COMPLETE DESCRIPTION
Filed of the Invention
The present invention is related to the novel oral combination comprising Acebrophylline and Olopatadine for the treatment of asthma and airway inflammation due to allergy and other pathological condition. The combination is also useful in treating the cough and airway blockage due to allergy and is effective in allergic rhinitis.
Related Prior Art for the invention
CN 101352415 (A) discloses a formulation of oral solution of acebromine theophylline and a preparation and belongs to the western medicine formulation field; the oral solution of acebromine theophylline has pH value of 3.0 to 6.5 and consists of the following ingredients with percentage: 0.1 to 2 percent (W/V) of acebromine theophylline, 0 to 30 percent (V/V) of glycerin and/or propylene glycol, moderate pH regulator, 0.001 to 50 percent of corrigent, 0.002 to 0.5 percent of bacteriostat and the solvent is water. The invention has the advantages that: the oral solution of acebromine theophylline of the invention has stable quality, the drug is dispersed in the medium in molecular state with large dispersity and fast absorption, the drug effect can be played and the bioavailability is improved; the oral solution of acebromine theophylline of the invention has convenient taking, easy dosage division, sour and sweet and smooth taste and fragrant smell and can improve patient compliance.
CN 101352419 (A) relates to an acebromine theophylline sugar-free granular agent and a preparation method thereof, in particular to a granular agent drug which takes the acebromine theophylline as active ingredients and a preparation method thereof, belonging to the western medicine formulation field; the acebromine theophylline sugar-free granular agent consists of the following ingredients by weight in every 1000 dose: 10 to 200g of acebromine theophylline materials, 400 to 4000g of diluents, 0 to 200g of disintegrating agents, 1 to 100g of adhesives, 5 to 300g of corrigents, 0 to 100g of solid fragrances and/or 0 to 200ml of liquid
fragrances and 0 to 10g of colorants. The an acebromine theophylline sugar-free granular agent of the invention has the advantages of the use of the novel corrigent and the fragrance covers, the self-bitter taste of the acebromine theophylline, avoids the use of sweeteners with a large quantity of sucrose, and the like, reduces the usage of excipients greatly, leads the packing quantity of single dosage of the preparation to be reduced obviously and leads the oral administration and taking of the medicine to be more convenient; simultaneously, the conversion problem of better dosage form of the acebromine theophylline materials is solved, especially the key problem of the stability of the granular agent; the production technique of the preparation of the invention is easy to realize production on scale extremely and is suitable to the national situation in China. CN 101695480 (A) discloses olopatadine hydrochloride dispersible tablets, a preparation method thereof and a quality control method thereof. The olopatadine hydrochloride dispersible tablets contain olopatadine hydrochloride serving as a main medicament and a disintegrating agent, a filler, a binding agent and a lubricating agent which serve as auxiliary materials. A wet-method is adopted for granulation and tabletting, and an internal disintegrating agent addition method is adopted. The olopatadine hydrochloride dispersible tablets have the advantages of excellent dispersion state, short disintegrating time, quick medicament digestion, convenient administration, low production cost, no special equipment, convenient and stable carrying and transport and the like. CN 101596173 (A) The invention discloses a capsule capable of stabilizing acebrophylline, comprising an active ingredient acebrophylline/stabilizing agent and a pharmaceutically acceptable accessory. The capsule with the acebrophylline of the invention solves the problem that the acebrophylline and monosaccharide or polysaccharide, in particular to lactose, are mixed and react unstably, has simple operation, saves cost and is more suitable for large-scale industrialized production.
CN 101607960 (A) The invention relates to a crystal form of acebrophylline, surfolase and a preparation method thereof. The invention also relates to a pharmaceutical composition containing the crystal form and the application
of the new crystal form in the preparation of medicine which is used for relieving cough and eliminating phlegm as well as has double functions of bronchiectasis and mucolysis.
MX 2009008548 (A) discloses the topical formulations of olopatadine for treatment of allergic or inflammatory disorders of the nose are disclosed. The aqueous formulations contain approximately 0.6 % (w/v) of olopatadine. JP 2009114213 (A) provide a topical formulation of olopatadine for treatment of allergic or inflammatory disorders of the eye and nose. ; SOLUTION: The aqueous formulations of this invention contain approximately 0.17 to 0.62%(w/v) of olopatadine and an amount of polyvinyl pyrrolidone or polystyrene sulfonic acid sufficient to enhance the physical stability of the formulation. The solution composition that can topically be administered for treatment of allergic or inflammatory disorders of eyes or noses is disclosed and the composition includes approximately 0.17 to 0.62%(w/v) of olopatadine and an amount of polyvinyl pyrrolidone or polystyrene sulfonic acid sufficient to enhance the physical stability of the formulation.
