TW200838523A - Methods for treating nasal congestion in pediatric patients - Google Patents

Abstract

Methods for treating, preventing or reducing nasal congestion associated with allergic rhinitis in a pediatric patient are provided. Methods may involve administering to a pediatric patient a therapeutically effective amount of a pharmaceutical composition including loratadine and montelukast or a pharmaceutically acceptable salt of montelukast.

Description

200838523 IX. INSTRUCTIONS: [Prior Art] People around the world are often suffering from allergic nasal congestion, which causes partial or complete obstruction of the airway. Nasal congestion and related symptoms often have undesired effects on the tormented person, for example, disruption of sleep, loss of work, and loss of school attendance. Although it has been shown that antihistamines are effective in preventing and remedy substances, «, rhinorrhea and octopus, they are not effective in relieving nasal obstruction associated with allergic reactions. Therefore, sympathomimetic excitatory amine decongestants are usually administered simultaneously, such as phenylpropanolamine or pseudoephedrine, which can be administered to ^^^^, 乍α>" adrenoceptor agonist. However, all non-allergic patients should use these decongestants 'because of the observation of 疚 疚 # # # # 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到 到Including anxiety, insomnia, tachycardia, angina and high blood pressure. Phenylpropanolamine has been withdrawn from the US market. There is a need for treatment of nasal allergies associated with allergic conditions, and 1 does not exhibit neurological or cardiovascular effects associated with sympathomimetic excitatory amines. SUMMARY OF THE INVENTION The present invention provides a method for treating or preventing | # 防j pediatric patients with nasal congestion associated with allergic rhinitis. In some grievances, the present invention provides a method for stimulating/recovering or reducing the amount of nasal chores associated with allergic rhinitis in a patient in need thereof, wherein the patient is 2 to 12 years old. η η., patient skill and therapeutically effective amount of a pharmaceutical composition comprising loratadine and momelulcast or a pharmaceutically acceptable salt of I2780l.doc 200838523. In an exemplary embodiment, the pharmaceutically acceptable montelukast salt is montelukast. In certain embodiments, the method can be used to treat pediatric patients between the ages of 2 to 6 or 6 to 12 years old. In some cases, the methods may include loratadine and montelukast or a pharmaceutically acceptable ratio thereof in a ratio of from about Μ to about Η mg/kg: the pharmaceutical: composition. In certain embodiments, the pharmaceutical composition comprises loratadine and montelukast at a ratio of about: i, gram of gram, , ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, Or a pharmaceutically acceptable salt thereof. > : A _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ The doctor of salt - the beam, and the mouth. In certain embodiments, the medicinal composition comprises about 10 mg of loratadine and a pharmaceutically acceptable salt of 10 gram of Montelukast ; ; ;; Set a dose of about 5 mg of montelukast or an equivalent amount of the doctor's order, and the salt can be doubled on the sputum; about 5 rituximab and about 5 mg of montelukast 戋箄, 专 4 A pharmaceutically acceptable salt of xiaoxia, or about 5 mg of loratadine and about 4 亳

Temple One See Montelukast or an equivalent amount of A medically acceptable salt. κ /, In some embodiments, the methods can be used to treat or prevent nasal congestion associated with allergic rhinitis or perennial allergic rhinitis. In some embodiments, the methods can be used to treat severe nasal congestion. In certain embodiments, the methods can be used to contain lorrastat or a pharmaceutically acceptable salt thereof, and to a composition of „,田塔疋和孟鲁药. An additional therapeutic agent 127801.doc 200838523 In a case of a shellfish, 'therapeutic combination can be administered orally, nasally or ocularly in a second shell.' These methods can be formulated into liquids, lozenges, capsules, suppositories, granules. , a pharmaceutical composition of a suspension or a film, which is orally, chewable or instant. - a certain method of "being" can be used for treating or preventing pediatric patients suffering from hyperglossism and allergic rhinitis The nose is congested. 儿 = 中 'The present invention provides a treatment or to reduce the need for small

A method for nasal congestion associated with a pediatric patient and an allergic sputum, which comprises administering to a sputum patient a medicine comprising about 10 mg of loratadine and about 5 mg of mullet or a equivalent amount of the medicine. A pharmaceutical composition of an acceptable salt. ^ In some aspects, the present invention provides for the treatment or alleviation of a pediatric patient associated with allergic rhinitis in a pediatric patient, comprising about 5 mg of loratadine and: 4 milli == or equivalent A pharmaceutical combination of pharmaceutically acceptable salts thereof: in one aspect, the present invention provides a method for treating or alleviating nasal congestion associated with allergic rhinitis in pediatric patients, to a 12-year-old pediatrician The patient is administered a drug containing about milligrams of lorata; ^5 to Gu 6: montelukast or an equivalent amount of a pharmaceutically acceptable salt thereof. In some aspects, the present invention provides a treatment or amelioration A method for nasal congestion associated with allergic rhinitis in a pediatric patient, 苴, a pediatric patient up to 5 years old, containing about 5 mg of chlorine to 2 montelukast or an equivalent amount of its pharmaceutically acceptable _, hair κ "Γ chewing tablets. 12780I.doc 200838523 [Embodiment]

