Active substance combination

• US 20050222136A1
• Filed: 11/12/2004
• Published: 10/06/2005
• Est. Priority Date: 04/05/2004
• Status: Abandoned Application

• Current Assignee: Laboratories Del Dr Esteve SA (Corporation Quimico Farmaceutica Esteve SA)
• Original Assignee: Laboratories Del Dr Esteve SA (Corporation Quimico Farmaceutica Esteve SA)
• Inventors: Buschmann, Helmut Heinrich, Gutierrez Silva, Bonifacio, Farre Gomis, Antonio, Holenz, Jorg
• Application Number:
  US10/987,803
• Publication Number:
  US 20050222136A1
• Time in Patent Office: Days
• US Class Current: 514/221
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/416 condensed with carbocyclic ring systems, e.g. indazole
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

The present invention relates to an active substance combination including at least one substituted carbinol compound and at least one non-steroidal anti-inflammatory drug (NSAID), a medicament including the active substance combination, a pharmaceutical formulation including the active substance combination and the use of the active substance combination for the manufacture of a medicament.

Claims

1. Active substance combination comprising

(A) at least one substituted carbinol compound of general formula I,

wherein

R¹ represents a hydrogen atom, a linear or branched alkyl radical, a linear or branched alkenyl radical, an optionally at least mono-substituted cycloaliphatic radical, which may contain at least one nitrogen atom as ring member, or a phenyl radical,

R² represents a hydrogen atom, an optionally at least one nitrogen atom as ring member containing cycloaliphatic radical, which may be at least mono-substituted by a linear or branched alkyl radical and/or which may be bound via a linear or branched alkylene group, an NR³R⁴-moiety, which is bound via a linear or branched alkylene group, or an NR⁵R⁶-moiety, which is bound via a linear or branched alkylene group,

R³ and R⁴, identical or different, represent a linear or branched alkyl radical or an unsubstituted benzyl radical,

R⁵ and R⁶ together with the bridging nitrogen atom represent a saturated, unsubstituted, optionally at least one further heteroatom as ring member containing heterocyclic radical,

X represents an optionally at least mono-substituted phenyl radical or an optionally at least mono-substituted thienyl radical, wherein in each case the substituents may be independently selected from the group consisting of a linear or branched alkyl radical, a linear or branched alkoxy group, a linear or branched alkyl radical, which is at least partially halogenated and a halogen atom,

Y represents a heteroaryl radical, which contains one or more nitrogen atoms as ring members and which is unsubstituted or at least mono-substituted by one or more substitutents independently from one another selected from the group consisting of a halogen atom, a linear or branched alkyl radical, a benzyl radical, a ciano group bound via a linear or branched C_1-4-alkylene group, a carboxy group bound via a linear or branched C_1-4-alkylene group, a methoxy carbonyl group bound via a linear or branched C:

L₄-alkylene group, a hydroxy group bound via a linear or branched C_1-4-alkylene group, an amino group bound via a linear or branched C_1-4-alkylene group, a (C_1-4) dialkylamino group bound via a linear or branched C_1-4-alkylene group, and a cycloaliphatic radical, which contains at least one nitrogen atom as ring member and which is bound via a linear or branched C_1-4-alkylene group, or Y represents an unsubstituted heteroaryl radical, which contains two nitrogen atoms as ring members and which is condensed with a saturated, one methyl-substituted nitrogen atom as ring member containing cycloaliphatic group,

optionally in form of one of its stereoisomers, preferably enantiomers or diastereomers, its racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate,

and

(B) optionally at least one non-steroidal anti-inflammatory drug (NSAID).

2. Active substance combination according to claim 1, characterized in that R¹ represents a hydrogen atom, a linear or branched C_1-4 alkyl radical, a linear or branched C_2-4 alkenyl radical, a 5- or 6-membered cycloaliphatic radical, which may contain at least one nitrogen atom as ring member and/or which may be at least mono-substituted by a linear or branched C_1-4 alkyl radical, or a phenyl radical, preferably a hydrogen atom, a linear or branched C_1-4 alkyl radical, a vinyl group, a cyclohexyl radical, an N-Methyl-piperidyl radical or a phenyl radical.

3. Active substance combination according to claim 1, characterized in that R² represents a hydrogen atom, an optionally at least one nitrogen atom as ring member containing, 5- or 6-membered cycloaliphatic radical, which may be at least mono-substituted by a linear or branched C_1-4-alkyl radical and/or which may be bound via a linear or branched C_1-4-alkylene group, a NR³R⁴-moiety, which is bound via a linear or branched C_1-4 alkylene group, or a NR⁵R⁶-moiety, which is bound via a linear or branched C_1-4 alkylene group, preferably a hydrogen atom, an optionally at least one nitrogen atom as ring member containing, 5- or 6-membered cycloaliphatic radical, which may be at least mono-substituted by a linear or branched C_1-4-alkyl radical and/or which may be bound via a linear or branched C_1-4-alkylene group, a NR³R⁴-moiety, which is bound via a linear or branched C_2-3 alkylene group, or a NR⁵R⁶-moiety, which is bound via a linear or branched C_2-3 alkylene group.

4. Active substance combination according to claim 1, characterized in that R³ and R⁴, identical or different, independently from one another represent a linear or branched C_1-4 alkyl radical or an unsubstituted benzyl radical, preferably a linear or branched C_1-4 alkyl radical.

5. Active substance combination according to claim 1, characterized in that R⁵ and R⁶ together with the bridging nitrogen atom represent a saturated, unsubstituted, optionally at least one oxygen atom as ring member containing, 5- or 6-membered heterocyclic radical.

6. Active substance combination according to claim 1, characterized in that X represents an optionally at least mono-substituted phenyl radical or an optionally at least mono-substituted thienyl radical, wherein in each case the substituents may be independently selected from the group consisting of a linear or branched C_1-4 alkyl radical, a linear or branched C_1-4 alkoxy radical, a linear or branched C_1-4 alkyl radical, which is at least partially fluorinated, a fluorine atom, a chlorine atom and a bromine atom, preferably represents an optionally at least mono-substituted phenyl radical or an optionally at least mono-substituted thienyl radical, wherein in each case the substituents may be independently selected from the group consisting of a methyl radical, a methoxy radical, a trifluoromethyl radical, a fluorine atom, a chlorine atom and a bromine atom.

