JP2007530620A - Composition comprising meloxicam - Google Patents

Abstract

  The present invention relates to a pharmaceutical composition comprising meloxicam or a pharmaceutically acceptable salt thereof and a second pharmaceutically active compound selected from the group consisting of antitussives, expectorants and anti-H1-histamines.

Description

  The present invention relates to a pharmaceutical composition comprising meloxicam or a pharmaceutically acceptable salt thereof and at least one second pharmaceutically active compound selected from the group consisting of antitussives, expectorants and anti-H1-histamines. The present invention further relates to oral pharmaceutical dosage forms comprising such compositions. A further subject of the present invention relates to the use of the composition and oral pharmaceutical dosage form. In addition, the present invention relates to the use of meloxicam and at least one second pharmaceutically active compound selected from the group consisting of antitussives, expectorants and anti-H1-histamines for the manufacture of such oral pharmaceutical dosage forms. Furthermore, the present invention treats or alleviates colds (including various symptoms such as fever, sore throat, chills, headache, joint pain, muscle pain, runny nose, clogged nose, sputum and / or sneeze). Regarding the method.

Common cold is a common disease: the average prevalence of common cold per person is 5-6 times a year. Rhinovirus, parainfluenza virus, or adenovirus induces upper respiratory infections after a temporary loss of autonomic regulation due to causes such as cold exposure. No drug that suppresses viral infection or growth that causes a cold has been found to date, except for drugs for some diseases such as influenza A. Therefore, symptomatic therapy is mainly used for the treatment of common colds, the main purpose of which is to prevent the loss of body strength. Drugs for symptomatic treatment that reduce various symptoms of common cold include non-steroidal anti-inflammatory drugs (NSAIDs) and antitussives or expectorants or anti-H1-histamines as active ingredients: Has inflammatory and antipyretic effects. Antitussives reduce symptoms such as coughing and sneezing. Expectorants alleviate symptoms such as hemorrhoids. Anti-H1-Histamine alleviates symptoms such as runny nose, clogged nose and sneezing. However, these drugs are not effective enough to treat or reduce common cold symptoms with respect to the balance between efficacy and safety.
Many NSAIDs are COX inhibitors, which non-specifically inhibit cyclooxygenase (COX), a rate limiting enzyme for biosynthesis of prostaglandins (PG) from arachidonic acid. Inhibition anti-inflammatory action by inhibiting the production of PGE ₂ in COX, contributed to analgesic and antipyretic effects, on the other hand, it is also unfavorable drug reactions, for example, resulting in digestive disorders and renal disorders. Coincidentally, COX contains two isoforms, COX-1 and COX-2. COX-1 is constitutively generated in most organs such as the stomach and kidneys (a certain amount of protein is generated regardless of growth or environmental changes). COX-2 has been shown to be induced by various inflammatory mediators or endotoxins in the region of local inflammation. Meloxicam is a known selective COX-2 inhibitor.
Treatment of common colds with enhanced efficacy and superior safety by reducing side effects such as gastrointestinal disorders and enhancing anti-inflammatory, analgesic, antipyretic, antitussive and / or expectorant effects An oral pharmaceutical composition for is desired.
A pharmaceutical composition comprising a selective COX-2 inhibitory NSAID and antiallergic agent or anti-H1-histamine (these are mequitazine, ketotifen, epinastine, chlorpheniramine and carbinoxamine effective for the treatment of rhinitis). It is disclosed in JP2001-247481A. Example 2 of said application discloses a composition comprising meloxicam in tablet form, epinastine hydrochloride, phenylpropanolamine hydrochloride, and lysozyme chloride.

The main objective of the present invention is to provide a more effective pharmaceutical composition for the treatment of colds with improved efficacy and safety.
A further object of the present invention is to reduce colds (including various symptoms such as fever, sore throat, chills, headache, joint pain, muscle pain, runny nose, clogged nose, phlegm and / or sneezing). It is to provide a more effective pharmaceutical composition.
Another object of the present invention is to provide a pharmaceutical composition and an oral pharmaceutical dosage form containing an antitussive having improved efficacy and safety.
Another object of the present invention is to provide a pharmaceutical composition and an oral pharmaceutical dosage form containing an expectorant with improved efficacy and safety.
The present invention also aims to provide pharmaceutical compositions and oral pharmaceutical dosage forms comprising certain anti-H1-histamines having improved efficacy and safety.
A further object of the present invention is the treatment of colds (including its various symptoms such as fever, sore throat, chills, headache, joint pain, muscle pain, runny nose, clogged nose, sputum and / or sneezing). Or to provide a mitigation method.

The present invention relates to a novel pharmaceutical composition comprising meloxicam or a pharmaceutically acceptable salt thereof and a second pharmaceutically active compound selected from the group consisting of antitussives, expectorants and anti-H1-histamines. Meloxicam or a salt thereof is preferably present in an amount effective to enable itself to provide anti-inflammatory, analgesic and antipyretic effects.
The advantages of the present invention allow the composition of the present invention to enhance therapeutic effects such as analgesic, anti-inflammatory, antipyretic, antitussive and / or expectorant effects without requiring increasing doses of meloxicam It is to be. It is possible to provide a pharmaceutical composition as an oral pharmaceutical dosage form with improved efficacy and safety. Possible side effects of normal NSAIDs, such as gastrointestinal disorders, are avoided or reduced by using meloxicam. Thus, the composition of the present invention can be used for colds (including various symptoms such as fever, sore throat, chills, headache, joint pain, muscle pain, runny nose, clogged nose, itching and / or sneezing). Particularly suitable for treatment or alleviation. An improved safety profile allows the use of such compositions in non-prescription drugs.

Meloxicam is a known selective COX-2 inhibitor that belongs to the acid enol carboxamide (oxicam) type of non-steroidal anti-inflammatory drug (NSAID). The compound (4-hydroxy-2-methyl-N- (5-methyl-2-thiazolyl) -2H1,2-benzothiazine-3-carboxamide 1,1-dioxide) is described in EP 0 002 482 B1 and U.S. Pat.No. 4,233,299. It is described in.
The present invention may use meloxicam itself or a pharmaceutically acceptable salt thereof. The pharmaceutically acceptable salts of meloxicam include, by way of example, the sodium, potassium, ammonium, meglumine, tris, and meloxicam salts with basic amino acids. Various salts of meloxicam are described in EP 0 002 482 B1, US Pat. No. 4,233,299 and WO 99/49867.
According to a first embodiment of the invention, the pharmaceutical composition comprises meloxicam or a pharmaceutically acceptable salt thereof and at least one antitussive.
In addition to meloxicam and one or more of the above antitussives, the composition of the first embodiment may also contain other pharmacologically active substances such as antacids and / or central nervous system stimulants.
Use of antacids as an additional component may result in improved bioavailability and / or reduced potential side effects in the digestive system.
The addition of central nervous system stimulants can enhance therapeutic effects such as analgesic, anti-inflammatory and antipyretic effects without the need to increase the dose of meloxicam.
Therefore, the pharmaceutical composition of this first embodiment may comprise meloxicam or a pharmaceutically acceptable salt thereof and one or more, preferably one antitussive and one or more, preferably one antacid. The composition may further comprise one or more, preferably one central nervous system stimulant.
The further pharmaceutical composition of this first embodiment may comprise meloxicam or a pharmaceutically acceptable salt thereof and one or more, preferably one antitussive and one or more, preferably one central nervous system stimulant. The composition may further comprise one or more, preferably one antacid.

