CN1480137A - Osmotic pump type controlled release preparation of kurarinone and its preparing method - Google Patents
Osmotic pump type controlled release preparation of kurarinone and its preparing method Download PDFInfo
- Publication number
- CN1480137A CN1480137A CNA031338542A CN03133854A CN1480137A CN 1480137 A CN1480137 A CN 1480137A CN A031338542 A CNA031338542 A CN A031338542A CN 03133854 A CN03133854 A CN 03133854A CN 1480137 A CN1480137 A CN 1480137A
- Authority
- CN
- China
- Prior art keywords
- kurarinone
- controlled release
- osmotic pump
- pump type
- release preparation
- 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.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A release controlled osmotic pump type kurarinol is prepared from kurarinol, diluent, osmosis promoter, lubricant and adhesive through pulverizing, sieving, mixing, adding alcohol, granulating, drying, adding lubricant, talbetting, and coating. Its advantages are long time for maintaining effective blood concentration, and less peak and valley of blood concentration.
Description
Technical field:
The present invention relates to the novel drugs dosage form of kurarinone, exactly it is kurarinone osmotic pump type controlled release preparation and preparation method thereof.
Background technology:
Kurarinone is the effective ingredient that extracts by in Chinese medicine Herba Sophorae alopecuroidis (Sophora alopecuroides L) or the Radix Sophorae Flavescentis (Sophora flavescens Ait), wherein oxymatrine (Oxymatrine) content is more than 98%, pharmacology and clinical research show that it has antitumor, antibiotic, antiviral, improves liver function and prevent effects such as hepatic fibrosis, transaminase lowering, human body immunity improving power.At present, kurarinone has been confirmed as treating the viral hepatitis emphasis and has promoted the engineering medicine, it can obviously suppress hepatitis B virus infection, detect through gene quantification, use after the kurarinone, the hepatitis B virus duplication level obviously descends in the infected cell, and this shows that this medical instrument has the effect that suppresses the viral growth breeding.A large amount of clinical research results confirm that through the kurarinone treatment, chronic viral hepatitis B patient glutamate pyruvate transaminase and bilirubin recover natural rate of interest and reach 81.6% and 69.9% respectively.Hospital expert is used animal experimental model, carries out the full genome transgenic mice test of hepatitis B virus, takes the lead at home and abroad using in 1999, and kurarinone can obviously reduce medicamentous liver lesion, confirms that this medicine can effectively prevent and treat liver cirrhosis.National treating hepatitis B " 95 " brainstorm subject of being finished by the cooperation of domestic 9 tame famous medical institutions: " research of chronic disease disposition hepatitis medicament treatment new departure " confirms: kurarinone has good antiviral, effects such as human body immunity improving power, seminar is thought, this medicine has promotional value widely under China's applied economics level, market prospect is very good, the preparation of kurarinone mainly contains injection at present, transfusion, quick-release capsules and tablet, prior dosage form can not be fit to needs clinically far away, exploitation once-a-day or twice slow releasing preparation meet the needs of medical market.
Osmotic pump preparation the earliest is nineteen fifty-five two Australian scholar's inventions, be used for the administration of domestic animal gastrointestinal, be called Rose-Nelson type osmotic pumps, the seventies, Theeuwes delivered the basic theories of relevant osmotic pumps, establish the special status of osmotic pump preparation in controlled release preparation, and proposed the notion and the structure of elementary elementary osmotic pump, simplified the infiltration pump structure, thereby make it to move towards the industrialization produce and clinical come many more, the also corresponding appearance of osmotic pumps product.The medicine of making osmotic pump preparation at present has albuterol, nifedipine, glipizide, diltiazem, doxazosin, indomethacin etc.Because osmotic pumps has: the strong dose thing can be provided; The character of scalable semipermeable membrane, thickness, surface area and release aperture etc. are to obtain required rate of releasing drug; Release and environment (as pH, stirring, feed situation etc.) are irrelevant, even irrelevant with the character of medicine, and the inside and outside dependency is good, so release situation in the available external release data prediction body; Can be used for regulating blood level; Can be by the different rates multiple medicine of controlled release simultaneously: reduce medicining times, improve compliance; Reduce advantages such as stimulation and untoward reaction, people are used more it pay close attention to.