7. Active substance combination according to claim 1, characterized in that Y represents an azole radical selected from the group consisting of

a) a pyrazole of the general formula (a):

in which R⁷ represents a linear or branched C_1-12 alkyl radical, a benzyl radical or a radical of the type;

in which n=1 or 2, and

R⁸ represents a hydrogen atom, a methyl radical or a halogen atom, preferably a hydrogen atom, a methyl radical, a bromine atom or a chlorine atom,

b) an imidazole of the general formula

in which R⁹ represents a hydrogen atom, a C_1-12 alkyl radical, a benzyl radical, or a radical of the general formula (b1);

R¹⁰—

(CH₂)_n—

 

 

(b1)

in which n is 2, 3 or 4 and R¹⁰ represents a piperidinyl radical, a phenyl radical, a cyano group, a hydroxyl radical, a carboxy radical, an amino group, a dimethylamino group, or a methyl ester (CH₃—

O—

C(═

O)—

) group,

and

(c) an imidazole of the following formula;

8. Active substance combination according to claim 1, characterized in that as component (A) at least one carbinol compound of general formula I

is present, wherein

R¹ represents a hydrogen atom, a methyl radical, an ethyl radical, an n-propyl radical, an iso-propyl radical, a sec-butyl radical, a tert-butyl radical, an n-butyl radical, a vinyl radical, a cyclohexyl radical, an N-methyl-piperidinyl group, or a phenyl group,

R² represents a hydrogen atom, a dimethylaminoethyl group, a pyrrolidinylethyl group, a piperidinylethyl group, a methyl-benzyl-aminoethyl group, a morpholinylethyl group, a diisopropylaminoethyl group, a dimethylaminopropyl group, a piperidinylpropyl group, a pyrrolidinylpropyl group, a morpholinylpropyl group, an N-methyl-2-piperidyl group, an N-ethyl-2-piperidyl group, an N-propyl-2-piperidyl group, an N-methyl-2-pyrrolidinyl group, an N-ethyl-2-pyrrolidinyl group, an N-propyl-2-pyrrolidinyl group, or a 2-dimethylaminoethyl-1-methyl group,

X represents a phenyl radical, a 2-methyl-phenyl radical, a 3-methyl-phenyl radical, a 4-methyl phenyl radical, a 2-chloro-phenyl radical, a 3-chloro-phenyl radical, a 4-chloro-phenyl radical, a 2-fluoro-phenyl radical, a 3-fluoro-phenyl radical, a 4-fluoro-phenyl radical, a 2-trifluoromethyl-phenyl radical, a 3-trifluoromethyl-phenyl radical, a 4-trifluoromethyl-phenyl radical, a 2-methoxy-phenyl radical, a 3-methoxy-phenyl radical, a 4-methoxy-phenyl radical, a 3,4,5-tris-methoxy phenyl radical, a 3,4-dichloro-phenyl radical, a 2,4-dichloro-phenyl radical, a thien-2-yl radical, a thien-3-yl radical, a 3-methyl-thien-2-yl radical, a 5-methyl-thien-2-yl-radical, a 5-bromo-thien-2-yl radical or a 4-bromo-thien-2-yl-radical,

Y represents an azole radical selected from the group consisting of

a) a pyrazole of the general formula (a):

in which

R⁷ represents a methyl radical, an ethyl radical, an n-propyl radical, an iso-propyl radical, an n-butyl radical, a sec-butyl radical or a tert-butyl radical,

R⁸ represents a hydrogen atom, a methyl radical, a bromine atom or a chlorine atom,

b) an imidazole of the general formula

in which R⁹ represents a hydrogen atom, a methyl radical, an ethyl radical, an n-propyl radical, an iso-butyl radical, an n-butyl radical, a sec-butyl radical a tert-butyl radical, an n-pentyl radical, an n-hexyl radical, an n-heptyl radical, an n-octyl radical, an n-nonyl radical, an n-decyl radical, an n-undecyl radical an n-dodecyl radical, a benzyl radical, or a radical of the general formula (b1);

R¹⁰—

(CH₂)_n—

 

 

(b1)

in which n is 2, 3 or 4 and R¹⁰ represents a piperidinyl radical, a phenyl radical, a cyano group, a hydroxyl radical, a carboxy radical, an amino group, a dimethylamino group, or a methyl ester group,

and

(c) an imidazole of the following formula;

optionally in form of one of its stereoisomers, preferably enantiomers or diastereomers, its racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate.

9. Active substance combination according to claim 1, characterised in that as component (A) one or more compounds selected from the group consisting of

[1] 2-{α

-[2-(dimethylamino)ethoxy]benzyl}-1-methyl-1H-imidazole,

[2] 2-{4-chloro-α

-[2-(dimethylamino)ethoxy]-α

-methylbenzyl}-1-methyl-1H-imidazole,

[3] 2-{4-chloro-α

-[2-(dimethylamino)ethoxy]benzyl}-1-methyl-1H-imidazole,

[4] 2-{3-chloro-α

-[2-(dimethylamino)ethoxy]benzyl}-1-methyl-1H-imidazole,

[5] 2-{4-chloro-α

-[2-(dimethylamino)ethoxy]-α

-methylbenzyl}-1-methyl-1H-imidazole,

[6] 2-{4-fluoro-α

-[2-(dimethylamino)ethoxy]-α

-methylbenzyl}-1-methyl-1H-imidazole,

[7] 2-{α

-[2-(dimethylamino)ethoxy]-α

-methyl-3-(trifluoromethyl)benzyl}-1-methyl-1H-imidazole,

[8] 2-{3-chloro-α

-[2-(dimethylamino)ethoxy]-α

-methylbenzyl}-1-methyl-1H-imidazole,

[9] 2-{3-chloro-α

-[2-(dimethylamino)ethoxy]-α

-propylbenzyl}-1-methyl-1H-imidazole,

[10] 1-butyl-2-{4-chloro-α

-[2-(dimethylamino)ethoxy]-α

-methylbenzyl}-1H-imidazole,

[11] 2-{α

-[2-(dimethylamino)ethoxy]-α

-methyl-4-methoxybenzyl)-1-methyl-1H-imidazole,

[12] 2-{3-chloro-α

-methyl-α

-[2-(N-pyrrolidinyl)ethoxy]benzyl}-1-methyl-1H-imidazole,

8 13] 2-{α

-[2-(dimethylamino)ethoxyl-α

-propyl-3,4,5-trimethoxybenzyl}-1-dodecyl-1H-imidazole,

[14] 1-butyl-2-{α

-[2-(dimethylamino)ethoxy]-4-(trifluoromethyl)benzyl}-1H-imidazole,

[15] 1-methyl-2-{α

-methyl-α

-[2-(N-piperidyl)ethoxy]-3-(trifluoromethyl)benzyl}-1H-imidazole,

[16] 2-{α

-cyclohexyl-3,4-dichloro-α

-[2-(dimethylamino)ethoxy]benzyl}-1-methyl-1H-imidazole,

[17] 2-{3,4-dichloro-α

-[2-(dimethylamino)ethoxy]-α

-propylbenzyl}-1-methyl-1H-imidazole,

[18] 2-{3,4-dichloro-α

-[2-(dimethylamino)ethoxy]-α

-methylbenzyl}-1-methyl-1H-imidazole,

[19] 2-{3,4-dichloro-α

-[2-(dimethylamino)ethoxy]benzyl}-1-methyl-1H-imidazole,

[20] 2-{4-chloro-α

-[2-(dimethylamino)ethoxy]-α

-methylbenzyl}-1-[2-(N-piperidyl)ethyl]-1H-imidazole,

[21] 2-{4-chloro-α

-[2-(dimethylamino)ethoxy]-α

-methylbenzyl}-1-[2-(N-piperidyl)propyl]-1H-imidazole,

[22] 1-(3-cyanopropyl)-2-{4-chloro-α

-[2-(dimethylamino)ethoxy]benzyl}-1H-imidazole,

[23] 2-{4-chloro-α

-[2-(dimethylamino)ethoxy]-α

-(N-methyl-4-piperidyl)benzyl}-1-methyl-1H-imidazole,

[24] 1-benzyl-2-{α

-[2-(N-benzyl-N-methylamino)ethoxy)-4-chlorobenzyl}-1H-imidazole,

[25] 2-{4-chloro-α

-[2-(dimethylamino)ethoxy]-α

-methylbenzyl}-7-methyl-6,7,8,9-tetrahydro-1H-imidazole[1,5-a][1,4]diazepine,

[26] 2-{4-chloro-α

-[2-(dimethylamino)ethoxy]benzyl}-7-methyl-6,7,8,9-tetrahydro-1H-imidazole[1,5-a] [1,4]diazepine,

