DE1617336A1 - Pharmaceutical preparations effective for the heart - Google Patents

Description

Case 1/259

Dr. Ve / Ba ^ ^Γ · ^ · Zumstein sen. - Dr, E. Assmann Dr. R. Koenigsbergor - Dipl. Phys. R. Holzbauer

Dr. F. Zumctcin jun. ri i ι ΛΜ. o.'X INi «ι λ Patent attorneys

New full registration documents

CH. Boehringer Sohn, Ingelheim am Rhein

Cardiac active pharmaceutical preparations

The invention relates to pharmaceutical preparations having a particularly beneficial effect against angina pectoris.

Bs "is already known to be among other heart diseases also the angina pectoris with the help of ß-adrenolytic effective l-aryloxy-2-hydroxy-3-aminopropanes can be treated (see e.g. the French BSM No. 3732, 4057, 4061, and 4161, Belgian patents nos. 652 336, 670 364, 675 967 and 676 821, Irish patent applications nos.

009850/1932

Documents (Art 7, Paragraph 1, Paragraph 2, No.

" ² " 161/336

946/65, 330/66, 331/66 and 430/66, the South African Patents Nos. 65/4447, 65/5403 and 65/5907, the Dutch Patent applications No. 64.10522 and 65.03196 · as well as DAS 1 227 462).

In the treatment of angina pectoris with such compounds however, one has to accept some therapeutic disadvantages. Connections of the above-mentioned Kehrer structural type. namely the coronary-expanding effect of the chemical carrier substances in the sympathetic nervous system, adrenaline and Norepinephrine, into a vasoconstrictor effect. It it has also been shown that all ß-adrenolytics also have a more or less large coronary constricting effect to have.

Despite an improvement in the anginal condition, this leads to the fact that Overall, the blood flow to the heart muscle decreases. In particular in the case of lack of oxygen and emotional excitement (conditions associated with an activation of the sympathetic nervous system are coupled), these mechanisms can lead to a current deficiency in blood flow to the heart muscle.

It has now been found that the disadvantages of treating the Angina pectoris with ß-adrenolytica can be resolved, if one the latter prescribed together with cyclic pyrimidine derivatives, As for example in the DBP 1 116 676 and the Belgian patents 568 931, 569 399, 649 347 and 649 are described. In particular, there are compounds of the general formula

I BAD ORIGINAL

R ₂

009 850/1932

161/336: -3 -

in question. In this formula:

R-j is a (N-hydroxy- or -diliydroxy-lower alkyl-il-hydro ^ cy- or dihydroxy-nlederalkylj-amino or a (ΐί — lower— acyloxy-lower alkyl-IT-lower acyloxy-lower alkyl) -ainino group, in which the chain length of the lower alkyl part of the two hydroxy or dihydroxy-lower alkyl or lower acyloxy-lower alkyl groups can be the same or different; one bound via the N atom and optionally with one or two lower alkyl groups or hydroxyl groups substituted morpholino, pyrrolidine, piperazine, 1,2,5,6, -iEetrahydropyrldin- or piperidine radical or a lower alkyl or alkylainino, an H-lower alkyl-H-hydroxy-lower alkyl aino radical or a K-Arylniedera.lkyl-I? Hydroxy-lower alkylaiflinorest,

R _{0 is} a bonded via the N atom and optionally snbstistuiertei with one or two lower alkyl groups or hydroxyl groups piperidine, 1, 2 ₁ 5 »6-tetrahydropyridine; Karpholine, piperazine or pyrrolidine radical, a lower alkoxy or alkylthio group, an (N-hydroxy- or dihydrody-lower-alkyl-1-hydroxy- or dihydroxy-lower-alkyl) -amino- or a (M-lower acyloxy-lower alkyl-II-nifideracyloxy-lower alkyl ) -aniino group _r in which the chain length of the ^{lower alk3 r} l part of the two. Hydroxy-lower alkyl or lliederacyloxy-lower alkyl groups can be the same or different; or an N-lower alkyl-N-hydroxy-lower alkyl or an N-aryl-lower alkyl-K-hydroxy-lower alkylamino radical and A is the group -N = C (R ₅ ) -N = C (R ^) -; the group -N = C (E ^) - C (R ₄ ) = N -; "the group -C (CH ₂ ) ^ or the group -S-

'■. ■■■. O

whereby , ;

BAD ORIGINAL

009850/193 2

161/336

EU is a (N-hydroxy- or M-hydroxy-lower alk / l-IJ-hydrüxy- or dihydroxy-lower alkyl) amino or a; (IT -: < ^r i <? deracyloxyniederalkyl-N-loweraeyloxy-lower alkyl) -aininogruppo, in which the chain length of the lower alkyl part of the two hydroxy-, lower-alkyl- or ITiederacyloxy-lower-alkyl groups can be or different, or given .nenfailH mono- or polysubstituted by halogen or lower alkyl "! Is phenyl, thienyl or puryl group

K ,, can have the same meanings as H ^ or Kp and may be the same as or different from these and ή is the number 2 or, 3.

Ss-Adrenolytica to be used with advantage for the combination with the substances of general formula I are racemisehe or optically active compounds of the general formula

ArOCH ₂ -CHOH-GH ₂ -NHR - II

in this formula: _

Ar is an unsubstituted or a mono- or polysubstituted iso-, homo- or heterocyclic Kent with at least one aromatic 6-ring that is bonded directly to the Kestmolek'il, where the substituents are preferably lower alkyl, tr! Fluorine thyl, Amino or nitrile groups and haloethio groups, as well as lower ferric alkoxy, lower aeyloxy, acyl, alkyloxy, alkynyl, alkyithio, mono- or dialkyl aino radicals , and also nitro, eyaroxy, etc. 3, ^ - Methylendioxygruppeii in question komoj'sn ^ irv '

R is an alkyl radical with 1-6 carbon atoms or an aralkyl radical with 7-10 carbon atoms, preferably the isopropyl or t-butyl group.

BADOR! 0iNÄL " Q 09-8 5 0/1 932

161/336

For the combination with such. ß-Adrenolytica especially The following Vex * bonds of the general formula I have proven to be suitable:

2,6-bis (diethanolamino) -4r3-dipiperidiiio-pyrimido- [5,4-d) -pyrimidine ■

2,6-bis (diethanolamino) -4, β-di- (2-methylpiperidino) -pyrim ι do ~ [5} 4-d3-pyrimidiii .

