WO1992000725A1 - Liquid oral pharmaceutical compositions having anti-inflammatory activity - Google Patents
Liquid oral pharmaceutical compositions having anti-inflammatory activity Download PDFInfo
- Publication number
- WO1992000725A1 WO1992000725A1 PCT/EP1991/001245 EP9101245W WO9200725A1 WO 1992000725 A1 WO1992000725 A1 WO 1992000725A1 EP 9101245 W EP9101245 W EP 9101245W WO 9200725 A1 WO9200725 A1 WO 9200725A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compositions according
- active ingredient
- ketoprofen
- cyclodextrins
- pharmaceutical compositions
- Prior art date
Links
- 239000007788 liquid Substances 0.000 title claims abstract description 6
- 239000008203 oral pharmaceutical composition Substances 0.000 title description 2
- 230000003110 anti-inflammatory effect Effects 0.000 title 1
- 239000004480 active ingredient Substances 0.000 claims abstract description 24
- MEJYDZQQVZJMPP-ULAWRXDQSA-N (3s,3ar,6r,6ar)-3,6-dimethoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan Chemical compound CO[C@H]1CO[C@@H]2[C@H](OC)CO[C@@H]21 MEJYDZQQVZJMPP-ULAWRXDQSA-N 0.000 claims abstract description 18
- 238000011282 treatment Methods 0.000 claims abstract description 7
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims abstract description 6
- 230000000699 topical effect Effects 0.000 claims abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims description 27
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 17
- 229960000991 ketoprofen Drugs 0.000 claims description 15
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical group OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 claims description 15
- 229920000858 Cyclodextrin Polymers 0.000 claims description 14
- 229920000642 polymer Polymers 0.000 claims description 8
- 239000000227 bioadhesive Substances 0.000 claims description 7
- 229960001680 ibuprofen Drugs 0.000 claims description 7
- -1 methyl isosorbide Chemical compound 0.000 claims description 7
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 6
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 5
- 229940097362 cyclodextrins Drugs 0.000 claims description 5
- 229960002702 piroxicam Drugs 0.000 claims description 5
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 claims description 5
- 229920001577 copolymer Polymers 0.000 claims description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 4
- 239000002244 precipitate Substances 0.000 claims description 3
- MDKGKXOCJGEUJW-VIFPVBQESA-N (2s)-2-[4-(thiophene-2-carbonyl)phenyl]propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C(=O)C1=CC=CS1 MDKGKXOCJGEUJW-VIFPVBQESA-N 0.000 claims description 2
- 239000004375 Dextrin Substances 0.000 claims description 2
- 229920001353 Dextrin Polymers 0.000 claims description 2
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims description 2
- IHHXIUAEPKVVII-ZSCHJXSPSA-N [(1s)-5-amino-1-carboxypentyl]azanium;2-[4-(2-methylpropyl)phenyl]propanoate Chemical compound OC(=O)[C@@H](N)CCCC[NH3+].CC(C)CC1=CC=C(C(C)C([O-])=O)C=C1 IHHXIUAEPKVVII-ZSCHJXSPSA-N 0.000 claims description 2
- 229960004892 acemetacin Drugs 0.000 claims description 2
- FSQKKOOTNAMONP-UHFFFAOYSA-N acemetacin Chemical compound CC1=C(CC(=O)OCC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 FSQKKOOTNAMONP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000679 carrageenan Substances 0.000 claims description 2
- 235000010418 carrageenan Nutrition 0.000 claims description 2
- 229920001525 carrageenan Polymers 0.000 claims description 2
- 229940113118 carrageenan Drugs 0.000 claims description 2
- 235000019425 dextrin Nutrition 0.000 claims description 2
- 229960001259 diclofenac Drugs 0.000 claims description 2
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 claims description 2
- 229960002390 flurbiprofen Drugs 0.000 claims description 2
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 claims description 2
- 229960000905 indomethacin Drugs 0.000 claims description 2
- 229960002009 naproxen Drugs 0.000 claims description 2
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims description 2
- 229960004492 suprofen Drugs 0.000 claims description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims description 2
- 229960005142 alclofenac Drugs 0.000 claims 1
