CN107982268A - A kind of tolvaptan preparation and its application - Google Patents
A kind of tolvaptan preparation and its application Download PDFInfo
- Publication number
- CN107982268A CN107982268A CN201711275703.5A CN201711275703A CN107982268A CN 107982268 A CN107982268 A CN 107982268A CN 201711275703 A CN201711275703 A CN 201711275703A CN 107982268 A CN107982268 A CN 107982268A
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- China
- Prior art keywords
- tolvaptan
- purposes
- content
- composition
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- 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.)
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
Abstract
The invention discloses a kind of tolvaptan preparation and its application, it is by tolvaptan, lactose, microcrystalline cellulose and pharmaceutically acceptable carrier is prepared.The preferable tolvaptan preparation of mobility, stability, dissolution rate can be obtained, so as to be adapted to industrialized production.The drug regimen of the present invention, reasonable mixture ratio, can produce the effect of fine with rapid delivery of pharmaceuticals to the illness.
Description
Technical field
The present invention relates to the purposes that tolvaptan is used to prepare medicine, is suitable for oral tablet and glue in particular for preparing
Wafer.
Background technology
Tolvaptan is to develop non-peptides selectivity antidiuretic hormone V2 receptor antagonists by Otsuka companies, 2009 5
Moon FDA approval tolvaptan piece（Tolvaptan, Samsca）Hyponatremia is treated, is uniquely to be approved to treat the oral type of the disease
Selective vasopressin antagonists.It is mainly used for comprehensive by congestive heart failure, hepatic sclerosis and antidiuretic hormone secretion deficiency to treat
Hyponatremia caused by simulator sickness.The multinomial randomized clinical control study for being used for CHF treatments for this product reported in recent years carries
Show, oral tolvaptan can raise Na ion concentration in blood plasma, help unnecessary moisture to be discharged from urine, can substantially mitigate trouble
Person's weight and oedema, and blood electrolyte balance is not destroyed.Tolvaptan better tolerance, is not necessarily limited the intake of water in treatment.With
Being approved for tolvaptan piece, a kind of doctor's new selections again more to treatment hyponatremia.【Products characteristics】Tolvaptan is
Uniquely it is approved to treat the oral type selectivity vasopressin antagonists of the disease, diuresis is strong, and without the increasing of electrolyte excretion
Add, available for treating various edema diseases, hyponatremia and patients with heart failure.Research is found, when Na ion concentration drops in blood plasma
When low, in order to keep the Na ion concentration of intraor extracellular to balance, extracellular liquid will enter into the cell, this like cell will
Swelling.When brain cell swelling, the symptom that may result in various hyponatremia occurs.Including dizzy, weak, headache, nausea, consciousness
Entanglement and consciousness decrement and generation of fainting from fear.Serious hyponatremia can cause stupor and death, and tolvaptan piece is in weight at present
Spend in low blood sodium patient also without corresponding research.Tolvaptan piece can raise Na ion concentration in blood plasma, help unnecessary water
Divide and discharged from urine.In clinical studies, this product is compared with placebo, hence it is evident that increases the Na ion concentration in patients blood plasma.
The black surround warning of tolvaptan piece must take for patient in the hospital of the close monitoring of concentration of serum sodium.Because concentration of serum sodium is such as
Fruit is elevated too fast will to cause serious Osmotic Demyelination Syndrome to occur.Tolvaptan is non-peptide by the exploitation of Otsuka companies
Class AVP2 receptor antagonists, it is only necessary to 1 times a day take orally.Report in recent years it is multinomial for this product be used for CHF treatments it is clinical with
Machine comparative study is prompted, and oral tolvaptan can substantially mitigate weight in patients and oedema, and does not destroy blood electrolyte balance, and
The concurrent low blood sodium of CHF patient can effectively be raised.Tolvaptan better tolerance, is not necessarily limited the intake of water in treatment.It is common not
Good reaction is dry, thirsty sense, dizzy, nauseous, low blood pressure etc..The medicine lists in the U.S., and price is every（15mg）500 is beautiful
Gold.
The content of the invention
The present invention relates to the pharmaceutical composition containing tolvaptan.
The invention further relates to the pharmaceutical composition containing tolvaptan Yu the oral administration of other drugs active material.The group
Compound is obtained by the surface for making the particle of pharmaceutically active substance adhere to carrier matrix.Pharmaceutically active substance calmness is set to exist
Method on carrier matrix is to make the aggregation of active material/carrier substrate particles be reduced at least.
The present invention relates to the pharmaceutical composition containing about 1mg--150 mg tolvaptans, said composition is administered three times a day
For treating gastric ulcer, the preferable pharmaceutical composition of duodenal ulcer contains the tolvaptan of about 5mg--50 mg, most preferably
Pharmaceutical composition contain the tolvaptan of about 10mg--50 mg.
