WO2004039408A1 - Medicinal composition - Google Patents
Medicinal composition Download PDFInfo
- Publication number
- WO2004039408A1 WO2004039408A1 PCT/JP2003/013988 JP0313988W WO2004039408A1 WO 2004039408 A1 WO2004039408 A1 WO 2004039408A1 JP 0313988 W JP0313988 W JP 0313988W WO 2004039408 A1 WO2004039408 A1 WO 2004039408A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- runny nose
- olopatadine
- pharmaceutical composition
- extract
- anticholinergic
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title abstract description 4
- 229960004114 olopatadine Drugs 0.000 claims abstract description 7
- JBIMVDZLSHOPLA-LSCVHKIXSA-N olopatadine Chemical compound C1OC2=CC=C(CC(O)=O)C=C2C(=C/CCN(C)C)\C2=CC=CC=C21 JBIMVDZLSHOPLA-LSCVHKIXSA-N 0.000 claims abstract description 7
- 241001106067 Atropa Species 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 7
- 230000001078 anti-cholinergic effect Effects 0.000 claims description 4
- 229940108858 belladonna total alkaloid Drugs 0.000 claims description 4
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 3
- 241001268392 Dalla Species 0.000 claims description 3
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 claims description 3
- DHUZAAUGHUHIDS-ONEGZZNKSA-N Isomyristicin Chemical compound COC1=CC(\C=C\C)=CC2=C1OCO2 DHUZAAUGHUHIDS-ONEGZZNKSA-N 0.000 claims description 3
- BFSMWENDZZIWPW-UHFFFAOYSA-N Isopropamide iodide Chemical compound [I-].C=1C=CC=CC=1C(C(N)=O)(CC[N+](C)(C(C)C)C(C)C)C1=CC=CC=C1 BFSMWENDZZIWPW-UHFFFAOYSA-N 0.000 claims description 3
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 claims description 3
- 229960001543 isopropamide iodide Drugs 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 229960005439 propantheline bromide Drugs 0.000 claims description 3
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 claims description 3
- 229960002646 scopolamine Drugs 0.000 claims description 3
- CDQGZJGHIVUWQA-UHFFFAOYSA-N 4-[2-(4-hydroxy-3,5-dimethylphenyl)butan-2-yl]-2,6-dimethylphenol Chemical compound C=1C(C)=C(O)C(C)=CC=1C(C)(CC)C1=CC(C)=C(O)C(C)=C1 CDQGZJGHIVUWQA-UHFFFAOYSA-N 0.000 claims description 2
- ZTVIKZXZYLEVOL-MCOXGKPRSA-N Homatropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(O)C1=CC=CC=C1 ZTVIKZXZYLEVOL-MCOXGKPRSA-N 0.000 claims description 2
- 229960000857 homatropine Drugs 0.000 claims description 2
- 229930003347 Atropine Natural products 0.000 claims 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 claims 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 claims 1
- 229960000396 atropine Drugs 0.000 claims 1
- 206010039101 Rhinorrhoea Diseases 0.000 abstract description 18
- 230000000694 effects Effects 0.000 abstract description 9
- 206010039085 Rhinitis allergic Diseases 0.000 abstract description 8
- 201000010105 allergic rhinitis Diseases 0.000 abstract description 8
- 239000000812 cholinergic antagonist Substances 0.000 abstract description 8
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 abstract description 5
- 208000010753 nasal discharge Diseases 0.000 abstract 1
- 208000036071 Rhinorrhea Diseases 0.000 description 17
- HVRLZEKDTUEKQH-NOILCQHBSA-N Olopatadine hydrochloride Chemical compound Cl.C1OC2=CC=C(CC(O)=O)C=C2C(=C/CCN(C)C)\C2=CC=CC=C21 HVRLZEKDTUEKQH-NOILCQHBSA-N 0.000 description 13
- 239000003814 drug Substances 0.000 description 13
- 229960003139 olopatadine hydrochloride Drugs 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 238000012360 testing method Methods 0.000 description 9
- 206010070834 Sensitisation Diseases 0.000 description 8
- 230000008313 sensitization Effects 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- 241000700198 Cavia Species 0.000 description 5
- 239000000739 antihistaminic agent Substances 0.000 description 5
- DVKJHBMWWAPEIU-UHFFFAOYSA-N toluene 2,4-diisocyanate Chemical compound CC1=CC=C(N=C=O)C=C1N=C=O DVKJHBMWWAPEIU-UHFFFAOYSA-N 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 229920000742 Cotton Polymers 0.000 description 3
- 206010028735 Nasal congestion Diseases 0.000 description 3
- 206010041349 Somnolence Diseases 0.000 description 3
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 3
- 230000001387 anti-histamine Effects 0.000 description 3
- 239000000043 antiallergic agent Substances 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 241000700199 Cavia porcellus Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- -1 Hydroxypropyl Chemical group 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 229960001948 caffeine Drugs 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 206010039083 rhinitis Diseases 0.000 description 2
- 206010041232 sneezing Diseases 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002921 anti-spasmodic effect Effects 0.000 description 1
- 229940124623 antihistamine drug Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 229960004342 cetirizine hydrochloride Drugs 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 229940124579 cold medicine Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 230000003419 expectorant effect Effects 0.000 description 1
- 229940066493 expectorants Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 238000004898 kneading Methods 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 230000002911 mydriatic effect Effects 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
Definitions
- the present invention is a pharmaceutical composition useful for suppressing runny secretions caused by allergic rhinitis and the like.
