CN1226424A - Slow releasing agent of tuduvanine and its preparing method - Google Patents
Slow releasing agent of tuduvanine and its preparing method Download PDFInfo
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- CN1226424A CN1226424A CN 98125657 CN98125657A CN1226424A CN 1226424 A CN1226424 A CN 1226424A CN 98125657 CN98125657 CN 98125657 CN 98125657 A CN98125657 A CN 98125657A CN 1226424 A CN1226424 A CN 1226424A
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- weight portion
- slow releasing
- sinomenine
- tuduvanine
- releasing agent
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Abstract
A slow-releasing agent of diversine for stabilizing the concentration of medicine in blood is prepared from diversine hydrochloride, starch, dextrin, lactose, hydroxypropyl methyl cellulose and magnesium stearate. It features low by-effect and elongating the action of medicine.
Description
The invention relates to the novel drugs dosage form of sinomenine, is relevant slow releasing agent of tuduvanine and preparation technology's thereof invention specifically, belongs to drug world.
Sinomenine is the effective ingredient preparation that extracts from the Chinese medicine Caulis Sinomenii, is effective Chinese medicine of treatment rheumatism, rheumatoid arthritis and chronic nephritis.1996 is national Chinese medicine protection kind by official approval, records in the 18 of the Sanitation Ministry medicine standard (Chinese traditional patent formulation preparation).Because this kind is evident in efficacy, marketing is good, has now become national common drug.From the feedback in clinical and market in recent years, single dosage form can not be met the need of market far away, and the clinician proposes especially, develop long-acting (slow release) preparation, prolongs this kind market life, increase kind dosage form, bigger ground meeting the market requirement.But since sinomenine particularly the water solublity of sinomenine hydrochloride is better, be not a simple thing selecting aspect the slow releasing agent framework material.It is the rate of release that is not easy to control sinomenine that its difficulty is on the one hand, is that the difference between product is criticized and criticized is big on the other hand, and product quality is difficult to control, can not carry out large-scale industrialization production.
The object of the invention is exactly in order to overcome existing preparation process difficulty, by the slow releasing preparation framework material, adjuvant and the each component consumption that are suitable for sinomenine are selected, invents a kind of process stabilizing, and convenient drug administration prolongs drug effect, reduces the slow releasing agent of side effect.
The present invention has carried out a series of screening experiment researchs in development process.At first the slow releasing agent kind is selected.
Being applicable at present industrially has: 1. osmotic pump controlled release tablet; 2. film coated tablet; 7. framework controlled release tablets.
Because, differing greatly between the film coated tablet is criticized in process of production and criticized, just the thickness of coatings is very big to the drug dissolution influence, should not select for use.And osmotic pump controlled release tablet needs the special modular system of laser boring, and working condition is had relatively high expectations, and therefore, we have selected the matrix sustained release tablet of preparation sinomenine.
Owing to the material of the framework material that can be used as matrix sustained release tablet is a lot, but be not each slow releasing preparation that all is suitable for preparing sinomenine hydrochloride, the inventor selects framework material through the series of selection test for this reason.
Beginning with ethyl cellulose is framework material, find through a series of experiments, because the water solublity of sinomenine hydrochloride is better, be that framework material is difficult to control its rate of release with ethyl cellulose.
After select the fatty framework material again for use, experimental result shows the slow releasing tablet that forms with this material preparation, production operation trouble not only, and product is criticized with criticize between release widely different.Be not suitable for suitability for industrialized production.
After a series of experiment screenings, it is framework material that the inventor has selected hydroxypropyl emthylcellulose, preparation hydrophilic gel matrix sustained release tablet.
In addition, the inventor selects by orthogonal experiment method for the consumption of each component on the basis that adjuvant is selected, and has finished the present invention.
Consisting of of slow releasing agent of the present invention:
Sinomenine 50-70 weight portion
Starch 15-25 weight portion
Dextrin 60-80 weight portion
Lactose 50-70 weight portion
Hydroxypropyl emthylcellulose 80-100 weight portion
Magnesium stearate 5-10 weight portion.
