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WO2008038423A1 - Composition antiphlogistique et analgésique pour une utilisation orale - Google Patents

Composition antiphlogistique et analgésique pour une utilisation orale Download PDF

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Publication number
WO2008038423A1
WO2008038423A1 PCT/JP2007/055214 JP2007055214W WO2008038423A1 WO 2008038423 A1 WO2008038423 A1 WO 2008038423A1 JP 2007055214 W JP2007055214 W JP 2007055214W WO 2008038423 A1 WO2008038423 A1 WO 2008038423A1
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WIPO (PCT)
Prior art keywords
inflammatory
darcosamine
ibuprofen
salt
acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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PCT/JP2007/055214
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English (en)
Japanese (ja)
Inventor
Yukiko Nagahata
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Kobayashi Pharmaceutical Co Ltd
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Kobayashi Pharmaceutical Co Ltd
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Publication of WO2008038423A1 publication Critical patent/WO2008038423A1/fr
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    • 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
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7008—Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • Oral pharmaceutical composition for anti-inflammatory analgesia is provided.
  • the present invention relates to an oral pharmaceutical composition for anti-inflammatory analgesia. More specifically, the present invention relates to an anti-inflammatory analgesic oral pharmaceutical composition containing a phenylpropionic anti-inflammatory agent as an active ingredient. Furthermore, the present invention relates to a method for reducing the bitter taste of a phenolpropionic acid anti-inflammatory analgesic having a bitter taste.
  • Ferpropionic acid-based anti-inflammatory analgesics such as ibuprofen have been widely used as drugs for inflammatory diseases and the accompanying pain and fever because they have excellent analgesic and anti-inflammatory properties.
  • ibuprofen is suitably used as a therapeutic agent for arthralgia accompanied by inflammation because it has a high anti-inflammatory action especially in the periphery among known anti-inflammatory analgesics.
  • phenylpropionic acid anti-inflammatory analgesics are prone to side effects such as peptic ulcer and gastrointestinal bleeding because they tend to cause damage to the gastric mucosa.
  • Various attempts have been made to devise measures for enhancing the action effect of the substance and to reduce the gastrointestinal disorder itself (see, for example, Patent Documents 1 to 10).
  • ibuprofen is a drug having a bitter taste
  • an internal preparation oral pharmaceutical composition
  • masking the bitter taste improves the ingestibility of the preparation and improves the dosage. This is important for discriminating against products.
  • various methods for masking and reducing the bitterness of anti-inflammatory analgesics such as ibuprofen have been proposed (see, for example, Patent Document 11 or 12).
  • Patent Document 1 Japanese Patent Publication No. 64-8602
  • Patent Document 2 Japanese Patent Publication No. 1-24131
  • Patent Document 3 JP-A-5-148139
  • Patent Document 4 JP-A-9-48728
  • Patent Document 5 JP-A-7-188004
  • Patent Document 6 JP-A-10-259130
  • Patent Document 7 JP-A-11-12187
  • Patent Document 8 Japanese Patent Laid-Open No. 11-158066
  • Patent Document 9 Japanese Unexamined Patent Application Publication No. 2006-920
  • Patent Document 10 Japanese Patent Application Laid-Open No. 2004-59579
  • Patent Document 11 Japanese Patent Laid-Open No. 2000-273037
  • Patent Document 12 Japanese Patent Laid-Open No. 2001-106639
  • An object of the present invention is to provide an anti-inflammatory analgesic oral pharmaceutical composition in which the anti-inflammatory action (anti-inflammatory action) of a phenylpropionic acid anti-inflammatory drug is enhanced.
  • an object of the present invention is to provide an oral pharmaceutical composition for anti-inflammatory analgesia in which side effects are reduced by enhancing the anti-inflammatory action (anti-inflammatory action) of a phenylpropionic anti-inflammatory analgesic.
  • the present invention provides a method for solving the problem of a phenolpropionic acid-type anti-inflammatory analgesic having a bitter taste while simultaneously enhancing the anti-inflammatory action and reducing the bitter taste.
