US 20090258948A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0258948 A1 BARTHOLOMAUS et al. (43) Pub. Date: Oct. 15, 2009

(54) PHARMACEUTICAL SALTS (30) Foreign Application Priority Data (75) Inventors: Johannes BARTHOLOMAUS, Aachen (DE); Heinrich Feb. 28, 2001 (DE) ...... 101 O9 763.8 Kugelmann, Aachen (DE) Correspondence Address: Publication Classification NORRIS, MCLAUGHILIN & MARCUS, PA (51) Int. Cl. 875 THIRDAVENUE, 18TH FLOOR A63L/38 (2006.01) NEW YORK, NY 10022 (US) A6IP 25/00 (2006.01) (73) Assignee: GRUNENTHAL GMBH, Aachen DE (DE) (52) U.S. Cl...... 514/649 (21) Appl. No.: 12/487,760 (22) Filed: Jun. 19, 2009 Related U.S. Application Data (57) ABSTRACT (60) Division of application No. 10/647,882, filed on Aug. The invention relates to pharmaceutical salts comprised of a 25, 2003, now abandoned, which is a continuation of pharmaceutical active Substance and of at least one Sugar application No. PCT/EP02/02169, filed on Feb. 28, Substitute, to medicaments containing these salts, and to the 2002. use of these salts for producing medicaments. US 2009/0258948 A1 Oct. 15, 2009

PHARMACEUTICAL SALTS hydrochloride. The corresponding literature description is hereby inserted as a reference and is thus regarded as part of the disclosure. 0001. The present invention relates to pharmaceutical salts 0008 According to the invention, suitable sugar substi of an active compound and at least one Sugar Substitute, tutes are all Sugar Substitutes which can form a salt with the medicaments comprising these salts, and the use of these salts respective pharmaceutical active compound with formation for the production of medicaments. ofanat least singly negatively charged form. According to the 0002 On oral administration, a large number of pharma invention, pharmaceutical salts are also included in which the ceutical active compounds having excellent activity lead to a pharmaceutical active compound has two or more different strongly bitter, often nauseating taste sensation in the patient. Sugar Substitutes as Salt components. Preferably, the pharma In some patients, lack of adherence to the dosage instructions ceutical salts according to the invention contain Saccharin, and a lack of acceptance of the corresponding medicaments cyclamate oracesulfam, particularly preferably saccharin, as which release Such an active compound as early as during salt-forming Sugar Substitutes. taking result from this negative taste experience. 0009. According to the invention, suitable active com 0003. The formulation of pharmaceutical active com pounds are all pharmaceutical active compounds which can pounds having very good water solubility to give medica forma Salt in anionic form with the respective Sugar Substitute ments frequently causes problems in pharmaceutical prac (s) with formation of an at least singly positively charged tice. Thus the preparation of pharmaceutical forms having form. controlled release is often made difficult on account of the 0010. In a further preferred embodiment of the present very good water solubility of active compound salts. A delay invention, the salt-forming active compound in the pharma ing of the release of these active compounds can in fact be ceutical salt according to the invention is selected from the achieved, for example, by coating the pharmaceutical forms group consisting of the salt-forming analgesics, antiobesity with release-delaying film coatings. This manner of delaying agents, analeptics, anti-hypoxemics, antirheumatics, opioid the release, however, is associated with a relatively high out antagonists, anthelmintics, antiallergics, antiarrhythmics, lay, since release-delaying film coatings from aqueous coat anti-biotics, antidementives (nootropics), antidiabetics, anti ing systems are frequently only an inadequate diffusion bar emetics, antivertiginous agents, antiepileptics, antihyperten rier for active compounds having very good water Solubility. sives, antihypotensives, antimycotics, antiinflammatories, The preparation of these delayed-release active compound antitussives, expectorants, arteriosclerosis agents, B-receptor preparations therefore requires relatively complicated coat blockers, calcium channel blockers, broncholytics, antiasth ing processes with multilayer films. If Such release-delaying matics, cholinergics, diuretics, circulation-promoting agents, coatings are applied from organic Solvents, the environmental weaning agents, geriatrics, hypnotics, sedatives, immuno and solvent residue problems associated therewith addition modulators, oral therapeutics, pharyngeal therapeutics, coro ally make the preparation of appropriate preparations more nary agents, hypolipidemics, local anesthetics, neural thera expensive. peutics, gastric agents, intestinal agents, migraine agents, muscle relaxants, anesthetics, neuropathy preparations, 0004. It was therefore the object of the present invention to opthalmologicals, otologicals, Parkinson agents, psycho make available pharmaceutical combinations of active com pharmaceuticals, rhinologicals, sinusitis agents, spasmolyt pounds which have no bitter taste. Preferably, the correspond ics, platelet aggregation inhibitors, tuberculosis agents, uro ing active compounds should be simpler to formulate and logicals and cytostatics. Particularly preferably, the salt their release should be more effectively delayed. forming active compound is selected from the group 0005 According to the invention, this object is achieved consisting of the salt-forming analgesics, analeptics, antihy by the provision of pharmaceutical salts, i.e. physiologically poxemics, antiallergics, antiarrhythmics, antiemetics, anti tolerable salts, from a pharmaceutical active compound and at Vertiginous agents, antihypertensives, anti-hypotensives, least one Sugar Substitute. antitussives, expectorants, B-receptor blockers, calcium 0006. The present invention therefore relates to pharma channel blockers, opthalmologicals, otologicals, spasmolyt ceutical salts of a pharmaceutical active compound and at ics and urologicals. Very particularly preferably, the salt least one Sugar Substitute, the respective pharmaceutical salts forming active compound is selected from the group consist of a Sugar Substitute and tramadol, (+)-tramadol, (-)-trama ing of the salt-forming analgesics, tramadol, (+)-tramadol, dol, (+)-demethyltramadol and (-)-demethyltramadol being (-)-tramadol, (+)-demethyltramadol and (-)-demethyltrama excepted. dol being excepted. 0007. In a preferred embodiment of the present invention, 0011. If the pharmaceutical active compound is a salt the solubility of the pharmaceutical salts according to the forming analgesic, it is preferably a salt-forming opioid or a invention in water is s250 mg/ml of water, preferably s200 salt-forming opioid analog, such as disclosed in E. Friderichs, mg/ml, particularly preferably s 150 mg/ml, Very particu T. Christoph, H. Buschmann, 'Analgesics and Antipyretics': larly preferably s100 mg/ml. This can also be seen in par Ullmann's Encyclopedia of Industrial Chemistry, Sixth Edi ticular in the fact that the water solubility of the pharmaceu tion on CD-ROM, Wiley-VCH. Weinheim, 2000 or in Phar tical salts according to the invention compared with the water maceuticals, J. L. McGuire (Editor), Analgesics and Anti solubility of the best water-soluble salt of the corresponding pyretics, Volume 2, pages 341-434, Wiley-VCH. Weinheim active compound according to PharmaZeutische Stoffliste or ephedrine, chloroquine, lidocaine, ethaverine, preglumeta Pharmaceutical Substance List, 12th edition ABDATA cin or triflupromazine. The corresponding disclosures are Pharma-Daten-Service, 65735 Eschborn/Taunus, is prefer hereby inserted as a reference and are thus regarded as part of ably lowered by at least 50%, preferably by at least 65%, the present disclosure. Particularly preferably, the salt-form particularly preferably by at least 75%, very particularly pref ing analgesic is selected from the group consisting of mor erably by at least 85%, compared with the corresponding phine, codeine, ethylmorphine, diacetylmorphine, dihydro US 2009/0258948 A1 Oct. 15, 2009 codeine, etorphine, hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone, pethidine, ketobe midone, fentanyl, alfentanil, remifentanil, Sufentanil, Ia levomethadone, levomethadyl, dextro-moramide, dextropro R5 poxyphene, diphenoxylate, piri-tramide, tilidine, buprenor phine, butorphanol, deZozine, meptazinol, nalbuphine, nalor --R'. phine, pentaZo-cine, flupirtin and nefopam or a representative sn of the group consisting of ephedrine, chloroquine, lidocaine, ethaverine, preglumetacin and triflupromazine. Very particu X H larly preferably, the salt-forming analgesic is a salt-forming opioid or opioid analog selected from the group consisting of R 'R2 morphine, codeine, hydrocodone, hydromorphone, oxyc odone, tilidine, fentanyl and buprenorphine. HC CH 0012. Likewise preferably, the salt-forming active com pound is a salt-forming compound of 1-phenyl-3-dimethy lamino-propane compounds of the general formula I 0015. Very particularly preferred is a salt-forming com pound of 1-phenyl-3-dimethylaminopropane compounds of the general formula I, selected from the group consisting of 0016 (1RS,2RS)-3-(3-dimethylamino-1-hydroxy-1,2- dimethyl-propyl)phenol, 0017 (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-meth ylpropyl)-phenol, 0018 (+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2-meth ylpropyl)-phenol, 0019 (2RS,3RS)-1-dimethylamino-3-(3-methoxyphe nyl)-2-methylpentan-3-ol, in which in each case 0020 (-)-(1S,2S)-3-(3-dimethylamino-1-ethyl-1-fluoro X is OH, F, Cl, Horan OCOR group, 2-methylpropyl)phenol, R" is a Cla-alkyl group, 0021 (+)-(1R,2R)-3-(3-dimethylamino-1-hydroxy-1,2- R’ is H or a C-alkyl group and R is H or a straight-chain dimethyl-propyl)phenol, C-alkyl group or the radicals R and R together form a 0022 (+)-(2R,3R)-1-dimethylamino-3-(3-methoxyphe C-7-cycloalkyl radical, and nyl)-2-methylpentan-3-ol and if R is H, R is meta-O-Z where Z is H, C-alkyl, PO(O- 0023 (-)-(2S,3S)-1-dimethylamino-3-(3-methoxyphe C-alkyl). CO(OCs-alkyl). CONH-CH (C- nyl)-2-methylpentan-3-ol. alkyl). CO C.H. R", where R7 is ortho-OCOC-alkyl or 0024. The preparation of the salt-forming compounds of meta- or para-CHN(R), where R is C-alkyl or 4-mor 1-phenyl-3-dimethylaminopropane compounds of the gen pholino, or R is meta-S-C1-alkyl, meta-Cl, meta-F, meta eral formula I and, if appropriate, the separation into the pure CRR'R'' where R, R'' and R'' are H or F, ortho-OH, optical antipodes can be carried out according to customary ortho-O C-alkyl, para-F or para-CRR'R'' where R. methods known to the person skilled in the art. Preferably, the R', R'' are H or F, or if R is para-C1, F. -OH or preparation and, if appropriate, the separation is carried out as —O-C-s-alkyl, R is meta-Cl, -F, -OH or —O-C-s- described in DE-A-4426245 or EP 0 693 475 B1, which are alkyl, or hereby inserted as reference and are thus regarded as part of R" and R together are 3,4-OCH=CH- or 3,4- the disclosure. OCH=CHO , 0025. In a further preferred embodiment of the present R is C-alkyl, invention, the pharmaceutical salt according to the invention in the form of their possible stereoisomers as racemates or contains as a salt-forming active compound a salt-forming diastereomerically pure enantiomers or in the form of mix compound of 6-dimethylaminomethyl-1-phenylcyclohexane tures of enantiomers, in which the respective enantiomers are compounds of the general formula II, present in nonequimolar amounts. 0013 Preferred is a salt-forming compound of 1-phenyl II 3-dimethylaminopropane compounds of the general formula I in which X is OH, F, Clor H. R' is a C-alkyl group, R is Hor CH, and R is Hor CH and if R is H, R is Meta-O- C-alkyl, meta-OH, meta-S-C1-alkyl, meta-F, meta-Cl, meta-CH meta-CF.H. meta-CF, or para-CF, or if R is a para-Clor-F, R is meta-Clor-F, or RandR together are 3,4-OCH-CH . 0014) Particularly preferred is a salt-forming compound of 1-phenyl-3-dimethylaminopropane compounds of the gen eral formula I in which the radicals R and R have different meanings and which are present in the form of their diaste reomers having the configuration Ia US 2009/0258948 A1 Oct. 15, 2009

in which in each case

R" is H, OH, C1 or F, preferably H, OH or F, III R and Rare identical or different and are H, C-alkyl, R1" benzyl, CF, OH, OCH CH, O C-alkyl, Clor F with ^ the proviso that at least one of the radicals R or R is H. R" is H, CH, PO(O C-alkyl). CO(OCs-alkyl). CO. NH-CH C-alkyl, CO C.H. R. CO Cls alkyl, CO-CHR NHR7 oran unsubstituted or substituted pyridyl, thienyl, thiazoyl sic or phenyl group, Y FZ. R is OC(O)C-alkyl in the ortho-position or CH N(R) R{ OH in the meta- or para-position, where R is C-alkyl or both radicals R together with N are the 4-morpholino radical, and R” and Rare identical or different and are H or C-alkyl, HC1 N NCH, 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, in which in each case in the form of their possible stereoisomers as racemates or diastereomerically pure enantiomers or in the form of mix A is O or S. tures of enantiomers, in which the respective enantiomers are 10032) R' is H. Co-alkyl, C-alkenyl, Cs, -cycloalkyl present in nonequimolar amounts. or halogenated C-alkyl, 0026. Preferred are salt-forming compounds of 6-dim ethylaminomethyl-1-phenylcyclohexane compounds of the 0033 the group general formula II, which are present in the configuration as in the general formula IIa, / -YEZ.

IIa is the group

-CH-CH,/ -CH=(( or -O-CH,/ \ V in which the phenyl ring and the dimethylaminomethyl group are in each case arranged in an equatorial position to one R" is C6-alkyl, Co-alkenyl, Cs 7-cycloalkylmethyl, Sub another. stituted or unsubstituted phenyl or substituted or unsubsti 0027 Particularly preferred is a salt-forming compound of tuted benzyl, b-dimethylaminomethyl-1-phenylcyclohexane compounds in the form of their possible stereoisomers as racemates or of the general formula II selected from the group consisting of diastereomerically pure enantiomers or in the form of mix 0028 (-)-(1R,2R)-3-(2-dimethylaminomethylcyclo tures of enantiomers, in which the respective enantiomers are hexyl)phenol, present in nonequimolar amounts. 0029 (1RS,3RS,6RS)-6-(dimethylaminomethyl)-1-(3- 0034 Preferred are salt-forming compounds of 1-phenyl 2-dimethylaminomethylcyclohexan-1-ol compounds of the methoxy-phenyl)cyclohexane-1,3-diol and (1RS,3RS, general formula III, in which R" is H, Ca-alkyl, 2'-methyl 6RS)-6-(dimethylaminomethyl)-1-(3-hydroxy-phenyl) 2'-propenyl, cyclopenty1 or fluoroethyl, with the proviso that cyclohexane-1,3-diol. R" is C-alkyl if A is S, 0030 The preparation of the salt-forming compounds of R" is Cla-alkyl, Ca-alkenyl, cyclopentylmethyl, phenyl, 6-dimethylaminomethyl-1-phenylcyclohexane compounds C-alkoxyphenyl, benzyl, C-alkylbenzyl, mono- or diha of the general formula II and, if appropriate, the separation logenated phenyl or mono- or dihalogenated benzyl. into the optically pure antipodes can be carried out according 0035 Particularly preferred are salt-forming compounds to customary methods known to the person skilled in the art. of 1-phenyl-2-dimethylaminomethylcyclohexan-1-ol com Preferably, the preparation and, if appropriate, the separation pounds of the general formula III, in which R" is H. methyl, are carried out as described in DE-A-19525137. The corre ethyl, isopropyl. 2'-methyl-2'-propenyl, cyclopentyl or fluo sponding literature description is hereby inserted as reference roethyl, with the proviso that R" is methyl if A is S, and is thus regarded as part of the disclosure. R" is methyl, propyl. 2'-methylpropyl, allyl. 2'-methyl-2'- 0031. In a further preferred embodiment of the present propenyl, cyclopentylmethyl, phenyl, 3-methoxyphenyl, invention, the pharmaceutical salt according to the invention benzyl, 4-tert-butylbenzyl, 4-chloro-benzyl, 4-fluorobenzyl contains as a salt-forming active compound a salt-forming or 3,4-dichlorobenzyl. compound of 1-phenyl-2-dimethylaminomethylcyclohexan 0036 Very particularly preferred are salt-forming com 1-ol compounds of the general formula III, pounds of 1-phenyl-2-dimethylaminomethylcyclohexan-1- US 2009/0258948 A1 Oct. 15, 2009 ol compounds of the general formula III which are present in R" is H, OH, C-alkyl, O C -alkyl, O-benzyl, CFs, the configuration of the formula IIIa, O CF, C1, For OR", with the proviso that two of the radicals R", R" or R." are H, O IIIa R" and R" together are -CH=C(R") O-or-CH=C (R") S , with the proviso that R" is H, or OH R" and R" together are CH=CH-C(OR'")=CH-, with the proviso that R'" is H, R" is Cis-alkyl, Cs-cycloalkyl, O-C-alkyl, O-benzyl, CF, Clor F, R" is CO Cls-alkyl, PO(O C-alkyl). CO C.H. R''", CO(O C-alkyl), CO CHR'?" NHR'", CO. NH-CH (R'"), oran unsubstituted or substituted pyridyl, thienyl, thiazoyl sic or phenyl group, in which the phenyl ring and the dimethylaminomethyl group R" is H or C-alkyl, are in each case arranged in an equatorial position to one R'" is H or C-alkyl, another. R'" is OC(O)—C-alkyl in the ortho-position or CH 0037 Most preferred is the salt-forming compound of N—(R'"), in the meta- or para-position, where R'" is C.