The methods provided herein include methods of treating, preventing, or ameliorating pediatric patients<# allergic rhinitis-related nasal congestion by administering a therapeutically effective amount of an antihistamine and a leukotriene D4 receptor antagonist to a pediatric patient Agent to #成. Examples of suitable antihistamines include, for example, chlorpheniramine maleate (Chlor-trimeton®), dexchlorpheniramine maleate, and diphenhydramine hydrochloride. (Benadryl®), doxylamine succinate, isopropyl hydrazine and triprolidine hydrochloride. Low sedative or non-sedating antihistamines can also be used in conjunction with the various methods described herein. Examples of suitable low-sedating or non-sedating antihistamines include, for example, loratadine (Claritin®), fexofenadine hydrochloride (Allegra®), cetirizine hydrochloride Examples of suitable leukotriene D4 receptor antagonists (Zyrtec®), levocetirizine (Xyzal®) and terfenadine (Teldane®) include, for example, montelukast ( Singulair®), Zafirlukast (Accolate®), Zileuton (Zyflo®) and pranlukast. In certain embodiments, the method of treating or preventing nasal congestion associated with allergic rhinitis in a pediatric patient described herein relates to administering to a pediatric patient a therapeutically effective amount of loratadine and montelukast or pharmaceutically acceptable Montelukast salt. As used herein, a pediatric patient means a human patient younger than 15 years old, a patient from 3 months to 14 years old, a patient from 3 months to 12 years old, a disease from 3 months to 10 years old 127801.doc 200838523 person, 3 months Patients up to 8 years old, patients from 3 months to 6 years old, 3 months to 2 years old, 3 months to 4 years old δ. Patients, 6 months to old & χ to 12 years old , 6 months% of patients, 6 months