  • phenylpropionic acid-based compounds are obtained by using darcosamine hydrochloride in combination with a phenolpropionic acid-based anti-inflammatory analgesic such as ibuprofen. It was found that the anti-inflammatory action of anti-inflammatory analgesics is enhanced, and that the anti-inflammatory action is further enhanced by using chondroitin sulfate in combination with this.
  • the present inventors have not only enhanced the anti-inflammatory effect by using dalcosamine hydrochloride or dalcosamine hydrochloride and chondroitin sulfate in combination with a phenylpropionic acid anti-inflammatory analgesic, but at the same time, the phenylpropionic acid anti-inflammatory agent. It was found that an oral preparation which can significantly mask the bitter taste of analgesics and is easy to take can be prepared. [0007]
  • the present invention has been developed on the basis of strong knowledge and has the following aspects:
  • An anti-inflammatory analgesic oral pharmaceutical composition comprising (a) a phenylpropionic acid anti-inflammatory analgesic and (b) darcosamine, a derivative thereof, or a salt thereof.
  • Item 2 The oral pharmaceutical composition for anti-inflammatory analgesia according to Item 1, further comprising (c) chondroitin, chondroitin sulfate or a salt thereof.
  • Item 3 Item 1 or 2 containing (b) darcosamine, a derivative thereof or a salt thereof in an amount of 0.001 to 5000 parts by weight per 1 part by weight of (a) a phenylpropionic acid anti-inflammatory analgesic Oral pharmaceutical composition for anti-inflammatory analgesia described in 1.
  • Item 4 The method according to Item 2 or 3, comprising (c) chondroitin, chondroitin sulfate or a salt thereof in a ratio of 0.0001 to 5 parts by weight with respect to 1 part by weight of the (a) phenylpropionic acid anti-inflammatory analgesic.
  • Oral pharmaceutical composition for anti-inflammatory analgesia comprising (c) chondroitin, chondroitin sulfate or a salt thereof in a ratio of 0.0001 to 5 parts by weight with respect to 1 part by weight of the (a) phenylpropionic acid anti-inflammatory analgesic.
  • Oral pharmaceutical composition for anti-inflammatory analgesia comprising (c) chondroitin, chondroitin sulfate or a salt thereof in a ratio of 0.0001 to 5 parts by weight with respect to 1 part by weight of the (a) phenylpropionic acid anti-inflammatory analgesic.
  • Oral pharmaceutical composition for anti-inflammatory analgesia comprising
  • Item 5 The oral pharmaceutical composition for anti-inflammatory analgesia according to any one of Items 1 to 4, wherein the phenol-propionic acid anti-inflammatory agent is ibuprofen.
  • Phenylpropionic acid anti-inflammatory analgesics having a bitter taste include (b) darcosamine, a derivative thereof or a salt thereof, or (b) darcosamine, a derivative thereof or a salt thereof and (c) chondroitin, chondroitin A method for reducing the bitter taste of the phenylpropionic acid anti-inflammatory analgesic, characterized by using sulfuric acid or a salt thereof together.
  • Item 7 The method of reducing bitterness according to Item 6, which is ibuprofen, a phenol propionic acid anti-inflammatory agent.
  • furpropionic acid antiphlogistic analgesic includes (b) darcosamine, a dalcosamine derivative or a salt thereof, or (b) darcosamine, dalcosamine.
  • the combined use of (c) chondroitin, chondroitin sulfate or its salt with a derivative or salt thereof significantly enhances the anti-inflammatory action inherent in furpropionic acid-based anti-inflammatory analgesics.
  • the effective amount of the propionic acid-type anti-inflammatory analgesic can be reduced, and as a result, an excellent anti-inflammatory effect can be exerted using a small amount of a phenol propionic acid-type anti-inflammatory analgesic. For this reason, it has been a problem that Side effects (gastrointestinal disorders) of lupropionic acid anti-inflammatory analgesics can be reduced.
  • Ibuprofen is an excellent antiphlogistic of peripheral joints such as joints, among the propylene acid antiphlogistic analgesics.
  • the anti-inflammatory analgesic oral pharmaceutical composition of the present invention containing ibuprofen as an active ingredient is an anti-inflammatory analgesic (internal use) for arthritis, tendonitis, or stiff shoulder with inflammation, joint pain, low back pain or neuralgia. Useful.