- 1-phenyl-2-dimethylaminomethylcyclohexan-1-ol CO alkyl or both radicals R'" together with N form the 4-mor pounds of the general formula III selected from the group pholino radical, consisting of R'" and R'" are identical or different and are H, Co-alkyl 0038 (+)-(1R,2R,4S)-2-(dimethylaminomethyl)-4-(4- or Css-cycloalkyl or R'" and R'" together are —(CH.) fluoro-benzyloxy)-1-(3-methoxyphenyl)cyclohexanol, R'"8—, is H, OH, C-alkyl, O Cl-,-alkyl, phenyl, O-aryl, 0039 (+)-(1R,2R,4S)-2-dimethylaminomethyl-4-(4- CF, C1 or F, with the proviso that the two radicals R'" are chlorobenzyloxy)-1-(3-methoxyphenyl)cyclohexanol and identical or different, 0040 (+)-(1R,2R,4S)-3-2-dimethylaminomethyl-4-(4- in the form of their possible stereoisomers as racemates or fluoro-benzyloxy)-1-hydroxycyclohexylphenol. diastereomerically pure enantiomers or in the form of mix 0041. The preparation of the salt-forming compounds of tures of enantiomers, in which the respective enantiomers are 1-phenyl-2-dimethylaminomethylcyclohexan-1-ol CO present in nonequimolar amounts. pounds of the general formula III and, if appropriate, the 0043 Preferred are salt-forming compounds of dimethyl separation into the optically pure antipodes can be carried out (3-arylbut-3-enyl)amine compounds of the general formula according to customary methods known to the person skilled IV, in which in the art. Preferably, the preparation and, if appropriate, the R" is C-alkyl and R" is H or C-alkyl, or R'" and separation are carried out as described in DE-A-19547766, R" together are —(CH) or —(CH2). CHR", which is hereby inserted as reference and is thus regarded as R" is H or C-alkyl, part of the disclosure. 0042. In a further preferred embodiment of the present R" is H, OH, CF, C1, For OR", invention, the pharmaceutical salt contains as a salt-forming 0044) R" is H, OH, C-alkyl, O C-alkyl, O-benzyl, active compound a salt-forming compound of dimethyl-(3- CHF, CF, C1, For OR" and arylbut-3-enyl)amine compounds of the general formula IV. R" is H, OH, O C-alkyl, O-benzyl, CF, Cl, For OR", in which sic with the proviso that two of the radicals R", R" or R." are H, O R", and R" together are -CH=C(R) O— or -CH=C IV (R") S , with the proviso that R" is H, or R" and R" together are CH=CH-C(OR'")=CH-, with the proviso that R" is H, and R" is C-alkyl, CF, C1 or F. 0045 Particularly preferred are salt-forming compounds of dimethyl-(3-arylbut-3-enyl)amine compounds of the gen eral formula IV, in which R" is CH or CH, and R" is H, CH or CHCH, or R'", and R" together are —(CH) or -(CH). CHR7", R" is H, CH or CHCH 0046 R" is Hor OH, Ri" is H, OH, OCH, CHF, or OR" the radical R" is Cis-alkyl and R" is Hor Cs-alkylor R'" and R" is H, OH or CF, with the proviso that two of the and R" together are -(CH2). , , -(CH2). CHR" or radicals R", Ri" or R" are H, or —CH CHR" CH , R" and R" together are -CH=C(CH)–S , with the R" is H or C-s-alkyl, proviso that R" is H, or R" is H, OH, C-alkyl, O C-alkyl, O-benzyl, CFs, R" and R'" together are -CH=CH-C(OH)—CH-, with O CF, Cl, For OR", the proviso that R" is H, and R" is H, OH, C-alkyl, O C-alkyl, O-benzyl, CHF, R" is CO C.H. R'" where R'" is OC(O) C-alkyl CF, O CF, Cl, For OR" and in the ortho-position. US 2009/0258948 A1 Oct. 15, 2009

0047 Very particularly preferred are salt-forming com 0.058 As salt-forming antidementive (nootropics), the pounds of dimethyl-(3-arylbut-3-enyl)amine compounds of pharmaceutical Salt according to the invention can preferably the general formula IV, in which contain butalamine, memantine, pyritinol, donepezil, mox R" is CH and R" is Hor CH or R'" and R" together are averine, meclofenoxate, dihydroergotoxin, Viquidil, naftidro —(CH2) - or —(CH2) -CH(CH)—, furyl, dihydroergocornine, dihydroergocristine, benzyclan, procaine, deamol. diisopropylamine or 3-pyridylmethanol. R" is H or CH, 0059. As a salt-forming antidiabetic, the pharmaceutical 0048 R" is H, R" is OH or OR", R" is H, and R" is salt according to the invention can preferably contain met CO C.H. R'" where R'" is OC(O)-CH in the ortho formin. position. 0060. As salt-forming antiemetics and/or antivertiginous 0049 Most preferred is the salt-forming compound of agents, the pharmaceutical salt according to the invention can dimethyl-(3-arylbut-3-enyl)amine compounds of the general preferably contain betahistidine, dolasetrone, meclozine, formula IV trans-(-)-(1R)-3-1-(2-dimethylamino-1-methyl hydroxycine, diphenhydramine, pyridoxine, granisetrone, ethyl)propenylphenol. triflupromazine, triethylperazine, betahistine, alizapride or 0050. The preparation of the salt-forming compounds of odansetrone, particularly preferably diphenhydramine. dimethyl-(3-arylbut-3-enyl)amine compounds of the general 0061. As a salt-forming antiepileptic, the pharmaceutical formula IV and, if appropriate, the separation into the opti salt according to the invention can preferably contain tiaga cally pure antipodes can be carried out according to custom bine. ary methods known to the person skilled in the art. Preferably, 0062. As salt-forming antihypertensives, the pharmaceu the preparation and, if appropriate, the separation of these tical salt according to the invention can preferably contain compounds are carried out as described in EP 0 799 819 A1. dihydralazine, prazosine, amiloride, bunaZosine, nicardipine, The corresponding literature description is hereby inserted as alprenolol, candesartancilexetil, metoprolol, Verapamil, pro reference and is thus regarded as part of the disclosure. pranolol, penbutolol, doxazosine, clonidine, benazepril, phe 0051. As salt-forming antiobesity agents, the pharmaceu noxybenzamine, diltiazem, diisopropylamine, urapide, car tical salt according to the invention can preferably contain teolol guanethidine, guanfacine, teraZosine, Oxprenolol. D-norpseudoephedrine, phenylpropanolamine, amfepra cicletanine, betaxolol, nebivolol, acebutolol, enalapril or mone, mefenorex or ephedrine. indoramine, particularly preferably Verapamil or diltiazem. 0052. As salt-forming analeptics and/or antihypoxemics, 0063 As salt-forming antihypotensives, the pharmaceuti the pharmaceutical salt according to the invention can pref cal salt according to the invention can preferably contain erably contain norfenefrine, heptaminol or amezinium, par etilefrine, pholedrine, norfenefrine, cafedrine, theodrenaline, ticularly preferably amezinium. oXilofrine, dobutamine, dopamine, phenylephrine, mido 0053 As salt-forming opioid antagonists, the pharmaceu drine, heptaminol, Oxedrine tartrate, pholedrine or gepefrine, tical salt according to the invention can preferably contain particularly preferably phenylephrine. levallorphan, naloxone or naltrexone. 0064 AS Salt-forming antimycotics, the pharmaceutical 0054 As a salt-forming anthelmintic, the pharmaceutical salt according to the invention can preferably contain benza salt according to the invention can preferably contain pyrv Ikonium, econazole, miconazole, methylrosanilinium, ter inium. binafine, amorolfine, fenticonazole, dequalinium, oxycona 0055 As salt-forming antiallergics, the pharmaceutical Zole, croconazole, isoconazole or Sertaconazole. salt according to the invention can preferably contain repro 0065. As a salt-forming antiinflammatory, the pharmaceu terol, triprolidine, hydroxy Zine, azelastine, diphenhy tical salt according to the invention can preferably contain dramine, promethazine, pheniramine, dexchlorpheniramine, orphenadrine. clemastine, tramaZoline, brompheniramine, dimetindene, 0066. As salt-forming antitussives and/or expectorants, levocabastine, doxylamine, cyproheptadine, carbinoxamine, the pharmaceutical salt according to the invention can pref meclozine, bamipine, chlorphenoxamine, ketotifenorcetiriz erably contain ambroXole, doxycycline, bromhexine, dex ine, particularly preferably diphenhydramine. tromethorphan, diphenhydramine, terbutaline, chlorphe 0056. As salt-forming antiarrhythmics, the pharmaceuti namine, eprazinone, ephedrine, chlorbutinol, pentoxyverine, cal salt according to the invention can preferably contain pipaZetate or benproperine, particularly preferably diphenhy orciprenaline, aprindine, Verapamil, metoprolol, quinidine, dramine. amiodarone, Sotalol, propafenone, diltiazem, disopyramide, 