CN106692082A - Rolapitant pharmaceutical composition and preparation method thereof - Google Patents
Rolapitant pharmaceutical composition and preparation method thereof Download PDFInfo
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- CN106692082A CN106692082A CN201510773597.8A CN201510773597A CN106692082A CN 106692082 A CN106692082 A CN 106692082A CN 201510773597 A CN201510773597 A CN 201510773597A CN 106692082 A CN106692082 A CN 106692082A
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- smooth
- roller
- pharmaceutical composition
- lactose
- magnesium stearate
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Abstract
The invention discloses rolapitant pharmaceutical composition with high bioavailability. The rolapitant pharmaceutical composition is prepared from rolapitant, steviosin, lactose, microcrystalline cellulose and magnesium stearate and is characterized in that the weight ratio of rolapitant to steviosin to lactose is 1:0.5:2. The rolapitant pharmaceutical composition has good stability, has more remarkable advantages in increase of product yield, reduction of the cost, industrialization and better application in clinic and can effectively improve the dissolvability. The bioavailability is notably improved. The pharmaceutical composition can be used for treating nausea and vomit caused by chemotherapy.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to smooth pharmaceutical composition of roller and preparation method thereof.
Background technology
The nausea and vomiting caused by chemotherapy（CINV）It is clinically very common, such as control it is bad will increase physician office visits, reduce Compliance With Chemotherapy, reduce chemotherapy, or even patient is refused further chemotherapy etc., have a strong impact on the quality of life and antineoplaston effect of patient.Therefore, the prevention and treatment of CINV are extremely important.CINV is the n and V caused by chemotherapy, and often 3 classes are divided into according to the time that vomiting occurs, acute（Occur within after chemotherapy starts first 24 hours）, Delayed onset（Occur at least 24 hours after chemotherapy starts）With expected property（Conditioned reflex, before betiding chemotherapy）.The drug factors such as species, the dosage and administration of chemotherapeutics are the influence most important determinants of CINV.
Tachykinin, such as P materials（SP）It is the peptide ligand of neurokinin receptor, neurokinin receptor, such as NK-1, NK-2, NK-3 participate in many biochemical processes.These three acceptors are G G-protein linked receptors, and wherein NK-1 acceptors distribution is most wide, also mostly important, only a few cell expression NK-2 acceptors and NK-3 acceptors.Wherein selective highest of the NK-1 acceptors to SP, binding ability is most strong, maincenter and peripheral nervous system are widely present in, are distributed in neuron, brain stem, vascular endothelial cell, muscle, intestines and stomach, urogenital tract, lung tissue, thyroid gland and various immunocytes.After NK-1 acceptors are with the SP combinations of its part, it is associated with phosphatidylinositol diphosphate second messenger system by G albumen, and the calcium channel on film is acted on by InsP3, cause the depolarising of film potential and the change of protein kinase activity, and then participate in pain and stress signal, played in inflammatory reaction and smooth muscle contraction process complexity physiological function.
" NK-1 " receptor antagonist has been shown as useful therapeutic agent, such as in treatment pain, inflammation, antimigraine, vomiting and grieved stimulation.The receptor antagonist of neurokinin 1（NK1RA）With antidepression, effect antianxity, and there is good therapeutic effect to the nausea and vomiting that chemotherapy causes；Being shared with other antiemetics can better control over Delayed emesis and postoperative vomiting.Go deep into to P materials and NK-1 acceptor researchs, the first granted NK-1 receptor antagonist pharmaceuticals Aprepitants for clinic are the Nausea and vomiting for preventing and treating chemotherapy induction within 2003（CINV）There is provided strong weapon.NEPA is first compound antiemetic, contains a kind of new high selectivity NK1RA class medicines（How appropriate pyrrole is smooth）With a kind of 5-HT3RA classes medicine（Palonosetron）.
On September 1st, 2015, FDA approval listing new drug rolapitant- rollers are smooth, for the related n and V of Prophylactic chemotherapy.It is a kind of oral NK1RA inhibitor of new high selectivity that roller pyrrole is smooth, and its plasma half-life is up to 180h.Identical with NEPA, the smooth tolerance of roller pyrrole is good, and it is consistent with expection with the security that antiemetic class medicine and chemotherapeutics are combined.From unlike aprepitant and NEPA, roller pyrrole is smooth can not to be induced or suppress CYP3A4.Therefore, when combination smooth with roller pyrrole, CYP3A4 is passed through without adjustment（Including DEX）The drug dose of metabolism.This may benefit some patientss, because drug interaction can be avoided well.
The present inventor has been surprisingly found that by studying for a long period of time, using the smooth pharmaceutical composition of roller prepared by special auxiliary material, special process, reliable in quality, dissolution rate is fast, not only successfully solves that roller is smooth to be not easy to Industrialization, and reduce production cost, it is easy to implement, remarkable in economical benefits.
