WO 2005/014005 PCT/EP2004/008029 COMBINATION OF AN ANTICHOLINERGIC AND A STEROID AND ITS USE TO TREAT RESPIRATORY DISORDERS BY INHALATION The present invention relates to novel pharmaceutical compositions based on steroids and 5 salts of an anticholinergic, processes for preparing them and their use in the treatment of respiratory complaints. Description of the invention The present invention relates to novel pharmaceutical compositions based on steroids and 10 salts of an anticholinergic of formula 1, processes for preparing them and their use in the treatment of respiratory complaints. Within the scope of the present invention the anticholinergic agents used are the salts of formula 1 15 O-N O O 0 0 0 X HO - S ,S 1 wherein X - denotes an anion with a single negative charge, preferably an anion selected from the group consisting of fluoride, chloride, bromide, iodide, sulphate, 20 phosphate, methanesulphonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate and p-toluenesulphonate, optionally in the form of the racemates, the enantiomers, and the hydrates thereof. Preferably, the salts of formula 1 are used wherein 25 X - denotes an anion with a single negative charge selected from among the fluoride, chloride, bromide, 4-toluenesulphonate and methanesulphonate, preferably bromide, optionally in the form of the racemates, the enantiomers, and the hydrates thereof. -1- WO 2005/014005 PCT/EP2004/008029 Most preferably, the salts of formula I1 are used wherein X - denotes an anion with a single negative charge selected from among the chloride, bromide and methanesulphonate, preferably bromide, optionally in the form of the racemates, the enantiomers, and the hydrates 5 thereof. Particularly preferred according to the invention is the salt of formula I1 wherein X - denotes bromide. 10 Of particular interest according to the invention are the enantiomers of formula 1-en O N0 00 - O X HO _- S \S 1- -en wherein X - may have the meanings an mentioned hereinbefore. Surprisingly, an unexpectedly beneficial therapeutic effect can be observed in the treatment 15 of inflammatory and/or obstructive diseases of the respiratory tract if the anticholinergic of formula 1 is used with one or more steroids 2. The beneficial therapeutic effect mentioned above may be observed both when the two active substances are administered simultaneously in a single active substance formulation 20 and when they are administered successively in separate formulations. According to the invention, it is preferable to administer the two active substance ingredients simultaneously in a single formulation. -2- WO 2005/014005 PCT/EP2004/008029 In the pharmaceutical combinations mentioned above the active substances may be combined in a single preparation or contained in two separate formulations. Pharmaceutical compositions which contain the active substances 1 and 2 in a single preparation are preferred according to the invention. 5 According to the instant invention preferred steroids 2 which are optionally also referred to as corticosteroids, denote compounds selected from among methyl prednisolone, prednisone, butixocort propionate, RPR-106541, flunisolide, beclomethasone, triamcinolone, budesonide, fluticasone, mometasone, ciclesonide, rofleponide, ST-126, 10 dexamethasone, 6a,9ac-difluoro-17(a-[(2-furanylcarbonyl)oxy]- 1 3-hydroxy-16c-methyl 3-oxo-androsta-1,4-diene-17p3-carbothioic acid (S)-fluoromethyl ester, and 6cX,9ct-difluoro 113-hydroxy-16-methyl-3-oxo-17a-propionyloxy-androsta-1,4-diene-17p-carbothioic acid (S)-(2-oxo-tetrahydro-furan-3S-yl) ester. 15 Preferably, the compound 2 is selected from among flunisolide, beclomethasone, triamcinolone, budesonide, fluticasone, mometasone, ciclesonide, rofleponide, ST-126, dexamethasone, 6c,9ac-difluoro-17ca-[(2-furanylcarbonyl)oxy]-110 3-hydroxy-16ac-methyl 3-oxo-androsta-1,4-diene-1703-carbothioic acid (S)-fluoromethyl ester, and 6a,9c-difluoro 11 0-hydroxy-16acc-methyl-3-oxo-17a-propionyloxy-androsta- 1,4-diene-1730-carbothioic 20 acid (S)-(2-oxo-tetrahydro-furan-3S-yl) ester. More preferably, the compound 2 is selected from among budesonide, fluticasone, mometasone, ciclesonide, and 6c,9oC-difluoro-17( [(2-furanylcarbonyl)oxy]- 1 13-hydroxy-16a-methyl-3-oxo-androsta-1,4-diene-173 carbothioic acid (S)-fluoromethyl ester, more preferably the compound 2 is selected from among budesonide, fluticasone, mometasone, ciclesonide. 25 Any reference to steroids 2 within the scope of the present invention includes a reference to the salts or derivatives which may be formed from the steroids. Examples of possible salts or derivatives include: sodium salts, sulphobenzoates, phosphates, isonicotinates, acetates, propionates, dihydrogen phosphates, palmitates, pivalates or furoates. In some 30 cases the compounds of formula 2 may also occur in the form of their hydrates. Any reference to steroids 2 within the scope of the present invention also includes a reference to the compounds 2 in the form of their diastereomers, mixtures of diastereomers or in the form of the racemates. -3- WO 2005/014005 PCT/EP2004/008029 In one aspect the present invention relates to the abovementioned pharmaceutical compositions which contain, in addition to therapeutically effective quantities of 1 and 2, a pharmaceutically acceptable carrier. In another aspect the present invention relates to the abovementioned pharmaceutical compositions which do not contain any pharmaceutically 5 acceptable carrier in addition to therapeutically effective quantities of 1 and 2. The present invention also relates to the use of therapeutically effective quantities of the salts 1 for preparing a pharmaceutical composition also containing steroids 2 for treating inflammatory or obstructive diseases of the respiratory tract. Preferably, the present 10 invention relates to the abovementioned use for preparing a pharmaceutical composition for treating asthma or COPD. Within the scope of the present invention the compounds 1 and 2 may be administered simultaneously