[27] 1-butyl-5-{α

-[2-(dimethylamino)ethoxy]benzyl}-1H-pyrazole,

[28] 5-{α

-(4-chlorophenyl) -α

-[2-(dimethylamino)ethoxy]benzyl}-1-methyl-1H-pyrazole,

[29] 1-butyl-5-{α

-[2-(dimethylamino)ethoxy]-3,4,5-trimethoxybenzyl}-1H-pyrazole,

[30] 1-butyl-5-{4-chloro-α

-[2-(dimethylamino)ethoxy]-α

-methylbenzyl}-1H-pyrazole,

[31] 5-{α

-[2-(dimethylamino)ethoxy]benzyl}-1-methyl-1H-pyrazole,

[32] 5-{α

-[2-(dimethylamino)ethoxy]-α

-methylbenzyl}-1-methyl-1H-pyrazole,

[33] 5-{α

- [2-(dimethylamino)ethoxy]-3,4,5-trimethoxybenzyl}-1-methyl-1H-pyrazole,

[34] 1-methyl-5-{α

-[2-(N-pyrrolidinyl)ethoxy]benzyl)-1H-pyrazole,

[35] 1-methyl-5-{α

-[2-(N-morpholinyl)ethoxy]benzyl}-1H-pyrazole,

[36] 5-{α

-[2-(dimethylamino)ethoxy]-α

-methyl-3,4,5-trimethoxybenzyl}-1-methyl-1H-pyrazole,

[37] 4-bromo-5-{α

-[2-(dimethylamino)ethoxy]benzyl}-1-methyl-1H-pyrazole,

[38] 1,3-dimethyl-5-{α

-[2-(dimethylamino)ethoxy)-α

-methylbenzyl}-1H-pyrazole,

[39] 1,3-dimethyl-5-{a-[2-(dimethylamino)ethoxy]benzyl}-1H-pyrazole,

[40] 5-{a-[2-(dimethylamino)ethoxy]-2-methylbenzyl}-1-methyl-1H-pyrazole,

[41] 4-chloro-5-{4-chloro-α

-[2-(dimethylamino)ethoxy)benzyl}-1-methyl-1H-pyrazole,

[42] 5-{4-chloro-α

-[2-(dimethylamino)ethoxy]benzyl}-1-methyl-1H-pyrazole,

[43] 5-{3-chloro-α

-[2-(dimethylamino)ethoxy]benzyl}-1-methyl-1H-pyrazole,

[44] 5-{α

-[2-(dimethylamino)ethoxy]-4-methylbenzyl}-1-methyl-1H-pyrazole,

[45] 5-{2-chloro-α

-[2-(dimethylamino)ethoxy]benzyl}-1-methyl-1H-pyrazole,

[46] 1-methyl-5-{α

-[2-(N-piperidyl)ethoxy]benzyl}-1H-pyrazole,

[47] 1-methyl-5-{α

-[2-(N-propyl-2-piperidyl)ethoxy]benzyl}-1H-pyrazole,

[48] 5-{α

-[2-(N-ethyl-2-piperidyl)ethoxylbenzyl}-1-methyl-1H-pyrazole,

[49] 1-methyl-5-{α

-[2-(N-methyl-2-pyrrolidinyl)ethoxy]benzyl}-1H-pyrazole,

[50] 5-{α

-[2-(diisopropylamino)ethoxy]benzyl}-1-methyl-1H-pyrazole,

[51] 1-methyl-5-{α

-[2-(N-methyl-2-piperidyl)ethoxyl]benzyl}-1H-pyrazole,

[52] 2-{4-chloro-α

-[3-(dimethylamino)propoxy]-α

-methylbenzyl}-1-methyl-1H-imidazole,

[53] 2-{3-chloro-α

-[3-(dimethylamino)propoxy]benzyl}-1-methyl-1H-imidazole,

[54] 2-{4-chloro-α

-[3-(dimethylamino)propoxy)-α

-ethylbenzyl}-1-methyl-1H-imidazole,

[55] 2-{α

-butyl-3-chloro-α

-[3-(dimethylamino)propoxy]benzyl}-1-methyl-1H-imidazole,

[56] 2-{α

-cyclohexyl-4-chloro-α

-[3-(dimethylamino)propoxy]benzyl}-1-methyl-1H-imidazole,

[57] 2-{α

-[3-(dimethylamino)propoxy]-4-fluoro-α

-methylbenzyl}-1-methyl-1H-imidazole,

[58] 2-{α

-[3-(dimethylamino)propoxy) -α

-methyl-3-(trifluoromethyl)benzyl}-1-methyl-1H-imidazole,

[59] 2-{2-chloro-α

-[3-(dimethylamino)propoxy]-α

-methylbenzyl}-1-methyl-1H-imidazole,

[60] 2-{3-chloro-α

-[3-(dimethylamino)propoxyl-α

-methylbenzyl}-1-methyl-1H-imidazole,

[61] 2-{α

-[3-(dimethylamino)propoxy]-α

-methyl-3,4,5-trimethoxybenzyl}-1-methyl-1H-imidazole,

[62] 2-{α

-[3-(dimethylamino)propoxy]-α

-methyl-4-methoxybenzyl}-1-methyl-1H-imidazole,

[63] 2-{4-chloro-α

-[3-(dimethylamino)propoxy]benzyl}-1-methyl-1H-imidazole,

[64] 2-{α

-[3-(dimethylamino)propoxy]-3,4,5-trimethoxybenzyl}-1-methyl-1H-imidazole,

[65] 2-{α

-[3-(dimethylamino)propoxy]-α

