CN105496970A - Composition containing linagliptin and preparation method thereof - Google Patents
Composition containing linagliptin and preparation method thereof Download PDFInfo
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- CN105496970A CN105496970A CN201510955848.4A CN201510955848A CN105496970A CN 105496970 A CN105496970 A CN 105496970A CN 201510955848 A CN201510955848 A CN 201510955848A CN 105496970 A CN105496970 A CN 105496970A
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- pharmaceutical composition
- pharmaceutic adjuvant
- linagliptin
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- preparation technology
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
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- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
- A61K9/1676—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface having a drug-free core with discrete complete coating layer containing drug
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A linagliptin DDP-4 inhibitor is used for treating type II diabetes mellitus, but the solubility (0.9 mg/ml) of the linagliptin DDP-4 inhibitor is extremely low in water. The invention discloses a pharmaceutical composition containing linagliptin and a preparation method thereof. The composition obtained through the technology is prepared into an acceptable drug dosage form, and therefore the dissolution rate of the linagliptin can be obviously improved.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of composition and method of making the same containing favourable Ge Lieting.
Background knowledge
Diabetes are a kind of chronic diseases perplexing the whole world, about there are 2.3 hundred million patients in the current whole world, estimate that diabetic number in 2025 will be increased to 300,000,000, the many sequela at 35 ~ 40 years old of type 2 diabetes mellitus, account for diabetic more than 90%, along with the sickness rate in growth in the living standard child also has the trend of rising in recent years.
Along with aged tendency of population trend and living-pattern preservation, increase year by year in China with nutrition and the closely-related type 2 diabetes mellitus patient that moves, according to the literature, China's diabetics has reached 9,300 ten thousand, wherein, based on type 2 diabetes mellitus patient.Therefore, for the glycemic control of type 2 diabetes mellitus patient, quality of making the life better, reduce long term complication and extend existence and become the problem that society shows great attention to.Find the research direction that how effective medicine and means are treating diabetes fields.
DPP-4 inhibitor is also called Ge Lieting class, is a up-to-date paradiabetes medicine.This kind of medicine can improve the insulin secretion of pancreatic beta cell, can suppress the glicentin secretion of α cell simultaneously thus reduce glycogen to export.Ge Lieting class can suppress the decomposition of GLP-1 thus improve the level of GLP-1 at blood plasma, the secretion of insulin and the secretion of suppression glicentin when this can promote to take food.Because these medicines improve insulin secretion when blood glucose raises, therefore can with the medicine of different mechanisms as euglycemic agent or metformin with the use of.In fact, adopt Ge Lieting class medicine list medicine in a large number and improve empty stomach and level of postprandial blood sugar with verified its of the clinical trial of other hypoglycemic medicine conbined usage, improve β cell function, improve the effects such as HbA1c level.
The ratio that China's diabetics merges hepatic and renal function damage is higher, and desirable treating diabetes takes into account blood glucose and multiple safety factors, comprises Liver and kidney safety.Comprise most of medicine of orally-taken blood sugar reducing medicine at present, all pass through liver metabolism and kidney removing.After hepatic and renal function is impaired, the adverse effect such as drug interaction and hypoglycemia occurrence risk all can correspondingly increase.The consciousness that diabetes management will have long-term risk to control, just payes attention to prevention impaired renal function as early stage, selects the medicine without Liver and kidney metabolism as far as possible.
Li Gelieting has unique pharmacological characteristic, it is unique few DPP-4 inhibitor (the ratio <5% through renal excretion) of being discharged by kidney, mainly excreted by bile and intestinal with original shape, no matter the full patient of general patient and Liver and kidney all can apply, without the need to adjusting dosage and additionally monitoring hepatic and renal function during application.
It is reported, Li Gelieting is through Chinese CFDA, U.S. FDA and European Union EMA and ratifies, uniquely in type 2 diabetes mellitus patient without the need to carrying out the DPP-4 inhibitor of dose titration according to hepatic and renal function; Also be that unique acquisition " Type 2 Diabetes In China guideline of prevention and treatment " is recommended to be used for different hepatic and renal function status patients without the need to adjusting the DPP-4 inhibitor of dosage.
