SE125128C1

SE125128C1 -

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Publication number: SE125128C1
Authority: SE
Publication date: 1949-01-01

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KLASS 30 h:2/ BESKRIVNING OFFENTLIGG3ORD AV KUNGL. CLASS 30 h: 2 / DESCRIPTION PUBLIC WORD BY KUNGL.

PATENT- OCH REGISTRERINGSVERKET BEVIL1AT DEN 7 APRIL 1949 PATENTTID FRAN DEN 1 JUNI 1944 PUBLICERAT DEN 7 JUNI 1949 Ans. den x/c 1944, nr 454111944. PATENT AND REGISTRATION AGENCY GRANTED ON 7 APRIL 1949 PATENT PERIOD FROM 1 JUNE 1944 PUBLISHED ON 7 JUNE 1949 Ans. on x / c 1944, no. 454111944.

THE JACQUES L()EWE RESEARCH FOUNDATION, INC., NEW YORK, N. Y., ANIERIKAS FORENTA STATER. THE JACQUES L () EWE RESEARCH FOUNDATION, INC., NEW YORK, N. Y., UNITED STATES OF AMERICA.

Satt att framstalla ett terapeutiskt preparat innehallande i vatten 15sliga terapeutiska model for intramuskular eller subkutan injektion samt ett menstruum avsett att anvandas vid framstallningen. Set to prepare a therapeutic preparation containing in water 15 such therapeutic model for intramuscular or subcutaneous injection and a menstrual intended for use in the preparation.

Uppfinaare: G. P. Pitkin. Inventor: G. P. Pitkin.

Foreliggande uppfinning hanfor sig till ett fOrfaringssatt fir framstallning av terapeutiska preparat for intramuskular eller subkutan injektion. Speciellt avser uppfinningen framstallning av preparat, som innehalla olika vattenliisliga terapeutiska medel (ensamma eller kombinerade), sasom stimulantia, narkotika, lugnande medel och antikoagulerande medel, yid vilka det terapeutiska medlet befinner sig ett menstruum (extraheringseller losningsmedel eller barare) av sadan beskaffenhet, att den dosis av det terapeutiska medlet, som kan inforas I kroppen och tidryinden for dess effektiva verkan kan hogeligen alias, jamfort med de hittills ernadda basta resultaten. The present invention relates to an experimental preparation of therapeutic compositions for intramuscular or subcutaneous injection. In particular, the invention relates to the preparation of compositions containing various water-soluble therapeutic agents (alone or in combination), such as stimulants, narcotics, sedatives and anticoagulants, in which the therapeutic agent is in a menstrual (extraction or solubilizing agent or bar) of such a nature that the dose of the therapeutic agent which can be introduced into the body and the time frame for its effective action can be highly aliased, compared with the best results obtained so far.

Uppfinningen innefattar Oxen ett nytt menstruum, avsett att anvandas vid framstallningen av namnda terapeutiska preparat, av sadan beskaffenhet att en ornsesidig paverkan slier mellan menstruet och vissa bestandsdelar i kroppen, speciellt blodet, och varigenom det terapeutiska medlet avskiljes sasom genom en semipermeabel membran, som tillater drogen att verka pa dess normala salt men med en kontrollerad, frail giftverkningar fri hastighet. The invention comprises Taurus a novel menstrual, intended for use in the manufacture of said therapeutic preparations, of such a nature that an adverse effect slides between the menstrual and certain constituents of the body, especially the blood, and thereby separates the therapeutic agent as through a semipermeable membrane, which allows the drug to act on its normal salt but with a controlled, free toxic effects free speed.