The content of the invention
The first object of the present invention is to provide a kind of smooth pharmaceutical composition of roller, and the smooth pharmaceutical composition of the roller to good stability, to improving product yield, realize industrialization, be preferably applied to clinic, with more obvious advantage by reduces cost.
The second object of the present invention is the preparation method for providing the smooth pharmaceutical composition of roller of the present invention, and the method is simple and easy to apply, the smooth pharmaceutical composition of prepared roller, steady quality reliability.
To realize two purposes of the invention, the present invention is adopted the following technical scheme that：
A kind of smooth pharmaceutical composition of roller, by roller is smooth, Steviosin, lactose, microcrystalline cellulose, magnesium stearate are constituted, it is characterised in that its middle roller is smooth：Steviosin：The weight ratio of lactose is 1:0.5:2.
A kind of smooth pharmaceutical composition of roller, the smooth pharmaceutical composition of roller described in every 1000, its formula composition be：
The smooth 45-90g of roller
Steviosin
6-30g
Lactose 50-200g
Microcrystalline cellulose 50-75g
Magnesium stearate 1-2g.
The smooth pharmaceutical composition of roller of the present invention is adopted and prepared with the following method：
1) prepare：Microcrystalline cellulose, lactose, magnesium stearate are dried 3 hours under the conditions of 80 DEG C, it is standby；
2) it is the Steviosin and roller of recipe quantity is smooth, put in container, after being well mixed, granularity is ground in 75 ± 10um, it is standby；
3) by 2）It is well mixed with the microcrystalline cellulose of recipe quantity, magnesium stearate；
4) compressing tablet：Regulation suitable stiff and piece weight, carry out compressing tablet；
5) pack：Packed using aluminium-plastic bubble plate packing machine；
6) be put in storage.
The smooth pharmaceutical composition of traditional roller, high to production equipment requirement, uniformity of dosage units otherness is big, and quality cannot ensure.
The present inventor has found that when the smooth pharmaceutical composition of roller is above-mentioned formula and preparation technology, described pharmaceutical composition uniformity of dosage units otherness is small, and quality is effectively ensured by substantial amounts of experimental study.
Compared with prior art, the invention has the advantages that：
1) the smooth composition of new roller provided by the present invention thoroughly solves uniformity of dosage units in the smooth production process of roller and differs greatly problem.
2) for improving the yield of the product, reducing production cost, be preferably applied to clinical treatment has very big help to the smooth pharmaceutical composition of roller provided by the present invention.
3) the smooth composition of new roller provided by the present invention is through industrialized production and study on the stability, it was demonstrated that product quality stabilization, through pharmacology, toxicological test, solution is non-stimulated to blood vessel, without allergic reaction, also without haemolysis, to human body fanout free region.
4) preparation method of the smooth composition of new roller provided by the present invention, the method is simple and easy to apply, the smooth pharmaceutical composition reliable in quality of prepared roller.
5) the smooth composition of new roller provided by the present invention, dissolution is fast, and with bioavilability higher, being rapidly reached needs concentration.
Specific embodiment
The present invention is described in further detail with reference to embodiment
Comparative example
The smooth pharmaceutical composition of roller described in every 1000, its formula composition be：
Roller is smooth
45g
Steviosin 60
Lactose 90g
Microcrystalline cellulose
50g
Magnesium stearate 2g.
Preparation technology：
1) prepare：Microcrystalline cellulose, lactose, magnesium stearate are dried 3 hours under the conditions of 80 DEG C, it is standby；
2) it is the Steviosin and roller of recipe quantity is smooth, put in container, after being well mixed, granularity is ground in 75 ± 10um, it is standby；
3) by 2）It is well mixed with the microcrystalline cellulose of recipe quantity, magnesium stearate；
4) compressing tablet：Regulation suitable stiff and piece weight, carry out compressing tablet；
5) pack：Packed using aluminium-plastic bubble plate packing machine；
6) be put in storage.
Embodiment
1
The smooth pharmaceutical composition of roller described in every 1000, its formula composition be：
Roller is smooth
45g
Steviosin 22.5g
Lactose 90g
Microcrystalline cellulose
50g
Magnesium stearate 2g.
Preparation technology：
1) prepare：Microcrystalline cellulose, lactose, magnesium stearate are dried 3 hours under the conditions of 80 DEG C, it is standby；
2) it is the Steviosin and roller of recipe quantity is smooth, put in container, after being well mixed, granularity is ground in 75 ± 10um, it is standby；
3) by 2）It is well mixed with the microcrystalline cellulose of recipe quantity, magnesium stearate；
4) compressing tablet：Regulation suitable stiff and piece weight, carry out compressing tablet；
5) pack：Packed using aluminium-plastic bubble plate packing machine；
6) be put in storage.
Embodiment
2
The smooth pharmaceutical composition of roller described in every 1000, its formula composition be：
Roller is smooth
90g
Steviosin 45g
Lactose 180g
Microcrystalline cellulose
65g
Magnesium stearate 2g.