JP 2008127365 (A) provides a pharmaceutical composition effective for prophylaxis and/or. treatment of allergic diseases such as atopic dermatitis, bronchial asthma and allergic rhinitis. ; SOLUTION: The prophylactic and/or therapeutic agent for allergic diseases comprises a histamine H1 receptor antagonist and a CCR3 (C-C chemokine receptor 3) antagonist. IgE production inhibitor comprises the histamine H1 receptor antagonist and the CCR3. The histamine H1 receptor antagonist is selected from olopatadine, cetirizine, loratadine, desloratadine, fexofenadin, astemizole, chlorpheniramine, etc. and the CCR3 antagonist is N-4-[[[[[[(2S)-4-(3,4-dichlorobenzyl)morpholin-2-
yl]methyl]amino]carbonyl]amino]methyl]benzamide or the like. WO 2006097458 (A1) relates to a combination of ciclesonide with olopatadine.
WO 2004039408 (A1) relates to a medicinal composition characterized by containing olopatadine and an anticholinergic agent which has an excellent effect of controlling nasal discharge in allergic rhinitis.
Objectives of the Invention
The objective of the present invention is to provide a combination which is highly effective in allergy.
Yet another objective of the invention is to provide patient's compliance by combining two drugs which are generally used for co-morbid indications. Another objective .of the present invention is to combine two drugs which are not interacting with each other and have a different mechanism of action, used for similar indications.
Detailed description of the invention
Allergy is a disorder of the immune system which is a form of hypersensitivity. Allergic reactions occur to normally harmless environmental substances known as allergens; these reactions are acquired, predictable, and rapid. Strictly, allergy is one of four forms of hypersensitivity and is called type I (or immediate) hypersensitivity. It is characterized by excessive activation of certain white blood cells called mast cells and basophils by a type of antibody known as IgE, resulting in an extreme inflammatory response. Common allergic reactions include eczema, hives, hay fever, asthma attacks, food allergies, and reactions to the venom of stinging insects such as wasps and bees. Mild allergies like hay fever are highly prevalent in the human population and cause symptoms such as allergic conjunctivitis, itchiness, and runny nose. Allergies can play a major role in conditions such as asthma. In some people, severe allergies to environmental or dietary allergens or to medication may result in life-threatening anaphylactic reactions. A variety of tests now exist to diagnose allergic conditions; these include testing the skin for responses to known allergens or analyzing the blood for the presence and. levels of allergen-specific IgE. Treatments for allergies include allergen avoidance, use of anti-histamines, steroids or other oral medications, immunotherapy to desensitize the response to allergen, and targeted therapy.
The pathophysiology of allergic responses can be divided into two phases. The first is an acute response that occurs immediately after exposure to an
allergen. This phase can either subside or progress into a "late phase reaction" which can substantially prolong the symptoms of a response, and result in tissue damage. Proteins have unique properties that allow them to become allergens. Specifically, stabilizing forces in the tertiary and quaternary structure of the proteins resist degradation. Subsequently, they interact improperly with IgE immune cells. Most potentially allergenic proteins cannot survive the destructive environment of the digestive tract; similarly, others that are harmless but have strong structure resist the acidic environment of the digestive system and are sometimes tagged by the immune system as harmful. In other reactions, toxins attach to an existing protein. The immune system considers the protein as harmful to the organism, and rejects the protein, causing a dermatological or systemic response.
Acute response
Degranulation process in allergy. 1 - antigen; 2 - IgE antibody; 3 - FceRI receptor; 4 - preformed mediators (histamine, proteases, chemokines, heparine); 5 - granules; 6 - mast cell; 7 - newly formed mediators (prostaglandins, leukotrienes, thromboxanes, PAF)ln the early stages of allergy, a type I hypersensitivity reaction against an allergen, encountered for the first time, causes a response in a type of immune cell called a TH2 lymphocyte, which belongs to a subset of T cells that produce a cytokine called interleukin-4 (IL-4). These TH2 cells interact with other lymphocytes called B cells, whose role is production of antibodies. Coupled with signals provided by IL-4, this interaction stimulates the B cell to begin production of a large amount of a particular type of antibody known as IgE. Secreted IgE circulates in the blood and binds to an IgE-specific receptor (a kind of Fc receptor called FceRI) on the surface of other kinds of immune cells called mast cells and basophils, which are both involved in the acute inflammatory response. The IgE-coated cells, at this stage are sensitized to the allergen.
