CN101773503A - Leukotriene antagonist and antihistaminics composition - Google Patents

Abstract

The invention relates to a pharmaceutical composition for treating asthma, allergic reaction and inflammation. The composition comprises a leukotriene antagonist, antihistaminics and medicinal carriers, wherein the leukotriene antagonist is Montelukast and salts thereof, and the antihistaminics is olopatadine hydrochloride and salts thereof. The composition is suitable for preventing and long-term treating of asthma for children and adults, and can treat asthma patients sensitive to aspirin, prevent bronchoconstriction induced by movement, treat pruritus concomitant with allergic rhinitis, urticaria and skin diseases, and the like. The composition has better curative effect compared with that the two medicines are used independently.

Description

A kind of leukotriene antagonist and antihistaminics composition

Technical field

The present invention relates to a kind of leukotriene antagonist and antihistaminics composition, is the compositions of Menglusitena and Olopatadine hydrochloride specifically.

Background technology

Bronchial asthma be a kind of be the respiratory tract chronic inflammatory reactive disorder of feature with the respiratory tract high response, its mechanism complexity relates to many inflammatory reaction media, cytokine, chemokines and relevant cell composition.Wherein leukotriene (LTs) is the main inflammatory reaction medium in the asthma generation evolution, also be at present with single material as the most promising approach of targeting, can not only promote the inflammatory reaction cell in respiratory tract, to assemble, increase the secretion of vascular permeability and mucus, can also cause that airway smooth muscle shrinks, promote respiratory tract structure cell proliferation, thus the generating process that participates in the reaction of respiratory tract inflammatory and reinvent.LTRA and leukotriene receptor (Cysh) selective binding that is positioned at positions such as bronchial smooth muscle play the effect of blocking-up cysteamine acyl leukotriene.

One of LTs receptor antagonist montelukast is a kind of potent selectivity LTs receptor antagonist, it can combine with CysLT1 receptor high selectivity among the human respiratory tract, thereby the pathological effect of blocking-up LTs, its mechanism of action: (1) suppresses respiratory tract eosinophilic granulocyte inflammatory reaction; (2) suppress inflammatory reaction medium and release of cytokines, wherein may comprise by suppressing IL-5 and IgE generation and having secreted anti-infectious function; (3) because of endogenous AA and metabolite thereof have participated in the nitric oxide production release of lipopolysaccharide-induced back macrophage, the phospholipase metabolic pathway can raise the synthetic of nitric oxide (NO) by synthetic LTs in macrophage, so montelukast can reduce the NO in the expired gas; (4) suppressing respiratory tract LTC discharges; (5) improve pulmonary function, reduce the respiratory tract high response; (6) suppressing respiratory tract reinvents.Other there are some researches show that montelukast also can reduce the protein level in the mouse asthmatic model bronchoalveolar lavage fluid.

Allergy claims anaphylaxis again, and modern medicine is called antigen antibody reaction with this reaction. disclosed the essence of this type of reaction.Allergy is divided into four types, clinical modal be the I type, call type again.Histamine is one of important medium of type i allergic reaction.Anaphylaxis is a kind of immunoreation, because anaphylactogen enters in the body, stimulates body to produce the immunoreation of IgE.IgE often is attached on the mastocyte, and when the second time, contact allergy was former, the antibody antigen reaction stoped the synthetic of the interior cyclic adenosine monophosphate of born of the same parents, and its level is descended, so take off the granule reaction.Along with degranulated release, many inflammatory mediators disengage from granule simultaneously, are mainly histamine, 5-hydroxy tryptamine, prostaglandin, leukotrienes and some peptide classes etc.Wherein the meaning of histamine is bigger, and it makes histamine 1 receptor (HlR) excitement in the tissue, shows following symptom: 1. the secretion of mucosas such as eye, nose increases, and causes rhinorrhea, with symptoms such as tears.2. bronchospasm makes hypopnea suitable. the sound of stridulating, even cause asthma.3. symptoms such as gastrointestinal angor appear in the gastrointestinal smooth muscular spasm.4. capillary permeability increases, and body fluid is leaked in tissue by blood capillary, and the part blush, edema, whole body occur and causes blood pressure drops because of blood volume descends again.5. the teleneuron irriate causes local gargalesthesia or pain symptom.Because the symptom that histamine causes is anaphylactoid cardinal symptom, use antihistaminic often can alleviate above symptom, so also claim antiallergic agent.And antihistamine H1 receptor antagonist is occupied an leading position in antihistaminic.