- type I allergic diseases such as allergic rhinitis show a biphasic reaction of an immediate phase reaction and a delayed phase reaction. Immediate reaction in this type I allergic disease induces sneezing, runny nose, and nasal congestion immediately after inducing antigen such as pollen. On the other hand, the delayed phase reaction is characterized by a nasal congestion that reappears several hours after the antigen is induced. Anti-histamine drug is used to treat sneezing, runny nose and nasal congestion due to allergic rhinitis.
- antiallergic drugs such as olopatadine hydrochloride and cetirizine hydrochloride, which have an inhibitory effect on the release of chemical media overnight and an inhibitory effect on the migration of inflammatory cells, in addition to the main antihistamine effect.
- anti-allergy drugs which have an antihistamine action as a main effect, have side effects such as drowsiness.
- olopatadine hydrochloride has a strong antihistamine action, it exhibited side effects of drowsiness in clinical trials Have been reported. ,
- Anticholinergic drugs are drugs that suppress or block the stimulating effect of cholinergic postganglionic fibers, and are known to have various effects such as antispasmodic, analgesic, mydriatic, secretory, and local anesthetic effects. ing. Many anticholinergic agents are known, such as belladonna total alkaloids, belladonna extract, atotopin, homatropin, scopolamine, funnel extract, isopropamide iodide, dalla extract, methyl penactidium bromide, and propantheline bromide. I have.
- An object of the present invention is to provide a pharmaceutical composition which has an effect of reducing side effects such as drowsiness and suppressing nasal inflammatory conditions, particularly runny nose.
- the present inventors have conducted intensive studies in order to solve such a problem, and as a result, by combining olopatadine or a salt thereof with an anticholinergic drug, the present invention has an excellent therapeutic effect on allergic rhinitis by synergistic action.
- the inventors have found that the dose can be reduced, and have completed the present invention.
- the present invention is a pharmaceutical composition
- a pharmaceutical composition comprising olopatadine or a salt thereof and an anticholinergic.
- the salt of olopatadine includes hydrochloride, nitrate, fumarate and the like. Particularly preferred is the hydrochloride.
- An effective amount of olopatadine or a salt thereof is a daily dose of 0.05 to: 100 mg in oral administration, preferably 0.5 to 20 mg.
- the effective amount of the anticholinergic agent is 0.1 to 2.0 mg, preferably 0.3 to 1.0 mg for belladonna total alkaloid, 5 to 200 mg for belladonna extract, preferably 10 to: LOOmg, at daily dose for oral administration.
- ⁇ 2.0mg preferably 0.3 ⁇ : 1.0mg for homato mouth pin, 0.1 ⁇ 2.0mg, preferably 0.3 ⁇ 2.0mg for scopolamine 1.0 mg, 5 to 200 mg for funnel extract, preferably 10 to: L00 mg, l to 50 mg for isopropamide iodide, preferably 2 to: LOmg, 0.1 to 2.0 mg for Dalla extract, preferably 0.3 to: L0 mg, odor
- the amount is 5 to 200 mg, preferably 10 to 100 mg, for methyl benactide bromide, and 5 to 200 mg, preferably 10 to 100 mg for propantheline bromide.
- the mixing ratio of olopatadine or a salt thereof to the anticholinergic agent in the pharmaceutical composition of the present invention is preferably from 0.00025 to 1000 parts by weight of olopatadine hydrochloride to 1 part by weight of the anticholinergic agent, and more preferably from 0.0025 to 200 parts by weight.
- the pharmaceutical composition of the present invention can be administered once or twice or three times a day.
- the pharmaceutical composition of the present invention is prepared into a preparation for oral or parenteral administration.
- Oral preparations include solid preparations such as tablets, pills, capsules, granules, powders, and chewable tablets, and liquid preparations such as syrups and drinks, and are manufactured by a conventional method.
- Parenteral preparations include sprays and liquids for nasal and eye drops, and ointments, creams and patches for administration to the skin.
- excipients When prepared as a solid preparation, excipients, lubricants, disintegrants and the like can be used as necessary.
- a surfactant When preparing a solution, spray, ointment, cream, or patch, a surfactant, a solubilizing agent, a buffer and the like can be used as necessary.
- preservatives flavors, pigments, sweeteners, flavoring agents, fresheners and the like can be used.
