Digoxosid, Neodigoxosid und Acetyldigoxin- γ , neue Glykoside aus den Blättern von Digitalis lanata Ehrh

Digoxosid, Neodigoxosid und Acetyldigoxin- γ , neue Glykoside aus den Blättern von Digitalis... Kurze Originalmitteilungen Die Naturwissenschalten Digoxosid, Neodigoxosid und Acetyldigoxin-~,, neue 61ykoside aus den Bliittern yon Digitalis lanata Ehrh.*) Die drei n e u e n G l y k o s i d e fandeli w i t in :RtickstXndeli, die bet der R e i n i g u n g des D i g o x i n s a m E n d e des P r o d u k t i o l i s g a n g e s anfallen. V o n b e s o l i d e r e m I n t e r e s s e s i n d D i g o x o s i d u n d Neodigoxosid, well hier die e r s t e n T e t r a d i g i t o x o s i d e vorliegen. -- Die Isolierulig der drei G l y k o s i d e * * ) g e l a n g d u r c h C h r o m a t o g r a p h i c des n a c h B e h a n d l u n g m i t A c e t o n u n d ~ t h a n o l w e i t g e h e n d y o n D i g o x i n befreiten A u s g a n g s m a t e r i a l s a n SXulen, die m i t einer M i s c h u n g y o n Celite 545 u n d Cellulosep u l v e r Schleicher u. SchfilI t 23 i m V e r h ~ l t n i s f : f, i m p r ~ g n i e r t m i t 40% :Formamid, geffillt waren. Die VortrenllUng erfolgte m i t C y c l o h e x a n - C h l o r o f o r m 1:7. Die D i g o x o s i d u n d Neodigoxosid e n t h a l t e n d e l i F r a k t i o n e n w u r d e n m i t B e n z o l - M e t h y l i i t h y l k e t o n 1 : 1 bet gleicher S/~ulenffillung g e t r e n n t . D a s D i g o x o s i d g i b t bet der n o r m a l e n G l y k o s i d s p a l t u l i g m i t Sgure D i g o x i g e n i n u n d Digitoxose. N a c h der part[ellen H y d r o l y s e mitt v e r d i i n n t e r SalzsXure in Methaliol z~) lassen sich p a p i e r c h r o m a t o g r a p h i s c h die S p a l t p r o d u k t e Digoxin, Digoxigenin-bis- u n d - m o n o - d i g i t o x o s i d u n d D i g o x i g e n i n n a c h w e i s e n . A u s e i n e m G e m i s c h dieser S p a l t p r o d u k t e a n F o r m a m i d c e l l u l o s e - S ~ u l e n m i t Cyclohexali-Chloroform t : 7 a b g e t r e n n t e s D i g o x i n h a t ein m i t a u t h e n t i s c h e m D i g o x i n i d e n t i s c h e s I R - S p e k t r u m . Die A n z a h l d e r Digitoxoseli e r g i b t sich a u s der DigitoxosebestimmuligX~). ] 3 e h a n d l u n g m i t s c h w a c h e m Alkali l~Bt d a s Glykosid u n v e r X n d e r t ; es e n t h ~ l t d e m n a c h keine A c y l g r u p p e n . A u s der m o l e k u l a r e n D r e h u n g e) ,~) is[ zu schlieBen, d a b die vierte D i g i t o x o s e fl-glykosidisch a n die elidst/~ndige D i g i t o x o s e des D i g o x i n s g e b u n d e l i [st. A u s d e m N e o d i g o x o s i d erh/~lt m a n bet der s a u r e n Glykosids p a l t u l i g ebenfalls D i g o x i g e n i n u n d Digitoxose. I n d e n P a p i e r c h r o m a t o g r a m m e n des d u r c h partielle H y d r o l y s e ents t e h e n d e n G e m i s c h e s finder m a n n e b e n D i g o x i g e n i n - m o n o u n d -bis-digitoxosid u n d D i g o x i g e n i n j e d o c h n i c h t Digoxin, s o n d e r n Neodigoxin~b). A u c h hier ergibt die D i g i t o x o s e