According to a second embodiment of the invention, the pharmaceutical composition comprises meloxicam or a pharmaceutically acceptable salt thereof and at least one expectorant.
In addition to meloxicam and one or more of the above expectorants, the composition of the second embodiment may also contain other pharmacologically active substances such as antacids, central nervous system stimulants and / or antitussives. Good.
The use of antacids as an additional component may result in improved bioavailability and / or reduced potential side effects in the digestive system.
The addition of central nervous system stimulants can enhance therapeutic effects such as analgesic, anti-inflammatory and antipyretic effects without the need to increase the dose of meloxicam.
The use of antitussives as an additional component provides additional relief of symptoms such as coughing and sneezing.
Hence, the pharmaceutical composition of this second embodiment may comprise meloxicam or a pharmaceutically acceptable salt thereof and one or more, preferably one expectorant and one or more, preferably one antacid. The composition may further comprise one or more, preferably one central nervous system stimulant and / or one or more, preferably one antitussive.
The further pharmaceutical composition of this second embodiment may comprise meloxicam or a pharmaceutically acceptable salt thereof and one or more, preferably one expectorant and one or more, preferably one central nervous system stimulant. The composition may further comprise one or more, preferably one antacid and / or one or more, preferably one antitussive.
Again, the further pharmaceutical composition of this second embodiment may comprise meloxicam or a pharmaceutically acceptable salt thereof and one or more, preferably one expectorant and one or more, preferably one antitussive. The composition may further comprise one or more, preferably one central nervous system stimulant and / or one or more, preferably one antacid.

According to a third embodiment of the invention, the pharmaceutical composition comprises meloxicam or a pharmaceutically acceptable salt thereof and at least one anti-H1-histamine.
In addition to meloxicam and one or more of the anti-H1-histamines described above, the composition of the third embodiment may also include other pharmacologically active substances such as antacids, central nervous system stimulants, antitussives, expectorants. And / or may contain vitamins.
The use of antacids as an additional component may result in improved bioavailability and / or reduced potential side effects in the digestive system.
The addition of central nervous system stimulants can enhance therapeutic effects such as analgesic, anti-inflammatory and antipyretic effects without the need to increase the dose of meloxicam.
The use of antitussives as an additional component provides additional relief of symptoms such as coughing and sneezing.
By using expectorants, additional relief of common cold symptoms such as fever, sore throat, chills, headache, joint pain, muscle pain, and / or epilepsy can be obtained.
By using vitamins as further components, enhanced analgesic, anti-inflammatory and antipyretic effects can be obtained.
Therefore, the pharmaceutical composition of this third embodiment comprises the meloxicam of the present invention or a pharmaceutically acceptable salt thereof and one or more, preferably one anti-H1-histamine and one or more, preferably one antacid. But you can. The composition is further one or more, preferably one central nervous system stimulant, one or more, preferably one or two antitussives, one or more, preferably one expectorant and / or one or more, preferably one Vitamins may be included.
The further pharmaceutical composition of this third embodiment comprises meloxicam of the present invention or a pharmaceutically acceptable salt thereof and one or more, preferably one anti-H1-histamine and one or more, preferably one central nervous system stimulant. May be included. The composition further comprises one or more, preferably one antacid, one or more, preferably one or two antitussives, one or more, preferably one expectorant and / or one or more, preferably one vitamin. May be included.
Again, the further pharmaceutical composition of this third embodiment comprises the meloxicam of the present invention or a pharmaceutically acceptable salt thereof and one or more, preferably one anti-H1-histamine and one or more, preferably one or two antitussives. May contain medicine. The composition further comprises one or more, preferably one central nervous system stimulant, one or more, preferably one antacid, one or more, preferably one expectorant and / or one, preferably one vitamin. May be included.

Again, the further pharmaceutical composition of this third embodiment comprises the meloxicam of the present invention or a pharmaceutically acceptable salt thereof and one or more, preferably one anti-H1-histamine and one or more, preferably one expectorant. But you can. This composition may further comprise one or more, preferably one central nervous system stimulant, one or more, preferably one antacid, one or more, preferably one or two antitussives and / or one or more, preferably one. May contain vitamins.
Again, the further pharmaceutical composition of this third embodiment may comprise the meloxicam of the present invention or a pharmaceutically acceptable salt thereof and one or more, preferably one anti-H1-histamine and one or more, preferably one vitamin. Good. This composition is further one or more, preferably one central nervous system stimulant, one or more, preferably one antacid, one or more, preferably one expectorant and / or one or more, preferably one or two. May include other antitussives.
Of the pharmaceutical compositions of the third embodiment comprising three or more active ingredients, the following pharmaceutical compositions are preferred:
-A pharmaceutical composition comprising meloxicam of the invention or a pharmaceutically acceptable salt thereof and one or more, preferably one anti-H1-histamine and one or more, preferably one or two antitussives;
-Meloxicam of the invention or a pharmaceutically acceptable salt thereof and one or more, preferably one anti-H1-histamine and one or more, preferably one or two antitussives and one or more, preferably one central nervous system stimulant. A pharmaceutical composition comprising:
-Meloxicam of the present invention or a pharmaceutically acceptable salt thereof and one or more, preferably one anti-H1-histamine and one or more, preferably one or two antitussives and one or more, preferably one central nervous stimulant, and A pharmaceutical composition comprising one or more, preferably one vitamin;
-Meloxicam of the present invention or a pharmaceutically acceptable salt thereof and one or more, preferably one anti-H1-histamine and one or more, preferably one or two antitussives and one or more, preferably one central nervous stimulant, and A pharmaceutical composition comprising one or more, preferably one kind of expectorant.

In the following, preferred active ingredients in the composition of the invention are described in more detail.
The composition of the present invention may contain one or more antitussives as the second active ingredient in addition to meloxicam. The antitussive used in the present invention is not limited when the drug exhibits antitussive action.
Examples of such antitussives are aloclamide hydrochloride, cloperastine hydrochloride, cloperastine phendiate, pentoxyberine citrate, tipepidine citrate, tipepidine hibenzate, dibutonate sodium, dextromethorphan bromide Hydrogenate, dextromethorphan phenolphthalein, codeine phosphate, dihydrocodeine phosphate, noscapine hydrochloride, noscapine, dl-methylephedrine hydrochloride, dl-methylephedrine saccharinate, ephedrine hydrochloride, ephedrine sulfate, di Memorphan phosphate, Eprazinone hydrobromide, Clofedanol hydrochloride, Benproperine phosphate, Forcodine, Fominoben hydrochloride, Ephedra herb (Ephedrae herba), Nantenjitsu (Nandinae frak) Scan (Nandinae fructus)), and the like. These antitussives can be used alone or mixed with more than two.
The ephedra herb and Nantenjitsu can be used as dry powder, dry extract, soft extract, liquid extract, tincture, oil, etc., preferably as dry extract, soft extract and liquid extract.
One or more antitussive drugs are tipepidine citrate, tipepidine hibenzate, dextromethorphan hydrobromide, codeine phosphate, dihydrocodeine phosphate, noscapine hydrochloride, noscapine, dl-methylephedrine hydrochloride, dimemorphan It is preferably selected from the group consisting of phosphate, ephedra herb and Nantenjitsu. More preferably, the one or more antitussives is selected from the group consisting of tipepidine citrate, dextromethorphan hydrobromide, dihydrocodeine phosphate, noscapine hydrochloride, noscapine, and dl-methylephedrine hydrochloride.