々 to 10 years old, 6 RR, 6 months to 6 years old to 8 years old, 6 months to 4 years old, 2 to 14 years old , 6 months to 2 years old eight people, 2 to! 2 year old, 2 to 8 year old patient, 2, 2 to 1 year old, z main 6 year old patient, 2 to 4, 14 year old patient, 6 to 12 year old patient, 6 to % < Patient, sputum 6 to 1 year old, patient, 8 to 14 years old, patient with conscience, patient with 4 to 6 years old, 0 patient with 8 to 12 years old, 10 to 14 wide 竑A, Patients between the ages of 8 and 10 to 14 years old, or patients between the ages of 1 and 12. The various methods described herein can be used in the treatment of sensitizing phlegm and phlegm and stagnation + mitigation or alleviation and allergic ^ "severe, moderate or mild nasal congestion, providing treatment or prevention of severe nasal congestion. The type of nasal congestion that is treated, prevented or alleviated in the second instance includes internasal nasal congestion and sputum filling. If the patient has a seizure usually at the time of daytime or at night, the blood can change the time of administration to most effectively treat the patient. In some ΛC* cases, a combination of loratadine and montelukast or a pharmaceutically acceptable salt thereof may be administered at night or at bedtime to treat, prevent or reduce nocturnal nasal congestion. In certain embodiments, a combination of loratadine and montelukast or a pharmaceutically acceptable salt thereof may be administered in the morning, after waking up, or at breakfast to prevent or reduce daytime nasal congestion. . In certain embodiments, the combination of loratadine and montelukast or a pharmaceutically acceptable salt thereof can be administered early, after waking or at breakfast to treat, prevent or ameliorate nocturnal nasal congestion. In certain embodiments, a combination of loratadine and montelukast or a pharmaceutically acceptable salt thereof can be administered at night or at bedtime to treat, prevent or reduce 127801.doc 200838523. - In certain embodiments, the methods described herein can be used to treat, prevent, or eradicate nasal congestion associated with allergic rhinitis, including seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (pAR). Seasonal allergic rhinitis includes season I season, or winter or allergies in combination. In certain embodiments, the methods include those that are useful for treating, preventing, or ameliorating allergic rhinitis associated with indoor allergens, outdoor allergens, or both. Examples of indoor allergens include, for example, dust, mold, and pet dander. Outdoor allergies = Examples include, for example, tree pollen, weeds, grass and flowers. Perennial is usually associated with indoor allergens, and seasonal allergic rhinitis is associated with outdoor allergens. In certain embodiments, a combination of pharmaceutically acceptable salts can be administered prophylactically to a patient. Prophylactic administration may include seven people, such as patients with allergic diseases associated with nasal congestion who are susceptible to seasonal allergic rhinitis, and susceptible heterosexual allergens (eg pet dander, grass, flowers, etc.) A patient who causes allergies. People ^ ^ ^ in 'with nasal congestion associated with allergic rhinitis', 0 have other conditions, such as asthma. A pediatric patient with nasal congestion associated with allergic rhinitis may also have /C, such as asthma, high A S, diabetes, or liver function decline. Various methods described in the article can alleviate nasal congestion and blood transfusion agents (for example, pseudo-presidents such as Ding brothers, pseudo-α-arsenic, related), crayfish', ephedrine, phenylpropanolamine or phenylephrine i η One of the goals is that it does not expect side effects, or significantly reduces the incidence and/or severity of such side effects 127801.doc 200838523. Side effects associated with administration of sympathomimetic excitatory amines may include (eg Insomnia, nervousness, nervousness, upset, anxiety, dry mouth, high blood pressure, tachycardia, headache, and dizziness. In some embodiments, the combination of loratadine and montelukast results in A side effect condition comparable to a placebo. In certain embodiments, one or more undesirable side effects of the sympathomimetic agent can be avoided while producing a relief of nasal congestion that is substantially the same as that obtained with a therapeutically effective amount of the sympathomimetic agent. The effect of relieving nasal congestion is substantially the same as that of the sympathomimetic agent, which means that the effect produced by the therapeutically effective amount of the sympathomimetic agent is 30 〇/〇, ±2〇0/. ±10% or ±5%, as determined by the standard procedure for measuring nasal congestion. In some embodiments, the same nasal venous effect as the sympathomimetic agent means that the effect produced is a therapeutically effective amount. The sympathomimetic agent produces at least 70%, 80%, 90%, 95% or more of the effect of relieving nasal congestion. In certain embodiments, the methods described herein are administered during a 24 hour period, initially after administration. The nasal congestion-enhancing effect is substantially the same as that of the sympathomimetic agent within 12 hours, or 12-24 hours after administration. In certain embodiments, the therapeutically effective amount of the sympathomimetic agent is effective during 24 hours. The amount of pseudoephedrine that is nasally congested. Such formulations of pseudoephedrine may be prepared by those skilled in the art or may be purchased from J. H. & (10) New Brunswick, NJ. In certain embodiments, 'this article The method can be used for treating, preventing or alleviating nasal congestion associated with allergic rhinitis in a pediatric patient, and the side effects of the sympathomimetic agent in # are poor for the patient. For example, the disease is 127801.doc 200838523 Human administration of a sympathomimetic agent can aggravate an existing condition (such as hypertension). In some embodiments, administration of a sympathomimetic agent may be contraindicated in this patient to 0 loratadine, ie 4-(8- Chloro-5,6-dihydro-11H-benzo[5,6]cycloheptaπ,2_b]pyridine-11-ylidene-hexahydropyridinecarboxylate, non-sedating histamine h-receptor Antagonist. Loratadine for the treatment of allergies is produced by SChering-Plough Health Care pr〇ducts

Daritin® is sold and can be prepared, for example, as described in U.S. Patent No. 4,282,233. Montelukast, 1-[[[(1R)小[3_[(10)-2_(7_气_2_嗜琳) vinyl]phenyl]-3-[2-(1-) Methylethyl)phenyl]propyl]thio]methyl]cyclopropylethylidene is a selective white tri-orbital receptor antagonist. The montelukast sodium used to treat allergies is marketed by Merck & c〇

Singuiah - sold and can be prepared, for example, as described in U.S. Patent No. 5,27,324. The effective Montelukast salt includes, for example, a salt prepared from a pharmaceutically acceptable non-toxic test (including inorganic bases and organic bases). The more inorganic bases are included, including salt, salt, salt, steel, iron, ferrous, bell, salt, salt, divalent, salt, potassium, salt, salt, and the like. . In certain embodiments, the pharmaceutically acceptable montelukast salt is montelukast sodium. Salts derived from pharmaceutically acceptable organic non-toxic bases include primary, secondary and secondary, substituted amines (including naturally substituted amines), cyclic amines, and anionic ion exchange resins (IV), such as arginine, beet, b addition of morphine base, N, N,-dibenzylethyl-amine, - ^ virgin monoethylamine, guanidine diethylaminoethanol, 2 _ 127801.doc 200838523 methylaminoethanolamine, ethylenediamine疋运运', glucosamine, glucosamine, histidine, amine (-), isopropylamine, lysine, methyl-reducing glucosamine: morpholine, hexamazine, hexahydropyridine, polyamine Salts of resin, procain:, gramine, cocoa, triethylamine, trimethylamine, tripropylamine, and amine butanediol. </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> form. Therefore, to determine the specific salt form: Etc. θ is the ratio of the amount of Mengzisite (free acid) multiplied by the ratio of the montelukast anion divided by the Mengmulit molecular weight (eg, montelukast sodium / Monroe is in the range of 1 gram * gram of montelukast (free acid). In some embodiments, the method provided herein comprises co-administering loratadine or a pharmaceutically acceptable salt thereof. Individuals are individually dosed (simultaneously or sequentially) to perform co-administration. In a certain =, loratadine and montelukast or its pharmaceutically acceptable salt vine two contain a co-mixture of two active agents The drug may be administered. The active agent may be formulated in a single dosage form comprising loratadine and montelukast or a pharmaceutically acceptable salt thereof. - Single-dose-daily dosage form, for example, administered once every day for 12 days or 2 days or longer. Regular blood, Ge, and early dosage forms are used to treat persistent allergies. Nasal filling may be sporadicly administered as needed to treat nasal congestion, sand acute and / 127801.doc -13· 200838523 or Sexual treatment. It can effectively treat, prevent or alleviate the amount of loratadine and Meng (4) or its pharmaceutically acceptable salt in nasal congestion associated with allergic rhinitis in pediatric patients. It can be related to age, sex, weight and general health. , nasal congestion severity, sputum and sputum, bioavailability of the formulation administered, selected dosage regimen, and concomitant drug use. The dosage and/or frequency of administration can be adjusted to meet the needs of the individual patient. Those who are familiar with this technology use conventional technology