0067. As a salt-forming antisclerosis agent, the pharma propranolol, ipatropium (sic), mexiletine, prajmaline, ceutical salt according to the invention can preferably contain procainamide, gallopamil, propafenone, detajmium, flecam butalamine. ide, oXprenolol or tocamide, particularly preferably Vera 0068. As B-receptor blockers and/or calcium channel pamil or diltiazem. blockers, the pharmaceutical salt according to the invention 0057. As salt-forming antibiotics, the pharmaceutical salt can preferably contain acebutolol, nicardipine, alprenolol. according to the invention can preferably contain Vancomy metoprolol, Verapamil, enalapril, bupranolol, penbutolol. cin, tetracycline, clindamycin, minocycline, lincomycin, propranolol, bisoprolol, esmolol, celiprolol, benazepril, dilt bacampicillin, amicacin, chlortetracycline, neomycin, tobra iazem, mepindolol, Sotalol, carteolol, gallopamil or Oxpre mycin, netilmicin, quinine, chloroquinine, ciprofloxacin, clin nolol, particularly preferably Verapamil or diltiazem. damycin, colistine, erythromycin, gentamicin, tobramycin 0069. As salt-forming broncholytics and/or antiasthmat sic, cefetametpivotil, amantadine, halofantrine, saquinavir, ics, the pharmaceutical salt according to the invention can mefloquine, framycetin, cefepime, bromhexine, cefpo preferably contain ketotifen, reproterol, orciprenaline, Salb doXimeproxetil, oxytetracycline, proguanil, pefloxacine, utamol, terbutaline, ephedrine, tulobuterol, ipatropium sic. polymyxin B. hydroxychloroquine, spectinomycin, Sultami fenoterol, terbutaline sic, formoterol, salbutamol sic. cillin, Valaciclovir or grepafloxacin. oxytropium or pirbuterol. US 2009/0258948 A1 Oct. 15, 2009

0070. As salt-forming cholinergics, the pharmaceutical I0087 As salt-forming Parkinson agents, the pharmaceuti salt according to the invention can preferably contain pyri cal salt according to the invention can preferably contain dostigmine, betanechol or neostigmine. amantadine, biperidene, selegiline, bromocriptine, trihex 0071. As salt-forming diuretics, the pharmaceutical salt yphenidyl, metrixene, benzaseride, lisuride, benzatropine, according to the invention can preferably contain amiloride or ropinirol, pergolide, bupidine, procyclidine, pramipexol. oXprenolol. bomapine or tiapride. 0072 AS salt-forming, circulation-promoting agents, the 0088 AS salt-forming psychopharmaceutical agents, the pharmaceutical Salt according to the invention can preferably pharmaceutical Salt according to the invention can preferably contain butalamine, naftidrofuryl, buflomedil, moXaverine, contain tranylcypromine, amitriptyline, doxepine, mapro bencyclan or meclofenoxate. tiline, clomipramine, opipramol, imipramine, trimipramine, 0073. As a salt-forming weaning agent, the pharmaceuti lofepramine, desipramine, dibenzepine, nortriptyline, cal salt according to the invention can preferably contain mianserine, citalopram, fluvoxamine, fluoxetil, traZodone, maltrexone, methadone, buprenorphine. paroxetin, nefazodone, Sertralin, Viloxacin, Venlafaxine, 0074 As salt-forming geriatrics, the pharmaceutical salt promethazine, chlorprothixene, Zuclopenthixol, pipamper according to the invention can preferably contain procaine or one, fluiphenazine, flupentixol, melperone, prothipendyl. deanolace. thioridazine, levomepromazine, quetiapine, triflupromazine, 0075. As salt-forming hypnotics and/or sedatives, the perazine, fenetylline, methylphenidate, hydroxycine, bus pharmaceutical Salt according to the invention can preferably pirone, deanolace or memantine. contain promethazine, Zolpidem tartrate, midazolam, melp I0089. As salt-forming rhinologicals/sinusitis agents, the erone or flurazepam. pharmaceutical Salt according to the invention can preferably 0076. As a salt-forming immunomodulator, the pharma contain diphenylpyraline, Xylometazoline, oxymetazoline, ceutical salt according to the invention can preferably contain tramaZoline, indanazoline, naphazoline or tetry Zoline. levamisole. 0090. As salt-forming spasmolytics, the pharmaceutical 0077. As salt-forming oral and/or pharyngeal therapeu salt according to the invention can preferably contain atro tics, the pharmaceutical salt according to the invention can pine, phenamazide, butylscopolaminium, propiverine, preferably contain chlorhexidine or cetylpyridinium. mebeverine, pipenZolate, oxybutynine, flavoxate, trospium, 0078. As a salt-forming coronary agent, the pharmaceuti denaverine or glycopyrronium. cal salt according to the invention can preferably contain 0091. As salt-forming platelet aggregation inhibitors, the oxyfedrine. pharmaceutical salt according to the invention can preferably 0079. As a salt-forming hypolipidemic, the pharmaceuti contain tirofiban, ticlopidine or clopidogrel. cal salt according to the invention can preferably contain colestipol. 0092. As a salt-forming tuberculosis agent, the pharma 0080. As salt-forming local anesthetics and/or neural ceutical salt according to the invention can preferably contain therapeutics, the pharmaceutical Salt according to the inven ethambutol. tion can preferably contain bupivacaine, lidocaine, mepiv 0093. As salt-forming urologicals, the pharmaceutical salt acaine, ropivacaine, procaine, articaine or prilocalne. according to the invention can preferably contain choline, 0081 AS salt-forming gastric and/or intestinal agents, the tolterodine, phenoxybenzamine, atropine, propiverine, dis pharmaceutical Salt according to the invention can preferably tigmine, emepronium, tamsulosine, doxazosine, teraZosine, contain pizotifen, pirenzepine, roXatidine, ranitidine, butino alfuZosine, bamethane, yohimbine or sildenafil. line, methanthelinium or metoclopramide. 0094. As salt-forming cytostatics, the pharmaceutical salt 0082 AS Salt-forming migraine agents, the pharmaceuti according to the invention can preferably contain aclarubicin, cal salt according to the invention can preferably contain nimustatin, doxorubicin, bleomycin, vinblastine, Vincristine, lisuride, methysergide, dihydroergotamine, ergotamine, daunorubicin, decarbazine, Vindesine, epirubicin, gemcitab Sumatriptan, rizatriptan or naratriptan. ine, procarbazil, mitoxantrone, bedamustine, idarubicin, 0083. As salt-forming muscle relaxants, the pharmaceuti aclarubicin sic, irinotecan, topotecan, toremifen or tamox cal salt according to the invention can preferably contain ifen. alcuronium, mivacuronium, atracurium, vecurmium, pancur 0.095 The pharmaceutical salts according to the invention mium, Suxamethonium, tolperisone, pridinol, orphenadrine can be prepared according to customary methods known to ortizamidine. the person skilled in the art. Preferably, for the preparation of 0084 As a salt-forming anesthetic, the pharmaceutical the pharmaceutical salts according to the invention, at least salt according to the invention can preferably contain ket one salt of the respective active compound and at least one salt amine or midazolam. of the respective Sugar Substitute are in each case dissolved 0085. As a salt-forming neuropathy preparation, the phar separately from one another in an amount of a solvent or maceutical salt according to the invention can preferably Solvent mixture which is as Small as possible, optionally with contain thiamine. Warming. I0086. As salt-forming opthalmologicals and/or otologi 0096. Both solutions are then combined, optionally mixed cals, the pharmaceutical salt according to the invention can and optionally cooled. If the pharmaceutical Salt according to preferably contain oxybuprocaine, proxymetacaine, kanamy the invention of the active compound and the Sugar Substitute cin, tolaZoline, tetry Zoline, tramazoline, phenylephrine, precipitates at least partially from the optionally cooled solu Xylomethazoli sic, naphazoline, timolol, metipranolol. tion, this is separated off according to customary methods, betaxolol, befunolol, levobunolol, brimonidine, clonidine, preferably by suction filtration. The pharmaceutical salt sepa pilocarpine, diplivefrine, aceclidine, apraclonidine, neostig rated off is then purified, if necessary, according to customary mine, dorzolamide, atropine, Scopolamine, cyclopentolate or methods known to the person skilled in the art, for example by homatropine, particularly preferably phenylephrine. recrystallization, washing or by stirring in a suitable solvent. US 2009/0258948 A1 Oct. 15, 2009