2,6-bis (diethanolamino) -4, S-di- (3-methylpiperidino) pyrini

2,6-bis (diethanolaminoj-4,8-di (1,2 ^ 16-tetrahydropyridino) pyrimido [5,4-d] pyrimidine

2, Q-bis- ^{(diätlianolamino:)} -4,8-di- (3-hydr oxypiper ictino) pyrimido [5,4 ~ d] -pyriii] idiii

2,6-Bis (diisopropanolamino) -4:, 8-dimorpholino-pyrimidO- [ ¹ J, 4-d 3-pyrimidine

2-DiethanΌlamino-6 - (l · I-ethanol-N-isopropanol) -amino-4r8-dipiperidijio-pyrimidO- [5,4-d ] -pyrimidine 2-Dlätiianolamino-6-Diisopropanolamino-4,8-dipiperiilino-

pyrimido-f5j4-ct] pyriinidine: - -.

2,6-bis- (di-ß-acetoxyethyl) -amino] -4,8-dipiperidino-pyrimido- [5 i4-d "] - pyrimidine

2,6-bis (diethanolamino) -4 ₁ 8-ethylthio-pyrimido- [5,4-d] -

pyrimidine ■ - .; "..: ■

2,6-bis - [(di-B-formyloxyethyl) amino] -4 »8-dipiperidinopyrimido - [, 5,4-d] pyrimidine :

2, b-Bl s- (diethanolamino ^ -äthylthio-S-piperidino-pyrirnido-

2., 4-, 7 _r -

2,7-Sifflo ^ pholinQ-4- (N-ethBnol-K ^ methyl) 2, T-Blmo ^ iiaiiiio-A- (iT-ethanol ^ N-ethyl) -amino; -6-phenylpteridine 2 If 7 ^ Mmarp] iolino-4- (N-ethanol-N-feenzyl) -amino-6-phenylpteridine 2,7-Diniarpiiölino-4 ~ (N * -ä "fchanol-N-inethyl) -amino-6-chloro-

2, T-IiiiDorphölino - ^ - (N- ^ Ethanol-li-isoprQpanol) -amino-6-phenylpteridine. - ^

Z) 7-Bia ^(2, 6-dime-^^ fehylmorphQlino) -4-diäthanolamino ^^) - 6-

pt.rlÄl * 009850/1932 ■

161/336 - 6 -

2,7-Dimorpholino-4 ~ (lI-ablianol-N-propanol) -amino-t .'- phf-nylpteridin 2,7-Diniorpholino-4- (lI-ß, ^ - dihydroxypropyl-N-raeth7l) - ' tiDino-6-phenylpteridine 2,7-dimorpholino-4- (lI-r3 - ^ '- dihydroxypropyl-ir- ^: iithyl) -airiino - ^ - phenylpteridine 2,7-diniorpholino-4-diisopropanolamino-6-phenylpteridiri 2.7 Dipyrrolidino-4- (lI-ethanol-II-isopropanol) -aiflirio-o-phen, yL-pteridine 2,7-bis- (2,6-dimethylmorpholino) -4-diisopropanolamine.j-bpüenylpteridine 2,7-dimorpholino -4- (lT-ethanol-ri-isopropanol) -amirio-6-m-tolyL-pteridine 2,7-dimorpholino-4- (N-ethanol-lI-ethyl) -amino-6-yne-t; / Lyl -pterL ii; _; 2,7-Dimorpholino-4- (N-ethanol-N-ethyl) -amino-6-p-fcolyl-pteriline 2,7-Dimorpholino-4-dii3opropanolamino-6-p-tolylpteridine 2,7-Dimorpholino- 4- (iI-ß _t ^ -dihydroxypropyl-ir-benayl) -o-phenyL-pteridine 2,7-dimorpholino-4- (N-ethanol-li-iaopropanol) -amino-6-thienylpteridine 2,7-dimorpholino- 4-diüopropylaEiino-6-thienyl-pteridine 2-morpholino-4-diisopropanolamino-6-ph.enyi-7-pyrrolidinopteridine 2-morpholino-4-diisopropanolamino-6-phenyl-7- (2-ui ^ fchylmorpholino) -pteridine 2 , 7-Di- (2-methylmorpholino) -4-diisopropanolainino-6-phf ^j r.ylpteridine 2,7-di- (2-diethylmorpholino) -4- (N-ethanol-li ~: isopropanol) -amino-6 -phenylpteridine 2,7-diniorpholino-'4-diisopropanolainino-6- (2-chlorofuryl) -pteri-

2-diisopropanolamine O-4,7-dimorpholino-6-phenylpteridine 2-pyrrolidino-> 4- (N-etherealol-N-isQpropan.ol) -amino-6-phenyl-7-morpholinopteridine 2-Pyrrolidino-4- (N ~ ethanol-H-isopropanol) ~ aiaino-6-ph.enyl ~ 7-2 - (- methylmorpholino) pteridine

009850/1932 BADORiGINAL

. ' - 7 - - '- ■■■■'

2-pyrrolidino ^ - (H-ätkanol-N-i sopropanol) -amino-6-phenyl-7- - ('5-hydroxypiperidino) -pterIdin

2,7-bis- (3-] iydroxypiperidine p) * - 4- (li ^ ethiol-NTisoprOpanol) -aroini-6-phenylpteridine

2- (2-methylmorpholino) -4- (K-ethanQl-iHisopropanOl) - amino-6-

phenyI-7-pyrrolidinopteTidine -

2- (2-Methylidorpholino) ~ 4- (iT-ethanql-N-isopropanol) -amino-6-phenyl-7-piperidinopteridln

2- (2-Methylmorpholino) -4- (N-ethanol-H-isopropanol) -amlno-6-p} ienyl-7- ('-hydroxypiperidinoO-pteridine ^; 2-DIisopropanolaIπino-4-IDOΓpholino-6-phenyl- 7-pyl. ■ 'rΌlidί no-

pteridin '

2 -: 'Ethylamino-4-niorpholino-dihydro thieno [3,2-d] pyrimidine 2- [ 1- (4-methyl) -piperazino] -4-isqbutoxy-dihydrothieno- [3.2 -d] -pyrimldin

2-ethyl-4-niurpholino-dihydrothiapyrano- [3t2-d] -pyriinidine 2-isopropyl-'4-morpholino-dihydrothiapyrano- [3,2-'d j-pyriinidine-

2,7-Di- (2-methylmorpholino) -4- (N-ethanol-IT-isopropaTiol) '- anino-tj-phenylpteridine '.