- the pharmaceutical composition of the present invention may further comprise a nonsteroidal anti-inflammatory drug, an anti-inflammatory enzyme drug, a bronchodilator, a sympathetic stimulant, another central nervous stimulant, an antitussive, Drugs selected from expectorants, antihistamines, other antiallergic drugs, vitamins, antacids, crude drugs, etc. may be appropriately compounded. These components can be used alone or in admixture with each other. Usually, the cold medicines listed in the OTC Pharmaceutical Manufacturing Guidelines (2000 edition, supervised by the Pharmaceutical Affairs Committee, published by Jiho Co., Ltd.) It is compounded in accordance with the standards and the internal medicine standards for rhinitis.
- Olopatadine hydrochloride 25 g Sudofuedrin 120 g Belladonna total alloid 0.4 g Anhydrous caffeine 100 g
- magnesium stearate 1 After stirring and granulating and drying, magnesium stearate 1
- Olopatadine hydrochloride 25 g Suedoephedrine 120 g Belladonna total alloid 0.4 g Anhydrous caffeine 100 g Potato starch 696 g Crystalline cellulose 10 g Hydroxypropyl cellulose 30 g Magnesium stearate 1 2 g Measure the above components and amounts, mix uniformly, pulverize, dry-granulate, mix and fill so that the content of 1 capsule is 30 Omg. Obtained.
- Test example 1 Guinea pig runny nose provocation test
- Hartrey guinea pigs male, 4 weeks were subjected to the experiment.
- Toluene-2,4-diisocyanate (TDI) and ethyl acetate were used as reagents, and olopatadine hydrochloride and belladonna total alkyloid were used as test drugs.
- the sensitization was performed by contacting a bilateral nasal vestibule of a Hartrey guinea pig with a 10% TDI ethyl acetate solution using a cotton swab for 10 seconds. Sensitization was performed once a day for 5 consecutive days from the first sensitization. ,
- guinea pigs were elicited by contacting the nasal vestibules of both sides with a 5% TDI ethyl acetate solution using a cotton swab for 10 seconds. After the agitation, the runny nose for 15 minutes was absorbed by a filter paper and weighed in a microtube. The amount of runny nose was calculated by subtracting the weight of the filter paper and the microtube, which were previously reduced, in advance. Based on the result of runny nose, guinea pigs were divided into four groups with 22 to 23 animals per group so that runny nose was even. In addition, a non-sensitized group without sensitization was prepared.
- test drugs olopatadine hydrochloride and belladonna total alloid were dissolved in distilled water for injection, respectively.
- Comparative administration group 1 olopatadine hydrochloride 32 mg / kg
- comparative administration group 2 belladonna total alroyloid 3.2 mg / kg
- administration group It was adjusted to olopatadine hydrochloride 32 mg / kg and belladonna total alkyloid 3.2 mg / kg.
- test drug was administered intraperitoneally to guinea pigs 31 to 33 days after the last sensitization.
- a control group was similarly administered using distilled water for injection.
- the guinea pigs of each group were elicited by contacting the nasal vestibule of both sides with a 5% TDI ethyl acetate solution using a cotton swab for 10 seconds. After the induction, a runny nose for 15 minutes was absorbed into a filter paper, and then carefully placed in a microtube and weighed. The amount of runny nose was calculated by subtracting the weights of the filter paper and the microtube that had been previously weighed out.
- Fig. 1 shows the results of runny nose. Each value is shown as mean ⁇ s.e. The mean difference between the groups was tested using Dunnett's multiple comparison test (p ⁇ 0.05 P ⁇ 0.01). As a result, the comparative administration group 1 and the comparative administration group 2 exhibited moderate suppression of the runny nose-induced reaction, but the administration group of the present invention showed a very strong runny nose reaction due to the synergistic action of both drugs. Was suppressed. It was confirmed that the administration group was comparable to the non-sensitized group, that is, almost completely suppressed the runny nose reaction.
- the pharmaceutical composition of the present invention extremely strongly suppresses runny nose caused by allergic rhinitis and is useful for treatment of allergic rhinitis.
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- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Otolaryngology (AREA)
- Immunology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A medicinal composition characterized by containing olopatadine and an anticholinergic agent which has an excellent effect of controlling nasal discharge in allergic rhinitis.
Description
医薬組成物 Pharmaceutical composition
技術分野 Technical field
本発明は、 アレルギー性鼻炎等による鼻水分泌の抑制に有用な医薬組成物で ある。 The present invention is a pharmaceutical composition useful for suppressing runny secretions caused by allergic rhinitis and the like.
