DE2253134C3 - Salts of substituted 2-anilinonicotinic acids with lysine - Google Patents
Salts of substituted 2-anilinonicotinic acids with lysineInfo
- Publication number
- DE2253134C3 DE2253134C3 DE19722253134 DE2253134A DE2253134C3 DE 2253134 C3 DE2253134 C3 DE 2253134C3 DE 19722253134 DE19722253134 DE 19722253134 DE 2253134 A DE2253134 A DE 2253134A DE 2253134 C3 DE2253134 C3 DE 2253134C3
- Authority
- DE
- Germany
- Prior art keywords
- lysine
- salts
- anilinonicotinic
- acid
- acids
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 239000011780 sodium chloride Substances 0.000 title claims description 13
- 150000003839 salts Chemical class 0.000 title claims description 12
- 239000004472 Lysine Substances 0.000 title claims description 11
- UUMMTMQODCACRH-UHFFFAOYSA-N 2-anilinopyridine-3-carboxylic acid Chemical class OC(=O)C1=CC=CN=C1NC1=CC=CC=C1 UUMMTMQODCACRH-UHFFFAOYSA-N 0.000 title claims description 4
- -1 2-methyl-3-chloro-anilino Chemical group 0.000 claims description 6
- GBEYOWVXSWBVBN-JEDNCBNOSA-N azane;(2S)-2,6-diaminohexanoic acid Chemical compound [NH4+].NCCCC[C@H](N)C([O-])=O GBEYOWVXSWBVBN-JEDNCBNOSA-N 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims 1
- 239000008177 pharmaceutical agent Substances 0.000 claims 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N nicotinic acid Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 10
- 241000700159 Rattus Species 0.000 description 9
- 229960003512 nicotinic acid Drugs 0.000 description 6
- 235000001968 nicotinic acid Nutrition 0.000 description 6
- 239000011664 nicotinic acid Substances 0.000 description 6
- JZFPYUNJRRFVQU-UHFFFAOYSA-N Niflumic acid Chemical class OC(=O)C1=CC=CN=C1NC1=CC=CC(C(F)(F)F)=C1 JZFPYUNJRRFVQU-UHFFFAOYSA-N 0.000 description 5
- 230000036269 ulceration Effects 0.000 description 5
- 229960002895 Phenylbutazone Drugs 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000003110 anti-inflammatory Effects 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 241000906446 Theraps Species 0.000 description 3
- 229960001138 acetylsalicylic acid Drugs 0.000 description 3
- 230000001154 acute Effects 0.000 description 3
- 230000000202 analgesic Effects 0.000 description 3
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 241000700157 Rattus norvegicus Species 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- JFSVGKRARHIICJ-UHFFFAOYSA-N 2-propoxyphenol Chemical compound CCCOC1=CC=CC=C1O JFSVGKRARHIICJ-UHFFFAOYSA-N 0.000 description 1
- CLOMYZFHNHFSIQ-UHFFFAOYSA-N Clonixin Chemical compound CC1=C(Cl)C=CC=C1NC1=NC=CC=C1C(O)=O CLOMYZFHNHFSIQ-UHFFFAOYSA-N 0.000 description 1
- 210000003754 Fetus Anatomy 0.000 description 1
- 210000002683 Foot Anatomy 0.000 description 1
- 229960000916 Niflumic Acid Drugs 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000011102 Thera Species 0.000 description 1
- 206010068760 Ulcers Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic Effects 0.000 description 1
- 230000000875 corresponding Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002757 inflammatory Effects 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000000241 respiratory Effects 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000002269 spontaneous Effects 0.000 description 1
- 231100000456 subacute toxicity Toxicity 0.000 description 1
- 230000001225 therapeutic Effects 0.000 description 1
- 230000002588 toxic Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002110 toxicologic Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000001562 ulcerogenic Effects 0.000 description 1
Description
COOHCOOH
2020th
(ID(ID
in der R die obige Bedeutung aufweist, mit Lysinin which R has the above meaning, with lysine
25 Gegenstand der Erfindung sind Salze substituierter 2-Anilinonicotinsäuren mit Lysin der allgemeinen Formel I 25 The invention relates to salts of substituted 2-Anilinonicotinsäuren with lysine of general formula I
[H3N-(CH2J4 — CHNH2 — COOH] *[H 3 N- (CH 2 J 4 - CHNH 2 - COOH] *
in der R entweder einen 3-Trifluormethyl- oder einen 2-Methyl-3-chlor-anilinorest bedeutet.in which R is either a 3-trifluoromethyl or a 2-methyl-3-chloro-anilino radical.
