US 2005O176790A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0176790 A1 Bartholomaus et al. (43) Pub. Date: Aug. 11, 2005

(54) PHARMACEUTICAL SALTS (30) Foreign Application Priority Data (76) Inventors: Johannes Bartholomaus, Aachen (DE); Feb. 28, 2001 (DE)...... 101 O9 763.8 Heinrich Kugelmann, Aachen (DE) Correspondence Address: Publication Classification Clarence A. Green E. REEN, LLP (51) Int. Cl...... A61K 31/425 Fairfield,OS. CTO. 06824 (US) (52) U.S. Cl...... 514/373

(21)21) AppAppl. No.: 10/647,8829 (57) ABSTRACT (22) Filed: Aug. 25, 2003 Related U.S. Application Data The invention relates to pharmaceutical Salts comprised of a pharmaceutical active Substance and of a least one Sugar (63) Continuation of application No. PCT/EP02/02169, Substitute, to medicaments containing these Salts, and to the filed on Feb. 28, 2002. use of these Salts for producing medicaments. US 2005/0176790 A1 Aug. 11, 2005

PHARMACEUTICAL SALTS particularly preferably by at least 85%, compared with the 0001. The present invention relates to pharmaceutical corresponding hydrochloride. The corresponding literature Salts of an active compound and at least one Sugar Substitute, description is hereby inserted as a reference and is thus medicaments comprising these Salts, and the use of these regarded as part of the disclosure. Salts for the production of medicaments. 0008 According to the invention, suitable Sugar substi 0002 On oral administration, a large number of pharma tutes are all Sugar Substitutes which can form a Salt with the ceutical active compounds having excellent activity lead to respective pharmaceutical active compound with formation a Strongly bitter, often nauseating taste Sensation in the of an at least Singly negatively charged form. According to patient. In Some patients, lack of adherence to the dosage the invention, pharmaceutical Salts are also included in instructions and a lack of acceptance of the corresponding which the pharmaceutical active compound has two or more medicaments which release Such an active compound as different Sugar Substitutes as Salt components. Preferably, early as during taking result from this negative taste expe the pharmaceutical Salts according to the invention contain Saccharin, cyclamate or aceSulfam, particularly preferably CCC. Saccharin, as Salt-forming Sugar Substitutes. 0003. The formulation of pharmaceutical active com pounds having very good water Solubility to give medica 0009. According to the invention, Suitable active com ments frequently causes problems in pharmaceutical prac pounds are all pharmaceutical active compounds which can tice. Thus the preparation of pharmaceutical forms having form a Salt in anionic form with the respective Sugar controlled release is often made difficult on account of the Substitute(s) with formation of an at least singly positively very good water Solubility of active compound Salts. A charged form. delaying of the release of these active compounds can in fact 0010. In a further preferred embodiment of the present be achieved, for example, by coating the pharmaceutical invention, the Salt-forming active compound in the pharma forms with release-delaying film coatings. This manner of ceutical Salt according to the invention is Selected from the delaying the release, however, is associated with a relatively group consisting of the Salt-forming analgesics, antiobesity high outlay, Since release-delaying film coatings from aque agents, analeptics, antihypoxemics, antirheumatics, opioid ous coating Systems are frequently only an inadequate antagonists, anthelmintics, antiallergics, antiarrhythmics, diffusion barrier for active compounds having very good antibiotics, antidementives (nootropics), antidiabetics, anti water Solubility. The preparation of these delayed-release emetics, antivertiginous agents, antiepileptics, antihyperten active compound preparations therefore requires relatively Sives, antihypotensives, antimycotics, antiinflammatories, complicated coating processes with multilayer films. If Such antituSSives, expectorants, arteriosclerosis agents, P-recep release-delaying coatings are applied from organic Solvents, tor blockers, calcium channel blockers, broncholytics, anti the environmental and Solvent residue problems associated asthmatics, cholinergics, diuretics, circulation-promoting there with additionally make the preparation of appropriate agents, Weaning agents, geriatrics, hypnotics, Sedatives, preparations more expensive. immunomodulators, oral therapeutics, pharyngeal therapeu 0004. It was therefore the object of the present invention tics, coronary agents, hypolipidemics, local anesthetics, neu to make available pharmaceutical combinations of active ral therapeutics, gastric agents, intestinal agents, migraine compounds which have no bitter taste. Preferably, the cor agents, muscle relaxants, anesthetics, neuropathy prepara responding active compounds should be simpler to formu tions, ophthalmologicals, otologicals, Parkinson agents, psy late and their release should be more effectively delayed. chopharmaceuticals, rhinologicals, Sinusitis agents, Spas molytics, platelet aggregation inhibitors, tuberculosis 0005 According to the invention, this object is achieved agents, urologicals and cytostatics. Particularly preferably, by the provision of pharmaceutical Salts, i.e. physiologically the Salt-forming active compound is Selected from the group tolerable Salts, from a pharmaceutical active compound and consisting of the Salt-forming analgesics, analeptics, anti at least one Sugar Substitute. hypoxemics, antiallergics, antiarrhythmics, antiemetics, 0006 The present invention therefore relates to pharma antivertiginous agents, antihypertensives, antihypotensives, ceutical Salts of a pharmaceutical active compound and at antituSSives, expectorants, B-receptor blockers, calcium least one Sugar Substitute, the respective pharmaceutical channel blockers, ophthalmologicals, otologicals, Spas Salts of a Sugar Substitute and tramadol, (+)-tramadol, (-)- molytics and urologicals. Very particularly preferably, the tramadol, (+)-demethyltramadol and (-)-demethyltramadol Salt-forming active compound is Selected from the group being excepted. consisting of the Salt-forming analgesics, tramadol, (+)- tramadol, (-)-tramadol, (+)-demethyltramadol and (-)-dem 0007. In a preferred embodiment of the present invention, ethyltramadol being excepted. the Solubility of the pharmaceutical Salts according to the invention in water is s250 mg/ml of water, preferably s 200 0011) If the pharmaceutical active compound is a salt mg/ml, particularly preferably s 150 mg/ml, Very particu forming analgesic, it is preferably a Salt-forming opioid or a larly preferably s 100 mg/ml. This can also be seen in Salt-forming opioid analog, Such as disclosed in E. Frider particular in the fact that the water solubility of the phar ichs, T. Christoph, H. Buschmann, “Analgesics and Anti maceutical Salts according to the invention compared with pyretics”; Ullmann's Encyclopedia of Industrial Chemistry, the water solubility of the best water-soluble salt of the Sixth Edition on CD-ROM, Wiley-VCH, Weinheim, 2000 or corresponding active compound according to Phar in Pharmaceuticals, J. L. McGuire (Editor), Analgesics and mazeutische Stoffliste Pharmaceutical Substance List, 12th Antipyretics, Volume 2, pages 341-434, Wiley-VCH, Wein edition ABDATA Pharma-Daten-Service, 65735 Eschborn/ heim or ephedrine, chloroquine, lidocaine, ethaverine, pre Taunus, is preferably lowered by at least 50%, preferably by glumetacin or triflupromazine. The corresponding disclo at least 65%, particularly preferably by at least 75%, very Sures are hereby inserted as a reference and are thus regarded US 2005/0176790 A1 Aug. 11, 2005 as part of the present disclosure. Particularly preferably, the is H or CH and R is H or CH and if R is H, R' is Salt-forming analgesic is Selected from the group consisting meta-O-C-alkyl, meta-OH, meta-S-C1-alkyl, meta-F, of morphine, codeine, ethylmorphine, diacetylmorphine, meta-Cl, meta-CH, meta-CFH, meta-CF or para-CF or if dihydrocodeine, etorphine, hydrocodone, hydromorphone, R is a para-Clor-F, R' is meta-Cl or -F, or R' and R' levorphanol, oxycodone, oxymorphone, pethidine, ketobe together are 3,4-OCH=CH-. midone, fentanyl, alfentanil, remifentanil, Sufentanil, levomethadone, levomethadyl, dextro-moramide, dextro 0022 Particularly preferred is a salt-forming compound propoxyphene, diphenoxylate, piri-tramide, tilidine, of 1-phenyl-3-dimethylaminopropane compounds of the buprenorphine, butorphanol, deZOZine, meptazinol, nalbu general formula I in which the radicals R and R have phine, nalorphine, pentaZo-cine, flupirtin and nefopam or a different meanings and which are present in the form of their representative of the group consisting of ephedrine, chloro diastereomers having the configuration Ia quine, lidocaine, ethaverine, preglumetacin and triflupro mazine. Very particularly preferably, the Salt-forming anal Ia gesic is a Salt-forming opioid or opioid analog Selected from R5 the group consisting of morphine, codeine, hydrocodone, hydromorphone, oxycodone, tilidine, fentanyl and buprenor phine. SN -HR'. 0012 Likewise preferably, the salt-forming active com X H pound is a Salt-forming compound of 1-phenyl-3-dimethy R1 laminopropane compounds of the general formula I "/R2