背景技術 Background art
ァレルギ一性鼻炎等の I型アレルギー疾患は即時相反応と遅発相反応の 2相 性反応を示すことが知られている。 この I型アレルギー疾患における即時相反 応は花粉等の抗原惹起直後にくしゃみ、 鼻水、 鼻づまりを誘発する。 一方で遅 発相反応は抗原惹起数時間後に再度発現する鼻づまりを特徴とするものである。 アレルギー性鼻炎等によるくしゃみ、 鼻水、 鼻づまりの治療のために、 抗ヒス 夕ミン薬が使用されている。 また、 近年では主作用である抗ヒスタミン作用に 加え、 ケミカルメデイエ一夕遊離抑制作用、 炎症性細胞の遊走抑制作用をも併 せ持つ塩酸ォロパタジン、 塩酸セチリジン等の抗アレルギー薬が開発されてき ている。 しかしながら、 これら抗ヒスタミン作用を主作用とするこれら抗ァレ ルギー薬は眠気等の副作用をもつものが多く、 塩酸ォロパタジンは強力な抗ヒ スタミン作用を持つ反面、 臨床試験において眠気の副作用を発現したことが報 告されている。 ， It is known that type I allergic diseases such as allergic rhinitis show a biphasic reaction of an immediate phase reaction and a delayed phase reaction. Immediate reaction in this type I allergic disease induces sneezing, runny nose, and nasal congestion immediately after inducing antigen such as pollen. On the other hand, the delayed phase reaction is characterized by a nasal congestion that reappears several hours after the antigen is induced. Anti-histamine drug is used to treat sneezing, runny nose and nasal congestion due to allergic rhinitis. In recent years, antiallergic drugs such as olopatadine hydrochloride and cetirizine hydrochloride, which have an inhibitory effect on the release of chemical media overnight and an inhibitory effect on the migration of inflammatory cells, in addition to the main antihistamine effect, have been developed. I have. However, most of these anti-allergy drugs, which have an antihistamine action as a main effect, have side effects such as drowsiness.While olopatadine hydrochloride has a strong antihistamine action, it exhibited side effects of drowsiness in clinical trials Have been reported. ,
抗コリン薬は、 コリン作動性神経節後線維の刺激効果を抑制又は遮断する薬 物であり、 鎮痙作用、 鎮痛作用、 散瞳作用、 分泌抑制作用、 局所麻酔作用等、 様々な作用が知られている。 抗コリン薬として、 ベラドンナ総アルカロイド、 ベラドンナエキス、 アト口ピン、 ホマトロピン、スコポラミン、 ロー卜エキス、 ヨウ化イソプロパミド、 ダッラエキス、 臭化メチルペナクチジゥム、 臭化プロ パンテリンなど多くの薬物が知られている。 Anticholinergic drugs are drugs that suppress or block the stimulating effect of cholinergic postganglionic fibers, and are known to have various effects such as antispasmodic, analgesic, mydriatic, secretory, and local anesthetic effects. ing. Many anticholinergic agents are known, such as belladonna total alkaloids, belladonna extract, atotopin, homatropin, scopolamine, funnel extract, isopropamide iodide, dalla extract, methyl penactidium bromide, and propantheline bromide. I have.
塩酸ォロパタジンまたはその塩と抗コリン薬との配合は未だ知られていない。
本発明は、 眠気等の副作用を軽減し、 鼻炎症状、 特に鼻水の抑制に優れた効 果を有する医薬組成物を提供することである。 The combination of olopatadine hydrochloride or a salt thereof with an anticholinergic drug is not yet known. An object of the present invention is to provide a pharmaceutical composition which has an effect of reducing side effects such as drowsiness and suppressing nasal inflammatory conditions, particularly runny nose.
発明の開示 Disclosure of the invention
本発明者らは、 かかる課題を解決するために鋭意研究した結果、 ォロパタジ ンまたはその塩と抗コリン薬とを組み合わせることで相乗作用により、 アレル ギー性鼻炎に対して優れた治療効果を有し、 用量を下げることが可能となるこ とを見出し、 本発明を完成した。 The present inventors have conducted intensive studies in order to solve such a problem, and as a result, by combining olopatadine or a salt thereof with an anticholinergic drug, the present invention has an excellent therapeutic effect on allergic rhinitis by synergistic action. The inventors have found that the dose can be reduced, and have completed the present invention.
すなわち、 本発明は、 ォロパタジンまたはその塩及び抗コリン薬を配合する ことを特徴とする医薬組成物である。 That is, the present invention is a pharmaceutical composition comprising olopatadine or a salt thereof and an anticholinergic.
本発明で、 ォロパタジンの塩としては、 塩酸塩、 硝酸塩、 フマル酸塩等であ る。 特に好ましくは塩酸塩である。 In the present invention, the salt of olopatadine includes hydrochloride, nitrate, fumarate and the like. Particularly preferred is the hydrochloride.
ォロパタジンまたはその塩の有効量は、 経口投与において 1日当たりの用量 0.05〜： lOOmgで、 好適には 0.5〜20mgである。 An effective amount of olopatadine or a salt thereof is a daily dose of 0.05 to: 100 mg in oral administration, preferably 0.5 to 20 mg.