-methyl-4-(trifluoromethyl)benzyl}-1-methyl-1H-imidazole,

[66] 2-{α

-[3-(dimethylamino)propoxy)-3-(trifluoromethyl)benzyl)-1-methyl-1H-imidazole,

[67] 2-{α

-[3-(dimethylamino)propoxy)-4-(trifluoromethyl)benzyl}-1-methyl-1H-imidazole,

[68] 2—

{α

-[3-(dimethylamino)propoxy]-4-methoxybenzyl}-1-methyl-1H-imidazole,

[69] 2-{α

-butyl-α

-[3-(dimethylamino)propoxy]-3-(trifluoromethyl)benzyl}-1-methyl-1H-imidazole,

[70] 1-butyl-2-{4-chloro-α

-[3-(dimethylamino)propoxy)-α

-methylbenzyl}-1H-imidazole,

[71] 1-butyl-2-{α

-butyl-α

-[3-(dimethylamino)propoxy]-3,4,5-trimethoxybenzyl}-1H-imidazole,

[72] 1-butyl-2-{α

-butyl-2-chloro-α

-[3-(dimethylamino)propoxy]benzyl}-1H-imidazole,

[73] 1-butyl-2-{α

-butyl-2,4-dichloro-α

-[3-(dimethylamino)propoxy]benzyl}-1H-imidazole,

[74] 1-butyl-2-{α

-[3-(dimethylamino)propoxy]-4-(trifluoromethyl)benzyl}-1H-imidazole,

[75] 2-{4-chloro-α

-[3-(N-piperidyl)propoxy]benzyl}-1-methyl-1H-imidazole,

[76] 1-methyl-2-{α

-methyl-α

-[3-(N-piperidyl)propoxy]-4-(trifluoromethyl)benzyl}-1H-imidazole,

[77] 2-{α

-butyl-2-chloro-α

-[3-(dimethylamino)propoxy)benzyl}-1-methyl-1H-imidazole,

[78] 2-{α

-butyl-3,4-dichloro-α

-[3-(dimethylamino)propoxy]benzyl}-1-methyl-1H-imidazole,

[79] 2-{3,4-dichloro-α

-[3-(dimethylamino)propoxy]-α

-methylbenzyl}-1-methyl-1H-imidazole,

[80] 2-{3,4-dichloro-α

-[3-(dimethylamino)propoxy]benzyl}-1-methyl-1H-imidazole,

[81] 2-{α

-cyclohexyl-3,4-dichloro-α

-[3-(dimethylamino)propoxy]benzyl}-1-methyl-1H-imidazole,

[82] 2-{4-chloro-α

-[3-(dimethylamino)propoxy)-α

-methylbenzyl}-α

-[2-(N-piperidyl)ethyl]-1H-imidazole,

[83] 2-{4-chloro-α

-[3-(dimethylamino)propoxy]-α

-methylbenzyl}-1-[2-(N-piperidyl) propyl]-1H-imidazole,

[84] 2-{4-chloro-α

-[3-(dimethylamino)propoxyl-α

-(N-methyl-4-piperidyl)benzyl}-1-methyl-1H-imidazole,

[85] 1-butyl-5-{α

-[3-(dimethylamino)propoxylbenzyl}-1H-pyrazole,

[86] 1-butyl-5-{4-chloro-α

-[3-(dimethylaminb)propoxy]-α

-methylbenzyl}-1H-pyrazole,

[87] 5-{α

-[3-(dimethylamino)propoxy)benzyl)-1-methyl-1H-pyrazole,

[88] 5-{α

-[3-(dimethylamino)propoxy]-α

-methylbenzyl}-1-methyl-1H-pyrazole,

[89] 1,3-dimethyl-5-{α

-[3-(dimethylamino)propoxy)-α

-methylbenzyl}-1H-pyrazole,

[90] 1,3-dimethyl-5-{α

-[3-(dimethylamino)propoxy]benzyl}-1H-pyrazole,

[91] 5-{α

-[3-(dimethylamino)propoxy]-2-methylbenzyl}-1-methyl-1H-pyrazole,

[92] 5-chloro-5-{4-chloro-α

-[3-(dimethylamino)propoxy)benzyl}-1-methyl-1H-pyrazole,

[93] 1-methyl-5-{α

-[3-(N-piperidyl)propoxy]benzyl}-1H-pyrazole,

[94] 1-methyl-5-{α

-[3-(N-pyrrolidinyl)propoxy]benzyl}-1H-pyrazole,

[95] 4-{4-chloro-α

-[2-(dimethylamino)ethoxy]benzyl}-1-methyl-1H-pyrazole,

[96] 4-{4-chloro-α

-[2-(dimethylamino)ethoxy]-α

-methylbenzyl}-1-methyl-1H-pyrazole,

[97] 4-{4-chloro-α

-[2-(N-propyl-2-piperidyl)ethoxy]benzyl}-1-methyl-1H-pyrazole,

[98] 4-{4-chloro-α

-[2-(N-methyl-2-piperidyl)ethoxy]benzyl}-1-methyl-1H-pyrazole,

[99] 4-{4-chloro-α

-[2-(N-ethyl-2-piperidyl)ethoxy]benzyl}-1-methyl-1H-pyrazole,

[100] 4-{4-chloro-α

-[2-(diisopropylamino)ethoxy]benzyl}-1-methyl-1H-pyrazole,

[101] 4-{4-chloro-(-[2-(N-methyl-2-pyrrolidinyl)ethoxy]benzyl}-1-methyl-1H-pyrazole,