HC CH X R1 2 21 R R3 0023 Very particularly preferred is a salt-forming com pound of 1-phenyl-3-dimethylaminopropane compounds of Rs-Hy -CH3 the general formula I, Selected from the group consisting of R4 N 0024 (1RS,2RS)-3-(3-dimethylamino-1-hydroxy-1, CH 2-dimethylpropyl)phenol, 0025 (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2- 0013) in which in each case methylpropyl)phenol, 0014 X is OH, F, Cl, H or an OCOR group, 0026 (+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2- 0015) R' is a C-alkyl group, methylpropyl)phenol, 0016 R is H or a C-alkyl group and R is Hora 0027 (2RS,3RS)-1-dimethylamino-3-(3-methox straight-chain C-alkyl group or the radicals R and yphenyl)-2-methylpentan-3-ol, R together form a C-7-cycloalkyl radical, and 0028 (-)-(1S,2S)-3-(3-dimethylamino-1-ethyl-1- 0017 if R is H, R" is meta-O-Z where Z is H, fluoro-2-methylpropyl)phenol, C-alkyl, PO(O-C-alkyl), CO(OCs-alkyl), CONH-CH (C-alkyl), CO-CH-R7, 0029 (+)-(1R,2R)-3-(3-dimethylamino-1-hydroxy where R is ortho-OCOC-alkyl or meta- or para 1,2-dimethylpropyl)phenol, CHN(R), where R is C, -alkyl or 4-morpholino, 0030 (+)-(2R,3R)-1-dimethylamino-3-(3-methox O R" is meta-S-C1-alkyl, meta-Cl, meta-F, meta yphenyl)-2-methylpentan-3-ol and CRR'R'' where R, R9 and R'' are H or F, ortho OH, ortho-O-C-alkyl, para-F or para-CRR'R'' 0031 (-)-(2S,3S)-1-dimethylamino-3-(3-methox where R, R', R'' are H or F, or if R is para-Cl, yphenyl)-2-methylpentan-3-ol. -F, -OH or -O-C-alkyl, R' is meta-Cl, -F, 0032. The preparation of the salt-forming compounds of -OH or -O-C-alkyl, or 1-phenyl-3-dimethylaminopropane compounds of the gen 0.018) R' and R together are 3,4-OCH=CH- or eral formula I and, if appropriate, the Separation into the pure 3,4-OCH=CHO , optical antipodes can be carried out according to customary methods known to the person skilled in the art. Preferably, 0.019 R is C-alkyl, the preparation and, if appropriate, the Separation is carried 0020 in the form of their possible stereoisomers as out as described in DE-A-4426245 or EP 0 693 475 B1, racemates or diastereomerically pure enantiomers or which are hereby inserted as reference and are thus regarded in the form of mixtures of enantiomers, in which the as part of the disclosure. respective enantiomers are present in nonequimolar 0033. In a further preferred embodiment of the present amountS. invention, the pharmaceutical Salt according to the invention 0021 Preferred is a salt-forming compound of 1-phenyl contains as a Salt-forming active compound a Salt-forming 3-dimethylaminopropane compounds of the general formula compound of 6-dimethylaminomethyl-1-phenylcyclohex I in which X is OH, F, C1 or H, R is a C-alkyl group, R ane compounds of the general formula II, US 2005/0176790 A1 Aug. 11, 2005

0045 (-)-(1R,2R)-3-(2-dimethylaminomethylcy clohexyl)phenol, II 0046 (1RS,3RS,6RS)-6-(dimethylaminomethyl)-1- (3-methoxyphenyl)cyclohexane-1,3-diol and 0047 (1RS,3RS,6RS)-6-(dimethylaminomethyl)-1- (3-hydroxyphenyl)cyclohexane-1,3-diol. 0048. The preparation of the salt-forming compounds of 6-dimethylaminomethyl-1-phenylcyclohexane compounds of the general formula II and, if appropriate, the Separation into the optically pure antipodes can be carried out accord ing to customary methods known to the person skilled in the art. Preferably, the preparation and, if appropriate, the Sepa ration are carried out as described in DE-A-19525137. The 0034 in which in each case corresponding literature description is hereby inserted as 0035) R' is H, OH, C1 or F, preferably H, OH or F, reference and is thus regarded as part of the disclosure. 0036) R' and Rare identical or different and are H, 0049. In a further preferred embodiment of the present C-alkyl, benzyl, CF, OH, OCH-CH, O-C- invention, the pharmaceutical Salt according to the invention 4-alkyl, Cl or F with the proviso that at least one of contains as a Salt-forming active compound a Salt-forming the radicals R or R is H, compound of 1-phenyl-2-dimethylamino-methylcyclo 0037) R' is H, CH, PO(O-C-alkyl), CO(OC. hexan-1-ol compounds of the general formula III, 5-alkyl), CO-NH-CH-C-alkyl, CO-CH-R, CO-C-s-alkyl, CO-CHR'- NHR7 or an unsubstituted or substituted pyridyl, III thienyl, thiazoyl sic or phenyl group, R1" 0038) Ris OC(O)C-alkyl in the ortho-position or A^ CH-N(R) in the meta- or para-position, where R is C-alkyl or both radicals R together with N are the 4-morpholino radical, and 0039) R' and R7 are identical or different and are H Y Z. or C-alkyl, 4. OH 0040 with the proviso that if both radicals R and Rare H, R" is not CH if R is H, OH or C1 or R' is not H if R is OH, 0041 in the form of their possible stereoisomers as N racemates or diastereomerically pure enantiomers or HC1 YCH, in the form of mixtures of enantiomers, in which the respective enantiomers are present in nonequimolar 0050 in which in each case amountS. 0.042 Preferred are salt-forming compounds of 6-dim 0051) A is O or S, ethylaminomethyl-1-phenylcyclohexane compounds of the 0052) R' is H, C-alkyl, C-alkenyl, Cs 7-cy general formula II, which are present in the configuration as cloalkyl or halogenated C-alkyl, in the general formula IIa, 0053) the group

IIa -YEZ.(

HC1 NCH, 0054) is the group

0.043 in which the phenyl ring and the dimethylaminom ethyl group are in each case arranged in an equatorial position to one another. 0044 Particularly preferred is a salt-forming compound of b-dimethylaminomethyl-1phenylcyclohexane com 0055) R' is C6-alkyl, C-alkenyl, Cs 7-cy pounds of the general formula II Selected from the group cloalkylmethyl, substituted or unsubstituted phenyl consisting of or substituted or unsubstituted benzyl, US 2005/0176790 A1 Aug. 11, 2005

0056 in the form of their possible stereoisomers as Separation into the optically pure antipodes can be carried racemates or diastereomerically pure enantiomers or out according to customary methods known to the perSon in the form of mixtures of enantiomers, in which the skilled in the art. Preferably, the preparation and, if appro respective enantiomers are present in nonequimolar priate, the Separation are carried out as described in DE-A- amountS. 19547766, which is hereby inserted as reference and is thus 0057 Preferred are salt-forming compounds of 1-phenyl regarded as part of the disclosure. 2-di-methylaminomethylcyclohexan-1-ol compounds of the 0068. In a further preferred embodiment of the present general formula III, in which R" is H, C-alkyl, 2-methyl invention, the pharmaceutical Salt contains as a Salt-forming 2'-propenyl, cyclopentyl or fluoroethyl, with the proviso that active compound a salt-forming compound of dimethyl-(3- R" is C-alkyl if A is S, arylbut-3-enyl)amine compounds of the general formula IV, 0.058 R" is C-alkyl, C-alkenyl, cyclopentylm in which sic ethyl, phenyl, C-alkoxyphenyl, benzyl, C-alky lbenzyl, mono- or dihalogenated phenyl or mono- or IV dihalogenated benzyl. 0059 Particularly preferred are salt-forming compounds of 1-phenyl-2-dimethylaminomethylcyclohexan-1-ol com pounds of the general formula III, in which R" is H, methyl, ethyl, isopropyl, 2-methyl-2'-propenyl, cyclopentyl or fluo roethyl, with the proviso that R'" is methyl if A is S, 0060 R" is methyl, propyl, 2-methylpropyl, allyl, 2-methyl-2'-propenyl, cyclopentylmethyl, phenyl, 3-methoxyphenyl, benzyl, 4-tert-butylbenzyl, CH 4-chloro-benzyl, 4-fluorobenzyl or 3,4-dichloroben Zyl. 0069 the radical R" is C-alkyl and R'" is H or 0061 Very particularly preferred are salt-forming com Cis-alkyl or R" and R" together are -(CH2) , pounds of 1-phenyl-2-dimethylaminomethylcyclohexan-1- ol compounds of the general formula III which are present -(CH-)-CHR" or -CH-CHRR"-CH-, in the configuration of the formula IIIa, 0070 R" is H or C-alkyl, 0.071) R'" is H, OH, C-alkyl, O-C-alkyl, IIIa O-benzyl, CF, O-CF, Cl, For OR", 0.072 R." is H, OH, C-alkyl, O-C-alkyl, OH O-benzyl, CHF, CF, O-CF, Cl, For OR" and 0.073 R'" is H, OH, C-alkyl, O-C-alkyl, YZ A O-benzyl, CF, O-CF, Cl, For OR", 2ft R An CH 0.074) with the proviso that two of the radicals R", HC R" or R." are H, or 0075 R" and R" together are -CH=C(R")– 0.062 in which the phenyl ring and the dimethylaminom O- or -CH=C(R)-S-, with the proviso that ethyl group are in each case arranged in an equatorial R" is H, or position to one another. 0.076 R" and R" together are -CH=CH 0.063 Most preferred is the salt-forming compound of C(OR")=CH-, with the proviso that R" is H, 1-phenyl-2-dimethylaminomethylcyclohexan-1-ol CO pounds of the general formula III Selected from the group 0.077 R7" is Cis-alkyl, Cs-cycloalkyl, O-C- consisting of alkyl, O-benzyl, CF, Cl or F. 0064 (+)-(1R,2R,4S)-2-(dimethylaminomethyl)-4- (0078), R is CO-C-alkyl, PO(O-C-alkyl). (4-fluorobenzyloxy)-1-(3-methoxyphenyl)cyclohex CO-CH-R''", CO(O-C-s-alkyl), CO-CHR'2" NHR'", CO-NH-CH,- anol, (R'") or an unsubstituted or substituted pyridyl, 0065 1(+)-(1R,2R,4S)-2-dimethylaminomethyl-4-(4- thienyl, thiazoyl sic or phenyl group, chlorobenzyloxy)-1-(3-methoxyphenyl)cyclohexanol and 0079 R" is H or C-alkyl, 0066 (+)-(1R,2R,4S)-3-2-dimethylaminomethyl 4-(4-fluorobenzyloxy)-1-hydroxycyclohexylphe 0080) R" is H or C-alkyl, nol. 0081) R'" is OC(O)-C-alkyl in the ortho-posi 0067. The preparation of the salt-forming compounds of tion or CH-N-(R'") in the meta- or para 1-phenyl-2-dimethylaminomethylcyclohexan-1-ol CO position, where R'" is C-alkyl or both radicals pounds of the general formula III and, if appropriate, the R'" together with N form the 4-morpholino radical, US 2005/0176790 A1 Aug. 11, 2005