抗コリン薬の有効量は、 経口投与において 1日量あたり、 ベラドンナ総アル カロイドでは 0.1〜2.0mg、 好適には 0.3〜1.0mg、 ベラドンナエキスでは 5〜 200mg、 好適には 10〜： LOOmg、 アト口ピンでは 0.1〜2.0mg、 好適には 0.3〜 l.Omg、 ホマト口ピンでは 0.：!〜 2.0mg、 好適には 0.3〜： 1.0mg、 スコポラミン では 0.1〜2.0mg、 好適には 0.3〜1.0mg、 ロートエキスでは 5〜200mg、 好適 には 10〜： L00mg、 ヨウ化イソプロパミドでは l〜50mg、 好適には 2〜： LOmg、 ダッラエキスでは 0.1〜2.0mg、 好適には 0.3〜： L0mg、 臭化メチルべナクチジ ゥムでは 5〜 200mg、好適には 10〜 100mg、臭化プロパンテリンでは 5〜200mg、 好適には 10〜100mgである。 The effective amount of the anticholinergic agent is 0.1 to 2.0 mg, preferably 0.3 to 1.0 mg for belladonna total alkaloid, 5 to 200 mg for belladonna extract, preferably 10 to: LOOmg, at daily dose for oral administration. 0.1 ~ 2.0mg, preferably 0.3 ~ l.Omg for mouth pin, 0:! ~ 2.0mg, preferably 0.3 ~: 1.0mg for homato mouth pin, 0.1 ~ 2.0mg, preferably 0.3 ~ 2.0mg for scopolamine 1.0 mg, 5 to 200 mg for funnel extract, preferably 10 to: L00 mg, l to 50 mg for isopropamide iodide, preferably 2 to: LOmg, 0.1 to 2.0 mg for Dalla extract, preferably 0.3 to: L0 mg, odor The amount is 5 to 200 mg, preferably 10 to 100 mg, for methyl benactide bromide, and 5 to 200 mg, preferably 10 to 100 mg for propantheline bromide.
本発明の医薬組成物におけるォロパタジンまたはその塩と抗コリン薬の配合 比は、抗コリン薬 1重量部に対して塩酸ォロパタジン 0.00025〜： 1000重量部が よく、 好ましくは 0.0025〜200重量部である。
本発明の医薬組成物は、 1日 1回又は 2〜 3回に分けて投与することができ る。 The mixing ratio of olopatadine or a salt thereof to the anticholinergic agent in the pharmaceutical composition of the present invention is preferably from 0.00025 to 1000 parts by weight of olopatadine hydrochloride to 1 part by weight of the anticholinergic agent, and more preferably from 0.0025 to 200 parts by weight. The pharmaceutical composition of the present invention can be administered once or twice or three times a day.
本発明の医薬組成物は、 経口または非経口投与製剤に調製される。 経口投与 製剤としては、 錠剤、 丸剤、 カプセル剤、 顆粒剤、 散剤、 チユアブル錠などの 固形製剤、 シロップ剤、 ドリンク剤などの液剤であり、 慣用的な方法で製造さ れる。非経口投与製剤としては、点鼻や点眼のため、スプレー剤、液剤であり、 皮膚への投与のため、 軟膏剤、 クリーム剤、 貼付剤などである。 The pharmaceutical composition of the present invention is prepared into a preparation for oral or parenteral administration. Oral preparations include solid preparations such as tablets, pills, capsules, granules, powders, and chewable tablets, and liquid preparations such as syrups and drinks, and are manufactured by a conventional method. Parenteral preparations include sprays and liquids for nasal and eye drops, and ointments, creams and patches for administration to the skin.
固形製剤として調製する場合には、 必要に応じて、 賦形剤、 滑沢剤、 崩壊剤 等を使用することができる。 液剤、 スプレー剤、 軟膏剤、 クリ一ム剤、 貼付剤 として調製する場合には、 必要に応じて、 界面活性剤、 溶解補助剤、 緩衝剤等 を使用することができる。 When prepared as a solid preparation, excipients, lubricants, disintegrants and the like can be used as necessary. When preparing a solution, spray, ointment, cream, or patch, a surfactant, a solubilizing agent, a buffer and the like can be used as necessary.
他に保存剤、 香料、 色素、 甘味剤、 嬌味剤、 清涼化剤等を使用することがで きる。 In addition, preservatives, flavors, pigments, sweeteners, flavoring agents, fresheners and the like can be used.
本発明の医薬組成物は、 以上の成分の他に必要に応じて非ステロイド性抗炎 症薬、 消炎酵素薬類、 気管支拡張薬、 交感神経興奮薬、 他の中枢神経興奮薬、 鎮咳薬、去痰薬、抗ヒスタミン薬、他の抗アレルギー薬、 ビタミン類、 制酸薬、 生薬等から選ばれる薬剤を適宜に配合しても良い。 なお、 これらの成分は単独 または相互に混合して用いることができ、 通常は一般用医薬品製造指針 （2 0 0 0年版 ·薬事審査研究会監修、 株式会社じほう発行） に収載されているかぜ 薬基準、 鼻炎用内服薬基準等に準拠して配合される。 The pharmaceutical composition of the present invention may further comprise a nonsteroidal anti-inflammatory drug, an anti-inflammatory enzyme drug, a bronchodilator, a sympathetic stimulant, another central nervous stimulant, an antitussive, Drugs selected from expectorants, antihistamines, other antiallergic drugs, vitamins, antacids, crude drugs, etc. may be appropriately compounded. These components can be used alone or in admixture with each other. Usually, the cold medicines listed in the OTC Pharmaceutical Manufacturing Guidelines (2000 edition, supervised by the Pharmaceutical Affairs Committee, published by Jiho Co., Ltd.) It is compounded in accordance with the standards and the internal medicine standards for rhinitis.