The kurarinone water solublity is fabulous, is not easy to control rate of releasing drug, and long-time steadily release of control medicine is its main difficulty, is that the difference between product is criticized and criticized is big on the other hand, is difficult for carrying out industrialized great production.
Summary of the invention:
The present invention carries out on the basis of gastrointestinal absorption situation having investigated kurarinone.Generally speaking, the medicine that can both absorb in whole section of gastrointestinal tract or very long part is the excellent drug of preparation controlled release formulations for oral administration.The inventor by isolated rat intestinal absorption experimentation the absorbing state of kurarinone different parts in intestinal, the difference that shows that there are no significant between duodenum, jejunum, ileum, each section of colon helps preparing controlled release preparation of the present invention (seeing accompanying drawing 1),
Purpose of the present invention can reach by following measure:
It is made up of following component:
Kurarinone 50～450 weight portions
Diluent 30～200 weight portions
Penetration enhancer 50～300 weight portions
Lubricant 2～30 weight portions
Binding agent is an amount of
The specification of kurarinone is per unit 50,75,150,300,450mg.With sieving behind the medicine of recipe quantity and diluent, the penetration enhancer pulverize separately, behind the mix homogeneously, add binding agent system soft material, 20 mesh sieves are granulated, 50 ± 5 ℃ of dryings, 18 mesh sieve granulate, dried granule add lubricant and suppress the heart in blocks.Label is placed in the coating pan, be blown into hot-air, when treating that the label temperature is 40 ℃ of left and right sides, carry out coating, the coating solution flow velocity is 5-10mL/min, and pressure is 0.8kg/cm
2The coating kettle temperature is about 40 ℃, the coating pan rotating speed is 10-20rpm, till reaching predetermined standard time to the thickness of label outer coatings film, continue to be blown into hot-air 0.5h, with coated tablet 40 ℃ of following dry 48h in drying baker, get the coated tablet that above-mentioned drying finishes then, break into the aperture that the aperture is 0.4mm with mechanical means in coated tablet one side, get product.
The diluent of the tablet described in the above-mentioned preparation method consist of starch, pregelatinized Starch, dextrin, lactose, microcrystalline Cellulose etc.
Penetration enhancer described in the above-mentioned preparation method be sodium chloride, potassium chloride, magnesium sulfate, magnesium chloride, potassium sulfate, sodium sulfate, d-mannitol, carbamide, glucose, sucrose, Magnesium succinate, tartaric acid etc.
The binding agent of the tablet described in the above-mentioned preparation method is the mixed solution of polyvinylpyrrolidone, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, methylcellulose, water, water or alcohol.
The lubricant of the tablet described in the above-mentioned preparation method is pharmaceutically useful adjuvant with lubrication, comprises magnesium stearate, Pulvis Talci, sodium lauryl sulphate.
The kurarinone controlled release tablet of utilizing the present invention to prepare, blood drug level is steady in the body of oral back, and side effect reduces, and administration number of times is few, and duration of efficacy is long.Kurarinone release in gastrointestinal tract is slow, and the concentration that medicine contacts with gastrointestinal mucosa is little, has also alleviated the stimulation that medicine causes gastrointestinal tract.
The kurarinone controlled release tablet of utilizing the present invention to prepare once-a-day, each 2～3, is applicable to disease patient in various degree.
Experiment shows, the ordinary preparation of kurarinone was taken medicine in a period of time at initial stage, and blood drug level is very low, after this rapid release, blood drug level raises suddenly, a tangible peak value occurs: release steadily, slowly discharged complete in 24 hours substantially in the dissolution medium of osmotic pump type controlled release tablet.External degree of the being released into situation of different preparations sees Table 1, table 2.