or successively, while it is preferable according to the invention to 15 administer compounds 1 und 2 simultaneously. The present invention further relates to the use of therapeutically effect amounts of salts 1 and steroids 2 for treating inflammatory or obstructive respiratory complaints, particularly asthma or COPD. 20 The proportions in which the active substances 1 and 2 may be used in the active substance combinations according to the invention are variable. Active substances 1 and 2 may possibly be present in the form of their solvates or hydrates. Depending on the choice of the compounds 1 and 2, the weight ratios which may be used within the scope of the 25 present invention vary on the basis of the different molecular weights of the various compounds and their different potencies. As a rule, the pharmaceutical combinations according to the invention may contain the cation 1 and a steroid 2 in ratios by weight ranging from 1:250 to 250:1; preferably from 1:150 to 150:1. In the particularly preferred pharmaceutical combinations which contain in addition to 1 a compound selected for 30 instance from among the group consisting of budesonide, fluticasone, mometasone, and ciclesonide as the steroid 2, the weight ratios of I to 2 are most preferably in a range from about 1:40 to 40:1, more preferably from 1:30 to 30:1. For example, without restricting the scope of the invention thereto, preferred combinations 35 of 1 and 2 according to the invention may contain 1 and one of the abovementioned -4- WO 2005/014005 PCT/EP2004/008029 preferred steroids 2 in the following weight ratios: 1:65, 1:64, 1:63, 1:62, 1:61, 1:60, 1:59, 1:58, 1:57, 1:56, 1:55, 1:54, 1:53, 1:52, 1:51, 1:50; 1:49; 1:48; 1:47; 1:46; 1:45; 1:44; 1:43; 1:42; 1:41; 1:40; 1:39; 1:38; 1:37; 1:36; 1:35; 1:34; 1:33; 1:32; 1:31; 1:30; 1:29; 1:28; 1:27; 1:26; 1:25; 1:24; 1:23; 1:22; 1:21; 1:20; 1:19; 1:18; 1:17; 1:16; 1:15; 1:14; 1:13; 5 1:12; 1:11; 1:10; 1:9; 1:8; 1:7; 1:6; 1:5; 1:4; 1:3; 1:2; 1:1; 2:1; 3:1; 4:1; 5:1; 6:1; 7:1; 8:1; 9:1; 10:1; 11:1; 12:1; 13:1; 14:1; 15:1; 16:1; 17:1; 18:1; 19:1; 20:1; 21:1; 22:1; 23:1; 24:1; 25:1; 26:1; 27:1; 28:1; 29:1; 30 :1. The pharmaceutical compositions according to the invention containing the combinations 10 of 1 and 2 are normally administered so that 1 and 2 are present together in doses of 0.1 to 10000 jg, preferably from 1 to 5000jg, more preferably from 10 to 3000ptg, better still from 100 to 2000jg per single dose. For example, combinations of I and 2 according to the invention contain a quantity of 1 and steroid 2 (as for instance budesonide, fluticasone, mometasone, ciclesonide) such that the total dosage per single dose is about 100g, 105gg, 15 110tg, 115ptg, 120 jg, 125 jg, 130g, 135jg, 140/g, 145p.g, 150Ag, 155g, 160/tg, 165/g, 170/pg, 175pjg, 180gg, 185pg, 190gg, 1951tg, 2 0 0 jg, 205/jg, 2104g, 215/zg, 2201Ag, 225pg, 230/Ag, 2351tg, 240/pg, 2451Ag, 2 50/jg, 255/pg, 260/ig, 265jig, 270jg, 275jg, 2801jg, 285pg, 290/g, 295pg, 300jg, 3051jg, 310Ag, 315pjg, 320pg, 3 251jg, 330Ag, 335/g, 340/Ag, 345/jg, 350ptg, 355pjg, 3601tg, 365/tg, 370Ag, 375/g, 3801Ag, 20 385itg, 3901tg, 395ig, 400jIg, 405ig, 410pAg, 415Ag, 420Ag, 4251jg, 430/jg, 4351jg, 440ig, 445/g, 450ig, 4551jg, 4601Ag, 465p g, 4701g, 475jg, 480/g, 485jg, 4 90Ag, 4951jg, 500ig, 5051jg, 510g, 515jg, 520pg, 525 tg, 530 tg, 535 jg, 540jg, 545 tg, 550jg, 555 tg, 560 jg, 565 jg, 570jg, 575pg, 580jg, 585jg, 590 jg, 595jg, 600jg, 605 jg, 610gg, 615pg, 620jg, 625 tg, 630jg, 635 jg, 640jg, 6 45jtg, 650jg, 655ptg, 25 660jg, 665 tg, 670jg, 675/jg, 680jg, 685 tg, 690 jg, 695jg, 700jg, 705jg, 710gg, 715pg, 720jg, 725jg, 730jg, 735jg, 740jg, 745 tg, 750jg, 755gg, 760jg, 765gg, 770jig, 775jg, 780jg, 785jg, 790gg, 795jg, 800jg, 805[tg, 8 10gg, 815[tg, 820jg, 825[jg, 830jig, 835pg, 840jg, 845 tg, 850[tg, 855jg, 860jg, 865Vjg, 870pg, 875gg, 880jg, 885jg, 890jg, 895pg, 900gg, 905gg, 910 tg, 915jg, 920tg, 925jg, 930jg, 30 935pg, 940 tg, 945 jg, 950jtg, 955jg, 960 tg, 965[tg, 970jg, 975 jg, 980pg, 985jg, 990 tg, 995 jg, 1000 jg, 1005jg, 1010gg, 1015jg, 1020tg, 1025gg, 1030tg, 1035jg, 1040jg, 1045 jg, 1050gg, 1055jg, 1060jg, 1065jg, 1070tg, 1075gg, 1080pg, 1085 jg, 1090jg, 1095jtg, 1100g, 1105tg, 1110g, 1115pLg, 1120tg, 1125jg, 1130jg, 1135jg, 1140jg, 1145Ag, 1150Ag, 1155g, 1160ig, 1165/pg, 1170/Ag, 1175/pg, l180jg, 1185pAg, 35 ll901tg, 1195/Ag, 1200jig, 1205pg, 1210OIg, 1215pg, 1220Ag, 1225pg, 1230Ag, 1235/pg, -5- WO 2005/014005 PCT/EP2004/008029 1240p/g, 1245pg, 1250pg, 1255gg, 1260Ag, 1265/Lg, 1270pg, 1275/g, 1280/Ag, 1 2 8 5pg, 12901Ag, 1295Ag, 1300gg, 1305tg, 1310pg, 1315kg, 1320ttg, 1325/Ag, 1330Ag, 1335Ag, 1340Ag, 1345pg, 1350/tg, 1355pg, 1360tg, 1365pg, 1370Ag, 1375pg, 1380pg, 1385jg, 13901tg, 1395jg, 1400/Ig, 1405jg, 1410/.tg, 1415/pg, 1420gg, 1425gg, 1 43 0/g, 1 4 3 5 pg, 5 1440Ag, 1445pg, 14501tg, 1455jig, 1460ig, 1 4 65[jg, 1470jg, 1475jg, 1480pg, 1485jig, 1490Ag, 1 49 5/tg, 1500/g, 1505pg, 1510Ipg, 1515Ag, 15201g, 1525gg, 1530g, 1535jg, 1540pLg, 1545jg, 1550g, 1555pg, 1560gg, 1565ptg, 1 5 70pg, 1575jg, 1580pg, 1585Pg, 1590g, 1595jg, 1 60 0pg, 1605jg, 1610gg, 1615lig, 1620jg, 1625jg, 1630jg, 1635jg, 1 6 40g, 1645jg, 1650gg, 1655ptg, 1660tg, 1665jg, 1670pg, 1675jg, 1680pg, 1 6 85[tg, 10 1690jg, 1695jg, 17009g, 1705 tg, 1710gg, 1715jg, 1720jg, 1725gg, 1730pg, 1735 tg, 1740 tg, 1745jg, 1750pg, 1755jg, 1760gg, 1765jg, 1770pg, 1775jg, 1780jg, 1785jg, 1790gg, 1795jg, 1800tg, 1805jg, 1810jg, 1815jg, 1820jg, 1825jg, 1830tg, 1835jg, 1840g, 1845jg, 1850pg, 1855jig, 1860tg, 1865jg, 1870g, 1875pg, 1880pg, 1885jg, 1890jg, 1895jg, 1900tg, 1905gjg, 1910g, 1915pg, 1920gg, 1925jg, 1930pg, 1935 tg, 15 1940pg, 1945jg, 1950pg, 1955pg, 1960tg, 1965jg, 1970pg, 1975 jg, 1980jg, 1985 tg, 1990tg, 1995jg, 2000jig or similar. It is clear to anyone skilled in the art that the suggested dosages per single dose specified above are not to be regarded as being limited to the numerical values actually stated. Fluctuations of about + 2.5 ptg, particularly in the decimal range, are also included, as