b e s t i m m u n g vier Digitoxosen. B e h a n d l u n g m i t Alkali I~gt d a s G l y k o s i d u n v e r g n d e r t . N e o d i g o x o s i d is[ d e m n a c h ein D i g o x i g e n i n - t e t r a d i g i t o x o s i d , bet d e m die v i e r t e D i g i t o x o s e w a h r s c h e i n i i c h fl-glykosidisch (s. oben) a n die e n d s t ~ n d i g e D i g i t o x o s e d e s N e o d i g o x i n s g e b n l i d e n is[. N e o d i g o x o s i d [st in Digitalis l a n a t a n u r zu e t w a 10% des D i g o x o s i d s elithalten. D i g o x o s i d selbst dfirfte in der Droge i m a l l g e m e i n e n k a u m 0, 5 % des G e h a l t e s a n D i g o x i n erreichen. Allerdings hubert w i t i m R a h m e n v o n Z i i c h t u n g s v e r s u c h e n eilizelne P f l a n z e n gesehen, die 0,05% D i g o x o s i d e n t h i e l t e n . D a s d r i t t e Glykosid w a r i m A u s g a n g s m a t e r i a l in n u r s e h r geringer M e n g e e n t h a l t e n . ]~s w u r d e a u s d e n e r s t e n F r a k t i o n e n der V o r t r e n n u n g a n ether Silicagels~iule m i t der L 6 s u n g s mittelfolge B e n z o l - E s s i g e s t e r l : J, 1 : 4, E s s i g e s t e r a b g e t r e n n t . D a IIur s e h r w e n i g n i c h t g a n z reines P r o d u k t anfiel, k o n n t e die S t r u k t u r a u f k l A r n n g n u r p a p i e r c h r o m a t o g r a p h i s c h erfolgen: Alkalisehe B e h a n d l u n g liefert D i g o x i n , S/~urespaltung Digoxig e n i n u n d Digitoxose. t 3 e h a n d l u n g m i t B l e i a c e t a t l 6 s u n g t) 1Xgt d a s Glykosid u n v e r ~ n d e r t . E s [st also k e i n Formnyl-, allem folgt, d a b die A c e t y l g r u p p e a n der m i t d e m Genili verk n t i p f t e n , , i n n e r e n " Digitoxose sitzen mul3. D e r a r t i g e Glykoside, A c e t y l d i g i t o x i n - y u n d Acetylgitoxin-~,, sind kfirzlich y o n I~. l-Ioj1 ~) a u s S a m e n y o n Digitalis p u r p u r e a e r h a l t e n worden. W i r schlieBen n n s dieser N a m e n g e b u n g an. Digoxosid. C ~ H ~ 4 O I ~ . H 2 0 (929,07). B e t . : C 60,76, H 8,25, D i g i t o x o s e 63,8. Gel.: C 60,77, H 8,41, D i g i t o x o s e 63,0. S c h m p . 2 6 5 - - 2 6 8 ~ ,~max = 217 m~z (log e = 4,22). LD K a t z e : 0,416 mg/kgS). Neodigoxosid. C4~H7401~ (91t,07). Ber.: C 61,96, H 8,t9, D i g i t o x o s e 65,I. Gef.: C 6t,82, H 8,09, D i g i t o x o s e 64,3. S e h m p . 2 3 5 - - 2 3 9 ~ ).rnax = 217 mtz (log e = 4,22). Forschungslaboratorien der Firma C. F, Boehringer u. Sdhne G.m.b.H., Mannheim-Waldho[ F. KAISER, E. HAAK u n d H. SPINGLER Eingegangen am 12. J u n i 1963 *) 19. Mitteilung fiber Herzglykoside. **) Unter der ausgezeiehneten experimentellen Mitarbeit yon Herrn H. GERLACm ~) KAISER, F., E. HAACK U. H. SPlXGL~R: a) Liebigs Ann. Chem. 603, 75 (t 957) ; - - b) Naturwissenschafteu 46, 447 (1959). - - ~) TSCH~SCHE, R., B. NIYOMPORN U. H . NACHLEIDT: Chem. Bet. 92, 2258 (1959). - - 3) LEWBART, M.L., W. WEHRLI, H. t~AUFMANN U. T. REICXSrEIN: Helv. claim. Acta 4a, 5t7 (t963}. - - ~) HAACK, E., F. KAISER, M. GUBE u. H . SPINGLER: Naturwissenschaften aS, 315 (1958). - - 