WO2012064305A2 - Formulations with improved physical characteristics - Google Patents
Formulations with improved physical characteristics Download PDFInfo
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- WO2012064305A2 WO2012064305A2 PCT/TR2011/000247 TR2011000247W WO2012064305A2 WO 2012064305 A2 WO2012064305 A2 WO 2012064305A2 TR 2011000247 W TR2011000247 W TR 2011000247W WO 2012064305 A2 WO2012064305 A2 WO 2012064305A2
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Classifications
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- 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
-
- 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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
Abstract
The present invention comprises a combination of an Hl-antihistaminic and a leukotriene receptor antagonist which is effective in prevention and/or treatment of allergic and inflammatory diseases of the skin or upper and lower respiratory tracts and relieving the symptoms thereof.
Description
FORMULATIONS WITH IMPROVED PHYSICAL CHARACTERISTICS
The present invention comprises a combination of an Hi-antihistaminic and a leukotnene receptor antagonist which is effective in prevention and/or treatment of allergic and inflammatory diseases of the skin or upper and lower respiratory tracts and relieving the symptoms thereof.
Levocetirizine (Formula I), chemical name of which is 2-[2-[4-[(R)-(4- chlorophenyl)- phenyl- methyl]piperazine-l-yl] ethoxy] acetic acid, is a non-sedating, long-acting Hl- histaminic.
Formula (I)
Cetirizine was first disclosed in the patent numbered EP0058146 Al. The patent numbered GB2225321 A for preparation process of levocetirizine and the patent numbered WO9406429 Al for use of levocetirizine in treatment of allergic diseases are among the first patents related to levocetirizine which is the R-enantiomer of cetirizine.
Levocetirizine which is the R-enantiomer of cetirizine is a piperazine derivative, potent and selective HI receptor antagonist. Levocetirizine is a new antihistaminic which binds to HI receptors with high affinity, even two times higher as compared to cetirizine.
Levocetirizine has anti-allergic and anti-inflammatory activity. The studies conducted have shown that levocetirizine inhibits a comprehensive series of reactions that induce and disseminate allergic inflammation.
As for montelukast (Formula II), chemical name of which is l-[[[(lR)-l-[3-[(lE)-2-(7-chloro- 2-quinolinyl)ethenyl]phenyl3-[2-(l-hydroxy-l-methyl-ethyl)phenyl]propyl]thio]methyl] cyclopropane acetic acid, is a leukotriene receptor antagonist.
Formula (II)
Montelukast was first disclosed in the patent numbered EP480717 Al. Processes for preparation of montelukast and also use of montelukast as leukotriene antagonist are clarified in the patent.
Montelukast is an orally-used, potent and selective antagonist of leukotriene D4 (LTD4) which is effective on cysteinyl leukotriene receptor (CysLTi) in the respiratory tract. Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are powerful inflammatory eicosanoids which are secreted by various cells including mast cell and eosinophils. These important pro-asthmatics mediators bind to cysteinyl leukotriene receptors (CysLTj) in the respiratory tract and cause a range of respiratory activities such as bronchoconstriction, intensive mucus secretion, vascular permeability and eosinophil accumulation.
Montelukast is a powerful compound which treats asthma inflammation parameters significantly. Montelukast binds to CysLTi receptor with a high affinity and selectivity and strongly inhibits physiological effects of LTC4, LTD4, LTE4 in CysLTi receptor without any agonist activity.
Use of levocetirizine and montekulast together is explained in the prior art. For instance, the patent numbered WO2003101434 discloses intranasal use of an antihistamine and a leukotriene inhibitor in the treatment and prevention of allergic rhinitis and symptoms thereof. The antihistaminic group active agent given here is presented as loratadine or desloratadine while the leukotriene inhibitor is presented as montelukast in said patent.
However, as a result of the studies conducted, the inventor has found that the combination product does not have enough hardness in some cases; for instance when said product is produced in tablet dosage form or when the product is required to be used as stored in blisters.
As it is known, tablet hardness relates to resistance of tablets against corrosion, breakage before storing, carrying, coating and use. Low-hardness tablets are exposed to corrosion, disintegration or breakage more. Such situations cause active agent loss.
Furthermore, there is a close correlation between tablet hardness and dispersibility. Since extra hard tablets cannot disintegrate and dissolve as required, the bioavailability of these tablets shall decrease and therefore it shall take longer to get the desired biological response. When all these parameters are taken into consideration, it is aimed that tablet hardness is low enough to enable the tablet to disintegrate fast in stomach while it is high enough to preserve tablet integrity from production to patients' use; during packing, carrying and storing.