Sattet att enligt foreliggande uppfinning framstalla ett terapeutiskt preparat, innehallande ett i vatten losligt terapeutiskt medel for intramuskular eller subkut ant injektion, kannetecknas i huvudsak darav, att man framstaller ett menstruum, innehallande 12 --30 % gelatin, 5-12 % dextros och 0,31,5 % attiksyra, genom gelatinets losning i sterilt, destillerat vatten samt tillsattning av dextrosen och attiksyran till gelatinlosningen, varpa det terapeutiska medlet loses i det framstallda menstruet, lampligen vid en ternperatur av cirka 38° C. Bland de omnamnda terapeutiska medlen ma namnas stimulantia, sasom suprarenin, digitalis, efedrin och adrenalin samt narkotika, sasom morfin, pan topon, dilaudid, kodein, den minnesforlust (amnesia) astadkommande drogen hyoscinhydrobromid, Oven benamnd skopolamin, det lugnande medlet natriumfenobarbital, antikoaguleringsmedlet heparin; de har namnda terapeutiska medlen Oro sadana, att de astadkomma en giftverkan, sa att endast relativt sma doser av dessa droger fO anvandas. The method of preparing a therapeutic composition according to the present invention, containing a water-soluble therapeutic agent for intramuscular or subcutaneous injection, is mainly characterized by the preparation of a menstrual cycle containing 12-30% gelatin, 5-12% dextrose and , 31.5% attic acid, by dissolving the gelatin in sterile, distilled water and adding the dextrose and attic acid to the gelatin solution, the therapeutic agent is dissolved in the produced menstrual period, suitably at a temperature of about 38 ° C. Stimulants such as suprarenin, digitalis, ephedrine and adrenaline as well as drugs such as morphine, pan topon, dilaudid, codeine, the amnesia-inducing drug hyoscin hydrobromide, also called scopolamine, the sedative sodium phenobarbin, anticoagulant; they have the said therapeutic agents Oro such that they produce a toxic effect, so that only relatively small doses of these drugs fO are used.