will be apparent to the skilled man. In these dosage 20 ranges, the active substances 1 and 2 may be present in the weight ratios given above. For example, without restricting the scope of the invention thereto, the combinations of 1 and 2 according to the invention may contain a quantity of cation 1 (if for instance the bromide is used as the preferred combination partner) and steroid 2 (as for instance 25 budesonide, fluticasone, mometasone, ciclesonide) such that, for each single dose 40Ag of 1 and 25/tg of 2, 40g of 1 and 50pg of 2, 40Ag of I and 100/pg of 2, 4 0jg of 1 and 2 0 0 1tg of 2, 40pg of t and 300/g of 2, 40Ag of I and 400Ig of 2, 40Ag of l and 500pg of 2, 4 0Ag of 1 and 600pg of 2, 40jg of 1 and 700Ig of 2, 40jg of I and 800pAg of 2, 4 0jg of 1 and 900Ig of 2, 40Ag of 1 and 1000 g of 2, 60pg of 1 and 2 5jg of 2, 6 0pg of 1 and 30 50g of 2, 60g of I and 100tg of 2, 60pg of I and 200pg of 2, 6 0/pg of I and 300pAg of 2, 60Ag of 1 and 400jg of 2, 60jg of 1 and 500/jg of 2, 60Ag of I and 600jg of 2, 6 0/pg of 1 and 700jg of 2, 60Ag of I and 800ig of 2, 601tg of1 and 900pjg of 2, 60Ag of 1 and 1000/tg of 2, 801tg of I and 25jig of 2, 80g of t and 50Ig of 2, 80/tg of t and 100g of 2, 80jg of I and 200jig of 2, 80/jg of ! and 3001tg of 2, 80jg of t and 400jg of 2, 80jg of 1 35 and 500pg of 2, 80jg of ! and 600jg of 2, 80pjg of l and 700pg of 2, 80jg of 1 and 800jg -6- WO 2005/014005 PCT/EP2004/008029 of 2, 801jg of 1 and 900/jg of 2, 80/ig of I and 100OAg of 2, 1001jg of 1 and 25jg of 2, lO0Ig of 1 and 50OIg of 2, 100pg of 1 and 100pg of 2, 100ig of 1 and 200ptg of 2, 100Ig of l and 3001jg of 2, 100 ig of l and 400/pg of 2, lO100g of 1 and 500ptg of 2, 100Jg of 1 and 600 g of 2, 100ig of 1 and 7001tg of 2, 100 Ag of 1 and 800/Ag of 2, lO0g of 1 and 5 900/jg of 2, 10/tg of 1 and 1000pg of 2, 150Ag of 1 and 25jg of 2, 150 g of 1 and 50pg of 2, 150tg of l and 100[jg of 2, 150/g of l and 200/pg of 2, 150/jg of l and 300Ag of 2, 150tg of I and 4001tg of 2, 150pg of 1 and 500pg of 2, 150/pg of I and 600/tg of 2, 150pg of 1 and 700pg of 2, 150/pg of I and 800g of 2, 150jg of 1 and 90 0 jg of 2, 150Ag of I and 100Ig of 2, 200pg of I1 and 25pjg of 2, 200/Ag of I and 50pg of 2, 200jpg of 1 and 10 100pg of 2, 200ig of 1 and 200gg of 2, 200pjg of I and 300/jg of 2, 200fjg of 1 and 400/tg of 2, 200pg of I and 5001jg of 2, 200/ig of l and 6 00[jg of 2, 200itg of 1 and 700jg of 2, 200/ig of 1 and 800pig of 2, 200[jg of 1 and 900pg of 2, 200pjg of 1 and 1000Jg of 2, 250jg of l and 25/g of 2, 2501tg of 1 and 50pg of 2, 250Ag of 1 and lO100g of 2, 250Jig of l and 200jig of 2, 250/tg of l and 300pIg of 2, 2 501tg of I and 400ptg of 2, 250Ag of 1 and 15 500g of 2, 2501Ag of ! and 600jig of 2, 2501tg of 1 and 700pg of 2, 250pg of l and 800 g of 2, 2 5 0jg of 1 and 900pig of 2, 250jg of 1 and 1000 g of 2, 4 0 0ig of I and 25/jg of 2, 4001tg of l and 50/pg of 2, 400ptg of l and 100jg of 2, 400jAg of 1 and 200pIg of 2, 400pg of 1 and 300/g of 2, 400jg of 1 and 400pg of 2, 400jg of 1 and 500/g of 2, 400/jg of I and 600[tg of 2, 400/jg of ! and 700jg of 2, 400/tg of l and 800jig of 2, 400/jg of I and 20 900ptg of 2 or 400pg of ! and 10001g of 2, 500jug of 1 and 25jg of 2, 500pg of 1 and 50pAg of 2, 500pg of l and lO0g of 2, 500/g of 1 and 200[tg of 2, 500 g of 1 and 300[jg of 2, 500/jg of l and 400 jg of 2, 500jg of ! and 500/g of 2, 500pg of ! and 600jg of 2, 500ig of ! and 700/Ag of 2, 500pig of l and 800/g of 2, 500pjg of I and 900/g of 2 or 500jg of ! and 1000[g of 2, 600/pg of I and 25/g of 2, 600tjg of I and 50g of 2, 6 00[tg 25 of I and 100 g of 2, 600ig of 1 and 200/ig of 2, 6 0 0 ig of l and 300pg of 2, 600pg of ! and 400jig of 2, 600pg ofl and 500 g of 2, 600pjg of I and 600/g of 2, 600jg of l and 700jIg of 2, 600/tg of ! and 800ptg of 2, 600jig of 1 and 9001tg of 2 or 600jig of 1 and 1000tg of 2, 700/ig of 1 and 25pg of 2, 700/jg of ! and 50pjg of 2, 700jg of I and 1001jg of 2, 700pIg of l and 200/jg of 2, 700/jg of ! and 300gg of 2, 700jig of I and 400/tg of 2, 30 700pg of ! and 500ptg of 2, 700jig of t and 600pg of 2, 700jg of I and 700pg of 2, 700jg of l and 800pg of 2, 700/g of and 900/g of 2, 700jg of t and 1000tg of 2, 800jig of ! and 25jg of 2, 8001tg of I and 501jg of 2, 800/g of 1 and lO100g of 2, 800jig of t and 200jg of 2, 800jig of 1 and 300jig of 2, 800 g of l and 400jig of 2, 800jig of l and 500g of 2, 800pg of I and 600jg of 2, 800pg of ! and 700pjg of 2, 800/jg of-1 and 800/jg of 2, 35 800/pg of ! and 900gg of 2, 800jig of 1 and 100OIg of 2, 9 0 0 /jg of I and 25jig of 2, 900jig -7- WO 2005/014005 PCT/EP2004/008029 of and 50kg of 2, 900/g of I and 1001tg of 2, 900Og of 1 and 200pg of 2, 900pg of I and 300[ig of 2, 9 00/tg of l and 400tg of 2, 900jg of I1 and 500pg of 2, 9 00/g of 1 and 600tg of 2, 900ug of 1 and 700pug of 2, 900ptg of I and 800/pg of 2, 9 00jug of 1 and 900kg of 2, 900pg of 1 and 1000pg of 2, 1000/g of 1 and 25pg of 2, 1000Ag of l and 50/ig of 2, 5 1000pg of l and 100g of 2, 1000pg of l and 200/pg of 2, 1000/tg of l and 300ig of 2, 1000g of I and 400fig of 2, 1000gg of 1 and 500ug of 2, 1000Og of 1 and 600gg of 2, 1000 g of l and 7 00/g of 2, 1000pg of 1 and 8001Ag of 2, 1000g of l and 900pg of 2 or 1000g of 1 and 1000/g of 2.are present. 