There are many patent applications that disclose montelukast formulations and production method thereof. For instance, the patent numbered WO2007092031 (Al) discloses montelukast formulations which have less than 1% of sulfoxide impurity and do not comprise microcrystalline cellulose, and processes for production thereof. Production of montelukast tablet formulations by wet granulation method is also clarified in this patent.
However, it has been seen that the tablet obtained when the formulation and production method of said patent are applied to montelukast and combinations thereof does not have desired mechanical properties.
As montelukast is rather prone to degrade easily, production method and formulation to be used for tablet production should be selected quite carefully in order to provide adequate mechanical properties. In addition to this, although use of different amounts of various pharmaceutically acceptable excipients in order to improve mechanical properties of the tablet is available in the prior art, this is quite a hard solution offer to be implemented for active agents which are affected by environmental conditions easily and incompatible with most of the pharmaceutical excipients.
When the prior art is taken into consideration, hardness problem of tablet formulations comprising montelukast and combinations thereof has not been referred to and therefore no solution has been suggested.
The present invention aims to provide a pharmaceutical formulation that can be used for preparation of highly stable tablets which have sufficient tablet hardness, also possess sufficient dispersibility and solubility characteristics.
As a result of the studies they conducted, the inventors have surprisingly achieved to produce stable pharmaceutical tablets which have sufficient hardness value and are also sufficiently well-dispersible and soluble by using two diluents having different features and different rates in montelukast formulations and combinations of these formulations with at least one other active agent.
The diluents in the formulations of the present invention are selected from a group comprising alkali metal carbonates, cellulose derivatives (microcrystalline cellulose, cellulose acetate etc.), dextrin, fructose, dextrose, glyceryl palmitostearate, lactitol, lactose, directly compressible lactose, maltose, mannitol, simethicone, sorbitol, starch, talc, xylitol and/or hydrates, anhydrates and/or derivatives thereof.
One characteristic feature of the formulations of the present invention is that the formulations comprise lactose or pharmaceutically acceptable hydrate or anhydrate and mannitol.
Another characteristic feature of the formulations of the present invention is that the ratio of the two diluents used in the formulations to each other (lactose or a pharmaceutically acceptable hydrate or anhydrate thereof : mannitol ) is in the range of 0.1 to 5 by weight.
Another characteristic feature of the formulations of the present invention is that the ratio of the two diluents used in the formulations to each other (lactose or a pharmaceutically acceptable hydrate or anhydrate thereof : mannitol) is in the range of 0.1 to 1 by weight.
Another characteristic feature of the formulations is that the ratio of the two diluents used in the formulations to each other (lactose or a pharmaceutically acceptable hydrate or anhydrate thereof : mannitol) is in the range of 0.6 to 1 by weight. Another characteristic feature of the formulations of the present invention is that the average particle size (D50) of lactose or a pharmaceutically acceptable hydrate or anhydrate thereof and mannitol used as diluent in the formulations is maximum 150 μπι.
Another characteristic feature of the formulations of the present invention is that the average particle size (D50) of lactose or a pharmaceutically acceptable hydrate or anhydrate thereof and mannitol used as diluent in the formulations is maximum 130 μηι.
Another characteristic feature of the formulations of the present invention is that the average particle size (D50) of lactose or a pharmaceutically acceptable hydrate or anhydrate thereof and mannitol used as diluent in the formulations is in the range of 1 to 120 μη .
The term "D (50) particle size" stated herein refers to particle size including 50% of the particles by volume.
Another characteristic feature of the formulations of the present invention is that the formulations comprise lactose monohydrate and mannitol as diluent.
Another characteristic feature of the formulations of the present invention is that the formulations comprise lactose anhydrate and mannitol as diluent. Another characteristic feature of the formulations of the present invention is that the formulations are in tablet, film coated tablet or bilayer tablet form.
Montelukast formulations of the present invention are used as combined with at least one other active agent.
The second active agent stated herein is preferably an antihistaminic and selected from a group comprising diphenhydramine, dimenhydrinate, carbinoxamine, chlorphenoxamine, mepyramine, antazoline, triple amine, dexchlorpheniramine, dexbrompheniramine, pheniramine, buclizine, hydroxyzine, cinnarizine, meclizine, alimemazine, promethazine, cyproheptadine, ebastine, astemizole, acrivastine, loratadine, desloratadine, ketotifen, cetirizine, levocetirizine or pharmaceutically acceptable salts, solvates, derivatives, polymorphs, hydrates or enantiomers thereof.