  • the oral pharmaceutical composition for anti-inflammatory analgesia of the present invention comprises (a) a furpropionic acid-based anti-inflammatory analgesic, (b) darcosamine, a dalcosamine derivative or a salt thereof, or (b) darcosamine, a dalcosamine derivative.
  • a furpropionic acid-based anti-inflammatory analgesic e.g., a furpropionic acid-based anti-inflammatory analgesic
  • darcosamine e.g., a dalcosamine derivative or a salt thereof
  • darcosamine a dalcosamine derivative
  • the bitterness of a phenol-propionic acid anti-inflammatory analgesic is masked by using the salt in combination with (c) chondroitin, chondroitin sulfate, or a salt thereof. it can.
  • the oral pharmaceutical composition for anti-inflammatory analgesia of the present invention comprises (a) a phenylpropionic acid-based anti-inflammatory analgesic
  • component (a) (Hereinafter also referred to as “component (a)”) and (b) darcosamine, a derivative thereof or a salt thereof (hereinafter collectively referred to as “darcosamines”) This is a feature.
  • the anti-inflammatory action of the phenyl-propionic acid-type anti-inflammatory analgesic is synergistically enhanced and has an excellent anti-inflammatory effect.
  • the bitterness of the phenol propionic acid anti-inflammatory analgesic is reduced, and an internal preparation that is easy to take can be obtained.
  • phenylpropionic acid anti-inflammatory analgesic means a drug having an antiphlogistic action, analgesic action or Z and antipyretic action having phenylpropionic acid skeleton, for example, aluminoprofen, ibuprofen. , Ketoprofen, oxaprozin, zaltoprofen, thiaprofenic acid, nabumetone, naproxen, fenoprofen (calcium salt), pranoprofen, flurbiprofen or loxoprofen (sodium salt). These can be used alone or in any combination of two or more.
  • flurbiprofen, ketoprofen, ibuprofen, planop Oral phen more preferably ibuprofen [a scientific name: 2- (4-isobutylphenol) propionic acid].
  • loxoprofen can be used as loxoprofen sodium dihydrate.
  • the ratio of the (a) phenylpropionic antiphlogistic analgesic contained in the antiphlogistic analgesic oral pharmaceutical composition is not limited, but usually, per day of the oral antiphlogistic analgesic oral pharmaceutical composition.
  • Component strength Sl is preferably 0 to 2000 mg, more preferably 100 to 1000 mg, more preferably 150 to 600 mg.
  • the content of component (a) in 100% by weight of the anti-inflammatory analgesic oral pharmaceutical composition is 0.1 to 99.9% by weight, preferably 0.2 to 90% by weight. It can adjust suitably from a range.
  • Darcosamines are, for example, monosaccharides constituting chitin contained in shells of shellfish such as salmon, shrimp or salmon, or cartilage cartilage, and chitosan obtained by hydrolyzing chitin with an acid such as concentrated hydrochloric acid.
  • darcosamine in addition to being used as darcosamine, it can also be used in the form of its derivative.
  • Derived darcosamine derivatives that have been confirmed in nature include acylated derivatives such as N-acetylated derivatives, sulfated derivatives such as N-sulfated derivatives and O-sulfated derivatives, N-glycolyl derivatives, etc. And glycolyl lysate derivatives thereof. N-Acetyldarcosamine is preferred.
  • darcosamines or derivatives thereof can also be used in the form of pharmacologically (pharmaceutically) or physiologically acceptable salts.
  • strong salts include lactate, acetate, butyrate, trifluoroacetate, fumarate, maleate, tartrate, succinate, succinate, malonate, methanesulfonate,
  • organic acid salts such as toluenesulfonate, tosylate, bartiminate and stearate
  • inorganic acid salts such as hydrochloride, sulfate, nitrate, hydrobromide and phosphate.
  • Preferred examples of the salt of darcosamine include darcosamine hydrochloride and darcosamine sulfate, more preferably darcosamine hydrochloride.