0082) R'" and R'" are identical or different and 01.04) R" is H or CH, are H, C-alkyl or Cs-cycloalkyl or R'" and R'" together are -(CH2) , 01.05) R" is H, R" is OH or OR", R" is H, and R" is CO-CH-R'" where R'" is OC(O)– 0083) R'" is H, OH, C 7-alkyl, O-C-7-alkyl, CH in the ortho-position. phenyl, O-aryl, CF, Clor F, with the proviso that the two radicals R'" are identical or different, 0106 Most preferred is the salt-forming compound of dimethyl-(3-arylbut-3-enyl)amine compounds of the general 0084 in the form of their possible stereoisomers as formula IV trans-(-)-(1R)-3-1-(2-dimethylamino-1-meth racemates or diastereomerically pure enantiomers or ylethyl)propenylphenol. in the form of mixtures of enantiomers, in which the respective enantiomers are present in nonequimolar 0107 The preparation of the salt-forming compounds of amountS. dimethyl-(3-arylbut-3-enyl)amine compounds of the general formula IV and, if appropriate, the Separation into the 0085 Preferred are salt-forming compounds of dimethyl optically pure antipodes can be carried out according to (3-arylbut-3-enyl)amine compounds of the general formula customary methods known to the person skilled in the art. IV, in which Preferably, the preparation and, if appropriate, the Separation 0086) R'" is C-alkyl and R" is H or C-alkyl, of these compounds are carried out as described in EP 0 799 or R'" and 819 A1. The corresponding literature description is hereby inserted as reference and is thus regarded as part of the (opsi R' together are -(CH2) - or -(CH2)- disclosure. 0.108 AS salt-forming antiobesity agents, the pharmaceu 0088 R" is H or C-alkyl, tical Salt according to the invention can preferably contain 0089 R" is H, OH, CF, Cl, For OR", D-norpseudoephedrine, phenylpropanolamine, amfepra 0090 R" is H, OH, C-alkyl, O-C-alkyl, mone, mefenorex or ephedrine. O-benzyl, CHF, CF, Cl, F or OR", and 0109 AS salt-forming analeptics and/or antihypoxemics, the pharmaceutical Salt according to the invention can 0091 R" is H, OH, O-C1-4 -alkyl, O-benzyl, CF,3. preferably contain norfenefrine, heptaminol or ameZinium, C1, For OR", particularly preferably ameZinium. 0092 with the proviso that two of the radicals R", 0110 AS Salt-forming opioid antagonists, the pharmaceu R" or R" are H, or tical Salt according to the invention can preferably contain 0093 R'" and R" together are -CH=C(R")– levallorphan, naloxone or naltrexone. O- or -CH=C(R)-S-, with the proviso that 0111 AS a Salt-forming anthelmintic, the pharmaceutical R" is H, or Salt according to the invention can preferably contain pyrV 0094) R" and R" together are -CH=CH inium. C(OR'")=CH-, with the proviso that R" is H, 0112 AS Salt-forming antiallergics, the pharmaceutical and Salt according to the invention can preferably contain repro 0.095 R7" is C-alkyl, CF, C1 or F. terol, triprolidine, hydroxy Zine, azelastine, diphenhy 0.096 Particularly preferred are salt-forming compounds dramine, promethazine, pheniramine, dexchlorpheniramine, of dimethyl-(3-arylbut-3-enyl)amine compounds of the gen clemastine, tramaZoline, brompheniramine, dimetindene, eral formula IV, in which R" is CH or CH, and R" is H, levocabastine, doxylamine, cyproheptadine, carbinoxamine, CH or CHCH, or R'" and R" together are -(CH-)-- meclozine, bamipine, chlorphenoxamine, ketotifen or ceti or -(CH2)-CHR", rizine, particularly preferably diphenhydramine. 0113 AS salt-forming antiarrhythmics, the pharmaceuti 0097 R" is H, CH, or CHCH cal Salt according to the invention can preferably contain 0098 R" is H or OH, R" is H, OH, OCH CHF orciprenaline, aprindine, Verapamil, metoprolol, quinidine, or ORs, and R'" is H, OH or CF, with the proviso amiodarone, Sotalol, propafenone, diltiazem, disopyramide, that two of the radicals R", R" or R." are H, or propranolol, ipatropium sic, mexiletine, prajmaline, procainamide, gallopamil, propafenone, detajmium, flecain 0099 R" and R" together are -CH=C(CH)– ide, Oxprenolol or tocainide, particularly preferably Vera S-, with the proviso that R'" is H, or pamil or diltiazem. 01.00 R" and R" together are -CH=CH 0114 AS Salt-forming antibiotics, the pharmaceutical salt C(OH)=CH-, with the proviso that R" is H, and according to the invention can preferably contain Vancomy 01.01 R" is CO-CH-R'" where R'" is cin, tetracycline, clindamycin, minocycline, lincomycin, OC(O)-C-alkyl in the ortho-position. bacampicillin, amicacin, chlortetracycline, neomycin, tobra mycin, netilmicin, quinine, chloroquine ciprofloxacin, clin 0102 Very particularly preferred are salt-forming com damycin, colistine, erythromycin, gentamicin, tobramycin pounds of dimethyl-(3-arylbut-3-enyl)amine compounds of sic, cefetametpivotil, amantadine, halofantrine, Saquinavir, the general formula IV, in which mefloquine, framycetin, cefepime, bromheXine, cefpo 01.03 R'" is CH and R" is H or CH or R'" and doXimeproxetil, Oxytetracycline, proguanil, pefloxacine, R" together are -(CH2)5- or -(CH2)- polymyxin B, hydroxychloroquine, Spectinomycin, Sultami CH(CH), cillin, Valaciclovir or grepafloxacin. US 2005/0176790 A1 Aug. 11, 2005

0115 AS salt-forming antidementive (nootropics), the tiazem, mepindolol, Sotalol, carteolol, gallopamil or Oxpre pharmaceutical Salt according to the invention can prefer nolol, particularly preferably Verapamil or diltiazem. ably contain butalamine, memantine, pyritinol, donepezil, 0.126 AS salt-forming broncholytics and/or antiasthmat moxaverine, meclofenoxate, dihydroergotoxin, Viquidil, ics, the pharmaceutical Salt according to the invention can naftidrofuryl, dihydroergocornine, dihydroergocristine, ben preferably contain ketotifen, reproterol, orciprenaline, Salb Zyclan, procaine, deamol, diisopropylamine or 3-pyridyl utamol, terbutaline, ephedrine, tulobuterol, ipatropium sic, methanol. fenoterol, terbutaline sic, formoterol, Salbutamol sic, 0116. As a Salt-forming antidiabetic, the pharmaceutical Oxytropium or pirbuterol. Salt according to the invention can preferably contain met 0127 AS Salt-forming cholinergics, the pharmaceutical formin. Salt according to the invention can preferably contain pyri 0117 AS salt-forming antiemetics and/or antivertiginous doStigmine, betanechol or neoStigmine. agents, the pharmaceutical Salt according to the invention 0128. As salt-forming diuretics, the pharmaceutical salt can preferably contain betahistidine, dolasetrone, mecloz according to the invention can preferably contain amiloride ine, hydroxycine, diphenhydramine, pyridoxine, granis or Oxprenolol. etrone, triflu promazine, triethyl-perazine, betahistine, aliza pride O odansetrone, particularly preferably 0.129 AS Salt-forming, circulation-promoting agents, the diphenhydramine. pharmaceutical Salt according to the invention can prefer 0118 AS a Salt-forming antiepileptic, the pharmaceutical ably contain butalamine, naftidrofuryl, buflomedil, mox Salt according to the invention can preferably contain tiaga averine, bencyclan or meclofenoxate. bine. 0.130. As a Salt-forming weaning agent, the pharmaceu tical Salt according to the invention can preferably contain 0119 AS Salt-forming antihypertensives, the pharmaceu naltrexone, methadone, buprenorphine. tical Salt according to the invention can preferably contain dihydralazine, praZosine, amiloride, bunaZOsine, nicar 0131 AS Salt-forming geriatrics, the pharmaceutical Salt dipine, alprenolol, candesartancileXetil, metoprolol, Vera according to the invention can preferably contain procaine pamil, propranolol, penbutolol, doxazosine, clonidine, or deanolace. benazepril, phenoxybenzamine, diltiazem, diisopropy 0.132. As salt-forming hypnotics and/or sedatives, the lamine, urapide, carteololl guanethidine, guanfacine, tera pharmaceutical Salt according to the invention can prefer ZoSine, Oxprenolol, cicletanine, betaxolol, nebivolol, acebu ably contain promethazine, Zolpidem tartrate, midazolam, tolol, enalapril or indoramine, particularly preferably melperone or flurazepam. Verapamil or diltiazem. 0.133 As a salt-forming immunomodulator, the pharma 0120 AS Salt-forming antihypotensives, the pharmaceu ceutical Salt according to the invention can preferably con tical Salt according to the invention can preferably contain tain levamisole. etillefrine, pholedrine, norfenefrine, cafedrine, theodrena line, OXilofrine, dobutamine, dopamine, phenylephrine, 0.134 AS Salt-forming oral and/or pharyngeal therapeu midodrine, heptaminol, Oxedrine tartrate, pholedrine or tics, the pharmaceutical Salt according to the invention can gepefrine, particularly preferably phenylephrine. preferably contain chlorhexidine or cetylpyridinium. 0121 AS Salt-forming antimycotics, the pharmaceutical 0.135 AS a Salt-forming coronary agent, the pharmaceu Salt according to the invention can preferably contain ben tical Salt according to the invention can preferably contain Zalkonium, econazole, miconazole, methylrosanilinium, ter oxyfedrine. binafine, amorolfine, fenticonazole, dequalinium, oxycona 0.136 AS a salt-forming hypolipidemic, the pharmaceu Zole, croconazole, isoconazole or Sertaconazole. tical Salt according to the invention can preferably contain 0122). As a Salt-forming antiinflammatory, the pharma colestipol. ceutical Salt according to the invention can preferably con 0.137 AS salt-forming local anesthetics and/or neural tain orphenadrine. therapeutics, the pharmaceutical Salt according to the inven 0123 AS Salt-forming antituSSives and/or expectorants, tion can preferably contain bupivacaine, lidocaine, mepiv the pharmaceutical Salt according to the invention can acaine, ropivacaine, procaine, articaine or prilocaine. preferably contain ambroXole, doxycycline, bromheXine, 0.138 AS Salt-forming gastric and/or intestinal agents, the dextromethorphan, diphenhydramine, terbutaline, chlorphe pharmaceutical Salt according to the invention can prefer namine, eprazinone, ephedrine, chlorbutinol, pentoxyverine, ably contain pizotifen, pirenzepine, roXatidine, ranitidine, pipaZetate or benproperine, particularly preferably diphen butinoline, methanthelinium or metoclopramide. hydramine. 0.139 AS Salt-forming migraine agents, the pharmaceuti 0.124. As a Salt-forming antisclerosis agent, the pharma cal Salt according to the invention can preferably contain ceutical Salt according to the invention can preferably con lisuride, methySergide, dihydroergotamine, ergotamine, tain butalamine. Sumatriptan, rizatriptan or naratriptan. 0.125 AS B-receptor blockers and/or calcium channel 0140 AS salt-forming muscle relaxants, the pharmaceu blocker the pharmaceutical Salt according to the invention tical Salt according to the invention can preferably contain can preferably contain acebutolol, nicardipine, alprenolol, alcuronium, mivacuronium, atracurium, Vecurmium, pan metoprolol, Verapamil, enalapril, bupranolol, penbutolol, curmium, Suxamethonium, tolperisone, pridinol, propranolol, bisoprolol, eSmolol, celiprolol, benazepril, dil orphenadrine or tizamidine. US 2005/0176790 A1 Aug. 11, 2005