10 The aforementioned examples of possible doses applicable for the combinations according to the invention are to be understood as referring to doses per single application. However, these examples are not be understood as excluding the possibility of administering the combinations according to the invention multiple times. Depending on the medical need patients may receive also multiple inhalative applications. As an example patients may 15 receive the combinations according to the invention for instance two or three times (e.g. two or three puffs with a powder inhaler, an MDI etc) in the morning of each treatment day. As the aforementioned dose examples are only to be understood as dose examples per single application (i.e. per puff) multiple application of the combinations according to the invention leads to multiple doses of the aforementioned examples. The application of the 20 combositions according to the invention can be for instance once a day, or depending on the duration of action of the anticholinergic agent twice a day, or once every 2 or 3 days. Moreover it is emphazised that the aforementioned dose examples are to be understood as examples of metered doses only. In other terms, the aforementioned dose examples are not 25 to be understood as the effective doses of the combinations according to the invention that do in fact reach the lung. It is clear for the person of ordinary skill in the art that the delivered dose to the lung is generally lower than the metered dose of the administered active ingredients. 30 The active substance combinations of I and 2 according to the invention are preferably administered by inhalation. For this purpose, ingredients 1 and 2 have to be made available in forms suitable for inhalation. Inhalable preparations according to the invention include inhalable powders, propellant-containing metered dose aerosols or propellant-free inhalable solutions. Inhalable powders according to the invention 35 containing the combination of active substances 1 and 2 may consist of the active -8- WO 2005/014005 PCT/EP2004/008029 substances on their own or of a mixture of the active substances with physiologically acceptable excipients. Within the scope of the present invention, the term carrier may optionally be used instead of the term excipient. Within the scope of the present invention, the term propellant-free inhalable solutions also includes concentrates or sterile inhalable 5 solutions ready for use. The preparations according to the invention may contain the combination of active substances 1 and 2 either together in one formulation or in two separate formulations. These formulations which may be used within the scope of the present invention are described in more detail in the next part of the specification. 10 A) Inhalable powder containing the combinations of active substances 1 and 2 according to the invention: The inhalable powders according to the invention may contain 1 and 2 either on their own or in admixture with suitable physiologically acceptable excipients. If the active substances 1 and 2 are present in admixture with physiologically acceptable 15 excipients, the following physiologically acceptable excipients may be used to prepare these inhalable powders according to the invention: monosaccharides (e.g. glucose or arabinose), disaccharides (e.g. lactose, saccharose, maltose, trehalose), oligo- and polysaccharides (e.g. dextran), polyalcohols (e.g. sorbitol, mannitol, xylitol), cyclodextrines (e.g. c-cyclodextrine, 3 -cyclodextrine, X-cyclodextrine, methyl-03 20 cyclodextrine, hydroxypropyl-3-cyclodextrine), salts (e.g. sodium chloride, calcium carbonate) or mixtures of these excipients with one another. Preferably, mono- or disaccharides are used, while the use of lactose, trehalose or glucose is preferred, particularly, but not exclusively, in the form of their hydrates. 25 Within the scope of the inhalable powders according to the invention the excipients have a maximum average particle size of up to 250tm, preferably between 10 and 150m, most preferably between 15 and 8 0 pm. It may sometimes seem appropriate to add finer excipient fractions with an average particle size of 1 to 9tm to the excipient mentioned above. These finer excipients are also selected from the group of possible excipients listed 30 hereinbefore. Finally, in order to prepare the inhalable powders according to the invention, micronised active substance 1 and 2, preferably with an average particle size of 0.5 to 10Im, more preferably from 1 to 6tm, is added to the excipient mixture. Processes for producing the inhalable powders according to the invention by grinding and micronising and by finally mixing the ingredients together are known from the prior art. The inhalable 35 powders according to the invention may be prepared and administered either in the form of -9- WO 2005/014005 PCT/EP2004/008029 a single powder mixture which contains both 1 and 2 or in the form of separate inhalable powders which contain only 1 or 2. The inhalable powders according to the invention may be administered using inhalers 5 known from the prior art. Inhalable powders according to the invention which contain one or more physiologically acceptable excipients in addition to 1 and 2 may be administered, for example, by means of inhalers which deliver a single dose from a supply using a measuring chamber as described in US 4570630A, or by other means as described in DE 36 25 685 A. The inhalable powders according to the invention which contain 1 and 2 10 optionally in conjunction with a physiologically acceptable excipient may be administered, for example, using the inhaler known by the name Turbuhaler® or using inhalers as disclosed for example in EP 237507 A. Preferably, the inhalable powders according to the invention which contain physiologically acceptable excipient in addition to 1 and 2 are packed into capsules (to produce so-called inhalettes) which are used in inhalers as 15 described, for example, in WO 94/28958. A particularly preferred inhaler for using the pharmaceutical combination according to the invention in inhalettes is shown in Figure 1. This inhaler (Handyhaler) for inhaling powdered pharmaceutical compositions from 20 capsules is characterised by a housing 1 containing two windows 2, a deck 3 in which there are air inlet ports and which is provided with a screen 5 secured via a screen housing 4, an inhalation chamber 6 connected to the deck 3 on which there is a push button 9 provided with two sharpened pins 7 and movable counter to a spring 8, and a mouthpiece 12 which is connected to the housing 1, the deck 3 and a cover 11 via a spindle 10 to enable it to be 25 flipped open or shot, as well as airholes 13 for adjusting the flow resistance. If the inhalable powders