  • the salt of darcosamine may be D, L, or DL. These can be used individually by 1 type or in combination of 2 or more types.
  • darcosamine hydrochloride is preferably darcosamine hydrochloride.
  • the ratio of darcosamines contained in the oral pharmaceutical composition for anti-inflammatory analgesia is not particularly limited, but usually 1 to 3000 mg of dalcosamines is administered per day of the oral pharmaceutical composition for anti-inflammatory analgesia. Preferably 40 to: It is desirable that it is contained in such a ratio that it becomes LOOOmg.
  • the content ratio of darcosamines in 100% by weight of the anti-inflammatory analgesic oral pharmaceutical composition is suitably adjusted within the range of 0.1 to 99.9% by weight, preferably 5 to 90% by weight. can do.
  • a suitable ratio of darcosamines that enhance the anti-inflammatory action of the phenylpropionic acid-based anti-inflammatory analgesic [component (a)] 0.001 to 5000 parts by weight relative to 1 part by weight of component (a), Preferably 0.1 to 500 parts by weight, more preferably 1 to 500 parts by weight can be mentioned.
  • the ratio of suitable darcosamines that enhance the anti-inflammatory action of the component (a) and mask its bitterness is 0.01 to 5000 parts by weight, preferably 0.1 to 1 part by weight of the component (a). -50 parts by weight, more preferably 0.1-3 parts by weight.
  • the oral pharmaceutical composition for anti-inflammatory analgesia of the present invention comprises (a) a ferpropionic acid-type anti-inflammatory analgesic and (b) darcosamines, and (c) chondroitin or chondroitin. Sulfuric acid or a salt thereof (hereinafter collectively referred to as “chondroitins”) can be blended.
  • Chondroitins can be extracted from the cartilage strength of fish such as sharks and mammals such as cows, regardless of their origin, but they are derived from fish from the viewpoint of safety.
  • the salt of chondroitin sulfate may be any salt that is pharmacologically (pharmaceutical) or physiologically acceptable, and is usually an alkali metal salt such as sodium salt or potassium salt, calcium salt. Examples thereof include alkaline earth metal salts such as salts, and aluminum salts. These can be used alone or in any combination of two or more.
  • the sodium salt is preferred.
  • chondroitin is preferably sodium chondroitin sulfate.
  • the ratio of chondroitin contained in the antiphlogistic analgesic oral pharmaceutical composition is not particularly limited, but usually, chondroitin caustic agent per day administration of the antiphlogistic analgesic oral pharmaceutical composition. ⁇ 2000mg, preferably 0.1 ⁇ : It is desirable to be included in harm ij such as LOOOmg! /. So that this range, appropriate content of chondroitin acids in 100 wt% for the oral pharmaceutical composition antiinflammatory, 0.000002 to 85 weight 0/0, preferably also range force of 0.0001 to 6 5 wt% Can be adjusted.
  • chondroitin that enhances the anti-inflammatory action of the phenylpropionic acid-type anti-inflammatory analgesic [component (a)] together with darcosamines
  • 0.001 part by weight of component (a) Up to 5 parts by weight, preferably ⁇ 0.005 to 2 parts by weight, and more preferably ⁇ 0.005 to 1 part by weight can be mentioned.
  • the anti-inflammatory effect of component (a) is enhanced together with darcosamines, and at the same time, the ratio of suitable chondroitins masking the bitter taste of component (a) is 0.0001-5 parts per 1 part by weight of component (a).
  • Part by weight preferably from 0.0005 to 2 parts by weight, more preferably from 0.0005 to 1 part by weight.
  • the oral pharmaceutical composition for anti-inflammatory analgesia of the present invention comprises (b) darcosamines or (b) darcosamines and (c) chondroitin in addition to the above-mentioned (a) phenylpropionic anti-inflammatory analgesics.
  • other medicinal components such as medicinal components used in anti-inflammatory, analgesic or antipyretic applications It does not limit the presence or absence of blending.