Release time (min) 10 20 30 40 50 60 90 dissolutions (%) 2.4 84.5 85.6 92.7 94.2 96.9 96.7 in the capsular water of table 1 kurarinone
Release times (h) 2468 10 12 16 24 water 14.8 25.6 35.5 48.6 61.4 69.1 76.3 92.7 of table 2 kurarinone osmotic pump type controlled release tablet in water
Theoretically, controlled release preparation is than ordinary preparation, and it is steady to have in the body blood drug level, the effective blood drug concentration length of holding time; Reduce blood drug level " peak valley " phenomenon, thereby alleviate the toxicity of medicine; Reduce administration number of times, characteristics such as make things convenient for administration and take.
From therapeutic complying with, former preparation is taken medicine for three times on the one, the patient often forgets easily take medicine daytime, take medicine for three times on the one, should be that per minute hour is administered once theoretically, but in fact very difficult, three times the interval of taking medicine daytime be shorter, the back of taking medicine evening long the time in the morning to, cause early morning and morning the time-out blood concentration low.Controlled release tablet was taken medicine once on the 1st, reduced medicining times, took medicine on time easily, keep 24 hours blood drug level steadily, so can overcome above-mentioned contradiction, be beneficial to patient treatment.
Advantage of the present invention is: the kurarinone osmotic pump type controlled release preparation, once-a-day, blood drug level is steady in the body, effective blood concentration is held time and is reached 24 hours, reduce the peak valley phenomenon of blood drug level, alleviated the toxicity of medicine, reduced administration number of times, improve patient's compliance, adapted to the needs of clinical development.
Description of drawings:
Fig. 1 accumulates the drug absorption discharge curves for the present invention at different intestinal segments
Among the figure-◆-duodenum ,-■-jejunum ,-▲-colon, * ileum
The specific embodiment:
Prescription scope among the following embodiment can be selected in the scope of above-mentioned weight ratio, and embodiment does not limit the range of choice.
Embodiment 1:
Sheet heart prescription:
Kurarinone 300.0g
Sodium chloride 200.0g
Lactose 77.0g
Magnesium stearate 3g
Sheet heart preparation: will sieve behind the medicine of recipe quantity and sodium chloride, the lactose pulverize separately, mix homogeneously is a wetting agent system soft material with 95% ethanol, 20 mesh sieves are granulated, tabletting promptly got 1000 sheet hearts after 50 ± 5 ℃ of dryings of wet granular, 18 mesh sieve granulate, dried granule added the lubricant mixing.
Coating fluid prescription:
Cellulose acetate 100g
PEG6000 12g
Dibutyl phthalate 13mL
Acetone 5L
Art for coating: label is placed in the coating pan, be blown into hot-air, when treating that the label temperature is 40 ℃ of left and right sides, carry out coating, the coating solution flow velocity is 5-10mL/min, pressure is 0.8kg/cm2, the coating kettle temperature is about 40, thickness to label outer coatings film reaches weightening finish 4.0～4.5%, continue to be blown into hot-air 0.5h, with coated tablet 40 ℃ of following dry 48h in drying baker, get the coated tablet that above-mentioned drying finishes then, break into the aperture that the aperture is 0.4mm with mechanical means in coated tablet one side, get product.
Embodiment 2:
Sheet heart prescription:
Kurarinone 300.0g
Sucrose 100.0g
Lactose 177.0g
Magnesium stearate 3g
Sheet heart preparation, with embodiment 1:
Coating fluid prescription:
Cellulose acetate 100g
PEG6000 12g
Dibutyl phthalate 5mL
Acetone 5L
Art for coating is with embodiment 1.
Embodiment 3:
Sheet heart prescription:
Kurarinone 300.0g
Sodium chloride 200.0g
Pregelatinized Starch 77.0g
Magnesium stearate 3g
Sheet heart preparation: with embodiment 1.