Diese Salze sind löslich und besitzen, eine bemerkenswerte entzündungshemmende Aktivität, die mit einer gegenüber bekannten Derivaten der Nifluminsäure [2-(3-Trifluormethylanilino)-nicotinsäure] beträchtlich verringerten Nebenreizwirkung kombiniert ist. Die pharmakologische Wirkung der neuen Salze ist erheblich stärker, zum Teil mehr als doppelt so stark wie die Wirkung der ihnen zugrunde liegenden Säuren. Die Salze sind auch wirksamer und weniger toxisch als das bekannte Mittel Phenylbutazon. Dies ergab sich bei der pharmakologischen Prüfung aus den nachfolgenden Versuchen insbesondere über die analgetische und die akute inflammatorische Wirkung. These salts are soluble and have a remarkable effect anti-inflammatory activity compared with a known derivative of nifluminic acid [2- (3-trifluoromethylanilino) nicotinic acid] considerably reduced side irritation combined is. The pharmacological effect of the new salts is considerably stronger, sometimes more than twice as much as strong as the effects of the acids on which they are based. The salts are also more effective and less effective toxic than the well-known agent phenylbutazone. This emerged from the pharmacological test the subsequent experiments in particular on the analgesic and acute inflammatory effects.
Toxikologische PrüfungToxicological test
1. LD50 (vgl. Litchfield und Wilcoxon, J. Pharmacol, exp. Therap., Bd.96 [1949], S.99)1. LD 50 (cf. Litchfield and Wilcoxon, J. Pharmacol, exp. Therap., Vol. 96 [1949], p.99)
WirkstoffActive ingredient
2-(3-Trifluor-2- (3-trifluoro
methylanilino)-methylanilino) -
nicotinsäurenicotinic acid
Lysinsalz der
2-(3-Trifluormethylanilino)-nicotinsäure Lysine salt of
2- (3-trifluoromethylanilino) nicotinic acid
Versuchstier LD50 ED50 Therapeutischer (mg/kg) IndexTest animal LD 50 ED 50 Therapeutic (mg / kg) index
Maus, ρ. ο. 480Mouse, ρ. ο. 480
Ratte, ρ. ο. 460Rat, ρ. ο. 460
Maus, ρ. ο. 515Mouse, ρ. ο. 515
Ratte, p.o. 472 31,6 14,94Rat, p.o. 472 31.6 14.94
WirkstoffActive ingredient
5050
2. Subakute Toxizität von Lysinsalz der2. Subacute toxicity of the lysine salt
2-(2-Methyl-3-chloranilino)-nicoti;nsäure2- (2-Methyl-3-chloroanilino) nicotic acid
bei Ratten (nach den FDA-Normen USA)in rats (according to the FDA standards USA)
Die Tests wurden an Wistarratten beiderlei Geschlechts mit einem Körpergewicht von etwa 15Og während 90 Tagen mit Dosen von 7,5,15,0 und 30,0 mg/ kg p. o. täglich durchgeführt. Es wurden keine humoralen, klinischen oder anatompathologischen Veränderungen beobachtet.The tests were carried out on Wistar rats of both sexes with a body weight of about 150 g for 90 days with doses of 7.5, 15.0 and 30.0 mg / kg p. o. carried out daily. There were no humoral, clinical, or anatomical changes observed.
3. Teratogenese von Lysinsalü der3. Teratogenesis of lysine saline
2-(2-Methyl-3-chloranilino)-nicol:insäure2- (2-Methyl-3-chloroanilino) -nicol: insic acid
Die Tests wurden an Wistarratten mit einer Dosis von 7,5, 15,0 und 30,0 mg/kg p. o. sowie an Kaninchen mit einer Dosis von 15,0 mg/kg subcutan durchgeführt. An den durch Spontangeburt geborenem Tieren sowie auch in den durch Kaiserschnitt gewonnenen Foeten wurden keine Konstitutionsanomalitäten beobachtet.The tests were carried out on Wistar rats at a dose of 7.5, 15.0 and 30.0 mg / kg p. o. as well as on rabbits performed subcutaneously at a dose of 15.0 mg / kg. In animals born through spontaneous delivery as well as in fetuses obtained through caesarean section no constitutional abnormalities were observed.
