WO1998035662A1 - Composition pharmaceutique pour l'administration orale de composes heterocycliques sous forme ammonium quaternaire - Google Patents
Composition pharmaceutique pour l'administration orale de composes heterocycliques sous forme ammonium quaternaire Download PDFInfo
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- WO1998035662A1 WO1998035662A1 PCT/FR1998/000298 FR9800298W WO9835662A1 WO 1998035662 A1 WO1998035662 A1 WO 1998035662A1 FR 9800298 W FR9800298 W FR 9800298W WO 9835662 A1 WO9835662 A1 WO 9835662A1
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 51
- 125000001453 quaternary ammonium group Chemical group 0.000 title abstract description 7
- 150000002391 heterocyclic compounds Chemical class 0.000 title abstract description 4
- 239000002904 solvent Substances 0.000 claims abstract description 40
- 239000003945 anionic surfactant Substances 0.000 claims abstract description 33
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims abstract description 22
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims abstract description 22
- 229920000053 polysorbate 80 Polymers 0.000 claims abstract description 22
- 229940068968 polysorbate 80 Drugs 0.000 claims abstract description 22
- 239000000470 constituent Substances 0.000 claims abstract description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 97
- 125000000217 alkyl group Chemical group 0.000 claims description 40
- 125000002947 alkylene group Chemical group 0.000 claims description 34
- 150000001875 compounds Chemical class 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 29
- 239000004480 active ingredient Substances 0.000 claims description 22
- 238000009472 formulation Methods 0.000 claims description 22
- 239000002775 capsule Substances 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
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- 239000001257 hydrogen Substances 0.000 claims description 14
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical group [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 12
- -1 formyloxy Chemical group 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
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- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
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- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
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- PQRLQZNKDQQMBC-LSYPWIJNSA-M benzenesulfonate;1-[(3s)-3-(3,4-dichlorophenyl)-3-[2-(4-phenyl-1-azoniabicyclo[2.2.2]octan-1-yl)ethyl]piperidin-1-yl]-2-(3-propan-2-yloxyphenyl)ethanone Chemical group [O-]S(=O)(=O)C1=CC=CC=C1.CC(C)OC1=CC=CC(CC(=O)N2C[C@](CC[N+]34CCC(CC3)(CC4)C=3C=CC=CC=3)(CCC2)C=2C=C(Cl)C(Cl)=CC=2)=C1 PQRLQZNKDQQMBC-LSYPWIJNSA-M 0.000 claims description 3
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- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 2
- RPDFDSQFBCJTDY-GAQXSTBRSA-N 1-[(3s)-3-(3,4-dichlorophenyl)-3-[2-(4-phenyl-1-azoniabicyclo[2.2.2]octan-1-yl)ethyl]piperidin-1-yl]-2-(3-propan-2-yloxyphenyl)ethanone Chemical group CC(C)OC1=CC=CC(CC(=O)N2C[C@](CC[N+]34CCC(CC3)(CC4)C=3C=CC=CC=3)(CCC2)C=2C=C(Cl)C(Cl)=CC=2)=C1 RPDFDSQFBCJTDY-GAQXSTBRSA-N 0.000 claims description 2
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 2
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- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 2
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- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 2
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- 239000004094 surface-active agent Substances 0.000 description 1
- 150000005691 triesters Chemical class 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
Classifications
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
Definitions
- composition for the oral administration of heterocyclic compounds in quaternary ammonium form
- the present invention relates to new pharmaceutical compositions containing as active ingredient a heterocyclic compound in the form of quaternary ammonium.
- compositions for oral administration containing as active ingredient a compound of formula:
- a ⁇ is a pharmaceutically acceptable anion
- Am® represents: i - either an Ami ® group of formula:
- - Arj represents a phenyl which is unsubstituted or substituted one or more times by a substituent chosen from a halogen atom, a hydroxy, a (C ⁇ -C) alkoxy, a (C ⁇ -C4) alkyl or a trifluoromethyl, said substituents being identical or different;
- - x is zero or one;
- - Wj represents a (C ⁇ -Cg) alkyl or a benzyl group; the substituent Wi being either in the axial position or in the equatorial position; ii - or an Arrn® group of formula:
- R_2 represents hydrogen; a (C ⁇ -C3) alkyl; a (C ⁇ -C3) alkylcarbonyl; iv - or an Am4® group of formula:
- - Ar represents a phenyl which is unsubstituted or substituted once or twice by a substituent chosen from a halogen atom, a (Cj-C3) alkoxy, a (C ⁇ -C3) alkyl or a trifluoromethyl, said substituents being identical or different; naphthyl; indolyl; - Q and Y represent one of the following groups of values: a) Qi and Y ⁇ ; b) Q2 and Y2 when Am® represents a group Ami ®, A ⁇ r?
