DE2652508A1 - Cardiac glycoside compsns. with good enteric resorption - with the glycoside dissolved or suspended in (mixed) fatty acid partial glycerides - Google Patents

Cardiac glycoside compsns. with good enteric resorption - with the glycoside dissolved or suspended in (mixed) fatty acid partial glycerides

Info

Publication number
DE2652508A1
DE2652508A1 DE19762652508 DE2652508A DE2652508A1 DE 2652508 A1 DE2652508 A1 DE 2652508A1 DE 19762652508 DE19762652508 DE 19762652508 DE 2652508 A DE2652508 A DE 2652508A DE 2652508 A1 DE2652508 A1 DE 2652508A1
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DE
Germany
Prior art keywords
compsns
glycoside
resorption
strophanthin
dissolved
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.)
Withdrawn
Application number
DE19762652508
Other languages
German (de)
Inventor
Reinhard Dr Med Hempel
Martin Dr Rer Nat Wischniewski
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Abbott Products GmbH
Original Assignee
Kali Chemie Pharma GmbH
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Kali Chemie Pharma GmbH filed Critical Kali Chemie Pharma GmbH
Priority to DE19762652508 priority Critical patent/DE2652508A1/en
Priority to IE137977A priority patent/IE45448B1/en
Priority to GB2798577A priority patent/GB1544576A/en
Priority to IL5247277A priority patent/IL52472A/en
Priority to NL7707567A priority patent/NL7707567A/en
Priority to US05/813,456 priority patent/US4202888A/en
Priority to DD7700199970A priority patent/DD131344A5/en
Priority to FR7721073A priority patent/FR2365338A1/en
Priority to PT66789A priority patent/PT66789B/en
Priority to GR53930A priority patent/GR70745B/el
Priority to FI772160A priority patent/FI57056C/en
Priority to DK313277A priority patent/DK313277A/en
Priority to ES460642A priority patent/ES460642A1/en
Priority to NO772444A priority patent/NO772444L/en
Priority to NZ18461277A priority patent/NZ184612A/en
Priority to SE7708040A priority patent/SE7708040L/en
Priority to CA282,536A priority patent/CA1087985A/en
Priority to JP8335477A priority patent/JPS5329917A/en
Publication of DE2652508A1 publication Critical patent/DE2652508A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

Compsn. consists of a soln. or microcrystalline suspension of cardiac glycosides (I) in partial glycerides (II) of medium chain-length fatty acids, or mixts. of glycerides. Pref. (II) are mono-and/or di-glycerides and the acid component has 6-12, esp. 8-10C. Suitably the compsns. are treated with an auxiliary to increase the viscosity or give it structure, and then filled into a gelatin capsule, opt. coated with a substance resistant to gastric acid. alternatively they are made up as suppositories. Compsn. is used for treatment of cardiac insufficiency. Compsns. has very high (=80%) enteric resorption for (I) which are normally very difficulty resorbable, e.g. strophanthin g or k, and proscillaridine. LD50's are lower in (II), e.g. for strophanthin g it is 5.2 mg/kg c.f. 34.8 mg-kg in water (orally in guinea pigs).

Description

Oral zu verabreichende Arzneimittel Oral drugs

Die Erfindung bezieht sich auf oral zu verabreichende Arzneimittel aus schwer resorbierbaren Wirkstoffen.The invention relates to drugs to be administered orally made of active ingredients that are difficult to absorb.

Es ist bekannt, daß gewisse Wirkstoffe mit ausgeprägten hydrophilen Eigenschaften oder in stark ionisierterForm im Intestinaltrakt nicht oder nur in geringem Maße resorbiert werden, da sie die Lipidmembran der Darmmukosa nicht ausreichend zu durchdringen vermögen.It is known that certain active ingredients with pronounced hydrophilic Properties or in a strongly ionized form in the intestinal tract or only in to a small extent are absorbed because they do not adequately cover the lipid membrane of the intestinal mucosa to be able to penetrate.

So'erreicht z.B. oral gegebenes g-Strophanthin nur etwa eine Resorptionsquote von. bis zu 5 Vo.For example, g-strophanthin given orally only achieves an absorption rate from. up to 5 Vo.