- ARHWPKZXBHOEEE-UHFFFAOYSA-N alclofenac Chemical compound OC(=O)CC1=CC=C(OCC=C)C(Cl)=C1 ARHWPKZXBHOEEE-UHFFFAOYSA-N 0.000 claims 1
- 229940000425 combination drug Drugs 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- 229960002479 isosorbide Drugs 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- 239000000243 solution Substances 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000000796 flavoring agent Substances 0.000 description 11
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 11
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 11
- 235000010234 sodium benzoate Nutrition 0.000 description 11
- 239000004299 sodium benzoate Substances 0.000 description 11
- 235000019634 flavors Nutrition 0.000 description 10
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 10
- 229920001214 Polysorbate 60 Polymers 0.000 description 9
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 8
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 8
- CNBGNNVCVSKAQZ-UHFFFAOYSA-N benzydamine Chemical compound C12=CC=CC=C2C(OCCCN(C)C)=NN1CC1=CC=CC=C1 CNBGNNVCVSKAQZ-UHFFFAOYSA-N 0.000 description 8
- 239000000600 sorbitol Substances 0.000 description 8
- 235000010356 sorbitol Nutrition 0.000 description 8
- 229960002920 sorbitol Drugs 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 5
- 239000003708 ampul Substances 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 229960000333 benzydamine Drugs 0.000 description 4
- 239000001116 FEMA 4028 Substances 0.000 description 3
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 3
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 3
- 229960004853 betadex Drugs 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229920001993 poloxamer 188 Polymers 0.000 description 3
- 229940044519 poloxamer 188 Drugs 0.000 description 3
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- SSVFMICWXDVRQN-UHFFFAOYSA-N ethanol;sodium Chemical compound [Na].CCO SSVFMICWXDVRQN-UHFFFAOYSA-N 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000005232 Glossitis Diseases 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 241000011102 Thera Species 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002882 anti-plaque Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000001013 cariogenic effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 208000007565 gingivitis Diseases 0.000 description 1
- 229940074774 glycyrrhizinate Drugs 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- MOYKHGMNXAOIAT-JGWLITMVSA-N isosorbide dinitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O[N+](=O)[O-])CO[C@@H]21 MOYKHGMNXAOIAT-JGWLITMVSA-N 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940040944 tetracyclines Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
Definitions
- the present invention relates to liquid pharmaceu ⁇ tical compositions for the oral topical treatment, containing non steroidal anti-inflammatory drugs as the active ingredients.
- Therapeutical treatment of inflammations of the oral cavity such as aspecific odontostomatologic af ⁇ fections, gingivitis, glossitis, stomatitis and the like, is particularly complex and, until the specific pathogenic agent has precisely been determined, treat- ment can be restricted to the use of disinfectants of the general type.
- Said drugs besides showing negative characteri ⁇ stics (remarkable side-effects) can cause severe and diffused allergy phenomena, so as to compel to immedia- tely interrupt treatment and to take suitable restora ⁇ tion measures.
- compositions comprising non steroidal anti-inflammatory drugs (FANS) in form of solutions intended for the oral topical tre ⁇ atment (collutories) , allow to obtain very good thera ⁇ Promotionical results without causing sensitization pheno ⁇ mena.
- FANS non steroidal anti-inflammatory drugs
- the compositions of the invention are characteri ⁇ zed by the presence of a specific excipient, dimethyl isosorbide, giving them advantageous antiseptic proper ⁇ ties together with an antiplaque action which is parti- cularly desired in this kind of preparations.
- Anti-in ⁇ flammatory properties of the active ingredients also turn out to be surprisingly enhanced through a synerge- tic interaction with dimethyl isosorbide.