Olopatadine is as a kind of novel high histamine H 1 receptor antagonist of relative selectivity, can either suppress mastocyte and discharge histamine, again histamine H1-receptor had selectivity height, antagonism that curative effect is strong, and the generation and the release of anaphylaxis chemical mediators such as leukotriene, thromboxane, platelet activating factor demonstrated inhibitory action, tachykinin release and eosinophilic granulocyte's infiltration also there is inhibitory action, to the not effect of alpha adrenergic receptor, serum receptor, dopamine receptor and M1 and M2 receptor do not have effect, and its central nervous system aspect untoward reaction is few.This medicine successively after multinational listings such as Europe, the United States, day, is used for the treatment of a series of irritated diseases and comprises allergic rhinitis, skin irritation, pleomorphism exudative erythema and urticaria.

Bronchial asthma is a kind of common immunity respiratory system disease. belong to I metallergy inflammation, its pathogeny both with inflammation-related, also relevant with allergy.Usually asthmatic patient is with anaphylaxis and inflammation.Leukotriene antagonist not only can improve the pulmonary function of asthmatic patient, and certain application value is also arranged in all many-sides such as antiinflammatory, immunity, but the treatment to the multiple symptom relevant with respiratory tract disease is not very effective, as the complication of seasonal allergic rhinitis, non-seasonal allergic rhinitis, common cold, sinusitis and allergic asthma.LTRA associating antihistamine drug then has better curative effect for asthma, allergy and inflammation.Histamine and leukotriene are the important medium of the free bronchoconstriction of people IgE mediation, and both play synergism in mediation bronchoconstriction process, the free bronchial tissue maximal contractile response time delay of antihistaminic energy IgE mediation, but do not influence shrinkage amplitude.LTRA can make shrinkage amplitude reduce, and The combined is used the contraction that then can suppress bronchial tissue.Both are with the release of inflammatory mediator in two kinds of different mechanism inhibition bodies, the reaction that reduces inflammation, thereby associating antianaphylaxis.

Leukotriene antagonist and antihistaminics composition have patent report, CN1210465A discloses a kind of method for the treatment of asthma, allergy and inflammation, comprises with in dosage form or be combined in leukotriene inhibitors in the single medicine preparation and loratadine administration is simultaneously treated independently respectively.CN1283115A discloses and has been used for the treatment of respiratory tract and dermopathic at least a leukotriene antagonist and at least a antihistaminics composition of containing.The patent of the compositions of Menglusitena and Olopatadine hydrochloride is not seen report.

Summary of the invention

The object of the present invention is to provide a kind of pharmaceutical composition for the treatment of asthma, allergy and inflammation, be specially the compositions of leukotriene antagonist montelukast and salt thereof and antihistaminic olopatadine and salt thereof.Compositions of the present invention can also contain other pharmaceutical carrier.

The said composition dosage form is tablet and capsule, and compositions is designed to oral administration.Each unit formulation contains montelukast 4-10mg, olopatadine 2.5-10mg.Wherein, montelukast 4mg/ olopatadine 2.5mg compositions, 2 years old to the 5 years old once oral a slice of patient/grain, once-a-day; Montelukast 5mg/ olopatadine 2.5mg compositions, 6 years old to the 14 years old once oral a slice of patient/grain, once-a-day; Montelukast 5mg/ olopatadine 5mg compositions, 6 years old to the 14 years old once oral a slice of patient/grain, once-a-day, the once oral a slice of patient/grain more than 15 years old and 15 years old, twice on the one; Montelukast 10mg/ olopatadine 5mg compositions, the once oral a slice of patient/grain more than 15 years old and 15 years old, once-a-day; Montelukast 10mg/ olopatadine 10mg compositions, the once oral a slice of patient/grain more than 15 years old and 15 years old, once-a-day.

Said composition is applicable to the prevention and the long-term treatment of child and adult's asthma, and treatment is to the bronchoconstriction of the asthmatic patient of aspirin sensitive and prevention exercise induced, and the pruritus that occurs together of allergic rhinitis, urticaria, dermatosis etc.The compositions therapeutic alliance is effective than two kinds of medicines self.