0097. If the pharmaceutical salt has still not completely larly preferably in the form of microtablets, granules or precipitated, the remaining solution is preferably concen pellets, optionally filled into capsules or compressed to give trated completely on a rotary evaporator and the pharmaceu tablets. tical salt according to the invention is extracted from the 0106 If the medicament according to the invention is residue according to customary methods known to the person present in the form of granules or pellets, these can preferably skilled in the art and purified as described above. have a size in the range from 0.1 to 3 mm, particularly pref 0098. The solvent or solvent mixture suitable in each case erably in the range from 0.5 to 2 mm. for the preparation and the Suitable reaction conditions. Such 0107 If the medicament according to the invention is as, for example, temperature or reaction time, can be deter present in the form of microtablets, these can preferably have mined by the person skilled in the art with the aid of simple a diameter in the range from 0.5 to 5 mm, particularly pref preliminary tests. If both the active compound salt and the salt erably in the range from 1 to 3 mm and very particularly of the Sugar Substitute have an adequate solubility in water, preferably in the range from 1 to 2 mm. the solvent used is preferably water. The salt of the respective 0.108 If the medicament according to the invention is active compound employed is preferably its hydrochloride, present in the form of active compound crystals, micro-par hydrobromide, phosphate, hydrogenphosphate, hydrogen ticles, micropellets or microcapsules, these can preferably sulfate, sulfate, nitrate or metilsulfate. The salt of the respec have a diameter in the range from 10Lm to 1 mm, particularly tive Sugar Substitute employed is preferably its sodium, potas preferably in the range from 15 um to 0.5 mm and very sium, calcium or ammonium salt. particularly preferably in the range from 30 Lum to 200 um. 0099. Of course, it is also possible to react the respective 0109) Depending on embodiment, the medicaments active compound per se with sic the free acid of a Sugar according to the invention can moreover contain the custom Substitute with one anotherina Suitable reaction medium and ary physiologically tolerable excipients known to the person to isolate and, if appropriate, to purify the pharmaceutical salt skilled in the art as further constituents. thus obtained according to customary methods known to the 0110. If the medicaments according to the invention are person skilled in the art. present in the form of tablets or microtablets, these can be 0100. A further subject of the present invention are medi present as physiologically tolerable excipients, preferably caments comprising at least one pharmaceutical salt accord microcrystalline cellulose, cellulose ethers, lactose, starch, ing to the invention and, if appropriate, physiologically tol starch derivatives, Sugar alcohols, calcium hydrogenphos erable excipients. The corresponding medicaments can be phate and the customary binders, flow regulators, lubricants used for the treatment of the indications known for the respec and/or disintegrants known to the person skilled in the art. tive active compounds. 0111. If the medicaments according to the invention are 0101 Preferably, medicaments according to the invention present in the form of gels or chewing gums, these can pref which contain at least one pharmaceutical salt according to erably contain methylparaben, propylparaben, Xylitol and/or the invention of a salt-forming opioid, opioid analog, ephe Xanthan gum as physiologically tolerable excipients. drine, chloroquine, lidocaine, ethaverine, preglumetacin or 0112) If the medicaments according to the invention are triflupromaazine or a salt-forming compound of the general present in the form of pellets, granules or micro-pellets, these formula I, II, III or IV indicated above and a sugar substitute can preferably contain microcrystalline cellulose, cellulose are employed for the control of pain. Preferably, the medica ethers, lactose, starch and starch derivatives, Sugar alcohols, ments according to the invention contain the corresponding calcium hydrogenphosphate, fatty alcohols, esters of glycerol saccharinates as pharmaceutical salts of these active com or fatty acid esters as physiologically tolerable excipients. pounds. 0113. If the medicaments according to the invention are 0102 For the treatment of urinary incontinence, medica present in the form of microcapsules or microparticles, these ments according to the invention are preferably employed can contain, depending on the nature of the process employed which contain at least one pharmaceutical salt of a salt-form for their preparation, the customary physiologically tolerable ing compound of the general formula I, II, III or IV indicated excipients known to the person skilled in the art. above, or a compound from the group consisting of oxybu 0114. The medicaments according to the invention can be tymine, tolterodine, propiverine and trospium and a Sugar prepared by customary methods known to the person skilled substitute. Preferably, the medicaments according to the in the art. invention contain the corresponding saccharinates as pharma 0115 If the medicaments according to the invention are ceutical salts of these active compounds. present in the form of tablets, preferably the pharmaceutical 0103) The medicaments according to the invention can be salt according to the invention and, if appropriate, the physi present in solid, semisolid or liquid form. Preferably, the ologically tolerable excipients are preferably mixed homoge medicaments according to the invention are suitable for oral neously with one another, processed to give granules by administration. means of moist, dry or melt granulation and compressed to 0104. In a preferred embodiment, the medicament accord give tablets or produced by direct tableting of the pharmaceu ing to the invention is present: formulated as a gel, chewing tical salt with further excipients. In addition, the tablets can gum, juice, spray, tablet, chewable tablet, coated tablet, pow preferably be produced by compression of optionally coated der, if appropriate filled into capsules, easily reconstitutable pellets, active compound crystals, micro-particles or micro dry preparations, preferably as a gel, as an aqueous or oily capsules. juice, as a Sublingual spray, tablets or chewable tablets. 0116. The medicaments according to the invention in the 0105. Likewise preferably, the medicament according to form of pellets can preferably be produced by mixing the the invention can also be present formulated in multiparticu pharmaceutical Salt and physiologically tolerable excipients, late form, preferably in the form of micro-tablets, microcap extrusion and spheronization, by build-up pelletization or by Sules, granules, active compound crystals or pellets, particu direct pelletization in a high-speed mixer or in the rotor flu US 2009/0258948 A1 Oct. 15, 2009 idized bed. The pellets are particularly preferably prepared by as a coating material. The coatings of ethylcellulose or cellu extrusion of moist masses and Subsequent spheronization. lose acetate are preferably applied from aqueous pseudolatex 0117 Microcapsules are prepared according to customary dispersion. Aqueous ethylcellulose-pseudolatex dispersions microencapsulation processes, such as, for example, by spray are stocked on the market as 30% strength by weight disper drying, spray Solidification or coacervation. sions (Aquacoat(R) or as 25% strength by weight dispersions 0118. The medicaments according to the invention in (Surelease R) and as Such are preferably also employed as a semisolid form, such as, for example, gels or chewing guns, coating material. are preferably suitable for the administration of the pharma I0126. As natural, semisynthetic or synthetic waxes, fats or ceutical salt according to the invention via the oral mucosa, fatty alcohols, the release-delaying coating in the medica the medicaments according to the invention in Solid or liquid ment according to the invention can preferably contain car form, such as, for example, oily or aqueous juices, tablets or nauba wax, beeswax, glycerol monostearate, glycerol multiparticulate forms are preferably suitable for the admin monobelhenate (Compritol ATO888(R), glycerol ditripalmito istration of the pharmaceutical salt according to the invention stearate (Precirol ATO5(R), microcrystalline wax, cetyl alco via the gastric