- compositions of the present invention can con- tain the active ingredient in amounts ranging from 0.001 to 20% by weight, whereas dimethyl isosorbide can be present in amounts ranging from 1 to 40% by weight.
- compositions of the invention can also contain other excipients and/or coadjuvants, such as surfactants, flavouring and sweetening agents, in order to give the preparation suitable organoleptic characteristics.
- excipients and/or co ⁇ adjuvants conventionally used for the preparation of collutories are described in "Remington's Pharm. Scien- ces Handbook", Mack Pub. Co., NY.
- the compositions of the invention will preferably contain natural and/or synthetic sweetening agents such as saccharine, ammo ⁇ nium glycyrrhizinate, cycla ate or, more preferably, not cariogenic carbohydrates such as xylitol and sorbi- tol.
- non steroidal anti- inflammatory drugs such as ketoprofen, ibuprofen, ibu- profen lysine salt, naproxen, suprofen, diclofenac, al- clofenac, indomethacin, acemethacin, benzidamine, flur- biprofen, piroxicam and the like, can be used as active ingredients, either in the free form or salified, in order to improve the solubility thereof.
- the active ingredients are present in combination with cyclodextrins or derivatives thereof, for example in form of physical admixtures, inclusion products or co- precipitates.
- Cyclodextrins or derivatives thereof such as hydroxypropyl beta-cyclodextrins, involve fa ⁇ vourable pharmacokinetic effects and, moreover, are useful to increase solubility and stability, or to im- prove the organoleptic characteristics of the medica ⁇ ment.
- Cyclodextrin contents can range from 0.5 to 50% by weight of the finished composition, but equimolecular ratios of active ingredient to cyclodextrin are prefe- rably used.
- cyclodex ⁇ trins (o , ⁇ , -) and the already cited hydroxypropyl ⁇ - cyclodextri ⁇ , dimethylcyclodextrins or other derivati ⁇ ves, possibly in a mixture thereof can also be used.
- polymers having an adhesive power towards ucosae are used as excipients.
- examples of said polymers are provided by carboxyvinyl polymers, ethyle e oxide - propylene oxide copolymers, cellulose derivatives such as carboxymethyl cellulose, calcium carboxymethyl cellulose, hydroxy- propylethyl cellulose, hydroxyethyl cellulose, hydroxy ⁇ propyl cellulose, carrageenan, dextrins, natural or synthetic gums and the like.
- Said excipients, which can be def ned bioadhesive polymers can be present in per ⁇ centages ranging from 0.5 to 30%, preferably from 1 to 5%.
- excipients allows to obtain sli ⁇ ghtly viscous solutions having adhesiveness towards mu- cosae, so as to achieve a better persistence of the preparation in contact with the area to be treated, thus obtaining a more effective and lasting action.
- compositions can also contain no dimethyl isosor- bide : said compositions also fall within the scope of the present invention.
- Each 15 ml ampoule contains: Active ingredient: ketoprofen Excipients:
- Ketoprofen is dissolved in an ethanol solution containing dimethyl isosorbide and Tween 60, the solu ⁇ tion is heated to 35 C C under stirring, to obtain a clear solution which is added with the other components. After filtration, a clear homogeneous solution (collutory) is obtained.
- Ketoprofen is added to a ⁇ -cyclodextrin aqueous solution (about 50 ml), which is heated to 30-40 e C for 30 hours. A solution is obtained which is added with dimethyl isosorbide and the other components, then fil ⁇ tered.