If later exposure to the same allergen occurs, the allergen can bind to the IgE molecules held on the surface of the mast cells or basophils. Cross-
linking of the IgE and Fc receptors occurs when more than one IgE-receptor complex interacts with the same allergenic molecule, and activates the sensitized cell. Activated mast cells and basophils undergo a process called degranulation, during which they release histamine and other inflammatory chemical mediators (cytokines, interleukins, leukotrienes, and prostaglandins) from their granules into the surrounding tissue causing several systemic effects, such as vasodilation, mucous secretion, nerve stimulation and smooth muscle contraction. This results in rhinorrhea, itchiness, dyspnea, and anaphylaxis. Depending on the individual, allergen, and mode of introduction, the symptoms can be system-wide (classical anaphylaxis), or localized to particular body systems; asthma is localized to the respiratory system and eczema is localized to the dermis.
Late-phase response
After the chemical mediators of the acute response subside, late phase responses can often occur. This is due to the migration of other leukocytes such as neutrophils, lymphocytes, eosinophils and macrophages to the initial site. The reaction is usually seen 2-24 hours after the original reaction. Cytokines from mast cells may also play a role in the persistence of long-term effects. Late phase responses seen in asthma are slightly different from those seen in other allergic responses, although they are still caused by release of mediators from eosinophils, and are still dependent on activity of TH2 cells.
Olopatadine is a selective histamine H1 receptor-antagonist possessing inhibitory effects on the release of inflammatory lipid mediators such as leukotrienes, thromboxane, platelet-activating factor (PAF), etc., from human polymorphonuclear leucocytes and eosinophils. It also inhibits the tachykininergic contraction in the bronchi of the allergen model by prejunctional inhibition of peripheral sensory nerves. Pharmacokinetics
After oral administration of a single dose of olopatadine hydrochloride 5 mg under fasting conditions, to healthy adults, olopatadine was absorbed rapidly and reached a maximum concentration Cmax of 107.66 + 22.01
ng/ml in about 0.5-2 hours (Tmax 1.00 + 0.32). The elimination half-life t1/2 was 8.75 + 4.63 hours, while the AUC parameter was 326 + 83 ng.hr/ml. The protein binding ratios in human plasma are in the range of 54.7-55.2%, and their main binding protein is human albumin. After oral administration of olopatadine hydrochloride at a dose of 80 mg, metabolites in the N oxide form (M3) and N -monodesmethyl form (M1) were detected in plasma at amounts of about 7% and 1% of the unchanged drug, respectively. The decrease in plasma concentrations of both the metabolites was parallel to the decrease of the unchanged drug. The N-didesmethyl form (M2) was not detected in plasma. When healthy adults were given a single oral dose of olopatadine hydrochloride 5 mg, the accumulated urine excretion percentage until 48 hours was in the range of 63.0-71.6% of the administered amount.
Olopatadine is indicated for the treatment of allergic rhinitis, urticaria and itching accompanied by skin diseases (eczema, dermatitis, pruritus cutaneous, psoriasis vulgaris, and erythema exudativum multiforme). Ambroxol theophylline-7-acetate (ACE) is the salt obtained by reaction of equimolar amounts of ambroxol (AMB), a drug showing mucolytic and expectorant properties, and theophylline-7-acetic acid (TAA), a xanthine derivative with specific bronchodilator activity.
Acebrophylline is an airway mucus regulator with antiinflammatory action. The drug's approach involves several points of attack in obstructive airway disease. The molecule contains ambroxol, which facilitates various steps in the biosynthesis of pulmonary surfactant, theophylline-7 acetic acid whose carrier function raises blood levels of ambroxol, thus rapidly and intensely stimulating surfactant production. The resulting reduction in the viscosity and adhesivity of the mucus greatly improves ciliary clearance. By deviating phosphatidylcholine towards surfactant synthesis, making it no longer available for the' synthesis of inflammatory mediators such as the leukotrienes, acebrophylline also exerts an inflammatory effect. This is confirmed in vivo by the reduction in aspecific bronchial hyper-responsiveness in patients with stable bronchial asthma. On a clinical level, acebrophylline is therapeutically effective in patients with acute or chronic
bronchitis, chronic obstructive or asthma-like bronchitis and recurrence of chronic bronchitis; it reduces the frequency of episodes of bronchial obstruction and reduces the need for beta2-agonists, and improves indexes of ventilatory function.