発明を実施するための最良の形態 BEST MODE FOR CARRYING OUT THE INVENTION
以下に、 本発明を実施例及び試験例を示し、 詳細に説明する。 Hereinafter, the present invention will be described in detail with reference to Examples and Test Examples.
実施例 1 顆粒剤 Example 1 Granules
塩酸ォロパタジン 5 g ベラドンナ総アルカロイド 0 . 4 g
マンニッ卜 9 0 0 g コーンスターチ 9 8 0 g ヒドロキシプロピルセル口 1 8 0 g 上記の各成分及び分量を秤量し均一に混合 ·粉砕した後、 エタノール 2 0 0 gを添加して練合した後、 押し出し造粒を行い、 乾燥後混合し 1包重量 1 2 0 O m gになるように分包し、 顆粒剤を得た。 Olopatadine hydrochloride 5 g Belladonna total alkaloid 0.4 g Mannit 900 g Corn starch 980 g Hydroxypropyl cell opening 180 g After weighing the above components and amounts, mixing and pulverizing uniformly, adding 200 g of ethanol and kneading, Extrusion granulation was carried out, dried and mixed, and divided into packets of 120 Omg in weight to obtain granules.
実施例 2 錠剤 Example 2 tablets
塩酸ォロパタジン 2 5 g シユードエフエドリン 1 2 0 g ベラドンナ総アル力ロイド 0 . 4 g 無水カフエイン 1 0 0 g Olopatadine hydrochloride 25 g Sudofuedrin 120 g Belladonna total alloid 0.4 g Anhydrous caffeine 100 g
'結晶セルロース 9 0 0 g ヒドロキシプロピルセルロース 1 5 0 g 低置換度ヒドロキシプロピルセル口一ス 4 0 0 g 上記の各成分及び分量を秤量し均一に混合 ·粉碎した後、 1 4 0 'Crystalline cellulose 900 g hydroxypropylcellulose 150 g Low-substituted hydroxypropyl cell mouth 400 g The above components and amounts were weighed and mixed uniformly.
ールを添加し攪拌造粒を行い乾燥後、 ステアリン酸マグネシウム 1 After stirring and granulating and drying, magnesium stearate 1
に混合し 1錠重量 3 0 O m gになるように打錠し、 錠剤を得た。 And tableting was performed so that the weight of one tablet became 30 O mg to obtain a tablet.
実施例 3 カプセル剤 Example 3 Capsules
塩酸ォロパタジン 2 5 g シユードエフェドリン 1 2 0 g ベラドンナ総アル力ロイド 0 . 4 g 無水カフエイン 1 0 0 g バレイショデンプン 6 9 8 g 結晶セルロース 1 0 g ヒドロキシプロピルセルロース 3 0 g
ステアリン酸マグネシウム 1 2 g 上記の各成分及び分量を抨量し均一に混合 ·粉碎した後、 乾式造粒を行った 後混合し 1カプセル内容量が 30 Omgとなるように充填し、 カプセル剤を得 た。 Olopatadine hydrochloride 25 g Suedoephedrine 120 g Belladonna total alloid 0.4 g Anhydrous caffeine 100 g Potato starch 696 g Crystalline cellulose 10 g Hydroxypropyl cellulose 30 g Magnesium stearate 1 2 g Measure the above components and amounts, mix uniformly, pulverize, dry-granulate, mix and fill so that the content of 1 capsule is 30 Omg. Obtained.
試験例 1 ：モルモット鼻水誘発試験 Test example 1: Guinea pig runny nose provocation test
1. 動物 1. animal
Hartrey系モルモット（雄、 4week)を実験に供した。 Hartrey guinea pigs (male, 4 weeks) were subjected to the experiment.
2. 試薬及び被験薬物 2. Reagents and test drugs
試薬として、 トルエン— 2, 4—ジイソシアナ一ト （TD I)、 酢酸ェチルを 使用、被験薬物は、塩酸ォロパタジン、ベラドンナ総アル力ロイドを使用した。 Toluene-2,4-diisocyanate (TDI) and ethyl acetate were used as reagents, and olopatadine hydrochloride and belladonna total alkyloid were used as test drugs.