according to the invention are packed into capsules (inhalers) for the preferred use described above, the quantities packed into each capsule should be 1 to 30mg per capsule. These capsules contain, according to the invention, either together or 30 separately, the doses of 1 or 2 mentioned hereinbefore for each single dose. B) Propellant gas-driven inhalation aerosols containing the combinations of active substances I and 2: Inhalation aerosols containing propellant gas according to the invention may contain 35 substances 1 and 2 dissolved in the propellant gas or in dispersed form. 1 and 2 may be -10- WO 2005/014005 PCT/EP2004/008029 present in separate formulations or in a single preparation, in which 1 and 2 are either both dissolved, both dispersed or only one component is dissolved and the other is dispersed. The propellant gases which may be used to prepare the inhalation aerosols according to the invention are known from the prior art. Suitable propellant gases are selected from among 5 hydrocarbons such as n-propane, n-butane or isobutane and halohydrocarbons such as fluorinated derivatives of methane, ethane, propane, butane, cyclopropane or cyclobutane. The propellant gases mentioned above may be used on their own or in mixtures thereof. Particularly preferred propellant gases are halogenated alkane derivatives selected from TG11, TG12, TG134a (1,1,1,2-tetrafluoroethane) and TG227 (1,1,1,2,3,3,3 10 heptafluoropropane) and mixtures thereof, of which the propellant gases TG134a, TG227 and mixtures thereof are preferred. The propellant-driven inhalation aerosols according to the invention may also contain other ingredients such as co-solvents, stabilisers, surfactants, antioxidants, lubricants and pH 15 adjusters. All these ingredients are known in the art. The inhalation aerosols containing propellant gas according to the invention may contain up to 5 wt.-% of active substance 1 and/or 2. Aerosols according to the invention contain, for example, 0.002 to 5 wt.-%, 0.01 to 3 wt.-%, 0.015 to 2 wt.-%, 0.1 to 2 wt.-%, 0.5 to 20 2 wt.-% or 0.5 to 1 wt.-% of active substance 1 and/or 2. If the active substances I1 and/or 2 are present in dispersed form, the particles of active substance preferably have an average particle size of up to 10tm, preferably from 0.1 to 6pgm, more preferably from 1 to 5gm. 25 The propellant-driven inhalation aerosols according to the invention mentioned above may be administered using inhalers known in the art (MDIs = metered dose inhalers). Accordingly, in another aspect, the present invention relates to pharmaceutical compositions in the form of propellant-driven aerosols as hereinbefore described combined 30 with one or more inhalers suitable for administering these aerosols. In addition, the present invention relates to inhalers which are characterised in that they contain the propellant gas containing aerosols described above according to the invention. The present invention also relates to cartridges fitted with a suitable valve which can be used in a suitable inhaler and which contain one of the above-mentioned propellant gas-containing inhalation aerosols 35 according to the invention. Suitable cartridges and methods of filling these cartridges with -11- WO 2005/014005 PCT/EP2004/008029 the inhalable aerosols containing propellant gas according to the invention are known from the prior art. C) Propellant-free inhalable solutions or suspensions containing the combinations of 5 active substances 1 and 2 according to the invention: Propellant-free inhalable solutions and suspensions according to the invention contain, for example, aqueous or alcoholic, preferably ethanolic solvents, optionally ethanolic solvents mixed with aqueous solvents. If aqueous/ethanolic solvent mixtures are used the relative proportion of ethanol compared with water is not limited but preferably the maximum is up 10 to 70 percent by volume, more particularly up to 60 percent by volume of ethanol. The remainder of the volume is made up of water. The solutions or suspensions containing 1 and 2, separately or together, are adjusted to a pH of 2 to 7, preferably 2 to 5, using suitable acids. The pH may be adjusted using acids selected from inorganic or organic acids. Examples of particularly suitable inorganic acids include hydrochloric acid, 15 hydrobromic acid, nitric acid, sulphuric acid and/or phosphoric acid. Examples of particularly suitable organic acids include ascorbic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, fumaric acid, acetic acid, formic acid and/or propionic acid etc. Preferred inorganic acids are hydrochloric and sulphuric acids. It is also possible to use the acids which have already formed an acid addition salt with one of the active 20 substances. Of the organic acids, ascorbic acid, fumaric acid and citric acid are preferred. If desired, mixtures of the above acids may be used, particularly in the case of acids which have other properties in addition to their acidifying qualities, e.g. as flavourings, antioxidants or complexing agents, such as citric acid or ascorbic acid, for example. According to the invention, it is particularly preferred to use hydrochloric acid to adjust the 25 pH. According to the invention, the addition of editic acid (EDTA) or one of the known salts thereof, sodium editate, as stabiliser or conmplexing agent is unnecessary in the present formulation. Other embodiments may contain this compound or these compounds. In a 30 preferred embodiment the content based on sodium editate is less than 100mg/100ml, preferably less than 50mg/100 ml, more preferably less than 20mg/100 ml. Generally, inhalable solutions in which the content of sodium editate is from 0 to 10mg/100ml are preferred. -12- WO 2005/014005 PCT/EP2004/008029 Co-solvents and/or other excipients may be added to the propellant-free inhalable solutions according to the invention. Preferred co-solvents are those which contain hydroxyl groups or other polar groups, e.g. alcohols - particularly isopropyl