In addition to meloxicam, the composition of the present invention may comprise one or more expectorants as a second active ingredient or a further active ingredient. The expectorant used in the present invention is not limited when the agent exhibits expectorant action. However, expectorants used in the field of non-prescription drugs are preferred in the case of minimal or no adverse drug safety.
Examples of such expectorants are potassium guaiacol sulfonate, guaifenesin, potassium cresol sulfonate, bromhexine hydrochloride, ambroxol hydrochloride, L-carbocysteine, L-methylcysteine hydrochloride, ethyl L-cysteine hydrochloride, hoodstein , Ipecac (Ipecacuanhae radix), Licorice bulb (Lycoridis bulbus), Fritillaria bulb (Fritillariae bulbus), Spruce (Pruni cortex (Pruni cortex) Platycodi radix), Senega (Senegae radix), Apricot (Armeniacae semen), Onji (Polygalae radix), Licorice (Glycilizae) (Glycyrrhizae radix), car front (Plantaginis semen), car front (Plantaginis herba). These expectorants can be used alone or mixed with more than two.
Licorice bulbs, fritillaria bulbs, Spruce, Kyocera, Senega, Onji, licorice, car ante and car forage can be used as dry powder, dry extract, soft extract, liquid extract, tincture, oil and the like.
The one or more expectorants are preferably selected from the group consisting of potassium guaiacol sulfonate, guaifenesin, bromohexine hydrochloride, ambroxol hydrochloride, L-carbocysteine, ethyl L-cysteine hydrochloride, fudostein, kyou and licorice. More preferably, the one or more expectorants are selected from the group consisting of guaifenesin, bromhexine hydrochloride, ambroxol hydrochloride, L-carbocysteine and fudstein.

In addition to meloxicam, as a second active ingredient or further ingredient, the composition according to the invention may comprise one or more anti-H1-histamines selected from the group listed above and below. These antihistamines can be used alone or can be mixed with more than two.
Anti-H1-histamine is diphenhydramine, diphenylpyralin, clemastine, triprolysine, promethazine, alimemazine, istipendil, iproheptin, dipheterol, tripelenamine, tondiramine, phenetadine, mesdirazine, mebuhydroline, cyproheptadine, homochlorcyclidine, hydroxyzine, eb And bepotastine, azelastine, oxatomide, fexofenadine, olopatadine, loratadine, acribastine, brompheniramine, and doxylamine (including pharmaceutically acceptable salts thereof).
The present invention may use non-salt form of anti-H1-histamine or a pharmaceutically acceptable acid addition salt thereof. The pharmaceutically acceptable acid addition salts of these anti-H1-histamines of the present invention include diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, diphenhydramine citrate, diphenylpyraline hydrochloride, diphenylpyraline theocrate, clemastine Fumarate, triprolidine hydrochloride, promethazine hydrochloride, promethazine methylene disalicylate, alimemazine tartrate, istipendyl hydrochloride, iproheptin hydrochloride, difeterol hydrochloride, difeterol phosphate, tripelenamine hydrochloride, tondilamine hydrochloride, Phenetazine hydrochloride, phenetadine tannate, mesdirazine hydrochloride, mebhydroline napadicylate, cyproheptadine hydrochloride, homochlorcyclidine hydrochloride, hydroxyzine hydrochloride, Examples include droxididine pamoate, cetirizine hydrochloride, emedastine difumarate, bepotastine besylate, azelastine hydrochloride, fexofenadine hydrochloride, olopatadine hydrochloride, brompheniramine maleate and doxylamine succinate It is done. Above and below, the term “anti-H1-histamine” includes both non-salt forms and pharmaceutically acceptable acid addition salts of anti-H1-histamines of the present invention.

One or more anti-H1-histamines are diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, diphenylpyraline hydrochloride, diphenylpyraline theoculoate, clemastine fumarate, triprolidine hydrochloride, promethazine hydrochloride, promethazine methylenedi Consists of salicylate, alimemazine tartrate, istipendil hydrochloride, iproheptin hydrochloride, dipheterol hydrochloride, dipheterol phosphate, tripelamine amine hydrochloride, tondiamine hydrochloride, phenetadine hydrochloride, mesdirazine hydrochloride and mebhydroline napadisilate Preferably selected from the group.
Examples of suitable antacids are aminoacetic acid, synthetic aluminum silicate, hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate, aluminum hydroxide gel, dry aluminum hydroxide gel, aluminum hydroxide-sodium bicarbonate coprecipitate, Magnesium carbonate, magnesium aluminometasilicate, magnesium hydroxide, sodium bicarbonate and calcium hydrogen phosphate.
Examples of suitable central nervous system stimulants are caffeine (3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione monohydrate), anhydrous caffeine (3,7- Dihydro-1,3,7-trimethyl-1H-purine-2,6-dione) and a complex salt of caffeine and sodium benzoate (caffeine and sodium benzoate). A combination of two or more central nervous system stimulants may also be used.
Examples of suitable vitamins are vitamin B ₁ , vitamin B ₂ , vitamin C and hesperidin.

According to a preferred embodiment, the pharmaceutical composition of the invention further comprises at least one pharmaceutically acceptable carrier and / or excipient. Suitable carriers and excipients are known to those skilled in the art and are described, for example, in the Japanese Pharmaceutical Excipients Dictionary 2000 (published by Yakuji Nippo, edited by the Japanese Pharmaceutical Excipients Association). Examples of suitable carriers and / or excipients are lactose, sucrose, glucose, mannitol, xylitol, corn starch, potato starch, wheat starch, rice starch, tapioca starch, sodium carboxymethyl starch, microcrystalline cellulose, ethyl cellulose, hydroxy Propylmethylcellulose, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, croscarmellose sodium, carmellose, carmellose potassium, carmellose calcium, carmellose sodium, polyvinylpyrrolidone, propylene glycol, polyethylene glycol, glycerol, vegetable oil, wax, crospovidone, Agar, light anhydrous silicic acid, magnesium stearate, talc, titanium dioxide, acacia, sodium alginate, etano A le and purified water.
In addition, the present invention relates to a pharmaceutical dosage form comprising the pharmaceutical composition of the present invention.
The amount of meloxicam used in the oral pharmaceutical dosage form described in the present invention is preferably in the range of 1-30 mg, more preferably in the range of 2.5-15 mg, most preferably in the range of 5-10 mg. These amounts represent a preferred dose range for adults and doses given once daily.
According to a first embodiment of the invention, the at least one second pharmaceutically active compound is selected from the group consisting of antitussives. The amount of one or more antitussives in the oral pharmaceutical dosage form of the present invention may vary depending on the type of antitussive used. It is preferably in the range of 1-12000 mg, more preferably in the range of 2-10000 mg. These amounts correspond to the preferred doses given daily to adults. Listed below are the preferred amounts (hereinafter referred to as “daily combined doses”) given daily to adults of suitable antitussives included in the compositions of the present invention.
The daily combined dose of alocramide hydrochloride for adults is usually 2 to 150 mg, preferably 5 to 100 mg, more preferably 7.5 to 75 mg.
The daily combined dose of cloperastine hydrochloride for adults is usually 1-60 mg, preferably 2-50 mg, more preferably 4.8-48 mg.