The second active agent used in the formulations is levocetirizine dihydrochloride.
The second active agent can be used with montekulast simultaneously, sequentially or separately. However, the two active agents are combined in a single dosage form in the preferred embodiment of the present invention. The term "montelukast" stated in the text refers to montelukast and its pharmaceutically acceptable salts, solvates, derivatives, polymorphs, hydrates or enantiomers. Preferably, montelukast used in the formulations of the present invention is in the form of sodium salt.
The formulations of the present invention can comprise other pharmaceutically suitable components such as additives and excipients selected from disintegrants, viscosity enhancing
components, filling agents, drying agents, stabilizing agents, lubricants, diluents, binders, glidants, anti-foaming agents, wetting agents, effervescent mixtures, sweeteners and flavourings agents.
The disintegrant that can be used in formulations of the present invention can be selected from highly dispersive polymers, for instance cross-linked hydroxypropyl cellulose, polyvinylpyrrolidone, high-molecular-weight polymers, microcrystalline cellulose, sodium starch glycolate, povidone, alginic acid, sodium alginate.
The binders that can be used in formulations of the present invention comprise one or more components selected from the group comprising potato starch, wheat starch or corn starch; microcrystalline cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, hypromellose and polyvinylpyrrolidone.
The lubricants that can be used in formulations of the present invention comprise one or more components selected from the group comprising highly metallic stearates (magnesium stearate, calcium stearate, aluminium stearate etc), fatty acid esters (sodium stearyl fumarate etc), fatty acids (stearic acid etc), fatty alcohols, glyceryl behenate, mineral oil, paraffins, L- Leucine, hydrogenated vegetable oil, leucine, polyethylene glycols (PEG), metallic lauryl sulphates (sodium lauryl sulphate, magnesium lauryl sulphate), sodium chloride, sodium benzoate, sodium acetate and talc and/or hydrates thereof.
The stabilizing agent that can be used in formulations of the present invention can be selected from alkaline metal salts such as sodium carbonate, sodium hydrogen carbonate, sodium hydroxide, sodium silicate, disodium hydrogen orthophosphate, sodium aluminate; alkaline- earth metal salts such as calcium carbonate, calcium hydroxide, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, calcium acetate, calcium gluconate, calcium glycerophosphate, magnesium carbonate, magnesium hydroxide, magnesium sulphate, magnesium acetate, magnesium silicate, magnesium aluminate; organic components such as primary, secondary and tertiary amines, cyclic amines, Ν,Ν'-dibenzyl ethylenediamine, diethanolamine, ethylenediamine, meglumine, monosodium glutamate, polacrilin sodium, sodium alginate and/or pharmaceutically acceptable hydrates and/or derivatives thereof.
The filling agents that can be used in formulations of the present invention comprises one or more components selected from the group comprising lactose, sugar, starch, modified starch, mannitol, sorbitol, inorganic salts, microcrystalline cellulose, cellulose, calcium sulphate, xylitol and lactitol.
The film coating agent that can be used in formulations of the present invention comprises components such as lactose, hydroxypropyl methyl cellulose, triacetine, titanium dioxide, polyvinyl alcohol, talc, lecithin, polyethylene glycol and/or combinations thereof.
The sweeteners that can be used in formulations of the present invention comprise one or more components selected from the group comprising aspartame, dextrose, fructose, sucralose, sodium cyclamate, mannitol, maltose, saccharine and/or pharmaceutically acceptable salts thereof.
The combined product of the present invention comprising levocetirizine dihydrochloride along with an effective amount of montelukast sodium is preferably in bilayer tablet form; basically composed of two different formulations.
The first formulation comprises an effective amount of levocetirizine dihydrochloride and a specific amount of lactose or a pharmaceutically acceptable hydrate or anhydrate thereof as diluent; the second formulation comprises an effective amount of montelukast sodium and a specific amount of mannitol as diluent.
The ratio of the diluents to each other (lactose or a pharmaceutically acceptable hydrate or anhydrate thereof : mannitol) in these two phases is in the range of 0.1 to 5 by weight, preferably in the range of 0.1 to 1 by weight, more preferably in the range of 0.6 to 1 by weight.