The said composition dosage form is tablet and capsule, and pharmaceutically suitable carrier comprises disintegrating agent, filler, binding agent and lubricant.Disintegrating agent can be microcrystalline Cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl cellulose sodium, crospolyvinylpyrrolidone etc., filler can be starch, sucrose, lactose, pregelatinized Starch, dextrin, mannitol, sorbitol etc., binding agent can be starch slurry, syrup, 30 POVIDONE K 30 BP/USP 30 alcoholic solution, hypromellose etc., and lubricant is magnesium stearate, polyethylene glycol 6000 etc.

The preparation technology of said composition can be direct powder compression/encapsulated, wet granule compression tablet/encapsulated and dry granulation tabletting/encapsulated method.

Specific embodiment the present invention can be illustrated with the following examples

Embodiment 1: the agent of montelukast olopatadine compound capsule

Prescription:

Montelukast 4g

Olopatadine 2.5g

Lactose 70

Starch 30

Carboxymethyl starch sodium 10g

Magnesium stearate 1g

10% starch slurry is an amount of

Make 1000 altogether

Preparation method:

(1) all supplementary materials were pulverized 100 mesh sieves, standby;

(2) take by weighing lactose, starch, the carboxymethyl starch sodium mix homogeneously of recipe quantity, material I, get the montelukast and the olopatadine of recipe quantity, equivalent adds material I, mix homogeneously, material II;

(3) material II is made suitable soft material in right amount with 10% starch slurry, cross 20 mesh sieves and granulate, in 50 ℃ of aeration-dryings, control moisture 1～2% is with 18 mesh sieve granulate.

(4) in dried granule, add magnesium stearate, mix homogeneously, the fill capsule, packing is promptly.

Embodiment 2: montelukast olopatadine compound tablet

Prescription:

Montelukast 5g

Olopatadine 5g

Microcrystalline Cellulose 40g

Hydroxypropyl cellulose 10

Mannitol 90g

Polyethylene glycol 6000 10

Make 1000 altogether

Preparation method:

(1) all supplementary materials were pulverized 80 mesh sieves, standby;

(2) take by weighing microcrystalline Cellulose, hydroxypropyl cellulose, mannitol, the polyethylene glycol 6000 mix homogeneously of recipe quantity, material I, get the montelukast and the olopatadine of recipe quantity, equivalent adds material I, mix homogeneously, material II;

(3) with material II direct compression under suitable pressure, packing promptly.

Embodiment 3: the agent of montelukast olopatadine compound capsule

Prescription:

Montelukast 10g

Olopatadine 10g

Crospolyvinylpyrrolidone 35g

Lactose 85

Pulvis Talci 5g

10%PVPk30 is an amount of

Make 1000 altogether

Preparation method:

(1) all supplementary materials were pulverized 100 mesh sieves, standby;

(2) take by weighing montelukast, olopatadine, crospolyvinylpyrrolidone, the lactose mix homogeneously of recipe quantity, material I;

(3) material I is made suitable soft material in right amount with 10%PVPk30, cross 20 mesh sieves and granulate, in 50 ℃ of aeration-dryings, control moisture 1～2% is with 18 mesh sieve granulate.

(4) in dried granule, add Pulvis Talci, mix homogeneously, the fill capsule, packing is promptly.

Claims (8)

1. the present invention relates to a kind of pharmaceutical composition for the treatment of asthma, allergy and inflammation, said composition comprises a kind of leukotriene antagonist and antihistaminic and pharmaceutically suitable carrier.Wherein, leukotriene antagonist is montelukast and salt thereof, and antihistaminic is olopatadine and salt thereof.Each unit formulation contains montelukast 4-10mg, olopatadine 2.5-10mg.

2. the described compositions of claim 1, it is characterized in that: each unit formulation contains montelukast 4mg, olopatadine 2.5mg.

3. the described compositions of claim 1, it is characterized in that: each unit formulation contains montelukast 5mg, olopatadine 2.5mg.

4. the described compositions of claim 1, it is characterized in that: each unit formulation contains montelukast 5mg, olopatadine 5mg.

5. the described compositions of claim 1, it is characterized in that: each unit formulation contains montelukast 10mg, olopatadine 5mg.

6. the described compositions of claim 1, it is characterized in that: each unit formulation contains montelukast 10mg, olopatadine 10mg.

7. the described compositions of claim 1, it is characterized in that: combination dosage form is tablet, capsule and granule.

8. the described compositions of claim 1 is characterized in that: compositions is designed to oral administration.