  • vitamins lipid-soluble vitamins such as vitamins A, D, E, K, U; water-soluble vitamins such as vitamins B, C, P
  • antipyretic 'analgesic' anti-inflammatory drugs Pyrine antipyretic analgesics such as sulpyrine; salicylic acid drugs such as sodium salicylate, aspirin, ethenzamide, salicylamide, and sazapyrine; alin drugs such as acetaminophen; ), Allylic acetates such as diclofenac sodium and indomethacin, pyrazolidines such as phenylbutazone and oxyphenylbutazone, pyrimidines such as bucolome, talented xycams such as piroxicam, isopropylantipyrine, etc.); antihistamine Drugs (clemastine fumarate, diphenhydramine hydrochloride, maleic acid Rufue - lamin, etc.); antitussives (e.g., Ko
  • benzonatate For example, bromhexine hydrochloride); mucosal solution such as L-cystine hydrochloride, L-methylcystine hydrochloride, and acetyl cysteine; mucus repairing agents such as carbocystine; hypnotic sedatives such as gallysopropylpyrucetyl urea; tranexamic acid, etc.
  • Antiplasmin agents; mucosal lubricants such as ambroxol hydrochloride; bronchodilators or asthma drugs (e.g. jew ephedrine, ephedrine hydrochloride, methylephedrine hydrochloride, terbutaline hydrochloride, isoproterenol, salbutamol, terbutaline)
  • xanthine drugs such as fylline, aminophylline, and proxyphylline, cromoglycic acid, etc.
  • caffeine antacid
  • amino acids amino acids
  • the dosage form of the anti-inflammatory analgesic oral pharmaceutical composition of the present invention is not particularly limited as long as it has an oral dosage form.
  • orally administered solid preparations such as powders, tablets, granules, pills, capsules (soft capsules, hard capsules), troches, chewable tablets and dry syrups; or solutions, suspensions and syrups, etc.
  • Orally administered liquid formulation may have a pharmaceutical form in which the release of medicinal ingredients is controlled (for example, immediate release preparation, sustained release preparation, etc.).
  • Formulations having a robust dosage form can be prepared according to conventional methods in the art.
  • the oral pharmaceutical composition for anti-inflammatory analgesia of the present invention is formulated into various oral dosage forms as described above, and for its stability, various carriers that are pharmaceutically acceptable for oral administration and supplementary carotenants.
  • various carriers that are pharmaceutically acceptable for oral administration and supplementary carotenants.
  • Carriers or additives for oral administration include lactose, sucrose, glucose, mannitol, sorbitol, corn starch, partially pregelatinized starch, crystalline cellulose, low-substituted hydroxypropylcellulose, carmellose sodium, talc Excipients such as starch, OC
  • Binders such as starch, agar, gelatin, gum arabic, dextrin, methylcellulose, ethyl cellulose, polyvinylpyrrolidone, hydroxypropylmethylcellulose, hydroxypropylcellulose, carboxymethylcellulose or its salts, crystalline cellulose; calcium carbonate, crospovidone, starch, Disintegration of carboxymethylcellulose calcium, low-substituted hydroxypropylcellulose, carboxymethyl starch, etc.
  • Lubricants such as magnesium stearate, talc, polyethylene glycol, and anhydrous carboxylic acid
  • Suspending agents such as polysorbate 80, polyoxyethylene hydrogenated castor oil, and pull nick
  • coating agents such as gum arabic, pullulan, strength lunauba wax and hydroxypropylmethyl phthalate
  • flavoring agents such as sucrose, glucose, sodium saccharin, sorbitol, citrate, and aspartame.
  • stabilizers In addition to the above components, as long as the effects of the present invention are not impaired, stabilizers, emulsifiers, dispersants, fluidizing agents, buffering agents, wetting agents, surfactants, and the like, which are usually acceptable as pharmaceutical additives, Optional components such as thickeners, preservatives, pH adjusters, colorants, solvents, and solubilizers can be added as desired.
  • the oral pharmaceutical composition for anti-inflammatory analgesia of the present invention can be prepared and administered as the aforementioned solid or liquid oral preparation (internal preparation).
  • the dose of the anti-inflammatory analgesic oral pharmaceutical composition of the present invention depends on the patient's age, sex, degree of symptoms to be treated, and administration method, and is contained in (a) phenyl.