The daily combined dose of cloperastine phendiate for adults is usually 2-105 mg, preferably 5-90 mg, more preferably 8.4-84 mg.
The daily combined dose of pentoxyverine citrate for adults is usually 1 to 120 mg, preferably 2 to 60 mg, more preferably 4.8 to 48 mg.
The daily combined dose of tipepidine citrate for adults is usually 1-120 mg, preferably 4-90 mg, more preferably 6-60 mg.
The daily combined dose of tipepidine hibenzate for adults is usually 1-120 mg, preferably 4-90 mg, more preferably 7.5-75 mg.
The daily combined dose of dibutate sodium for adults is usually 1-180 mg, preferably 4-120 mg, more preferably 9-90 mg.
The daily combined dose of dextromethorphan hydrobromide for adults is usually 1-120 mg, preferably 2-96 mg, more preferably 4.8-48 mg.
The daily combined dose of dextromethorphan phenolphthalein for adults is usually 1-120 mg, preferably 2-96 mg, more preferably 7.2-72 mg.
The daily combined dose of codeine phosphate for adults is usually 1-60 mg, preferably 2-50 mg, more preferably 4.8-48 mg.
The daily combined dose of dihydrocodeine phosphate for adults is usually 1-30 mg, preferably 2-25 mg, more preferably 2.4-24 mg.

The daily combined dose of noscapine hydrochloride and noscapine for adults is usually 1-120 mg, preferably 2-96 mg, more preferably 4.8-48 mg.
The daily combined dose of dl-methylephedrine hydrochloride and dl-methylephedrine saccharinate for adults is usually 1-150 mg, preferably 3-75 mg, more preferably 6-60 mg.
The daily combined dose of ephedrine hydrochloride and ephedrine sulfate for adults is usually 1 to 75 mg, preferably 2 to 50 mg, more preferably 3 to 37.5 mg.
The daily combined dose of dimemorphan phosphate for adults is usually 1-60 mg, preferably 2-45 mg, more preferably 3-30 mg.
The daily combined dose of Eprazinone hydrochloride for adults is usually 1-90 mg, preferably 3-75 mg, more preferably 6-60 mg.
The daily combined dose of clofedanol hydrochloride for adults is usually 1-150 mg, preferably 5-100 mg, more preferably 7.5-75 mg.
The daily combined dose of benproperine phosphate for adults is usually 2 to 160 mg, preferably 4 to 120 mg, more preferably 8 to 80 mg.
The daily combined dose of forcodin for adults is usually 3 to 180 mg, preferably 6 to 135 mg, more preferably 9 to 90 mg.
The daily combined dose of fminoben hydrochloride for an adult is usually 6 to 480 mg, preferably 12 to 360 mg, more preferably 24 to 240 mg.
The daily combined dose of ephedra herb for adults is usually 10-5000 mg, preferably 20-4500 mg, more preferably 40-4000 mg as ephedra herb substance.
The daily combined dose of Nantenjitsu for adults is usually 10-12000 mg, preferably 20-11000 mg, more preferably 50-10000 mg as ephedra herb substance.
According to a second embodiment of the invention, the at least one second pharmaceutically active compound is selected from the group of expectorants. The amount of one or more expectorants in the oral pharmaceutical dosage form of the present invention may vary depending on the type of expectorant. It is preferably in the range of 0.1 to 12000 mg, more preferably in the range of 1 to 10,000 mg. These amounts correspond to the preferred doses given daily to adults. Listed below are the preferred amounts (hereinafter referred to as “daily combined doses”) given daily to adults of suitable expectorants included in the compositions of the present invention.

The daily combined dose of potassium guaiacol sulfonate for adults is usually 5 to 500 mg, preferably 10 to 350 mg, more preferably 25 to 250 mg.
The daily combined dose of guaifenesin for adults is usually 5 to 900 mg, preferably 10 to 500 mg, more preferably 25 to 250 mg.
The daily combined dose of potassium cresol sulfonate for adults is usually 5-540 mg, preferably 10-360 mg, more preferably 27-270 mg.
The daily combined dose of bromhexine hydrochloride for adults is usually 0.1-24 mg, preferably 0.5-18 mg, more preferably 1-12 mg.
The daily combined dose of ambroxol hydrochloride for adults is usually 1-90 mg, preferably 2-60 mg, more preferably 4-45 mg.
The daily combined dose of L-carbocysteine for adults is usually 25-1500 mg, preferably 50-1050 mg, more preferably 75-750 mg.
The daily combined dose of L-methylcysteine hydrochloride and ethyl L-cysteine hydrochloride for adults is usually 10-600 mg, preferably 20-450 mg, more preferably 30-300 mg.
The daily combined dose of fudostein for adults is usually 30-2400 mg, preferably 60-1800 mg, more preferably 120-1200 mg.
The daily combined dose of Ipecac as Ipecac substance for adults is usually 1-60 mg, preferably 2-55 mg, more preferably 5-50 mg.
The daily combined dose of licorice bulb as a licorice bulb substance for adults is usually 4 to 1000 mg, preferably 6 to 900 mg, more preferably 8 to 800 mg.
The daily combined dose of fritillaria bulb as a fritillaria bulb substance for adults is usually 5 to 4000 mg, preferably 10 to 3000 mg, more preferably 25 to 2500 mg.
The daily combined doses of Spruce, Scotch, Senega or Anzu, each in the form of crude drug substance for adults, is usually 10-5000 mg, preferably 20-4500 mg, more preferably 40-4000 mg.
The daily combined doses of Onzi, Licorice or Precursor respectively in the form of crude drug substance for adults is usually 10-6000 mg, preferably 25-5500 mg, more preferably 50-5000 mg.
The daily combined dose of car forage as a car forerunner material for adults is usually 10-12000 mg, preferably 50-11000 mg, more preferably 100-10000 mg.

According to a third embodiment of the invention, the at least one second pharmaceutically active compound is selected from the group consisting of anti-H1-histamine. The amount of one or more anti-H1-histamines in the oral pharmaceutical dosage form of the present invention may vary depending on the type of anti-H1-histamine, but it is preferably in the range of 0.1 to 450 mg, more preferably 0.1 to 150 mg. It is in the range. These amounts correspond to the preferred doses given daily to adults. Listed below are the preferred amounts (hereinafter referred to as “daily combined doses”) given daily to adults of suitable anti-H1-histamine included in the oral pharmaceutical dosage form of the present invention.
The daily combined dose of diphenhydramine hydrochloride, diphenhydramine citrate, diphenhydramine salicylate and diphenhydramine tannate for adults is usually 5-450 mg, preferably 10-150 mg, more preferably 15-75 mg.
The daily combined dose of diphenylpyraline hydrochloride and diphenylpyraline theocuroate for adults is usually 0.1-15 mg, preferably 0.5-10 mg, more preferably 1-5 mg.
The daily combined dose of clemastine fumarate for adults is usually 0.1 to 4.5 mg, preferably 0.2 to 3 mg, more preferably 0.3 to 1.5 mg.
The daily combined dose of triprolidine hydrochloride for adults is usually 0.1-9 mg, preferably 0.3-6 mg, more preferably 0.5-4 mg.
The daily combined dose of promethazine hydrochloride and promethazine methylene disalicylate for adults is usually 1-75 mg, preferably 3-60 mg, more preferably 5-40 mg.
The daily combined dose of alimemazine tartrate for adults is usually 0.1-10 mg, preferably 0.5-7.5 mg, more preferably 1-5 mg.
The daily combined dose of istipendil hydrochloride for adults is usually 0.1-24 mg, preferably 0.5-12 mg, more preferably 1-7 mg.