The present invention discloses the oral dosage formulation comprising Acebrophylline and Olopatadine.
The particles of the invention are obtained by wet granulation method. For granulation pharmaceutically acceptable organic solvents or mixtures thereof, or binder dispersion in an organic solvent are used. Preferred solvents include acetone, ethanol and acetonitrile, in particular acetone. The particles may be spherical or irregular in shape.
Olopatadine may be in the form of Olopatadine Hydrochloride. The range of Olopatadine varies from 1 mg to 20 mg, preferably 5 mg, while the range of Acebrophylline varies from 50 mg to 400 mg preferably 100mg to 200mg, most preferably 100mg immediate release in the combination. The particles of the present invention may comprise, in addition to the active substances, also excipients such as fillers, binders, disintegrants, glidants and lubricants. Suitable fillers are microcrystalline cellulose, powdered cellulose, lactose, starch, pregelatinized starch, sucrose, glucose, mannitol, sorbitol, calcium phosphate, calcium hydrogen phosphate, aluminium silicate, sodium chloride, potassium chloride, calcium carbonate, calcium sulfate, dextrates, dextrin, maltodextrin, glycerol palmitostearate, hydrogenated vegetable oil, kaolin, magnesium carbonate, magnesium oxide, polymethacrylates, talc and others, preferably microcrystalline cellulose and lactose. Suitable binders are starch, pregelatinized starch, gelatine, sodium carboxymethylcellulose, polyvinylpyrrolidone, alginic acid, sodium alginate, acacia, carbomer, dextrin, ethylcellulose, guar gum, hydrogenated vegetable oil, methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, glucose syrup, magnesium aluminium silicate, maltodextrin, polymethacrylates, zein, preferably hydroxypropyl cellulose, hydroxypropyl methylcellulose and polyvinylpyrrolidone. Suitable disintegrants are starch, pregelatinized starch,
sodium starch glycolate, sodium carboxymethylcellulose, cross-linked sodium carboxymethylcellulose, calcium carboxymethylcellulose, methylcellulose, microcrystalline cellulose, powdered cellulose, potassium polacrilinin, cross-linked polyvinylpyrrolidone, alginic acid, sodium alginate, colloidal silicon dioxide, guar gum, magnesium aluminium silicate and others, preferably sodium starch glycolate, cross-linked sodium carboxymethylcellulose and cross-linked polyvinylpyrrolidone. Suitable glidants are magnesium stearate, calcium stearate, aluminium stearate, stearic acid, palmitic acid, cetanol, stearol, polyethylene glycol of different molecular weights, magnesium trisilicate, calcium phosphate, colloidal silicon dioxide, talc, powdered cellulose, starch and others, preferably colloidal silicon dioxide. Suitable lubricants are steraic acid, calcium, magnesium, zinc or aluminium stearate, siliconized talc, glycerol monostearate, glycerol palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, mineral oil, light mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, talc and others. Preferred lubricants are magnesium and calcium stearate, and stearic acid.
The formed particles of the present invention have good flow and compressible properties.
Formed particles of the invention may optionally be coated with a release controlling coating or with a protective coating. The coating may be prepared from polymer or nonpolymer substances. Suitable polymers that may be used are hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, ethylcellulose, hydroxyethyl cellulose, sodium carboxymethylcellulose, cellulose phthalate acetate, polyvinyl acetate phthalate, hydroxymethyl cellulose phthalate, polyvinyl alcohol, methylhydroxyethy'l cellulose, polymers of acrylic and methacrylic acid, maltodextrin and others. Nonpolymer substances that may be used are camauba wax, cetyl alcohol, sucrose, glucose, shellac and others. The coating may optionally comprise other coating agents conventionally used in coating such as fillers, e.g. talc, lactose, polysaccharides and others, plasticizers, e.g. dibutyl sebacate, triethyl citrate, polyethylene glycol, adipic
acid, coconut oil, oleic acid and others, colourants, e.g. titanium dioxide, lakes, pigments and others, antioxidants and others. The object of the present invention are also pharmaceutical compositions comprising the above described formed particles. Coated and/or uncoated particles may be used. They may be filled into sachets or capsules, they may be compressed together with suitable excipients into tablets or they mey be used for reconstitution into suspension. Tablets may be single- or multilayer, dispersible, orodispersible, effervescent, chewing, pastilles. The tablets of the invention are hard and have suitable physical technological properties. By the addition of suitable excipients the release of the active substance from the tablet may be controlled. Excipients to be added to the formed particles for the preparation of the previously stated pharmaceutical compositions may be different fillers, binders, disintegrants, glidants and lubricants.