- - Q 1 represents hydrogen
- - Y represents hydrogen: a (Cj-C4) alkyl; a ⁇ - (C ⁇ -C4) alkoxy- (C2-C4) alkylene; a ⁇ - (C ⁇ -C4) alkylcarbonyloxy- (C2-C4) alkylene; ⁇ -benzoyloxy- (C2-C4) alkylene; ⁇ -hydroxy- (C2-C4) alkylene; a ⁇ - (C ⁇ -C4) alkylthio- (C2-C4) alkylene; a ⁇ - (C ⁇ -C4) alkylcarbonyl- (C2-C4) alkylene; ⁇ -carboxy- (C2-C4) alkylene; a ⁇ - (C ⁇ -C4) alkoxycarbonyl- (C2-C4) alkylene; a ⁇ -benzyloxy-
- T represents - either a group -CO- when Q and Y represent the group Qi and Y ⁇ , the group Q2 and Y2 or the group Q4 and Y4 in which Q4 and Y4 together constitute a radical Ai), A5) or Ag );
- A represents either a direct bond or a methylene group when T is -CO-, or a direct bond when T is -CH2-;
- Z represents: a phenyl which is unsubstituted or substituted one or more times by a substituent chosen from a halogen atom; trifluoromethyl; a cyano; hydroxy; a nitro; an amino unsubstituted or substituted one or more times by a (C j -C4) alkyl; a benzylamino; carboxy; a (C ⁇ -C ⁇ o) alkyl; non (C3-C 7 ) cycloalkyl substituted or substituted one or more times with methyl; a (C ⁇ -C ⁇ o) alkoxy; a (C3-C 7 ) cycloalkyloxy unsubstituted or substituted one or more times with methyl; a mercapto; a (C ⁇ -C ⁇ o) alkylthio; a (
- - R3 represents a (C ⁇ -C 7 ) alkyl or a phenyl
- R4 and R5 each independently represent a hydrogen or a (C 1 -C 7 ) alkyl; R5 can also represent a (C3-C 7 ) cycloalkyl, a (C3-
- R4 and R5 together with the nitrogen atom to which they are linked constitute a heterocycle chosen from azetidine, pyrrolidine, piperidine, morpholine, thiomorpholine, perhydroazepine or piperazine unsubstituted or substituted in position 4 by a (C ⁇ -C 4 ) alkyl;
- - R ⁇ represents a hydrogen, a (C ⁇ -C 7 ) alkyl, a vinyl, a phenyl, a benzyl, a pyridyl or a (C3-C 7 ) cycloalkyl unsubstituted or substituted by one or more methyls;
- - R represents a hydrogen or a (C ⁇ -C 7 ) alkyl
- - Rg represents a (C ⁇ -C 7 ) alkyl or a phenyl
- R9 represents a (C ⁇ -C 7 ) alkyl; an amino unsubstituted or substituted by one or two (C ⁇ -C) alkyls; phenyl unsubstituted or substituted one or more times by a substituent chosen from a halogen atom, a (Cj-C 7 ) alkyl, a trifluoromethyl, a hydroxy, a (C ⁇ -C) alkoxy, a carboxy, a (Ci - C 7 ) alkoxycarbonyl, a (C ⁇ -C 7 ) alkylcarbonyloxy, a cyano, a nitro or an amino not substituted or substituted by one or two (C ⁇ -C 7 ) alkyls, said substituents being identical or different;
- - RlO represents hydrogen or a (C ⁇ -C4) alkyl; as well as its possible salts with mineral or organic acids and their possible solvates.
- the compounds of formula (I) useful for the invention include the racemates, the optically pure isomers, as well as the axial and equatorial isomers when in the compound of formula (I), Am® represents an Am® group, a group Airn® or an Am3® group.
- the invention relates to pharmaceutical compositions for the oral administration of (S) -l- ⁇ 2- [3- (3,4-dichlorophenyl) -l- (3-isopropoxyphenylacetyl) piperidin-3-yl ] ethyl ⁇ -4-phenyl-1-azoniabicyclo [2.2.2] octane, or SR 140333, of formula:
- a ( - ⁇ is a pharmaceutically acceptable anion.