- EXAMPLE 4 Collutory containing ketoprofen, dimethyl isosorbide and bioadhesive polymers (in form of solution) 100 ml of collutory contain (% composition): Active ingredient: ketoprofen 0.05 Excipients:
- Each 15 ml ampoule contains : Active ingredient: Benzidamine 2 to 20 mg ExciDients: Tween 60 5 mg alpine herb flavor 52,503 T 15 mg dimethyl isosorbide 1500 mg
- Collutory containing piroxicam (in form of solution) 100 ml of collutory contain (% composition) : Active ingredient:
- Each 15 ml ampoule contains: Active ingredient: Piroxicam Excipients:
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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nutrition Science (AREA)
- Nanotechnology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- General Chemical & Material Sciences (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Crystallography & Structural Chemistry (AREA)
- Biochemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1991911791 DE491897T1 (de) | 1990-07-13 | 1991-07-04 | Fluessige entzuendungshemmende oral anzuwendende arzneimittel. |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT20944A/90 | 1990-07-13 | ||
| IT02094490A IT1243342B (it) | 1990-07-13 | 1990-07-13 | Composizioni farmaceutiche orali liquide ad attivita' antiinfiammatoria |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1992000725A1 true WO1992000725A1 (en) | 1992-01-23 |
Family
ID=11174427
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1991/001245 WO1992000725A1 (en) | 1990-07-13 | 1991-07-04 | Liquid oral pharmaceutical compositions having anti-inflammatory activity |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0491897A1 (enrdf_load_stackoverflow) |
| AU (1) | AU8093591A (enrdf_load_stackoverflow) |
| CA (1) | CA2066731A1 (enrdf_load_stackoverflow) |
| ES (1) | ES2034926T1 (enrdf_load_stackoverflow) |
| GR (1) | GR930300021T1 (enrdf_load_stackoverflow) |
| IT (1) | IT1243342B (enrdf_load_stackoverflow) |
| WO (1) | WO1992000725A1 (enrdf_load_stackoverflow) |
Cited By (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993025190A1 (en) * | 1992-06-10 | 1993-12-23 | Eastman Kodak Company | Surface modified nsaid nanoparticles |
| WO1994028936A1 (en) * | 1993-06-08 | 1994-12-22 | Ciba-Geigy Ag | Process for the preparation of an oral solid dosage form containing diclofenac |
| WO1995007104A1 (en) * | 1993-09-11 | 1995-03-16 | Smithkline Beecham Plc | Inclusion complexes of beta-cyclodextrin with flurbiprofen, ketoprofen and naproxen |
| WO1995023591A1 (en) * | 1994-03-03 | 1995-09-08 | The Procter & Gamble Company | Oral vehicle compositions |
| EP0627915A4 (en) * | 1992-12-04 | 1996-02-07 | Mayor Pharma Lab Inc | SPRAYABLE ANALGETIC COMPOSITION AND METHOD FOR USE THEREOF. |
| US5552160A (en) * | 1991-01-25 | 1996-09-03 | Nanosystems L.L.C. | Surface modified NSAID nanoparticles |
| WO1997003655A1 (en) * | 1995-07-20 | 1997-02-06 | Pharmacia & Upjohn Company | Stable clear solutions of non-steroidal anti-inflammatory drugs for incorporation into gelatin capsules |
| US5626837A (en) * | 1993-08-12 | 1997-05-06 | Lion Corporation | Oral composition |
| WO1997018802A1 (en) * | 1995-11-22 | 1997-05-29 | The Boots Company Plc | Pharmaceutical compositions comprising flurbiprofen |