Also the following, which do not fall under the general formula J Active ingredients or their physiologically compatible acid addition salts have one in combination with ß-adrenolytics favorable influence on these:

3— (ß-diethylaniinoethyl) -4-methyl-7-earboxy ⁱ -methoxy-2 ^ oxo- (1,2-chromene)

3,3 '- (N, N'-Diine thyläthylendiainino) -bis- (propyl * 3j 4,5-

triaethoxyberizoate)

N-3 ^t -Phenylropyl- (2 ') ^ 3, 1-diphenyl- (3) -aiiiin uncf a-IsoprOpyl-1-CH-Cmethyl-N-homoveratrylJ-y-aminopropyl] 3,4-dimethoxy-phenylacetonitrile and

Ii-U- (ß-Hydroxy-a-methyl-pheivylethylamino) -3-methoxy-

propiophenone. ■

009 a; 5 0/1 332 SADORIQJNAL,

-it

As for the combination with the substances mentioned above Particularly suitable β-adrenolytics have been found to be those compounds of formula II in which Ar is one optionally one or more times with halogen atoms or lower alkyl, trifluoromethyl, amino and / or ITitrile groups substituted phenyl, naphthyl, tetrahydronaphthyl or indanyl radical and R is an isopropyl or tert. Means butyl group. Even those connections that are in the 2-position are substituted by lower straight-chain alkoxy, alkylthio, alkenyl or alkynyl groups, in Preparations according to the invention are used. For example, the following substances should be highlighted:

1- (3 ^l -Tolyloxy) -2-hydroxy-3-isopropylamine> propane ^{1- (3 l} -chlorophenoxy) -2-hydroxy-3-iBopropylaminopropane 1- (2 ·, .3'-xylyloxy) -2-hydroxy -3-isopropylaminopropane 1- (3 ', 5'-xylyloxy) -2-hydroxy-3-isopropylaminopropane 1- (2', 4'-dichlorophenoxy) -2-hydroxy-3-isopropylamiriopropane 1- (3 '»5 ^l -Dichlorphenoxy) -2-hydroxy-3-isopropylaminopropan l- (3'-sec-butyl phenoxy) -2-hydroxy-3-isopropylaminopropan l- (2'-methyl-5 ^r -nitrilophenoxy) -2-hydroxy-3- isopropylaminopropane

1- (2-methylthiophenoxy) - * 2-hydroxy. 3. isopropyl aminopropane 1- (2-propargyloxyphenoxy) -2-hydroxy-3-isopropylaminopropane 1- (2-Allylphenoxy) -2-hydroxy-3-isopropylaminopropane 1- (1-laphthoxy) -2-hydroxy-3-isopropylaminopropane 1- (3-methyl-1-naphthoxy) -2-hydroxy-3-isopropylaminopropane 1- (4-indanyloxy) -2-hydroxy-3-isopropyl arainopropane 1- (6-methyl-4-indanyloxy) -2-hydroxy-3-isopropyl aminopropane 1- (3-methyl-5,6,7,8-tetrahydro-1-naphthoxy) -2-hydroxy-3-isopropylarainopropane

1- (2-1 • nitrilo-3-methylphenoxy) -2-hydroxy-3-isopropylarainopropane 1- (3-nitrilo-4-methylphenoxy) -2-hydroxy-3-isopropylaminopropane 1- (2-bromophenoxy) -2-hydroxy-3-isopropylaminopropane 1- (2-methyl-5-aminophenoxy) -2-hydroxy-3-isopropylaminopropane 1- (2-chloro-4-aminophenoxy) -2-hydroxy-3-isopropylamino propane

00 9 8 50/1932

l- (4 sec,

1- (4-tert-Butylphenoxy) -2-hydrogen Qxy- * 3-isopr Ppylamine-propane 1- (4-tert, -Amylphenoxy) -2-hydroxy-3-isqp, rqpylamine _i inopi: opane

1- (2-Mitrolophenoxy) -2-hydroxy-3-tert-butylaminopropane 1- (2-ltjynylphenoxy) -2-hydroxy-3-ter-fc. -butylaminopropane 1- (2 ^ chloro-5-methylphenoxy) -2 »hydroxy-3-isppropylaminopa: qpan 1- (2-Nitrilophenoxy) -2-hydroxy-3-ispprppylan} inpropane 1- (2-Ethynylphenoxy) -2-h; hydroxy-3-iQPprQpylaminopropane

Also, the following "two niclit μηϋβϊ · the general formula II falling substances have favorable ß-adrenolytic properties, which enable them to be used in combination preparations according to the invention:

1- ( 4-Methylsulfonylaminppheny ^^ - l-hydroxy - ^ - isopropylamino-

1- (4-Hitrophenyl) -l-hydrpxy-2-ispprppylam, inoethane.

The compounds of the general formula J are expediently incorporated directly into pharmaceutical preparations; B'4-compounds of the formula II or those mentioned, which do not fall under either of the two Iorinels, are involved On the other hand, they are about relatively strong bases. They will be dähy for dip iJinbildung in pharmaceutical ^ rä |) arate beneficial in their physiplqgisQh. yerträgliPhe,? ¹ Sa ^ readditionssalze transferred · suitable for this purpose are Säur.en example, hydrochloric acid, sulfuric acid, Phpsplaorsäure, methane sulf oiisäiire, Milphs ^ re, tartaric acid, Bern $ teinsäume p ^ he 8-Ghlqrthepphyllin. "

The registration according to en ¥ irks _; t off -Combinations a ^ s connections of the iOrmeln I un ^ '■ II b ^ w. besides the pb en specially named?!, uiiter kei || _f e dei; two Eo ^ me ^ ln f ^ lle.-iiden

161/336

substances as well as their physiologically compatible acid addition salts in the usual galenic applications, such as tablets, coated tablets, solutions, emulsions, powders, Capsules or depot forms are brought to their production the usual pharmaceutical auxiliary materials as well as the Usual manufacturing methods can be used, for example, by mixing the active ingredients with known Hili'ostoffe, for example inert diluents such as calcium carbonate, Calium phosphate or lactose, disintegrating agents, such as Corn starch or alginic acid, binders such as starch or gelatin, Lubricants, such as magnesium stearate or talc, and / or agents for achieving a depot effect, such as carboxypolymethylene, Carboxymethyl cellulose, gelulose acetate phthalate, or polyvinyl acetate. -

The tablets can also be ordered in several layers. Corresponding coated tablets can be made by covering them in the same way as the Taolettes manufactured cores with usually in Dra ^ re-eübfir-2ügen means used, for example Kollidon or shellac, Gum arabic, talc, titanium dioxide or sugar. To achieve a depot effect or to "avoid incompatibilities the core can also consist of several layers. The coated tablet shell can also be used in the same way to achieve a depot effect consist of several layers, whereby "the above for the: Tablets mention auxiliary substances can be used.