- compound A The benzenesulfonate of SR 140333 hereinafter called compound A is very particularly preferred.
- the international nonproprietary name for compound A is nolpitantium besilate.
- the compounds of formula (I) have been described as antagonists of substance P which is the natural agonist of the NK1 receptors, and therefore have an affinity for these receptors. To administer such compounds orally, it is necessary that they exhibit good absorption, which implies both good solubility in aqueous medium and good capacity to cross the intestinal membrane (M. Rowland and TN Tozer in Clinical pharmacokinetics, concepts and applications, Lea and Fehiger ed., 1989, 2nd edition, p. 113-130).
- solubility of the compounds of formula (I) has been studied in different media: their solubility in water is generally less than 5 mg / ml but they are soluble in hydrophilic solvents such as alcohols or glycols.
- the compounds of formula (I) being quaternary ammonium remain in ionized form whatever the pH of the medium in which they are found in particular at neutral pH which is the pH of the intestinal medium.
- the Caco-2 cell line has the distinction of differentiating in vitro to form an epithelial monolayer. This line is conventionally used to evaluate the epithelial permeability of the compounds (Crit. Rev. Ther. Drug Carrier System, 1991, 8 (4), 105-330).
- the permeability of compound A is 3.4. 10 "? Cm / s. Furthermore, correlations made between the in-vitro results and the in-vivo results have shown that a permeability coefficient of this order corresponds to an absorption of less than 5% for molecules which are completely solubilized. In the present case, studies carried out in rats with compound A in 0.6% aqueous solution in methylcellulose have shown that its estimated absorption is less than 1%.
- Derivatives which are in semi-solid form at ordinary temperature and which, having both a lipid and an amphiphilic nature can be used to solubilize lipophilic active principles and facilitate their intestinal absorption (Bull. Techn. Gattefossé, 1994, 87, 49-54).
- Such compounds are chosen from saturated polyglycosylated glycerides consisting of a mixture of monoesters, diesters and triesters of glycerol and of fatty acids whose carbon chains are in Cg-Cig, and of mono and diesters of polyethylene glycol and of fatty acids whose carbon chains are in Cg-Cig. The most interesting of them are:
- the formulation thus obtained makes it possible to improve the bioavailability of the active principle. It is also advantageous to dissolve a compound of formula (I) in a saturated polyglycosylated glyceride by adding both a hydrophilic solvent and an anionic surfactant.
- the present invention relates to a pharmaceutical composition for the oral administration of a compound of formula (I) containing: - active principle 0.1% to 15% by weight,
- the concentration of active principle is less than or equal to 30% by weight of the concentration of hydrophilic solvent.
- macrogoglyceride means the products Gélucire® 44-14, Gélucire® 50-13 or Labrasol® as described above, the product
- Gélucire® 44-14 being preferred.
- hydrophilic solvent an alcohol such as ethanol or a glycol derivative such as propylene glycol or the product Transcutol® which is a monoethyl ether of diethylene glycol can be used.
- Propylene glycol is the preferred hydrophilic solvent.
- a bile salt such as sodium taurocholate or a sodium alkyl sulphate such as sodium octyl sulphate or preferably sodium lauryl sulphate can be used, the latter being a preferred anionic surfactant according to the invention.
- the pharmaceutical compositions according to the invention can be in different forms intended for oral administration: capsules, sachets, drops, drinkable ampoules or bottles for example.
- the present invention relates to a pharmaceutical composition containing: - active ingredient 0.1% to 15% by weight
- the present invention relates to a pharmaceutical composition for the oral administration of a compound of formula (I) containing: - active ingredient 0.1 to 15% by weight,
- the present invention relates to a pharmaceutical composition for the oral administration of a compound of formula (I) containing:
- the anionic surfactant is preferably in stoichiometric quantity with respect to the active principle.
- the anionic surfactant being introduced in concentrated aqueous solution, the above pharmaceutical composition contains from 0.1 to 12% of water.
- the hydrophilic solvent content of the pharmaceutical composition must be compatible with gelatin.
- the present invention more particularly relates to pharmaceutical compositions for the preparation of capsules containing:
- compositions are preferred for the preparation of capsules containing:
- compositions are also preferred for the preparation of capsules containing:
- the anionic surfactant is preferably in stoichiometric quantity with respect to the active principle.