A suitable total daily dose range can be readily determined. The daily dose can be administered in a single dose or in divided doses. It may be from about 1:5 mg/mg to about 5:1 mg/mg, from about u mg/mg to about 3:13⁄4 g/mg, from about 1:2 mg/mg to about 2: 丨mg/mg, about 2 : 1 mg/mg, : L25: 1 mg/mg, or about ι:ι mg/mg ratio containing loratadine and montelukast or a pharmaceutically acceptable salt thereof, administered to lorata A combination of Monroe 4 Temple or its pharmaceutically acceptable salt. In general, loratadine and montelukast or a pharmaceutically acceptable salt thereof are effective for treating, preventing or ameliorating allergic rhinitis in pediatric patients and associated nasal congestion for administration in a single dose or in separate doses. i to about 2 mg of loratadine and about 1 to about 20 mg of montelukast or an equivalent amount of a pharmaceutically acceptable salt thereof, about 2 to about 20 mg of loratadine and about 2 to about 2 〇 mg of montelukast or an equivalent amount of a pharmaceutically acceptable salt thereof, from about 2 to about 1 mg of loratadine and from about 2 to about 10 mg of montelukast or an equivalent amount thereof Accepted salts, or from about 2 to about 5 grams of loratadine and from about 2 to about 5 milligrams of montelukast or an equivalent amount of a pharmaceutically acceptable salt thereof. In certain embodiments, the amount of loratadine and montelukast or a pharmaceutically acceptable salt thereof is about 127801.doc -14. 200838523 mg loratadine and about 1 mg to Rusit or An equivalent amount of a pharmaceutically acceptable salt thereof, about 10 mg of loratadine and about 5 mg of montelukast or an equivalent amount of a pharmaceutically acceptable salt thereof, about 5 mg of loratadine and about 5 Mg of montelukast or an equivalent amount of a pharmaceutically acceptable salt thereof, or about 5 mg of loratadine and about 4 mg of montelukast or an equivalent amount of a pharmaceutically acceptable salt thereof.

In certain embodiments, the methods described herein comprise administering to a pediatric patient having nasal congestion associated with allergic rhinitis a single daily dosage form comprising 1 mg of lorata, mG. 4 mg of montelukast, 1 () mg of loratadine and 5.2 mg of montelukast sodium, 5 mg of loratadine and 52 mg of montelukast sodium, or 5 mg of loratadine and 4.2 mg of montelukast sodium. In certain embodiments, pediatric patients between 1 and 12 years of age, 1 to 14 years of age, or 12 to 14 years of age may be administered with 10 mg of loratadine and 1 mg of montelukast or equivalent. A single dose of a pharmaceutically acceptable salt thereof. In certain embodiments, it may be 6 to 14 years old, 8 to 14 years old, 1 to 14 years old, 12 to 14 years old, 6 to 12 years old, 8 to 12 years old, 1 to 12 years old, 6 to 1 inch. A pediatric patient aged -8 years, or 6 to 8 years old, is administered a single dose of guanidine containing 1 mg of loratadine and 53⁄4 g of montelukast or an equivalent amount of a pharmaceutically acceptable salt thereof. In certain embodiments, it can be 2 to 12 years old, 2 to 10 years old, 2 to 8 years old, 2 to 6 years old, 2 to 4 years old, 4 to 12 years old, 4 to 10 years old, 4 to 8 years old, 4 Pediatric patients up to 6 years old, 6 to 12 years old, 6 to 10 years old, or 6 to 8 years old, who administer 5 mg of loratadine and 5 mg of montelukast or equivalent amounts of their pharmaceutically acceptable salts One dose earlier. 127801.doc -15- 200838523 In certain embodiments, may be from 3 months to 8 years, 3 months to 6 years, 3 months to 4 years, 3 months to 2 years, 6 months to 8 years old , 6 months to 6 years, 6 months to 4 years, 6 months to 2 years, 3 months to 6 months, 2 to 12 years, 2 to 10 years, 2 to 8 years, 2 to 6 years old Pediatric patients, 2 to 4 years old, 4 to 12 years old, 4 to 10 years old, 4 to 8 years old, 4 to 6 years old, 6 to 12 years old, 6 to 10 years old, or 6 to 8 years old, are administered with 5 mg of chlorine. A single dose of rituxetidine and 4 mg of montelukast or an equivalent amount of its pharmaceutically acceptable salt.

