Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
  • A61K31/365—Lactones
  • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
  • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
  • A61K9/0007—Effervescent
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2013—Organic compounds, e.g. phospholipids, fats
  • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P11/00—Drugs for disorders of the respiratory system
  • A61P11/10—Expectorants
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P11/00—Drugs for disorders of the respiratory system
  • A61P11/14—Antitussive agents

Definitions

• the present invention is related to pharmaceutical compositions comprising erdosteine and ascorbic acid as active agents, and use of such compositions for treatment of coughing and expectoration.
• Erdosteine is a thiol derived mucolytic drug. It exhibits muco-modulator and free radical scavenger activities.
• Erdosteine whose chemical name is (+/-)-(+/-)-( ⁇ ((Tetrahydro-2-oxo-3- thienyl) carbamoyl) methyl ⁇ thio) acetic acid, has been described in the Patent Application US4411909 for the first time. In said document, it has been described that erdosteine is effective in the treating respiratory diseases due to its mucolytic activity.
• Erdosteine can be found in the market in l50mg and 300mg capsule and l75mg suspension forms.
• Ascorbic acid (Vitamin C) which may dissolve in water contained in various fruits and vegetables is a required vitamin for producing collagen and tissue repair.
• Ascorbic acid whose chemical name is R)- 5-[(S)-l,2-Dihydroxyethil]-3,4-dihydroxy-5H-furan-2-one, has been described according to the studies in the state of art as being effective in the treatment of diseases such as common cold, gingiva infection, acne, depression and fertility. Furthermore, it is known that ascorbic acid is used as nutritional support.
• Ascorbic acid may be found in the market in various forms such as, 500 mg and lOOOmg effervescent tablets, chewable tablets, syrups, capsules, film-coated tablets and pastilles.
• compositions in which ascorbic acid is used together or simultaneously with erdosteine exhibits much higher therapeutic efficacy in comparison to compositions in which the active agents are used separately.
• erdosteine and ascorbic acid provides a shorter period of time for therapeutic effect to be observed and a stronger effect in comparison when these two active agents are used separately. In this way it is possible to provide a more efficient treatment for patients.
• these positive effects can be seen in combinations when these two active agents are given sequentially and said positive effects can be seen when these two active agents are given inside a dosage form at the same time or inside independent dosage forms simultaneously. High therapeutic benefits can also be observed as long term effects.
• the present invention is related to pharmaceutical compositions comprising erdosteine and ascorbic acid together to be administered sequentially inside separate dosage forms, simultaneously inside separate dosage forms or simultaneously in the same dosage form.
• the present invention is a pharmaceutical composition
• erdosteine and ascorbic acid and/or pharmaceutically acceptable derivatives thereof as active agents are erdosteine and ascorbic acid and/or pharmaceutically acceptable derivatives thereof as active agents.
• the present invention is related to pharmaceutical compositions comprising a pharmaceutically active amount of erdosteine and ascorbic acid and at least one pharmaceutically acceptable agent.
• erdosteine and ascorbic acid may be formulated together in a single composition together with at least a pharmaceutically acceptable excipient and they may also be formulated as a composition with at least a pharmaceutically acceptable excipient in which erdosteine and ascorbic acid are separate from each other.
• the different compositions that are obtained can be combined in a single dosage form or they may be prepared as separate dosage forms.
• said dosage forms may be the same with each other or they may be different from one another.
• the present invention is also related to a suitable erdosteine and ascorbic acid for preparing a drug to be used in combination therapy in expectoration and cough treatment through simultaneous, sequential or separate administration.
• Erdosteine which is found in the pharmaceutical compositions according to the invention can be in the form of pharmaceutically acceptable salts, hydrates, solvates, esters, enantiomers, diastereomers, racemates and/or in any polymorphic form such as amorphous, crystals or combination thereof.
• Ascorbic acid which is found in the pharmaceutical compositions according to the invention can be in the form of pharmaceutically acceptable salts, hydrates, solvates, esters, enantiomers, diastereomers, and racemates and/or in any polymorphic form such as amorphous crystals or combinations thereof.
• composition of the invention comprising erdosteine and ascorbic acid may be prepared in the form of any dosage forms such as tablets, effervescent tablets, effervescent granules, effervescent dry powder, film coated tablets, enteric coated tablets, dry powder, granules, capsules, prolonged release tablet, modified release tablet, delayed release tablet, orodispersible tablets and chewable tablets.
• Pharmaceutical compositions comprising erdosteine and ascorbic acid together may not only be in any form of these dosage forms but said compositions can be in the form of any one of these dosage forms if erdosteine and ascorbic acid are stored in separate dosage forms from each other.
• compositions comprising the combination suitable to the invention may be in the form of any one of the aforementioned dosage forms or as combinations of these dosage forms or in the form of a treatment package consisting of this combination.