Vid anvandning av narkotika ha goda resultat ernfitts med pfi foljande sat framstallda losningar: 1) gelatin 15 g, dextrospulver 7,g, attiksyra 0,35 g, suprarenin 200 mg, morfinsulfat 5 g, hyoscin-hydrobromid 90 mg saint destillerat vatten i sO stor mangd, aft blandningen blir 100 cm'; i genomsnitt 1 cm' ax denna losning Or lamplig dosis for att anvandas fore operation i kirurgiska fall. 2) Suprarenin 2 mg, hyoscin-hydrobromid 0,9 mg, morfinsulfat 50 mg, gelatin 150 mg, dextros 75 mg, attiksyra 3,5 mg, destillerat vatten 1 cm'. Denna sammansattning Or sfirskilt lamp-hg for kirurgiska fall, da man an-vander rygginargsbedovning, for att minska radslan, fall i blodtrycket, chock och smarta efter operationen. Vid inhalationsbeayningsmedel kan mangden suprarenin per cm' minskas till 0,3 mg utan att paverka verkningstiden for morfinen eller skopolaminen. Om hjartverksamheten Or lag (langsam), kan efedrin (50 mg) inforas i stallet for suprarenin. Ingredienserna i losningen kunna kombineras pa foljande sat: 15 g gelatin losas i BO cm' steriIt, destillerat vatten Over ett vattenbad, i vilket ternperaturen Mlles mellan 85 och 90° C. Ternperaturen far falla till mellan 50 och 55°, nar dextrosen, attiksyran och en procent isoamyl-hydrocuprein (eucupin)-dihydroklorid (anestetiskt konserveringsmedel) tillsattes f Or att forhindra oxidation av attiksyran, nar den upphettas, varjamte en tillracklig mangd vat-ten tillsattes for att det hela skall bliva 95 cm'. Vatskan placeras i sterila behallare och fOr- varas, underkastas prov pa bakteriefororening 2— — och provas aven for yaraktigheten av viskositeten. Sasom tidigare namnts, ãr losningen anvandbar for varje terapeutiskt medel, som vanligen anyandes f8r intramuskular eller subkutan injektion. Om losningen befinnes tillfredsstallande, uppvarmes den till c:a 40° C, :suprareninet, hyoscin-hydrobromiden och morfinen tillsattas, losas under omroring och en tillracklig mangd destillerat vatten tillsattes slutligen, sa att hela yolymen blir 100 cm'. Emellertid är det lampligare att framstalla ett menstruum med dubbel styrka och likaledes en losning av det terapeutiska medlet med dubbel styrka och att darefter sammanblanda dessa tva. Exempelvis kunna 100 cm' menstruum med 32 % gelatin, 15 % dextros och 1 % attiksyra beredas pa foljande satt: Till 320 g medicinskt rent gelatin s5.ttas 4 kallt, sterilt, destillerat vatten och omrorning sker konstant, sa att alla gelatinpartiklar fuktas. Gelatinet smaltes pa ett vattenbad och eventuella klumpar gnuggas bort. Om sh onskas, kan gelatinlosningen underkastas vakuum for borttagande av luftblasor, varefter den kyles, Mr stelna, anyo gores yalskeformig, anyo behandlas med vakuum saint sedan uppvarmes. 150 g dextros i pulveriserat skick sates till gelatinl5sningen, vilken ornrores tills dextrosen gatt i losning; eller ock kan man tillsatta 150 cm' klar glykos. Oin sa. onskas, kan lOsningen kokas i vakuum. Masson silas och 10 cm' isattiksyra tillsattas. Hartill är det lampligt att satta 2 g eucupin samt att omrora, tills den gatt I losning, varefter man for att forhindra fororening (bakteriesmitta) till-salter 10-50 cm' av 10 %-ig klorbutanol i alkohol (antiseptiskt konserveringsmedel). Lasningen utspades till 1000 cm'. Den utgor en fast kropp vid rumstemperatur. NO.r det anvanda terapeutiska medlet är stimulerande, narkotiskt eller lugnande (sasom t. ex. de ovan omnamnda medlen. eller andra av analog karaktar och med analoga. egenskaper) 18ses den onskade mangden av medlet eller medlen i 900 cm' destillerat vatten och darafter skall .dess temperatur aldrig hoj as Over 43° C, och lampligen icke Over 38° C. Gelatinblandningen uppvarmes till approximativt 38° C och den andra losningen utspades till 1000 cm'. De hada losningarna blandas omsorgsfullt, sa. ,att procenttalet f Or komponentema nedgar till half ten; blandningen far svalna, gores darefter any-o -vatskefornaig och insmaltes i ampuller. Ampullerna tillslutas under vakuum eller ock later man syret ersattas av kvave. When using drugs, good results have been obtained with the following solutions prepared: 1) gelatin 15 g, dextrose powder 7, g, acetic acid 0.35 g, suprarenin 200 mg, morphine sulphate 5 g, hyoscin hydrobromide 90 mg of saint distilled water in 50 g large amount, aft the mixture becomes 100 cm '; on average 1 cm 'ax this solution Or appropriate dose to be used before surgery in surgical cases. 2) Suprarenin 2 mg, hyoscin hydrobromide 0.9 mg, morphine sulphate 50 mg, gelatin 150 mg, dextrose 75 mg, attic acid 3.5 mg, distilled water 1 cm 2. This composition is especially useful for surgical cases, when spinal anesthesia is used, to reduce radar, drops in blood pressure, shock and pain after surgery. With inhalation inhibitors, the amount of suprarenin per cm 2 can be reduced to 0.3 mg without affecting the duration of action of the morphine or scopolamine. About the heart activity Or lag (slow), ephedrine (50 mg) can be introduced in the stable of suprarenin. The ingredients of the solution can be combined in the following way: 15 g of gelatin are dissolved in BO cm 'sterile, distilled water Over a water bath, in which the temperature is measured between 85 and 90 ° C. The temperature may drop to between 50 and 55 °, when the dextrose, the acetic acid and one percent isoamyl-hydrocuprein (eucupine) dihydrochloride (anesthetic preservative) was added to prevent oxidation of the attic acid when heated, and a sufficient amount of water was added to make the whole 95 cm 3. The liquid is placed in sterile containers and stored, subjected to tests for bacterial contamination 2 - and also tested for the accuracy of the viscosity. As previously mentioned, the solution is useful for any therapeutic agent, as is usually the case for intramuscular or subcutaneous injection. If the solution is found to be satisfactory, it is heated to about 40 ° C, the suprarenin, the hyoscin hydrobromide and the morphine are added, dissolved with stirring and a sufficient amount of distilled water is finally added so that the whole volume is 100 cm 3. However, it is more convenient to produce a double-strength menstrual and also a solution of the double-strength therapeutic agent and then to mix the two. For example, 100 cm of menstrual with 32% gelatin, 15% dextrose and 1% acetic acid can be prepared as follows: To 320 g of medically pure gelatin is added 4 cold, sterile, distilled water and stirring is done constantly, so that all gelatin particles are moistened. The gelatin was melted on a water bath and any lumps were rubbed off. If desired, the gelatin solution can be subjected to vacuum to remove air bubbles, after which it is cooled, Mr solidified, anyo gores yellowish, anyo treated with vacuum saint then heated. 150 g of dextrose in powdered state is added to the gelatin solution, which is stirred until the dextrose has dissolved; or you can add 150 cm 3 of clear glucose. Oin sa. if desired, the solution can be boiled in vacuo. Masson is filtered and 10 cm 3 of glacial acetic acid are added. To this end, it is advisable to add 2 g of eucupine and to stir until it has dissolved, after which 10-50 cm 3 of 10% chlorobutanol in alcohol (antiseptic preservative) are added to prevent contamination (bacterial infection). The weld was diluted to 1000 cm 3. It forms a solid body at room temperature. If the therapeutic agent used is stimulating, narcotic or sedative (such as the above-mentioned agents or others of an analogous nature and having analogous properties), the desired amount of the agent or agents is present in 900 cm 3 of distilled water and thereafter, its temperature should never rise above 43 ° C, and probably not above 38 ° C. The gelatin mixture is heated to approximately 38 ° C and the second solution is diluted to 1000 cm 3. The hated solutions are mixed thoroughly, he said. , that the percentage f Or the components decrease to half ten; the mixture is allowed to cool, then made into any-o -vatskefornaig and dissolved in ampoules. The ampoules are closed under vacuum or the oxygen is replaced by nitrogen.