tract. If the absorption of active compound hol, cetylstearyl alcohol, or a mixture of at least two of these from the medicament according to the invention in Solid form components. is only intended via the gastric tract, they must have at least I0127. If the release-delaying coating is based on a water one enteric coating. This enteric coating enables them to pass insoluble, optionally modified natural and/or synthetic poly through the gastric tract undissolved and the pharmaceutical mer, the coating dispersion or Solution can contain, in addi salt is only released in the intestinal tract. Preferably, the tion to the corresponding polymer, a customary enteric coating dissolves at a pH of between 5 and 7.5. physiologically tolerable plasticizer known to the person 0119 The medicament according to the invention can con skilled in the artin order to lower the minimum film tempera tain the pharmaceutical salt according to the invention also ture necessary. partially or completely in delayed-release form. I0128 Suitable plasticizers are, for example, lipophilic 0120. The delaying of the release of active compound is diesters of an aliphatic or aromatic dicarboxylic acid of preferably based on the application of a release-delaying C-C and an aliphatic alcohol of C-Cs. Such as, for coating, on embedding in a release-delaying matrix, binding example, dibutyl phthalate, diethyl phthalate, dibutyl seba to an ion-exchange resin or on a combination of these above cate or diethyl sebacate, hydrophilic or lipophilic esters of mentioned release-delaying methods. citric acid, Such as, for example, triethyl citrate, tributyl cit 0121 Preferably, the release-delaying coating is based on rate, acetyltributyl citrate or acetyltriethylcitrate, polyalky a water-insoluble, optionally modified natural or synthetic lene glycols, such as, for example, polyethylene glycols or polymer or on a natural, semisynthetic or synthetic wax or fat propylene glycols, esters of glycerol. Such as, for example, or fatty alcohol or a mixture of at least two of these above triacetin, My vacet(R) (acetylated mono- and diglycerides, mentioned components. CHOs to CHO), medium-chain triglycerides (Mig 0122 Water-insoluble polymers employed for the prepa ration of a release-delaying coating are preferably poly lyol(R), oleic acid or mixtures of at least two of the above (meth)acrylates, particularly preferably poly(C) alkyl mentioned plasticizers. (meth)acrylates, poly(C)dialkylamino-(C)-alkyl (meth) I0129. Preferably, aqueous dispersions of Eudragit RS(R) acrylates and/or their copolymers, very particularly prefer and optionally Eudragit RLR) contain triethyl citrate as a ably ethyl acrylate/methyl methacrylate copolymers having a plasticizer. molar ratio of the monomers of 2:1, ethyl acrylate/methyl 0.130 Preferably, the release-delaying coating contains methacrylate/trimethylammonium ethyl methacrylate chlo the plasticizer(s) in amounts of 5 to 50% by weight, particu ride copolymers having a molar ratio of the monomers of larly preferably 10 to 40% by weight and very particularly 1:2:0.1, ethyl acrylate/methyl methacrylate/trimethylammo preferably 10 to 30% by weight, based on the amount of the nium ethyl methacrylate chloride copolymers having a molar polymer employed. ratio of the monomers of 1:2:0.2 or a mixture of at least two I0131. In individual cases, for example for cellulose of these abovementioned polymers as a coating material. acetate, higher amounts of plasticizers, preferably up to 110% 0123. These coating materials are obtainable on the mar by weight, based on the amount of cellulose acetate, can also ket as 30% strength by weight aqueous latex dispersions be employed. under the names Eudragit RS30D', Eudragit NE30D' and 0.132. In addition, the release-delaying coating can contain Eudragit RL30D' and are preferably also employed as a coat further customary excipients known to the person skilled in ing material as such. the art, such as, for example, lubricants, preferably talc or 0.124 Likewise preferably, the water-insoluble polymers glycerol monostearate, color pigments, preferably iron employed for the preparation of the release-delaying coating oxides or titanium dioxide, or Surfactants, such as, for for the medicaments according to the invention can be poly example, Tween 80R. vinyl acetates, optionally in combination with further excipi I0133. The release profile of the delayed active compound ents. These are obtainable on the market as an aqueous dis component can be adjusted by the customary methods known persion containing 27% by weight of polyvinyl acetate, 2.5% to the person skilled in the art, such as, for example, by the by weight of povidone and 0.3% by weight of sodium lauryl thickness of the coating or by the use of further excipients as sulphate (Kollicoat SR 30 DR). constituents of the coating. Suitable excipients are, for 0.125. In a further preferred embodiment, the release-de example, hydrophilic or pH-dependent pore-forming agents, laying coatings of the medicaments according to the inven Such as, for example, sodium carboxymethylcellulose, cellu tion are based on water-insoluble cellulose derivatives, pref lose acetate phthalate, hydroxypropylmethylcellulose acetate erably alkylcelluloses. Such as, for example, ethylcellulose, Succinate, lactose, polyethylene glycol or mannitol or water or on cellulose esters, such as, for example, cellulose acetate, soluble polymers, such as, for example, polyvinylpyrrolidone US 2009/0258948 A1 Oct. 15, 2009 or water-soluble celluloses, preferably hydroxypropylmeth 0141 Wax coatings can be applied by melt coating in the ylcellulose or hydroxy-propylcellulose. fluidized bed and cooled attemperatures below the respective 0134. The release-delaying coating can also contain melt range after the coating for complete Solidification. The insoluble or lipophilic excipients, such as, for example, alky application of wax coatings can also be carried out by spray lized silicone, which is stocked on the market, for example, as ing on their solutions in organic solvents. Aerosil R972(R), or magnesium stearate for the further inten 0.142 For the modification of the active compound release sification of the delaying. profile, the medicament according to the invention can con 0135 The respective formulation of the medicament tain the pharmaceutical salt whose release is to be delayed according to the invention can optionally also contain, in also in a release-delaying matrix, preferably uniformly dis addition to the release-delaying coating, at least one further persed. coating. This can be, for example, a coating for improving the 0.143 Matrix materials which can be used are physiologi taste or an enteric coating. cally tolerable, hydrophilic materials which are known to the 0136. The enteric coating is preferably based on meth person skilled in the art. Preferably, the hydrophilic matrix acrylic acid/methyl methacrylate copolymers having a molar materials used are polymers, particularly preferably cellulose ratio of the respective monomers of 1:1 (Eudragit L(R), meth ethers, cellulose esters and/or acrylic resins. Very particularly acrylic acid/methyl methacrylate copolymers having a molar preferably, the matrix materials employed are ethylcellulose, ratio of the respective monomers of 1:2 (Eudragit S(R), meth hydroxy-propylmethylcellulose, hydroxypropylcellulose, acrylic acid/ethyl acrylate copolymers having a molar ratio of hydroxy-methylcellulose, poly(meth)acrylic acid and/or the respective monomers of 1:1 (Eudragit L30D-55R), meth their derivatives, such as, for example, their salts, amides or acrylic acid/methyl acrylate/methyl methacrylate copoly esterS. mers having a molar ratio of the respective monomers of 7:3:1 0144. Likewise preferred are matrix materials made of (Eudragit FSR), shellac hydroxy-propylmethylcellulose hydrophobic materials, such as hydrophobic polymers, acetate Succinate, cellulose acetate phthalate or a mixture of waxes, fats, long-chain fatty acids, fatty alcohols or appropri at least two of these abovementioned components, which can ate esters or ethers or mixtures of at least two of the above optionally also be employed in combination with the above mentioned materials. Particularly preferably, the hydropho mentioned water-insoluble poly(meth)acrylates, preferably bic materials employed are mono- or diglycerides of C-Co in combination with Eudragit NE30DR) and/or Eudragit RLR) fatty acids and/or C-Co-fatty alcohols and/or waxes or and/or Eudragit RS(R). mixtures of at least two of the abovementioned materials. 