The two different formulations prepared are produced in the form of bilayer tablet by direct compression method by being fed separately to the tablet compression machine. Values of tablet hardness analysis which was run under approximately 15 kN pressure using 10 samples taken from different production lines of the bilayer tablets produced this way are identified and showed in the table below.
Tablets which have enough breaking load and hardness can be produced by providing enough flow rate of the dry powder formulation in direct compression method. Hardness value of the bilayer tablets produced according to the invention is at least 10 kP, preferably in the range of 10-50 kP, more preferably in the range of 10-20 kP.
Sufficient fluidity property and tablet hardness in the formulations of the present invention have been solved by adjusting the amount, the type and particle size of the diluents used in the formulations.
The present invention also provides a production method for production of tablet formulations given above.
Tablet formulations of the present invention can also be produced by any method in the prior art; for instance, wet granulation, dry granulation, dry blending though said production method preferably comprises the following steps:
1. Preparation of the first formulation
a. Mixing and sieving montelukast or a pharmaceutically acceptable salt, ester, solvate, derivative, polymorph or hydrate thereof; mannitol and at least one other pharmaceutical excipient,
b. Adding a pharmaceutically acceptable lubricant into the mixture obtained in the first step and preparing the first formulation by mixing the mixture.
2. Preparation of the second formulation
c. Mixing and sieving levocetirizine or a pharmaceutically acceptable salt, ester, solvate, derivative, polymorph or hydrate thereof; lactose or a pharmaceutically acceptable hydrate or anhydrate and at least one other pharmaceutical excipient, d. Adding a pharmaceutically acceptable lubricant into the mixture obtained in the first step and preparing the second formulation by mixing the mixture.
3. Preparation of bilayer tablet dosage form
e. Preparing bilayer tablet dosage form by feeding the two formulations to tablet compression machine consecutively.
4. Coating
The bilayer tablet dosage form prepared is coated with film.
The coating agent used in this step is preferably a film-coating agent and preferably comprises an effective amount of titanium dioxide. The coating agent comprising titanium dioxide enables montelukast, which is prone to degrade due to environmental conditions, to remain stabile during its shelf life.
In addition, the inventors have seen that the mixing times of the lubricants in step "b" and "d" of the bilayer tablet formulation which is prepared according to the production method clarified above affect mechanical properties of the end production.
Mixing time for montelukast formulation in step "b" is preferably 1-10 minutes, more preferably 1-5 minutes; mixing time for levocetirizine formulation in step "d" is preferably 1-
20 minutes, more preferably 1-15 minutes in production of the formulations of the present invention.
The bilayer tablet dosage form produced by said method has sufficient mechanical properties.
Hardness values of the bilayer tablet dosage form produced according to example I of the invention are given below:
Table I. Tablet hardness data
Examples of pharmaceutical tablet formulations of the present invention are presented below. These examples are given in order to clarify the subject of the invention; yet the subject of the invention is not limited to these examples.
EXAMPLES
Example 1: Film Coated Tablet Formulation
The film coated tablet formulation given above is prepared according to the production method explained in detail in description.
Claims
1. A bilayer tablet formulation comprising montelukast and levocetirizine and/or pharmaceutically acceptable salts thereof characterized in that at least two different diluents having an average particle size of maximum 150 μηι are used in the formulations.
2. The bilayer tablet formulation according to claim 1 characterized in that at least two different diluents having an average particle size of maximum 130 μηι are used in the formulations.
3. The bilayer tablet formulation according to claim 2 characterized in that at least two different diluents having an average particle size in the range of 1 - 120 μπι are used in the formulations.
4. The bilayer tablet formulation according to any preceding claims characterized in that at least two different diluents selected from a group comprising alkali metal carbonates, cellulose derivatives, dextrin, fructose, dextrose, glyceryl palmitostearate, lactitol, lactose, directly compressible lactose, maltose, mannitol, simethicone, sorbitol, starch, talc, xylitol and/or hydrates, anhydrates and/or derivatives thereof are used in the formulations.
5. The bilayer tablet formulation according to any preceding claims characterized in that lactose or a pharmaceutically acceptable hydrate or anhydrate thereof and mannitol are used as diluent in the formulations.
6. The bilayer tablet formulation according to claim 5 characterized in that lactose monohydrate and mannitol are used as lubricant in the formulations.
7. The bilayer tablet formulation according to claim 5 characterized in that lactose anhydrate and mannitol are used as diluent in the formulations.
