团股份有限公司 | Chinese medicine granule containing Huangyangning and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1460478A (en) | 2003-12-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1686121A (en) | Phenylsulfonic acid amido chloro diping dispersion tablet and its preparation method | |
| CN1943618A (en) | Red sage root effective part standard extract and its preparing method and use | |
| CN1224383C (en) | Blood sugar reducing compound | |
| CN1231219C (en) | Huangyangning slow-releasing preparation | |
| CN1827112A (en) | Dispersion tablet for treating cardiovascular diseases and its preparation method | |
| CN101036707A (en) | Pill for easing heart and the method for preparing the same | |
| CN1850069A (en) | Method for preparing Tengchasu dispersibletablet and its use | |
| CN100337615C (en) | Oral disintegration tablet prepared from general saponin of notoginseng for treating thrombosis, and preparing technique | |
| CN1287808C (en) | Ginkgo leaf extract composition | |
| CN101897717B (en) | Chinese medicinal composition for treating diabetes and application | |
| CN1212143C (en) | Medicine for treating coronary disease and its preparation method | |
| CN1490000A (en) | Hippophae rhamnoide flavone drops and preparation thereof | |
| CN1830460A (en) | Xuesaitong (thrombus clearout) chewing tablet and its preparation method | |
| CN1316992C (en) | Medicine for treating heart brain embulus disease and its preparation method | |
| CN1853711A (en) | Xinmaikangzhong Chinese medicinal composition and preparation thereof | |
| CN102327545B (en) | Application of traditional Chinese medicinal composition in preparation of medicine for treating metabolic syndromes | |
| CN1689579A (en) | Application of burdock glycoside or its aglycon in preparation of medicine for treating diabetes or its complications | |
| CN1481796A (en) | Medication for adiposity | |
| CN1868482A (en) | Aspirin slow-release tablet and its prepn. method | |
| CN1530114A (en) | Sustained releasing breviscapine tablets | |
| CN1418621A (en) | WEILAPAMI oral disintegrant for treating irrhythmia, and its prepn. method | |
| CN1281206C (en) | Orally disintegrating tablet of 'Xinxuekang | |
| CN1931206A (en) | Compound oral prepn of muskone and total arasaponin and its application | |
| CN1872248A (en) | Application of medication of containing alisma rhizome in treating resistant medication of aspirin | |
| CN1528320A (en) | Acetyl rhizoma gastrodiae extract drop pill and preparing method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20051214 Termination date: 20120605 |