Om gelatinet icke utsattes f8r h5gre varme eller kokas, bevaras den ljusa barnstensfargen. Klorbutanol kan inforlivas i den andra losningen, om sA. onskas. Den alkohol, vani klorbutanolen är lost, verkar sasom ett konserveringsmedel och ett hardningsmedel for gelatinet. Den forhindrar att massan blir flytande med tiden. Det är lampligt att anvan da lika mangder av de hada lOsningarna, ehuru detta icke an nodvandigt, och procentsatserna kunna variera pa. nedan angivet satt. Vidstrackt anvandning ay heparin, som an ett viktigt medel for forebyggande och botande av blodpropp (trombosis) och tendenser hartill, har forhindrats av nodvandigheten att anvanda detta lakemedel genom kontinuerlig venos droppning eller genom upprepade intravenosa injektioner. Denna besvarliga och dyrbara teknik, som krAver konstant kontroll av utbildad personal och bast utfores p0. ett sjukhus, kan icke anvandas under de langvariga behandlingar, som 5.ro nodvandiga fOr vissa trombotiska tillstand. Dessutom skulle de enorma mangder heparin, som erfordras vid denna teknik for ernaende av erforderlig terapeutisk niva, medfora kostn.ader, som ofta forhindra anvandningen av detta vardefulla medel. Genom att heparin, inkorporerat i det nya menstruet enligt uppfinningen, infores I kroppen subkutant eller intramuskulart, ernas en langsam och jamn frigoring av heparinet, anvandningen av lakemedlet forenklas och det for ernaende av de onskade resultaten erforderliga kvantumet heparin minskas vasentligt. Pa detta satt kan heparin alltsh sakert, praktiskt och ekonomiskt aavandas under langa tidsperioder. If the gelatin is not exposed to higher heat or boiled, the light amber color is preserved. Chlorobutanol can be incorporated into the second solution, if sA. onskas. The alcohol, vani chlorobutanol is dissolved, acts as a preservative and a hardener for the gelatin. It prevents the mass from becoming liquid over time. It is appropriate to use equal amounts of the solutions provided, although this is not necessary, and the percentages may vary. set below set. Extensive use of heparin, as an important agent for the prevention and cure of blood clots (thrombosis) and its tendencies, has been prevented by the necessity of using this drug by continuous venous drip or by repeated intravenous injections. This costly and expensive technology, which requires constant control of trained personnel and is carried out p0. a hospital, can not be used during the long-term treatments, which are necessary for certain thrombotic conditions. In addition, the enormous amounts of heparin required in this technique to achieve the required therapeutic level would entail costs which often prevent the use of this valuable agent. By introducing heparin, incorporated into the new menstrual cycle according to the invention, into the body subcutaneously or intramuscularly, a slow and even release of the heparin, the use of the drug is simplified and the quantity of heparin required to achieve the desired results is significantly reduced. In this way, heparin can be used safely, practically and economically for long periods of time.