| US5674854A (en) * | 1993-10-08 | 1997-10-07 | Farmarc Nederland Bv | Inclusion complex of beta-cyclodextrin and diclofenac, its preparation and use |
| US5679660A (en) * | 1993-12-02 | 1997-10-21 | Farmarc Nederland Bv | Pharmaceutical composition comprising diclofenac and cyclodextrin |
| DE19651055A1 (de) * | 1996-12-09 | 1998-06-10 | Beiersdorf Ag | Kosmetische und dermatologische Lichtschutzformulierungen mit einem Gehalt an Triazinderivaten und Dimethylisosorbid |
| WO1998052539A1 (en) * | 1997-05-22 | 1998-11-26 | The Boots Company Plc | Process for making flurbiprofen lozenges |
| US6071964A (en) * | 1996-03-27 | 2000-06-06 | Hexal Ag | Diclofenac/gamma-cyclodextrin inclusion compounds |
| ES2171110A1 (es) * | 2000-03-03 | 2002-08-16 | Aplicaciones Farmacodinamicas | Composicion farmaceutica a base de ibuprofeno y procedimiento para su preparacion. |
| WO2003094905A1 (en) * | 2002-05-10 | 2003-11-20 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. | Diclofenac-based composition for the topical treatment of oropharyngeal cavity disorders |
| WO2005074885A1 (fr) * | 2004-02-03 | 2005-08-18 | Philippe Perovitch | Procede de diffusion de molecules insolubles en milieu aqueux et composition mettant en oeuvre ce procede |
| GB2416123B (en) * | 2003-04-07 | 2007-06-06 | Jurox Pty Ltd | Stable carprofen composition |
| ES2347754A1 (es) * | 2009-04-27 | 2010-11-03 | Laboratorios De Aplicaciones Farmacodinamicas, S.A | Suspension oral de lisinato de ibuprofeno. |
| GB2486567A (en) * | 2010-12-15 | 2012-06-20 | Reckitt Benckiser Healthcare Int Ltd | Solutions of an NSAID and one or more cyclodextrins |
| JP2012525359A (ja) * | 2009-04-27 | 2012-10-22 | ラボラトリオ デ アプリカシオネス ファルマコディナミカス，エセ．アー． | イブプロフェンリシナートの経口投与用の懸濁液 |
| US8580954B2 (en) | 2006-03-28 | 2013-11-12 | Hospira, Inc. | Formulations of low dose diclofenac and beta-cyclodextrin |
| WO2019105957A1 (en) * | 2017-11-30 | 2019-06-06 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. | Stable liquid composition of ketoprofen, salts and enantiomers thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0215423A2 (de) * | 1985-09-12 | 1987-03-25 | Dolorgiet GmbH & Co. KG | Transdermal resorbierbare, wasserhaltige Zubereitungen von Arylpropionsäurederivaten und Verfahren zur Herstellung derselben |
| EP0284588A1 (fr) * | 1987-03-13 | 1988-09-28 | "PHARLYSE", Société Anonyme | Préparation pharmaceutique à base d'indométacine |
| WO1989004179A1 (en) * | 1987-11-03 | 1989-05-18 | Also Laboratori S.A.S. | Pharmaceutical formulations for transdermal administration |
-
1990
- 1990-07-13 IT IT02094490A patent/IT1243342B/it active IP Right Grant
-
1991
- 1991-07-04 EP EP91911791A patent/EP0491897A1/en not_active Withdrawn
- 1991-07-04 ES ES199191911791T patent/ES2034926T1/es active Pending
- 1991-07-04 CA CA002066731A patent/CA2066731A1/en not_active Abandoned
- 1991-07-04 AU AU80935/91A patent/AU8093591A/en not_active Abandoned
- 1991-07-04 WO PCT/EP1991/001245 patent/WO1992000725A1/en not_active Application Discontinuation
-
1993
- 1993-04-28 GR GR930300021T patent/GR930300021T1/el unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0215423A2 (de) * | 1985-09-12 | 1987-03-25 | Dolorgiet GmbH & Co. KG | Transdermal resorbierbare, wasserhaltige Zubereitungen von Arylpropionsäurederivaten und Verfahren zur Herstellung derselben |