0141 AS a Salt-forming anesthetic, the pharmaceutical 0152 The pharmaceutical salts according to the inven Salt according to the invention can preferably contain ket tion can be prepared according to customary methods known amine or midazolam. to the person skilled in the art. Preferably, for the preparation of the pharmaceutical Salts according to the invention, at 0142. As a Salt-forming neuropathy preparation, the phar least one Salt of the respective active compound and at least maceutical Salt according to the invention can preferably one Salt of the respective Sugar Substitute are in each case contain thiamine. dissolved Separately from one another in an amount of a 0.143 AS Salt-forming ophthalmologicals and/or otologi Solvent or Solvent mixture which is as Small as possible, cals, the pharmaceutical Salt according to the invention can optionally with warming. preferably contain oxybuprocaine, proxymetacaine, kana 0153. Both solutions are then combined, optionally mycin, tolazoline, tetryZoline, tramaZoline, phenylephrine, mixed and optionally cooled. If the pharmaceutical Salt Xylomethazoli sic, naphazoline, timolol, metipranolol, according to the invention of the active compound and the betaxolol, befunolol, levobunolol, brimonidine, clonidine, Sugar Substitute precipitates at least partially from the pilocarpine, diplivefrine, aceclidine, apraclonidine, neoStig optionally cooled Solution, this is separated off according to mine, dorZolamide, atropine, Scopolamine, cyclopentolate or customary methods, preferably by suction filtration. The homatropine, particularly preferably phenylephrine. pharmaceutical Salt Separated off is then purified, if neces 0144 AS Salt-forming Parkinson agents, the pharmaceu Sary, according to customary methods known to the perSon tical Salt according to the invention can preferably contain skilled in the art, for example by recrystallization, Washing amantadine, biperidene, Selegiline, bromocriptine, trihex or by Stirring in a Suitable Solvent. yphenidyl, metrixene, benzaseride, lisuride, benzatropine, ropinirol, pergolide, bupidine, procyclidine, pramipexol, 0154) If the pharmaceutical salt has still not completely precipitated, the remaining Solution is preferably concen bomapine or tiapride. trated completely on a rotary evaporator and the pharma 0145 AS Salt-forming psychopharmaceutical agents, the ceutical Salt according to the invention is extracted from the pharmaceutical Salt according to the invention can prefer residue according to customary methods known to the ably contain tranylcypromine, amitriptyline, doxepine, person skilled in the art and purified as described above. maprotiline, clomipramine, opipramol, imipramine, trimi pramine, lofepramine, desipramine, dibenzepine, nortrip O155 The solvent or solvent mixture suitable in each case tyline, mianserine, citalopram, fluvoxamine, fluoxetil, traZ for the preparation and the Suitable reaction conditions, Such odone, paroxetin, nefazodone, Sertralin, Viloxacin, as, for example, temperature or reaction time, can be deter Venlafaxine, promethazine, chlorprothixene, Zuclopenthixol, mined by the person skilled in the art with the aid of simple pipamperone, fluphenazine, flupentiXol, melperone, pro preliminary tests. If both the active compound Salt and the thipendyl, thioridazine, levomepromazine, quetiapine, trif Salt of the Sugar Substitute have an adequate Solubility in lupromazine, perazine, fenetyline, methylphenidate, water, the solvent used is preferably water. The salt of the respective active compound employed is preferably its hydroxycine, buSpirone, deanolace or memantine. hydrochloride, hydrobromide, phosphate, hydrogenphos 0146 AS Salt-forming rhinologicals/sinusitis agents, the phate, hydrogensulfate, Sulfate, nitrate or metilsulfate. The pharmaceutical Salt according to the invention can prefer Salt of the respective Sugar Substitute employed is preferably ably contain diphenylpyraline, Xylometazoline, Oxymetazo its Sodium, potassium, calcium or ammonium Salt. line, tramaZoline, indanazoline, naphazoline or tetry Zoline. 0156. Of course, it is also possible to react the respective 0147 AS Salt-forming spasmolytics, the pharmaceutical active compound perse with Sic the free acid of a Sugar Salt according to the invention can preferably contain atro Substitute with one another in a Suitable reaction medium pine, phenamazide, butylscopolaminium, propiverine, and to isolate and, if appropriate, to purify the pharmaceu mebeverine, pipenzolate, oxybutynine, flavoxate, troSpium, tical Salt thus obtained according to customary methods denaverine or glycopyrronium. known to the perSon Skilled in the art. 0148 AS Salt-forming platelet aggregation inhibitors, the O157 A further subject of the present invention are pharmaceutical Salt according to the invention can prefer medicaments comprising at least one pharmaceutical Salt ably contain tirofiban, ticlopidine or clopidogrel. according to the invention and, if appropriate, physiologi 0149. As a salt-forming tuberculosis agent, the pharma cally tolerable excipients. The corresponding medicaments ceutical Salt according to the invention can preferably con can be used for the treatment of the indications known for tain ethambutol. the respective active compounds. 0150 AS salt-forming urologicals, the pharmaceutical 0158 Preferably, medicaments according to the inven Salt according to the invention can preferably contain cho tion which contain at least one pharmaceutical Salt according line, tolterodine, phenoxybenzamine, atropine, propiverine, to the invention of a Salt-forming opioid, opioid analog, distigmine, emepronium, tamsulosine, doxazosine, tera ephedrine, chloroquine, lidocaine, ethaverine, preglumeta ZoSine, alfuZosine, bamethane, yohimbine or Sildenafil. cin or triflupromaazine or a Salt-forming compound of the 0151 AS Salt-forming cytostatics, the pharmaceutical Salt general formula I, II, III or IV indicated above and a Sugar according to the invention can preferably contain aclarubi substitute are employed for the control of pain. Preferably, cin, nimustatin, doxorubicin, bleomycin, vinblastine, Vinc the medicaments according to the invention contain the ristine, daunorubicin, decarbazine, Vindesline, epirubicin, corresponding Saccharinates as pharmaceutical Salts of these gemcitabine, procarbazil, mitoxantrone, bedamustine, ida active compounds. rubicin, aclarubicin sic, irinotecan, topotecan, toremifen or 0159 For the treatment of urinary incontinence, medica tamoxifen. ments according to the invention are preferably employed US 2005/0176790 A1 Aug. 11, 2005

which contain at least one pharmaceutical Salt of a Salt calcium hydrogenphosphate, fatty alcohols, esters of glyc forming compound of the general formula I, II, III or IV erol or fatty acid esters as physiologically tolerable excipi indicated above, or a compound from the group consisting entS. of Oxybutymine, tolterodine, propiverine and troSpium and a 0170 If the medicaments according to the invention are Sugar Substitute. Preferably, the medicaments according to present in the form of microcapsules or microparticles, these the invention contain the corresponding Saccharinates as can contain, depending on the nature of the process pharmaceutical Salts of these active compounds. employed for their preparation, the customary physiologi 0160 The medicaments according to the invention can be cally tolerable excipients known to the person skilled in the present in Solid, semisolid or liquid form. Preferably, the art. medicaments according to the invention are Suitable for oral 0171 The medicaments according to the invention can be administration. prepared by customary methods known to the person skilled 0.161 In a preferred embodiment, the medicament in the art. according to the invention is present formulated as a gel, 0172 If the medicaments according to the invention are chewing gum, juice, Spray, tablet, chewable tablet, coated present in the form of tablets, preferably the pharmaceutical tablet, powder, if appropriate filled into capsules, easily Salt according to the invention and, if appropriate, the reconstitutable dry preparations, preferably as a gel, as an physiologically tolerable excipients are preferably mixed aqueous or oily juice, as a Sublingual spray, tablets or homogeneously with one another, processed to give granules chewable tablets. by means of moist, dry or melt granulation and compressed 0162 Likewise preferably, the medicament according to to give tablets or produced by direct tableting of the phar the invention can also be present formulated in multipar maceutical Salt with further excipients. In addition, the ticulate form, preferably in the form of micro-tablets, micro tablets can preferably be produced by compression of capsules, granules, active compound crystals or pellets, optionally coated pellets, active compound crystals, micro particularly preferably in the form of microtablets, granules particles or microcapsules. or pellets, optionally filled into capsules or compressed to 0173 The medicaments according to the invention in the give tablets. form of pellets can preferably be produced by mixing the 0163) If the medicament according to the invention is pharmaceutical Salt and physiologically tolerable excipients, present in the form of granules or pellets, these can prefer extrusion and Spheronization, by build-up pelletization or by ably have a Size in the range from 0.1 to 3 mm, particularly direct pelletization in a high-speed mixer or in the rotor preferably in the range from 0.5 to 2 mm. fluidized bed. The pellets are particularly preferably pre pared by extrusion of moist masses and Subsequent Spher 0164. If the medicament according to the invention is onization. present in the form of microtablets, these can preferably have a diameter in the range from 0.5 to 5 mm, particularly 0.174 Microcapsules are prepared according to custom preferably in the range from 1 to 3 mm and very particularly ary microencapsulation processes, Such as, for example, by preferably in the range from 1 to 2 mm. Spray drying, Spray Solidification or coacervation. 0.165 If the medicament according to the invention is 0.175. The medicaments according to the invention in present in the form of active compound crystals, micropar Semisolid form, Such as, for example, gels or chewing guns, ticles, micropellets or microcapsules, these can preferably are preferably suitable for the administration of the phar have a diameter in the range from 10 um to 1 mm, particu maceutical Salt according to the invention via the oral larly preferably in the range from 15 um to 0.5 mm and very mucosa, the medicaments according to the invention in Solid particularly preferably in the range from 30 um to 200 um. or liquid form, Such as, for example, oily or aqueous juices, tablets or multiparticulate forms are preferably suitable for 0166 Depending on embodiment, the medicaments the administration of the pharmaceutical Salt according to according to the invention can moreover contain the cus the invention via the gastric tract. If the absorption of active tomary physiologically tolerable excipients known to the compound from the medicament according to the invention person skilled in the art as further constituents. in Solid form is only intended via the gastric tract, they must 0167 If the medicaments according to the invention are have at least one enteric coating. This enteric coating present in the form of tablets or microtablets, these can be enables them to pass through the gastric tract undissolved present as physiologically tolerable excipients, preferably and the pharmaceutical Salt is only released in the intestinal microcrystalline cellulose, cellulose ethers, lactose, Starch, tract. Preferably, the enteric coating dissolves at a pH of Starch derivatives, Sugar alcohols, calcium hydrogenphos between 5 and 7.5. phate and the customary binders, flow regulators, lubricants 0176) The medicament according to the invention can and/or disintegrants known to the person skilled in the art. contain the pharmaceutical Salt according to the invention 0168 If the medicaments according to the invention are also partially or completely in delayed-release form. present in the form of gels or chewing gums, these can 0177. The delaying of the release of active compound is preferably contain methylparaben, propylparaben, Xylitol preferably based on the application of a release-delaying and/or Xanthan gum as physiologically tolerable excipients. coating, on embedding in a release-delaying matrix, binding 0169. If the medicaments according to the invention are to an ion-exchange resin or on a combination of these present in the form of pellets, granules or micropellets, these abovementioned release-delaying methods. can preferably contain microcrystalline cellulose, cellulose 0.178 Preferably, the release-delaying coating is based on ethers, lactose, Starch and Starch derivatives, Sugar alcohols, a water-insoluble, optionally modified natural or Synthetic US 2005/0176790 A1 Aug. 11, 2005