Coating fluid prescription: with embodiment 1.
Art for coating: with embodiment 1.
Claims (8)
1, kurarinone osmotic pump type controlled release preparation is characterized in that: it is made up of following component:
Kurarinone 50～450 weight portions
Diluent 30～200 weight portions
Penetration enhancer 50～300 weight portions
Lubricant 2～30 weight portions
Binding agent is an amount of
2, kurarinone osmotic pump type controlled release preparation according to claim 1 is characterized in that: the specification of kurarinone is per unit 50,75,150,300,450mg.
3, according to the described kurarinone osmotic pump type controlled release preparation of claim 1, it is characterized in that: diluent consist of starch, pregelatinized Starch, dextrin, lactose, microcrystalline Cellulose etc.
4, the kurarinone osmotic pump type controlled release preparation of stating according to claim 1 is characterized in that: binding agent is the mixed solution of polyvinylpyrrolidone, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, methylcellulose, water, water or alcohol.
5, the kurarinone osmotic pump type controlled release preparation of stating according to claim 1 is characterized in that: penetration enhancer be sodium chloride, potassium chloride, magnesium sulfate, magnesium chloride, potassium sulfate, sodium sulfate, d-mannitol, carbamide, glucose, sucrose, Magnesium succinate, tartaric acid etc.
6, the kurarinone osmotic pump type controlled release preparation of stating according to claim 1 is characterized in that: lubricant is pharmaceutically useful adjuvant with lubrication, comprises magnesium stearate, Pulvis Talci, sodium lauryl sulphate.
7, a kind of preparation method of kurarinone osmotic pump type controlled release preparation as claimed in claim 1, it is characterized in that: in above-mentioned weight proportion scope, select kurarinone, diluent, penetration enhancer, lubricant, binding agent and 95% ethanol an amount of, to sieve behind medicine and diluent, the penetration enhancer pulverize separately, mix homogeneously, with 95% ethanol is wetting agent system soft material, and 20 mesh sieves are granulated, wet grain drying, tabletting promptly got the sheet heart after 18 mesh sieve granulate, dried granule added the lubricant mixing.
8, the preparation method of kurarinone osmotic pump type controlled release preparation according to claim 7, it is characterized in that: filmogen is a cellulose acetate, plasticizer is PEG1500, PEG4000, PEG6000, phthalic acid ester, glyceride, succinate, benzoate, phosphate ester, adipate ester, tartrate, citrate etc., the coating solvent is mixed solvents such as acetone, acetone and isopropyl alcohol, acetone and chloroform, art for coating: the coating solution flow velocity is 5-10mL/min, and pressure is 0.8kg/cm
2, the coating kettle temperature is about 40 ℃, and the coating pan rotating speed is 10～20rpm, and the punching diameter is 0.4～0.6mm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031338542A CN100415231C (en) | 2003-07-04 | 2003-07-04 | Osmotic pump type controlled release preparation of kurarinone and its preparing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031338542A CN100415231C (en) | 2003-07-04 | 2003-07-04 | Osmotic pump type controlled release preparation of kurarinone and its preparing method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1480137A true CN1480137A (en) | 2004-03-10 |
| CN100415231C CN100415231C (en) | 2008-09-03 |
Family
ID=34154364
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB031338542A Expired - Fee Related CN100415231C (en) | 2003-07-04 | 2003-07-04 | Osmotic pump type controlled release preparation of kurarinone and its preparing method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100415231C (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101152228B (en) * | 2006-09-28 | 2010-08-18 | 成都中医药大学 | Genseng total sapnin micropore permeation pump, and its preparing method |