5) ttOjl, K.: Chem. ])harm. Bull. (Japan) 9, 7 (1961). - ~) KAISER, F.: Chem. Bet. 88, 556 ( 1 9 5 5 ) . - 7) Literaturwerte nach CH. TA~M, in ZEC~MEISTER, Fortschritte der Chemic organiseher Naturstoffe, Bd. 13, S. 207. Wien: Springer 1956. - - 8) F/Jr die Toxizitfitsbestimmung danken wir Herrn Professor Dr. K.K. C~EN, Indianapolis. A Method tForDetermination of the Exact Localization of Radiostrontium and for Continuous Quantitative Follow-Up of Radiostrontium Metabolism in a Live Animal I t h a s b e e n s h o w n t h a t r a d i o s t r o n t i u m is n o t irreversibly b o u n d i n t o t h e skeleton, b u t t h a t o n t h e c o n t r a r y it is mobile b e t w e e n d i f f e r e n t t i s s u e c o m p a r t m e n t s w i t h i n tlae l i m i t s of i t s o w n e q u i l i b r i u m s y s t e m 1~, b). T h i s p r o p e r t y of r a d i o s t r o n t i u m in t h e o r g a n i s m could n o t be d e m o n s t r a t e d u n t i l we h a d b e g u n utilizing t h e e x t r a r e n a l m i n e r a l / f l u i d - b a l a n c e r e g u l a t o r y a n d e x c r e t o r y s y s t e m (i.e., a n o r d i n a r y cell activity), i n s t e a d of t h e r e n a l e x c r e t o r y s y s t e m (i.e., g l o m e r u l a r nltrafiltratioli a n d t u b u l a r reabsorption), as a r o u t e of exit for t h e radionuclidelr T h e f o r m e r s y s t e m is e a s y to a c t i v a t e w i t h o u t d i s t u r b i n g its p h y s i o l o g y , a n d its general e x c r e t o r y c a p a c i t y is e x t r e m e l y h i g h 2 ~, b). A d m i n i s t r a t i o n of large q u a n t i t i e s of r a d i o s [ r o u t [ u r n to e x p e r i m e n t a l animals, g u i d i n g t h e radionuclide o u t of t h e b o d y , a n d collecting a n d m e a s u r i n g it a f t e r e x c r e t i o n are m e r e l y o n e facet of t h e w i t h d r a w a l procedure. A t t h e s a m e t i m e i n f o r m a t i o n is n e e d e d o n t h e following p r o b l e m s : (1) t h e accretioli speed of t h e radionuclide into different regions w i t h i n t h e bones, (2) t h e precise localization of t h e r a d i o s t r o n t i u m in t h e bones, (3) physiologic c h a n g e s in t h e q u a n t i t y of t h e radios t r o n t i u m in a g i v e n skeletal region, (4) t h e effect of t h e blood c i r c u l a t i o n on m e t a b o l i s m of r a d i o s t r o n t i u m , (5) t h e a m o u n t a n d r a t e of d e p a r t u r e of t h e r a d i o s t r o n t i u m f r o m specific p a r t s of t h e skeleton, (6) t h e t o t a l a m o u n t of s u c h d e p a r t u r e , a n d (7) t h e period required for elimination. All t h e s e d a t a c a n be o b t a i n e d f r o m a g i v e n individual, live a n i m a l u n d e r controlled h e a l t h conditions. T h e principles of o u r n e w m e t h o d for q u a n t i t a t i v e followu p of t h e i n t e r n a l m e t a b o l i s m of r a d i o s t r o l i t i u m in live mice c a n be o u t l i n e d as follows. T h e c a u d a l s p i n e of t h e mouse, a v e r a g i n g 25 v e r t e b r a e a n d w i t h artificial fractures, p s e u d o a r t h r o s e s , etc., was u s e d as t a r g e t tissue (Fig. l a, b). R o e n t g e n o g r a m s of t h e c a u d a l s p i n e were m a g n i f i e d s o m e 15 times, so t h a t its l e n g t h in t h e p i c t u r e s b e c a m e a b o u t 150 cm. T h i s p e r m i t t e d s t u d y of t h e osseous s t r u c t u r e . Calibrated q u a n t i t i e s of radios[rout[urn, e i t h e r as a n isotope e m i t t i n g b o t h b e t a a n d g a m m a r a y s (Sr 85, Sr sg, Sr 9~, Sr ~2) or as one e m i t t i n g b e t a r a y s o n l y (Srg~ were instilled i n t r a g a s t r i c a l l y to t h e a n i m a l s . F o r q u a n t i t a t i v e follow-up, t h e living m o u s e w a s placed in a p e r s p e x c h a m b e r , a n d its tail w a s s t r a i g h t e n e d o u t a n d i m m o b i l i z e d w i t h p i a s t e r to a f o u n d a t i o n plate. A l i g h t w e i g h t d e t e c t o r could n o w be m o v e d a l o n g t h e whote l e n g t h of t h e m o u s e taii; if t h e d e t e c t o r w a s h e a v y , t h e a n i m a l c h a m b e r h a d to be m o v e d instead. A s y n c h r o m o t o r w i t h a d j u s t a b l e s p e e d / m i n w a s u s e d to m o v e t h e d e t e c t o r or t h e m o u s e . T h e a p p a r a t u s was joined to a measuring cabinet (type S i e m e n s & Halske, Jdarlsrnhe, G e r m a n y ) e q u i p p e d w i t h a l - c h a n n e l a n a l y z e r , a n electric Tabelle. h-RF-Werte ( = RF" 100) und spezi[ische Drehung der Digoxigeninglyhoside Lgsungsmittel XMKK BzMf~K Cf [C~]D Pyridin Digoxosid . . . . . . . . 13 42 80 + 18,5 ~ Neodigoxosid . . . . . . . 17 50 85 + 5 6 ~ Digoxin . . . . . . . . . 16 44 58 + 13,7 ~ Neodigoxin . . . . . . . . ~2 30 29 + 1~0~ Digoxigenin-bis-digitoxosid . 17 45 34 + 4,7 ~ Digoxigenin-mono-digitoxosid 19 47 19 - - 7,3 ~ Digoxigenin . . . . . . . . 32 6O 25 + 10,4 ~ Acetyldigoxin-~ . . . . . . 39 85 F + 18 ~ ~) Aeetyldigoxin-B . . . . . . 45 90 F + 29,2 ~ 7) Acetyldigoxin-7 . . . . . . 29 65 93 -X M ~ K = Xylol-Methyl~th Aketou 1 : 1, BzM~IK = Benzol-Methyl~thylketon 1:1, Cf = Chloroform. Papier: Schleicher & Schfill 2043b Mgl, m i t Formamid impr/igniert"), Format t6,5 • 45 cln Laufzeit t5 h. s o n d e r n ein A c e t y l d i g o x i n . 13el der part[ellen s a u r e n H y d r o lyse e n t s t e h e n D i g o x i g e n i n u n d zwei Spaltglykoside, die i m rnit C y c l o h e x a n - C h l o r o f o r m I :8 a u f F o r m a m i d p a p i e r e n t w i c k e l t e n C h r o m a t o g r a m m z w i s c h e n D i g o x i n u n d Acetyldigoxin-c~ liegen u n d n i c h t m i t D i g o x i g e n i n - m o n o - u n d -bisdigitoxosid i d e n t i s c h stud. B e h a n d e l t m a n d a s G e m i s c h a n schlieBend m i t s c h w a c h e m Alkali, so e l i t s t e h t a u s d e n be[den S p a l t g l y k o s i d e n D i g o x i g e n i n - m o n o - u n d -bis-digitoxosid. A u s http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Naturwissenschaften Springer Journals

Digoxosid, Neodigoxosid und Acetyldigoxin- γ , neue Glykoside aus den Blättern von Digitalis lanata Ehrh

Naturwissenschaften, Volume 50 (21) – Jan 1, 1963