• compositions of the invention comprising erdosteine preferably are in the form of effervescent tablets or film coated tablets, capsules, suspension forms, particularly preferably in the form of effervescent tablets.
• Pharmaceutical compositions of the invention comprising ascorbic acid preferably are in the form effervescent tablets or film coated tablets, capsules, suspension forms, particularly preferably in the form of effervescent tablets.
• compositions comprising erdosteine and ascorbic acid of the invention are preferably in the form of effervescent tablets or film coated tablets, capsules, suspension forms, particularly preferably in the form of effervescent tablet forms.
• compositions of the invention comprising erdosteine and ascorbic acid may comprise in addition to the erdosteine and ascorbic acid which are active agents, a variety of excipients.
• the present invention is related to a pharmaceutical composition in which erdosteine and ascorbic acid are present together in a single dosage form, wherein said composition is in the form of effervescent tablets or capsule form.
• the dispersant which may be used in pharmaceutical compositions of the invention may be selected form a group comprising carboxymethyl cellulose, carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, microciystalline cellulose, methyl cellulose, chitosan, starch and sodium starch glycolate.
• the diluents which may be used in pharmaceutical compositions of the invention may be selected from a group comprising calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, microcrystalline cellulose, dextrose, fructose, lactitol, lactose, magnesium oxide, maltitol, maltodextrin, maltose, mannitol, simethicone, sorbitol, starch, sodium chloride, sucrose, talc and xylitol.
• the glidant which may be used in pharmaceutical compositions of the invention may be selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, sodium benzoate, potassium benzoate, sodium lauryl sulfate, talc, stearic acid and zinc stearate.
• the lubricant which may be used in pharmaceutical compositions of the invention may be selected from a group comprising tribasic calcium phosphate, colloidal silicone dioxide, magnesium silicate, magnesium trisilicate and talc.
• the binder which may be used in pharmaceutical compositions of the invention may be selected from a group comprising carboxymethyl cellulose sodium, ethyl cellulose, gelatin, hydroxymethyl cellulose, hydroxypropyl cellulose, hypermellose, magnesium aluminum silicate, maltodextrin, methyl cellulose, povidone and starch.
• At least one acidic agent and at least one basic agent which can be used in pharmaceutical compositions according to the invention forms the effervescent pair, wherein the acidic agent, can be selected from the group consisting of organic acids such as malic acid, citric acid, tartaric acid, fumaric acid and the basic agent can be selected from the group consisting of agents such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate.
• the acidic agent can be selected from the group consisting of organic acids such as malic acid, citric acid, tartaric acid, fumaric acid
• the basic agent can be selected from the group consisting of agents such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate.
• the pH adjusting agent which can be used in pharmaceutical compositions can be selected from citrate, phosphate, carbonate, tartarate, fumarate, acetate and amino acid salts.
• the surfactant which can be used in pharmaceutical compositions according to the invention can be selected from the agents such as sodium lauryl sulfate, polysorbate, polyoxyethylene, polyoxypropylene glycol etc.
• the stabilizer which can be used in pharmaceutical compositions according to the invention can be selected from the group comprising tocopherol, tetrasodium edetate, nicotinamide and cyclodextrin.
• the sweetener and/or flavoring agent which can be used in pharmaceutical compositions according to the invention can be selected from the group comprising acesulfame, aspartame, dextrose, fructose, maltitol, maltose, mannitol, saccharine, saccharine sodium, sodium cyclamate, sorbitol, sucralose, sucrose, xylitol and sodium chloride.
• the aroma agent which can be used in pharmaceutical compositions according to the invention can be selected from aromas such as menthol, lemon, orange, vanilla, strawberry, raspberry, caramel, etc.
• erdosteine is available at a ratio of 0.1 to 99%, preferably at a ratio of 1 to 98%, particularly preferably at a ratio of 5 to 95% by weight.
• ascorbic acid is available at a ratio of 0.1 to 99%, preferably at a ratio of 1 to 98%, particularly preferably at a ratio of 5 to 95% by weight.
• erdosteine is available at a range of 10 mg to 750 mg, preferably at a range of 10 mg to 650 mg, particularly preferably at a range of 10 mg to 500 mg per unit dosage form.
• ascorbic acid is available at a range of 10 mg to 1500 mg, preferably at a range of 10 mg to 1450 mg, particularly preferably at a range of 10 mg to 1400 mg per unit dosage form.
• a third active agent in additional to erdosteine and ascorbic acid can be available.