Above-mentioned composition can add an amount of 80% ethanol when being prepared into slow releasing tablet, as wetting agent, the amount of its adding is advisable to make soft material after each component can being mixed.
The said sinomenine of the present invention can be its pharmaceutical salts that human body can be accepted, the example hydrochloric acid sinomenine.
The preferred weight proportioning of above-mentioned composition is:
Sinomenine 58-61 weight portion
Starch 18-20 weight portion
Dextrin 68-72 weight portion
Lactose 62-66 weight portion
Hydroxypropyl emthylcellulose 95-98 weight portion
Magnesium stearate 5-7 weight portion.
80% ethanol is an amount of.
The concentration of alcohol that the present invention selects for use can be 70-90%, but preferred 80%.
The method for making of medicine of the present invention is as follows:
To sieve behind medicine and starch, dextrin, lactose, the hydroxypropyl emthylcellulose pulverize separately, mix homogeneously, the ethanol with 80% are wetting agent system soft material, granulate with 16 mesh sieves, wet granular is 55 ℃ of dryings, 14 mesh sieve granulate, dried granule adds tabletting behind the magnesium stearate mixing, promptly.
Sinomenine hydrochloride is the medicine of treatment rheumatism and rheumatoid arthritis, and present preparation is the enteric film coat sheet.After being made into slow releasing preparation, compare with ordinary preparation, its main feature is that blood drug level is steady in the body, and side effect reduces, and administration number of times reduces, and duration of efficacy is long etc.
Experiment shows, the ordinary preparation of sinomenine 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.And the novel formulation slow releasing tablet steadily discharges in dissolution medium, reaches about 50% in 4 hours, reaches substantially fully in 12 hours to discharge.Former preparation and novel formulation release in vitro degree situation see Table 1 and table 2.
The release of table 1 sinomenine hydrochloride sheet in phosphate buffer
| Time (min) | ???10????20????30?????40?????50?????60?????90 |
| Dissolution (%) | ???2.1???6.5???15.5???70.8???95.2???96.8???96.6 |
Sinomenine hydrochloride sustained-released release in different medium of table 2
Theoretically, slow releasing 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 to be administered once in per 8 hours 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.Slow releasing tablet is taken medicine for twice on the one, reduces medicining times, and each once takes medicine on time easily sooner or later, keep 24 hours blood drug level steadily, so can overcome above-mentioned contradiction, be beneficial to patient treatment.
Above-mentioned experimental result proves that the more former tablet of this slow releasing tablet has than outstanding feature: 1 external solution is made result of the test and shown: slow releasing tablet all can steadily discharge in 12 hours in three kinds of media of 0.1M hydrochloric acid solution and PH6.8 phosphate buffer at water; And former preparation (enteric coatel tablets) not stripping in water and 0.1M hydrochloric acid solution, only stripping in PH6 8 phosphate buffers, the result is that 30 minutes dissolution rates of pro-are very low, only is about 15%, stripping fast in 40-60 minute reached complete stripping substantially in 60 minutes.
Human pharmacokinetics and relative bioavailability result show: the cmax value of slow releasing tablet and former tablet is respectively 88.7 ± 25.5ng/ml and 143 8 ± 34.2ng/ml, proves that the former dosage form blood drug level peak value in back of taking medicine is far longer than slow releasing tablet; After blood drug level reached steady statue, the Cssmax slow releasing tablet was lower than ordinary tablet (142.2 ± 45.3ng/ml VS, 176.2 ± 43.6ng/ml, P＜0.05); And the Cssmin slow releasing tablet is higher than ordinary tablet (78.9 ± 17.7 VS, 65.2 ± 13.5ng/ml, P＜0.05); The DF value of slow releasing tablet is significantly less than ordinary tablet (59.3% ± 20.0% VS, 104.9% ± 22.7%P＜0.05), and the result proves, it is poor that the more former dosage form of slow releasing tablet has overcome significantly " peak valley ".Compare with ordinary tablet, the relative bioavailability of slow releasing tablet is 104% ± 9%.Evidence: Sinomenine hydrochloride sustained-released with former ordinary tablet have bioequivalence, slow releasing tablet has tangible sustained releasing character.
