DE917564C - Process for the production of permanent aqueous solutions of khellin - Google Patents

Process for the production of permanent aqueous solutions of khellin

Info

Publication number
DE917564C
DE917564C DEK11413A DEK0011413A DE917564C DE 917564 C DE917564 C DE 917564C DE K11413 A DEK11413 A DE K11413A DE K0011413 A DEK0011413 A DE K0011413A DE 917564 C DE917564 C DE 917564C
Authority
DE
Germany
Prior art keywords
khellin
solution
production
aqueous solutions
water
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
Application number
DEK11413A
Other languages
German (de)
Inventor
Dr Heinz Flammersfeld
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.)
Kali Chemie AG
Original Assignee
Kali Chemie AG
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 AG filed Critical Kali Chemie AG
Priority to DEK11413A priority Critical patent/DE917564C/en
Application granted granted Critical
Publication of DE917564C publication Critical patent/DE917564C/en
Expired legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12Carboxylic acids; Salts or anhydrides thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner

Description

  • Verfahren zur Herstellung von beständigen wäßrigen Lösungen des Khellins Es ist bereits bekannt (vgl. die Zeitschrift »Medizinische Welt« von I95I, Heft 14, 5. 461), daß man Khellinlösungen mittels Theophyllin als Lösungsvermittler (20 mg Khellin mit 120 bis 150 mg Theophyllin in 10 ml Lösung) herstellen kann. Wegen eventueller Nebenwirkungen des Theophyllins, wie Schwindel, Nausea und ähnlicher Erscheinungen, sind diese Lösungen bei der Injektion manchmal unangenehm. Außerdem ist zu berücksichtigen, daß Theophyllin pharmakologische Eigenwirkungen hat, die die des Khellins nicht voll zur Wirkung kommen lassen. Es ist ferner bekannt, 20 mg Khellin mit 400 mg Natriumsalicylat in 10 ml wäßriger Flüssigkeit zu lösen (I. c.).Process for the preparation of stable aqueous solutions of khellin It is already known (cf. the magazine "Medical World" from 195I, issue 14, 5. 461) that you can use khellin solutions using theophylline as a solubilizer (20 mg Can produce khellin with 120 to 150 mg theophylline in 10 ml solution). Because of possible Side effects of theophylline, such as dizziness, nausea and similar phenomena, these solutions are sometimes uncomfortable to inject. In addition, it must be taken into account that theophylline has its own pharmacological effects that those of khellin do not let it come into its own. It is also known to 20 mg of khellin with 400 mg Dissolve sodium salicylate in 10 ml of aqueous liquid (I. c.).
  • Demgegenüber wurde nun gefunden, daß es gelingt, ein Mehrfaches dieser Khellinmenge in 10 ml Flüssigkeit zu lösen, wenn man die Salze der 2, 4-Dioxybenzoesäure mit Alkalien oder starken organischen Basen als Lösungsvermittler verwendet. In contrast, it has now been found that it is possible to achieve a multiple of this Amount of khellin to dissolve in 10 ml of liquid, if one uses the salts of 2, 4-dioxybenzoic acid used with alkalis or strong organic bases as solubilizers.
  • So kann man z. B. in 6,5 ml der wäßrigen Lösung des Dimethylaminsalzes der 2, 4-Dioxybenzoesäure 110 mg Khellin lösen. Dabei sind die wasserlöslichen Salze der Dioxybenzoesäure mit Alkalien oder starken organischen Basen ungiftig und gut verträglich. So you can z. B. in 6.5 ml of the aqueous solution of the dimethylamine salt Dissolve the 2,4-dioxybenzoic acid 110 mg khellin. Here are the water-soluble salts of dioxybenzoic acid with alkalis or strong organic bases is nontoxic and good compatible.
  • So zeigt beispielsweise ein Kaninchen nach intravenöser Verabreichung von 1,5 g (je Kilogramm Kaninchengewicht) keinerlei Symptome einer toxischen Wirkung. Der pu-Wert der wasserlöslichen Salze der Dioxybenzoesäure mit Alkalien und starken organischen Basen liegt zwischen 5 und 6. Die Herstellung solcher Lösungen sollen folgende Beispiele zeigen: Beispiel I I,6329 g 2, 4-Dioxybenzoesäure wurden in 9,7 ml n-Natronlauge gelöst, 60 mg Khellin zugefügt und mit Wasser auf 20 ml aufgefüllt. Der pn-Wert der Lösung beträgt 5,2.For example, a rabbit shows after intravenous administration of 1.5 g (per kilogram of rabbit weight) no symptoms of a toxic effect. The pu value of the water-soluble salts of dioxybenzoic acid with alkalis and strong organic bases is between 5 and 6. The preparation of such solutions should the following examples show: Example I I, 6329 g of 2,4-dioxybenzoic acid were dissolved in 9.7 ml of n-sodium hydroxide solution, 60 mg of khellin were added and water was added 20 ml filled up. The pn value of the solution is 5.2.
  • Beispiel 2 6,325 g 2, 4-Dioxybenzoesäure wurden mit 1,380 g Lithiumcarbonat in 20 ml Wasser eingetragen. Nachdem Lösung eingetreten war, wurde auf 50 ml aufgefüllt. Der pu-Wert der Lösung beträgt 5,2. In Io ml dieser Flüssigkeit lösen sich 60 mg Khellin. Example 2 6.325 g of 2,4-dioxybenzoic acid were mixed with 1.380 g of lithium carbonate entered in 20 ml of water. After solution had entered, it was made up to 50 ml. The pu value of the solution is 5.2. 60 mg dissolve in 10 ml of this liquid Khellin.