  • Examples of the propionic acid-based anti-inflammatory analgesic dose power per adult can be 0 to 2000 mg, preferably 100 to 1000 mg, more preferably 150 to 600 mg. Within this dosage range, the dosage can be divided into 1 to several times a day.
  • the oral pharmaceutical composition for anti-inflammatory analgesia of the present invention can be preferably used for the purpose of suppressing inflammation.
  • the ferulpropionic acid anti-inflammatory analgesic which is an active ingredient, has both an analgesic action and an antipyretic action. It can also be used for the purpose of suppressing palliative (analgesic) fever (antipyretic).
  • the oral pharmaceutical composition for anti-inflammatory analgesia of the present invention is a joint with arthritis, tendonitis or inflammation. It can be suitably used for the purpose of improving (anti-inflammatory) or analgesic peripheral inflammation such as pain, low back pain, neuralgia, muscle pain or stiff shoulders.
  • the oral pharmaceutical composition for anti-inflammatory analgesia of the present invention comprises (a) a phenylpropionic acid-based anti-inflammatory analgesic, wherein (b) darcosamine or (b) darcosamine and (c) chondroitin described above
  • a phenylpropionic acid-based anti-inflammatory analgesic wherein (b) darcosamine or (b) darcosamine and (c) chondroitin described above
  • the anti-inflammatory action of the phenylpropionic acid anti-inflammatory analgesic is enhanced, and an excellent anti-inflammatory action can be exerted in a small amount. For this reason, It is possible to avoid the occurrence of side effects such as gastrointestinal disorders, which have been a problem with on-acid anti-inflammatory analgesics, and can also be used as a preferred anti-inflammatory analgesic in terms of efficacy and side effects.
  • the oral pharmaceutical composition for anti-inflammatory analgesia of the present invention comprises (a) a phenylpropionic acid anti-inflammatory analgesic, wherein (b) darcosamine, or (b) darcosamine and (c) chondroitin described above are used.
  • a phenylpropionic acid anti-inflammatory analgesic wherein (b) darcosamine, or (b) darcosamine and (c) chondroitin described above are used.
  • a phenylpropionic acid anti-inflammatory analgesic is used by combining (b) darcosamines described above or (b) darcosamines and (c) chondroitins. Can be implemented.
  • Examples of the target phenylpropionic anti-inflammatory analgesics include the drugs described in (I) above and having a bitter taste. Preferred are ibuprofen, ketoprofen and pranoprofen, and more preferred is ibuprofen.
  • the darcosamines used in combination with the phenpropionic acid-type anti-inflammatory analgesic include the dalcosamines and dalcosamine derivatives (preferably N-acetyldarcosamine) described in (I) above or the like. Can be mentioned.
  • Preferred is a pharmaceutically acceptable salt of darcosamine, preferably darcosamine hydrochloride or dalcosamine sulfate, more preferably darcosamine hydrochloride.
  • the ratio of the darcosamines used in combination with a phenolpropionic anti-inflammatory analgesic is that the propylene-based anti-inflammatory analgesia without adversely affecting the anti-inflammatory effect enhanced by the combined use of both.
  • a range force of usually 0.01 to 5000 parts by weight can be appropriately selected.
  • the range is preferably 0.1 to 50 parts by weight, more preferably 0.1 to 3 parts by weight.
  • chondroitin used in combination with (a) a phenolpropionic anti-inflammatory analgesic and (b) darcosamines include chondroitin and chondroxin described in (I) above.
  • a reuterine sulfate or its salt can be mentioned.
  • Preferred is a pharmaceutically acceptable salt of chondroitin sulfate, and more preferred is sodium chondroitin sulfate.
  • the proportion of chondroitin used in combination with a ferropropionic acid-type anti-inflammatory analgesic and darcosamines is such that there is no adverse effect on the anti-inflammatory effect enhanced by the combined use of the three components.
  • a range force of usually 0.0001 to 5 parts by weight can be appropriately selected. The range is preferably 0.0005 to 2 parts by weight, more preferably 0.0005 to 1 part by weight.
  • a furpropionic acid anti-inflammatory drug is used in combination with (b) darcosamine or (b) darcosamine and (c) chondroitin as described above.