Ferner sind aus der Gruppe der quarternären Ammoniumsalze zahlreiche Wfrkstoffe bekannt, bei denen die therapeutisch wirksame Dosis im Falle einer für die enterale Resorption vorgesehenalArzneiform wegen der geringen Resorptionsquote um ein Mehrfaches höher sein muß als bei einer entsprechenden Injektionsform.Furthermore, there are numerous from the group of the quaternary ammonium salts Active ingredients known for which the therapeutically effective dose in the case of a for enteral absorption is provided as a drug because of the low absorption rate must be several times higher than with a corresponding injection form.

Schließlich werden zahlreiche Arzneistoffe auch wegen ihrer geringen Wasserlöslichkeit nur in geringem Maße von der Mukose des Intestinaltraktes resorbiert. In solchen Fällen kann zwar .durch gewisse technologische Behandlungen des Wirkstõffes, wie etwa Mikronisierung, Bildung von Adsorbaten oder Zusatz von Lösungsvermittlern eine gesteigerte Resorption erzielt werden, Jedoch liegt die zu applizierende Dosis fast immer erheblich über der Wirkstoffmenge, die zur Erzielung einer therapeutischen Wirkung bei vollständiger Bioverfügbarkeit erforderlich wäre.Finally, numerous drugs are also used because of their low levels Water solubility only to a small extent of the mucosa of the intestinal tract absorbed. In such cases, certain technological treatments of the active ingredient, such as micronization, formation of adsorbates or the addition of Solubilizers an increased absorption can be achieved, However, the The dose to be applied is almost always considerably higher than the amount of active ingredient required to achieve it a therapeutic effect with complete bioavailability would be required.

Es besteht aber ein Bedürfnis, schwer resorbierbare Wirkstoffe nicht nur in Injektionsform, sondern auch in oral applizierbarer Form mit hoher enteraler Resorptionsquote bereitzustellen.However, there is a need to not absorb active ingredients that are difficult to absorb only in injection form, but also in orally administrable form with a high enteral rate Provide absorption rate.

Es wurde nun gefunden, daß sich derartige schwer resorbierbare Wirkstoffe zu einer Arzneiform mit hoher enteraler Resorptionsquote verarbeiten lassen, wenn sie in einem Mono-Diglyzerid-Gemisch von. Fettsäuren, bevorzuge der Kettenlänge C6 - C12, gelöst werden.It has now been found that such difficult to absorb active ingredients can be processed into a dosage form with a high enteral absorption rate, if them in a mono-diglyceride mixture of. Fatty acids, prefer the chain length C6 - C12.

Mono-Diglyzerid-Gemische mittelkettiger Fettsauren eignen sich besonders als Vehikelsubstanzen für schwer re.sorbierbare Stoffe, da sie ausgezeichnete Lösungseigenschaften sowohl für hydrophile als auch für lipophile Substanzen besitzen. Wegen der bekannten Tatsache, daß diese Partialglyzeride nach der Resorption direkt über die Pfortadervenen in den Blutkreislauf weitergeleitet werden, ist gewährleIstet, daß der Wirkstoff im Organismus rasch an den Ort seiner Wirkung gelangt.Mono-diglyceride mixtures of medium-chain fatty acids are particularly suitable as vehicle substances for substances that are difficult to absorb, as they have excellent dissolving properties for both hydrophilic and lipophilic substances. Because of the well-known The fact that these partial glycerides after absorption directly via the portal veins are passed on into the bloodstream, it is guaranteed that the active substance quickly reaches its place of action in the organism.

Falls es aus therapeutischen Gründen erwünscht ist, die Resorption erst im Duodenum beginnen zu lassen, ist es zweckmäßig, das Arzneimittel magensaftresistent zuzubereiten, beispielsweise durch Abfüllen der Wirkstofflösung in eine Gelatine-Kapsel mit magensaftresistentem Überzug.If it is desired for therapeutic reasons, resorption To start only in the duodenum, it is advisable to make the drug enteric-coated to prepare, for example by filling the active ingredient solution into a gelatin capsule with enteric coating.

Dadurch wird sichergestellt, daß die Wirkstoffe an den optimalen Ort ihrer Resorption herangeführt werden und in gelöstem Zustand mit dem Mono-Diglyzerid-Gemisch die Lipidmembran der Mukosa durchdringen.This ensures that the active ingredients are in the optimal place their absorption are brought up and in a dissolved state with the mono-diglyceride mixture penetrate the lipid membrane of the mucosa.