  • Beispiel 3 1,226 g 87,4Ol0iges Diäthanolamin wurden mit 1,6329 g 2, 4-Dioxvbenzoesäure in 10 mol Wasser gelöst. Der pH-Wert der Lösung beträgt 5,2. In der erhaltenen Flüssigkeit wurden in der Wärme insgesamt 6o mg Khellin gelöst. Example 3 1.226 g of 87.4 oily diethanolamine were added with 1.6329 g 2, 4-Dioxvbenzoic acid dissolved in 10 mol of water. The pH of the solution is 5.2. A total of 60 mg of khellin were dissolved in the heat in the liquid obtained.
  • Beispiel 4 I,I620 g 2, 4-Dioxybenzoesäure wurden mit 0,975 g 330/obiger Dimethylaminlösung vermischt und mit Wasser auf 6,5 ml aufgefüllt. Der pn-Wert der Lösung beträgt 5,2. Hierin lösen sich 110 mg Khellin. Example 4 I, 1620 g of 2,4-dioxybenzoic acid were added with 0.975 g of 330 / above Dimethylamine solution mixed and made up to 6.5 ml with water. The pn value of the Solution is 5.2. This dissolves 110 mg of khellin.
  • Beispiel 5 0,98I5 g ßResorcylsäure wurden in 3 ml Wasser suspendiert und 0,6725 g ß-Diäthylaminoäthanol zugefügt. Der pH-Wert der Lösung beträgt 5,2. Hierin wurden 50 mg Khellin bei Zimmertemperatur gelöst. Example 5 0.9815 g of β-resorcylic acid were suspended in 3 ml of water and 0.6725 g of ß-diethylaminoethanol were added. The pH of the solution is 5.2. 50 mg of khellin were dissolved therein at room temperature.
  • Beispiel 6 1,620 g 2, 4-Dioxybenzoesäure wurden in 4 ml Wasser suspendiert, mit 0,975 g 3301obiger Dimethylaminlösung versetzt (pH-Wert = 5,2) und mit Wasser auf 6,5 ml aufgefüllt. Darin wurden 100 mg Khellin gelöst. Example 6 1.620 g of 2,4-dioxybenzoic acid were suspended in 4 ml of water, with 0.975 g of 3301 above dimethylamine solution (pH = 5.2) and with water made up to 6.5 ml. 100 mg of khellin were dissolved in it.
  • I4,2857 g 7001obiger Invertzuckerlösung wurden mit der oben angegebenen Lösung versetzt und hierzu eine Lösung von o,ooI2s g Strophantin in 10 ml Wasser gegeben. Die vereinigten Lösungen wurden auf 50 ml Wasser aufgefüllt. Diese Lösung enthält in 10 mol 114 mg Strophantin, 20 mg Khellin und 2 g Invertzucker. I4.2857 g of 7001 of the above invert sugar solution were mixed with the above Solution is added and for this purpose a solution of 0.012 g strophantine in 10 ml of water given. The combined solutions were made up to 50 ml of water. This solution contains 114 mg strophantine, 20 mg khelline and 2 g invert sugar in 10 mol.
  • Es ist ferner bekannt, gewisse Salze der 2, 4 Dioxybenzoesäuren zum Inlösungbringen folgender ganz bestimmter Stoffgruppen zu verwenden: I. o-Kresyla-glycerinäther, 2. Theophyllin, 3. Lactoflavine (vgl. z. B. die deutschenPatentschriften 8co 876 und 709 I76 sowie die schweizerische Patentschrift 221 459). It is also known to use certain salts of 2, 4 dioxybenzoic acids Bringing the following very specific groups of substances into solution: I. o-cresyla-glycerin ether, 2. Theophylline, 3. Lactoflavine (see e.g. the German patents 8co 876 and 709 I76 as well as Swiss patent specification 221 459).
  • Diese vorerwähnten Stoffgruppen haben jedoch offensichtlich mit Khellin chemisch keinerlei Ähnlichkeit, so daß der Zusatz bestimmter Salze der 2, 4 Dioxybenzoesäuren, wie gemäß der Erfindung, als Lösungsvermittler speziell für Khellin nicht als naheliegend angesehen werden kann, zumal nachweislich verschiedene andere bekannte Lösungsvermittler für organische Substanzen, wie z. B. die Salze von Purinessigsäuren bzw. die Alkalisalze von Aminosäuren, bei Khellin versagen. However, these aforementioned groups of substances obviously have with khellin chemically no similarity, so that the addition of certain salts of the 2, 4 dioxybenzoic acids, as in accordance with the invention, as a solubilizer especially for khellin not as obvious can be viewed, especially since various other known solubilizers have been proven for organic substances such as B. the salts of purine acetic acids or the alkali salts of amino acids, when khellin fails.
  • Auch die bekannte Anwendung von Natriumsalicylat als Lösungsvermittler für Khellin hat gegenüber den Salzen der 2, 4-Dioxybenzoesäure den Nachteil, daß die damit hergestellten Khellinlösungen leicht Kristalle ausscheiden, was in vielen Fällen sehr störend ist. Also the well-known use of sodium salicylate as a solubilizer for khellin has the disadvantage compared to the salts of 2,4-dioxybenzoic acid that the khellin solutions produced with it easily precipitate crystals, which in many Cases is very annoying.
  • Als weiterer Vorteil kommt hinzu, daß die nach der vorliegenden Erfindung gewonnenen Khellinlösungen besonders beständig, gut verträglich und ungiftig sind. Another advantage is that according to the present invention Khellin solutions obtained are particularly stable, well tolerated and non-toxic.