| EP0284588A1 (fr) * | 1987-03-13 | 1988-09-28 | "PHARLYSE", Société Anonyme | Préparation pharmaceutique à base d'indométacine |
| WO1989004179A1 (en) * | 1987-11-03 | 1989-05-18 | Also Laboratori S.A.S. | Pharmaceutical formulations for transdermal administration |
Cited By (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5552160A (en) * | 1991-01-25 | 1996-09-03 | Nanosystems L.L.C. | Surface modified NSAID nanoparticles |
| WO1993025190A1 (en) * | 1992-06-10 | 1993-12-23 | Eastman Kodak Company | Surface modified nsaid nanoparticles |
| EP0627915A4 (en) * | 1992-12-04 | 1996-02-07 | Mayor Pharma Lab Inc | SPRAYABLE ANALGETIC COMPOSITION AND METHOD FOR USE THEREOF. |
| WO1994028936A1 (en) * | 1993-06-08 | 1994-12-22 | Ciba-Geigy Ag | Process for the preparation of an oral solid dosage form containing diclofenac |
| US5702724A (en) * | 1993-06-08 | 1997-12-30 | Ciba-Geigy Corporation | Process for the preparation of an oral solid dosage form containing diclofenac |
| US5626837A (en) * | 1993-08-12 | 1997-05-06 | Lion Corporation | Oral composition |
| WO1995007104A1 (en) * | 1993-09-11 | 1995-03-16 | Smithkline Beecham Plc | Inclusion complexes of beta-cyclodextrin with flurbiprofen, ketoprofen and naproxen |
| US5674854A (en) * | 1993-10-08 | 1997-10-07 | Farmarc Nederland Bv | Inclusion complex of beta-cyclodextrin and diclofenac, its preparation and use |
| US5679660A (en) * | 1993-12-02 | 1997-10-21 | Farmarc Nederland Bv | Pharmaceutical composition comprising diclofenac and cyclodextrin |
| AU702889B2 (en) * | 1994-03-03 | 1999-03-11 | Procter & Gamble Company, The | Oral vehicle compositions |
| WO1995023591A1 (en) * | 1994-03-03 | 1995-09-08 | The Procter & Gamble Company | Oral vehicle compositions |
| WO1997003655A1 (en) * | 1995-07-20 | 1997-02-06 | Pharmacia & Upjohn Company | Stable clear solutions of non-steroidal anti-inflammatory drugs for incorporation into gelatin capsules |
| WO1997018802A1 (en) * | 1995-11-22 | 1997-05-29 | The Boots Company Plc | Pharmaceutical compositions comprising flurbiprofen |
| US5889057A (en) * | 1995-11-22 | 1999-03-30 | The Boots Company Plc | Flurbiprofen lozenge for the treatment of sore throat |
| AU707749B2 (en) * | 1995-11-22 | 1999-07-22 | Reckitt Benckiser Healthcare (Uk) Limited | Medical Treatment |
| US6166083A (en) * | 1995-11-22 | 2000-12-26 | The Boots Company, Plc | Suckable flurbiprofen lozenges for treatment of sore throat |
| US6071964A (en) * | 1996-03-27 | 2000-06-06 | Hexal Ag | Diclofenac/gamma-cyclodextrin inclusion compounds |
| DE19651055B4 (de) * | 1996-12-09 | 2006-03-16 | Beiersdorf Ag | Kosmetische und dermatologische Lichtschutzformulierungen mit einem Gehalt an Triazinderivaten und Dimethylisosorbid und deren Verwendung |
| DE19651055A1 (de) * | 1996-12-09 | 1998-06-10 | Beiersdorf Ag | Kosmetische und dermatologische Lichtschutzformulierungen mit einem Gehalt an Triazinderivaten und Dimethylisosorbid |
| WO1998052539A1 (en) * | 1997-05-22 | 1998-11-26 | The Boots Company Plc | Process for making flurbiprofen lozenges |
| US6194003B1 (en) | 1997-05-22 | 2001-02-27 | The Boots Company Plc | Process for making flurbiprofen lozenges |
| ES2171110A1 (es) * | 2000-03-03 | 2002-08-16 | Aplicaciones Farmacodinamicas | Composicion farmaceutica a base de ibuprofeno y procedimiento para su preparacion. |