Various methods of treating, preventing or ameliorating nasal congestion associated with allergic rhinitis in a pediatric patient described herein can include administering loratadine and montelukast or a pharmaceutically acceptable salt thereof and at least one other therapeutic agent. Such therapeutic agents may include, for example, non-narcotic analgesics (eg, acetaminophen (Tylenol®) or cyclooxygenase-2 inhibitors (eg, celecoxib (Celebrex 2), valdecoxib (valdecoxib) (Bextra®), lumiracoxib (Prexige8), etoricoxib (Arcoxia®), etc.); non-steroidal anti-inflammatory drugs (eg aspirin (aspid), indomethacin) (indomethacin) (Indocin®), ibuprofen (Motrin8), naproxen (Naprosyn®), piroxicam (Feldene®), and naproxen (nabumetone) ( Relafen®), etc.; long-acting β2-adrenergic agonists (LAB A) (eg salmeterol, formoterol, bambuterol, etc.); corticosteroids (eg Prednisone, prednisolone, guanidinoprednisolone, mometasone furoate monohydrate, beclomethasone, flunisolide, acetone Triamcinolone acetonide, C 127801.doc -16- 200838523 Fluticasone propionate, dexamethasone sodium phosphate, budeoriicie, etc.; or antitussives (eg dextromethorphan, codeine, Hydrocodone, etc.). The additional therapeutic agents may be formulated separately and administered separately to the patient or may be co-formulated with loratadine and montelukast or a pharmaceutically acceptable salt thereof.

One or more physiologically acceptable carriers or excipients may be used in a conventional manner for a five-week co-mixture of thunder and montelukast or a pharmaceutically acceptable salt thereof. General techniques and formulations can be found in A. Gennar〇 (ed).

Remington’s Pharmaceutical Sciences 18th Edition, (1990), Mack

Publishing, Easton, PA. According to the various methods described herein, any suitable route of administration can be employed to provide the patient with an effective amount of loratadine and montelukast or a pharmaceutically acceptable salt thereof. For example, oral, intraoral, rectal, parenteral, transdermal, transdermal, subcutaneous, intramuscular, intranasal, sublingual, intradural, intraocular, intraoral, oral or nasal. Inhalation and similar forms of administration.

A variety of suitable dosage forms can be used to administer loratadine and montelukast or it! The sputum can be further salt, and the dosage forms include, for example, tablets, chewable fins, quick-melting formulations, tablets, dispersions, granules, suspensions, solution capsules, patches, liquids, syrups , ugly agent, gel, powder, milk poly #1 ^ #J . |L#J ^ ^ ^ ^ B disc-shaped agent, agent, film, nasal or oral spray, aerosol and the like. Because it is easy to use, n M h uses the tablets and capsules to represent the best oral dose.

In the form of a unit, a solid pharmaceutical carrier can be used in this case. The tablet may be coated by a quasi-aqueous or non-aqueous technique by the standard 127801.doc -17- 200838523. In some embodiments, the continuous release of the composition can be continued to control the release of loratadine and / or the rate at which montelukast or its medical company kills acceptable salts to optimize treatment outcomes. Formulations suitable for use in the continuous release include a layered lozenge comprising a plurality of disintegrations having different disintegration rates or having a split of the active component and shaped into a tablet form. A layer that controls the release of a polymeric matrix; or a capsule that encapsulates the impregnated or embedded porous polymeric matrix. Solid form preparations include powders, lozenges, μ-mango troches, dispersible granules, capsules, cachets, and suppositories.嗲辇y 4 #Solid dosage form can be prepared by using two pharmaceutically acceptable excipients, such as a binder (for example, pre-corn starch, poly-glycolyl or the propylmethyl fiber), Daily cellulose or calcium hydrogen phosphate; magnesium sulfate, talc or dioxin; a disintegrant (such as potato sour); or a solution (such as sodium sulphate). The active ingredient can constitute a solid. The dosage form is about 5% to about 95% of the tenth to the weight. The tablet, the private agent, the diamond tablet, the sachet, and the m^ table J are used as a solid dosage form suitable for oral administration. A method well known in the art comprises a tablet. A method of preparing a key agent, for example, by (as needed) with one or more auxiliary ingredients, a pressure-type formula is used to prepare the "H". It can be prepared by compressing the active form of a free-flowing report in a mobile form (such as a powder or a granule) in a suitable machine, and the active ingredient can be prepared with a binder, a lubricant, or an inert diluent. Surfactant 哎 b b ^ ^ — knife 蜊 rolling. Molded tablets can be used in the machine Molding with an inert liquid core were prepared. Compound powder mixture moistened night donor diluent 127801.doc -18- 200838523