[102] 4-{α

-[3-(dimethylamino)propoxy]benzyl}-1-methyl-1H-pyrazole,

[103] 4-{4-chloro-α

-[3-(N-morpholinyl)propoxy]benzyl}-1-methyl-1H-pyrazole,

[104] 4-{4-chloro-α

-[3-(N-pyrrolidinyl)propoxy]benzyl}-1-methyl-1H-pyrazole,

[105] 2-(α

-hydroxybenzyl)-1H-imidazole,

[106] 2-(4-chloro-α

-hydroxybenzyl)-1H-imidazole,

[107] 2-(4-chloro-α

-hydroxybenzyl)-1-methyl-1H-imidazole,

[108] 2-(3-chloro-α

-hydroxybenzyl)-1-methyl-1H-imidazole,

[109] 2-(4-fluoro-α

-hydroxybenzyl)-1-methyl-1H-imidazole,

[110] 2-[α

-hydroxy-3-(trifluoromethyl)benzyl]-1-methyl-1H-imidazole,

[111] 2-[α

-hydroxy-4-(trifluoromethyl)benzyl)-1-methyl-1H-imidazole,

[112] 2-(α

-hydroxy-3,4,5-trimethoxybenzyl)-1-methyl-1H-imidazole,

[113] 2-(3,4-dichloro-α

-hydroxybenzyl)-1-methyl-1H-imidazole,

[114] 1-butyl-2-[α

-hydroxy-4-(trifluoromethyl)benzyl]-1H-imidazole,

[115] 1-butyl-2-(3,4-dichloro-α

-hydroxybenzyl)-1H-imidazole,

[116] 1-butyl-2-(4-chloro-α

-hydroxybenzyl)-1H-imidazole,

[117] 1-butyl-2-(α

-hydroxy-3,4,5-trimethoxybenzyl)-1H-imidazole,

[118] 1-dodecyl-2-(α

-hydroxy-3,4,5-trimethoxybenzyl)-1H-imidazole,

[119] 2-(α

-butyl-3-chloro-α

-hydroxybenzyl)-1-methyl-1H-imidazole,

[120] 2-(3-chloro-α

-hydroxy-α

-methylbenzyl)-1-methyl-1H-imidazole,

[121] 2-(4-chloro-α

-hydroxy-α

-methylbenzyl)-1-methyl-1H-imidazole,

[122] 2-[4-chloro-α

-hydroxy-α

-(N-methyl-4-piperidyl)benzyl]-1-methyl-1H-imidazole,

[123] 2-(4-chloro-α

-ethyl-α

-hydroxybenzyl)-1-methyl-1H-imidazole,

[124] 2-(α

-butyl-4-chloro-α

-hydroxybenzyl)-1-methyl-1H-imidazole,

[125] 2-(α

-cyclohexyl-4-chloro-α

-hydroxybenzyl)-1-methyl-1H-imidazole,

[126] 2-(2-chloro-α

-hydroxy-α

-methylbenzyl)-1-methyl-1H-imidazole,

[127] 2-(α

-butyl-2-chloro-α

-hydroxybenzyl)-1-methyl-1H-imidazole,

[128] 2-[α

-hydroxy-α

-methyl-3-(trifluoromethyl)benzyl]-1-methyl-1H-imidazole,

[129] 2-[α

-butyl-α

-hydroxy-3-(trifluoromethyl)benzyl]-1-methyl-1H-imidazole,

[130] 2-[α

-cyclohexyl-α

-hydroxy-3-(trifluoromethyl)benzyl)-1-methyl-1H-imidazole,

[131] 2-[α

-hydroxy-α

-methyl-4-(trifluoromethyl)benzyl]-1-methyl-1H-imidazole,

[132] 2-(4-fluoro-α

-hydroxy-α

-methylbenzyl)-1-methyl-1H-imidazole,

[133] 2-(α

-hydroxy-α

-methyl-4-methoxybenzyl)-1-methyl-1H-imidazole,

[134] 2-(3,4-dichloro-α

-hydroxy-α

-methylbenzyl)-1-methyl-1H-imidazole,

[135] 2-(α

-butyl-3,4-dichloro-α

-hydroxybenzyl)-1-methyl-1H-imidazole,

[136] 2-(α

-cyclohexyl-3,4-dichloro-α

-hydroxybenzyl)-1-methyl-1H-imidazole,

[137] 2-(α

-hydroxy-α

-methyl-3,4,5-trimethoxybenzyl)-1-methyl-1H-imidazole,

[138] 1-butyl-2-(4-chloro-α

-hydroxy-α

-methylbenzyl)-1H-imidazole,

[139] 1-butyl-2-(α

-butyl-4-chloro-α

-hydroxybenzyl]-1H-imidazole,

[140] 1-butyl-2-[4-chloro-α

-hydroxy-α

-(N-methyl-4-piperidyl)benzyl]-1H-imidazole,

[141] 1-butyl-2-(α

-butyl-α

-hydroxy-3,4,5-trimethoxybenzyl)-1H-imidazole,

[142] 1-butyl-2-(α

-butyl-2-chloro-α

-hydroxybenzyl)-1H-imidazole,

[143] 1-butyl-2-[α

-ethyl-α

-hydroxy-3-(trifluoromethyl)benzyl]-1H-imidazole,

[144] 1-butyl-2-(α

-butyl-2,4-dichloro-α

-hydroxybenzyl)-1H-imidazole,

[145] 2-(4-chloro-α

-hydroxy-α

-methylbenzyl)-1-[2-(N-piperidyl)ethyl]-1H-imidazole,

[146] 2-(4-chloro-α

-hydroxy-α

-methylbenzyl)-1-(3-dimethylaminopropyl)-1H-imidazole,

[147] 2-(α

-butyl-α

-hydroxy-3,4,5-trimethoxybenzyl)-1-dodecyl-1H-imidazole,

[148] 1-benzyl-2-[α

-butyl-α

-hydroxy-3-(trifluoromethyl)benzyl]-1H-imidazole,

[149] 1-benzyl-2-(4-chloro-α

-hydroxy-α

-methylbenzyl)-1H-imidazole,

[150] 1-(2-cyanoethyl)-2-(4-chloro-α

-hydroxybenzyl)-1H-imidazole,

[151] 1-(3-aminopropyl)-2-(4-chloro-α

-hydroxybenzyl)-1H-imidazole,

[152] 3-[2-(3-chloro-α

-hydroxybenzyl)-1H-imidazole-1-yl]propanoic acid,

[153] 2-(4-chloro-α

-hydroxybenzyl)-1-(3-hydroxypropyl)-1H-imidazole,

[154) 3-[2-(3-chloro-α

-hydroxybenzyl)-1H-imidazole-1-yl]methyl-propanoate,

[155] 2-(α

-hydroxybenzyl)-1-(3-hydroxypropyl)-1H-imidazole,

[156] 2-(α

-hydroxy-4-methylbenzyl)-1-(3-hydroxypropyl)-1H-imidazole,

[157] 2-(α

-hydroxy-4-methoxybenzyl)-1-(3-hydroxypropyl)-1H-imidazole,

[158] 2-(3,4-dichloro-α

-hydroxybenzyl)-1-(3-hydroxypropyl)-1H-imidazole,

[159] 3-{2-(α

-hydroxybenzyl)-1H-imidazole-1-yll}-methyl propanoate,

[160] 2-(4-chloro-a-hydroxybenzyl)-1-(4-hydroxybutyl)-1H-imidazole,

[161] 1-(3-cyanopropyl)-2-(4-chloro-α

-hydroxybenzyl)-1H-imidazole,

[162] 4-[2-(4-chloro-α

-hydroxybenzyl)-1H-imidazole-1-yl]butanoic acid,

[163] 4-[2-(4-chloro-α

-hydroxybenzyl)-1H-imidazole-1-yl]-methyl butanoate,

[164] 1-butyl-5-(α

-hydroxybenzyl)-1H-pyrazole,

[165] 5-(4-chloro-α

-hydroxybenzyl)-1-methyl-1H-pyrazole,

[166] 5-(α

-hydroxy-3,4,5-trimethoxybenzyl)-1-methyl-1H-pyrazole,

[167] 1-butyl-5-(α

-hydroxy-3,4,5-trimethoxybenzyl)-1H-pyrazole,

[168] 4-bromo-5-(α

-hydroxybenzyl)-1-methyl-1H-pyrazole,

[169] 5-[α

-(4-chlorophenyl)-α

-hydroxybenzyl]-1-methyl-1H-pyrazole,

[170] 1-butyl-5-(4-chloro-α

-hydroxy-α

-methylbenzyl)-1H-pyrazole,

[171] 5-(α

-hydroxy-α

-methylbenzyl)-1-methyl-1H-pyrazole,

[172] 5-(α

-hydroxy-α

-methyl-3,4,5-trimethoxybenzyl)-1-methyl-1H-pyrazole,

[173] 1,3-dimethyl-5-(α

-hydroxy-α

-methylbenzyl)-1H-pyrazole,

[174] 1-butyl-5-(α

-hydroxy-α

-vinylbenzyl)-1H-pyrazole,

[175] 1-butyl-5-(4-chloro-α

-hydroxy-α

-vinylbenzyl)-1H-pyrazole,

[176] 4-chloro-5-(α

-hydroxybenzyl)-1-methyl-1H-pyrazole,

[177] 5-(α

-hydroxy-2-methylbenzyl)-1-methyl-1H-pyrazole,

[178] 5-(3-chloro-α

-hydroxybenzyl)-1-methyl-1H-pyrazole,