alcohol, glycols - particularly propyleneglycol, polyethyleneglycol, polypropyleneglycol, glycolether, glycerol, 5 polyoxyethylene alcohols and polyoxyethylene fatty acid esters. The terms excipients and additives in this context denote any pharmacologically acceptable substance which is not an active substance but which can be formulated with the active substance or substances in the pharmacologically suitable solvent in order to improve the qualitative properties of the active substance formulation. Preferably, these substances have no pharmacological effect 10 or, in connection with the desired therapy, no appreciable or at least no undesirable pharmacological effect. The excipients and additives include, for example, surfactants such as soya lecithin, oleic acid, sorbitan esters, such as polysorbates, polyvinylpyrrolidone, other stabilisers, complexing agents, antioxidants and/or preservatives which guarantee or prolong the shelf life of the finished pharmaceutical 15 formulation, flavourings, vitamins and/or other additives known in the art. The additives. also include pharmacologically acceptable salts such as sodium chloride as isotonic agents. The preferred excipients include antioxidants such as ascorbic acid, for example, provided that it has not already been used to adjust the pH, vitamin A, vitamin E, tocopherols and similar vitamins and provitamins occurring in the human body. 20 Preservatives may be used to protect the formulation from contamination with pathogens. Suitable preservatives are those which are known in the art, particularly cetyl pyridinium chloride, benzalkonium chloride or benzoic acid or benzoates such as sodium benzoate in the concentration known from the prior art. The preservatives mentioned above are 25 preferably present in concentrations of up to 50mg/100ml, more preferably between 5 and 20mg/100ml. Preferred formulations contain, in addition to the solvent water and the combination of active substances 1 and 2, only benzalkonium chloride and sodium editate. In another 30 preferred embodiment, no sodium editate is present. The propellant-free inhalable solutions according to the invention are administered in particular using inhalers of the kind which are capable of nebulising a small amount of a liquid formulation in the therapeutic dose within a few seconds to produce an aerosol 35 suitable for therapeutic inhalation. Within the scope of the present invention, preferred -13- WO 2005/014005 PCT/EP2004/008029 inhalers are those in which a quantity of less than 100L, preferably less than 50pL, more preferably between 20 and 3OpL of active substance solution can be nebulised in preferably one spray action to form an aerosol with an average particle size of less than 20gm, preferably less than 10gm, in such a way that the inhalable part of the aerosol 5 corresponds to the therapeutically effective quantity. An apparatus of this kind for propellant-free delivery of a metered quantity of a liquid pharmaceutical composition for inhalation is described for example in International Patent Application WO 91/14468 and also in WO 97/12687 (cf. in particular Figures 6a and 6b). 10 The nebulisers (devices) described therein are known by the name Respimat@. This nebuliser (Respimat®) can advantageously be used to produce the inhalable aerosols according to the invention containing the combination of active substances 1 and 2. Because of its cylindrical shape and handy size of less than 9 to 15 cm long and 2 to 4 cm wide, this device can be carried at all times by the patient. The nebuliser sprays a defined 15 volume of pharmaceutical formulation using high pressures through small nozzles so as to produce inhalable aerosols. The preferred atomiser essentially consists of an upper housing part, a pump housing, a nozzle, a locking mechanism, a spring housing, a spring and a storage container, 20 characterised by - a pump housing which is secured in the upper housing part and which comprises at one end a nozzle body with the nozzle or nozzle arrangement, - a hollow plunger with valve body, - a power takeoffflange in which the hollow plunger is secured and which is located 25 in the upper housing part, - a locking mechanism situated in the upper housing part, - a spring housing with the spring contained therein, which is rotatably mounted on the upper housing part by means of a rotary bearing, - a lower housing part which is fitted onto the spring housing in the axial direction. 30 The hollow plunger with valve body corresponds to a device disclosed in WO 97/12687. It projects partially into the cylinder of the pump housing and is axially movable within the cylinder. Reference is made in particular to Figures 1 to 4, especially Figure 3, and the relevant parts of the description. The hollow plunger with valve body exerts a pressure of 35 5 to 60 Mpa (about 50 to 600 bar), preferably 10 to 60 Mpa (about 100 to 600 bar) on the -14- WO 2005/014005 PCT/EP2004/008029 fluid, the measured amount of active substance solution, at its high pressure end at the moment when the spring is actuated. Volumes of 10 to 50 microlitres are preferred, while volumes of 10 to 20 microlitres are particularly preferred and a volume of 15 microlitres per spray is most particularly preferred. 