Rapidly disintegrating or dissolving dosage forms (e.g., quick-melting formulations) can be used for rapid absorption of pharmaceutically active agents, especially for buccal and sublingual absorption. Rapid-melting formulations such as lozenges can be prepared using standard techniques. For example, the granules of the fast-melt lozenge prepared by spray drying or pre-compacting process can be mixed with excipients and compressed into tablets using a conventional tablet preparation machine. The granules can be combined with various carriers (including low density high mold processing saccharides, low mold processing saccharides, polyols) and then directly pressed into ingots exhibiting improved solubility and disintegration conditions. Agent. Fast melt tablets typically have a hardness of from about 2 to about 6 Strong-Cobb units (scu). The tablet in this hardness range can rapidly disintegrate or dissolve upon chewing. In addition, the tablets rapidly disintegrate in water. On average, t' is disintegrated in 1-3 minutes without disturbing the mixture. This rapid disintegration facilitates the delivery of the active material. See, for example, U.S. Patent No. 5,112,616 and U.S. Patent No. 4,616,047; The liquid preparation for oral administration can be, for example, a solution, a sugar-polymerizing agent, a Wei or a suspension, or it can be present in the form of an anhydrous product to be passed through water or other suitable structure before use. The liquid preparation can be prepared by a conventional method using a pharmaceutically acceptable additive such as a suspending agent (for example, a sorbitol syrup, a cellulose derivative or a hydrogenated food); an emulsifier (for example, an Indian knee). Non-aqueous vehicles (such as oil, oil vinegar, ethanol or refined vegetable oil); and preservatives (for example, methyl or propyl p-hydroxyl-formate or, as the case may be, such preparations may also contain buffer salts, bridge odorants, Pigments and sweeteners. The preparations can be suitably formulated to control the release of the compound. The parenteral form can be administered intravenously, intramuscularly or subcutaneously. 127801.doc 19 200838523 is usually in the form of a sterile solution. And human osmotic adjustment agent (a 戋 及 及 及 缓冲 。 。 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体 液体Gas (eg, _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Private) 4 suitable and promote the delivery of active agents If you add σ g package or sprayer, Zidan glue, you can use the valve to deliver the measured amount to determine the dosage unit. The capsule and tube can be blended with the ^^ human input device. A mixture of powders such as Ming (10) such as lactose or house powder: σ can also be delivered transdermally in combination with a suitable powder base, loratadine and montelukast or its acceptable salts. The composition may be used in the form of a remedy, rinsing, aerosol, and/or lotion I and may be included in an industrial type of transdermal patch for this purpose. In certain embodiments, the pharmaceutical dosage form is in the form of an early dosage form. In this form, the preparation can be subdivided into an appropriate amount of saponin, for example, in an effective phantom active ingredient that achieves the intended purpose. Unit dosage of suitable specifications. It can be used to enhance the yoghurt and gamma compliance of chlorhexidine and montelukast or ruler/salt-acceptable salts. The pharmaceutical formulation uses any type of taste masking method. y, a method for hiding taste K soil ^ and the use of sweeteners, flavoring agents or foaming agents to mask or mask the active ingredients to take the ancient taste. For example, the preparation can be used to complement or exhibit a longer lasting strength and stronger taste than the drug. Suqiao scent. It is often used as a high-concentration sweetener to suppress bitterness with sweetness. Suitable for 127801.doc -20· 200838523 sweeteners include bran; ^, , sugar, etc., sugar/sweeteners, such as sugar ( For example, glucose 1 temple) saccharin, dipeptide sweetener (such as: (-)) and sugar alcohol (such as, for example, sorbitol, - can also be used by menthol or sacred corpse you soil 10% sugar% 4 Use the body agent to anesthetize the flavor. Many formulas make the flavoring agent. The towel is a mother-of-pearl, cherry, orange or grape flavor used to conceal the biochemical ancient, soil, and shore. Reacts with the bitter taste receptor site thereby inhibiting the response to the bitter taste of the drug. Other methods of concealing are based on physical means such as agglomeration, coating and microcapsule release = for masking taste, promoting swallowing and/or delaying the release of the active ingredient. The release rate of the drug in the body. : can: = = release mechanism to control the thickness of the drug coating and the choice can be achieved by (4) two formulas, such as conditioning package ... special coating type of coating composition of the coating polymerization can also be made into pellets or granules to reduce the surface The area is then provided with an anti-saliva coating. ^Apply various types of coatings to the outside of the tablets and powders to achieve the desired period. The enteric coating is designed to be soluble in the intestine (where the pH is 6.5 or higher) = insoluble in the stomach (where the pH is lower) . On the other hand, the enteric coating is: Ten = partially soluble in the stomach (i.e., under acidic or lower pH conditions), thereby releasing the drug during the month. Ugly sac sac is a process by which a coating is applied to small solid particles, small droplets or a liquid to form microcapsules. This technique differs from other coating programs in that the size of 127801.doc -21 · 200838523 is usually between a few tenths of a micron and a diameter of 5 micro