[179] 5-(α

-hydroxy-4-methylbenzyl)-1-methyl-1H-pyrazole,

[180] 5-(2-chloro-α

-hydroxybenzyl)-1-methyl-1H-pyrazole,

[181] 5-(α

-hydroxy-4-methoxybenzyl)-1-methyl-1H-pyrazole,

[182] 5-{α

-[2-(dimethylamino)ethoxy]-2-thienylmethyl}-1-methyl-1H-pyrazole,

[183] 5-{α

-[2-(dimethylamino)ethoxy]-2-thienylmethyl)-1-methyl-1H-pyrazole citrate,

[184] 5-{(-[2-(dimethylamino)ethoxy]-3-thienylmethyl}-1-methyl-1H-pyrazole,

[185] 2-{α

-[2-(dimethylamino)ethoxy]-2-thienylmethyl}-1-methyl-1H-imidazole,

[186] 5-{α

-[2-(dimethylamino)ethoxy]-3-methyl-2-thienylmethyl}-1-methyl-1H-pyrazole,

[187] 5-{α

-[2-(dimethylamino)ethoxyl-5-methyl-2-thienylmethyl}-1-methyl-1H-pyrazole,

[188] 5-{5-bromo-α

-[2-(dimethylamino)ethoxy]-2-thienylmethyl}-1-methyl-1H-pyrazole,

[189] 5-{4-bromo-α

-[2-(dimethylamino)ethoxy]-2-thienylmethyl}-1-methyl-1H-pyrazole,

[190] 5-{α

-(2-(dimethylamino)ethoxy]-α

-methyl-2-thienylmethyl}-1-methyl-1H-pyrazole,

[191] 5-{α

-[2-(dimethylamino)ethoxy]benzyl}-1-methyl-1H-pyrazole citrate,

[192] (±

)-5-{α

-[2-(dimethylamino)-1-(methyl)ethoxy]benzyl}-1-methyl-1H-pyrazole,

[193] (±

)-5-{α

-[2-(dimethylamino)-1-(methyl)ethoxy]benzyl}-1-methyl-1H-pyrazole,

[194] (+)-5-{α

-[2-(dimethylamino)ethoxy]-2-thienylmethyl}-1-methyl-1H-pyrazole,

[195] (−

)-5-{α

-[2-(dimethylamino)ethoxy]-2-thienylmethyl}-1-methyl-1H-pyrazole,

[196] (+)-5-{α

-[2-(dimethylamino)ethoxy]-2-thienylmethyl}-1-methyl-1H-pyrazole citrate,

[197] (−

)-5-{α

-[2-(dimethylamino)ethoxy]-2-thienylmethyl}-1-methyl-1H-pyrazole citrate,

[198] (+)-5-{α

-[2-(dimethylamino)ethoxy]-2-thienylmethyl}-1-methyl-1H-pyrazole-D-ditoluyltartrate,

[199] (−

)-5-{α

-[2-(dimethylamino)ethoxyl-2-thienylmethyl}-1-methyl-1H-pyrazole D-ditoluyltartrate,

[200] (+)-5-{α

-[2-(dimethylamino)ethoxy]benzyl}-1-methyl-1H-pyrazole citrate,

[201] (−

)-5-{α

-[2-(dimethylamino)ethoxy]benzyl)-1-methyl-1H-pyrazole citrate,

[202] 5-(α

-hydroxy-2-thienylmethyl)-1-methyl-1H-pyrazole,

[203] 5-(α

-hydroxy-3-methyl-2-thienylmethyl)-1-methyl-1H-pyrazole,

[204] 5-(α

-hydroxy-5-methyl-2-thienylmethyl)-1-methyl-1H-pyrazole,

[205] 5-(5-bromo-α

-hydroxy-2-thienylmethyl)-1-methyl-1H-pyrazole,

[206] 5-(4-bromo-α

-hydroxy-2-thienylmethyl)-1-methyl-1H-pyrazole and

[207] 5-(α

-hydroxy-α

-methyl-2-thienylmethyl)-1-methyl-1H-pyrazole

are present.

10. Active substance combination according to claim 1, characterized in that as component (b) one or more nonsteroidal anti-inflammatory drugs are present, which are selected from the group consisting of Acemetacin, Acetylsalicylic acid, Bufexamac, Diclofenac, Diflunisal, Ethenzamide, Etofenamate, Fenbufen, Fenoprofen, Feprazone, Flobufen, Flufenamic acid, Flurbiprofen, Ibuprofen, Indomethacin, Isoxicam, Kebuzone, Ketoprofen, Ketorolac, Lonazolac, Lornoxicam, Meclofenamic acid, Mefenamic acid, Metamizol, Mofebutazone, Nabumetone, Naproxen, Niflumic acid, Oxaprozin, Oxyphenbutazone, Paracetamol, Phenidine, Phenylbutazone, Piroxicam, Propacetamol, Propyphenazone, Salicylamide, Sulindac, Tenoxicam, Tiaprofenic acid, Tolmetin, Celecoxib, Etodolac, Etoricoxib, Meloxicam, Nimesulide, Parecoxib, Rofecoxib, Valdecoxib and physiologically acceptable salts thereof.

11. Active substance combination according to claim 10, characterized in that as component (b) one or more one or more nonsteroidal anti-inflammatory drugs are present, which are selected from the group consisting of Acemetacin, Acetylsalicylic acid, Bufexamac, Diclofenac, Diflunisal, Ethenzamide, Etofenamate, Fenbufen, Fenoprofen, Feprazone, Flobufen, Flufenamic acid, Flurbiprofen, Ibuprofen, Indomethacin, Isoxicam, Kebuzone, Ketoprofen, Ketorolac, Lonazolac, Lomoxicam, Meclofenamic acid, Mefenamic acid, Metamizol, Mofebutazone, Nabumetone, Naproxen, Niflumic acid, Oxaprozin, Oxyphenbutazone, Paracetamol, Phenidine, Phenylbutazone, Piroxicam, Propacetamol, Propyphenazone, Salicylamide, Sulindac, Tenoxicam, Tiaprofenic acid, Tolmetin, Etodolac, Meloxicam, Nimesulide and physiologically acceptable salts thereof.

12. Active substance combination according to claim 10, characterized in that as component (b) one or more one or more nonsteroidal anti-inflammatory drugs are present, which are selected from the group consisting of Acemetacin, Acetylsalicylic acid, Bufexamac, Diclofenac, Diflunisal, Ethenzamide, Etofenamate, Fenbufen, Fenoprofen, Feprazone, Flobufen, Flufenamic acid, Flurbiprofen, Ibuprofen, Indomethacin, Isoxicam, Kebuzone, Ketoprofen, Ketorolac, Lonazolac, Lomoxicam, Meclofenamic acid, Mefenamic acid, Metaminzol, Mofebutazone, Nabumetone, Naproxen, Niflumic acid, Oxaprozin, Oxyphenbutazone, Paracetamol, Phenidine, Phenylbutazone, Piroxicam, Propacetamol, Propyphenazone, Salicylamide, Sulindac, Tenoxicam, Tiaprofenic acid, Tolmetin and physiologically acceptable salts thereof, preferably selected from the group consisting of Acetylsalicylic acid, Diclofenac, Ibuprofen, Naproxen and physiologically acceptable salts thereof, more preferably selected from the group consisting of Diclofenac, Ibuprofen, Naproxen and physiologically acceptable salts thereof.

13. Active substance combination according to claim 1, characterized in that the molar ratio of component (A) to component (B) is in the range of 1:

10 to 10;

1, preferably from 1;

4 to 4;

1.

14. Active substance combination according to claim 1, characterized in that component (A) and component (B) are at least partially present as a salt formed from these components.