Claims (1)

  1. PATENTANSPRUCH: Verfahren zur Herstellung von beständigen wäßrigen Lösungen des Khellins, dadurch gekennzeichnet, daß als Lösungsvermittler Salze der 2, 4-Dioxybenzoesäure mit Alkalien oder starken organischen Basen Verwendung finden. PATENT CLAIM: Process for the production of resistant aqueous Solutions of khellin, characterized in that salts are used as solubilizers 2, 4-Dioxybenzoic acid with alkalis or strong organic bases are used.
    Angezogene Druckschriften: Deutsche Patentschriften Nr. 709 I76, 8OO 876; schweizerische Patentschrift Nr. 221 459; französische Patentschrift Nr. 88o 132. Attached publications: German patent specifications No. 709 I76, 8OO 876; Swiss Patent No. 221 459; French patent specification no. 88o 132.
DEK11413A 1951-09-26 1951-09-26 Process for the production of permanent aqueous solutions of khellin Expired DE917564C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DEK11413A DE917564C (en) 1951-09-26 1951-09-26 Process for the production of permanent aqueous solutions of khellin

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DEK11413A DE917564C (en) 1951-09-26 1951-09-26 Process for the production of permanent aqueous solutions of khellin

Publications (1)

Publication Number Publication Date
DE917564C true DE917564C (en) 1954-09-06

Family

ID=7213313

Family Applications (1)

Application Number Title Priority Date Filing Date
DEK11413A Expired DE917564C (en) 1951-09-26 1951-09-26 Process for the production of permanent aqueous solutions of khellin

Country Status (1)

Country Link
DE (1) DE917564C (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE951756C (en) * 1952-04-20 1956-10-31 Upha Chem Pharm Praeparate G M Process for the production of concentrated, long-lasting aqueous solutions of furanochromones
EP0031561A2 (en) * 1979-12-20 1981-07-08 Merck & Co. Inc. A rectally administered suppository comprising a drug and an adjuvant