Framstallning av ampuller innehallande heparin kan ske p0. fOljande salt: Menstruum av dubbel styrka beredes pa ovan angivet salt. Heparinlosningen beredes genom att epinefrin loses i nagra fa droppar 19 %-ig HC1, varefter destillerat vatten tillfores i tillrãcklig mangd for att losa efedrinsulfat, eucupin-dihydroklorid, klorbutanol och heparin. Harefter tillsattes tillraeldigt mycket destillerat yatten for an giva den for dubbel styrka erforderliga volymen och slutligen tillsattes menstruet, sa att den slutliga volymen erhalles. En lamplig sammansattning Kristalliserat natriumsalt av heparin 100,o mg Epinefrin-hydroklorid 1,0 » Efedrin-sulf at 23,o » Klorbutanol 0,» Eucupin-dihydroklorid 1,o » Menstruum ay dubbel styrka q.s. ad. 2,o cm° Dubbla mangden heparin kan anvandas; de karlsammandragande amnena epinefrin-hydroklorid och efedrinsulfat kunna utelamnas, om de icke aro onskvarda, och kvantiteten menstruum kan minskas till ungefar halften, men da tenderar heparinet att forbliya i kristallform. Efter omsorgsfull blandning fylles produkten i narvaro ay kvave pa ambrafargade (barnstensfargade) ampuller och utsattes f8r angsterilisering under tre pa varandra f01- jande dagar under 15 min. varje dag. Varje sats underkastas sterilitetsproy och kontrol.. av pH-vardet. — —3 Ehuru losningar kunna beredas med en sammanhallande, seg substans, shsom gelatin, for att astadkomma i huvudsak en molekylar inkapsling av drogen vid injektion, liar det utronts att nar preparaten beredas med gelatin enbart och injicieras i kroppen, de icke bibehollo sina viskosa, sammanhallande egenskaper yid kontakt med de alkaliska kroppsvatskorna. Den. geleliknande massa, som bildades, var nagot kornig, brots ned vid latt tryck och var nastan oloslig. Den liknar kommersiellt gelatin till utseendet och har lik- nande styrka. Den forsamringgelatinet, som astadkommes i levande vavnader, kan demonstreras genom att neddoppa rent gelatin i citratblod, blodserum eller vattenlosning och hâlla det vid kroppstemperatur under 3 a 4 timmar. Genom att de sammanhallande egenskaperna ga fOrlorade, sker darf Or en fOr tidig frigoring eller utlosning av de terapeutiska medlen. Det liar utronts att cm losningen surgores pled 99 %-ig attiksyra i tillracklig mangd for att hstadkomma ett pH-varde forenligt med kroppsvavnaden, t. ex, 7 a losningens viskositet kan bibehallas under en langre tid och verkan av de terapeutiska medlen utstrackas i samma forhallande. Det har vidare utronts att omdextros till- sattes till losningen, dennas forsamring kan fOrhindras oeh dess adhesivverkan forlangas till och Over 24 timmar. Genom att Oka alla tre ingredienserna till olika styrkor kan primarabsorption fordroj as under 3 a. 4 timmar och den totals_ elimineringen forhindras vida mer an 42 timmar. Dessutom har man fun-nit, att attiksyran genom att bryta ned de rOda blodkropparna skapar en relativt neutral zon, som salunda fOrbattrar eller fOrstarker den semipermeabla viskosa skiljevaggen eller membranen och i varje fall fororsakar att drogmangden i sin helhet inkapslas; detta utgor det andra fordrojnings- och kontrollsteget for medlets absorption. Ampoules containing heparin can be prepared p0. THE FOLLOWING SALT: Double-strength menstrual menstruation is prepared on the salt indicated above. The heparin solution is prepared by dissolving epinephrine in a few drops of 19% HCl, after which distilled water is added in a sufficient amount to dissolve ephedrine sulphate, eucupine dihydrochloride, chlorobutanol and heparin. Then a sufficiently much distilled yatten was added to give the volume required for double strength, and finally the menstrual period was added so that the final volume was obtained. A suitable composition Crystallized sodium salt of heparin 100, o mg Epinephrine hydrochloride 1.0 »Ephedrine sulf at 23, o» Chlorobutanol 0, »Eucupine dihydrochloride 1, o» Menstruum ay double strength q.s. A.D. 2.0 cm Double the amount of heparin can be used; the male astringents epinephrine hydrochloride and ephedrine sulphate can be omitted if they are not unsightly, and the quantity of menstruum can be reduced to about half, but then the heparin tends to remain in crystalline form. After thorough mixing, the product is filled in the presence of nitrogen on amber-colored (amber-colored) ampoules and subjected to anxiety sterilization for three consecutive days for 15 minutes. every day. Each batch is subjected to sterility spray and control .. by the pH value. Although solutions can be prepared with a cohesive, tough substance, such as gelatin, to effect essentially a molecular encapsulation of the drug upon injection, it is believed that when the preparations are formulated with gelatin alone and injected into the body, they do not retain their viscous , cohesive properties yid contact with the alkaline body washes. The. gel-like mass, which formed, was somewhat grainy, broke down at light pressure and was almost insoluble. It resembles commercial gelatin in appearance and has similar strength. The pre-aggregation gelatin, which is produced in living tissues, can be demonstrated by immersing pure gelatin in citrate blood, blood serum or aqueous solution and keeping it at body temperature for 3 to 4 hours. As the cohesive properties are lost, premature release or release of the therapeutic agents must take place. It has been found that the solution is acidified with 99% attic acid in a sufficient amount to achieve a pH value compatible with the body tissue, e.g., the viscosity of the solution can be maintained for a long time and the effect of the therapeutic agents is extended in the same procrastinating. It has further been suggested that omdextrose was added to the solution, its pre-aggregation can be prevented and its adhesive action required for up to 24 hours. By increasing all three ingredients to different strengths, primary absorption can be delayed for 3 to 4 hours and the total elimination is prevented by far more than 42 hours. In addition, it has been found that the attic acid, by breaking down the red blood cells, creates a relatively neutral zone, which thus improves or strengthens the semipermeable viscous septum or membranes and in any case causes the amount of drug to be encapsulated in its entirety; this constitutes the second step of displacement and control of the absorption of the agent.