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Springer Journals
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Copyright © 1963 by Springer-Verlag
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Life Sciences; Life Sciences, general; Environment, general
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Abstract

Kurze Originalmitteilungen Die Naturwissenschalten Digoxosid, Neodigoxosid und Acetyldigoxin-~,, neue 61ykoside aus den Bliittern yon Digitalis lanata Ehrh.*) Die drei n e u e n G l y k o s i d e fandeli w i t in :RtickstXndeli, die bet der R e i n i g u n g des D i g o x i n s a m E n d e des P r o d u k t i o l i s g a n g e s anfallen. V o n b e s o l i d e r e m I n t e r e s s e s i n d D i g o x o s i d u n d Neodigoxosid, well hier die e r s t e n T e t r a d i g i t o x o s i d e vorliegen. -- Die Isolierulig der drei G l y k o s i d e * * ) g e l a n g d u r c h C h r o m a t o g r a p h i c des n a c h B e h a n d l u n g m i t A c e t o n u n d ~ t h a n o l w e i t g e h e n d y o n D i g o x i n befreiten A u s g a n g s m a t e r i a l s a n SXulen, die m i t einer M i s c h u n g y o n Celite 545 u n d Cellulosep u l v e r Schleicher u. SchfilI t 23 i m V e r h ~ l t n i s f : f, i m p r ~ g n i e r t m i t 40% :Formamid, geffillt waren. Die VortrenllUng erfolgte m i t C y c l o h e x a n - C h l o r o f o r m 1:7. Die D i g o x o s i d u n d Neodigoxosid e n t h a l t e n d e l i F r a k t i o n e n w u r d e n m i t B e n z o l - M e t h y l i i t h y l k e t o n 1 : 1 bet gleicher S/~ulenffillung g e t r e n n t . D a s D i g o x o s i d g i b t bet der n o r m a l e n G l y k o s i d s p a l t u l i g m i t Sgure D i g o x i g e n i n u n d Digitoxose. N a c h der part[ellen H y d r o l y s e mitt v e r d i i n n t e r SalzsXure in Methaliol z~) lassen sich p a p i e r c h r o m a t o g r a p h i s c h die S p a l t p r o d u k t e Digoxin, Digoxigenin-bis- u n d - m o n o - d i g i t o x o s i d u n d D i g o x i g e n i n n a c h w e i s e n . A u s e i n e m G e m i s c h dieser S p a l t p r o d u k t e a n F o r m a m i d c e l l u l o s e - S ~ u l e n m i t Cyclohexali-Chloroform t : 7 a b g e t r e n n t e s D i g o x i n h a t ein m i t a u t h e n t i s c h e m D i g o x i n i d e n t i s c h e s I R - S p e k t r u m . Die A n z a h l d e r Digitoxoseli e r g i b t sich a u s der DigitoxosebestimmuligX~). ] 3 e h a n d l u n g m i t s c h w a c h e m Alkali l~Bt d a s Glykosid u n v e r X n d e r t ; es e n t h ~ l t d e m n a c h keine A c y l g r u p p e n . A u s der m o l e k u l a r e n D r e h u n g e) ,~) is[ zu schlieBen, d a b die vierte D i g i t o x o s e fl-glykosidisch a n die elidst/~ndige D i g i t o x o s e des D i g o x i n s g e b u n d e l i [st. A u s d e m N e o d i g o x o s i d erh/~lt m a n bet der s a u r e n Glykosids p a l t u l i g ebenfalls D i g o x i g e n i n u n d Digitoxose. I n d e n P a p i e r c h r o m a t o g r a m m e n des d u r c h partielle H y d r o l y s e ents t e h e n d e n G e m i s c h e s finder m a n n e b e n D i g o x i g e n i n - m o n o u n d -bis-digitoxosid u