Embodiment 1
Prescription:
Sinomenine hydrochloride 60.0g
Starch 19.3g
Dextrin 70.7g
Lactose 64.0g
Hydroxypropyl emthylcellulose 96.0g
Magnesium stearate 6.4g
80% ethanol 500ml
Method for making: will sieve behind medicine and starch, dextrin, lactose, the hydroxypropyl emthylcellulose pulverize separately, mix homogeneously, ethanol with 80% is wetting agent system soft material, granulate with 16 mesh sieves, wet granular is 55 ℃ of dryings, 14 mesh sieve granulate, dried granule add tabletting behind the magnesium stearate mixing, make 1000 promptly.
Embodiment 2
Prescription:
Sinomenine hydrochloride 580 grams
Starch 180 grams
Dextrin 680 grams
Lactose 600 grams
Hydroxypropyl emthylcellulose 900 grams
Magnesium stearate 600 grams
Method for making: will sieve behind medicine and starch, dextrin, lactose, the hydroxypropyl emthylcellulose pulverize separately, mix homogeneously, ethanol with 80% is wetting agent system soft material in right amount, granulate with 16 mesh sieves, wet granular is 55 ℃ of dryings, 14 mesh sieve granulate, dried granule add tabletting behind the magnesium stearate mixing, make 10000 promptly.
Embodiment 3
Prescription:
Sinomenine hydrochloride 61 grams
Starch 18 grams
Dextrin 68 grams
Lactose 62 grams
Hydroxypropyl emthylcellulose 98 grams
Magnesium stearate 7 grams
Method for making: will sieve behind medicine and starch, dextrin, lactose, the hydroxypropyl emthylcellulose pulverize separately, mix homogeneously, ethanol with 80% is wetting agent system soft material in right amount, granulate with 16 mesh sieves, wet granular is 55 ℃ of dryings, 14 mesh sieve granulate, dried granule add tabletting behind the magnesium stearate mixing, make 1000 promptly.
Claims (7)
1, a kind of slow releasing agent of tuduvanine is characterized in that it is made up of following component:
Sinomenine 50-70 weight portion
Starch 15-25 weight portion
Dextrin 60-80 weight portion
Lactose 50-70 weight portion
Hydroxypropyl emthylcellulose 80-100 weight portion
Magnesium stearate 5-10 weight portion.
2,, it is characterized in that it is made up of following component according to the slow releasing agent of tuduvanine of claim 1:
Sinomenine 58-61 weight portion
Starch 18-20 weight portion
Dextrin 68-72 weight portion
Lactose 62-66 weight portion
Hydroxypropyl emthylcellulose 95-98 weight portion
Magnesium stearate 5-7 weight portion.
3,, it is characterized in that described sinomenine is its pharmaceutical salts according to the slow releasing agent of tuduvanine of claim 1 or 2.
4, according to the slow releasing agent of tuduvanine of claim 3, the pharmaceutical salts that it is characterized in that said sinomenine is a sinomenine hydrochloride.
5,, it is characterized in that also containing 80% an amount of alcohol according to the slow releasing agent of tuduvanine of claim 1 or 2.
6,, it is characterized in that the weight proportion of each component is according to the slow releasing agent of tuduvanine of claim 4:
60.0 parts of sinomenine hydrochlorides
19.3 parts of starch
70.7 parts in dextrin
64 parts of lactose
The ylmethyl cellulose is 96.0 parts in the hydroxyl
6.4 parts of magnesium stearate
80% ethanol is an amount of.