Suitable fillers may be microcrystalline cellulose, powdered cellulose, lactose, starch, pregelatinized starch, sucrose, glucose, mannitol, sorbitol, calcium phosphate, calcium hydrogen phosphate, aluminium silicate, sodium chloride, potassium chloride, calcium carbonate, calcium sulfate, dextrates, dextrin, maltodextrin, glycerol palmitostearate, hydrogenated vegetable oil, kaolin, magnesium carbonate, magnesium oxide, polymethacrylates, talc and others, preferably microcrystalline cellulose and lactose.
Suitable binders are starch, pregelatinized starch, gelatin, sodium carboxymethylcellulose, polyvinylpyrrolidone, alginic acid, sodium alginate, acacia, carbomer, dextrin, ethylcellulose, guar gum, hydrogenated vegetable oil, methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, glucose syrup, magnesium aluminium silicate, maltodextrin, polymethacrylates, zein, preferably hydroxypropyl .cellulose, hydroxypropyl methylcellulose and polyvinylpyrrolidone.
Suitable disintegrants are starch, pregelatinized starch, sodium starch glycolate, sodium carboxymethylcellulose, cross-linked sodium carboxymethylcellulose, calcium carboxymethylcellulose, methylcellulose,
microcrystalline cellulose, powdered cellulose, potassium polacrilinin, cross-linked polyvinylpyrrolidone, alginic acid, sodium alginate, colloidal silicon dioxide, guar gum, magnesium aluminium silicate and others, preferably sodium starch glycolate, cross-linked sodium carboxymethylcellulose and cross-linked polyvinylpyrrolidone.
Suitable glidants are magnesium stearate, calcium stearate, aluminium stearate, stearic acid, palmitic acid, cetanol, stearol, polyethylene glycols of different molecular weights, magnesium trisilicate, calcium phosphate, colloidal silicon dioxide, talc, powdered cellulose, starch and others, preferably, colloidal silicon dioxide.
Suitable lubricants are stearic acid, calcium, magnesium, zinc or aluminium stearate, siliconized talc, glycerol monostearate, glycerol palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, mineral oil, light mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate and others. Preferred lubricants are calcium or magnesium stearate and stearic acid.
Capsules and tablets may optionally be coated with a coating which may be applied from an aqueous or non-aqueous medium. A coating may control the release or it is only a protective coating. The coating may be prepared from polymer or nonpolymer substances. Suitable polymers that may be used are polyethylene glycol, hydroxyl propyl cellulose, hydroxyl propyl methylcellulose, methylcellulose, ethyl cellulose, hydroxyl ethyl cellulose, sodium carboxy methylcellulose, cellulose acetate phthalate, polyvinyl acetate phthalate, hydroxymethyl cellulose phthalate, polyvinyl alcohol, methylhydroxyethyl cellulose, polymers of acrylic and methacrylic acid, maltodextrin and others. Nonpolymer substances may be carnauba wax, cetyl alcohol, sucrose, glucose, shellac and others.
The coating may also comprise other conventionally used coating agents such as fillers, e.g. talc, lactose, polysaccharides and others, plasticizers, e.g. dibytil sebacate, trietyl citrate, polyethylene glycol and others; colorants, e.g. titanium dioxide, lakes, pigments and others, antioxidants and others. The formed particles are suitable for the preparation of multiple unit forms such as capsules or tablets with the primary formed particles wherein a
multiple unit form disintegrates to individual primary formed particles from
which the active substance is released. The formed particles are also
suitable for the preparation of multiple unit forms such as sachets and
dozers for multiple unit systems and others. Uncoated and/or coated
particles may be used.