Det har utronts att stabila, palitliga, intramuskulart eller subkutant anvandbara lOsningar kunna framstallas genom att dari inkludera ett sammanhallande adhesivmedel, lampligen av gelatinkaraktar, surgjort med attiksyra och forstarkt med dextros f8r att Oka och stabilisera dess viskositet tillrackligt mycket utan att vasentligen forhindra absorption av de terapeutiska medicinska amnena, och f Or att fOrlanga och fordroja frigorandet av terapeutiska amnen eller medel, sasom heparin, suprarenin, morfin och/eller skopolamin under en avsevard tidrymd utan att fordrOja deras eliminering, sedan deras terapeutiska funktioner fullgjorts. I allmanhet kunna vasentliga avvikelser goras i de anvanda proportionerna. Dessa proportioner kunna avsevart varieras beroende ph olika faktorer, av vilka vissa omsesidigt paverka varandra. Bland dessa faktorer Oro egenskaperna hos den specielle patient, som behandlas, patien tens ,allmanna tillstand, den grad av kansloloshet eller bedovning, som skall astadkommas, det blodtryck, som skall uppratthallas, behandlingens varaktighet, beskaffenheten av de anvanda terapeutiska medlen, lakarens teknik och uppfattning, och talrika andra faktorer. De lampligaste losningarna innehalla i viktsprocent: 12-Vo gelatin, 5-12 % dextros, 0,3-1,5 % attiksyra for ernaende av ett med kroppsvavnaderna forenligt pH-varde, t. ex. 7 0 8, den vattenlosliga drogen eller drogerna samt destillerat vatten. Dylika mangder gelatin, dextros och attiksyra ha befunnits tillrackliga for att forstarka losningen och reglera elimineringen av de terapeutiska medlen fran 24 till 30 timmar. It has been contemplated that stable, palatable, intramuscular or subcutaneously useful solutions may be prepared by including a cohesive adhesive, preferably of gelatin character, acidified with acetic acid and fortified with dextrose to increase and stabilize its viscosity sufficiently without absorbing it sufficiently. therapeutic medicinal substances, and for prolonging and delaying the release of therapeutic substances or agents, such as heparin, suprarenin, morphine and / or scopolamine for a considerable period of time without requiring their elimination, after their therapeutic functions have been performed. In general, significant deviations can be made in the proportions used. These proportions can be considerably varied depending on different factors, some of which mutually influence each other. These factors include concerns about the characteristics of the particular patient being treated, the patient's condition, general condition, the degree of unconsciousness or anesthesia to be achieved, the blood pressure to be maintained, the duration of treatment, the nature of the therapeutic agents used, the physician's technique and perception, and numerous other factors. The most suitable solutions contain by weight: 12-Vo gelatin, 5-12% dextrose, 0.3-1.5% acetic acid to obtain a pH value compatible with the body tissues, e.g. 7 0 8, the water-soluble drug or drugs and distilled water. Such amounts of gelatin, dextrose and acetic acid have been found to be sufficient to enhance the release and regulate the elimination of the therapeutic agents from 24 to 30 hours.