Preparation technology：With embodiment 1.
Test example
1
The test example is to investigate the stability of the smooth composition of roller provided by the present invention.
The accelerated test of the smooth pharmaceutical composition of roller
Method according to the embodiment of the present invention 1 prepares three batches of smooth pharmaceutical compositions of roller（Lot number is respectively 1005001,1005002,1005003）According to commercially available back, at 40 DEG C ± 2 DEG C, the condition of RH75% ± 5% is placed 6 months, and period sampled respectively at the 1st, 2,3,6 months, was detected according to stability inspection project, and compare with 0 day data.
1st, project high spot reviews is investigated：Proterties, about material and content.
2nd, accelerated test result
Above conclusion (of pressure testing) can be seen that：This product places 6 months every Testing index no significant differences, good stability compared with 0 month under the conditions of accelerated test.
Claims (5)
1. the smooth pharmaceutical composition of a kind of roller, by roller is smooth, Steviosin, lactose, microcrystalline cellulose, magnesium stearate are constituted, it is characterised in that its middle roller is smooth：Steviosin：The weight ratio of lactose is 1:0.5:2.
2. the smooth pharmaceutical composition of roller according to claim 1, it is characterised in that the smooth pharmaceutical composition of roller described in it, every 1000 its formula compositions are：
The smooth 45-90g of roller
Steviosin
6-30g
Lactose 50-200g
Microcrystalline cellulose 50-75g
Magnesium stearate 1-2g.
3. the smooth pharmaceutical composition of roller according to claim 2, it is characterised in that the smooth pharmaceutical composition of roller described in it, every 1000 its formula compositions are：
Roller is smooth
45g
Betadex 22.5g
Lactose 90g
Microcrystalline cellulose
50g
Magnesium stearate 2g.
4. the smooth pharmaceutical composition of roller according to claim 2, it is characterised in that the smooth pharmaceutical composition of roller described in it, every 1000 its formula compositions are：
Roller is smooth
90g
Betadex 45g
Lactose 180g
Microcrystalline cellulose
65g
Magnesium stearate 2g.
5. the preparation method of the smooth pharmaceutical composition of roller according to claim 1, it is characterised in that the method comprises the following steps：
1) prepare：Microcrystalline cellulose, lactose, magnesium stearate are dried 3 hours under the conditions of 80 DEG C, it is standby；2) it is the Steviosin and roller of recipe quantity is smooth, put in container, after being well mixed, granularity is ground in 75 ± 10um, it is standby；3) by 2）It is well mixed with the microcrystalline cellulose of recipe quantity, magnesium stearate；4) compressing tablet：Regulation suitable stiff and piece weight, carry out compressing tablet；
5) pack：Packed using aluminium-plastic bubble plate packing machine；6) be put in storage.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510773597.8A CN106692082A (en) | 2015-11-13 | 2015-11-13 | Rolapitant pharmaceutical composition and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510773597.8A CN106692082A (en) | 2015-11-13 | 2015-11-13 | Rolapitant pharmaceutical composition and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106692082A true CN106692082A (en) | 2017-05-24 |
Family
ID=58922959
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510773597.8A Pending CN106692082A (en) | 2015-11-13 | 2015-11-13 | Rolapitant pharmaceutical composition and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107823207A (en) * | 2017-12-16 | 2018-03-23 | 姚蕾 | A kind of combination of oral medication for treating atherosclerosis |
| CN107951885A (en) * | 2017-12-16 | 2018-04-24 | 侯瑞玲 | A kind of combination of oral medication for treating capillary leak syndrome |
| CN115282147A (en) * | 2022-08-31 | 2022-11-04 | 深圳市宝安区人民医院 | Application of Lapidan or/and Lapidan derivative in anti-mycobacterium tuberculosis drugs |
-
2015
- 2015-11-13 CN CN201510773597.8A patent/CN106692082A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107823207A (en) * | 2017-12-16 | 2018-03-23 | 姚蕾 | A kind of combination of oral medication for treating atherosclerosis |
| CN107951885A (en) * | 2017-12-16 | 2018-04-24 | 侯瑞玲 | A kind of combination of oral medication for treating capillary leak syndrome |
| CN107823207B (en) * | 2017-12-16 | 2018-07-24 | 姚蕾 | A kind of combination of oral medication for treating atherosclerosis |
| CN107951885B (en) * | 2017-12-16 | 2018-09-18 | 侯瑞玲 | A kind of combination of oral medication for treating capillary leak syndrome |
| CN115282147A (en) * | 2022-08-31 | 2022-11-04 | 深圳市宝安区人民医院 | Application of Lapidan or/and Lapidan derivative in anti-mycobacterium tuberculosis drugs |
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| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170524 |
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| WD01 | Invention patent application deemed withdrawn after publication |