Juices of the active ingredients or combinations of active ingredients according to the invention can also contain a sweetener, such as saccharin, cyclaraate, gyleerin or sugar, and a flavor-enhancing agent, for example aromatic substances, such as vanillin or orange extract; they can also contain suspending, auxiliary or binding agents , like IJatriumcarbqxymethyl-pel.lu ^ qse, wetting agents, for example condensate ^ qnsgrodukte von Eetlallcp3i.pl.en | Dit Äthy / le.noxic}, or Schützetpffe, "like p-HyilrpxvTb ^ nzp ^ tje _? included.

Injection solutions are used in the usual way, e.g. with the addition of preservatives, such as p-hydroxybenzoates, or stabilizers, such as complexones, produced and in Injection bottles or ampoules filled «.

Containing the active ingredients or combinations of active ingredients Capsules can be manufactured, for example, by mixes the active ingredients with inert carriers such as lactose or sorbitol and encapsulates them in gelatine capsules.

Suitable suppositories can be made, for example, by mixing of the active substances or combinations of active substances provided for this purpose with common carriers such as neutral fats or polyethylene glycol or its derivatives.

For oral use of the preparations according to the invention comes for active ingredients of the formula I as well as for those mentioned above similarly 5 active substances a single dose of 5 - 500 mg and for active ingredients of formula II as well as the above-mentioned, similarly acting 2 substances a dosage of 10-500 mg into consideration. If, for example, 2,6-bis (diethanolamno) -4r8-dipiperidino-pyrimido- [5.4 ~ cl] -pyrimidine is used as active ingredient of the formula I, this can be dosed with 10-100 mg; when using 2,7 DimOrpholino-4-diisopropanolamino-ophenylpteridine a dose of 5 to 75 mg can be used as the active ingredient of the formula I. If you also use "for example l-m-Tolyloxy-2-hydrQxy-3-isopropylamino-propane hydrochloride as Active ingredient of formula II, this is to be dosed with 25 - 120 mg, while when using ^ - (a-naphthoxy) -2-hydroxy-3-isopropylaminopropane hydrochloride a dose of 10-100 is possible.

For parenteral use, i.e. for injection solutions, however, low doses are appropriate. For connections of the general formula I or the above additionally mentioned, similarly acting 2 substances 1-15 mg are proposed. That.

009850/1932

2,6-bis- (diethariolamino) -4, 8-dipiperidino-pyriinido- [5 ».4-d] -pyrimidine is for example with 10 mg, the l-tolyloxy-2-hydroxy-3-isopropylaminopropane hydrochloride dose with 5 mg.

The following examples illustrate the invention without it to restrict:

Example 1 (coated tablets) '

1 dragee contains:

2, T-Dimorpholino - ^ - diisopropanolamino-o-

phenylpteridine x 40.0 mg

1- (1-naphthyloxy) ^ -hydroxy ^ -iso-propyl-

aminopropane hydrochloride Lactose

Potato starch polyvinylpyrrolidone magnesium stearate

Production: The mixture of the active ingredients with the milk sugar and the potato starch is moistened with a 25% strength ethanolic solution of the polyvinylpyrrolidone, passed through a sieve with a mesh size of 1.5 mm and dried at A ¹ J ⁰ O. The dried granules are never beaten through a sieve with a mesh size of 1 mm and smeared with the magnesium stearate. Drageo kernels are pressed from this mixture.

The cores obtained εο are in the usual way with a Covered, which consists essentially of sugar and talc. The coated tablets obtained in this way are with the help of Beeswax polished. Final weight: 150 mg.

BADORiGJNAL 009850/1332

20.0 rag 30.0 mg 16.0 mg 3.0 mg 1.0 mg 110.0 mg

60.0 mg 65.0 mg 55.0 mg 15.0 mg 7.0 mg 3.0 ^m ii 280.0 mg

- 13 -

Example 2 (coated tablets).

1 dragee contains:

2,6-bis- (diätlianolamino) -4,8-dipiperid ino-

pyrimido [5,4-d] pyrimidine 75.0 mg

l- (3'-ToIyIoXy) ^ - hydroxy ^ -isopropylamino-

propane hydrochloride lactose

Potato starch

Talk

Gelatin.

Magnesium stearate

Production: The active ingredients are mixed with milk sugar, potato starch and talc and then with a 10% aqueous solution Granulated solution of gelatin (sieve: 1.5 mm mesh size); then it is dried at 40.degree. The dried granules will pressed again through the above sieve and with magnesium stearate mixed. Dragee cores are pressed from the mixture. Core weight: 280 mg.

The cores produced in this way are in the usual way with a Covered mainly from sugar and talcum powder. The finished coated tablets are polished with the help of beeswax. Final coated weight: 480 mg.

Example 3 (wafers.capsules) 1 capsule contains:.

2,7-Di- (2-methylmorpholino) -4- (N-ethanol-H-isopropanol) -amino-6-phenylpteridine 50.0 mg

1- (2-Allyloxyphenoxy) -2-hydroxy-3-isopropylaminopropane hydrochloride 75.0 mg

Lactose sugar (crystalline) 75.0 mg

Talc 20.0 mg

220.0 mg

■ · 0Q985D / 1932

16 1/336

Production: Through a sieve with a 0.75 mm mesh size
sifted active substances are mixed intensively with the auxiliary substances and placed in oblate capsules of a suitable size
bottled. Capsule filling: 220 mg.

Example 4 (ampoules)
1 ampoule contains:

2-pyrrolidino-4- (H-ethanol-N-isopropanol) -amino-

6-phenyl-7- (2-methylmorpholino) pteridine 10.0 mg 1- (2-nitrilophenoxy) -2-hydroxy-3-tert. butyl

aminopropane sulfate 5.0 mg

Sodium pyrοsulphite 2.0 mg

bidist. Water ad 2.0 ml

Preparation: In boiled and cooled to room temperature
bidist. Water, sodium pyrosulphite and the two active ingredients are dissolved one after the other while gassing with nitrogen. The solution is made up to the specified volume and filtered free of suspended particles.

Filling: In brown ampoules (under nitrogen)
Sterilization * 20 min. At 120 ^° C.