7, a kind of Sinomenine hydrochloride sustained-released preparation method is characterized in that method comprises:
The raw material prescription:
Sinomenine hydrochloride 60.0g
Starch 19.3g
Dextrin 70.7g
Lactose 64.0g
Hydroxypropyl emthylcellulose 96.0g
Magnesium stearate 6.4g
80% ethanol is an amount of
Method for making: will sieve behind medicine and starch, dextrin, lactose, the hydroxypropyl emthylcellulose pulverize separately, mix homogeneously, ethanol with 80% is wetting agent system soft material, granulate with 16 mesh sieves, wet granular is 55 ℃ of dryings, 14 mesh sieve granulate, tabletting after granule adds the magnesium stearate mixing is made 1000 promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN98125657A CN1076604C (en) | 1998-12-24 | 1998-12-24 | Slow releasing agent of tuduvanine and its preparing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN98125657A CN1076604C (en) | 1998-12-24 | 1998-12-24 | Slow releasing agent of tuduvanine and its preparing method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1226424A true CN1226424A (en) | 1999-08-25 |
| CN1076604C CN1076604C (en) | 2001-12-26 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN98125657A Expired - Lifetime CN1076604C (en) | 1998-12-24 | 1998-12-24 | Slow releasing agent of tuduvanine and its preparing method |
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| Country | Link |
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| CN (1) | CN1076604C (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1332669C (en) * | 2004-12-13 | 2007-08-22 | 北京正大绿洲医药科技有限公司 | Dripping pills for reducing swelling and easing pain and its preparing method |
| CN101375849B (en) * | 2007-08-27 | 2011-01-19 | 湖南正清制药集团股份有限公司 | Novel dosage form of sinomenine medicament or hydrochlorate thereof and preparation technique thereof |
| CN104906477A (en) * | 2015-06-16 | 2015-09-16 | 中山火炬职业技术学院 | Preparation method for stemona total alkaloid sustained-release tablets |
| CN109364077A (en) * | 2018-10-23 | 2019-02-22 | 三峡大学 | Application of the cucoline on the drug of preparation treatment rheumatoid arthritis |
| CN112494449A (en) * | 2020-04-29 | 2021-03-16 | 湖南正清制药集团股份有限公司 | Sinomenine hydrochloride sustained release agent prepared by inorganic solvent |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1316971C (en) * | 2004-04-28 | 2007-05-23 | 湖南正清制药集团股份有限公司 | Pharmaceutical composition with sustained release function and its preparing process |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1186668A (en) * | 1996-12-31 | 1998-07-08 | 四川太极制药有限公司 | Sinomenine hydrocloride preparation and its preparing process |
-
1998
- 1998-12-24 CN CN98125657A patent/CN1076604C/en not_active Expired - Lifetime
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1332669C (en) * | 2004-12-13 | 2007-08-22 | 北京正大绿洲医药科技有限公司 | Dripping pills for reducing swelling and easing pain and its preparing method |
| CN101375849B (en) * | 2007-08-27 | 2011-01-19 | 湖南正清制药集团股份有限公司 | Novel dosage form of sinomenine medicament or hydrochlorate thereof and preparation technique thereof |
| CN104906477A (en) * | 2015-06-16 | 2015-09-16 | 中山火炬职业技术学院 | Preparation method for stemona total alkaloid sustained-release tablets |
| CN104906477B (en) * | 2015-06-16 | 2019-03-29 | 中山火炬职业技术学院 | A kind of preparation method of total alkaloids of sessile stemona root sustained release tablets |
| CN109364077A (en) * | 2018-10-23 | 2019-02-22 | 三峡大学 | Application of the cucoline on the drug of preparation treatment rheumatoid arthritis |
| CN112494449A (en) * | 2020-04-29 | 2021-03-16 | 湖南正清制药集团股份有限公司 | Sinomenine hydrochloride sustained release agent prepared by inorganic solvent |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1076604C (en) | 2001-12-26 |
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Granted publication date: 20011226 |
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