5 The valve body is preferably mounted at the end of the hollow plunger facing the valve body. The nozzle in the nozzle body is preferably microstructured, i.e. produced by 10 microtechnology. Microstructured nozzle bodies are disclosed for example in WO 94/07607; reference is hereby made to the contents of this specification, particularly Figure 1 therein and the associated description. The nozzle body consists for example of two sheets of glass and/or silicon firmly joined together, at least one of which has one or more microstructured channels which connect the 15 nozzle inlet end to the nozzle outlet end. At the nozzle outlet end there is at least one round or non-round opening 2 to 10 microns deep and 5 to 15 microns wide, the depth preferably being 4.5 to 6.5 microns while the length is preferably 7 to 9 microns. In the case of a plurality of nozzle openings, preferably two, the directions of spraying of the nozzles in the nozzle body may extend parallel to one another or may be inclined 20 relative to one another in the direction of the nozzle opening. In a nozzle body with at least two nozzle openings at the outlet end the directions of spraying may be at an angle of 20 to 1600 to one another, preferably 60 to 150', most preferably 80 to 100'. The nozzle openings are preferably arranged at a spacing of 10 to 200 microns, more preferably at a spacing of 10 to 100 microns, most preferably 30 to 70 microns. Spacings of 50 microns 25 are most preferred: The directions of spraying will therefore meet in the vicinity of the nozzle openings. The liquid pharmaceutical preparation strikes the nozzle body with an entry pressure of up to 600 bar, preferably 200 to 300 bar, and is atomised into an inhalable aerosol through the nozzle openings. The preferred particle or droplet sizes of the aerosol are up to 20 30 microns, preferably 3 to 10 microns. The locking mechanism contains a spring, preferably a cylindrical helical compression spring, as a store for the mechanical energy. The spring acts on the power takeoff flange as an actuating member the movement of which is determined by the position of a locking 35 member. The travel of the power takeoff flange is precisely limited by an upper and lower -15- WO 2005/014005 PCT/EP2004/008029 stop. The spring is preferably biased, via a power step-up gear, e.g. a helical thrust gear, by an external torque which is produced when the upper housing part is rotated counter to the spring housing in the lower housing part. In this case, the upper housing part and the power takeoff flange have a single or multiple V-shaped gear. 5 The locking member with engaging locking surfaces is arranged in a ring around the power takeoff flange. It consists, for example, of a ring of plastic or metal which is inherently radially elastically deformable. The ring is arranged in a plane at right angles to the atomiser axis. After the biasing of the spring, the locking surfaces of the locking member 10 move into the path of the power takeoff flange and prevent the spring from relaxing. The locking member is actuated by means of a button. The actuating button is connected or coupled to the locking member. In order to actuate the locking mechanism, the actuating button is moved parallel to the annular plane, preferably into the atomiser; this causes the deformable ring to deform in the annular plane. Details of the construction of the locking 15 mechanism are given in WO 97/20590. The lower housing part is pushed axially over the spring housing and covers the mounting, the drive of the spindle and the storage container for the fluid. When the atomiser is actuated the upper housing part is rotated relative to the lower 20 housing part, the lower housing part taking the spring housing with it. The spring is thereby compressed and biased by means of the helical thrust gear and the locking mechanism engages automatically. The angle of rotation is preferably a whole-number fraction of 360 degrees, e.g. 180 degrees. At the same time as the spring is biased, the power takeoff part in the upper housing part is moved along by a given distance, the 25 hollow plunger is withdrawn inside the cylinder in the pump housing, as a result of which some of the fluid is sucked out of the storage container and into the high pressure chamber in front of the nozzle. If desired, a number of exchangeable storage containers which contain the fluid to be 30 atomised may be pushed into the atomiser one after another and used in succession. The storage container contains the aqueous aerosol preparation according to the invention. The atomising process is initiated by pressing gently on the actuating button. As a result, the locking mechanism opens up the path for the power takeoff member. The biased spring pushes the plunger into the cylinder of the pump housing. The fluid leaves the 35 nozzle of the atomiser in atomised form. -16- WO 2005/014005 PCT/EP2004/008029 Further details of construction are disclosed in PCT Applications WO 97/12683 and WO 97/20590, to which reference is hereby made. The components of the atomiser (nebuliser) are made of a material which is suitable for its 5 purpose. The housing of the atomiser and, if its operation permits, other parts as well, are preferably made of plastics, e.g. by injection moulding. For medicinal purposes, physiologically safe materials are used. Figures 6a/b of WO 97/12687, show the nebuliser (Respimat®) which can advantageously 10 be used for inhaling the aqueous aerosol preparations according to the invention. Figure 6a of WO 97/12687 shows a longitudinal section through the atomiser with the spring biased while Figure 6b of WO 97/12687 shows a longitudinal section through the atomiser with the spring relaxed. The upper housing part (51) contains the pump housing (52) on the end of which is 15 mounted the holder (53) for the atomiser nozzle. In the holder is the nozzle body (54) and a filter (55). The hollow plunger (57) fixed in the power takeoff flange (56) of the locking mechanism projects partially into the cylinder of the pump housing. At its end the hollow plunger carries the valve body (58). The hollow plunger is sealed off by means of the seal (59). Inside the upper housing part is the stop (60) on which the power takeoff flange 20 abuts when the spring is relaxed. On the power takeoff flange is the stop (61) on which the power takeoff flange abuts when the spring is biased. After the biasing of the spring the locking member (62) moves between the stop (61) and a support (63) in the upper housing part. The actuating button (64) is connected to the locking member. The upper housing part ends in the mouthpiece (65) and is sealed off by means of the protective cover (66) 25 which can be placed thereon. The spring housing (67) with compression spring (68) is rotatably mounted on the upper housing part by means of the snap-in lugs (69) and rotary bearing. The lower housing part (70) is pushed over the spring housing. Inside the spring housing is the exchangeable storage container (71) for the fluid (72) which is to be atomised. The storage container is 30 sealed off by the stopper (73) through which the hollow plunger projects into the storage container and is immersed at its end in the fluid (supply of active substance solution). The spindle (74) for the mechanical counter is mounted in the covering of the spring housing. At the end of the spindle facing the upper housing part is the drive pinion (75). The slider (76) sits on the spindle. 