Above-mentioned Tolvaptan medicinal composition for being administered daily less regular can also be administered some patients.This
Kind of maintaining treatment scheme include daily deficiency once take Tolvaptan medicinal composition.For example, administration one in every three or four days
It is secondary that just it is enough.
The Tolvaptan medicinal composition of the present invention can be configured to the form through any appropriate approach administration, such as preferably
It can be tablet, capsule, particle or powder type that combination, which is administered orally,.According to method well known in the art, tolvaptan medicine
Composition can also be configured to the form of non-gastrointestinal, rectum or via intranasal application administration.This kind of preparation may include pharmaceutically acceptable excipient, institute
Stating excipient includes common filler, glidant, lubricant, disintegrant, adhesive etc. in this based composition.The present invention also wraps
Include sustained release preparation.
Tablet and capsule preparations containing about 1mg -150mg tolvaptans can be prepared by the following method, to ensure
The efficient of product and good uniformity.Composition will be prepared on the surface of tolvaptan calmness to carrier matrix first.
The step is completed by following operation：The solution of tolvaptan and adhesive material is formed, is then kept in carrier substrate particles
The solution is applied while movement in a manner of spraying.Control condition is so that the aggregation of particle is preferably minimized.
Any other component that will be included after drying in particle and composition, such as disintegrant/glidant/lubricant mix
Close.Then obtained powder is pressed into piece or is filled into capsule.
Preferred solvent in the above method is the ethanol of water or various concentrations.
Adhesive material is preferably the polymer with high-consistency.Suitable material includes povidone, methylcellulose, hydroxyl
Methylcellulose, hypromellose, hydroxypropyl cellulose, hydroxyethyl cellulose, povidone, hydroxymethyl cellulose are preferred
's.The content of adhesive material is preferably the about 1%-- about 10% of composition gross weight in whole composition（Weight）.
The disintegrant content that whole composition includes is preferably the about 1%--7% of composition gross weight.Suitable disintegrant includes
Crospovidone, cross-linked carboxymethyl cellulose, low-substituted hydroxypropyl methylcellulose, Explotab, pregelatinized starch and corn
Starch, crospovidone are preferable.
The lubricant content that whole composition includes is preferably the about 1%--5% of composition gross weight.Suitable lubricant includes
Superfine silica gel powder, magnesium stearate, stearic acid, stearyl fumarate and NaLS, superfine silica gel powder, magnesium stearate are preferred
's.
Embodiment
The following example illustrates the tolvaptan composition of the present invention
Embodiment 1
5 milligrams of tolvaptan capsules are prepared using the above method
| Component | Measure %（W/w） | Amount/grain |
| Tolvaptan | 3.3 | 5mg |
| Microcrystalline cellulose | 26.7 | 40 mg |
| Lactose | 46.7 | 70 mg |
| Povidone | 6.7 | 10 mg |
| Low-substituted hydroxypropyl methylcellulose | 13.3 | 20.0mg |
| Magnesium stearate | 1.3 | 2.0mg |
| Silica | 2 | 3.0 mg |
| Purified water | In right amount | In right amount |
| Amount to | 100.00 | 150.00 mg |
Embodiment 2
10 milligrams of tolvaptan capsules are prepared using the above method
| Component | Measure %（W/w） | Amount/grain |
| Tolvaptan | 5.5 | 10 mg |
| Microcrystalline cellulose | 27.5 | 50 mg |
| Lactose | 54.9 | 100 mg |
| Povidone | 5.5 | 10mg |
| Crospovidone | 5.5 | 10mg |
| Silica | 1.1 | 2.00mg |
| Purified water | In right amount | In right amount |
| Amount to | 100.00 | 182.00 mg |
Embodiment 3
20 milligrams of tolvaptan capsules are prepared using the above method
| Component | Measure %（W/w） | Amount/piece |
| Tolvaptan | 9.4 | 20 mg |
| Microcrystalline cellulose | 23.6 | 50 mg |
| Lactose | 47.2 | 100 mg |
| Povidone | 4.7 | 10 mg |
| Crospovidone | 9.4 | 20 mg |
| Low-substituted hydroxypropyl methylcellulose | 4.7 | 10 mg |
| Magnesium stearate | 0.9 | 2 mg |
| Purified water | In right amount | In right amount |
| Amount to | 100.00 | 212.0 mg |
Embodiment 4
30 milligrams of tolvaptan capsules are prepared using the above method
| Component | Measure %（W/w） | Amount/piece |
| Tolvaptan | 14 | 1 mg |
| Microcrystalline cellulose | 23.4 | 50 mg |
| Lactose | 46.7 | 70 mg |
| Povidone | 4.7 | 10 mg |