Example 5 (drag fees)
1 dragee contains

N-3 ^l -phenylpropyl- (2> -l, l-diphebyl (3) -amine lactate 45.0 mg l- (l-phenylphenoxy) -2-hydroxy-3-isopropylaminopropane hydrochloride 25.0 mg

Milk sugar 20.0 mg

Potato starch 16.0 mg

Polyvinylpyrrolidone 3.0 mg

Magnesium stearate 1.0 mg

110.0 mg

The finished coated tablets are produced analogously to the example

009850/193 2

BpI ^ rIeI ο (suppository)! Suppository contains:,

;-( 3-diethylaminoethyl) ■ ^ ■ ^ m
Inetnoxy-P-oxo-Cl ^ -chromenJ-hydrochloride:! - ('+ - nitropheriylO-l-hydroxy-S-isopropylaminoethane hydrochloride
Säpfcheiuaasse, e.g. * WItepsol H 12

125.0 mg 75.0 mg 1600.0 ιβοο, ο mg

Herateilung: is stirred the feinge'pulverte Wirlcsubotanz at 40 ⁰ C in the molten suppository mass. The mass is homogenized and at about 35 ⁰ O i
poured out. Sapfcheng ^ weight: 1.7

homogenized and at about 35 ⁰ O in Idcht pre-cooled forms

Example 7 (oblate caps) 1 capsule contains:

2,7-Di- (2-Methy ^ iDorpiiölinö) -4- (K-ethanol-N-isopropanol) -amino-6 «phenyliJterldin "50.0 mg 1- (2'-allyloxyphenoxy) -2 * hydroxy-3'-isopropyl-

aminopropene hydrochloride Lactose (crystalline)

Talktim ^

. :. '_ ■' 220, c

Production / Oie through a sieve with a mesh size of 0.75 mm sifted active substances are intensively processed with the help mixed substances and in oblate capsules of suitable size bottled. Capsule filling: 200 mg. ·

75. 0 mg 75 0 m; * r 20 _r 0

Ö0985G / 1932

. ■ ■ 161/336

10, 0 ing ¹ y, 0 mg 2, 0 ing 2, 0 ml

Example 8 (ampoules) 1 ampoule contains:

2-PyrrOlidino-4- (N-ethanol-N-isopropanol) ~ amino ~ 6-phenyl-7- (2-methylmorpholino) pteridine 1- (2'-nitrilo-phenoxy) -2-hydroxy-3-tert.-butyl-

aminopropane sulfate sodium pyrosulfite

bidist. V / ater ad

Preparation: In boiled and cooled to room temperature bidist. Water, sodium pyrosulphite and the two active ingredients are dissolved one after the other while gassing with nitrogen. The lecture is made up to the specified volume and free of suspended particles: filtered.

Filling: into brown ampoules (under nitrogen) Sterilization: 20 minutes at 120 ⁰ C.

Example 9 (coated tablets) 1 coated tablet core contains:

N-3 ^l -Phenylpropyl (2) -l, l-diphenyl (3) -amine lactate 45.0 mg 1- (I ^l -Naphthyloxy) -2-hydroxy-3-isopropylamino-

propane hydrochloride 2 ^, 0 mg

Lactose

Potato starch polyvinylpyrrolidone magnesium mearate

1.10.0 in *

The Ρ "Γεΐ ·. Llur., - cer f ^ -v.tigen dragee." takes place an.aJ.or .'ieißpi <·!

20.0 rar 16.0 mg 7.0 rag 1.0

BATH ORIGINAL

0 0 9 8 5 G / 1 3 3 2

Example 10 (suppository)
1 suppository contains:

3- (ß-diethylaininoethyl) -4-methyl-7-carbethoxy-.

methoxy-2-oxo- (1,2 ~ chromeii) hydrochloride - 125.0 mg l - ^ - MtropheiiylO-l-hydroxy ^ -isOpropylamino-

ethane hydrochloride 75.0 mg

Suppository mass, for example Witepsol H 12 1600.0 mp;

. Ic-OO, Ό mg

Production: In the melted suppository liquid wii'cl at 40 ° C the finely powdered active ingredient is stirred in. The Hasse is homogenized and placed in slightly pre-chilled molds at around 35 ° C poured out. Suppository weight: 1.7 g

BADORIOiNAL 009850/1932

Claims (1)