8. The bilayer tablet formulation according to any preceding claims characterized in that the ratio of the two different diluents in the formulations to each other is in the range of 0.1 to 5 by weight.
9. The bilayer tablet formulation according to claim 8 characterized in that the ratio of the two different diluents in the formulations to each other is in the range of 0.1 to 1 by weight.
10. The bilayer tablet formulation according to claim 9 characterized in that the ratio of the two diluents in the formulations to each other is in the range of 0.6 to 1 by weight.
11. The bilayer tablet formulation according to any preceding claims characterized in that said formulation comprises montelukast sodium and levocetirizine dihydrochloride.
12. A method for production of the bilayer tablet formulation according to any preceding claims characterized in that the production method is composed of the following steps; a. Mixing and sieving montelukast or a pharmaceutically acceptable salt, ester, solvate, derivative, polymorph or hydrate thereof; mannitol and at least one other pharmaceutical excipient,
b. Adding a pharmaceutically acceptable lubricant into the mixture obtained in the first step and preparing the first formulation by mixing the mixture, c. Mixing and sieving levocetirizine or a pharmaceutically acceptable salt, ester, solvate, derivative, polymorph or hydrate thereof; lactose or a pharmaceutically acceptable hydrate or anhydrate thereof and at least one other pharmaceutically acceptable excipient,
d. Adding a pharmaceutically acceptable lubricant into the mixture obtained and preparing the second formulation by mixing the mixture,
e. Preparing bilayer tablet dosage form by feeding the two formulations to tablet compression machine consecutively,
f. Coating the bilayer tablet dosage form prepared with film.
13. The tablet formulation according to any preceding claims characterized in that said formulation is used for prevention and/or treatment of allergic and inflammatory diseases of the skin or upper and lower respiratory tract diseases such as seasonal allergic rhinitis, perennial allergic rhinitis, allergic sinusitis, atopic dermatitis, urticaria, allergic asthma, aspirin induced asthma, exercise induced asthma and for relieving the symptoms thereof.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2010/09398 | 2010-11-11 | ||
| TR2010/09398A TR201009398A2 (en) | 2010-11-11 | 2010-11-11 | Tablet formulations with improved physical properties |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2012064305A2 true WO2012064305A2 (en) | 2012-05-18 |
| WO2012064305A3 WO2012064305A3 (en) | 2012-08-09 |
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/TR2011/000243 WO2012064301A2 (en) | 2010-11-11 | 2011-11-03 | Physically improved tablet formulations |
| PCT/TR2011/000247 WO2012064305A2 (en) | 2010-11-11 | 2011-11-03 | Formulations with improved physical characteristics |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/TR2011/000243 WO2012064301A2 (en) | 2010-11-11 | 2011-11-03 | Physically improved tablet formulations |
Country Status (2)
| Country | Link |
|---|---|
| TR (1) | TR201009398A2 (en) |
| WO (2) | WO2012064301A2 (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9717684B2 (en) | 2014-04-25 | 2017-08-01 | R.P. Scherer Technologies, Llc | Stable montelukast solution |
| EP3222279A1 (en) | 2016-03-21 | 2017-09-27 | Invest Bielany Spolky z Ograniczona Odpowiedzialnoscia | Oral pharmaceutical formulation of montelukast and levocetirizine and method for its production |
| RU2677649C2 (en) * | 2013-02-21 | 2019-01-18 | Глэнмарк Фармасьютикалс Лимитед | Pharmaceutical compositions of montelucast and levocetirisine |
| EP3463324A4 (en) * | 2016-06-03 | 2020-01-29 | Irr, Inc. | Levocetirizine and montelukast in the treatment of radiation-mediated conditions |
| WO2020143744A1 (en) * | 2019-01-10 | 2020-07-16 | Jiangyin Mucocare Pharmaceutical Co., Ltd. | New formulations containing leukotriene receptor antagonists |
| US10792281B2 (en) | 2014-09-15 | 2020-10-06 | IRR, Inc. | Levocetirizine and montelukast in the treatment of inflammation mediated conditions |