- the pharmaceutical composition according to the invention contains an amount greater than or equal to 1% by weight of hydrophilic solvent, particularly preferably an amount greater than or equal to 1% by weight of propylene glycol.
- enteric formulations can also be prepared.
- Such formulations are used to protect the active ingredient from high stomach acidity.
- Such formulations are prepared by coating the capsule with a polymer film insoluble in an acidic environment and soluble in a basic environment.
- a film for coating mention may be made of cellulose acetophthalate, polyvinyl acetophthalate, hydroxypropylmethylcellulose phthalate or methacrylic acid copolymers.
- methacrylic acid copolymer type C examples of methacrylic acid copolymer type C, sold under the trademark EUDRAGIT ® L30 D-55 by Rohm or copolymer of ethyl acrylate and methacrylic acid marketed under the brand name KOLLICOAT MAE 30D by
- plasticizers can be added, such as for example: a polyethylene glycol, 1,2-propylene glycol, dibutyl phthalate or a citrate.
- a film coating consisting of a pre-coating before the enteric coating.
- the pre-coating can be done for example with hydroxypropylcellulose, povidone or a methacrylic acid copolymer combined with suitable excipients.
- the present invention relates to a pharmaceutical composition for the oral administration of compound A containing: compound A 0.1 to 9% by weight, propylene glycol 1 to 30% by weight, sodium lauryl sulfate 0 to 3% by weight,
- the present invention relates to a pharmaceutical composition of formula: compound A 0, 1 to 7% by weight, propylene glycol 5 to 20% by weight,
- the present invention also relates to a pharmaceutical composition of formula: compound A 0.1 to 7% by weight, propylene glycol 1 to 15% by weight, sodium lauryl sulfate 0.03 to 2% by weight,
- the present invention relates to a pharmaceutical composition for the preparation of capsules containing: compound A 3.6% by weight, propylene glycol 15.9% by weight,
- the present invention relates to a pharmaceutical composition for the preparation of capsules containing: compound A - 3.4% by weight, propylene glycol 15.3% by weight, sodium lauryl sulfate 1.5% by weight, water 2.7% by weight,
- a pharmaceutical composition for the preparation of a pharmaceutical composition as described above, one can proceed as follows when there is no anionic surfactant in the composition: the active principle is placed in suspension in the hydrophilic solvent and heated with stirring to a temperature between 60 ° C and 80 ° C depending on the concentration of active ingredient introduced into the hydrophilic solvent. We add 90% of the macrogoglyceride melted at 60 ° C and then optionally the polysorbate 80. Finish by adjusting to 100% with the sufficient amount of macrogoglyceride.
- the active principle is mixed in 90% of the macrogoglyceride heated to 60 ° C.
- the anionic surfactant dissolved in hot water is added in the minimum amount of water, then, if necessary, the hydrophilic solvent and optionally polysorbate 80 are added.
- the final step is adjusted to 100% by the sufficient amount of macrogoglyceride.
- the coating of a capsule according to the invention may contain a pre-coating film and a coating film having the following constitutions.
- Pre-coating methacrylic acid copolymer of type C 46.6% by weight glycerin 4.6% by weight aqueous solution of polysorbate 80 to 33% 4.6% by weight water 44.2% by weight
- compositions according to the invention will appear in the light of the description below, from the compositions given by way of examples.
- percentages expressed are percentages by weight.
- the instant solubility is evaluated, at ambient temperature, by successive additions of the solvent studied on the compound A in a hemolysis tube, until the clarity is observed.
- solubilities are determined by weight / weight.
- water 0.33 mg / g ethanol 36.5 mg / g methanol 365.0 mg / g benzyl alcohol> 450.0 mg / g
- Transcutol® 5.0 mg / g polyethylene glycol 400 0.45 mg / g propylene glycol 12 mg / g glycerol oleate 0.64 mg / g peanut oil ⁇ 0.2 mg / g
- compound A is soluble in dimethylsulfoxide (DMSO) at 168 mg / ml. 1.3. Variation of solubility as a function of temperature in propylene glycol.
- Each of these formulations causes a marked improvement in the transepithelial passage of compound A and none of these formulations has caused an alteration of the epithelial monolayer.
- the active ingredient is mixed with 90% of Gélucire® 44-14 heated to 60 ° C.
- the aqueous solution of sodium lauryl sulfate is added and then adjusted with the remaining Gélucire® 44-14. It is incorporated into the capsule after cooling to 40 ° C.