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE709176C (en) * 1937-12-08 1941-08-08 Chemisch Pharmazeutische A G B Process for the production of long-life aqueous solutions containing k-strophanthin, theophylline and grape sugar
CH221459A (en) * 1940-05-25 1942-05-31 Chemiewerk Homburg Aktiengesel Process for the preparation of a solvent for theophylline.
FR880132A (en) * 1941-11-11 1943-03-15 Improvements to devices such as obliterating pliers
DE800876C (en) * 1949-09-06 1950-12-11 Mack Chem Pharm Process for the production of durable, aqueous solutions of o-cresyl-ªÍ-glycerine ether

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE709176C (en) * 1937-12-08 1941-08-08 Chemisch Pharmazeutische A G B Process for the production of long-life aqueous solutions containing k-strophanthin, theophylline and grape sugar
CH221459A (en) * 1940-05-25 1942-05-31 Chemiewerk Homburg Aktiengesel Process for the preparation of a solvent for theophylline.
FR880132A (en) * 1941-11-11 1943-03-15 Improvements to devices such as obliterating pliers
DE800876C (en) * 1949-09-06 1950-12-11 Mack Chem Pharm Process for the production of durable, aqueous solutions of o-cresyl-ªÍ-glycerine ether

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE951756C (en) * 1952-04-20 1956-10-31 Upha Chem Pharm Praeparate G M Process for the production of concentrated, long-lasting aqueous solutions of furanochromones
EP0031561A2 (en) * 1979-12-20 1981-07-08 Merck & Co. Inc. A rectally administered suppository comprising a drug and an adjuvant
EP0031561A3 (en) * 1979-12-20 1982-08-11 Merck & Co. Inc. A rectally administered drug form comprising a drug and an adjuvant
DK156121B (en) * 1979-12-20 1989-06-26 Merck & Co Inc PROCEDURE FOR PREPARING A RECTAL ADMINISTRATIVE SUPPLY WITH A ADJUVANCE

Similar Documents

Publication Publication Date Title
DE917564C (en) Process for the production of permanent aqueous solutions of khellin
DE753235C (en) Process for the production of aqueous lactoflavin solutions
DE686413C (en) Process for the production of concentrated theophylline and caffeine solutions
DE1470012A1 (en) 7-Theophyllinyl-n-propane-omega-sulfonic acid and a process for its preparation
DE712162C (en) Process for the preparation of new derivatives of p-aminobenzenesulfonamide
DE638030C (en) Process for the production of a concentrated, durable, aqueous theophylline solution
DE858455C (en) Process for the production of neutral or weakly acidic solutions of substituted xanthines
DE966373C (en) Process for the production of stable, aqueous solutions from a streptomycin and a sulfanilamide
DE646706C (en) Process for the preparation of substituted 6, 7-dioxy-1, 2, 3, 4-tetrahydroisoquinoline-1-carboxylic acids
DE722340C (en) Process for the preparation of an arsenic-containing azo compound
DE904652C (en) Process for the production of concentrated, durable aqueous solutions of furanochromones
DE954726C (en) Process for the production of complex compounds of calcium
AT211958B (en) Process for the production of pure neomycin or its salts
DE831882C (en) Process for the production of concentrated, injectable and undecomposed sterilizable solutions of iron (3) polyoxycarboxylic acid complex compounds
DE749305C (en) Process for the preparation of ªÏ-methylsulfonic acids from tetrahydroquinoline bases
DE1076891B (en) Process for the preparation of stable aqueous solutions for injection of sulfapyrimidine
DE556368C (en) Process for the preparation of readily soluble sodium salts of acylaminophenolar acids
AT133143B (en) Process for the preparation of readily soluble sodium salts of 4-oxy-3-acylaminobenzolaric acids (1) or their substitution products.
DE951756C (en) Process for the production of concentrated, long-lasting aqueous solutions of furanochromones
DE936110C (en) Process for the preparation of stable aqueous solutions of dihydrostreptomycin salts
DE907056C (en) Process for the preparation of salts of the esters from N-substituted aminoalkanols and substituted or unsubstituted p-aminobenzoic acid
DE881858C (en) Process for the preparation of solutions of sulfathiourea
DE944953C (en) Process for the preparation of a therapeutic agent consisting of the calcium salt of Ca-ethylene diamine tetraacetic acid
AT67679B (en) Process for the preparation of alkali-soluble derivatives of piaselenol.
AT133505B (en) Process for the preparation of ω-Oxyacylaminobenzolarsin- or -stibinoxden or ω-Oxyacylaminobenzolarsin- or -stibinsäuren.