15. Active substance combination according to claim 1, characterized in that component (A) and component (B) are present in form of a 1:

1 salt.

16. Active substance combination according to claim 15, characterized in that the salt is selected from the group consisting of

(a) R-(+)-5-[α

- [2-(Dimethylamino)ethoxylbenzyl]-1-methyl-1H-pyrazole naproxenate (R-(+)-Cizolirtine naproxenate),

(b) S-(−

)-5-[α

- [2-(Dimethylamino)ethoxy]benzyl]-1-methyl-1H-pyrazole naproxenate(S-(−

)-Cizolirtine naproxenate),

(c) R-(+)-5-[α

-[2-(Dimethylamino)ethoxy]benzyl]-1-methyl-1H-pyrazole diclofenacate (R-(+)-Cizolirtine diclofenacate),

(d) S-(−

)-5-[α

-[2-(Dimethylamino)ethoxy]benzyl]-1-methyl-1H-pyrazole diclofenacate (R-(+)-Cizolirtine diclofenacate),

(e) R-(+)-5-[α

-[2-(Dimethylamino)ethoxy]benzyl]-1-methyl-1H-pyrazole S-(+)-ibuprofenate (R-(+)-Cizolirtine S-(+)-ibuprofenate) and

(f) S-(−

)-5-[α

-[2-(Dimethylamino)ethoxy]benzyl]-1-methyl-1H-pyrazole S-(+) ibuprofenate (R-(+)-Cizolirtine S-(+)-ibuprofenate).

17. Active substance combination according to claim 1, characterized in that it further comprises as component (C) at least one agent, which is suitable to prevent the abuse of component (A) and/or component (B).

18. Active substance combination according to claim 17, characterized in that said agent(s) of component (C) is selected from the group consisting of aversive agents and/or gelling agents.

19. Medicament comprising an active substance combination according claim 1 and optionally at least one further active substance and/or optionally at least one auxiliary substance.

20. Medicament according to claim 19 for the treatment of pain, whereby said pain is preferably selected from the group consisting of neuropathic pain, acute pain, chronic pain, post-operative pain, chronic lower back pain, cluster headaches, herpes neuralgia, phantom limb pain, central pain, dental pain, resistant pain, visceral pain, surgical pain, bone injury pain, pain during labor and delivery, pain resulting from burns, pain resulting from sunburns, post partum pains, migraine, angina pain, genitourinary tract-related pain, pain from cystitis and nociceptive pain, for the prophylaxis and/or treatment of neurogenic inflammation, for the prophylaxis and/or treatment of urinary incontinence, for the prophylaxis and/or treatment of depression, for the prophylaxis and/or treatment of inflammation and/or for the prophylaxis and/or treatment of inflammation related disorders, whereby said inflammation-related disorders may preferably be selected from the group consisting of arthritis, rheumatoid arthritis, spondyloarthropathies, gouty arthritis, osteoarthritis, systemic lupus erythematosus, juvenile arthritis, rheumatic fever, symptoms associated with influenza or other viral infections, common cold, lower back pain, neck pain, dysmenorrhea, headache, toothache, sprains, strains, myositis, neuralgia, synovitis, gout, ankylosing spondylitis, bursitis, edema, inflammations following dental procedures, inflammations following dental procedures, vascular diseases, migraine headaches, periarteritis nodosa, thyroiditis, aplastic anemia, Hodkin'"'"'s disease, sclerodoma, type I diabetes, myasthenia gravis, sarcoidosis, nephrotic syndrome, Behcet'"'"'s syndrome, polymyositis, gingivitis, hypersensivity, conjunctivitis, swelling ocurring after injury and myocardia ischemia, for the prophylaxis and/or treatment of asthma, for the prophylaxis and/or treatment of bronchitis, for the prophylaxis and/or treatment of tendinitis, for the prophylaxis and/or treatment of bursitis, for the prophylaxis and/or treatment of skin related conditions, whereby said skin related conditions may preferably be selected from the group consisting of psoriasis, eczema, burns and dermatitis, for the prophylaxis and/or treatment of gastrointestinal disorders, whereby said gastrointestinal disorders may preferably be selected from the group consisting of inflammatory bowel disease, Crohn'"'"'s disease, gastritis, irritable bowel syndrome and ulcerative colitis, or for treatment of fever, or for the prophylaxis and/or treatment of cancer or a cancer-related disorders, whereby said cancer or related disorder may preferably be selected from the group consisting of brain cancer, bone cancer, epithelial cell-derived neoplasia (epithelial carcinoma), basal cell carcinoma, adenocarcinoma, gastrointestinal cancer, lip cancer, colon cancer, liver cancer, bladder cancer, pancreas cancer, ovary cancer, cervical cancer, lung cancer, breast cancer, skin cancer, squamous cell cancer, prostate cancer, renal cell carcinoma and other known cancers that effect epithelial cells throughout the body, for the prophylaxis and/or treatment of polyps, for the prophylaxis and/or treatment of angiogenesis mediated disorders, preferably selected from the group consisting of metastasis, corneal graft rejection, ocular neovascularization, retinal neovascularisation, diabethic retinopathy, retrolental flbroplasia, neovascular glaucoma, gastric ulcer, infantile hemaginomas, angiofibroma of the nasopharynx, avascular necrosis of the bone and endometriosis.

21. Medicament according to claim 19 for the treatment of pain, whereby said pain is preferably selected from the group consisting of neuropathic pain, acute pain, chronic pain, post-operative pain, chronic lower back pain, cluster headaches, herpes neuralgia, phantom limb pain, central pain, dental pain, resistant pain, visceral pain, surgical pain, bone injury pain, pain during labor and delivery, pain resulting from burns, pain resulting from sunburns, post partum pains, migraine, angina pain, genitourinary tract-related pain, pain from cystitis and nociceptive pain.

22. Medicament according to claim 19 for the prophylaxis and/or treatment of inflammation and/or for the prophylaxis and/or treatment of inflammation related disorders, whereby said inflammation-related disorders may preferably be selected from the group consisting of arthritis, rheumatoid arthritis, spondyloarthropathies, gouty arthritis, osteoarthritis, systemic lupus erythematosus, juvenile arthritis, rheumatic fever, symptoms associated with influenza or other viral infections, common cold, lower back pain, neck pain, dysmenorrhea, headache, toothache, sprains, strains, myositis, neuralgia, synovitis, gout, ankylosing spondylitis, bursitis, edema, inflammations following dental procedures, inflammations following dental procedures, vascular diseases, migraine headaches, periarteritis nodosa, thyroiditis, aplastic anemia, Hodkin'"'"'s disease, sclerodoma, type I diabetes, myasthenia gravis, sarcoidosis, nephrotic syndrome, Behcet'"'"'s syndrome, polymyositis, gingivitis, hypersensivity, conjunctivitis, swelling ocurring after injury and myocardia ischemia.