When the active drug is formulated as a whole lotion or capsule, the taste of the active ingredient is generally not a problem 'because the capsule prevents the active ingredient from contacting the mouth and the tablet can be coated for storage in the mouth. Prevent the active ingredient from coming into contact with the π cavity for a short period of time. In contrast, the unpleasant taste characteristics of the masking active agent in the liquid and in the pharmaceutical formulation are a very important factor, liquid or pharmaceutically acceptable, and the palatability of the chewable type is the key to ensuring patient compliance. Liquid formulation is disclosed in US Patent No. 5,599,556. Wherein the active ingredient is coated with a single layer polymeric outer coating derived from prolamin granule protein and a plasticizer. The coatings are designed such that the coating exits the mouth 15 and the coating rapidly degrades.

Because of the difference between these particles. U.S. Patent No. 5,489,436 discloses a chewable preparation prepared from a coated drug wherein the coating is designed to be soluble in the acidic pH of the stomach but relatively insoluble in the oral cavity &quot;intestinal coating&quot;; The f coating comprises a polymer blend of dimethylaminoethyl methacrylate with a neutral methacrylate and a cellulose ester. U.S. Patent No. 6,136,347 discloses liquid suspension formulations, especially for oil-based juices or taste-masked microcapsules in suitable liquids such as water. The microcapsules comprise particles of the active ingredient coated by a single layer of polymer outer coating, the outer coating being derived from a film forming back J such as a polymethacrylic acid neutral methyl ester compound. The 忒4 coating is designed to be water insoluble and the coating rapidly degrades once the composition reaches the acidic environment of the stomach. 127801.doc • 22-200838523 US Patent No. 6,027,746 discloses a soft chewy gelatin capsule in which a drug adsorbate is dispersed in a solid or liquid filling material. The drug is absorbed onto the flaky particles of the adsorbate such as magnesium tricaprate, citrate dioxide or a mixture thereof. The capsule filling material in which the adsorbate is dispersed includes flavoring agents, sweeteners, corn syrup, solvents, and other food-grade excipients that help stabilize and mask the bitterness of the drug. U.S. Patent No. 7,067,116 discloses an instant orally consuming film which contains a taste masking agent such as an ion exchange resin to mask the taste of the pharmaceutically active agent formulated in the film. U.S. Patent No. 4,581,232 discloses the use of magnesium tristearate for the formation of pharmaceutical adsorbates to render bitter-tasting drugs odorless in liquids, lozenges and chewable dosage forms. These dosage forms reach the low pH environment of the stomach in the adsorbate. It can be easily utilized by the organism. A number of studies have been published on the evaluation of combination therapies with montelukast and loratadine. For example, a double-blind, placebo-controlled trial evaluated montelukast, loratadine, and combination therapy with montelukast and raldastatin for patients with seasonal allergic rhinitis in the fall Validity and tolerability (see Nayak, AS et al., (d) d 〇 / montelukast alone or in combination with loratadine in seasonal allergic rhinitis: a multicenter, randomized, double-blind, placebo-controlled trial performed in the fcdl,

Annals of Allergy, Asthma &amp; Immunology 88: 592-600 (2002)). The study concluded that the use of montelukast alone or in combination with loratadine is well tolerated in patients with seasonal allergic rhinitis 127801.doc -23- 200838523 and provides clinical and quality of life benefits. Another study evaluated the efficacy of loratadine in combination with montelukast in subjects with seasonal allergic rhinitis with severe nasal congestion (see Prenner, B. et al., of loratadine (L)-Monielukast (M) Combination (LMC) in seasonal allergic rhinitis (SAR) subjects with severe nasal congestion (NC) without a history of perennial allergic rhinitis (PAR), Annals of Allergy, Asthma &amp; Immunology 90: 122 (Abstract page 30) (2003) And Rachelefsky, G. et al.