Claims ' 1. Pharmaceutical preparations containing -eino as active ingredients or several substances of the general formula in which R-, an (N-hydroxy- or dihydroxy-lower alkyl-N-dihydroxy- or hydroxy-lower alkyl) amino or an (N-lower acyloxy lower alkyl-N-lower acyloxy-lower alkyl) amino group, in which the chain length of the lower alkyl part of the two hydroxy or dihydric lower alkyl or lower acyloxy lower alkyl groups can be the same or different; a via the N Atora bound, and optionally with a ^second or lower two .Alkyl ^ 'groups or hydroxy-substituted morpholino, pyrrolidine, piperazine, 1,2,5 »6-tetrahydropyridine or piperidine group or a lower alkyl or Alkylainino -, an N-liiederalkyl-li-hydroxy-lower alkylamino radical or an N-aryl-lower alkyl-M-hydroxy-lower alkylamino radical, "· - '■ Kp a bonded via the II atom and optionally with one or two lower alkyl groups or hydroxyl groups substituted piperidine, 1,2,5,6-tetrahydropyridine, morpholine, Piperazine or pyrrolidine residue, a lower alkoxy or alkylthio group, a (N-hydroxy- or dihydroxy-lower alkyl-N-hydroxy- "bew. dihydroxy-lower alkyl) -amino- or a - IAP ÖRS61NM. ! t * 009850/1 932 '- .., - ■ New documents (Art 7, Section 1, Paragraph 2, No. I, Clause 3 of the amendment »·. V. 4.9. F * · *" - "" "amino group -, -" in which the chain length of the lower alkyl part of the both hydroxy-lower alkyl or lower acyloxy-lower alkyliZruFpeη can be the same or different; or an N-ITied eralkyl-IT-S-Hyaroxv-nieJeralkyl- or, a li-aryl-iiied er alkyl N-ß-hydroxy-lower alkylaininörest and A the group «e.-iJ = C (R ₅ ) Hi = C (R ^) -; the group -IT = CCR ₅ ) -C (E ₄ ) - \ l \ the group '-S (GHo)., - or the group -S- (CHp.) - mean, · R _{x is} a (K-hydroxy-bi: w. Miaydroxy-lower alkyl) -N-hydroxybsw. Dihyaroxy-lower alkyl) -amino or a (U-lower acyl-lower alkyl-IT-nie (LeraGyloxy-lower alkyl) -amine group, in which the chain length of the lower alkyl part of the two hydroxy lower alkyl or Nlederaeyloxy lower alkyl groups can be the same or different, or is a phenyl, thienyl or pury group which is optionally monosubstituted or polysubstituted by halogen or lower alkyl / Hj the same. "Can have meanings · \ tf-ie R- ^ or lip and with can be the same or different from these and where V ..'.-- ■ "" ■■, - ■ ' η the number 2 or 3 is _r ■. "■■ ^ in combination of one or more terms of the general Formula:, in the Ar a uixsubstituierten or one _: mono- or polysubstituted iso- , homo- or heterocyclis -'- hen ^ Hest · - with at least one aromatic 6-Rint *, which goes directly to the _R / * * ': - ^; : - ■■ - 0 0 9850 / 1.9.32 - \ iÄ ORIGiNAt Remaining molecule is bound, preferably as substituents lower alkyl, irifluoromethyl, amino or nitrile groups and halogen atoms as well as lower straight-chain alkoxy, lower acyloxy, acyl, alkenyl, alkynyl, alkylthio, Mono- or dialkylamino, also nitro, hydroxy and 3,4-methylenedioxy groups come into play and R is an alkyl group with 1-6 carbon atoms, as well as with customary pharmaceutical auxiliaries and / or carriers. 2.) Pharmaceutical P: preparations containing as active ingredients one or more substances of the general formula in which R-, R ₂ and A have the abovementioned meaning, in combination with one or more compounds of the general formula Ar ₁ OGH ₂ -CHOH-CJi ₂ -NHR III 00 9850/1932 in the 'Ar-, an unsubstituted or with one or more Halogen atoms, lower alkyl groups, nitrile, amino and / or Trifluoromethyl groups substituted phenyl, naphthyl, tetrahydronaphthyl or indenyl radical and R is an isopropyl or tert. Means butyl radical, as well as common pharmaceutical auxiliaries and / or carriers. 3.) Pharmaceutical preparations containing one as active ingredients or several substances from the group 2,6-bis (diethanolamino) -4,8-dipiperidino-pyrimido- [5,4-d] -pyrimidine 2,6-bis- (diethanolamino) -4,8-di- (2-methylpiperidino) -pyrimid-o- [3,4-d ] pyrimidine 2,6-bis- (diethanolamino) -4 ₎ 8-di- (3'-niethylpiperidino) -pyrirDi- do- [5 »4-d] pyrimidine. 2,6-bis (diethanolamino) -4, S-di [3- (1,2,5 »6, -tetrahydro- pyridino)] pyrimido [5,4-d] pyrimidine 2,6-bis- (diethanolamino) -4,8-di- (3-hydroxypiperid ino) - pyrimido [5,4-d] pyrimidine ■ -. .; 2,6-bis (diisopropanolamino) -4 j 8-dimorpholino-pyrimido- [5,4-d] -pyrimidine 2-diethanolamino-6-N-ethanol-N-isopropanol-amino-4, S-dipiperidino-pyrimido- [5 * 4-d3-pyrimidine 2-diet . 2, o-Bis ^ fidi-β-acetoxyethyl) amino] -4> 8-dipiperidino-py-> rimido- [5,4-d] -p; vrimidin, 2,6-bis (diethanolamino) -4,8-ethylthio-pyrimido- [5,4-d] -pyrimidine 2,6-bis - [(di-β-formyloxyethyl) amino -] - 4,8-dipiperidino-pyrimido- [5 »4-d] -pyrimidine 2,6-bis- (diethanolamino) -ethylbhio-3-piperidino-pyrimido- [5 »4-d] -pyrimidine ■ 2,4,7-Trimorpholino-ö-phenylpteridine 2,7-Dίmorpholino-4- (M'-ethanΌl-l Γ-methyl) -amino-6-phenylpteridine 2,7-dimorpholino-4- (F- ethanol) amino-6-r phenylpte idin BADORIQiNAL 009850/1932 ■ '-22 - 2.7 ~ BimorpholinQ-4- (N-ethanol-N-benzyl) -amino-6-phenylpteridine 2,7-Dimorpholino-4- (N-ethanol-N-methyl) -amino-6-p-chlorophenylpteridine 2, 7-DimorpholinO-4- (N'-Ethanol-N-isopropanol) -ainino-6-phenylpteridine 2,7-bis- (2,6-dimethylmorpholino) -4-diethanolamino-6-phenylpteridine 2,7 ~ Dimorpholino-4 - (N-ethanol-N-propanol) -amino-6-phenylpteridine 2,7-Diπlorp] lolino-4- (ϊ ⁱ Γ-ßJ ^ '- diilydroxypropyl-l · T-Ineΐhyl) -amino-6-piienylpteridin 2 , 7-Difflorpholin.o) -4- (N ₉ ßrV-dihydroxypropyl-N-ethyl-arnino-ophenylp t lirid in 2, _i ~ jimorpholino-4-diisopropanolamino-6-phenylpteridine 2,7-dipyrrolidino-4- ( ir-ethanol ~ lJ-isopropanol) -ainin.o-6-phenylpteridine 2,7-bis ~ (2,6-dimethylmorpholino) -4-diisopropanolaraino-6-phenylpteridine 2,7-diinorpholino-4- (N-ethanol- L-isopropa £ lol) -amino-6 ~ m-tol, 7ipteridine 2,7-dimorpholino-4- (li-ethanol ~ N-ethyl) -amino-6-m-tülyl-pteridiri 2,7-dimorpholino -4- (N-ethanol-N-ethyl) -araino-6-p-tolyl-ptericin 2,7-diniorpholino-4-diii; opropanolainino-6-p-tolyl-pteriuin ■ 2,7-dimorpholino-4- (N - β- (J-dihydroxypropyl-N-benz7 / L) -6-phenylpteridine 2,7-dimorpholino-4- (li-ethanol-N'-isopropanol) -aininu-D-thienylpteridine 2,7-dimorpholino-4-diupropylaniino -6-thienyl-pteriaine 2-morpholino-4-diisopropanolamino-6-ph .