23. Use of an active substance combination according to claim 1 for the manufacture of a medicament for the treatment of pain, whereby said pain is preferably selected from the group consisting of neuropathic pain, acute pain, chronic pain, post-operative pain, chronic lower back pain, cluster headaches, herpes neuralgia, phantom limb pain, central pain, dental pain, resistant pain, visceral pain, surgical pain, bone injury pain, pain during labor and delivery, pain resulting from burns, pain resulting from sunburns, post partum pains, migraine, angina pain, genitourinary tract-related pain, pain from cystitis and nociceptive pain, for the prophylaxis and/or treatment of urinary incontinence, for the prophylaxis and/or treatment of neurogenic inflammation for the prophylaxis and/or treatment of depression, for the prophylaxis and/or treatment of inflammation and/or for the prophylaxis and/or treatment of inflammation related disorders, whereby said inflammation-related disorders may preferably be selected from the group consisting of arthritis, rheumatoid arthritis, spondyloarthropathies, gouty arthritis, osteoarthritis, systemic lupus erythematosus, juvenile arthritis, rheumatic fever, symptoms associated with influenza or other viral infections, common cold, lower back pain, neck pain, dysmenorrhea, headache, toothache, sprains, strains, myositis, neuralgia, synovitis, gout, ankylosing spondylitis, bursitis, edema, inflammations following dental procedures, inflammations following dental procedures, vascular diseases, migraine headaches, periarteritis nodosa, thyroiditis, aplastic anemia, Hodkin'"'"'s disease, sclerodoma, type I diabetes, myasthenia gravis, sarcoidosis, nephrotic syndrome, Behcet'"'"'s syndrome, polymyositis, gingivitis, hypersensivity, conjunctivitis, swelling ocurring after injury and myocardia ischemia, for the prophylaxis and/or treatment of asthma, for the prophylaxis and/or treatment of bronchitis, for the prophylaxis and/or treatment of tendinitis, for the prophylaxis and/or treatment of bursitis, for the prophylaxis and/or treatment of skin related conditions, whereby said skin related conditions may preferably be selected from the group consisting of psoriasis, eczema, burns and dermatitis, for the prophylaxis and/or treatment of gastrointestinal disorders, whereby said gastrointestinal disorders may preferably be selected from the group consisting of inflammatory bowel disease, Crohn'"'"'s disease, gastritis, irritable bowel syndrome and ulcerative colitis, or for treatment of fever, or for the prophylaxis and/or treatment of cancer or a cancer-related disorders, whereby said cancer or related disorder may preferably be selected from the group consisting of brain cancer, bone cancer, epithelial cell-derived neoplasia (epithelial carcinoma), basal cell carcinoma, adenocarcinoma, gastrointestinal cancer, lip cancer, colon cancer, liver cancer, bladder cancer, pancreas cancer, ovary cancer, cervical cancer, lung cancer, breast cancer, skin cancer, squamous cell cancer, prostate cancer, renal cell carcinoma and other known cancers that effect epithelial cells throughout the body, for the prophylaxis and/or treatment of polyps, for the prophylaxis and/or treatment of angiogenesis mediated disorders, preferably selected from the group consisting of metastasis, comeal graft rejection, ocular neovascularization, retinal neovascularisation, diabethic retinopathy, retrolental fibroplasia, neovascular glaucoma, gastric ulcer, infantile hemaginomas, angiofibroma of the nasopharynx, avascular necrosis of the bone and endometriosis.

24. Use according to claim 23 for the manufacture of a medicament for the treatment of pain, whereby said pain is preferably selected from the group consisting of neuropathic pain, acute pain, chronic pain, post-operative pain, chronic lower back pain, cluster headaches, herpes neuralgia, phantom limb pain, central pain, dental pain, resistant pain, visceral pain, surgical pain, bone injury pain, pain during labor and delivery, pain resulting from burns, pain resulting from sunburns, post partum pains, migraine, angina pain, genitourinary tract-related pain, pain from cystitis and nociceptive pain.

25. Use according to claim 23 for the manufacture of a medicament for the prophylaxis and/or treatment of inflammation and/or for the prophylaxis and/or treatment of inflammation related disorders, whereby said inflammation-related disorders may preferably be selected from the group consisting of arthritis, rheumatoid arthritis, spondyloarthropathies, gouty arthritis, osteoarthritis, systemic lupus erythematosus, juvenile arthritis, rheumatic fever, symptoms associated with influenza or other viral infections, common cold, lower back pain, neck pain, dysmenorrhea, headache, toothache, sprains, strains, myositis, neuralgia, synovitis, gout, ankylosing spondylitis, bursitis, edema, inflammations following dental procedures, inflammations following dental procedures, vascular diseases, migraine headaches, periarteritis nodosa, thyroiditis, aplastic anemia, Hodkin'"'"'s disease, sclerodoma, type I diabetes, myasthenia gravis, sarcoidosis, nephrotic syndrome, Behcet'"'"'s syndrome, polymyositis, gingivitis, hypersensivity, conjunctivitis, swelling ocurring after injury and myocardia ischemia.

26. Pharmaceutical formulation comprising an active substance combination according to claim 1 and optionally at least one further active substance and/or optionally at least one auxiliary.

27. Pharmaceutical formulation according to claim 26, characterized in that it is suitable for oral or parenteral administration, preferably for oral, intravenous, intraperitoneal, intramuscular, subcutaneous, intrathekal, rectal, transdermal, transmucosal or nasal administration.

28. Pharmaceutical formulation for oral administration according to claim 27, characterized in that it is in the form of a tablet, a drageé

, a capsule, drops, a gel, juice, sirup, solution or suspension.

29. Pharmaceutical formulation for oral administration according to claim 27, characterized in that is in form of multiparticulates, preferably pellets or granules, optionally compressed into a tablet, filled into a capsule or suspended in a suitable liquid.

30. Pharmaceutical formulation for oral administration according to claim 27, characterized in that it comprises at least one enteric coating.

31. Pharmaceutical formulation according to claim 26 characterized in that it comprises component (A) and/or component (B) at least partially in a sustained-release form.

32. Pharmaceutical formulation according to claim 31, characterized in that the sustained release is achieved by at least one coating or matrix comprising at least one sustained-release material.

33. Pharmaceutical formulation according to claim 32, characterized in that the sustained-release material is based on an optionally modified, water-insoluble, natural, semisynthetic or synthetic polymer, or a natural, semisynthetic or synthetic wax or fat or fatty alcohol or fatty acid, or on a mixture of at least two of these afore mentioned components.

34. Pharmaceutical formulation according to claim 33, characterized in that the water-insoluble polymer is based on an acrylic resin, which is preferably selected from the group of poly(meth)acrylates, poly(C₁4dialkylamino (Ci-4alkyl (meth)acrylates and/or copolymers thereof or a mixture of at least two of the afore-mentioned polymers.

35. Pharmaceutical formulation according to claim 33, characterized in that the water-insoluble polymers are cellulose derivatives, preferably alkyl cellulose, particularly preferably ethyl cellulose, or cellulose esters.

36. Pharmaceutical formulation according to claim 33, characterized in that the wax is camauba wax, beeswax, glycerol monostearate, glycerol monobehenate, glycerol ditripalmitostearate, microcrystalline wax or a mixture of at least two of these components.

37. Pharmaceutical formulation according to claim 33, characterized in that the polymers have been used in combination with one or more plasticizers.

38. Pharmaceutical formulation according to claim 31, characterized in that it comprises component (A) and/or (B) in immediate-release form as well as in sustained release form.