- EXAMPLE 3 Liquid form for vial compound A 6.0% propylene glycol 34.0%
- EXAMPLE 8 Liquid for vial compound A 7.5% propylene glycol 20.5% polysorbate 80 2.0% sodium lauryl sulfate 2.6% water 4.9%
- a capsule is prepared according to Example 1 and a coating is applied in 2 layers: one for pre-coating and the other for coating. Pre-coating:
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- Health & Medical Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BR9807694A BR9807694A (pt) | 1997-02-17 | 1998-02-17 | de um princìpio ativo |
EP98909549A EP0969825A1 (fr) | 1997-02-17 | 1998-02-17 | Composition pharmaceutique pour l'administration orale de composes heterocycliques sous forme ammonium quaternaire |
CA002281560A CA2281560A1 (fr) | 1997-02-17 | 1998-02-17 | Composition pharmaceutique pour l'administration orale de composes heterocycliques sous forme ammonium quaternaire |
AU64049/98A AU6404998A (en) | 1997-02-17 | 1998-02-17 | Pharmaceutical composition for oral administration of heterocyclic compounds in the form of quaternary ammonium |
JP53543298A JP2001511795A (ja) | 1997-02-17 | 1998-02-17 | 四級アンモニウムの形態にあるヘテロサイクリック化合物の経口投与のための薬学的組成物 |
NO993928A NO993928L (no) | 1997-02-17 | 1999-08-16 | Farmasöytisk blanding for oral administrasjon av heterosykliske forbindelser i form av kvaternær ammonium |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9701825A FR2759584B1 (fr) | 1997-02-17 | 1997-02-17 | Composition pharmaceutique pour l'administration orale de composes heterocycliques sous forme ammonium quaternaire |
FR97/01825 | 1997-02-17 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1998035662A1 true WO1998035662A1 (fr) | 1998-08-20 |
Family
ID=9503804
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/FR1998/000298 WO1998035662A1 (fr) | 1997-02-17 | 1998-02-17 | Composition pharmaceutique pour l'administration orale de composes heterocycliques sous forme ammonium quaternaire |
Country Status (11)
Country | Link |
---|---|
EP (1) | EP0969825A1 (fr) |
JP (1) | JP2001511795A (fr) |
AR (1) | AR011805A1 (fr) |
AU (1) | AU6404998A (fr) |
BR (1) | BR9807694A (fr) |
CA (1) | CA2281560A1 (fr) |
FR (1) | FR2759584B1 (fr) |
HR (1) | HRP980075A2 (fr) |
NO (1) | NO993928L (fr) |
WO (1) | WO1998035662A1 (fr) |
ZA (1) | ZA981289B (fr) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102188424B (zh) * | 2011-03-23 | 2013-03-27 | 浙江理工大学 | Sr140333的抗血癌作用 |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0512901A1 (fr) * | 1991-05-03 | 1992-11-11 | Sanofi | Composés polycycliques aminés et leurs énantiomères, procédé pour leur préparation et compositions pharmaceutiques en contenant |
EP0515240A1 (fr) * | 1991-05-03 | 1992-11-25 | Sanofi | Nouveaux composés N-alkylènepipéridino et leurs énantiomères, procédé pour leur préparation et compositions pharmaceutiques les contenant |
EP0559538A1 (fr) * | 1992-03-03 | 1993-09-08 | Sanofi | Sels quaternaires de pipéridines 4-substitués, leur préparation et compositions pharmaceutiques les contenant |
EP0591040A1 (fr) * | 1992-09-30 | 1994-04-06 | Sanofi | Amides basiques quaternaires comme tachykinines antagonistes |
WO1995026339A1 (fr) * | 1994-03-25 | 1995-10-05 | Sanofi | Sels de composes heteroaromatiques azotes substitues, procede pour leur preparation et compositions pharmaceutiques en contenant |
WO1996006094A1 (fr) * | 1994-08-25 | 1996-02-29 | Merrell Pharmaceuticals Inc. | Nouvelles piperidines substituees utiles pour le traitement d'affections allergiques |
EP0708101A1 (fr) * | 1994-10-21 | 1996-04-24 | Adir Et Compagnie | Nouveaux dérivés de pipéridine utiles comme antagonistes des récepteurs des neurokinines |