3 43 4
Pharmakologische PrüfungPharmacological examination
A. 2-(3-Trifluormethylanilino)-nicotinsäure und ihr LysinsalzA. 2- (3-Trifluoromethylanilino) nicotinic acid and its lysine salt
1. Analgetische Wirkung (Kontorsionsmethode von K ο s t e r et al., vgl. Fed. Proc, Bd. 18 [1959], S. 412)1. Analgesic effect (contorsion method by K o s ter et al., See Fed. Proc, Vol. 18 [1959], p. 412)
Parameterparameter
Freie Säure LysinsalzLysine free acid salt
33 mg/kg p. o. 1OO mg/kg p. o. 300 mg/kg p. o. 33 mg/kg p. o. 100 mg/kg p. o. 300 mg/kg p. o.33 mg / kg p. o.1OO mg / kg p. o. 300 mg / kg p. o. 33 mg / kg p. o. 100 mg / kg p. o. 300 mg / kg p. O.
% Verringerung der
Kontorsionen, η = 6% Reduction in
Contorsions, η = 6
0 52,7 79,10 52.7 79.1
113 (49,13—259,90)113 (49.13-259.90)
36,66 63,53 98,2636.66 63.53 98.26
58,50 (30,31—112,90)58.50 (30.31-112.90)
2. Akute antiinflammatorische Wirkung (Carrageenin-Pfotenödem, vgl. W i η t e r et al., Proc. Soc. exp. Biol. Med., Bd. 111 [1962], S. 544)2. Acute anti-inflammatory effect (carrageenin paw edema, cf. W i η t e r et al., Proc. Soc. Exp. Biol. Med., Vol. 111 [1962], p. 544)
Parameterparameter
Freie Säure LysinsalzLysine free acid salt
50 mg/kg p. o. 100 mg/kg p. o. 200 mg/kg p. o. 22,5 mg/kg p. o. 45 mg/kg p. o. 900 mg;kt; p. o.50 mg / kg p. o. 100 mg / kg p. o. 200 mg / kg p. o. 22.5 mg / kg p. o. 45 mg / kg p. o. 900 mg; kt; p. O.
% Verringerung, η - 6 43,12 ED50 85,50% Reduction, η - 6 43.12 ED 50 85.50
57,57 64,6657.57 64.66
(37,17—196,65) 42,60
38,70(37.17-196.65) 42.60
38.70
57,70 ύ2,1057.70 2.10
(15,48—96.75)(15.48-96.75)
3. Geschwürerregende Wirkung3. Ulcerogenic effects
Der Test wurde an Ratten durchgeführt. Der Grad der Geschwürbildung wurde 7 Stunden nach Verabreichung des Wirkstoffes nach der Methode von Pauls et al., vgl. Gastroenterology, Bd. 8 (1947), S. 774, bewertet und der Index d-;r Geschwürbildung aus dem Geschwürbildungsgrad, bezogen auf den Prozentsatz befallener Tiere, dividiert durch 100, berechnet (vgl. M a r t i η e ζ et al., La Semana Medica, Bd. 142 [1973], S. 721).The test was carried out on rats. The degree of ulceration was determined 7 hours after the administration of the active ingredient according to the method of Pauls et al., see Gastroenterology, Vol. 8 (1947), P. 774, and the index d-; r ulceration from the degree of ulceration, based on the Percentage of infected animals divided by 100, calculated (see M a r t i η e ζ et al., La Semana Medica, Vol. 142 [1973], p. 721).
B. 2-(2-Methyl-3-chloranilino)-nicotinsäure und ihr LysinsalzB. 2- (2-Methyl-3-chloroanilino) nicotinic acid and its lysine salt
1. Analgetische Wirkung1. Analgesic effect
a) Kontorsionsmethode (vgl. K ο s t e r et al., 1. c.)a) Contortion method (cf. K ο s t e r et al., 1. c.)
Parameterparameter
Freie Säure, mg/kg p.o. 10 20 40Free acid, mg / kg p.o. 10 20 40
Lysinsalz, mg/kg p. o.
2,5 5 10Lysine salt, mg / kg po
2.5 5 10
Acetylsalicylsäure, mg/kg p. o. 33,3 100 300Acetylsalicylic acid, mg / kg p. o. 33.3 100 300
Mittelwert der Kontorsionen, »i = 6
PotenzMean value of the contortions, »i = 6
power
37,66 31,50 22,50 45,67 29 14,50 58,17 30,17 11,6737.66 31.50 22.50 45.67 29 14.50 58.17 30.17 11.67
5,87 (4,34—7,96) 23,61 (18,9—29,5) 15.87 (4.34-7.96) 23.61 (18.9-29.5) 1
b) Thermische Methode (vgl. Grotto und Suiman, Arch. int. Pharmacodyn., Bd. 165 [1967], S. 152),durchgeführt an Mäusen, p.o.b) Thermal method (see Grotto and Suiman, Arch. Int. Pharmacodyn., Vol. 165 [1967], p. 152), performed on mice, p.o.