| CN101862363B (en) * | 2006-09-28 | 2011-12-21 | 成都中医药大学 | General ginsenoside primary osmotic pump tablet and preparation method thereof |
| CN101816691B (en) * | 2006-09-28 | 2012-04-18 | 成都中医药大学 | Gensenosides osmotic pump capsule and preparation method thereof |
| CN105769797A (en) * | 2016-03-11 | 2016-07-20 | 常州欧法玛制药技术有限公司 | Kurarinone osmotic pump controlled release tablets and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1111533C (en) * | 2000-11-18 | 2003-06-18 | 宁夏药物研究所 | The preparation technology of Oxymatyine |
| CN1439371A (en) * | 2003-02-18 | 2003-09-03 | 宁夏元康医药新技术有限公司 | Matrine sustained releasing agent and its preparing process |
-
2003
- 2003-07-04 CN CNB031338542A patent/CN100415231C/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101152228B (en) * | 2006-09-28 | 2010-08-18 | 成都中医药大学 | Genseng total sapnin micropore permeation pump, and its preparing method |
| CN101862363B (en) * | 2006-09-28 | 2011-12-21 | 成都中医药大学 | General ginsenoside primary osmotic pump tablet and preparation method thereof |
| CN101816691B (en) * | 2006-09-28 | 2012-04-18 | 成都中医药大学 | Gensenosides osmotic pump capsule and preparation method thereof |
| CN105769797A (en) * | 2016-03-11 | 2016-07-20 | 常州欧法玛制药技术有限公司 | Kurarinone osmotic pump controlled release tablets and preparation method thereof |
| CN105769797B (en) * | 2016-03-11 | 2018-10-02 | 常州欧法玛制药技术有限公司 | A kind of kushenin osmotic pump controlled release tablet and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100415231C (en) | 2008-09-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103006612B (en) | Lisinopril controlled-release tablet and preparation method thereof | |
| CN1895233A (en) | Medicament formulation with a controlled release of an active agent | |
| CN1903183A (en) | Dispersion tablets of telbivudine and its prepn. method | |
| CN1682696A (en) | Timing slow-releasing micrpill and its preparation | |
| CN103550183A (en) | Trimetazidine hydrochloride osmotic pump controlled-release tablet and preparation method thereof | |
| CN101045053A (en) | Slow-releasing micro-pills of sophocarpidine and its preparing method | |
| CN1480137A (en) | Osmotic pump type controlled release preparation of kurarinone and its preparing method | |
| CN102319225B (en) | Trimetazidine hydrochloride sustained release tablet and preparation method thereof | |
| CN101032462A (en) | Mexiletine Hydrochloride slow release reagent and preparing method thereof | |
| CN1254246C (en) | Oral disintegration tablet of silaenafil and its pharmaceutically receptible salt and its preparing method | |
| CN1608621A (en) | Fine bicyclic alcohol powder and oral bicyclic alcohol release controlling prepn | |
| CN101480415B (en) | Cordyceps sinensis sustained and controlled release capsule and preparation method thereof | |
| CN101461832A (en) | Bioadhesive paster for treating mouth ulcer | |
| CN1247202C (en) | Dioscin oral disintegration tablet and its preparing method | |
| CN1439371A (en) | Matrine sustained releasing agent and its preparing process | |
| CN109453132B (en) | Time-lag controlled-release tablet for treating coronary heart disease and preparation method thereof | |
| CN1568954A (en) | Mesalazine colon target releasing micro pills and preparation method thereof | |
| CN1287797C (en) | Gancilorvir dispersable tablet and its preparation | |
| CN1586470A (en) | Silibinin oral disintegration tablet and its preparing method | |
| CN1247203C (en) | Helicidum oral disintegation tablet and its preparing method | |
| CN101040850A (en) | Colchicine sustained-release pellets and the preparing method | |
| CN1297263C (en) | Calcium gluconate oral disintegrating tablet and its preparation process | |
| CN1895250A (en) | Gliquilone slow-releasing preparation | |
| CN1589782A (en) | Dimethyl biguanidine hydrochloride slow release particle and its preparation method | |
| CN1965822A (en) | Sustained release formulation of bilobalide-B and preparation process 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: 20080903 Termination date: 20110704 |