The daily combined dose of iproheptin hydrochloride for adults is usually 10 to 225 mg, preferably 20 to 200 mg, more preferably 30 to 150 mg.
The daily combined dose of dipheterol hydrochloride and dipheterol phosphate for adults is usually 5 to 180 mg, preferably 10 to 135 mg, more preferably 18 to 90 mg.
The daily combined dose of tripelenamine hydrochloride for adults is usually 5 to 200 mg, preferably 10 to 150 mg, more preferably 20 to 100 mg.
The daily combined dose of tondiramine hydrochloride for adults is usually 2-100 mg, preferably 5-75 mg, more preferably 10-50 mg.
The daily combined dose of phenetazine hydrochloride for adults is usually 2-180 mg, preferably 5-90 mg, more preferably 10-50 mg.
The daily combined dose of phenetadine tannate for adults is usually 5 to 270 mg, preferably 15 to 200 mg, more preferably 27 to 135 mg.
The daily combined dose of mesdirazine hydrochloride for adults is usually 0.1-16 mg, preferably 0.5-12 mg, more preferably 1-8 mg.
The daily combined dose of mebhydroline napadisilate for adults is usually 10-300 mg, preferably 20-225 mg, more preferably 30-150 mg.
The daily combined dose of cyproheptadine hydrochloride for adults is usually 0.1-12 mg, preferably 0.5-8 mg, more preferably 1-6 mg.
The daily combined dose of homochlorcyclidine hydrochloride for adults is usually 1-60 mg, preferably 3-45 mg, more preferably 6-30 mg.
The daily combined dose of hydroxyzine hydrochloride for adults is usually 1-60 mg, preferably 3-45 mg, more preferably 6-30 mg.

The daily combined dose of hydroxyzine pamoate for adults is usually 5 to 140 mg, preferably 10 to 105 mg, more preferably 15 to 70 mg.
The daily combined dose of ebastine for adults is usually 0.1-10 mg, preferably 0.5-7.5 mg, more preferably 1-5 mg.
The daily combined dose of cetirizine hydrochloride for adults is usually 0.5-20 mg, preferably 1-15 mg, more preferably 2-10 mg.
The daily combined dose of emedastine difumarate for adults is usually 0.1-4 mg, preferably 0.2-3 mg, more preferably 0.4-2 mg.
The daily combined dose of bepotastine besylate for adults is usually 1-40 mg, preferably 2-30 mg, more preferably 3-20 mg.
The daily combined dose of azelastine hydrochloride for adults is usually 0.1-4 mg, preferably 0.2-3 mg, more preferably 0.4-2 mg.
The daily combined dose of oxatomide for adults is usually 1-60 mg, preferably 3-45 mg, more preferably 6-30 mg.
The daily combined dose of fexofenadine hydrochloride for adults is usually 5-240 mg, preferably 10-180 mg, more preferably 20-120 mg.
The daily combined dose of olopatadine hydrochloride for adults is usually 0.5-20 mg, preferably 1-15 mg, more preferably 2-10 mg.
The daily combined dose of loratadine for adults is usually 0.5-20 mg, preferably 1-15 mg, more preferably 2-10 mg.
The daily combined dose of acribastine for adults is usually 0.5-24 mg, preferably 1-18 mg, more preferably 2-12 mg.
The daily combined dose of brompheniramine maleate for adults is usually 1-32 mg, preferably 2-28 mg, more preferably 4-24 mg.
The daily combined dose of doxylamine succinate for adults is usually 5-150 mg, preferably 10-100 mg, more preferably 15-75 mg.

The oral pharmaceutical dosage forms of the present invention may be administered orally in divided doses, for example 2, 3 or 4 doses daily. However, oral pharmaceutical dosage forms are preferably administered orally once a day. Dose adjustments for meloxicam and antitussives can reflect age, weight, and onset symptoms.
The oral pharmaceutical dosage forms described in the present invention are tablets, granules, fine granules, powders, capsules, caplets, soft capsules, pills, oral solutions, syrups, dry syrups, chewable tablets, troches, effervescent tablets, drops, suspensions. Including suspensions, fast dissolving tablets or oral dispersible tablets. Any of these formulations may be prepared using conventional methods, and in addition to the above ingredients, commonly used additives may be used based on the preparation of these formulations as necessary. In addition, formulations formed into microparticles, such as microcapsules, nanocapsules, microspheres, nanospheres, and liposomes may also be included in the formulation.
In addition, the formulation of further components and all components of the oral pharmaceutical dosage form is selected in view of the desired mechanical stability, chemical stability and biological stability, release rate, taste masking, visual appearance, etc. It is preferred that
For example, the pharmaceutically active substance, i.e. meloxicam or a pharmaceutically acceptable salt thereof and the second pharmaceutically active agent may be a separate granule, multilayer granule, multilayer tablet or dry coated tablet, isolated granule tablet, microcapsule, etc. Can be dispensed into. Coated preparations such as sugar-coated tablets, film-coated tablets, coated granules, as well as chewable tablets, oral rapid dispersible tablets, matrix tablets, matrix granules, effervescent tablets, dusting powders, solid solutions and the like can be used. These methods can also be combined. In addition, the properties of the oral pharmaceutical dosage forms of the present invention, such as stability, release, continuity, disintegration, distinglation, dissolution, taste masking, improved use, etc., are known in the art. It can be adjusted by adding an agent.

According to a preferred embodiment, the oral dosage form is a combination of a first dosage form comprising meloxicam or a pharmaceutically acceptable salt thereof and a second dosage form comprising at least a second pharmaceutically active compound. It is preferred that the first dosage form releases the active ingredient faster than the second dosage form. The first dosage form may further comprise a second pharmaceutically active compound and optionally further active ingredients. The second dosage form may contain additional active ingredients. It is preferred that the second dosage form does not contain meloxicam.
For example, the dosage form may comprise a first layer of meloxicam or a pharmaceutically acceptable salt thereof and optionally a second pharmaceutically active compound, such as an antitussive or expectorant or anti-H1-histamine, and optionally further active ingredients and medicaments It is a bilayer tablet containing an acceptable carrier and / or excipient. The second layer comprises a second pharmaceutically active compound, such as an antitussive or expectorant or anti-H1-histamine, and optionally further active ingredients and pharmaceutically acceptable carriers and / or excipients, whereby The second layer has a slow release characteristic compared to the first layer.
According to a further example, the dosage form is a capsule comprising two types of granules. The first type of granule is meloxicam or a pharmaceutically acceptable salt thereof and optionally a second pharmaceutically active compound such as an antitussive or expectorant or anti-H1-histamine and optionally further active ingredients and pharmaceutically acceptable Contains carriers and / or excipients. The second type of granule comprises a second pharmaceutically active compound, for example an antitussive or expectorant or anti-H1-histamine, and optionally further active ingredients and pharmaceutically acceptable carriers and / or excipients, Thus, the second type of granules has a slow release characteristic compared to the first type of granules.
These formulations are generally available pharmaceutical additives using conventional methods such as excipients, binders, disintegrants, lubricants, coatings, sugar coatings, plasticizers, antifoaming agents, polishes, foaming agents. Agent, antistatic agent, desiccant, surfactant, solubilizer, buffer, solubilizer, solubilizer, solvent, diluent, stabilizer, emulsifier, suspension, suspending agent, dispersing agent, isotonic Agent, adsorbent, reducing agent, antioxidant, wetting agent, wetting improver, filler, extender, adhesive, thickener, softener, pH improver, antiseptic, preservative, sweetener, taste-masking agent It can be prepared by adding freezing agents, flavoring agents, fragrances, fragrances, and colorings to the pharmaceutically active compound.
Examples of such additives are described in Japanese Pharmaceutical Excipient Dictionary 2000 (published by Yakuji Nippo, edited by Japan Pharmaceutical Excipients Association).
These preparations are preferably produced by adding pharmaceutical additives to pharmacologically active compounds.
The pharmaceutical compositions and dosage forms of the present invention are advantageously beneficial as analgesics, antipyretics, antitussives, expectorants and / or antihistamines.