3. 抗原感作 3. Antigen sensitization
3-1 感作 3-1 sensitization
感作は、 Hartrey系モルモットの両側鼻前庭部に、 10%TD Iの酢酸ェチル 溶液を綿棒を使用して、 10秒間接触させることで行った。 感作は、 1日 1回、 初回感作から 5日間連続で行った。 ， The sensitization was performed by contacting a bilateral nasal vestibule of a Hartrey guinea pig with a 10% TDI ethyl acetate solution using a cotton swab for 10 seconds. Sensitization was performed once a day for 5 consecutive days from the first sensitization. ,
3- 2 群分け 3- 2 Grouping
最終感作後 24〜26 日に、 モルモットの両側鼻前庭部に、 5%TD Iの酢酸 ェチル溶液を綿棒を使用して、 10秒間接触させて、 惹起した。 惹起後、 15分 間の鼻水を濾紙に吸収させて、 密詮マイクロチューブに入れて秤量した。 鼻水 量は、 予め抨量しておいた濾紙及び密詮マイクロチューブの重量を差し引いて 算出した。 鼻水量の結果に基づいて、 鼻水量が均等になるように、 モルモット を各群 22〜23匹になるように 4つの群に分けた。 また、 更に、 感作を行わな い無感作群を用意した。 Twenty-four to twenty-six days after the final sensitization, guinea pigs were elicited by contacting the nasal vestibules of both sides with a 5% TDI ethyl acetate solution using a cotton swab for 10 seconds. After the agitation, the runny nose for 15 minutes was absorbed by a filter paper and weighed in a microtube. The amount of runny nose was calculated by subtracting the weight of the filter paper and the microtube, which were previously reduced, in advance. Based on the result of runny nose, guinea pigs were divided into four groups with 22 to 23 animals per group so that runny nose was even. In addition, a non-sensitized group without sensitization was prepared.
4. 評価 · 4. Evaluation ·
4- 1 被験薬物の調整と投与方法
被験薬物の塩酸ォロパタジンとベラドンナ総アル力ロイドはそれぞれ注射用 蒸留水に溶解し、 比較投与群 1 ：塩酸ォロパタジン 32mg/kg、 比較投与群 2 ： ベラドンナ総アル力ロイド 3.2mg/kg、 投与群：塩酸ォロパタジン 32mg/kg及 びベラドンナ総アル力ロイド 3.2mg/kgに調整した。 4- 1 Preparation and administration of test drug The test drugs olopatadine hydrochloride and belladonna total alloid were dissolved in distilled water for injection, respectively. Comparative administration group 1: olopatadine hydrochloride 32 mg / kg, comparative administration group 2: belladonna total alroyloid 3.2 mg / kg, administration group: It was adjusted to olopatadine hydrochloride 32 mg / kg and belladonna total alkyloid 3.2 mg / kg.
各被験薬物は最終感作後 31〜33 日に、 モルモットの腹腔内に投与した。 対 照群として、 注射用蒸留水を用いて同様に投与した。 Each test drug was administered intraperitoneally to guinea pigs 31 to 33 days after the last sensitization. A control group was similarly administered using distilled water for injection.
4-2 薬物評価 4-2 Drug evaluation
各群のモルモッ卜の両側鼻前庭部に、 5 % T D Iの酢酸ェチル溶液を綿棒を 使用して、 10秒間接触させて、 惹起した。 惹起後、 15分間の鼻水を濾紙に吸 収し、 密詮マイクロチューブに入れて抨量した。 鼻水量は、 予め枰量しておい た濾紙及び密詮マイクロチューブの重量を差し引いて算出した。 The guinea pigs of each group were elicited by contacting the nasal vestibule of both sides with a 5% TDI ethyl acetate solution using a cotton swab for 10 seconds. After the induction, a runny nose for 15 minutes was absorbed into a filter paper, and then carefully placed in a microtube and weighed. The amount of runny nose was calculated by subtracting the weights of the filter paper and the microtube that had been previously weighed out.
5 . 統計処理と結果 5. Statistical processing and results
鼻水量の結果を第 1図に示す。 各値は mean± s.eで示した。 多群間の平均値 の差の検定は Dunnettの多重比較検定法を用いた (pく 0.05 P<0.01)。その結果、 比較投与群 1及び比較投与群 2では、 鼻水誘発反応に対して中等度の抑制であ つたが、 本発明である投与群は、 両薬物の相乗作用により非常に強力に鼻水反 応を抑制した。 投与群は非感作群と同程度、 即ちほぼ完全に鼻水反応を抑制す ることが確認された。 Fig. 1 shows the results of runny nose. Each value is shown as mean ± s.e. The mean difference between the groups was tested using Dunnett's multiple comparison test (p <0.05 P <0.01). As a result, the comparative administration group 1 and the comparative administration group 2 exhibited moderate suppression of the runny nose-induced reaction, but the administration group of the present invention showed a very strong runny nose reaction due to the synergistic action of both drugs. Was suppressed. It was confirmed that the administration group was comparable to the non-sensitized group, that is, almost completely suppressed the runny nose reaction.