ED50 Lysinsalz: 15,0 mg/kg.ED 50 lysine salt: 15.0 mg / kg.
ED50 Acetylsalicylsäure: 75,0 mg;/kgED 50 acetylsalicylic acid: 75.0 mg; / kg
6060
c) Heißplattenmethode (vgl. W ο ο I f e und McDonald, J. Pharmacol, and Exper. Therap., 65 113,10). Bd.80 [1944], S.300), durchgeführt an Mäusen, p.o. ED50 Lysinsalz: 23,50 (13,43—41,12)mg/kg. ED50 Propoxyphenol: 15,50 (8,71—27,90) mg/kg.c) Hot plate method (cf. W ο ο I fe and McDonald, J. Pharmacol, and Exper. Therap., 65 113,10). Vol. 80 [1944], p.300), carried out on mice, po ED 50 lysine salt: 23.50 (13.43-41.12) mg / kg. ED 50 propoxyphenol: 15.50 (8.71-27.90) mg / kg.
2. Antithermische Wirkung (vgl. Winder und2. Antithermal effect (see Winder and
Mitarb., J. Pharmacol, and Exper. Therap., Bd. 133 [1961], S. 117), durchgeführt an RattenAssoc., J. Pharmacol, and Exper. Therap., Vol. 133 [1961], p. 117), carried out on rats
ED50 Lysinsalz: 15,0 mg/kg (5,77—39,0). ED50 Acetylsalicylsäure: 58 mg/kg (29,74 undED 50 lysine salt: 15.0 mg / kg (5.77-39.0). ED 50 acetylsalicylic acid: 58 mg / kg (29.74 and
3. Antiinflammatorische Wirkung3. Anti-inflammatory effect
a) akut (vgl. W i η i e r et al., 1. c.)a) acute (cf.W i η i e r et al., 1. c.)
Parameter Freie S;lure, mg/kg p. o. Lysinsalz. mg/kg p. o. Phenylbutazon, mg/kg p. o.Parameter Free acid, mg / kg p. o. lysine salt. mg / kg p. o. phenylbutazone, mg / kg p. O.
4; 90 180 22.5 45 90 45 90 !804; 90 180 22.5 45 90 45 90! 80
% Verringerung, η = 6 40.8 69,95 75,75 51,6 57,22 78,98 51,39 56,6 72,22% Reduction, η = 6 40.8 69.95 75.75 51.6 57.22 78.98 51.39 56.6 72.22
Potenz 1,11(0,71 — 1,73) 2,31(1,34-3,99) 1Potency 1.11 (0.71-1.73) 2.31 (1.34-3.99) 1
b) chronisch (vgl. Algodon Pellets, M e i e r et al., Experientia, Bd. 6 [1950], S. 469)b) chronic (cf. Algodon Pellets, Mei e r et al., Experientia, Vol. 6 [1950], p. 469)
Parameter Freie Saure, mg/kg ρ. ο. Lysinsalz. mg/kg ρ. ο. Phenylbutazon, mg/kg p. o.Free acid parameter, mg / kg ρ. ο. Lysine salt. mg / kg ρ. ο. Phenylbutazone, mg / kg p. O.