n d D i g o x i g e n i n j e d o c h n i c h t Digoxin, s o n d e r n Neodigoxin~b). A u c h hier ergibt die D i g i t o x o s e b e s t i m m u n g vier Digitoxosen. B e h a n d l u n g m i t Alkali I~gt d a s G l y k o s i d u n v e r g n d e r t . N e o d i g o x o s i d is[ d e m n a c h ein D i g o x i g e n i n - t e t r a d i g i t o x o s i d , bet d e m die v i e r t e D i g i t o x o s e w a h r s c h e i n i i c h fl-glykosidisch (s. oben) a n die e n d s t ~ n d i g e D i g i t o x o s e d e s N e o d i g o x i n s g e b n l i d e n is[. N e o d i g o x o s i d [st in Digitalis l a n a t a n u r zu e t w a 10% des D i g o x o s i d s elithalten. D i g o x o s i d selbst dfirfte in der Droge i m a l l g e m e i n e n k a u m 0, 5 % des G e h a l t e s a n D i g o x i n erreichen. Allerdings hubert w i t i m R a h m e n v o n Z i i c h t u n g s v e r s u c h e n eilizelne P f l a n z e n gesehen, die 0,05% D i g o x o s i d e n t h i e l t e n . D a s d r i t t e Glykosid w a r i m A u s g a n g s m a t e r i a l in n u r s e h r geringer M e n g e e n t h a l t e n . ]~s w u r d e a u s d e n e r s t e n F r a k t i o n e n der V o r t r e n n u n g a n ether Silicagels~iule m i t der L 6 s u n g s mittelfolge B e n z o l - E s s i g e s t e r l : J, 1 : 4, E s s i g e s t e r a b g e t r e n n t . D a IIur s e h r w e n i g n i c h t g a n z reines P r o d u k t anfiel, k o n n t e die S t r u k t u r a u f k l A r n n g n u r p a p i e r c h r o m a t o g r a p h i s c h erfolgen: Alkalisehe B e h a n d l u n g liefert D i g o x i n , S/~urespaltung Digoxig e n i n u n d Digitoxose. t 3 e h a n d l u n g m i t B l e i a c e t a t l 6 s u n g t) 1Xgt d a s Glykosid u n v e r ~ n d e r t . E s [st also k e i n Formnyl-, allem folgt, d a b die A c e t y l g r u p p e a n der m i t d e m Genili verk n t i p f t e n , , i n n e r e n " Digitoxose sitzen mul3. D e r a r t i g e Glykoside, A c e t y l d i g i t o x i n - y u n d Acetylgitoxin-~,, sind kfirzlich y o n I~. l-Ioj1 ~) a u s S a m e n y o n Digitalis p u r p u r e a e r h a l t e n worden. W i r schlieBen n n s dieser N a m e n g e b u n g an. Digoxosid. C ~ H ~ 4 O I ~ . H 2 0 (929,07). B e t . : C 60,76, H 8,25, D i g i t o x o s e 63,8. Gel.: C 60,77, H 8,41, D i g i t o x o s e 63,0. S c h m p . 2 6 5 - - 2 6 8 ~ ,~max = 217 m~z (log e = 4,22). LD K a t z e : 0,416 mg/kgS). Neodigoxosid. C4~H7401~ (91t,07). Ber.: C 61,96, H 8,t9, D i g i t o x o s e 65,I. Gef.: C 6t,82, H 8,09, D i g i t o x o s e 64,3. S e h m p . 2 3 5 - - 2 3 9 ~ ).rnax = 217 mtz (log e = 4,22). Forschungslaboratorien der Firma C. F, Boehringer u. Sdhne G.m.b.H., Mannheim-Waldho[ F. KAISER, E. HAAK u n d H. SPINGLER Eingegangen am 12. J u n i 1963 *) 19. Mitteilung fiber Herzglykoside. **) Unter der ausgezeiehneten experimentellen Mitarbeit yon Herrn H. GERLACm ~) KAISER, F., E. HAACK U. H. SPlXGL~R: a) Liebigs Ann. Chem. 603, 75 (t 957) ; - - b) Naturwissenschafteu 46, 447 (1959). - - ~) TSCH~SCHE, R., B. NIYOMPORN U. H . NACHLEIDT: Chem. Bet. 92, 2258 (1959). - - 3) LEWBART, M.L., W. WEHRLI, H. t~AUFMANN U. T. REICXSrEIN: Helv. claim. Acta 4a, 5t7 (t963}. - - ~) HAACK, E., F. KAISER, M. GUBE u. H . SPINGLER: Naturwissenschaften aS, 315 (1958). - - 5) ttOjl, K.: Chem. ])harm. Bull. (Japan) 9, 7 (1961). - ~) KAISER, F.: Chem. Bet. 88, 556 ( 1 9 5 5 ) . - 7) Literaturwerte nach CH. TA~M, in ZEC~MEISTER, Fortschritte der Chemic organiseher Naturstoffe, Bd. 13, S. 207. Wien: Springer 1956. - - 8) F/Jr die Toxizitfitsbestimmung danken wir Herrn Professor Dr. K.K. C~EN, Indianapolis. A Method tForDetermination of the Exact Localization of Radiostrontium and for Continuous Quantitative Follow-Up of Radiostrontium Metabolism in a Live Animal I t h a s b e e n s h o w n t h a t r a d i o s t r o n t i u m is n o t irreversibly b o u n d i n t o t h e skeleton, b u t t h a t o n t h e c o n t r a r y it is mobile b e t w e e n d i f f e r e n t t i s s u e c o m p a r t m e n t s w i t h i n tlae l i m i t s of i t s o w n e q u i l i b r i u m s y s t e m 1~, b). T h i s p r o p e r t y of r a d i o s t r o n t i u m in t h e o r g a n i s m could n o t be d e m o n s t r a t e d u n t i l we h a d b e g u n utilizing t h e e x t r a r e n a l m i n e r a l / f l u i d - b a l a n c e r e g u l a t o r y a n d e x c r e t o r y s y s t e m (i.e., a n o r d i n a r y cell activity), i n s t e a d of t h e r e n a l e x c r e t o r y s y s t e m (i.e., g l o m e r u l a r nltrafiltratioli a n d t u b u l a r reabsorption), as a r o u t e of exit for t h e radionuclidelr T h e f o r m e r s y s t e m is e a s y to a c t i v a t e w i t h o u t d i s t u r b i n g its p h y s i o l o g y , a n d its general e x c r e t o r y c a p a c i t y is e x t r e m e l y h i g h 2 ~, b). A d m i n i s t r a t i o n of large q u a n t i t i e s of r a d i o s [ r o u t [ u r n to e x p e r i m e n t a l animals, g u i d i n g t h e radionuclide o u t of t h e b o d y , a n d collecting a n d m e a s u r i n g it a f t e r e x c r e t i o n are m e r e l y o n e facet of t h e w i t h d r a w a l procedure. A t t h e s a m e t i m e i n f o r m a t i o n is n e e d e d o n t h e following p r o b l e m s : (1) t h e accretioli speed of t h e radionuclide into different regions w i t h i n t h e bones, (2) t h e precise localization of t h e r a d i o s t r o n t i u m in t h e bones, (3) physiologic c h a n g e s in t h e q u a n t i t y of t h e radios t r o n t i u m in a g i v e n skeletal region, (4) t h e effect of t h e blood c i r c u l a t i o n on m e t a b o l i s m of r a d i o s t r o n t i u m , (5) t h e a m o u n t a n d r a t e of d e p a r t u r e of t h e r a d i o s t r o n t i u m f r o m specific p a r t s of t h e skeleton, (6) t h e t o t a l a m o u n t of s u c h d e p a r t u r e , a n d (7) t h e period required for elimination. All t h e s e d a t a c a n be o b t a i n e d f r o m a g i v e n individual, live a n i m a l u n d e r controlled h e a l t h conditions. T h e principles of o u r n e w m e t h o d for q u a n t i t a t i v e followu p of t h e i n t e r n a l m e t a b o l i s m of r a d i o s t r o l i t i u m in live mice c a n be o u t l i n e d as follows. T h e c a u d a l s