35 -17- WO 2005/014005 PCT/EP2004/008029 The nebuliser described above is suitable for nebulising the aerosol preparations according to the invention to produce an aerosol suitable for inhalation. If the formulation according to the invention is nebulised using the method described above (Respimat®) the quantity delivered should correspond to a defined quantity with a 5 tolerance of not more than 25%, preferably 20% of this amount in at least 97%, preferably at least 98% of all operations of the inhaler (spray actuations). Preferably, between 5 and 30 mg of formulation, most preferably between 5 and 20 mg of formulation are delivered as a defined mass on each actuation. 10 However, the formulation according to the invention may also be nebulised by means of inhalers other than those described above, e.g. jet stream inhalers or other stationary nebulisers. Accordingly, in a further aspect, the invention relates to pharmaceutical formulations in the 15 form of propellant-free inhalable solutions or suspensions as described above combined with a device suitable for administering these fornmlations, preferably in conjunction with the Respimat®. Preferably, the invention relates to propellant-free inhalable solutions or suspensions characterised by the combination of active substances 1 and 2 according to the invention in conjunction with the device known by the name Respimat®. In addition, the 20 present invention relates to the above-mentioned devices for inhalation, preferably the Respimat®, characterised in that they contain the propellant-free inhalable solutions or suspensions according to the invention as described hereinbefore. According to the invention, inhalable solutions which contain the active substances 1 and 2 in a single preparation are preferred. The term "single preparation" also includes 25 preparations which contain the two ingredients 1 and 2 in two-chamber cartridges, as disclosed for example in WQ 00/23037. Reference is hereby made to this publication in its entirety. The propellant-free inhalable solutions or suspensions according to the invention may take 30 the form of concentrates or sterile inhalable solutions or suspensions ready for use, as well as the above-mentioned solutions and suspensions designed for use in a Respimat@. Formulations ready for use may be produced from the concentrates, for example, by the addition of isotonic saline solutions. Sterile formulations ready for use may be administered using energy-operated free-standing or portable nebulisers which produce -18- WO 2005/014005 PCT/EP2004/008029 inhalable aerosols by means of ultrasound or compressed air by the Venturi principle or other principles. Accordingly, in another aspect, the present invention relates to pharmaceutical 5 compositions in the form of propellant-free inhalable solutions or suspensions as described hereinbefore which take the form of concentrates or sterile formulations ready for use, combined with a device suitable for administering these solutions, characterised in that the device is an energy-operated free-standing or portable nebuliser which produces inhalable aerosols by means of ultrasound or compressed air by the Venturi principle or other 10 methods. The Examples which follow serve to illustrate the present invention in more detail without restricting the scope of the invention to the following embodiments by way of example. 15 Examples of Formulations The following examples of formulations, which may be obtained analogously to methods known in the art, serve to illustrate the present invention more fully without restricting it to the contents of these examples. In the following exmples the enantiomerically pure form of the preferred enantiomer of the bromide of formula I (i.e. formula 1-en) is used as the 20 active ingredient. Inhalable powders: 1) Ingredients gg per capsule 1-en (bromide) 250 budesonide 200 lactose 12050 Total 12500 25 2) Ingredients gg per capsule 1-en (bromide) 200 Fluticasone-propionate 125 -19- WO 2005/014005 PCT/EP2004/008029 lactose 4675 Total 5000 3) Ingredients ag per capsule 1-en (bromide) 250 Mometasone-furoate X H 2 0 250 lactose 12000 Total 12500 5 4) Ingredients gg per capsule 1-en (bromide) 200 Ciclesonide 250 lactose 12050 Total 12500 5) Ingredients pg per capsule 1-en (bromide) 100 budesonide 125 lactose 4775 Total 5000 6) Ingredients gg per capsule 1-en (bromide) 150 Fluticasone-propionate 200 lactose 4650 Total 5000 10 -20- WO 2005/014005 PCT/EP2004/008029 7) Ingredients _ g per capsule 1-en (bromide) 150 Mometasone-furoate X H 2 0 250 lactose 4600 Total 5000 8) Ingredients pg per capsule 1-en (bromide) 100 Ciclesonide 250 lactose 4650 Total 5000 5 B) Propellant-containing aerosols for inhalation: 1) Suspension aerosol: Ingredients % b weight 1-en (bromide) 0.1 budesonide 0.4 soya lecithin 0.2 TG 134a: TG227 = 2:3 ad 100 10 2) Suspension aerosol: Ingredients % by weight 1-en (bromide) 0.2 Fluticasone-propionate 0.3 Isopropyl myristate 0.1 TG 227 ad 100 3) Suspension aerosol: -21- WO 2005/014005 PCT/EP2004/008029 Ingredients % by weight 1-en (bromide) 0.1 Mometasone-furoate X H20 0.6 Isopropyl myristate 0.1 TG 227 ad 100 4) Suspension aerosol: Ingredients % by weight 1-en (bromide) 0.1 Ciclesonide 0.4 Isopropyl myristate 0.1 TG 134a: TG227 = 2:3 ad 100 -22-