polymer or on a natural, Semisynthetic or Synthetic wax or Co-Co and an aliphatic alcohol of C-Cs. Such as, for fat or fatty alcohol or a mixture of at least two of these example, dibutyl phthalate, diethyl phthalate, dibutyl Seba abovementioned components. cate or diethyl Sebacate, hydrophilic or lipophilic esters of 0179 Water-insoluble polymers employed for the prepa citric acid, Such as, for example, triethyl citrate, tributyl ration of a release-delaying coating are preferably poly citrate, acetyltributyl citrate or acetyltriethyl citrate, poly (meth)acrylates, particularly preferably poly(C) alkyl alkylene glycols, Such as, for example, polyethylene glycols (meth)acrylates, poly(C)dialkylamino-(C1)-alkyl (meth or propylene glycols, esters of glycerol, Such as, for )acrylates and/or their copolymers, very particularly prefer example, triacetin, MyVacete (acetylated mono- and dig ably ethyl acrylate/methyl methacrylate copolymers having lycerides, CHOs to Cash,O7), medium-chain triglyc a molar ratio of the monomers of 2:1, ethyl acrylate/methyl erides (Miglyol(R), oleic acid or mixtures of at least two of methacrylate/trimethylammonium ethyl methacrylate chlo the abovementioned plasticizers. ride copolymers having a molar ratio of the monomers of 0187 Preferably, aqueous dispersions of Eudragit RS(R) 1:2:0.1, ethyl acrylate/methyl methacrylate/trimethylammo and optionally Eudragit RLE contain triethyl citrate as a nium ethyl methacrylate chloride copolymers having a plasticizer. molar ratio of the monomers of 1:2:0.2 or a mixture of at 0188 Preferably, the release-delaying coating contains least two of these abovementioned polymers as a coating the plasticizer(s) in amounts of 5 to 50% by weight, par material. ticularly preferably 10 to 40% by weight and very particu 0180. These coating materials are obtainable on the mar larly preferably 10 to 30% by weight, based on the amount ket as 30% Strength by weight aqueous lateX dispersions of the polymer employed. under the names Eudragit RS30D(R), Eudragit NE30D(R) and 0189 In individual cases, for example for cellulose Eudragit RL30D(R) and are preferably also employed as a acetate, higher amounts of plasticizers, preferably up to coating material as Such. 110% by weight, based on the amount of cellulose acetate, 0181 Likewise preferably, the water-insoluble polymers can also be employed. employed for the preparation of the release-delaying coating for the medicaments according to the invention can be 0190. In addition, the release-delaying coating can con polyvinyl acetates, optionally in combination with further tain further customary excipients known to the perSon excipients. These are obtainable on the market as an aqueous skilled in the art, Such as, for example, lubricants, preferably dispersion containing 27% by weight of polyvinyl acetate, talc or glycerol monostearate, color pigments, preferably 2.5% by weight of povidone and 0.3% by weight of sodium iron oxides or titanium dioxide, or Surfactants, Such as, for lauryl Sulphate (Kollicoat SR 30 D(R). example, Tween 800F). 0182. In a further preferred embodiment, the release 0191 The release profile of the delayed active compound delaying coatings of the medicaments according to the component can be adjusted by the customary methods invention are based on water-insoluble cellulose derivatives, known to the perSon Skilled in the art, Such as, for example, preferably alkylcelluloses, Such as, for example, ethylcellu by the thickness of the coating or by the use of further lose, or on cellulose esters, Such as, for example, cellulose excipients as constituents of the coating. Suitable excipients acetate, as a coating material. The coatings of ethylcellulose are, for example, hydrophilic or pH-dependent pore-forming or cellulose acetate are preferably applied from aqueous agents, Such as, for example, Sodium carboxymethylcellu pseudolatex dispersion. lose, cellulose acetate phthalate, hydroxypropylmethylcel lulose acetate Succinate, lactose, polyethylene glycol or 0183 Aqueous ethylcellulose-pseudolatex dispersions mannitol or water-Soluble polymers, Such as, for example, are stocked on the market as 30% strength by weight polyvinylpyrrollidone or water-Soluble celluloses, preferably dispersions (Aquacoat(R) or as 25% strength by weight hydroxypropylmethylcellulose or hydroxypropylcellulose. dispersions (Surelease(R) and as Such are preferably also 0.192 The release-delaying coating can also contain employed as a coating material. insoluble or lipophilic excipients, Such as, for example, 0184 AS natural, semisynthetic or synthetic waxes, fats alkylized Silicone, which is Stocked on the market, for or fatty alcohols, the release-delaying coating in the medi example, as Aerosil R972(E), or magnesium Stearate for the cament according to the invention can preferably contain further intensification of the delaying. carnauba wax, beeswax, glycerol monoStearate, glycerol monobelhenate (Compritol ATO888(R), glycerol ditripalmi 0193 The respective formulation of the medicament tostearate (Precirol ATO5(R), microcrystalline wax, cetyl according to the invention can optionally also contain, in alcohol, cetylstearyl alcohol, or a mixture of at least two of addition to the release-delaying coating, at least one further these components. coating. This can be, for example, a coating for improving the taste or an enteric coating. 0185. If the release-delaying coating is based on a water 0194 The enteric coating is preferably based on meth insoluble, optionally modified natural and/or Synthetic poly acrylic acid/methyl methacrylate copolymers having a molar mer, the coating dispersion or Solution can contain, in ratio of the respective monomers of 1:1 (Eudragit L(R), addition to the corresponding polymer, a customary physi methacrylic acid/methyl methacrylate copolymers having a ologically tolerable plasticizer known to the person skilled molar ratio of the respective monomers of 1:2 (Eudragit in the art in order to lower the minimum film temperature S(R), methacrylic acid/ethyl acrylate copolymers having a neceSSary. molar ratio of the respective monomers of 1:1 (Eudragit 0186 Suitable plasticizers are, for example, lipophilic L30D-550B), methacrylic acid/methyl acrylate/methyl meth diesters of an aliphatic or aromatic dicarboxylic acid of acrylate copolymerS having a molar ratio of the respective US 2005/0176790 A1 Aug. 11, 2005 monomers of 7:3:1 (Eudragit FS(R), shellac hydroxy-propy hydroxypropylcellulose, hydroxymethylcellulose, poly lmethylcellulose acetate Succinate, cellulose acetate phtha (meth)acrylic acid and/or their derivatives, Such as, for late or a mixture of at least two of these abovementioned example, their Salts, amides or esters. components, which can optionally also be employed in 0202) Likewise preferred are matrix materials made of combination with the abovementioned water-insoluble poly hydrophobic materials, Such as hydrophobic polymers, (meth)acrylates, preferably in combination with Eudragit waxes, fats, long-chain fatty acids, fatty alcohols or appro NE30D(R) and/or Eudragit RLCE) and/or Eudragit RS(R). priate esters or ethers or mixtures of at least two of the 0.195 The coatings can be applied by customary pro abovementioned materials. Particularly preferably, the ceSSes Suitable for the respective coating and known to the hydrophobic materials employed are mono- or diglycerides person skilled in the art, Such as, for example, by Spraying of C-Co-fatty acids and/or C1-Co-fatty alcohols and/or on Solutions, dispersions or Suspensions, by melt processes waxes or mixtures of at least two of the abovementioned or by powder application processes. The Solutions, disper materials. Sions or Suspensions can be employed in the form of aqueous and/or organic Solutions or dispersions. In this context, 0203. It is also possible to employ mixtures of the above aqueous dispersions are preferably employed. Organic Sol mentioned hydrophilic and hydrophobic materials as a vents which can preferably be used are alcohols, for example release-delaying matrix material. ethanol or isopropanol, ketones, Such as, for example, 0204. The release-delaying matrix can be prepared by the acetone, esters, for example ethyl acetate, chlorinated hydro customary methods known to the person skilled in the art. carbons, Such as, for example, dichloromethane, with alco 0205. A further subject of the invention is also the use of hols or ketones being particularly preferably employed. It is at least one pharmaceutical Salt according to the invention also possible to employ mixtures of at least two of the and, if appropriate, physiologically tolerable excipients for abovementioned Solvents. the production of a medicament. The corresponding medi 0196. If the medicament is present in multiparticulate caments can be used for the treatment of the indications form and the active compound is to be released at least known for the respective active compounds. partially in delayed form, the release-delaying coating is preferably applied Such that the multiparticulate forms com 0206 Preferred is the use of at least one pharmaceutical prising the active compound Salt are coated after their Salt of a Salt-forming opioid, opioid analog, ephedrine, preparation with the corresponding polymers and, if appro chloroquine, lidocaine, ethaverine, preglumetacin, truflu priate, another active compound and/or the same active promazine or a salt-forming compound of the general for compound Salt and, if appropriate, further physiologically mula I, II, III or IV indicated above for the production of a tolerable excipients from aqueous and/or organic media, medicament for the control of pain, the Salts of these active preferably from aqueous media, with the aid of the fluidized compounds used preferably being their Saccharinates. bed proceSS and the coating is preferably simultaneously 0207 Likewise preferred is the use of at least one phar dried in the fluidized bed at customary temperatures and, if maceutical Salt of a Salt-forming compound of the general appropriate, annealed if necessary. formula I, II, III or IV indicated above for the production of 0197) Preferably, the drying of the coating is carried out a medicament for the treatment of urinary incontinence, the for poly(meth)acrylate coatings at a feed air temperature in Salts of these active compounds used preferably being their the range from 30 to 50, particularly preferably in the range Saccharinates. from 35 to 45° C. 0208. The total amount of the respective pharmaceutical 0198 For coatings based on cellulose, such as, for Salt to be administered to the patient varies, for example, example, ethylcellulose or cellulose acetate, the drying is depending on the the weight of the patient, on the indication preferably carried out at a temperature in the range from 50 and the degree of severity of the pain or of the disorder. It to 80 C., particularly preferably in the range from 55 to 65 is known to the person skilled in the art on account of the C. properties of the respective active compounds in what doses these are to be administered in order to achieve the desired 0199 Wax coatings can be applied by melt coating in the effect. fluidized bed and cooled at temperatures below the respec 0209 The pharmaceutical salts according to the inven tive melt range after the coating for complete Solidification. tion of a pharmaceutical active compound and a Sugar The application of wax coatings can also be carried out by Substitute are distinguished compared with the convention Spraying on their Solutions in organic Solvents. ally used Salts of these active compounds customarily by a 0200 For the modification of the active compound lower solubility in water. Preferably, these are the saccha release profile, the medicament according to the invention rinates of the respective active compounds, whose water can contain the pharmaceutical Salt whose release is to be solubility is usually s 250 mg/ml and, compared with the delayed also in a release-delaying matrix, preferably uni water solubility of the conventional salts of the correspond formly dispersed. ing active compound, is usually lowered by at least 50%. 0201 Matrix materials which can be used are physiologi 0210. By this means, the formulation of these pharma cally tolerable, hydrophilic materials which are known to the ceutical Salts to give medicaments, for example the prepa person skilled in the art. Preferably, the hydrophilic matrix ration of granules by extrusion, is also simplified. On materials used are polymers, particularly preferably cellu account of the altered Solubility, the pharmaceutical Salts lose ethers, cellulose esters and/or acrylic resins. Very par according to the invention further enable more effective ticularly preferably, the matrix materials employed are eth release-delaying of the active compound using customary ylcellulose, hydroxypropylmethylcellulose, delaying processes in comparison to Salts customarily used. US 2005/0176790 A1 Aug. 11, 2005