WO1996012479A1 (fr) * | 1994-10-21 | 1996-05-02 | Sanofi | Utilisation d'antagonistes des recepteurs nk1 pour la preparation de medicaments a action cardioregulatrice |
EP0723959A1 (fr) * | 1995-01-30 | 1996-07-31 | Sanofi | Composés hétérocycliques comme antagonistes de récepteurs de la tachykinine, procédé pour leur préparation et compositions pharmaceutiques en contenant |
WO1996023787A1 (fr) * | 1995-01-30 | 1996-08-08 | Sanofi | Composes heterocycliques substitues, procede pour leur preparation et compositions pharmaceutiques les contenant |
-
1997
- 1997-02-17 FR FR9701825A patent/FR2759584B1/fr not_active Expired - Fee Related
-
1998
- 1998-02-16 AR ARP980100675A patent/AR011805A1/es unknown
- 1998-02-16 HR HR9701825A patent/HRP980075A2/hr not_active Application Discontinuation
- 1998-02-17 WO PCT/FR1998/000298 patent/WO1998035662A1/fr not_active Application Discontinuation
- 1998-02-17 JP JP53543298A patent/JP2001511795A/ja active Pending
- 1998-02-17 CA CA002281560A patent/CA2281560A1/fr not_active Abandoned
- 1998-02-17 AU AU64049/98A patent/AU6404998A/en not_active Abandoned
- 1998-02-17 BR BR9807694A patent/BR9807694A/pt not_active Application Discontinuation
- 1998-02-17 EP EP98909549A patent/EP0969825A1/fr not_active Withdrawn
- 1998-02-17 ZA ZA981289A patent/ZA981289B/xx unknown
-
1999
- 1999-08-16 NO NO993928A patent/NO993928L/no unknown
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0512901A1 (fr) * | 1991-05-03 | 1992-11-11 | Sanofi | Composés polycycliques aminés et leurs énantiomères, procédé pour leur préparation et compositions pharmaceutiques en contenant |
EP0515240A1 (fr) * | 1991-05-03 | 1992-11-25 | Sanofi | Nouveaux composés N-alkylènepipéridino et leurs énantiomères, procédé pour leur préparation et compositions pharmaceutiques les contenant |
EP0559538A1 (fr) * | 1992-03-03 | 1993-09-08 | Sanofi | Sels quaternaires de pipéridines 4-substitués, leur préparation et compositions pharmaceutiques les contenant |
EP0591040A1 (fr) * | 1992-09-30 | 1994-04-06 | Sanofi | Amides basiques quaternaires comme tachykinines antagonistes |
WO1995026339A1 (fr) * | 1994-03-25 | 1995-10-05 | Sanofi | Sels de composes heteroaromatiques azotes substitues, procede pour leur preparation et compositions pharmaceutiques en contenant |
WO1996006094A1 (fr) * | 1994-08-25 | 1996-02-29 | Merrell Pharmaceuticals Inc. | Nouvelles piperidines substituees utiles pour le traitement d'affections allergiques |
EP0708101A1 (fr) * | 1994-10-21 | 1996-04-24 | Adir Et Compagnie | Nouveaux dérivés de pipéridine utiles comme antagonistes des récepteurs des neurokinines |
WO1996012479A1 (fr) * | 1994-10-21 | 1996-05-02 | Sanofi | Utilisation d'antagonistes des recepteurs nk1 pour la preparation de medicaments a action cardioregulatrice |
EP0723959A1 (fr) * | 1995-01-30 | 1996-07-31 | Sanofi | Composés hétérocycliques comme antagonistes de récepteurs de la tachykinine, procédé pour leur préparation et compositions pharmaceutiques en contenant |
WO1996023787A1 (fr) * | 1995-01-30 | 1996-08-08 | Sanofi | Composes heterocycliques substitues, procede pour leur preparation et compositions pharmaceutiques les contenant |
Also Published As
Publication number | Publication date |
---|---|
HRP980075A2 (en) | 1998-10-31 |
CA2281560A1 (fr) | 1998-08-20 |
FR2759584B1 (fr) | 1999-06-11 |
NO993928D0 (no) | 1999-08-16 |
EP0969825A1 (fr) | 2000-01-12 |
AU6404998A (en) | 1998-09-08 |
ZA981289B (en) | 1998-08-26 |
NO993928L (no) | 1999-08-16 |
BR9807694A (pt) | 2000-03-21 |
AR011805A1 (es) | 2000-09-13 |
JP2001511795A (ja) | 2001-08-14 |
FR2759584A1 (fr) | 1998-08-21 |
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