p i n e of t h e mouse, a v e r a g i n g 25 v e r t e b r a e a n d w i t h artificial fractures, p s e u d o a r t h r o s e s , etc., was u s e d as t a r g e t tissue (Fig. l a, b). R o e n t g e n o g r a m s of t h e c a u d a l s p i n e were m a g n i f i e d s o m e 15 times, so t h a t its l e n g t h in t h e p i c t u r e s b e c a m e a b o u t 150 cm. T h i s p e r m i t t e d s t u d y of t h e osseous s t r u c t u r e . Calibrated q u a n t i t i e s of radios[rout[urn, e i t h e r as a n isotope e m i t t i n g b o t h b e t a a n d g a m m a r a y s (Sr 85, Sr sg, Sr 9~, Sr ~2) or as one e m i t t i n g b e t a r a y s o n l y (Srg~ were instilled i n t r a g a s t r i c a l l y to t h e a n i m a l s . F o r q u a n t i t a t i v e follow-up, t h e living m o u s e w a s placed in a p e r s p e x c h a m b e r , a n d its tail w a s s t r a i g h t e n e d o u t a n d i m m o b i l i z e d w i t h p i a s t e r to a f o u n d a t i o n plate. A l i g h t w e i g h t d e t e c t o r could n o w be m o v e d a l o n g t h e whote l e n g t h of t h e m o u s e taii; if t h e d e t e c t o r w a s h e a v y , t h e a n i m a l c h a m b e r h a d to be m o v e d instead. A s y n c h r o m o t o r w i t h a d j u s t a b l e s p e e d / m i n w a s u s e d to m o v e t h e d e t e c t o r or t h e m o u s e . T h e a p p a r a t u s was joined to a measuring cabinet (type S i e m e n s & Halske, Jdarlsrnhe, G e r m a n y ) e q u i p p e d w i t h a l - c h a n n e l a n a l y z e r , a n electric Tabelle. h-RF-Werte ( = RF" 100) und spezi[ische Drehung der Digoxigeninglyhoside Lgsungsmittel XMKK BzMf~K Cf [C~]D Pyridin Digoxosid . . . . . . . . 13 42 80 + 18,5 ~ Neodigoxosid . . . . . . . 17 50 85 + 5 6 ~ Digoxin . . . . . . . . . 16 44 58 + 13,7 ~ Neodigoxin . . . . . . . . ~2 30 29 + 1~0~ Digoxigenin-bis-digitoxosid . 17 45 34 + 4,7 ~ Digoxigenin-mono-digitoxosid 19 47 19 - - 7,3 ~ Digoxigenin . . . . . . . . 32 6O 25 + 10,4 ~ Acetyldigoxin-~ . . . . . . 39 85 F + 18 ~ ~) Aeetyldigoxin-B . . . . . . 45 90 F + 29,2 ~ 7) Acetyldigoxin-7 . . . . . . 29 65 93 -X M ~ K = Xylol-Methyl~th Aketou 1 : 1, BzM~IK = Benzol-Methyl~thylketon 1:1, Cf = Chloroform. Papier: Schleicher & Schfill 2043b Mgl, m i t Formamid impr/igniert"), Format t6,5 • 45 cln Laufzeit t5 h. s o n d e r n ein A c e t y l d i g o x i n . 13el der part[ellen s a u r e n H y d r o lyse e n t s t e h e n D i g o x i g e n i n u n d zwei Spaltglykoside, die i m rnit C y c l o h e x a n - C h l o r o f o r m I :8 a u f F o r m a m i d p a p i e r e n t w i c k e l t e n C h r o m a t o g r a m m z w i s c h e n D i g o x i n u n d Acetyldigoxin-c~ liegen u n d n i c h t m i t D i g o x i g e n i n - m o n o - u n d -bisdigitoxosid i d e n t i s c h stud. B e h a n d e l t m a n d a s G e m i s c h a n schlieBend m i t s c h w a c h e m Alkali, so e l i t s t e h t a u s d e n be[den S p a l t g l y k o s i d e n D i g o x i g e n i n - m o n o - u n d -bis-digitoxosid. A u s

Journal

NaturwissenschaftenSpringer Journals

Published: Jan 1, 1963

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