Delayed-release medicaments which contain these pharma determined. The solubility of the respective salt per 1 ml of ceutical Salts according to the invention can therefore be water was then calculated according to the following for produced more Simply and more inexpensively. This also mula: applies for other modifications of the medicaments accord ing to the invention, Such as, for example, with enteric coatings. Water solubility of the active compound salt in mg ml of water = 0211 From the medicaments according to the invention, (CfA) + (CfD) which are employed for the administration of the respective 2 pharmaceutical Salt via the oral mucosa or the gastric tract, a largely controlled release of the respective active com 0217) If the amount Badded (in mg) of the respective salt pound without the use of a release-delaying matrix and/or a did not dissolve immediately and a turbidity resulted, after release-delaying coating, but if appropriate with an enteric the addition of the Salt the mixture was stirred for a further coating, is moreover achieved. 10 minutes. If undissolved salt still remained then, the 0212. The medicaments according to the invention in the undissolved portion was brought into Solution by addition of form to be administered orally, which release the respective Small amounts of water with Stirring. After obtainment of a active compound as early as on or immediately after admin clear Solution, the Sum E (in ml) of the amounts of water istration, furthermore have the advantage that their Strongly employed was determined. The solubility of the respective bitter or nauseating taste is compensated by the Simulta Salt per 1 ml of water was then calculated according to the neous release of the Sugar Substitute. The adherence to the following formula: dosage instructions in the patients thereby improves and the medicaments which contain the respective active compound as a Salt experience a greater acceptance. The medicaments Water solubility of the active compound salt in mg/ml of water = E according to the invention are moreover also Suitable for diabetics. 0213 For a large number of the abovementioned active 0218. The invention is explained below with the aid of compounds, the water Solubility of the conventional active examples. These explanations are only by way of example compound salts is known, for example from Phar and do not restrict the general inventive concept. mazeutische Stoffliste Pharmaceutical Substance List, 12th edition ABDATA Pharma-Daten-Service, 65735 Eschborn/ EXAMPLES Taunus. The corresponding disclosure sic is hereby inserted as reference and is thus regarded as part of the Example 1 disclosure. 0219. The preparation and the Subsequent separation of the optically pure compound (+)-(1S,2S)-3-(3-dimethy 0214) If the water solubility of an active compound salt is lamino-1-ethyl-2-methylpropyl)phenol was carried out not known, it can be determined according to the method according to DE-A-4426245. The corresponding part of the indicated below, according to which the water solubility of the pharmaceutical Salts according to the invention has also disclosure Sic) is hereby inserted as reference and is thus been determined: regarded as part of the disclosure. 0220 For the preparation of (+)-(1S,2S)-3-(3-dimethy 0215. In a clear colorless vessel made of transparent lamino-1-ethyl-2-methylpropyl)phenol Saccharinate, 2.58 g material, Such as, for example, glass or plastic, 1 ml of (10 mmol) of (+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2- ion-free water or a fraction (amount A in ml) thereof is methylpropyl)phenol hydrochloride and 2.42 g (10 mmol) of introduced at a temperature of 20° C. While stirring with a Saccharin-Sodium dihydrate were in each case completely magnetic Stirrer rod, the conventional active compound Salt dissolved with warming in an amount of water which was as to be tested or the pharmaceutical Salt according to the small as possible. Both solutions were then mixed with one invention was then added in portions. another with Stirring and then placed in a cool place over 0216) If the amount of salt Badded (in mg) completely night. The precipitated (+)-(1S,2S)-3-(3-dimethylamino-1- dissolved, further amounts of the respective salt were slowly ethyl-2-methylpropyl)phenol Saccharinate was separated off added. Each further addition was recorded and the Solution from the Supernatant mother liquor, purified with ethanol behavior observed. As soon as the first turbidity due to and isolated according to conventional methods. undissolved Salt was found by observation against a Suitable Example 2 background, Stirring was continued for a further 10 minutes. Ifundissolved constituents Subsequently remained, the Sum 0221 For the preparation of diphenhydramine sacchari C (in mg) of the amount of Substance employed was nate, 5.0 g (17.1 mmol) of diphenhydramine hydrochloride determined. If a clear Solution resulted again on Stirring, and 4.13 g (17.1 mmol) of saccharin-sodium dihydrate were further Small amounts of the respective Salt were added and in each case completely dissolved with warming in an the mixture was in each case Stirred again for 10 minutes amount of water which was as Small as possible. Both until a first turbidity remained on account of undissolved Solutions were then mixed with one another with Stirring and Salts. The exceSS amount of undissolved Substance was then then placed in a cool place overnight. The precipitated brought into solution with stirring by addition of small diphenhydramine Saccharinate was separated off from the amounts of water. After a clear Solution had been obtained, Supernatant mother liquor, purified with ethanol and isolated the sum D (in ml) of the amount of water employed was according to conventional methods. US 2005/0176790 A1 Aug. 11, 2005

Example 3 stirring with 0.075 g of orange-mandarin flavor 10888-56 0222 For the preparation of Verapamil saccharinate, 415 (Givaudan Roure Flavors Ltd. CH 8600 Dibendorf). mg (0.845 mmol) of Verapamil hydrochloride and 204 mg (0.845 mmol) of saccharin-sodium dihydrate were in each Example 8 case completely dissolved with warming in an amount of 0228. In this example, the water solubility of certain water which was as Small as possible. Both Solutions were then mixed with one another with Stirring and then placed in pharmaceutical Salts and of conventional Salts of the corre a cool place overnight. The precipitated Verapamil Saccha sponding active compound was determined according to the rinate was separated off from the Supernatant mother liquor, method indicated above. The solubility values thus obtained purified with ethanol and isolated according to conventional are presented in table 1 below: methods. TABLE 1. Example 4 Comparison of the water solubilities of certain pharmaceutical salts according to the invention and 0223 For the preparation of morphine saccharinate, 285 corresponding conventional salts of these active mg (0.76 mmol) of morphine hydrochloride trihydrate and compounds. The conventional salt employed in each case 183 mg (0.76 mmol) of saccharin-sodium dihydrate were in is indicated in brackets. each case completely dissolved with warming in an amount Solubility of of water which was as small as possible. Both solutions were Solubility of the active then mixed with one another with Stirring and then placed in the active compound a cool place overnight. The precipitated morphine Saccha compound salt saccharinate rinate was separated off from the Supernatant mother liquor, in mg/ml of in mg/ml of purified with ethanol and isolated according to conventional Active compound water water methods. (-)-(1R,2R)-3-(3- 261 31 dimethylamino-1-ethyl- (hydrochloride) 2-methylpropyl)phenol Example 5 (1RS,3RS,6RS)-6- 500 71 dimethylaminomethyl-1- (hydrochloride) 0224 For the preparation of an oral gel, 0.33 g of (3-methoxy methylparaben, 0.05 g of propylparaben and 75.0 g of xylitol phenyl)cyclohexane were first dissolved in 198.0 g of purified water at a 3-diol sic (+)-(1S,2S)-3-(3- 650 55 temperature of 80 C. and the mixture was then cooled to dimethylamino-1-ethyl- (hydrochloride) 40° C. Then, initially 0.94 g of diphenhydramine sacchari 2-methylpropyl)phenol nate obtained according to example 2 and Subsequently 2 g (-)-(1S,2S)-3-(3- 568 130 of Xanthan gum were added with Stirring, Stirring was dimethylamino-1-ethyl- (hydrochloride) -fluoro-2-methyl continued for one hour and evaporated water was replaced. propyl)phenol After cooling to a temperature of 20 to 25 C., the mixture (-)-(2S,3S)-1- 2OOO 90 was flavored with 0.625g of Tutti-Frutti 9/008897 (Dragoco dimethylamino-3-(3- (hydrochloride) Gerberding & Co. AG, 37603 Holzminden) while stirring. methoxyphenyl)- 2-methylpentan-3-ol (+)-(1R,2R,4S)-2- 33 1O Example 6 dimethylaminomethyl-4- (hydrochloride) (4-fluorobenzyl-Oxy)- 0225, 5 g of comminuted chewing gum mass (Popeye -(3-methoxy Amural Confections, Yorkville, Ill., USA) were warmed to phenyl)cyclohexanol a temperature of 30 to 40 C. in a Fanta dish. 187.9 mg of Morphine 52 25 (hydrochloride diphenhydramine Saccharinate obtained according to trihydrate) example 2 were then incorporated into the Viscous chewing Amezinium 25 8 gum mass using a pestle. The homogeneous mass was then (metilsulfate) portioned into teflonized molds to give portions of 1 g each. Phenylephrine 1250 38O (hydrochloride) 0226. The taste test showed that the chewing gums which Verapamil 2OO 7 (hydrochloride) contained the diphenhydramine Saccharinate had an excel Diphenhydramine 1OOO 7 lent taste at the Start and were still enjoyable even after a (hydrochloride) relatively long chewing time. Benzalkonium 500 <2 (hydrochloride) Codeine 250 2OO Example 7 (phosphate hemihydrate) 0227 For the preparation of a juice on an aqueous basis, Hydromorphone 330 130 0.33 g of methylparaben, 0.05 g of propylparaben and 75.0 (hydrochloride) g of xylitol were dissolved in 199.22 g of purified water at Buprenorphine 4 2 a temperature of 80 C. The mixture was cooled to 40 C. (hydrochloride) and 78.5 mg of (+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2- methylpropyl)phenol Saccharinate obtained according to example 1 were added with Stirring. 0.25 g of Xanthan gum 0229 AS can be seen from the solubility values according was then added, Stirring was continued for one hour and to table 1, the Solubility of the respective active compound evaporated water was replaced. After cooling to lacuna Saccharinates is lowered compared with the corresponding temperature of 20 to 25 C., the mixture was flavored while conventional active compound Salts. US 2005/0176790 A1 Aug. 11, 2005