| WO2003094905A1 (en) * | 2002-05-10 | 2003-11-20 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. | Diclofenac-based composition for the topical treatment of oropharyngeal cavity disorders |
| CN1303992C (zh) * | 2002-05-10 | 2007-03-14 | 方济各安吉利克化学联合股份有限公司 | 用于局部治疗口咽腔疾病的基于双氯芬酸的组合物 |
| GB2416123B (en) * | 2003-04-07 | 2007-06-06 | Jurox Pty Ltd | Stable carprofen composition |
| US8846083B2 (en) | 2004-02-03 | 2014-09-30 | Philippe Perovitch | Method for the diffusion of molecules which are insoluble in an aqueous medium and composition using said method |
| WO2005074885A1 (fr) * | 2004-02-03 | 2005-08-18 | Philippe Perovitch | Procede de diffusion de molecules insolubles en milieu aqueux et composition mettant en oeuvre ce procede |
| EP1711162B1 (fr) | 2004-02-03 | 2017-11-01 | Philippe Perovitch | Composition pour l'utilisation dans le traitement local des affections bucco-pharyngées comprenant de l'ibuprofène ou du kétoprofène |
| RU2388468C2 (ru) * | 2004-02-03 | 2010-05-10 | Филипп ПЕРОВИЧ | Способ диффузии молекул, не растворимых в водной среде, и композиция для осуществления этого способа |
| US8946292B2 (en) | 2006-03-28 | 2015-02-03 | Javelin Pharmaceuticals, Inc. | Formulations of low dose diclofenac and beta-cyclodextrin |
| US8580954B2 (en) | 2006-03-28 | 2013-11-12 | Hospira, Inc. | Formulations of low dose diclofenac and beta-cyclodextrin |
| JP2012525359A (ja) * | 2009-04-27 | 2012-10-22 | ラボラトリオ デ アプリカシオネス ファルマコディナミカス，エセ．アー． | イブプロフェンリシナートの経口投与用の懸濁液 |
| ES2347754B1 (es) * | 2009-04-27 | 2011-09-29 | Laboratorios De Aplicaciones Farmacodinamicas, S.A | Suspension oral de lisinato de ibuprofeno. |
| ES2347754A1 (es) * | 2009-04-27 | 2010-11-03 | Laboratorios De Aplicaciones Farmacodinamicas, S.A | Suspension oral de lisinato de ibuprofeno. |
| WO2012080718A1 (en) * | 2010-12-15 | 2012-06-21 | Reckitt Benckiser Healthcare International Limited | Novel pharmaceutical formulation comprising nsaid and cyclodextrin |
| GB2486567B (en) * | 2010-12-15 | 2014-09-10 | Reckitt Benckiser Healthcare Int Ltd | Pharmaceutical formulation |
| GB2486567A (en) * | 2010-12-15 | 2012-06-20 | Reckitt Benckiser Healthcare Int Ltd | Solutions of an NSAID and one or more cyclodextrins |
| US9138482B2 (en) | 2010-12-15 | 2015-09-22 | Reckitt Benckiser Healthcare International Limited | Pharmaceutical formulation comprising NSAID and cyclodextrin |
| RU2607592C2 (ru) * | 2010-12-15 | 2017-01-10 | Рекитт Бенкизер Хелскэа Интернэшнл Лимитед | Новая фармацевтическая композиция, включающая нпвс и циклодекстрин |
| US10363316B2 (en) | 2010-12-15 | 2019-07-30 | Reckitt Benckiser Healthcare (Uk) Limited | Pharmaceutical formulation comprising NSAID and cyclodextrin |
| WO2019105957A1 (en) * | 2017-11-30 | 2019-06-06 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. | Stable liquid composition of ketoprofen, salts and enantiomers thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| AU8093591A (en) | 1992-02-04 |
| GR930300021T1 (enrdf_load_stackoverflow) | 1993-04-28 |
| EP0491897A1 (en) | 1992-07-01 |
| CA2066731A1 (en) | 1992-01-14 |
| IT9020944A0 (it) | 1990-07-13 |
| IT9020944A1 (it) | 1992-01-13 |
| ES2034926T1 (es) | 1993-04-16 |
| IT1243342B (it) | 1994-06-10 |
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