Wird. beispielsweise g-Strophanthin in der erfindungsgemäßen Lösung in dem Mono-Diglyzerid-Gemisch Katzen appliziert, so wird eine Resorptionsquote bis zu 80 % erreicht. Damit wird eine bisher nicht erreichbare orale g-Strophanthin-Therapi e mit einem hohen Maß an Zuverlässigkeit möglich.Will. for example g-strophanthin in the solution according to the invention Applied to cats in the mono-diglyceride mixture, an absorption rate is established reached up to 80%. This is a previously unattainable oral g-strophanthin therapy e possible with a high degree of reliability.

Ferner konnte am Beispiel des schwer resorbierbaren Gestagens lledrogestone gezeigt werden, daß gegenüber einer Tablettenform mit mikronisiertem Wirkstoff ein um ca. 300 % erhöhter Blutspiegel erreicht werden kann, wenn der Wirkstoff in der erfindungsgemäßen Form appliziert wird.Furthermore, using the example of the difficult-to-absorb progestogen Iledrogestone be shown that compared to a tablet form with micronized active ingredient a Blood levels increased by approx. 300% can be achieved if the active ingredient is in the Form according to the invention is applied.

Der Beweis für die erhöhte Resorption der erfindungsgemäß zubereiteten Wirkstoffe wurde für das g-Strophanthin mit dem modifizierten Hatcher-Verfahren (Lenke und Schneider, Arznelmittelforschung, 19 (1969), S. 687-693; 20 (1970), S. 1199-126; 20 (1970), S. 1765-1770) geführt.The proof of the increased absorption of the prepared according to the invention Active ingredients were modified for the g-strophanthin using the hatcher method (Lenke and Schneider, Arznelmittelforschung, 19 (1969), pp. 687-693; 20 (1970), pp. 1199-126; 20 (1970), pp. 1765-1770).

Dazu wurde Katzen beiderlei Geschlechts in Chloralose-Urethan-Narkose 100 ng/kg Strophanthin in der erfindungsgemäßen Zubereitung intraduodenal appliziert (bei einer solchen Dosis, die sonst nicht tödlich wirkt, starben bereits 2 von 34 Katzen). 4 Stunden danach wurde mittels i.v. Infusion bis zum Herzstillstand "aufgefüllt". Je nach vorgegebener Überlebenzeit ergaben sich dabei mittlere statistische Resorptionsquoten von 60 - 80 %.For this purpose, cats of both sexes were anesthetized with chloralose urethane 100 ng / kg strophanthin administered intraduodenally in the preparation according to the invention (At such a dose, which is otherwise not fatal, 2 out of 34 died Cats). 4 hours later, i.v. Infusion "filled up" to cardiac arrest. Average statistical resorption rates were obtained depending on the given survival time from 60 - 80%.

intraduodenale vorgegebene errechnete enterale Applikation Überlebens- (mittlere) Wirksamzeit (min) Strophanthin- keit (%) "Auffüll-Dosis" i.v.intraduodenal predetermined calculated enteral application survival (mean) effective time (min) strophanthinism (%) "top-up dose" i.v.

(g/kg) g-Strophanth-n 50 63,9 80,8 in Witafrol (R) 100 49,7 60,7 100 µg/kg Witafrol0 50 144,7 0;1 mlXkg 100 110,4' Für den Nachweis der erhöhten Resorption von Medrogestone in der erfindungsgemäßen Zubereitung wurden an nüchternen Hunden Medrogestone-Blutspiegeluntersuchungen nach Verabreichung von Medrogestone-Tabletten mit 25 mg mikronisiertem Wirkstoff und Medrogestone-Kapseln mit der gleichen Wirkstoffdosis gelöst in Witafrol durchgeführt. Dabei wurde eine statistisch hoch signifikante Differenz der Serum-Konzentrationen gefunden. (g / kg) g-strophanth-n 50 63.9 80.8 in Witafrol (R) 100 49.7 60.7 100 µg / kg Witafrol0 50 144.7 0; 1 mlXkg 100 110.4 'For the detection of the increased Resorption of medrogestones in the preparation according to the invention were on an empty stomach Dogs with medrogestone blood tests after administration of medrogestone tablets with 25 mg micronized active ingredient and Medrogestone capsules with the same active ingredient dose dissolved in witafrol. This was a statistically highly significant Difference in serum concentrations found.