  • Phenolpropionic acid anti-inflammatory analgesics are known as drugs that exert anti-inflammatory and antipyretic analgesic activity by inhibiting the production of inflammatory mediators such as prostaglandin E2 (PGE2). Therefore, ibuprofen was used as a phenylpropionic anti-inflammatory analgesic and the inhibition rate of PGE2 production against cultured cells was measured to evaluate the anti-inflammatory effect of the oral anti-inflammatory analgesic composition of the present invention (Chong-Jeh Lo et al. al., Journal of trauma, Vol. 45, No.l,
  • darcosamine hydrochloride was used as darcosamines
  • sodium chondroitin sulfate was used as chondroitins.
  • the mouse macrophage cell line RAW264 (RIKEN BioResource 0.2 g / mL in the presence of the test compositions listed in Table 1 (Comparative Examples 1-12, Examples 1-4) or in the absence of the test composition (control group).
  • the culture supernatant was collected by incubating with a medium containing endotoxin (LPS) (MEM medium containing 10% fetal calf serum (FCS)) for 24 hours (stimulated with LPS).
  • LPS endotoxin
  • FCS fetal calf serum
  • FIG. 1 shows a graph comparing the results of Comparative Examples 5 and 8 and Example 1
  • Fig. 2 shows a graph comparing the results of Comparative Examples 5, 8, 11 and 12 and Examples 1 and 2
  • Comparative Example A graph comparing the results of Examples 2, 4, and 6 with Examples 3 and 4 is shown in FIG.
  • ibuprofen 0.1 ⁇ g / mL alone has a PGE2 production inhibition rate of 20% (Comparative Example 2), but this can be achieved by combining darcosamine hydrochloride 50 g / mL.
  • ibuprofen 0.5 ⁇ g / mL alone has almost the same inhibitory effect on PGE2 production, and ibuprofen 0.1 ⁇ g / mL was added with darcosamine 500 g / mL.
  • the PGE2 production inhibitory effect almost equivalent to that of ibuprofen 10 ⁇ g / mL alone (Comparative Example 6) was obtained.
  • Ficher344 male rats (5 weeks old) weighing approximately 100 g (Nihon SLC Co., Ltd.) were inoculated with dairy cattle bacteria as an adjuvant on the rear left foot to induce arthritis.
  • Test composition daily from day 12 after inoculation [Comparative Example 13: ibuprofen (daily dose 30 mg / kg body weight), Example 5 (3-component combination): ibuprofen (daily dose 30 mg / kg body weight) + Darcosamine hydrochloride (daily dose 33.2mg / kg body weight) + chondroitin sulfate sodium (daily dose) 0.00264 mg / kg body weight)] was orally administered, and the foot volume of the left foot (adjuvant injured foot) was measured on the 10th and 15th day after administration. As a control, the foot volume of the left foot (adjuvant-inoculated foot) was measured in the same manner in the untreated group that was not treated after adjuvant inoculation.
  • each component described in Table 4 was formulated according to a general powder manufacturing method to prepare a powdery formulation (Comparative Examples 14-15, Examples 6-15). This was taken by a taste paneler consisting of 6 members (holding in the mouth for 10 seconds) and, according to the following evaluation criteria, (1) bitterness, (2) mouthfeel [feeling of irritation when taken ( The presence or absence of tingling) was scored. (3) The overall feeling of taking (comparison example 14 (ibuprofen lOOmg)) compared with the feeling of improving the feeling of taking was calculated by multiplying each person's points (1) and (2).
  • Example 16 Formulation of 6 tablets (daily dose)
  • FIG. 1 In Experimental Example 1, Comparative Example 5 (ibuprofen 1 ⁇ g / mL), Comparative Example 8 (darcosamine hydrochloride 1 ⁇ g / mL), Example 1 (Ibuprofen 1 ⁇ g / mL) The graph which compared the PGE2 production inhibitory effect of mL + darcosamine hydrochloride 1 microgram / mL) is shown.