- "-nyl-7-pyrroleIdinopteridin 2-morpholinO-4-diisopropanolaniino-6-phenyl-7- (2-! Aethylruorpholino) -pteridine 2, 7-Di- (2-methylmorpholino) ^ - diisopropanolamino-ö-phenylpteridine 2,7-Di- (2-methylmorpholino) -4-ethanol-M-ioopropaii ~ 1) -amino-6-phenylpteridine 2,7-DiiQorpholino- 4-diisopropanolaniino-D- (2-clilori'uryl) - pteridine 0 0 9 8 50/1932 BATH ORIGINAL - ■ 23- - ■■■. ■■■ 2-Diisopropanolamino-4,7-dimorpholino-6-pJh.enyl.pf eridiii 2-Pyrrolidino-4- (III-Ethanol-H-isopropyliol) = -ainino-6-pIienyl-7-morpholinopteridine 2-pyrrolidino-4- (H-ethanol-iT-isopropanol) -amino-6-phenyl-7-2-methylmorpholino) pteridine 2-pyrrolidino-4- (l I-ätllaIlol-ίί- * isopropanol); - aIIlino-6-pllenyϊ-7- (3-hydroxypiperidino) pteridine V 2,7-bis (3-hydroxypiperidino) -4- (N-ethanol-N-isOprOpanol) -anino-6-phenylpteridine 2- (2-methylmorpholino) -4- (ir-ethanol-l'T-isopropanol) -ainino-6-phenyl-7-pyrrolidinopte. * Idin 2- (2-Methylmor.pholino) -4- (li-ethanol-M-isopropanol) -aniino-6-phenyl-7-piperidinopteridine '. . ■, 2- (2-Methylrüorpholino) -4- (K ⁱ -ä'thanol-N-isopropanol) -an] ino-6 · - phenyl-7 - ('3'-hydroxypincridino) -pteridine · ^ -LiiöopropanolaIDino-4- morpholino-b-phellyl-7-pyrrolidino- 2-MethylmBino-4-morphoiino-dihydr'3tliieno- [3 ₁ 2-d l-py 2- [1- (4-methyl) -piperasino] -4-ίsobutoxy-dihydrothieno - [? ■, 2-d] - pyrimidine 2-iί.thyl-4 '-' morpholino-dihydrothiapyrano-] 3,2-d] -pyriinidine 2-isopropyl-4-n} orpholino-dihydrothiapyrano- [3,2-d] - pyrimidine-i> -oxide _ 2,7-Di- (2-ja.e thy liaorpho lino) -4- (N-ethanol-N-isopropane ^ l) -arnino-6-phenyl-pteridiii 5- (t> -I) iäthylaniinoäthyl) -4-iDetiiyl- ^; 7-oarbethoxy-ethoxy-2-OXo- (1,2-chro:! Ien) or its calze 3.3 ^I - (l · ^ N ^l -DiIIιethyläthyl · enälaInial) bis (propyl-3,4 ^ -tri-. methoxybenEoat) or its tal.se W-? '-Phenylpropyl- (2') -1,1-diphenyl- ( Ά ) -aain or des ^ n Sa 1 r, e BAD'ORIGINAL - ; 009850/193 2 ²⁴ - 161/336 σ-Ιsopropyl - τ- [N- (methyl-N-homo-veratryl) - r-aminopropyl] - ■ i ^ l-climpthoxyphenylacetonitrile or its salts and L- (O- (ß-Hyct roxy-r-methy 1-pheny läthylamino) -3-methoxypropiopiienon or denoen salts in amounts of 5 - 500 niss, in combination with one or more active ingredients from the group l- (3 ^t -Tolyloxy) -2-hydroxy-3-isopropylajninopropan l- (3 ^l -Chlorphenoxy) -2-hyaroxy-2-ISOT> rapylaininopropan l- (2 ', 3'-xylyloxy) -2-hydroxy- 3-isopropylarainopropane 1- (3 ', 5'-xylyloxy) -2-hydroxy-3-isopropylaminopropane 1- (2', 4'-dichlorophenoxy) -2-hyaroxy-3-isopylaminopropane 1- (3 '> 5 -Dichlorophenoxy) -2-hydroxy-3-isopropylaminopropane 1- (3'-sec-butylphenoxy) -2-hydroxy-3-isopropylaminopropane 1- (2'-methyl-5 ^l -nitrilophenoxy) -2-hydroxy-3- isopropylaminopropane 1- (2-methylthiophenoxy) -2-hydroxy-3-isopropylaminopropane 1- (2-propargylphenoxy) -2-hydroxy-3-isopropylaminopropane 1- (2-Allylphentxy) -2-hydroxy-3-isopropylaminopropane 1- (1-Naphthoxy) -2-hydroxy-3-isopropylaminopropane 1- (3-methyl-1-naphthoxy) -2-hydroxy-3-isopropylaminopropane 1- (4-indanyloxy) -2-hydroxy-3-isopropylaminopropane 1- (6-methyl-4-indanyloxy) -2-hydroxy-3-iBopropylaminopropane 1- (3-methyl-5,6,7,8-tetrahydro-1-naphthoxy> 2-hydroxy-3-isopropylaminopropane 1- (2-nitrilo-3-methylphenoxy) -2-hydroxy-3-isopropylaminopropane 1- (3-Nitrilo-4-methylphenoxy) -2-hydroxy-3-iBopropylinopropane 1- (2-bromophenoxy) -2-hydroxy-3 ■ -isopropylalinopropane 1- (2-methyl-5-aminophenoxy) -2-hydroxy-3-isopropylaminopropane 1- (2-chloro-4-aminophenoxy) -2-hydroxy-3-isopropylinopropane 1- (4-sec-butylphenoxy) -2-hydroxy-3-isopropylaminopropane 1- (4-tert-butylphenoxy) -2-hydroxy-3-isopropylaminopropane 1- (4-tert-amylphenoxy) -2-hydroxy-3-isopropylaminopropane 1- (4-nitrilophenoxy) -2-hydroxy-3-isopropyraminopropane, 1- (2-nitrilophenoxy) -2-hydroxy-3-tert-butylaminopropane 1- (2-Xthynylphenoxy) -2-hydroxy-3-tert-butylaminopropane 1- (2-chloro-5-methylphenoxy) -2-hydroxy-3-isopropylaminopropane 1- (2-nitrilophenoxy) -2-hydroxy-3-isopropylaminopropane 009 850/193 2 , 25 - .. ■■■. ■ "■ ... ■ - ■■. 1- (2-XtMn / 1-phenoxy) ™ 2 ^ hydrOxy-3 ^ isopxopyiaminopropane 1- (4 ^ Methylsulf Onylaminophenyl) -l-hydroxy-S-isopropylaraino- ethane '------- 1- (4-MtrQphenyl) -l ~ hydj: Qxy-2-isopropylaminoethane or their physi.o-logis.eh compatible acid addition salts in amounts of 10-300 mg as well as usual pharmaceutical ones Hills and / or carriers. 4. Method for the treatment of angina pectorls »thereby characterized in that the patient is prescribed preparations according to claim,, ' 5. A process for the production of pharmaceutical preparations according to claim 3, characterized in that the in Substances listed with the usual diluents' agents, disintegrants, binders, lubricants or agents to achieve "a depot effect mixed and in common galenic application forms " 6. Pharmaceutical preparations containing as active ingredients 2,6-bis (diethanolamino) -4,8-dipiperidino-pyrimido- [5 »4-d] -pyrimidine in amounts of 10 - 100 mg in combination with raoemic or optically active 1- (3 '^ tolyloxy) -2 * -hydroxy-3'-isopropylaminopi'opane or its physiologically compatible acid addition salts in amounts of 25-120 mg as well as usual Pharmaceutical substances and / or carriers. 