1. A pharmaceutical Salt of a pharmaceutical active com Salt-forming compound of 1-phenyl-3-dimethylaminopro pound and at least one Sugar Substitute with the exception of pane compounds of the general formula I the respective pharmaceutical Salt of a Sugar Substitute and tramadol, (+)-tramadol, (-)-tramadol, (+)-demethyltramadol and (-)-demethyltramadol. X R1 2. The pharmaceutical Salt as claimed in claim 1, char 21 s acterized in that the solubility of the salt in water is s250 mg/ml of water, preferably s 200 mg/ml, particularly pref Rs-H erably s 150 mg/ml, very particularly preferably s 100 5 y -CH mg/ml. R4 3. The pharmaceutical Salt as claimed in claim 1, char CH acterized in that the Salt-forming Sugar Substitute is Saccha rin, cyclamate or aceSulfam, preferably Saccharin. in which 4. The pharmaceutical Salt as claimed in claim 1, char X is OH, F, Cl, H or an OCOR group, acterized in that the Salt-forming active compound is Selected from the group consisting of the Salt-forming anal R" is a C-alkyl group, gesics, antiobesity agents, analeptics, antihypoxemics, anti R’ is H or a C-alkyl group and R is H or a straight rheumatics, opioid antagonists, anthelmintics, antiallergics, chain C-alkyl group or the radicals R and R' antiarrhythmics, antibiotics, anti-dementives (nootropics), together form a C-7-cycloalkyl radical, and antidiabetics, anti-emetics, antivertiginous agents, antiepi leptics, antihypertensives, antihypotensives, antimycotics, if R is H, R" is meta-O-Z where Z is H, C-alkyl, antiinflammatories, antituSSives, expectorants, arteriosclero PO(O-C-alkyl), CO(OC-alkyl), CONH sis agents, 3-receptor blockers, calcium channel blockers, CH-(C3-alkyl), CO-CH-R", where R is broncholytics, anti-asthmatics, cholinergics, diuretics, circu ortho-OCOC-alkyl or meta- or para-CHN(R) lation-promoting agents, Weaning agents, geriatrics, hypnot where R is C-alkyl or 4-morpholino, or R' is meta ics, Sedatives, immunomodulators, oral therapeutics, pha S-C3-alkyl, meta-Cl, meta-F, meta-CR'R'R'' ryngeal therapeutics, coronary agents, hypolipidemics, local where R, R', R'' are H or F, ortho-OH, ortho-O- anesthetics, neural therapeutics, gastric agents, intestinal C3-alkyl, para-F or para-CRR'R'' where R, R', agents, migraine agents, muscle relaxants, anesthetics, neu R" are H or F, or if R is para-Cl, -F, -OH or ropathy preparations, ophthalmologicals, otologicals, Par -O-C-alkyl, R' is meta-Cl, -F, -OH or kinson agents, psychopharmaceuticals, rhinologicals, Sinusi -O-C-alkyl, or tis agents, Spasmolytics, platelet aggregation inhibitors, tuberculosis agents, urologicals and cytostatics. R" and R together are 3,4-OCH=CH- or 3,4- 5. The pharmaceutical Salt as claimed in claim 4, char OCH=CHO-, acterized in that the active compound is Selected from the R is C-alkyl, group consisting of the Salt-forming analgesics, analeptics, antihypoxemics, antiallergics, antiarrhythmics, antiemetics, in the form of their possible Stereoisomers as racemates or antivertiginous agents, antihypertensives, antihypotensives, diastereomerically pure enantiomers or in the form of antituSSives, expectorants, B-receptor blockers, calcium mixtures of enantiomers, in which the respective enan channel blockers, ophthalmologicals, otologicals, Spas tiomers are present in nonequimolar amounts. molytics and urologicals, preferably from the group consist 10. The pharmaceutical salt as claimed in claim 9, char ing of the Salt-forming analgesics. acterized in that X is OH, F, Clor H, R' is a C-alkyl group, 6. The pharmaceutical Salt as claimed in claim 4, char R is H or CH and R is H or CH and if R is H, R' is acterized in that the Salt-forming analgesic is Selected from meta-O-C-alkyl, meta-OH, meta-S-C1-alkyl, meta-F, the group consisting of the Salt-forming opioids, the Salt meta-Cl, meta-CH, meta-CFH, meta-CF or para-CF or if forming opiod analogs, ephdrine, chloroquine lidocaine, R is a para-Clor-F, R' is meta-Cl or -F, or R' and R' ethaverine, preglumetacin and triflupromazine. together are 3,4-OCH=CH-. 7. The pharmaceutical Salt as claimed in claim 6, char 11. The pharmaceutical Salt as claimed in claim 9, char acterized in that the Salt-forming opioid or opioid analog is acterized in that the radicals R and R have different Selected from the group consisting of morphine, codeine, meanings and the compounds of the general formula I as ethylmorphine, diacetylmorphine, dihydrocodeine, etor claimed in claim 9 are present in the form of their diaste phine, hydrocodone, hydromorphone, levorphanol, oxyc reomers having the configuration Ia odone, oxymorphone, pethidine, ketobemidone, fentanyl, alfentanil, remifentanil, Sufentanil, levomethadone, Ia levomethadyl, dextromoramide, dextropropoxyphene, R5 diphenoxylate, piritramide, tilidine, buprenorphine, butor phanol, deZOZine, nalbuphine, nalorphine, pentazocine, -H R. N nefopam, flupirtin and meptazinol. X H 8. The pharmaceutical Salt as claimed in claim 7, char acterized in that the Salt-forming opioid is Selected from the R1 group consisting of morphine, codeine, hydrocodone, hydro 'R2 morphone, oxycodone, tilidine, fentanyl and buprenorphine. 9. The pharmaceutical Salt as claimed in claim 1, char HC CH acterized in that the Salt-forming active compound is a US 2005/0176790 A1 Aug. 11, 2005

12. The pharmaceutical Salt as claimed in claim 9, char in the form of their possible Stereoisomers as racemates or acterized in that the Salt-forming 1-phenyl-3-dimethylami diastereomerically pure enantiomers or in the form of nopropane compound is Selected from the group consisting mixtures of enantiomers, in which the respective enan of tiomers are present in nonequimolar amounts. (1RS,2RS)-3-(3-dimethylamino-1-hydroxy-1,2-dimeth 14. The pharmaceutical Salt as claimed in claim 13, ylpropyl)phenol, characterized in that R' is H, OH or F. 15. The pharmaceutical salt as claimed in claim 13, (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropy characterized in that the compounds of the general formula l)phenol, II have a configuration in which the phenyl ring and the (+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2-methylpropy dimethylaminomethyl group are in each case arranged in an l)phenol, equatorial position to one another. 16. The pharmaceutical Salt as claimed in claim 13, (2RS,3RS)-1-dimethylamino-3-(3-methoxyphenyl)-2- characterized in that the Salt-forming 6-dimethylaminom methylpentan-3-ol, ethyl-1-phenylcyclohexane compound is Selected from the (-)-(1S,2S)-3-(3-dimethylamino-1-ethyl-1-fluoro-2-me group consisting of thylpropyl)phenol, (-)-(1R,2R)-3-(2-dimethylaminomethylcyclohexy (+)-(1R,2R)-3-(3-dimethylamino-1-hydroxy-1,2-dimeth l)phenol, ylpropyl)phenol, (1RS,3RS,6RS)-6-(dimethylaminomethyl)-1-(3-methox (+)-(2R,3R)-1-dimethylamino-3-(3-methoxyphenyl)-2- yphenyl)cyclohexane-1,3-diol and methylpentan-3-ol and (1RS,3RS,6RS)-6-(dimethylaminomethyl)-1-(3-hydrox (-)-(2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2- yphenyl)cyclohexane-1,3-diol. methylpentan-3-ol. 17. The pharmaceutical Salt as claimed in claim 1, char 13. The pharmaceutical Salt as claimed in claim 1, char acterized in that the Salt-forming active compound is a acterized in that the Salt-forming active compound is a Salt-forming compound of 1-phenyl-2-dimethylaminometh Salt-forming compound of 6-dimethylaminomethyl-1-phe ylcyclohexan-1-ol compounds of the general formula III, nylcyclohexane compounds of the general formula II,