The present invention treats and alleviates colds (including various symptoms such as fever, sore throat, chills, headache, joint pain, muscle pain, cough, runny nose, clogged nose, phlegm and / or sneeze) Relates to the use of pharmaceutical compositions for oral and oral pharmaceutical dosage forms (both as described above).
The pharmaceutical compositions and dosage forms of the present invention may have a cold (its various symptoms such as fever, sore throat, chills, headache, joint pain, muscle pain, cough, runny nose, clogged nose, phlegm and / or sneeze. Effective).
Furthermore, the present invention treats colds (including its various symptoms such as fever, sore throat, chills, headache, joint pain, muscle pain, cough, runny nose, clogged nose, sputum and / or sneezing). Or the use of said pharmaceutical composition for the manufacture of a medicament for alleviation.
In addition, the present invention relates to the use of meloxicam or a pharmaceutically acceptable salt thereof for the manufacture of the oral pharmaceutical dosage form of the present invention.
Thus, the present invention also relates to the use of a pharmaceutically active compound selected from the group consisting of antitussives, expectorants and anti-H1-histamines for the manufacture of the oral pharmaceutical dosage forms of the invention.
Accordingly, the present invention further comprises orally administering to the patient the pharmaceutical composition of the present invention, a cold of a patient in need of such treatment (its various symptoms such as fever, sore throat, chills, headache, (Including arthralgia, muscle pain, cough, runny nose, clogged nose, sputum and / or sneeze).
The patient to be treated according to the present invention is a mammal, preferably a human.
A preferred daily dose for oral administration to a patient according to the present invention is in the range of 1-30 mg meloxicam, more preferably 2.5-15 mg meloxicam, and
a) if the second pharmaceutically active compound is an antitussive, an antitussive in an amount of 1 to 12000 mg, more preferably 2 to 10,000 mg;
b) when the second pharmaceutically active compound is an expectorant, 0.1-12000 mg, more preferably an amount of 1-10000 mg expectorant;
c) When the second pharmaceutically active compound is anti-H1-histamine, it is anti-H1-histamine in an amount of 0.1-450 mg, more preferably 0.1-150 mg.

Preferred doses for the various second pharmaceutically active compounds are specified above. Therefore, the amount of dosage form taken by the patient daily, ie the number of tablets, capsules, caplets, troches, etc. or the amount of granules, syrups, solutions, suspensions, etc. (measured in grams or milliliters, for example) Is such that the preferred daily dose specified above is obtained.
Meloxicam or a pharmaceutically acceptable salt thereof and at least one pharmaceutically active compound are preferably combined in a single oral dosage form as described above. Both meloxicam or a salt thereof and at least one pharmaceutically active compound may also be administered simultaneously in two separate oral dosage forms, one comprising meloxicam or a salt thereof and the other comprising a second pharmaceutically active compound.
The compositions and dosage forms of the present invention are illustrated by the following examples, which do not limit the scope of the invention. Examples 1.1 to 1.6 show the first embodiment of the present invention, Examples 2.1 to 2.6 show the second embodiment of the present invention, and Examples 3.1 to 3.6 show the third embodiment of the present invention. .

Example 1.1
Tablet The following ingredients were mixed uniformly. The obtained mixed particles were compressed with a mold to prepare tablets of 250 mg each.
Meloxicam 45g
Tipepidine hibenzate 150g
dl-Methylephedrine hydrochloride 120g
Lactose 579g
Microcrystalline cellulose 576g
Light anhydrous silicic acid 15g
Talc 9g
Magnesium stearate 6g
Example 1.2
Powder The following ingredients were mixed uniformly. The obtained mixed particles were divided into 500 mg portions to prepare a powder composition.
Meloxicam 15g
Dimemorphan phosphate 20g
Corn starch 475g
Lactose 480g
Magnesium stearate 10g

Example 1.3
Two-layer tablet The following ingredients of layer A and layer B were processed in the usual way to obtain mixed particles, respectively, and the particles were compressed to form 220 mg bilayer tablets (layer A 100 mg, layer B 120 mg), respectively.
Layer A
Meloxicam 45g
Dihydrocodeine phosphate 48g
dl-Methylephedrine hydrochloride 120g
Noscapine 96g
Lactose 429g
Microcrystalline cellulose 426g
Sodium lauryl sulfate 12g
Light anhydrous silicic acid 12g
Talc 6g
Magnesium stearate 6g
Layer B
Dihydrocodeine phosphate 96g
dl-Methylephedrine hydrochloride 240g
Noscapine 192g
Lactose 226g
Fumaric acid 132g
Hydroxypropyl methylcellulose 2208 180g
Hydrogenated oil 120g
Stearic acid 120g
Fatty acid glycerol ester 120g
Magnesium stearate 14g

Example 1.4
Granules The following ingredients were prepared as granules by conventional methods to prepare mixed particles and filled to obtain an amount of 1500 mg per pack for the granules.
Meloxicam 15g
Dextromethorphan hydrobromide 32g
Ephedra herb extract 440g
(Equivalent to 2kg ephedra herb)
Nantenjitsu extract 700g
(Equivalent to 3.84 kg of Nantenjitsu)
Calcium carboxymethyl cellulose 240g
Mannitol 1260g
Corn starch 280g
Aspartame 15g
Acesulfame potassium 15g
Fragrance 3g

Example 1.5
Capsules The following ingredients are prepared in the usual way as quick release granules and sustained release granules and filled into capsules in an amount of 225 mg per capsule (rapid release granules: 75 mg, sustained release granules: 150 mg) Got.
Quick release granules Meloxicam 60g
Dihydrocodeine phosphate 64g
dl-Methylephedrine hydrochloride 160g
Noscapine 128g
Microcrystalline cellulose 788g
Controlled release granules Dihydrocodeine phosphate 128g
dl-Methylephedrine hydrochloride 320g
Noscapine 256g
176 g of fumaric acid
Microcrystalline cellulose 1304g
Ethylcellulose (coating layer) 128g
Hydroxypropyl methylcellulose (coating layer) 32g
Fatty acid glycerol ester (coating layer) 44g
Talc (coating layer) 12g

Example 1.6
Capsules The following ingredients are prepared in the usual way as quick release granules and sustained release granules and filled into capsules in an amount of 225 mg per capsule (rapid release granules: 75 mg, sustained release granules: 150 mg) Got.
Quick release granules Meloxicam 60g
Cloperastine hydrochloride 128g
dl-Methylephedrine hydrochloride 160g
Anhydrous caffeine 200g
652g microcrystalline cellulose
Controlled release granules Cloperastine hydrochloride 256g
dl-Methylephedrine hydrochloride 320g
400g anhydrous caffeine
240g fumaric acid
Microcrystalline cellulose 704g
Methacrylic acid copolymer S (coating layer) 336g
Fatty acid glycerol ester (coating layer) 100g
Talc (coating layer) 44g

Example 2.1
Tablet The following ingredients were mixed uniformly. The obtained mixed particles were compressed with a mold to prepare tablets of 250 mg each.
Meloxicam 45g
Spruce Extract 240g
(Equivalent to 400 g of spruce)
Lactose 591g
Microcrystalline cellulose 594g
Light anhydrous silicic acid 15g
Talc 9g
Magnesium stearate 6g
Example 2.2
Powder The following ingredients were mixed uniformly. The obtained mixed particles were divided into 750 mg portions to prepare a powder composition.
Meloxicam 15g
L-Carbocysteine 500g
Corn starch 490g
Lactose 480g
Magnesium stearate 15g