• the third active agent can be selected from anti-acid, anti-cholinergic, anti-spasmodic, anti-emetic, antibiotic, anti-propulsive, anti-allergic, anti-diarrheal, anti-obesity, anti-thrombotic, anti-fibrinolytic, anti- anemic, anti-hypertensive, antifungal, antipruritic, anti-psoriatic, antibiotic, antiseptic, anti-acne antibacterial, antimicotic, antiviral, anti-neoplastic, anti-arrhythmic, anti-adrenergic, anti-epileptic, anti-parkinson, anti-protozoal, anthelmintic, anti-inflammatory, diuretic, laxative, sulfonamide, imidazol, corticosteroids,
• composition according to the invention can be obtained by a method consisting of:
• the pharmaceutical composition according to the invention is in the form of an effervescent tablet, the composition comprises at least one pharmaceutically acceptable effervescent acid and at least one effervescent base in addition to the active agents and excipients.
• Effervescent acids in accordance with the invention which can be used within the effervescent compositions comprising erdosteine and ascorbic acid are selected from a group composed of organic acids such as citric acid and acetic acid, tartaric acid, fumaric acid, adipic acid, malic acid or pharmaceutically acceptable hydrates, anhydrates, salts and similar forms thereof or from combinations thereof.
• Effervescent bases which can be used within the effervescent compositions in accordance with the invention, comprising erdosteine and ascorbic acid can be selected from a group composed of alkaline or alkaline earth metal carbonates or bicarbonates or from mixtures thereof.
• preferred effervescent bases in the compositions according to the invention are potassium carbonate, potassium bicarbonate, potassium citrate, potassium hydroxide, sodium carbonate and sodium bicarbonate or combinations thereof.
• Effervescent compositions according to the invention comprising erdosteine and ascorbic acid comprise at least one pharmaceutically acceptable effervescent acid and at least one effervescent base ranging from 10% to 95%, preferably from 15% to 95%, specifically preferably from 20% to 95% by the total weight of the composition.
• the ratio of at least one pharmaceutically acceptable effervescent acid and at least one effervescent base to each other, within the effervescent compositions in accordance with the invention comprising erdosteine and ascorbic acid is from 0,1 to 10 by weight.
• compositions according to the invention may be prepared as tablets as well, if desired. If the compositions are in the form of tablets, obtained tablets can be treated with coating compositions comprising film coating agents, for example with sugar-based coating agents, water-soluble film coating agents, enteric coating agents, delayed-release coating agents and any compositions thereof.
• film coating agents for example with sugar-based coating agents, water-soluble film coating agents, enteric coating agents, delayed-release coating agents and any compositions thereof.
• saccharose may be used alone or optionally with any of the agents such as talc, calcium carbonate, calcium phosphate, calcium sulphate, gelatin, gum arabic, polyvinilpyrrolidone and pullulan or any of the combinations thereof.
• agents such as talc, calcium carbonate, calcium phosphate, calcium sulphate, gelatin, gum arabic, polyvinilpyrrolidone and pullulan or any of the combinations thereof.
• the water-soluble film coating agent can be selected from cellulose derivatives such as hydoxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, methyl hyrdoxyethyl cellulose and sodium carboxymethyl cellulose; synthetic polymers such as polyvinylacetaldiethylaminoacetate, aminoalkyl methacrylate copolymers and polyvinyl pyrrolidone; and polysaccharides such as pullulan or from combinations thereof.
• cellulose derivatives such as hydoxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, methyl hyrdoxyethyl cellulose and sodium carboxymethyl cellulose
• synthetic polymers such as polyvinylacetaldiethylaminoacetate, aminoalkyl methacrylate copolymers and polyvinyl pyrrolidone
• polysaccharides such as pullulan or from combinations thereof.
• Enteric coating agents can be selected from cellulose derivatives such as hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose acetate succinate, carboxymethyl ethyl cellulose, cellulose acetate phthalate; acrylic acid derivatives such as methacrylic acid copolymer L, methacrylic acid copolymer LD and methacrylic acid copolymer S; and natural substances such as shellac or from combinations thereof.
• cellulose derivatives such as hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose acetate succinate, carboxymethyl ethyl cellulose, cellulose acetate phthalate
• acrylic acid derivatives such as methacrylic acid copolymer L, methacrylic acid copolymer LD and methacrylic acid copolymer S
• natural substances such as shellac or from combinations thereof.
• Delayed-release coating agents can be selected from cellulose derivatives such as ethyl cellulose; acrylic acid derivatives such as aminoalkyl methacrylate copolymer RS, ethyl acrylate-methyl methacrylate copolymer emulsion or from combinations thereof.
• compositions according to the invention can be used in the prevention and treatment of expectoration and coughing.
• EXAMPLE Effervescent tablet composition comprising erdosteine and ascorbic acid
• Erdosteine and ascorbic acid being active agents, are granulated and mixed by adding the excipients of the formulation and the granulation is pressed to form effervescent tablets.

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• 2017
  • 2017-12-30 TR TR2017/23198A patent/TR201723198A2/tr unknown
• 2018
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