The release of Acebrophylline and Olopatadine from the pharmaceutical
formulations of the present invention can be immediate or modified,
controlled, delayed, sustained, and extended. The release rate for both
active drugs can be the same or different.
The pharmaceutical formulations of the present invention may comprise
formed particles with the same composition or formed particles with different
composition and different release rate of Acebrophylline and Olopatadine.
The present invention also relates to the process for the preparation of the
formed particles regular and irregular in shape. They are prepared by the
wet granulation with organic solvent. For granulation either a solvent or
binder dispersion in an organic solvent may be used.
The present invention can be formulated, but not limited to, in the following
manner-
NO. INGREDIENTS Unite Total Qtv
1 Acebrofylline gm 103.0z
2 Olopatadine Hydrochloride gm 5.20
3 Starch gm 69.0
4 Micro Crystalline Cellulose gm 90.0
5 H.P.C gm 5.6
6 Purified water ml 160
7 Magnesium Sterate gm 2.8
8 Talcum gm 2.8
9 Colloidal Silicon dioxide gm 1.5
10 Sodium starch glycolate gm 6.0
Coating material
Sr. Total
NO. INGREDIENTS Unite Qty
1 H.P.M.C gm 8.40
2 Talcum gm 1.0
3 Titanium dioxide gm 2.0
4 P.E.G. gm 2.0
5 I.P.A ml 120
6 Methline Chloride ml 120
MANUFACTURING PROCESS
1. WEIGHING: Weigh all the ingredients and mark as given in weighment sheet
2. SIFTING: Dry the Excipients if necessary.
Sr.No. Ingredients Sieved Through
1 Acebrofylline #24
2 Olopatadine #24
Hydrochloride
3 Starch #100
. Micro Crystalline #80
Cellulose
3. DRY MIXING:
Take sifted materials of step 2 and transfer in RMG, Run the RMG for 10 Minutes .
4. BINDER PREPARATION:
(A) AQUEOUS
a) Dissolve .HPC 5.6gm in 100ml Purified water.
b) Make the slurry of 28 gm .starch and 1.5 gm Colloidal Silicon
dioxide by dispersing it into purified water.
c) Pour the slurry of step (b) in boiled water. Cool this paste at room
temperature.
d) To the paste of step (c) add solution of step (a).
(B) NON-AQUEOUS
a) Dissolve HPC 5.6 gm in 50.ml/Lit Isopropyl Alcohol with stirring.
5. WETMIXING:
(A) Pour the binder in the RMG containing dried mixed material Switch on the RMG.
6. WET MILLING: Pass the wet mass using # 8 manually.
7. DRYING: Dry the wet milled material in FBD/Tray drier at a temp
40-50° Air Dry for the time 60 mins. to get a moisture content
between 1.2%
8. SIFTING: Sift the dried granules threw 24 # sieve note the weight
of dried and sieved granules it is 118.2 kg/ gm
9. LUBRICATION: Take dried granules of step 8, to it add sieved
material of following table and mixed manually in PP bag for 15
minutes.

10. COMPRESSION: Compressed the lubricated granules using
required dies & Punches.

Claims
1. A method of treating respiratory disease in a human suffering from
an allergic and/or inflammatory condition which comprises
administering to such human in need of such treating an effective
amount of acebrophylline, or a pharmaceutically acceptable salt
thereof, in combination with an effective amount of Olopatadine or a
pharmaceutically acceptable salt thereof and preparation of the
pharmaceutically acceptable dosage formulation thereof.
2. As claimed in claim 1, wherein the effective amount of acebrophylline
is about 100 mg/day to about 400 mg/day.
3. As claimed in claim 2, wherein the effective amount of acebrophylline
is about 150 mg/day to about 300 mg/day.
4. As claimed in claim 3, wherein the effective amount of acebrophylline
is 200 mg/day.
5. As claimed in claim 1, wherein the effective amount of Olopatadine is
about 1 mg/day to about 20 mg/day.
6. As claimed in claim 6, wherein the effective amount of Olopatadine is
about 10 mg/day.
7. The pharmaceutically acceptable dosage formulation may include
oral, nasal, intravenous, and transdermal.
8. The preferable oral dosage formulation as claimed in claim 8 may be tablets, capsules or liquid oral formulation.
9. As claimed in claim 1, wherein the allergic and/or inflammatory is seasonal allergic rhinitis, perennial allergic rhinitis, atopic dermatitis, urticaria or allergic asthma