Li Gelieting is that the one of BOEHRINGERINGELHEIM company research and development is potent, selective d PP-4 inhibitor, obtain U.S. FDA approval listing in May, 2011, in June, 2011, listing is got permission in Europe, on August 26th, 2015, carry out by Boehringer Ingelheim-gift the Li Gelieting that pharmacy diabetes alliance releases jointly
one line list medicine and two wires duplex indication obtain state food pharmaceuticals administration general bureau (CFDA) approval listing, become China's DPP-4 inhibitor that at present unique indication is the most complete (single medicine/combine with metformin/with metformin and sulfonylurea drugs conbined usage), for vast diabetics provides a kind of potent, safe and easy therapeutic scheme.
8-[(3R)-3-amino-piperidino]-7-(2-butyne base-1)-3,7-dihydro-3-methyl isophthalic acid-[(4-methyl-2-quinazolyl) methyl]-1H-purine-2,6-diketone (Li Gelieting).
Summary of the invention
The invention provides a kind of pharmaceutical composition containing favourable Ge Lieting, its existing forms is solid state; This pharmaceutical composition is the stable form of a kind of Li Gelieting, and stripping is rapid.This pharmaceutical composition can be used for the acceptable solid pharmaceutical preparations such as granule, capsule and tablet.
Pharmaceutical composition of the present invention, wherein Li Gelieting is as active component, and acceptable drug excipient: plant core, binding agent, solubilizing agent, correctives, solvent etc.
Its kind of core be Parteck deltaM, lactose 316, Su Lixin one or more, preferred Parteck deltaM, lactose 316.Binding agent is one or more in hyprolose, hypromellose, polyvidone, starch slurry, dextrin, preferred hyprolose, hypromellose.Solubilizing agent is one or more in poloxamer, glycerol, Tween 80, sodium lauryl sulphate, preferred poloxamer, glycerol.For covering the abnormal flavour of active component, need increase correctives, correctives is essence, saccharin sodium, aspartame, Mentholum, preferred aspartame, Mentholum.Solvent is water, ethanol, isopropyl alcohol wherein one or more or the mixed solvent of wherein both different proportions, preferred water, ethanol.
For obtained stable pharmaceutical composition, and can obtain stripping compositions rapidly, preparation technology is fluidized bed granulation technique simultaneously; Be dissolved in solvent by active component and remaining drug excipient, be sprayed on kind of core, dry, screening, the particle size range of obtained pharmaceutical composition is 0.1mm ~ 0.3mm, the preferably pharmaceutical composition of 0.15 ~ 0.25mm.
This pharmaceutical composition has following features: dissolve rapidly, active component is stablized, and mobility is good, good mouthfeel, is convenient to prepare other solid pharmaceutical dosage formulations.
Accompanying drawing explanation
Fig. 1 is that embodiment sample and former triturate stripping curve contrast.
Detailed description of the invention
Next the present invention is further elaborated in conjunction with the embodiments, but the invention process is not limited thereto.
Embodiment 1
Table 1
Preparation technology:
1. take the part hyprolose solution being prepared into suitable concn soluble in water, be sprayed at Parteck deltaM surface, heat drying;
2. Li Gelieting is dissolved in ethanol, hyprolose (surplus), poloxamer, aspartame are soluble in water, and both mixing, are sprayed at the particle surface of step " 1 " gained;
3. in step " 2 ", gained heating particles is dry, to obtain final product.
Embodiment 2
Table 2
Preparation technology:
1. take the granule prepared, mix homogeneously with lactose monohydrate;
2. step " 1 " gained mixture is added silicon dioxide mix homogeneously;
3., by gained mixture subpackage in step " 2 ", to obtain final product.
Embodiment 3
Table 3
Preparation technology:
1. take the granule prepared, mix homogeneously with lactose monohydrate, polyvinylpolypyrrolidone;
2. step " 1 " gained mixture is added magnesium stearate mix homogeneously;
3., by gained mixture tabletting in step " 2 ", to obtain final product.
Carry out stripping curve investigation to sample prepared by embodiment 1,2,3, stripping condition determination is: paddle method, and rotating speed is 50rpm, and dissolution medium is pH1.0 acid solution, and stripping volume is 900ml;
Table 4
Result shows, the product that the compositions adopting this patent to provide and preparation technology obtain, and prepares sample have a clear superiority in stripping than common process; Quick release, oral absorption is rapid.
Claims (8)
1. Yi Zhong Li Gelieting pharmaceutical composition, is characterized in that containing favourable Ge Lieting and pharmaceutically acceptable pharmaceutic adjuvant.
2. pharmaceutical composition according to claim 1, is characterized in that preparation technology is fluid bed preparation technology.