したがって、 塩酸ォロパタジン及びベラドンナ総アル力ロイドの単独ではァ レルギ一性鼻炎による鼻水に対して十分な作用を示さない投与量においても、 塩酸ォロパタジン及びベラドンナ総アル力ロイドの併用であれば、 アレルギー 性鼻炎による鼻水を非常に強力に抑制することが判明した。 Therefore, even if the dose of olopatadine hydrochloride and belladonna total algicloid alone does not show a sufficient effect on runny nose due to allergic rhinitis, the combined use of olopatadine hydrochloride and belladonna total alloidoid will cause allergic It has been found that runny nose caused by rhinitis is very strongly suppressed.
産業上の利用可能性 Industrial applicability
本発明の医薬組成物は、アレルギ一性鼻炎による鼻水を極めて強力に抑制し、 アレルギー性鼻炎の治療に関して有用である。
INDUSTRIAL APPLICABILITY The pharmaceutical composition of the present invention extremely strongly suppresses runny nose caused by allergic rhinitis and is useful for treatment of allergic rhinitis.
Claims
1 . ォロパタジンまたはその塩及び抗コリン薬を配合することを特徴とする医 薬組成物。 1. A pharmaceutical composition comprising olopatadine or a salt thereof and an anticholinergic.
2 . 抗コリン薬が、 ベラドンナ総アルカロイド、 ベラドンナエキス、 アトロピ ン、 ホマトロピン、 スコポラミン、 ロートエキス、 ヨウ化イソプロパミド、 ダ ッラエキス、 臭化メチルペナクチジゥム及び臭化プロパンテリンからなる群か ら選ばれる 1種又は 2種以上である請求項 1記載の医薬組成物。
2. The anticholinergic is selected from the group consisting of belladonna total alkaloids, belladonna extract, atropine, homatropin, scopolamine, funnel extract, isopropamide iodide, dalla extract, methyl penactidium bromide and propantheline bromide. 2. The pharmaceutical composition according to claim 1, which is one or more kinds.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011020960A (en) * | 2009-07-16 | 2011-02-03 | Takada Seiyaku Kk | Solid olopatadine preparation and method for producing olopatadine tablet |
| JP2019127488A (en) * | 2018-01-24 | 2019-08-01 | 第一三共ヘルスケア株式会社 | Pharmaceutical compositions comprising olopatadine |
| WO2020032159A1 (en) * | 2018-08-10 | 2020-02-13 | 日本臓器製薬株式会社 | Particulate composition and production method therefor |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07188040A (en) * | 1993-12-27 | 1995-07-25 | Taisho Pharmaceut Co Ltd | Composition for treating rhinitis |
| JPH10298107A (en) * | 1997-04-25 | 1998-11-10 | Taisho Pharmaceut Co Ltd | Pharmaceutical composition |
-
2003
- 2003-10-31 AU AU2003280678A patent/AU2003280678A1/en not_active Abandoned
- 2003-10-31 WO PCT/JP2003/013988 patent/WO2004039408A1/en active Application Filing
- 2003-10-31 JP JP2004548101A patent/JPWO2004039408A1/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07188040A (en) * | 1993-12-27 | 1995-07-25 | Taisho Pharmaceut Co Ltd | Composition for treating rhinitis |
| JPH10298107A (en) * | 1997-04-25 | 1998-11-10 | Taisho Pharmaceut Co Ltd | Pharmaceutical composition |
Non-Patent Citations (2)
| Title |
|---|
| KAISE TOSHIHIKO ET AL.: "Inhibitory effect of olo patadine hydrochloride on the sneezing response induced by intranasal capsaicin challenge in guinea pigs", JPN. J. PHARMACOL., vol. 86, 2001, pages 258 - 261, XP002979109 * |
| OMORI TAKEMORI ET AL.: "Ko-allergy yaku ensan olo patadene (Arerokku-Jo), no yakuri sayo yakubutsu dotai oyobi rinsho seiseki", NICHIYAKURI SHI, vol. 118, 2001, pages 51 - 58, XP002979108 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011020960A (en) * | 2009-07-16 | 2011-02-03 | Takada Seiyaku Kk | Solid olopatadine preparation and method for producing olopatadine tablet |
| JP2019127488A (en) * | 2018-01-24 | 2019-08-01 | 第一三共ヘルスケア株式会社 | Pharmaceutical compositions comprising olopatadine |
| JP7325969B2 (en) | 2018-01-24 | 2023-08-15 | 第一三共ヘルスケア株式会社 | Pharmaceutical composition containing olopatadine |
| WO2020032159A1 (en) * | 2018-08-10 | 2020-02-13 | 日本臓器製薬株式会社 | Particulate composition and production method therefor |
| CN112566635A (en) * | 2018-08-10 | 2021-03-26 | 日本脏器制药株式会社 | Granular composition and process for producing the same |
| JPWO2020032159A1 (en) * | 2018-08-10 | 2021-08-10 | 日本臓器製薬株式会社 | Granular composition and its production method |
| JP7442193B2 (en) | 2018-08-10 | 2024-03-04 | 日本臓器製薬株式会社 | Granular composition and method for producing the same |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003280678A1 (en) | 2004-05-25 |
| JPWO2004039408A1 (en) | 2006-02-23 |
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