0.137 The coatings can be applied by customary processes (0145. It is also possible to employ mixtures of the above Suitable for the respective coating and known to the person mentioned hydrophilic and hydrophobic materials as a skilled in the art, Such as, for example, by spraying on solu release-delaying matrix material. tions, dispersions or Suspensions, by melt processes or by 0146 The release-delaying matrix can be prepared by the powder application processes. The solutions, dispersions or customary methods known to the person skilled in the art. Suspensions can be employed in the form of aqueous and/or 0147 A further subject of the invention is also the use of at organic solutions or dispersions. In this context, aqueous least one pharmaceutical salt according to the invention and, dispersions are preferably employed. Organic solvents which if appropriate, physiologically tolerable excipients for the can preferably be used are alcohols, for example ethanol or production of a medicament. The corresponding medica isopropanol, ketones, such as, for example, acetone, esters, ments can be used for the treatment of the indications known for example ethyl acetate, chlorinated hydrocarbons, such as, for the respective active compounds. for example, dichloromethane, with alcohols or ketones 0148 Preferred is the use of at least one pharmaceutical being particularly preferably employed. It is also possible to salt of a salt-forming opioid, opioid analog, ephedrine, chlo employ mixtures of at least two of the abovementioned sol roquine, lidocaine, ethaverine, preglumetacin, truflu pro VentS. mazine or a salt-forming compound of the general formula I, 0138 If the medicament is present in multiparticulate II, III or IV indicated above for the production of a medica form and the active compound is to be released at least par ment for the control of pain, the salts of these active com tially in delayed form, the release-delaying coating is prefer pounds used preferably being their saccharinates. ably applied Such that the multiparticulate forms comprising 0149 Likewise preferred is the use of at least one pharma the active compound Salt are coated after their preparation ceutical salt of a salt-forming compound of the general for with the corresponding polymers and, if appropriate, another mula I, II, III or IV indicated above for the production of a active compound and/or the same active compound salt and, medicament for the treatment of urinary incontinence, the if appropriate, further physiologically tolerable excipients salts of these active compounds used preferably being their from aqueous and/or organic media, preferably from aqueous saccharinates. media, with the aid of the fluidized bed process and the 0150. The total amount of the respective pharmaceutical coating is preferably simultaneously dried in the fluidizedbed salt to be administered to the patient varies, for example, at customary temperatures and, if appropriate, annealed if depending on the weight of the patient, on the indication and necessary. the degree of severity of the pain or of the disorder. It is known 0139 Preferably, the drying of the coating is carried out to the person skilled in the art on account of the properties of for poly(meth)acrylate coatings at a feed air temperature in the respective active compounds in what doses these are to be the range from 30 to 50°, particularly preferably in the range administered in order to achieve the desired effect. from 35 to 45° C. 0151. The pharmaceutical salts according to the invention 0140 For coatings based on cellulose, such as, for of a pharmaceutical active compound and a Sugar Substitute example, ethylcellulose or cellulose acetate, the drying is are distinguished compared with the conventionally used preferably carried out at a temperature in the range from 50 to salts of these active compounds customarily by a lower solu 80°C., particularly preferably in the range from 55 to 65°C. bility in water. Preferably, these are the saccharinates of the US 2009/0258948 A1 Oct. 15, 2009

respective active compounds, whose water Solubility is usu excess amount of undissolved substance was then brought ally s250 mg/ml and, compared with the water solubility of into Solution with stirring by addition of Small amounts of the conventional salts of the corresponding active compound, water. After a clear solution had been obtained, the sum D (in is usually lowered by at least 50%. ml) of the amount of water employed was determined. The 0152. By this means, the formulation of these pharmaceu solubility of the respective salt per 1 ml of water was then tical salts to give medicaments, for example the preparation of calculated according to the following formula: granules by extrusion, is also simplified. On account of the 0159. Water solubility of the active compound salt altered solubility, the pharmaceutical salts according to the invention further enable more effective release-delaying of the active compound using customary delaying processes in comparison to salts customarily used. Delayed-release medi in mg/ml of water = (CIA),C,D caments which contain these pharmaceutical salts according to the invention can therefore be produced more simply and 0.160) If the amount Badded (in mg) of the respective salt more inexpensively. This also applies for other modifications did not dissolve immediately and a turbidity resulted, after the of the medicaments according to the invention, such as, for addition of the salt the mixture was stirred for a further 10 example, with enteric coatings. minutes. If undissolved salt still remained then, the undis 0153. From the medicaments according to the invention, solved portion was brought into solution by addition of small which are employed for the administration of the respective amounts of water with stirring. After obtainment of a clear pharmaceutical salt via the oral mucosa or the gastric tract, a solution, the sum E (in ml) of the amounts of water employed largely controlled release of the respective active compound was determined. The solubility of the respective salt per 1 ml without the use of a release-delaying matrix and/or a release of water was then calculated according to the following for delaying coating, but if appropriate with an enteric coating, is mula: moreover achieved. 0.161 Water solubility of the active compound salt 0154 The medicaments according to the invention in the form to be administered orally, which release the respective active compound as early as on or immediately after admin istration, furthermore have the advantage that their strongly in mg ml of water = EB bitter or nauseating taste is compensated by the simultaneous release of the Sugar substitute. The adherence to the dosage instructions in the patients thereby improves and the medica 0162 The invention is explained below with the aid of ments which contain the respective active compound as a salt examples. These explanations are only by way of example experience a greater acceptance. The medicaments according and do not restrict the general inventive concept. to the invention are moreover also suitable for diabetics. 