Example 2.3
Two-layer tablet The following ingredients of layer A and layer B were processed in the usual way to obtain mixed particles, respectively, and the particles were compressed to form 220 mg bilayer tablets (layer A 100 mg, layer B 120 mg), respectively.
Layer A
Meloxicam 45g
Ambroxol hydrochloride 90g
Dihydrocodeine phosphate 48g
dl-Methylephedrine hydrochloride 120g
Lactose 435g
Microcrystalline cellulose 426g
Sodium lauryl sulfate 12g
Light anhydrous silicic acid 12g
Talc 6g
Magnesium stearate 6g
Layer B
Ambroxol hydrochloride 180g
Dihydrocodeine phosphate 96g
dl-Methylephedrine hydrochloride 240g
Lactose 181g
129 g of fumaric acid
Hydroxypropyl methylcellulose 2208 180g
Hydrogenated oil 120g
Stearic acid 120g
Fatty acid glycerol ester 120g
Magnesium stearate 14g

Example 2.4
Granules The following ingredients were prepared as granules by conventional methods to prepare mixed particles and filled to obtain an amount of 1200 mg per pack for the granules.
Meloxicam 15g
Licorice extract 180g
(Equivalent to 1.5 kg of licorice)
Kyokyo Extract 200g
(Equivalent to 2kg of Kyoki)
SENEGA EXTRACT 72g
(Equivalent to Senega 1.2kg)
Calcium carboxymethyl cellulose 240g
Mannitol 1360g
Corn starch 307g
Aspartame 12g
Acesulfame potassium 12g
Fragrance 2g

Example 2.5
Capsules The following ingredients are prepared in the usual way as quick release granules and sustained release granules and filled into capsules in an amount of 225 mg per capsule (rapid release granules: 75 mg, sustained release granules: 150 mg) Got.
Quick release granules Meloxicam 60g
Ambroxol hydrochloride 120g
Dihydrocodeine phosphate 64g
dl-Methylephedrine hydrochloride 160g
Noscapine 128g
Microcrystalline cellulose 668g
Controlled release granules Ambroxol hydrochloride 240g
Dihydrocodeine phosphate 128g
dl-Methylephedrine hydrochloride 320g
Noscapine 256g
240g fumaric acid
Microcrystalline cellulose 1000g
Ethylcellulose (coating layer) 128g
Hydroxypropyl methylcellulose (coating layer) 32g
Fatty acid glycerol ester (coating layer) 44g
Talc (coating layer) 12g

Example 2.6
Capsules The following ingredients are prepared in the usual way as quick release granules and sustained release granules and filled into capsules in an amount of 350 mg per capsule (rapid release granules: 115 mg, sustained release granules: 235 mg) Got.
Quick release granules Meloxicam 60g
Guayphenesine 666.4g
dl-Methylephedrine hydrochloride 160g
Anhydrous caffeine 200g
Microcrystalline cellulose 753.6g
Controlled granules Guaifenesin 1333.6g
dl-Methylephedrine hydrochloride 320g
400g anhydrous caffeine
480 g of fumaric acid
Microcrystalline cellulose 714.4g
Methacrylic acid copolymer S (coating layer) 360g
Fatty acid glycerol ester (coating layer) 104g
Talc (coating layer) 48g

Example 3.1
Two-layer tablet The following ingredients of layer A and layer B are processed by conventional methods to obtain mixed particles, respectively, and the particles are compressed to form 300-mg double-layer tablets (layer A 100 mg, layer B 200 mg), respectively.
Layer A
Meloxicam 45g
Diphenhydramine hydrochloride 150g
Ambroxol hydrochloride 90g
Dihydrocodeine phosphate 48g
dl-Methylephedrine hydrochloride 120g
Anhydrous caffeine 300g
Lactose 435g
Microcrystalline cellulose 558g
Sodium lauryl sulfate 18g
Light anhydrous silicic acid 18g
Talc 9g
Magnesium stearate 9g
Layer B
Diphenhydramine hydrochloride 300g
Ambroxol hydrochloride 180g
Dihydrocodeine phosphate 96g
dl-Methylephedrine hydrochloride 240g
600g anhydrous caffeine
Lactose 168g
Fumaric acid 300g
60g succinic acid
Hydroxypropyl methylcellulose 2208 540g
Hydrogenated oil 360g
Stearic acid 360g
Fatty acid glycerol ester 360g
Magnesium stearate 36g

Example 3.2
Two-layer tablet The following ingredients of layer A and layer B are processed by conventional methods to obtain mixed particles, respectively, and the particles are compressed to form 200 mg bilayer tablets (layer A 80 mg, layer B 120 mg), respectively.
Layer A
Meloxicam 45.0g
Diphenylpyraline hydrochloride 8.0g
Noscapine 60.0g
dl-Methylephedrine hydrochloride 60.0g
Anhydrous caffeine 192.0g
Lactose 491.8g
Microcrystalline cellulose 540.0g
Sodium lauryl sulfate 14.4g
Light silicic acid 14.4g
Talc 7.2g
Magnesium stearate 7.2g
Layer B
Diphenylpyraline hydrochloride 16.0g
Noscapine 120.0g
dl-Methylephedrine hydrochloride 120.0g
Anhydrous caffeine 384.0 g
Lactose 310.4g
Fumaric acid 162.0g
Hydroxypropyl methylcellulose 2208 180.0g
Hydrogenated oil 282.0g
Stearic acid 282.0g
Fatty acid glycerol ester 282.0g
Magnesium stearate 21.6g

Example 3.3
Granules The following ingredients are prepared as granules by conventional methods to prepare mixed particles and packed to obtain an amount of 1000 mg per pack for the granules.
Meloxicam 37.5g
Cremastine fumarate 6.7g
Dihydrocodeine phosphate 40.0g
dl-Methylephedrine hydrochloride 100.0g
Bromhexine hydrochloride 20.0g
Anhydrous caffeine 250.0g
Calcium carboxymethyl cellulose 500.0g
Mannitol 3500.0g
Corn starch 490.8g
Aspartame 25.0g
Acesulfame potassium 25.0g
Fragrance 5.0g

Example 3.4
Capsules The following ingredients are prepared in the usual way as quick release granules and sustained release granules and filled into capsules in an amount of 270 mg per capsule (rapid release granules: 90 mg, sustained release granules: 180 mg) Get.
Rapid release granules Meloxicam 60.0g
Triprolidine hydrochloride 9.6g
Tipepidine hibenzate 160.0g
dl-Methylephedrine hydrochloride 160.0g
Anhydrous caffeine 240.0g
Microcrystalline cellulose 810.4g
Extended-release granules Triprolidine hydrochloride 19.2g
Tipepidine hibenzate 320.0g
dl-Methylephedrine hydrochloride 320.0g
Anhydrous caffeine 480.0g
Fumaric acid 288.0g
Microcrystalline cellulose 1236.8g
Ethylcellulose (coating layer) 136.0g
Hydroxypropyl methylcellulose (coating layer) 24.0g
Fatty acid glycerol ester (coating layer) 44.0g
Talc (coating layer) 12.0g