III II R1" A^

YZ 4. OH

N in which HC1 YCH, R" is H, OH, C1 or F, R and Rare identical or different and are H, C-alkyl, in which in each case benzyl, CF, OH, OCH-CH, O-C-alkyl, C1 or A is O or S, F with the proviso that at least one of the radicals R' R" is H, C,c-alkyl, C-alkenyl, Cs 7-cycloalkyl or or R is H, halogenated C6-alkyl, R" is H, CH, PO(O-C-alkyl), CO(O-C-s-alkyl), CO-NH-CH-C-alkyl, CO-CH-R, the group CO-C-s-alkyl, CO-CHR-NHR' or an unsubsti tuted or Substituted pyridyl, thienyl, thiazoyl sic or phenyl group, / / ( R is OC(O)C-alkyl in the ortho-position or CH -YEZ. -CH-CH -CH= N(R) in the meta- or para-position, where R is \ is \ s O C-alkyl or both radicals R together with N are the / 4-morpholino radical, and -O-CH R and R7 are identical or different and are H or C s alkyl, with the proviso that if both radicals R and Rare H, R' R" is C6-alkyl, C6-alkenyl, Cs-7-cycloalkyl-methyl, is not CH if R is H, OH or C1 or R' is not H if R' Substituted or unsubstituted phenyl or substituted or is OH, unsubstituted benzyl, US 2005/0176790 A1 Aug. 11, 2005

in the form of their possible Stereoisomers as racemates or R" is H, OH, C-alkyl, O-C-alkyl, O-benzyl, diastereomerically pure enantiomers or in the form of CHF, CF, O-CF, Cl, For OR" and mixtures of enantiomers, in which the respective enan tiomers are present in nonequimolar amounts. R" is H, OH, C-alkyl, O-C-alkyl, O-benzyl, CFs, 18. The pharmaceutical salt as claimed in claim 17, O–CF, Cl, For OR", characterized in that R'" is H, C-alkyl, 2'-methyl-2'- with the proviso that two of the radicals R", R" or R." propenyl, cyclopentyl or fluoroethyl, with the proviso that are H, or R" is C-alkyl if A is S, R" and R" together are -CH=C(R'")-O- or R" is C-alkyl, C-alkenyl, cyclopentylmethyl, phe -CH=C(R")-S-, with the proviso that R" is H, nyl, C-alkoxyphenyl, benzyl, C-alkylbenzyl, O mono- or dihalogenated phenyl or mono- or dihaloge nated benzyl. R" and R" together are -CH=CH 19. The pharmaceutical salt as claimed in claim 17, C(OR'")=CH-, with the proviso that R" is H, characterized in that R" is H, methyl, ethyl, isopropyl, R" is Cis-alkyl, Css-cycloalkyl, O-C-alkyl, O-ben 2-methyl-2'-propenyl, cyclopentyl or fluoroethyl, with the Zyl, CF, C1 or F, proviso that R'" is methyl if A is S, R8." is CO-C-s-alkyl, PO(O-C-alkyl), R" is methyl, propyl, 2-methylpropyl, allyl, 2-methyl CO-CH-R", CO(O-C-alkyl), 2'-propenyl, cyclopentylmethyl, phenyl, 3-methoX CO-CHR" -NHR'. ", CO-NH-CH (R"). yphenyl, benzyl, 4-tert-butylbenzyl, 4-chlorobenzyl, or an unsubstituted or Substituted pyridyl, thienyl, 4-fluorobenzyl or 3,4-dichlorobenzyl. thiazoyl sic or phenyl group, 20. The pharmaceutical salt as claimed in claim 17, characterized in that the compounds of the general formula R" is H or C-alkyl, III have a configuration in which the phenyl ring and the R" is H or C-alkyl, dimethylaminomethyl group are in each case arranged in an equatorial position to one another. R" is OC(O)-C-alkyl in the ortho-position or CH 21. The pharmaceutical Salt as claimed in claim 17, N-(R'") in the meta- or para-position, where R'" is characterized in that the Salt-forming 1-phenyl-2-dimethy C-alkyl or both radicals R'" together with N form laminomethylcyclohexan-1-ol compound of the general for the 4-morpholino radical, mula III is Selected from the group consisting of R'" and R'" are identical or different and are H, (+)-(1R,2R,4S)-2-(dimethylaminomethyl)-4-(4-fluo C-alkyl or Cs-cycloalkyl or R'" and R'" together robenzyloxy)-1-(3-methoxyphenyl)cyclohexanol, are -(CH2) , (+)-(1R,2R,4S)-2-dimethylaminomethyl-4-(4-chloro R" is H, OH, C-alkyl, O-C-7-alkyl, phenyl, O-aryl, benzyloxy)-1-(3-methoxyphenyl)cyclohexanol and CF, Clor F, with the proviso that the two radicals R'" (+)-(1R,2R,4S)-3-2-dimethylaminomethyl-4-(4-fluo are identical or different, robenzyloxy)-1-hydroxycyclohexylphenol. in the form of their possible Stereoisomers as racemates or 22. The pharmaceutical Salt as claimed in claim 1, char diastereomerically pure enantiomers or in the form of acterized in that the Salt-forming active compound is a mixtures of enantiomers, in which the respective enan Salt-forming dimethyl-(3-arylbut-3-enyl)amine compound tiomers are present in nonequimolar amounts. of the general formula IV, in which sic 23. The pharmaceutical Salt as claimed in claim 22, characterized in that R" is C-alkyl and R" is H or Cis-alkyl, or R'" and R together are -(CH2)2- or IV -(CH-)-CHR", R" is H or C-alkyl, R" is H, OH, CF, Cl, For OR", R" is H, OH, C-alkyl, O-C-alkyl, O-benzyl, CHF, CF, Cl, For OR" and -CH3 R" is H, OH, O-C-alkyl, O-benzyl, CF, Cl, F or OR", CH with the proviso that two of the radicals R", R" or R." are H, or the radical R" is Cis-alkyl and R" is H or C-s-alkyl or R" and R" together are -CH=C(R'")-O- or R" and R" together are -(CH) -, -(CH)- -CH=C(R")-S-, with the proviso that R" is H, CHR 7" or -CH-CHR 7"—CH2—, O R" is H or C-alkyl, R" and R" together are -CH=CH R" is H, OH, C-alkyl, O-C-alkyl, O-benzyl, CF, C(OR'")=CH-, with the proviso that R" is H, and O-CF, Cl, For OR", R" is C-alkyl, CF, Cl or F. US 2005/0176790 A1 Aug. 11, 2005

24. The pharmaceutical Salt as claimed in claim 22, preferably in the form of microtablets, microcapsules, gran characterized in that R" is CH or CH, and R" is H, CH ules, active compound crystals or pellets, particularly pref or CHCH, or R'" and R" together are -(CH-)-- or erably in the form of microtablets, granules or pellets, -(CH-)-CHR7", optionally filled into capsules or compressed to give tablets. R" is H, CH or CHCH, 32. The medicament as claimed in claim 27, characterized R" is H or OH, R" is H, OH, OCH, CHF, or OR" and in that the Salt is present at least partially in delayed-release R" is H, OH or CF, with the proviso that two of the form. radicals R", R" or R" are H, or 33. The medicament as claimed in claim 32, characterized in that delaying of the release is carried out by applying a R" and R" together are -CH=C(CH-)-S-, with the release-delaying coating, embedding in a release-delaying proviso that R" is H, or matrix, binding to an ion-exchange resin or by a combina R" and R" together are -CHOCH-C (OH)=CH-, tion of at least two of these methods. with the proviso that R" is H, and 34. The medicament as claimed in claim 33, characterized R" is CO-CH-R'" where R'" is OC(O)-C- in that the release-delaying coating is based on a water alkyl in the ortho-position. insoluble, optionally modified natural or Synthetic polymer, 25. The pharmaceutical Salt as claimed in claim 22, optionally in combination with a customary plasticizer, or on characterized in that a natural, Semisynthetic or Synthetic wax or fat or fatty R" is CH and R" is H or CH or R'" and R'" together alcohol or a mixture of at least two of these components. are -(CH2)2- or -(CH-)-CH(CH-)-, 35. The medicament as claimed in claim 33, characterized in that the matrix is based on a hydrophilic matrix material, R" is H or CH, preferably hydrophilic polymers, particularly preferably on R" is H, R" is OH or OR", R" is H, and R" is cellulose ethers, cellulose esters and/or acrylic resins, very CO-CH-R'" where R'" is OC(O)-CH in the particularly preferably on ethylcellulose, hydroxypropylm ortho-position. ethylcellulose, hydroxypropylcellulose, hydroxymethylcel 26. The pharmaceutical Salt as claimed in claim 22, lulose, poly(meth)acrylic acid and/or their their Salts, amides characterized in that the salt-forming dimethyl-(3-arylbut and/or esters. 3-enyl)amine compound present is trans-(-)-(1R)-3-1-(2- 36. The medicament as claimed in claim 33, characterized dimethylamino-1-methylethyl)propenylphenol. in that the matrix is based on a hydrophobic matrix material, 27. A medicament comprising at least one pharmaceutical preferably hydrophobic polymers, waxes, fats, long-chain Salt as claimed in claim 1 and, if appropriate, physiologically fatty acids, fatty alcohols or appropriate esters or ethers or tolerable excipients. their mixtures, particularly preferably on mono- or diglyc 28. A medicament comprising at least one pharmaceutical erides of C-C fatty acids and/or C-Co-fatty alcohols Salt as claimed in claim 6 for the control of pain. and/or waxes or their mixtures. 29. A medicament comprising at least one pharmaceutical 37. The medicament as claimed in claim 27, characterized Salt as claimed in claim 9 for the control of urinary incon in that it has a protective coating, preferably an enteric tinence. protective coating. 30. The medicament as claimed in claim 27, characterized in that it are sic present formulated in the form of gels, 38. The use of at least one pharmaceutical Salt as claimed chewing gums, juices, sprays, tablets, chewable tablets, in claim 6 for the production of a medicament for the control coated tablets, powders, if appropriate filled into capsules, of pain. easily reconstitutable dry preparations, preferably in the 39. The use of at least one pharmaceutical salt as claimed form of gels, aqueous or oily juices, Sublingual SprayS, in claim 9 for the production of a medicament for the tablets or chewable tablets. treatment of urinary incontinence. 31. The medicament as claimed in claim 27, characterized in that it is present formulated in multiparticulate form,