Enar menstruet Or vattenhaltigt, bora de anvanda medlen. vara tillrackligt vattenlosliga for att bibehalla spanningslikhet eller tonicitet (osmotiskt tryck) med losningen for att f Orhindra nagon drog fran att fallas ut, nar blandningen har statt under en langre tid. Till foljd av menstruets sammansattning sker en inkapsling av drogen eller det terapeutiska medlet i tva stadier eller steg, f5rst molekylar inkapsling eller inkapsling i finfordelat tillstand med tillhj alp av en viskOs vehikel, vans viskositet icke far vara sa lag, att den tillater alltfor hastig frigoring av medlet och icke sa hog, att den retarderar frigaringen av medlet sh mycket, att dess effektivitet reduceras. Det Or att observera, att gelatin, dextros och attiksyra samverka for astadkommande air onskad viskositet. Detta forsta inkapslingssteg Or icke tillrackligt f Or ernhende av de har asyftade resultaten, enar det icke Or tillrackligt stabilt under vasentlig tidslangd och kan fkorsaka for tidig frigoring av drogen med darav foljande icke-onskvarda resultat, sasom ovan framhallits. Det andra inkapslingssteget Or inkapsling i massa, alltsa av medlet i dess helhet, ph grund av verkan av attiksyran i narbelagna delar av vavnaderna och harigenom astadkommes full kontroll under en Hug tidsperiocl utan flagon osaker och slumpvis verkan. Molekylarinkapslingen Or emellertid viktig for kontroll under den tid, under vilken attiksyran kan verka, och astadkommer frigoring av attiksyran, sedan den injicierade massan liar bildat en ficka i vavnaden, sh att de erforderliga stabila forhallandena for inkapsling av drogmassan dess helhet har astadkommits. Den hemolytiska (blodlosliga) membranen for inkapslingen forsvinner vanligen ph tva 0 fyra dagar. Unite menstruation Or aqueous, drill the used means. be sufficiently water-soluble to maintain tension similarity or tonicity (osmotic pressure) with the solution to prevent any substance from falling out when the mixture has been standing for a long time. As a result of the composition of the menstrual cycle, the drug or therapeutic agent is encapsulated in two stages or steps, first molecules are encapsulated or encapsulated in a finely divided state with the aid of a viscous vehicle, the viscosity of which must not be so low as to allow too rapid release. of the agent and not so high that it retards the release of the agent sh much, that its efficiency is reduced. It should be noted that gelatin, dextrose and acetic acid work together to achieve desired air viscosity. This initial encapsulation step is insufficient to obtain any of the intended results, it is not sufficiently stable for a significant period of time and may cause premature release of the drug with consequent undesirable results, as noted above. The second encapsulation step Or encapsulation in pulp, i.e. of the agent as a whole, ph due to the action of the attic acid in adjacent parts of the tissues and thereby achieves full control during a Hug period of time without flawlessness and random effect. However, the molecular encapsulation is important for control during the time during which the attic acid can act, and provides release of the attic acid, after the injected mass has formed a pocket in the tissue, so that the necessary stable conditions for encapsulation of the drug mass as a whole have been achieved. The hemolytic (bloodless) membrane of the encapsulation usually disappears at two to four days.

Kliniska experiment ha visat, att den nya subkutant anvandbara losningen, som Or verksam tillsammans med de fiesta terapeutiska medel, som anvandas for subkutant eller intramuskulart bruk, forlanger de terapeutiska verkningarna av narkotika, sasom morfin, pantopon, kodein, dilaudid och lugnande medel frau de hittills sasom maximala — — ansedda tre a fyra timmarna till 24-36 timmar, sarntidigt som mojligheterna eller riskerna for giftverkningar undanroj as. Relativt stora doser morfin, t. ex. 005 g med 0,065 g pantopon, kan anvandas och behandlingen med heparin ken vasentligt forbattras. Nar mera an en dreg tillsattes for terapeutiska andamai, frigoras dessa droger fran losningen och absorberas i kroppsvavnaderna eller vatskorna i omsesidigt beroende av -varandra; d. v. s. en. drog kan icke frigtiras mera eller absorberas hastigare an de andra medfoljande drogerna. Clinical experiments have shown that the new subcutaneously useful solution, which is effective in conjunction with most therapeutic agents used for subcutaneous or intramuscular use, requires the therapeutic effects of drugs such as morphine, pantopone, codeine, diludid and sedatives. hitherto as the maximum - - considered three to four hours to 24-36 hours, as long as the possibilities or risks of toxic effects are eliminated. Relatively large doses of morphine, e.g. 005 g with 0.065 g pantopone, can be used and the treatment with heparin ken significantly improved. When more than one drug is added for therapeutic purposes, these drugs are released from the solution and absorbed into the body tissues or fluids in interdependence; d. v. s. en. drug can no longer be released or absorbed more rapidly than the other accompanying drugs.