Example 3.5
Capsules The following ingredients are prepared in the usual way as quick release granules and sustained release granules and filled into capsules in an amount of 350 mg per capsule (rapid release granules: 115 mg, sustained release granules: 235 mg) Get.
Rapid release granules Meloxicam 60.0g
Isotipendil hydrochloride 24.0g
Guayphenesine 666.4g
dl-Methylephedrine hydrochloride 160.0g
Anhydrous caffeine 200.0g
Microcrystalline cellulose 729.6g
Controlled release granules Isotipendil hydrochloride 32.0g
Guaifenesin 1333.6g
dl-Methylephedrine hydrochloride 320.0g
Anhydrous caffeine 400.0g
Fumaric acid 400.0g
Succinic acid 80.0g
682.4g microcrystalline cellulose
Methacrylic acid copolymer S (coating layer) 360.0g
Fatty acid glycerol ester (coating layer) 104.0g
Talc (coating layer) 48.0g

Example 3.6
Tablet Mix the following ingredients uniformly. The obtained mixed particles are compressed with a mold to prepare tablets of 250 mg each.
Meloxicam 15g
Ebastine 10g
Noscapine 40g
100g anhydrous caffeine
Ascorbic acid 200g
Lactose 200g
420g microcrystalline cellulose
Light anhydrous silicic acid 5g
Talc 6g
Magnesium stearate 4g

Claims (25)

  A pharmaceutical composition comprising meloxicam or a pharmaceutically acceptable salt thereof and a second pharmaceutically active compound selected from the group consisting of antitussives, expectorants and anti-H1-histamines.   The pharmaceutical composition according to claim 1, comprising meloxicam or a pharmaceutically acceptable salt thereof and at least one antitussive.   The pharmaceutical composition according to claim 1, comprising meloxicam or a pharmaceutically acceptable salt thereof and at least one expectorant.   The pharmaceutical composition according to claim 1, comprising meloxicam or a pharmaceutically acceptable salt thereof and at least one anti-H1-histamine.   4. The pharmaceutical composition according to claim 3, further comprising at least one antitussive agent.   The pharmaceutical composition according to claim 4, further comprising at least one antitussive agent.   The pharmaceutical composition according to claim 4 or 6, further comprising at least one expectorant.   The pharmaceutical composition according to claim 4, 6 or 7, further comprising at least one vitamin.   9. The pharmaceutical composition according to one or more of claims 1 to 8, further comprising one or more antacids.   10. A pharmaceutical composition according to one or more of claims 1 to 9, further comprising one or more central nervous system stimulants.   11. The pharmaceutical composition according to one or more of claims 1 to 10, further comprising at least one pharmaceutically acceptable carrier and / or excipient.   Antitussives are aloclamide hydrochloride, cloperastine hydrochloride, cloperastine phendiate, pentoxyberine citrate, tipepidine citrate, tipepidine hibenzate, dibutate sodium, dextromethorphan hydrobromide, dextst Lomethorphan phenolphthalein, codeine phosphate, dihydrocodeine phosphate, noscapine hydrochloride, noscapine, dl-methylephedrine hydrochloride, dl-methylephedrine saccharinate, ephedrine hydrochloride, ephedrine sulfate, dimemorphan phosphate The pharmaceutical composition according to any one of claims 1 to 11, selected from the group consisting of:, eprazinone hydrobromide, clofedanol hydrochloride, benproperine phosphate, forcodine, finobenben hydrochloride, ephedra herb and nantenjitsu.   An expectorant is potassium guaiacol sulfonate, guaifenesin, potassium cresol sulfonate, bromhexine hydrochloride, ambroxol hydrochloride, L-carbocysteine, L-methylcysteine hydrochloride, ethyl L-cysteine hydrochloride, Hudstein, ipecac Radix), licorice bulb (Ricoligis bulbus), fritillaria bulb (fritillariae brubus), persimmon (pruni cortex), kyoukyo (prachicoji radix), senega (Senegae radix), apricot kernel (Armeniacae Semen), onji The pharmaceutical composition according to claim 1, which is selected from the group consisting of (polygalae radix), licorice (kanzoue radix), car antec (plantaguinis semmen), car anteca (plantaguinis herba).   Anti-H1-histamine is diphenhydramine, diphenylpyralin, clemastine, triprolysine, promethazine, alimemazine, isothipentyl, iproheptin, dipheterol, tripelenamine, tondilamine, phenetadine, mesdirazine, mebhydroline, cyproheptadine, homochlorcyclidine, hydroxyzine, eb A pharmaceutical composition according to any one of claims 1 to 13, selected from the group consisting of: bepotastine, azelastine, oxatomide, fexofenadine, olopatadine, loratadine, acribastine, brompheniramine and doxylamine (including pharmaceutically acceptable salts thereof). object.   Anti-H1-histamine is diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, diphenylpyraline hydrochloride, diphenylpyraline theocrate, clemastine fumarate, triprolidine hydrochloride, promethazine hydrochloride, promethazine methylene disalicylate, Selected from the group consisting of alimemazine tartrate, isothipentyl hydrochloride, iproheptin hydrochloride, dipheterol hydrochloride, dipheterol phosphate, tripelenamine hydrochloride, tondiamine hydrochloride, phenetadine hydrochloride, mesdirazine hydrochloride and mebhydroline napadisilate The pharmaceutical composition according to claim 14.   An oral pharmaceutical dosage form comprising the pharmaceutical composition according to one or more of claims 1 to 15.   The oral pharmaceutical dosage form according to claim 16, wherein the amount of meloxicam or a pharmaceutically acceptable salt thereof ranges from 1 to 30 mg. The amount of the second pharmaceutically active compound is
a) in the range of 1 to 12000 mg when the second pharmaceutically active compound is one or more antitussives,
b) in the range of 0.1 to 12000 mg when the second pharmaceutically active compound is one or more expectorants,
18. An oral pharmaceutical dosage form according to claim 16 or 17 which is in the range of 0.1 to 450 mg when c) the second pharmaceutically active compound is one or more anti-H1-histamines.   Use of an oral pharmaceutical dosage form according to one or more of claims 16 to 18 as an analgesic, antipyretic, antitussive, expectorant and / or antihistamine.   For the treatment or relief of colds (including various symptoms such as fever, sore throat, chills, headache, joint pain, muscle pain, cough, runny nose, clogged nose, sputum and / or sneeze) Use of an oral pharmaceutical dosage form according to one or more of claims 16-18.   Of drugs for the treatment or relief of colds (including various symptoms such as fever, sore throat, chills, headache, joint pain, muscle pain, runny nose, clogged nose, sputum and / or sneeze) Use of a pharmaceutical composition according to one or more of claims 1 to 15 for the manufacture.   Treatment of patients in need of treatment for colds (including various symptoms such as fever, sore throat, chills, headache, joint pain, muscle pain, runny nose, clogged nose, sputum and / or sneeze) or A method of alleviation, which comprises orally administering a pharmaceutical composition according to one or more of claims 1 to 15 to a patient. 1-30 mg meloxicam or a pharmaceutically acceptable salt thereof to the patient and
a) if the second pharmaceutically active compound is an antitussive, an antitussive in an amount of 1 to 12000 mg;
b) when the second pharmaceutically active compound is an expectorant, in an amount of 0.1-12000 mg expectorant,
23. The method of claim 22, wherein when the second pharmaceutically active compound is anti-H1-histamine, the anti-H1-histamine in an amount of 0.1 to 450 mg is orally administered.   Use of meloxicam or a pharmaceutically acceptable salt thereof for the manufacture of an oral pharmaceutical dosage form according to one or more of claims 16-18.   Use of a pharmaceutically active compound selected from the group consisting of antitussives, expectorants and anti-H1-histamines for the manufacture of an oral pharmaceutical dosage form according to one or more of claims 16-18.