  • FIG. 3 In Experimental Example 1, Comparative Example 2 (ibuprofen 0.1 g / mL), Comparative Example 4 (ibuprofen 1 ⁇ g / mL), Comparative Example 6 (ibuprofen 10 ⁇ g / mL), Example 3 ( The graph which compared the PGE2 production inhibitory effect of ibuprofen 0.1 microgram / mL + darcosamine hydrochloride 50 microgram / mL) and Example 4 (ibuprofen 0.1 microgram / mL + darcosamine hydrochloride 500 microgram / mL) is shown.

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Abstract

L'invention concerne une composition antiphlogistique et analgésique pour une utilisation orale, dans laquelle l'effet antiphlogistique (effet anti-inflammatoire) d'un agent antiphlogistique et analgésique à base d'acide phénylpropionique a été potentialisé. L'invention concerne également un procédé de potentialisation de l'effet antiphlogistique d'un agent antiphlogistique et analgésique à base d'acide phénylpropionique ayant une amertume et atténuant simultanément l'amertume. A savoir, (a) un agent antiphlogistique et analgésique à base d'acide phénylpropionique est utilisé conjointement avec (b) la glucosamine, son dérivé ou un sel de celle-ci ou (b) la glucosamine, son dérivé ou un sel de celle-ci et (c) la chondroïtine, le sulfate de chondroïtine ou son sel.
PCT/JP2007/055214 2006-09-28 2007-03-15 Composition antiphlogistique et analgésique pour une utilisation orale Ceased WO2008038423A1 (fr)

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WO2010013551A1 (fr) * 2008-07-30 2010-02-04 サントリーホールディングス株式会社 Préparation pour administration orale renfermant du sulfate de chondroïtine extrait à l'eau et du glycoside de quercétine
JP6554839B2 (ja) * 2014-04-02 2019-08-07 大正製薬株式会社 経口用組成物
MX2019006769A (es) * 2016-12-11 2019-12-05 Seanergy Dermatology Ltd Composiciones que comprenden polisacaridos sulfatados.
JP7229013B2 (ja) * 2018-12-25 2023-02-27 小林製薬株式会社 内服用医薬組成物

Citations (6)

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JP2002145779A (ja) * 2000-11-10 2002-05-22 Rohto Pharmaceut Co Ltd 関節痛治療または予防用組成物
US20020068718A1 (en) * 2000-10-03 2002-06-06 Pierce Scott W. Chondroprotective/restorative compositions and methods of use thereof
JP2004002482A (ja) * 2003-09-09 2004-01-08 Rohto Pharmaceut Co Ltd アミノ糖含有製剤
JP2004026846A (ja) * 2003-09-09 2004-01-29 Rohto Pharmaceut Co Ltd 関節痛治療または予防用組成物
JP2006028134A (ja) * 2004-07-21 2006-02-02 Rohto Pharmaceut Co Ltd 内服用組成物
JP2006290812A (ja) * 2005-04-12 2006-10-26 Rohto Pharmaceut Co Ltd 鎮痛製剤

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Publication number Priority date Publication date Assignee Title
US20020068718A1 (en) * 2000-10-03 2002-06-06 Pierce Scott W. Chondroprotective/restorative compositions and methods of use thereof
JP2002145779A (ja) * 2000-11-10 2002-05-22 Rohto Pharmaceut Co Ltd 関節痛治療または予防用組成物
JP2004002482A (ja) * 2003-09-09 2004-01-08 Rohto Pharmaceut Co Ltd アミノ糖含有製剤
JP2004026846A (ja) * 2003-09-09 2004-01-29 Rohto Pharmaceut Co Ltd 関節痛治療または予防用組成物
JP2006028134A (ja) * 2004-07-21 2006-02-02 Rohto Pharmaceut Co Ltd 内服用組成物
JP2006290812A (ja) * 2005-04-12 2006-10-26 Rohto Pharmaceut Co Ltd 鎮痛製剤

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Title
TALLARIDA R.J. ET AL.: "Antinociceptive synergy, additivity, and subadditivity with combinations of oral glucosamine plus nonopioid analgesics in mice", THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 307, no. 2, 2003, pages 699 - 704, XP003021790 *

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