7. Pharmaceutical preparations containing as active ingredients 2,7-Dimorpholino-4-diisopropanolamino-6-phenylpteridium in amounts of 5-75 mg, in combination with racemic or optically active 1- (3 '- * TolylQxy) ^ 2-hydroxy-3-iSQpropylami7iopropane or its physiologically acceptable acid addition salts in amounts of 1 - 120 mg and customary pharmaceuticals Auxiliary and / or carrier materials ». ■ '' 0 018 -U ^if f 1B 3 161/336 β. Pharmaceutical preparations containing as active ingredients 3- (ß-Diethylaminoethyl) -4-methyl-7-carbäthoxy-methoxy-2-oxo- (1,2-chrorene) or its physiologically acceptable acid addition salts in amounts of 5 - 250 mg in combination with racemic or optically active l- (l-naphthoxy) -2-hydroxy-3-isopropylamine or its physiologically acceptable acid addition salts in amounts of 1 - 100 mg as well as customary pharmaceutical auxiliaries and / or carriers. 9. Pharmaceutical preparations containing as active ingredients 3,3 '- (N, If -dimethylethylenediamino) -bis- (propyl-3,4,5-trimethoxybenzoate) or its physiologically acceptable acid addition salts in amounts of 5 - 250 mg in combination with racemic or optically active l- (l-l-taphthoxy) -2-hydroxy-3-isopropylinopropane or its physiologically acceptable acid addition salts in amounts of 1 - 100 mg as well as usual pharmaceutical auxiliaries and / or carriers. 10. Pharmaceutical preparations containing ir-3'-phenylpropyl- (2 ') -l, l-diphenyl- (3) -amine as active ingredients. or its Physiologically compatible acid addition salts in amounts of 5 - 250 mg in combination with racemic or optical active 1- (1-haphthoxy) -2-hydroxy-3-isopropylaminopropane or its physiologically acceptable acid addition salts in amounts of 1-100 mg and customary auxiliaries and / or carriers. 11. Pharmaceutical preparations containing as active ingredients α-Isopropyl-oc- [li- (methyl-F-homoveratryl) - ^ - aminopropyl] -3,4-dimethoxyphenylacetonitrile or its physiologically acceptable acid addition salts in amounts of 5 - 250 mg in combination with racemic or optically active l- (l-naphthoxy) ^ - hydroxy ^ -isopropylaminopropane or its physiologically acceptable acid addition salts in quantities from 1 - 100 mg as well as usual pharmaceutical auxiliaries and / or Carriers, ■ BADORIGiNAt. DQ985O / 1032 161/336 12. Pharmaceutical preparations, containing as active ingredients L-tO- (i3-Hyära>: yi-inethylphenyläthylaniino) - ^ - methoxy-propiophenone or its physiologically, tolerable acid additionnalise in amounts of t) - 250 mg in combination with racemic or optically active! - (l'-NaphthoxyJ ^ -hydroxy-i-isopropryl-aininopr jpar. or its physiologically tolerable acid anu-onss.ilzeii in amounts of 1 - 100 mg as well as usual auxiliaries and / or carriers. 13. Pharmaceutical preparations containing as active ingredients 3- (ß-diethylawinoethyl) ^ -methyl-Y-carbäthoxy-iiiethoxy ^ -oxo- (1,2-chroraen) or its physiologically acceptable acid addition salts in amounts of 5-250 mg in combination with racemic or optically active 1- (2'-allylphenoxy) -2-hydroxy-3-isopropylaminopropane or its physiologically compatible acid addition salts in amounts of 1-100 mg as well customary pharmaceutical auxiliaries and / or carriers. 14. Pharmaceutical preparations containing as. "". Active ingredients " '* >> 3 "' - (N, II '-Dime tliyläthylend iamirio =) - bis- (propyl- 3,415-1 r ine th- oxybenzoate) or ae & s en physiologically acceptable acid addition salts in amounts of b - 2pO mg in combination with racemic or optically active 1- (2'-AIItI-phenoxy) -2-hydroxy-3-isopropylaniinopropane or its physiologically tolerable acid addition salts in amounts of 1-100 mg and customary pharmaceutical auxiliaries and / or carriers. 15. Pharmaceutical preparations _{containing t} as active ingredient.e H-? ^1- phenylpropyl- (2 ') - l, l-giphenyl- (3) -amine or its: physioloriseh compatible acid addition salts in amounts of b - 2i> 0 mg in combination with racemic or optically active l- (2'-AlIyJ- phenoxy) -2-hydroxy-3-isopropylaminopropane or its physiologically tolerable acid addition salts in amounts of 1-100 mg and customary pharmaceutical auxiliaries / or carriers are open. ^BAD OfflGfts / AL "GQ 9 8 5 0/19 3 2 '! 617336 16. Pharmaceutical preparations containing ala active ingredients a-isopropyl-a- [N- (methyl-N-homoveratryl) - ^ - aminopropyl] -3 »4-dimothoxyphenylacetonitrile or its physiologically acceptable acid addition salts in amounts of 5 - 250 mg in Combination with racemic or optically active l- (2 ^f -allylphenoxy) -2-hydro: xy-3-isopropylaminopropane or its physiologically acceptable acid addition salts in amounts of 1 - 100 mg and customary pharmaceutical auxiliaries and / or carriers. 17. Pharmaceutical preparations containing L- \ i> - (ß-Hydroxy-a-aiethylphenyläthylainino) -3-methoxypropionylphenone or its physiologically acceptable acid addition salt in amounts of 5 - 250 mg in combination with racemic or optically active 1- ( .2 · -Ally! Phenoxy) -2-hydroxy-3-isopropylarainopronane or its physiologically acceptable acid addition salts in amounts of 1 - 100 rag as well as customary auxiliaries and / or carriers. BATH COPY r, η I _1,.