Die maximalen Medrogestone-Blutspiegelwerte erreichen bei der Kapselform nach 1 Stunde mit 122, ng/ml Serum etwa das 3-fache des Höchstwertes von 35,9 ng/ml Serum nach Medrogestone-Tabletten.The maximum medrogestone blood level values are reached with the capsule form after 1 hour with 122. ng / ml serum about 3 times the maximum value of 35.9 ng / ml Serum after Medrogestone tablets.

thnliche Ergebnisse werden erreicht bei Valethamate-Bromid, Pinaverium-Bromid, Griseofulvin, Testosteron, Anetholtrithion, Aescin oder Valepotriaten als Wirkstoffe, die nur als Beispiele aufzufassen sind, ohne die Erfindung hierauf zu beschränken, vorausgesetzt, daß sich die Wirkstoffe in Mono-Diglyzerid-Gemischen von Fettsäuren ausreichend lösen.Similar results are achieved with valethamate bromide, pinaverium bromide, Griseofulvin, testosterone, anetholtrithione, aescin or valepotriates as active ingredients, which are to be understood as examples only, without restricting the invention to them, provided that the active ingredients are in mono-diglyceride mixtures of fatty acids solve sufficiently.

Die Zubereitung der erfindungsgemäßen Arzneimittel für die Human-Therapie wird durch nachfolgende Beispiele erläutert: Beispiel 1 10 g g-Strophanthin werden in 5 kg Mono-Diglyzerid-Gemisch mit der Kettenlänge C8 - C10 gelöst und in Weichgelatinekapseln mit einer Füllmenge von 250 mg entsprechend 0,5 mg g-Strophanthin pro Kapsel abgefüllt und magensaftresistent überzogen.The preparation of the medicaments according to the invention for human therapy is illustrated by the following examples: Example 1 10 g of g-strophanthin become dissolved in 5 kg mono-diglyceride mixture with the chain length C8 - C10 and in soft gelatin capsules with a filling quantity of 250 mg corresponding to 0.5 mg g-strophanthin per capsule and enteric coated.

Beispiel 2 250 g Medrogestone werden in 5 kg Mono-Diglyzerid-Gemisch mit der Kettenlänge C8 - C10 *) gelöst und in Weichgelatinekapseln mit einer Füllmenge von 500 mg entsprechend 25 mg Medrogestone pro Kapsel abgefüllt.Example 2 250 g of medrogestone are dissolved in 5 kg of mono-diglyceride mixture with the chain length C8 - C10 *) and in soft gelatin capsules with a filling quantity of 500 mg corresponding to 25 mg medrogestone per capsule.

) erhältlich von der Fa. Dynamit Nobel unter dem Tjarenzeichen Witafrol R 7420 ) available from Dynamit Nobel under the Tjaren symbol Witafrol R 7420

Claims (5)

Patentansprüche 1. Oral zu verabreichende Arzneimittel aus schwer resorbierbaren Wirkstoffen, dadurch gekennzeichnet, daß sie die Wirkstoffe in einem Mono-Diglyzerid-Gemisch mittelkettiger Fettsäuren gelöst enthalten. Claims 1. Orally administered drugs from difficult absorbable active ingredients, characterized in that they are the active ingredients in one Contains a mono-diglyceride mixture of medium-chain fatty acids in dissolved form. 2. Arzneimittel nach Anspruch 1, dadurch gekennzeichnet, daß die Fettsäuren eine Kettenlänge von 6 bis 12 C-Atomen haben.2. Medicament according to claim 1, characterized in that the fatty acids have a chain length of 6 to 12 carbon atoms. 3. Arzneimittel nach Anspruch 1 oder 2, dadurch gekennzeichnet, daß der Wirkstoff g-Strophanthin ist.3. Medicament according to claim 1 or 2, characterized in that the active ingredient is g-strophanthin. 4. Arzneimittel nach Anspruch 1 oder 2, dadurch gekennzeichnet, daß der Wirkstoff Medrogestone ist.4. Medicament according to claim 1 or 2, characterized in that the active ingredient is medrogestone. 5. Arzneimittel nach Anspruch 1 oder 2, dadurch gekennzeichnet, daß die Wirkstoffe Valethamate-Bromi, Pinaverium-Bromid, Griseofulvin, Testosteron, Anetholtrithion, Aesci.n oder Valepotriate sind.5. Medicament according to claim 1 or 2, characterized in that the active ingredients valethamate bromi, pinaverium bromide, griseofulvin, testosterone, Are anetholtrithione, aesciōn or valepotriate.
DE19762652508 1976-07-12 1976-11-18 Cardiac glycoside compsns. with good enteric resorption - with the glycoside dissolved or suspended in (mixed) fatty acid partial glycerides Withdrawn DE2652508A1 (en)