0155 For a large number of the abovementioned active EXAMPLES compounds, the water solubility of the conventional active compound salts is known, for example from PharmaZeutische Example 1 Stoffliste Pharmaceutical Substance List, 12th edition 0163 The preparation and the subsequent separation of ABDATA Pharma-Daten-Service, 65735 Eschborn/Taunus. the optically pure compound (+)-(1S,2S)-3-(3-dimethy The corresponding disclosure sic is hereby inserted as ref lamino-1-ethyl-2-methylpropyl)phenol was carried out erence and is thus regarded as part of the disclosure. according to DE-A-4426245. The corresponding part of the 0156 If the water solubility of an active compound salt is disclosure sic is hereby inserted as reference and is thus not known, it can be determined according to the method regarded as part of the disclosure. indicated below, according to which the water solubility of 0164. For the preparation of (+)-(1S,2S)-3-(3-dimethy the pharmaceutical salts according to the invention has also lamino-1-ethyl-2-methylpropyl)phenol saccharinate, 2.58 g been determined: (10 mmol) of (+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2- 0157. In a clear colorless vessel made of transparent mate methylpropyl)phenol hydrochloride and 2.42 g (10 mmol) of rial. Such as, for example, glass or plastic, 1 ml of ion-free saccharin-Sodium dihydrate were in each case completely water or a fraction (amount A in ml) thereof is introduced at dissolved with warming in an amount of water which was as a temperature of 20° C. While stirring with a magnetic stirrer small as possible. Both solutions were then mixed with one rod, the conventional active compound salt to be tested or the another with stirring and then placed in a cool place over pharmaceutical salt according to the invention was then night. The precipitated (+)-(1S,2S)-3-(3-dimethylamino-1- added in portions. ethyl-2-methylpropyl)-phenol saccharinate was separated off 0158 If the amount of salt Badded (in mg) completely from the Supernatant mother liquor, purified with ethanol and dissolved, further amounts of the respective salt were slowly isolated according to conventional methods. added. Each further addition was recorded and the solution behavior observed. As soon as the first turbidity due to undis Example 2 Solved salt was found by observation against a Suitable back ground, stirring was continued for a further 10 minutes. If 0.165 For the preparation of diphenhydramine sacchari undissolved constituents Subsequently remained, the Sum C nate, 5.0 g (17.1 mmol) of diphenhydramine hydrochloride (in mg) of the amount of Substance employed was deter and 4.13 g (17.1 mmol) of saccharin-sodium dihydrate were mined. If a clear Solution resulted again on stirring, further in each case completely dissolved with warming in an amount small amounts of the respective salt were added and the of water which was as small as possible. Both solutions were mixture was in each case stirred again for 10 minutes until a then mixed with one another with stirring and then placed in first turbidity remained on account of undissolved salts. The a cool place overnight. The precipitated diphenhydramine US 2009/0258948 A1 Oct. 15, 2009 saccharinate was separated off from the Supernatant mother added, stirring was continued for one hour and evaporated liquor, purified with ethanol and isolated according to con water was replaced. After cooling to lacuna temperature of ventional methods. 20 to 25°C., the mixture was flavored while stirring with 0.075 g of orange-mandarin flavor 10888-56 (Givaudan Example 3 Roure Flavors Ltd. CH 8600 Dübendorf). 0166 For the preparation of Verapamil saccharinate, 415 mg (0.845 mmol) of Verapamil hydrochloride and 204 mg Example 8 (0.845 mmol) of saccharin-sodium dihydrate were in each case completely dissolved with warming in an amount of 0172. In this example, the water solubility of certain phar water which was as small as possible. Both solutions were maceutical salts and of conventional salts of the correspond then mixed with one another with stirring and then placed in ing active compound was determined according to the a cool place overnight. The precipitated Verapamil sacchari method indicated above. The solubility values thus obtained nate was separated off from the Supernatant mother liquor, are presented in table 1 below: purified with ethanol and isolated according to conventional methods. TABLE 1 Comparison of the water solubilities of certain pharmaceutical Example 4 salts according to the invention and corresponding conventional 0167 For the preparation of morphine saccharinate, 285 salts of these active compounds. mg (0.76 mmol) of morphine hydrochloride trihydrate and Solubility of Solubility of the active the active 183 mg (0.76 mmol) of saccharin-sodium dihydrate were in compound salt compound saccharinate each case completely dissolved with warming in an amount of Active compound in mg/ml of water in mg/ml of water water which was as small as possible. Both solutions were (-)-(1R,2R)-3-(3- 261 31 then mixed with one another with stirring and then placed in dimethylamino-1-ethyl- (hydrochloride) a cool place overnight. The precipitated morphine Sacchari 2-methylpropyl)phenol nate was separated off from the Supernatant mother liquor, (1RS,3RS,6RS)-6- 500 71 purified with ethanol and isolated according to conventional dimethylaminomethyl-1- (hydrochloride) methods. (3-methoxy phenyl)cyclohexane 1,3-diol sic Example 5 (+)-(1S,2S)-3-(3- 6SO 55 dimethylamino-1-ethyl- (hydrochloride) 0168 For the preparation of an oral gel, 0.33 g of meth 2-methylpropyl)phenol ylparaben, 0.05 g of propylparaben and 75.0 g of xylitol were (-)-(1S,2S)-3-(3- 568 130 first dissolved in 198.0 g of purified water at a temperature of dimethylamino-1-ethyl- (hydrochloride) 1-fluoro-2-methyl 80° C. and the mixture was then cooled to 40° C. Then, propyl)phenol initially 0.94 g of diphenhydramine saccharinate obtained (-)-(2S,3S)-1- 2OOO 90 according to example 2 and Subsequently 2 g of Xanthan gum dimethylamino-3-(3- (hydrochloride) were added with stirring, stirring was continued for one hour methoxyphenyl)- and evaporated water was replaced. After cooling to a tem 2-methylpentan-3-ol perature of 20 to 25°C., the mixture was flavored with 0.625 dimethylaminomethyl-4- (hydrochloride) g of Tutti-Frutti 9/008897 (Dragoco Gerberding & Co. AG, (4-fluorobenzyl-oxy)- 37603 Holzminden) while stirring. 1-(3-methoxy phenyl)cyclohexanol Morphine 52 25 Example 6 (hydrochloride trihydrate) 0169 5 g of comminuted chewing gum mass (Popeye Amezinium 25 8 Amural Confections, Yorkville, Ill., USA) were warmed to a (metilsulfate) temperature of 30 to 40° C. in a Fanta dish. 187.9 mg of Phenylephrine 12SO 380 diphenhydramine saccharinate obtained according to (hydrochloride) Verapamil 200 7 example 2 were then incorporated into the viscous chewing (hydrochloride) gum mass using a pestle. The homogeneous mass was then Diphenhydramine 1OOO 7 portioned into teflonized molds to give portions of 1 g each. (hydrochloride) Benzalkonium 500 <2 0170 The taste test showed that the chewing gums which (hydrochloride) contained the diphenhydramine saccharinate had an excellent Codeine 250 200 taste at the start and were still enjoyable even after a relatively (phosphate long chewing time. hemihydrate) Hydromorphone 330 130 (hydrochloride) Example 7 Buprenorphine 14 2 0171 For the preparation of a juice on an aqueous basis, (hydrochloride) 0.33 g of methylparaben, 0.05 g of propylparaben and 75.0 g The conventional salt employed in each case is indicated in brackets. of xylitol were dissolved in 199.22 g of purified water at a temperature of 80°C. The mixture was cooled to 40° C. and 0173 As can be seen from the solubility values according 78.5 mg of (+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2-meth to table 1, the solubility of the respective active compound ylpropyl)phenol saccharinate obtained according to example saccharinates is lowered compared with the corresponding 1 were added with stirring. 0.25 g of Xanthan gum was then conventional active compound salts. US 2009/0258948 A1 Oct. 15, 2009

1.-39. (canceled) 43. The pharmaceutical salt according to claim 40, wherein 40. A pharmaceutical salt of a salt-forming pharmaceutical the salt-forming pharmaceutical active compound is (-)-(1R, active compound and at least one salt-forming Sugar Substi 2R)-3-(2-Dimethylaminomethyl-cyclohexyl)-phenol. tute, wherein the salt-forming pharmaceutical active com pound is a salt-forming 1-phenyl-3-dimethylaminopropane 44. A pharmaceutical composition comprising a therapeu compound selected from the group consisting of: (a)(-)-(1R, tically effective amount of the pharmaceutical salt according 2R)-3-(3-Dimethylamino-1-ethyl-2-methyl-propyl)-phenol; to claim 40 and optionally one or more physiologically tol (b) (1RS,3RS,6RS)-6-Dimethylaminomethyl-1-(3-meth erable excipients. oxy-phenyl)-cyclohexane-1,3-diol; and (c) (-)-(1R,2R)-3- 45. A method of controlling pain comprising administering (2-Dimethylaminomethyl-cyclohexyl)-phenol. to a patient in need thereof a pain-controlling effective 41. The pharmaceutical salt according to claim 40, wherein amount of the pharmaceutical salt of claim 40. the salt-forming pharmaceutical active compound is (-)-(1R, 46. A method of controlling urinary incontinence compris 2R)-3-(3-Dimethylamino-1-ethyl-2-methyl-propyl)-phenol. ing administering to a patient in need thereof an urinary 42. The pharmaceutical salt according to claim 40, wherein incontinence-controlling effective amount of the pharmaceu the salt-forming pharmaceutical active compound is (1RS, tical salt of claim 40. 3RS,6RS)-6-Dimethylaminomethyl-1-(3-methoxyphenyl)- cyclohexane-1,3-diol.