De olika ingredienserna och sammansattningarna i denna beskrivning aro endast avsedda sasom exempel och andra kunna vara ekvivalenta harmed Mom ramen for uppfinningen. Det kanske bor tillaggas, att det nya preparatet liknar blodserum, speciellt manniskoblodserum, till sitt utseende och sin konsistens, men har betydligt storre viskositet, varjamte det är pa ett onskvart sat fritt fran olj or, fetter och proteinamnen med undantag av att det innehaller en kolloidal substans, namligen gelatin. Med andra ord liknar det nya preparatet koncentrerat blodserum och har fibrinogen-liknande blodkoagulerande egenskaper med retardation av oxidationen (som normalt sker Mom 20 min.) av sadana instabila terapeutiska medel som adrenalin, efedrin, pituitrin, antuitrin, pitressin, pitoein och andra. Menstruet maste givetvis till slut kunna resorberas av patienten och icke kvarlamna flagon frammande kropp. The various ingredients and compositions of this specification are intended to be exemplary only and others may be equivalent within the scope of the invention. It may be added that the new preparation is similar to blood serum, especially human blood serum, in appearance and consistency, but has a significantly higher viscosity, whereas it is in a black form free from oils, fats and protein substances except that it contains a colloidal substance, namely gelatin. In other words, the new preparation resembles concentrated blood serum and has fibrinogen-like blood coagulating properties with retardation of the oxidation (which normally occurs in 20 minutes) of such unstable therapeutic agents as adrenaline, ephedrine, pituitrin, antuitrin, pitressin, pitoein and others. The menstrual cycle must, of course, eventually be resorbed by the patient and the non-paralyzed flaking foreign body.

Enar gelatin, dextros och attiksyra aro inaktiva utom pa det sattet, att de fungera for att kontrollera frigorandet av drogen eller det terapeutiska medlet, och det synes m8jligt att med fordel anvanda denna blandning med de manga droger, som ovan namnts, är det troligt att den ocksa kan anvandas for liknande andamal tillsammans med vasentligen alla vattenlosliga droger, som aro lampliga for subkutan eller intramuskular injektion, Tare sig de aro redan kanda eller i framtiden kunna bliva upptackta. Both gelatin, dextrose and acetic acid are inactive except that they act to control the release of the drug or therapeutic agent, and it seems possible to use this mixture to advantage with the many drugs mentioned above, it is likely that it can also be used for similar purposes together with substantially all water-soluble drugs, which are suitable for subcutaneous or intramuscular injection, although they may already be known or may be detected in the future.

Claims

Patentanspra.k:

A salt for the preparation of a therapeutic preparation containing a water-soluble therapeutic agent for intramuscular or subcutaneous injection, characterized in that a menstrual preparation containing 12-30% gelatin, 5-12% dextrose and 0.3 —Ls% acetic acid, by dissolving the gelatin in sterile, distilled water and adding the dextrose and acetic acid to the gelatin solution, warps the therapeutic agent to dissolve in the produced menstruation, suitably at a temperature of about 38 ° C.

2. according to claim 1, characterized in that the gelatin solution is subjected to a vacuum for disposing of air bubbles, before the dextrose and the attic acid are dissolved therein.

Salt according to claim 1, characterized in that the gelatin solution is cooled, solidified, liquefied again and subjected to vacuum again, before the dextrose and acetic acid are added, after which the mixture is boiled in vacuo.

4. Set according to some of the preceding patent claims, characterized in that an anesthetic and antiseptic preservative was added to the menstruation.

5. according to claim 1, characterized in that the added therapeutic agent contains one or more of the following suprarenin, digitalis, ephedrine, adrenaline, morphine, pantopone, dilaudid, codeine, hyoscin hydrobromide, sodium phenobarbital and heparin.

6. Set according to patent language 1, characterized in that a male astringent was added to the produced menstruation.

7. A kit according to claim 1, characterized in that the menstruation, containing the therapeutic agent, is allowed to solidify and then anyo gores liquid at a temperature below about 45 ° C and is enclosed in ampoules in the presence of oxygen.

8. A kit according to claim 1, characterized in that the therapeutic agent is dissolved in distilled water before the menstrual period is added, which contains dissolved gelatin, dextrose and acetic acid in a correspondingly higher percentage for dilution with the dissolved therapeutic agent. A menstrual preparation for a therapeutic preparation, intended to be used in the performance of the method according to any one of the preceding claims, characterized in that it contains 12-30% gelatin, 5-12% dextrose and 0.3-1.3% acetic acid, dissolved in distilled water. Stocknolm 191

9. ICungl. Boktr. P. A. Norstedt & Muer 490089