3. pharmaceutical composition according to claim 1, is characterized in that the particle size range of this pharmaceutical composition is 0.1mm ~ 0.3mm.
4. pharmaceutical composition according to claim 1, is characterized in that pharmaceutically acceptable pharmaceutic adjuvant has kind of a core, binding agent, correctives and solvent.
5. pharmaceutic adjuvant according to claim 4, it is characterized in that kind of core be selected from Parteck deltaM, lactose 316, Su Lixin one or more.
6. pharmaceutic adjuvant according to claim 4, is characterized in that one or more that binding agent is selected from hyprolose, hypromellose, polyvidone, starch slurry, dextrin.
7. pharmaceutic adjuvant according to claim 4, is characterized in that correctives is selected from essence, saccharin sodium, aspartame, Mentholum, one or more in preferred aspartame, Mentholum.
8. pharmaceutic adjuvant according to claim 4, it is characterized in that solvent be selected from water, ethanol, isopropyl alcohol wherein one or more, or its different proportion mixed solvent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510955848.4A CN105496970A (en) | 2015-12-18 | 2015-12-18 | Composition containing linagliptin and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510955848.4A CN105496970A (en) | 2015-12-18 | 2015-12-18 | Composition containing linagliptin and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105496970A true CN105496970A (en) | 2016-04-20 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510955848.4A Pending CN105496970A (en) | 2015-12-18 | 2015-12-18 | Composition containing linagliptin and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106137991A (en) * | 2016-08-01 | 2016-11-23 | 合肥远志医药科技开发有限公司 | A kind of Li Gelieting sheet method of granulating |
| CN106236754A (en) * | 2016-07-31 | 2016-12-21 | 合肥远志医药科技开发有限公司 | A kind of compositions comprising Li Gelieting active component and preparation method thereof |
Citations (5)
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|---|---|---|---|---|
| CN101500541A (en) * | 2006-08-11 | 2009-08-05 | 旭化成化学株式会社 | Process for production of spherical granule containing slightly water-soluble substance |
| US20110311594A1 (en) * | 2010-06-22 | 2011-12-22 | Shou-Chiung Chen | Controlled release compositions with reduced food effect |
| CN102670521A (en) * | 2012-05-18 | 2012-09-19 | 珠海润都制药股份有限公司 | Esomeprazole magnesium enteric-coated pellet and preparation method thereof |
| CN103391771A (en) * | 2011-03-07 | 2013-11-13 | 勃林格殷格翰国际有限公司 | Pharmaceutical compositions comprising metformin and a dpp-4 inhibitor or a sglt-2 inhibitor |
| CN104644563A (en) * | 2013-11-23 | 2015-05-27 | 天津市汉康医药生物技术有限公司 | Linagliptin composition and preparation method thereof |
-
2015
- 2015-12-18 CN CN201510955848.4A patent/CN105496970A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101500541A (en) * | 2006-08-11 | 2009-08-05 | 旭化成化学株式会社 | Process for production of spherical granule containing slightly water-soluble substance |
| US20110311594A1 (en) * | 2010-06-22 | 2011-12-22 | Shou-Chiung Chen | Controlled release compositions with reduced food effect |
| CN103391771A (en) * | 2011-03-07 | 2013-11-13 | 勃林格殷格翰国际有限公司 | Pharmaceutical compositions comprising metformin and a dpp-4 inhibitor or a sglt-2 inhibitor |
| CN102670521A (en) * | 2012-05-18 | 2012-09-19 | 珠海润都制药股份有限公司 | Esomeprazole magnesium enteric-coated pellet and preparation method thereof |
| CN104644563A (en) * | 2013-11-23 | 2015-05-27 | 天津市汉康医药生物技术有限公司 | Linagliptin composition and preparation method thereof |
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| 单利，等: "基于流化床包衣工艺的伊曲康唑速释微丸的制备和评价研究", 《中国药学杂志》 * |
| 李葆林，等: "流化床包衣技术在药物制剂中的应用现状", 《河北医科大学学报》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106236754A (en) * | 2016-07-31 | 2016-12-21 | 合肥远志医药科技开发有限公司 | A kind of compositions comprising Li Gelieting active component and preparation method thereof |
| CN106137991A (en) * | 2016-08-01 | 2016-11-23 | 合肥远志医药科技开发有限公司 | A kind of Li Gelieting sheet method of granulating |
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Application publication date: 20160420 |