Assessment of the efficacy of loratadine (L)-Montelukast (M) combination (LMC) in seasonal allergic rhinitis (SAR) subjects with severe nasal congestion (NC), Annals of Allergy, Asthma &amp; Immunology 90: 123 (Abstract page 31 ) (2003)). The study concluded that the use of the combination was comparable to the effect of loratadine alone. Another randomized, double-blind study compared the combination of fensapride-pseudoephedrine with loratadine- montelukast in the treatment of seasonal allergic rhinitis (see Moinuddin, R. et al., Comparison of the combinations of fexofenadine-pseudoephedrine) And loratadine-mnontelukast in the treatment of seasonal allergic rhinitis} Annals of Allergy, Asthma &amp; Immunology 92: 73-79 (2004)) 〇 This study concluded that fesoteine-pseudoephedrine and chlorhexidine in seasonal allergic rhinitis He destined-Montalupast was equally effective in improving symptoms, rhinitis and conjunctivitis quality of life survey (RQLQ) scores and nasal congestion. Equivalents The present invention provides, inter alia, a method of treating, preventing or ameliorating pediatric patients and allergic 127801.doc -24-200838523. Although the specific embodiment of the present invention has been discussed, the above is illustrative and not limiting. Many variations of the invention will become apparent to those skilled in the art after reading this description. The full scope of the invention and the full scope of its equivalents and the full scope of the modifications are intended to be

127801.doc -25-

Claims (1)

200838523 X. Patent application scope: 1 · A method for treating or alleviating nasal congestion associated with allergic rhinitis in a patient in need thereof, wherein the patient is 6 months to 12 years old, and the method includes administering the treatment effective to the patient A pharmaceutical composition comprising loratadine and montelukast or a pharmaceutically acceptable salt thereof. 2. A method of claiming wherein the pharmaceutically acceptable montelukast salt is Montelukner. The method of claim 1, wherein the pediatric patient is 2 to 6 years old. The method of claim 1, wherein the pediatric patient is 6 to 12 years old. The method of claim 1, wherein the pharmaceutical composition comprises loratadine and montelukast or a pharmaceutically acceptable salt thereof in a ratio of from about 1:2 to about 2d milligrams per gram. The method of claim 1, wherein the pharmaceutical composition comprises loratadine and montelukast or a pharmaceutically acceptable salt thereof in a ratio of about 1.25:1 mg/g. The method of claim 1, wherein the pharmaceutical composition comprises loratadine and montelukast or a pharmaceutically acceptable salt thereof in a ratio of about 2:1 mg/mg. 8 as shown in Table 1 vv ^, Wherein the pharmaceutical composition comprises about 1 mg of chlorhexidine and about 5 g of montelukast or an equivalent amount of a pharmaceutically acceptable salt thereof. ', and 9 · If requested by q, the method, wherein the pharmaceutical composition comprises about 5 mg of thunder and about 4 4 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , 200838523 10. The method of claim + 9 1 wherein the allergic rhinitis is seasonal allergic rhinitis. 11. The method of claim 1, wherein the allergic rhinitis is perennial allergic rhinitis. 12. The method of claim 1, wherein the nasal congestion is severely nasal congestion. 1 3 ·If the Qing Dynasty 1 And a method wherein the pharmaceutical composition further comprises at least one additional therapeutic agent. 14. If the request is made, the pharmaceutical composition is administered orally by the Lu. , verbose $ 15 · The method of claim 1 , tablets, capsules, suppositories, 16. The method of claim 15 is dissolved. Wherein the pharmaceutical composition is formulated as a liquid, granule, suspension or film. Wherein the tablet is orally, chewable or fast = item 1, which causes the pediatric patient to have asthma. Guan Zhijun: The need for pediatric patients to treat or alleviate the method of allergic rhinitis with 10 ancient blood. 'This method includes administering to the pediatric patient that it contains about 〇冤克克雷雷定 and about 5 mg Meng j or etc. A pharmaceutical composition of a therapeutically acceptable salt thereof. /, 19 · Kinds of pediatric patients in need of treatment of pain, $P s waste or alleviate allergic rhinitis, the method of I congestion, including 5 to the vouchers ~ a &quot; J, pediatric patients included Approximately </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; , - Liang Shang 2〇 · - for the pediatric patients in need of treatment or relief and allergic rhinitis phase 127801.doc 200838523 closed nasal congestion t ^ heart stone method, which includes the delivery of pediatric patients from 6 to 12 years old A (four) lozenge comprising about 10 sets of cumin &amp; ruthenium tromethamine and about 5 mg of montelukast or an equivalent amount of 2 of its pharmaceutically acceptable salt. Guan's treatment or alleviation of allergic rhinitis, café; two ounces of delicious and chewy scented with acceptable salt. Or 4 127801.doc 200838523 VII. Designated representative map: (1) The representative representative of the case is: (none) (2) The symbolic symbol of the representative figure is simple: 8. If there is a chemical formula in this case, please reveal the best display of the characteristics of the invention. Chemical formula: (none) 127801.doc