| US11103500B2 (en) | 2013-03-13 | 2021-08-31 | IRR, Inc. | Use of levocetirizine and montelukast in the treatment of traumatic injury |
| US11344545B2 (en) | 2013-03-13 | 2022-05-31 | IRR, Inc. | Use of levocetirizine and montelukast in the treatment of autoimmune disorders |
| WO2023068839A1 (en) * | 2021-10-21 | 2023-04-27 | 한화제약주식회사 | Film-coated tablet with improved stability containing montelukast or pharmaceutically acceptable salt thereof and levocetirizine or pharmaceutically acceptable salt thereof |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20130050952A (en) | 2010-06-16 | 2013-05-16 | 브루스 챈들러 메이 | Use of levocetirizine and montelukast in the treatment of influenza, common cold and inflammation |
| AU2014249534B2 (en) | 2013-03-13 | 2018-08-30 | IRR, Inc. | Use of levocetirizine and montelukast in the treatment of vasculitis |
| KR102110304B1 (en) * | 2017-06-30 | 2020-05-14 | 한미약품 주식회사 | Composite chewable tablet comprising levocetirizine and montelukast with improved stability and adaptability of taking medicine and a process for the preparation thereof |
| MX2018011699A (en) * | 2018-09-26 | 2019-07-24 | Federico Amezcua Amezcua | A synergistic pharmaceutical composition of leukotriene receptor antagonist and a histamine h1 inverse agonist. |
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| GB2225321A (en) | 1988-11-23 | 1990-05-30 | Ucb Sa | Process for preparation of a 1-piperazine-ethoxyacetic acid |
| EP0480717A1 (en) | 1990-10-12 | 1992-04-15 | Merck Frosst Canada Inc. | Unsaturated hydroxyalkylquinoline acids as leukotriene antagonists |
| WO1994006429A1 (en) | 1992-09-24 | 1994-03-31 | Sepracor, Inc. | Compositions for treating allergic disorders using (-) cetirizine |
| WO2003101434A2 (en) | 2001-12-21 | 2003-12-11 | Sampad Bhattacharya | Intranasal pharmaceutical compositions comprising an antihistamine and a leukotriene inhibitor |
| WO2007092031A1 (en) | 2006-02-09 | 2007-08-16 | Teva Pharmaceutical Industries Ltd. | Stable pharmaceutical formulations of montelukast sodium |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| PL1976522T5 (en) * | 2005-12-30 | 2019-12-31 | Krka Tovarna Zdravil, D.D., Novo Mesto | Pharmaceutical composition containing montelukast |
| US20090124657A1 (en) * | 2007-08-14 | 2009-05-14 | Ramesh Kappala | Pharmaceutical compositions comprising montelukast |
| WO2009122187A2 (en) * | 2008-04-03 | 2009-10-08 | Cipla Limited | Pharmaceutical composition |
| WO2010107404A1 (en) * | 2009-03-16 | 2010-09-23 | Mahmut Bilgic | Stable pharmaceutical combinations |
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2010
- 2010-11-11 TR TR2010/09398A patent/TR201009398A2/en unknown
-
2011
- 2011-11-03 WO PCT/TR2011/000243 patent/WO2012064301A2/en active Application Filing
- 2011-11-03 WO PCT/TR2011/000247 patent/WO2012064305A2/en active Application Filing
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|---|---|---|---|---|
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| US10792281B2 (en) | 2014-09-15 | 2020-10-06 | IRR, Inc. | Levocetirizine and montelukast in the treatment of inflammation mediated conditions |
| US11590125B2 (en) | 2014-09-15 | 2023-02-28 | IRR, Inc. | Levocetirizine and montelukast in the treatment of inflammation mediated conditions |
| EP3222279A1 (en) | 2016-03-21 | 2017-09-27 | Invest Bielany Spolky z Ograniczona Odpowiedzialnoscia | Oral pharmaceutical formulation of montelukast and levocetirizine and method for its production |
| EP3463324A4 (en) * | 2016-06-03 | 2020-01-29 | Irr, Inc. | Levocetirizine and montelukast in the treatment of radiation-mediated conditions |
| WO2020143744A1 (en) * | 2019-01-10 | 2020-07-16 | Jiangyin Mucocare Pharmaceutical Co., Ltd. | New formulations containing leukotriene receptor antagonists |
| WO2023068839A1 (en) * | 2021-10-21 | 2023-04-27 | 한화제약주식회사 | Film-coated tablet with improved stability containing montelukast or pharmaceutically acceptable salt thereof and levocetirizine or pharmaceutically acceptable salt thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2012064301A3 (en) | 2012-07-19 |
| WO2012064305A3 (en) | 2012-08-09 |
| WO2012064301A2 (en) | 2012-05-18 |
| TR201009398A2 (en) | 2012-05-21 |
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