30 60 120 12 24 48 15 26 4530 60 120 12 24 48 15 26 45
% Verringerung, n = 6 32,47 62,91 69,29 9,28 43,46 56,99 29,62 69,48 75,38% Reduction, n = 6 32.47 62.91 69.29 9.28 43.46 56.99 29.62 69.48 75.38
Potenz 0,40(0,32—0,49) 0,63 (0.51 ^),78) 1Power 0.40 (0.32-0.49) 0.63 (0.51 ^), 78) 1
4. Geschwürerregende Wirkung (vgl. Pauls Beispieil4. Ulcer-inducing effect (cf. Paul's example
et al.. I. c: M a r 11 η e ζ el al., 1. c.) ^ Z(J |56 m| einer wäßrjgen Lösung von Ammonium-et al .. I. c.:. M ar 11 η e ζ el al, 1 c) ^ Z (J | 56 m | a j gen aq solution of ammonium
Durchgeführt an Ratten 7 Stunden nach Verab- lysinat (entsprechend einer Konzentration von 18,2 gCarried out on rats 7 hours after administrinate (corresponding to a concentration of 18.2 g
reichung des Lysinsalzes der 2-(2-Methyl-3-chIorani- Lysinbase) wurden 54,8 g 2-(3-Trifluormethy!anilino)-enrichment of the lysine salt of 2- (2-methyl-3-chlorani- lysine base), 54.8 g of 2- (3-trifluoromethy! anilino) -
lino)-nicotinsäure. Der Grad der Geschwürbildung nicotinsäure (Nifluminsäure) gegeben. Darauf wurdelino) nicotinic acid. The degree of ulceration given nicotinic acid (nifluminic acid). Then it was
wurde gewertet nach der Methode von Pa u 1 s und Benzol zugefügt und das Wasser abgetrennt. Eswas evaluated according to the method of Pa u 1 s and benzene was added and the water was separated off. It
Mitarb, und der Geschwürbildungsindex nach Mar- 30 kristallisierte das Lysinsalz der Säure aus.Mitarb, and the ulceration index according to Mar-30, the lysine salt of the acid crystallized out.
t i η e ζ und Pico. , „no/ ti η e ζ and Pico. , "No /
Bei einer Dosis von 50 und 100 mg/kg war der Ausbeute 1»2_184 rAt a dose of 50 and 100 mg / kg the yield was 1 »2_184 r
Index 0 und bei einer Dosis von 200 mg/kg 0,65. P Index 0 and at a dose of 200 mg / kg 0.65. P.
, ... .. , . . . , ., , Die spektralphotometrische Wertbestimmung ergab, ... ..,. . . ,.,, The spectrophotometric value determination gave
5. Weitere pharmakologische Versuche 3J ejnen /ntej, ^n 65>5% 2-(3-Trifluormethylanilino)-5. Further pharmacological experiments 3Jnen / ntej , ^ n 65> 5% 2 - (3-trifluoromethylanilino) -
Bis zur Dosis von 8 mg/kg i. v. wurden beim Hund nicotinsäure, was einem Reinheitsgrad von 99% ent-Up to a dose of 8 mg / kg i.p. v. were nicotinic acid in the dog, which corresponds to a degree of purity of 99%
keine elektrocardiographischen Atmungs- oder Arte- spricht. Das Lysin wurde durch sein Rotationsver-no electrocardiographic respiratory or arte-speaks. The lysine was
rialdruckveränderungen festgestellt. mögen bewertet, sein Reinheitsgrad war 99%.rial pressure changes determined. Like rated, its purity was 99%.
Die erfindungsgemäßen Salze werden dadurch hergestellt, daß man eine 2-Anilinonicotinsäure der all- 40 B e i s ρ i e 1 2
gemeinen Formel IIThe salts according to the invention are prepared by adding a 2-anilinonicotinic acid of the all- 40 B is ρ ie 1 2
common formula II
y\ 26,3 g2-(2-MethyI-3-chloranilino)-nicotinsäurewur- y \ 26.3 g 2- (2-MethyI-3-chloroanilino) nicotinic acid
( η— COOH den in 100 ml Wasser suspendiert und dann tropfen- ( η— COOH suspended in 100 ml of water and then dropwise
(II) weise mit 31 ml einer basischen Lysinlösung 48% ver-(II) use 31 ml of a basic lysine solution 48%
!\N )— R 45 setzt. Darauf wurde die Lösung lyophilisiert.! \ N ) - R 45 sets. The solution was then lyophilized.
Fp. des Salzes: 205 bis 2100C (Zersetzung).Fp. Of the salt: 205 to 210 0 C (decomposition).
in der R die obige Bedeutung aufweist, mit Lysin Die Salze können zusammen mit üblichen pharma-in which R has the above meaning, with lysine The salts can be used together with customary pharmaceutical
oder Ammoniumlysinat in an sich bekannter Weise zeutischen Hilfsmitteln als Antiphlogistica und Anti-or ammonium lysinate in a manner known per se zeutischen auxiliaries as anti-inflammatory and anti-
umsetzt. pyretica verwendet werden.implements. pyretica can be used.
Claims (3)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AR23873471 | 1971-10-28 | ||
| AR23873471 | 1971-10-28 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2253134A1 DE2253134A1 (en) | 1973-05-03 |
| DE2253134B2 DE2253134B2 (en) | 1976-02-12 |
| DE2253134C3 true DE2253134C3 (en) | 1976-10-07 |
Family
ID=
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