Priority Applications (18)

Application Number Priority Date Filing Date Title
DE19762652508 DE2652508A1 (en) 1976-11-18 1976-11-18 Cardiac glycoside compsns. with good enteric resorption - with the glycoside dissolved or suspended in (mixed) fatty acid partial glycerides
IE137977A IE45448B1 (en) 1976-07-12 1977-07-04 Enterally highly-absorbable preparations of cardiac glycosides which by themselves are absorbable with difficulty and process for the production of such preparations
GB2798577A GB1544576A (en) 1976-07-12 1977-07-04 Enterally highly-absorbable preparations of cardiac glycosides which by themselves are absorbable with difficulty and process for the production of such preparations
IL5247277A IL52472A (en) 1976-07-12 1977-07-06 Enterally absorbable preparations of cardiac glycosides and their production
NL7707567A NL7707567A (en) 1976-07-12 1977-07-07 Cardiac glycoside compsns. with good enteric resorption - with the glycoside dissolved or suspended in (mixed) fatty acid partial glycerides
US05/813,456 US4202888A (en) 1976-07-12 1977-07-07 Readily enterally absorbable pharmaceutical compositions of cardiac glycosides and preparation thereof
DD7700199970A DD131344A5 (en) 1976-07-12 1977-07-08 ENTERAL HIGHLY RECESSIBLE PREPARATIONS OF HARD RESORBENT HERZGLYCOSIDES AND METHOD FOR PRODUCING SUCH PREPARATIONS
FR7721073A FR2365338A1 (en) 1976-07-12 1977-07-08 PREPARATIONS WITH A HIGH CAPACITY OF RESORPTION BY ENTERIC ROUTE OF CARDIAC GLYCOSIDES REBUILD WITH DIFFICULTY AND PROCESS FOR MANUFACTURING SUCH PREPARATIONS
PT66789A PT66789B (en) 1976-07-12 1977-07-08 Process for the preparation of pharmaceutical compositionshaving high rate of resorption from heart glicosides for itself hardly resorptive to be parenterically administered
GR53930A GR70745B (en) 1976-07-12 1977-07-09
FI772160A FI57056C (en) 1976-07-12 1977-07-11 FOERFARANDE FOER FRAMSTAELLNING AV ENTERALT HOEGRESORBERBARA PRODUKTER AV I SIG SVAORT RESORBERBARA HJAERTGLYKOSIDER
DK313277A DK313277A (en) 1976-07-12 1977-07-11 PROCEDURE FOR THE PREPARATION OF AN ENTERAL HIGH-RESORBABLE PREPARATION OF HEAVY-RESORTABLE HEART GLUCOSIDES
ES460642A ES460642A1 (en) 1976-07-12 1977-07-11 Readily enterally absorbable pharmaceutical compositions of cardiac glycosides and preparation thereof
NO772444A NO772444L (en) 1976-07-12 1977-07-11 PROCEDURES FOR THE PREPARATION OF ENTERAL HEAT RESORBABLE PREPARATIONS OF DIFFICULT RESORBABLE HEART GLYCOSIDS
NZ18461277A NZ184612A (en) 1976-07-12 1977-07-11 Enterally absorbale preparations containing cardiac glycosides
SE7708040A SE7708040L (en) 1976-07-12 1977-07-11 ENTERAL HIGHLY RESORBABLE PREPARATIONS OF IN AND FOR ANSWER RESPONSIBLE
CA282,536A CA1087985A (en) 1976-07-12 1977-07-12 Readily enterally absorbable pharmaceutical compositions of cardiac glycosides and preparation thereof
JP8335477A JPS5329917A (en) 1976-07-12 1977-07-12 Production of preparating agent wtht high absorbing propety through intestine containing difficult absorbing heart stimulant

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19762652508 DE2652508A1 (en) 1976-11-18 1976-11-18 Cardiac glycoside compsns. with good enteric resorption - with the glycoside dissolved or suspended in (mixed) fatty acid partial glycerides

Publications (1)

Publication Number Publication Date
DE2652508A1 true DE2652508A1 (en) 1978-05-24

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DE19762652508 Withdrawn DE2652508A1 (en) 1976-07-12 1976-11-18 Cardiac glycoside compsns. with good enteric resorption - with the glycoside dissolved or suspended in (mixed) fatty acid partial glycerides

Country Status (1)

Country Link
DE (1) DE2652508A1 (en)

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