| Low-substituted hydroxypropyl methylcellulose | 9.3 | 20 mg |
| Magnesium stearate | 0.9 | 2 mg |
| Silica | 0.9 | 2 mg |
| Purified water | In right amount | In right amount |
| Amount to | 100.00 | 183.0 mg |
Embodiment 5
10 milligrams of tolvaptan pieces are prepared using the above method
| Component | Measure %（W/w） | Amount/grain |
| Tolvaptan | 5.5 | 10 mg |
| Microcrystalline cellulose | 27.5 | 50 mg |
| Lactose | 54.9 | 100 mg |
| Povidone | 5.5 | 10mg |
| Crospovidone | 5.5 | 10mg |
| Silica | 1.1 | 2.00mg |
| Purified water | In right amount | In right amount |
| Amount to | 100.00 | 182.00 mg |
Embodiment 6
20 milligrams of tolvaptan pieces are prepared using the above method
| Component | Measure %（W/w） | Amount/piece |
| Tolvaptan | 9.4 | 20 mg |
| Microcrystalline cellulose | 23.6 | 50 mg |
| Lactose | 47.2 | 100 mg |
| Povidone | 4.7 | 10 mg |
| Crospovidone | 9.4 | 20 mg |
| Low-substituted hydroxypropyl methylcellulose | 4.7 | 10 mg |
| Magnesium stearate | 0.9 | 2 mg |
| Purified water | In right amount | In right amount |
| Amount to | 100.00 | 212.0 mg |
Claims (9)
1. tolvaptan is used for the purposes of the pharmaceutical composition of tablet or capsule form, wherein described pharmaceutical composition contains
The tolvaptan of 1mg -150mg.
2. the purposes of claim 1, wherein the content of the tolvaptan is 1mg -50mg.
3. the purposes of claim 1, wherein the content of the tolvaptan is 1mg -30mg.
4. the purposes of claim 3, wherein the content of the tolvaptan is 5mg.
5. the purposes of claim 3, wherein the content of the tolvaptan is 10mg.
6. the purposes of claim 3, wherein the content of the tolvaptan is 20mg.
7. the purposes of claim 3, wherein the content of the tolvaptan is 1mg.
8. the purposes of claim 1, the composition therein contains one or more other drugs active materials.
9. the purposes of claims 1, wherein the filler is selected from lactose, xylitol, microcrystalline cellulose, dextrin, sweet dew
Alcohol, sorbierite, sucrose, starch, pregelatinized starch, glucose, calcium phosphate, calcium monohydrogen phosphate, calcium carbonate, and its mixture, and
The tolvaptan is to be sticked together by the polymerization emplastic with enough stickiness on the filler.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711275703.5A CN107982268A (en) | 2017-12-06 | 2017-12-06 | A kind of tolvaptan preparation and its application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711275703.5A CN107982268A (en) | 2017-12-06 | 2017-12-06 | A kind of tolvaptan preparation and its application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107982268A true CN107982268A (en) | 2018-05-04 |
Family
ID=62036438
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711275703.5A Pending CN107982268A (en) | 2017-12-06 | 2017-12-06 | A kind of tolvaptan preparation and its application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107982268A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109646391A (en) * | 2018-12-20 | 2019-04-19 | 常州市阳光药业有限公司 | Tolvaptan sustained release preparation and preparation method thereof |
| CN112121051A (en) * | 2020-09-30 | 2020-12-25 | 郑州大学 | Application of mozavatan in preparation of anti-digestive tract tumor medicine |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102512393A (en) * | 2011-12-19 | 2012-06-27 | 浙江华海药业股份有限公司 | Oral disintegrated tablet containing tolvaptan |
| CN106880611A (en) * | 2015-12-16 | 2017-06-23 | 天津泰普药品科技发展有限公司 | A kind of tolvaptan preparation of tolvaptan and water soluble adjuvant containing micronizing |
| CN107432867A (en) * | 2016-05-26 | 2017-12-05 | 天津市汉康医药生物技术有限公司 | A kind of tolvaptan piece |
-
2017
- 2017-12-06 CN CN201711275703.5A patent/CN107982268A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102512393A (en) * | 2011-12-19 | 2012-06-27 | 浙江华海药业股份有限公司 | Oral disintegrated tablet containing tolvaptan |
| CN106880611A (en) * | 2015-12-16 | 2017-06-23 | 天津泰普药品科技发展有限公司 | A kind of tolvaptan preparation of tolvaptan and water soluble adjuvant containing micronizing |
| CN107432867A (en) * | 2016-05-26 | 2017-12-05 | 天津市汉康医药生物技术有限公司 | A kind of tolvaptan piece |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109646391A (en) * | 2018-12-20 | 2019-04-19 | 常州市阳光药业有限公司 | Tolvaptan sustained release preparation and preparation method thereof |
| CN112121051A (en) * | 2020-09-30 | 2020-12-25 | 郑州大学 | Application of mozavatan in preparation of anti-digestive tract tumor medicine |
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| PB01 | Publication | ||
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Application publication date: 20180504 |