DE2003914A1 - Immunochemical product for killing cancer cells - Google Patents
Immunochemical product for killing cancer cellsInfo
- Publication number
- DE2003914A1 DE2003914A1 DE19702003914 DE2003914A DE2003914A1 DE 2003914 A1 DE2003914 A1 DE 2003914A1 DE 19702003914 DE19702003914 DE 19702003914 DE 2003914 A DE2003914 A DE 2003914A DE 2003914 A1 DE2003914 A1 DE 2003914A1
- Authority
- DE
- Germany
- Prior art keywords
- helix
- cancer cells
- immunochemical
- agglutinins
- phosphate
- 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.)
- Pending
Links
- 230000000984 immunochemical effect Effects 0.000 title claims abstract description 12
- 206010028980 Neoplasm Diseases 0.000 title abstract description 48
- 201000011510 cancer Diseases 0.000 title abstract description 40
- 239000000910 agglutinin Substances 0.000 claims abstract description 18
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 10
- 229910019142 PO4 Inorganic materials 0.000 claims abstract description 4
- 229960003964 deoxycholic acid Drugs 0.000 claims abstract description 4
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 claims abstract description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims abstract description 4
- 239000010452 phosphate Substances 0.000 claims abstract description 4
- 238000003756 stirring Methods 0.000 claims abstract description 4
- 101710186708 Agglutinin Proteins 0.000 claims abstract description 3
- 101710146024 Horcolin Proteins 0.000 claims abstract description 3
- 101710189395 Lectin Proteins 0.000 claims abstract description 3
- 101710179758 Mannose-specific lectin Proteins 0.000 claims abstract description 3
- 101710150763 Mannose-specific lectin 1 Proteins 0.000 claims abstract description 3
- 101710150745 Mannose-specific lectin 2 Proteins 0.000 claims abstract description 3
- 229940009976 deoxycholate Drugs 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 7
- 239000000243 solution Substances 0.000 claims description 6
- 239000003613 bile acid Substances 0.000 claims description 5
- 230000005880 cancer cell killing Effects 0.000 claims description 4
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims description 4
- 239000002953 phosphate buffered saline Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 2
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims 1
- 239000012266 salt solution Substances 0.000 claims 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 abstract description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 abstract description 4
- 206010020843 Hyperthermia Diseases 0.000 abstract description 4
- 239000008280 blood Substances 0.000 abstract description 4
- 210000004369 blood Anatomy 0.000 abstract description 4
- 239000008103 glucose Substances 0.000 abstract description 4
- 230000036031 hyperthermia Effects 0.000 abstract description 4
- 102000004190 Enzymes Human genes 0.000 abstract description 2
- 108090000790 Enzymes Proteins 0.000 abstract description 2
- 238000001802 infusion Methods 0.000 abstract description 2
- 230000002132 lysosomal effect Effects 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 abstract description 2
- 239000011780 sodium chloride Substances 0.000 abstract 2
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 230000001472 cytotoxic effect Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 38
- 239000000126 substance Substances 0.000 description 6
- 239000002253 acid Substances 0.000 description 3
- 231100000614 poison Toxicity 0.000 description 3
- 239000002574 poison Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 1
- 101710112752 Cytotoxin Proteins 0.000 description 1
- 241000237858 Gastropoda Species 0.000 description 1
- 206010020601 Hyperchlorhydria Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- -1 bile acid derivative deoxycholate Chemical class 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000003157 cancerolytic effect Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000009102 step therapy Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
Abstract
Description
Immunochen@@rches Pharmakon zur Abtätigung von Kristallen und Verfahren zu seiner Herstellung Die Erfinsungbetrifft ein immunochemisches Pharmakon zur selektiven btötung von Krebszellen von Menschen der Blutgruppen B und 0 und ein Verfahren zur Herstellung dieses Pharmakons.Immunochen @@ rches Pharmacon for the removal of crystals and processes to its production The invention concerns an immunochemical drug for selective killing of cancer cells from people of blood groups B and 0 and a method for Manufacture of this drug.
Zur @@ fu@@ und @vbtung von Tumoren bzw. von Krebszellen sind sowohl e@ @oth@ru@ent sche@@@rucke als such Physikalisch-technische einem @un@smethoden bekannt werden.To @@ fu @@ and @vbtung of tumors or cancer cells are both e @ @ oth @ ru @ ent sche @@@ jerks as looking for physical-technical methods become known.
Bei einer n@u@r@ @s bekannt @@r@@en Krebs-m@rschritt-Therapie wird durch e@ti@derte Tumoräbers@uerung mit einem pH-Wert von @@d 6,0 bis 6,5 durch Verrielfaschung des Slut-Glukosespielels plus Hyd@@rthermie wird selektive isolierierung der Krebszellen im Menschlichen Körper bewirkt.With a n @ u @ r @ @s known @@ r @@ en cancer-m @ rstep therapy becomes through erased tumor erosion with a pH value of 6.0 to 6.5 through verrielfaschung the slut glucose game plus hyd @@ rthermie is selective isolation of cancer cells effected in the human body.
Weiterhin ist es bekannt, das sie wirkungsvolle Abst@tung der Krebszellen in Menschlichen Körper ein Problem ist, das eine @@@ror@@lcih hohe Selektivität der Tiers @ie veringt.Furthermore, it is known that it is effective in eliminating cancer cells There is a problem in the human body that has a high selectivity the Tiers @ie veringt.
Alle Mittel, die zur Abtätung der Krebszellen verwendet werden, müssen so diese ohne schädigung der @@zunden Zellen oder anderer Organe im menschlichen Körper herangebracht werden. Die bischer üblichen krebszellenabtätehren Gifte haben den Nachteil, nicht nur die Krebszellen, sondern auch gesumte Sellen mit zu schäbigen. zur Oberwirkung dieser Schwirigkeit ist es befeits bekannt geworsen, derartige Zellgifte mittels eines Trägers an die Krebszelle daranober in sie Eizeinzuschleppen.All means used to kill cancer cells must be so this without damaging the cells or other organs can be brought up in the human body. The usual cancer cell killers Poisons have the disadvantage not only of cancer cells, but also of fringed cells with too shabby. it is well known to the effect of this difficulty, to carry such cell poisons by means of a carrier to the cancer cell on top of it in their egg.
Die Erfindung hat den Zweck, ein immunochemisches Pharmakon mit Hocherseig selektiven Abtötungweisenschaften Für Krebszellen zu schaffen.The invention has the purpose of an immunochemical pharmaceutical with Hocherseig To create selective killing traits for cancer cells.
Der Erfindung leigt die @@@gase z@@r@n@e, ein @ellgift nach dem Schelepperprinzip an die Krebszellen @eranzubringen und sein Wirksamkeit durch eine gleichzeitige selektive Labilisierung der Krebszellen nochgrasig zu verstärken.The invention leigt the @@@ gases z @@ r @ n @ e, a @ellgift based on the Schelepper principle to the cancer cells @eranz and its effectiveness through a simultaneous selective labilization of the cancer cells to reinforce even grassy.
Die Aufgabe wird dadurch gelöst, das eine Schleppersubstanz mit einem Zeilgift zu einem neuen Stoff verbunden wird.The object is achieved in that a carrier substance with a Zeilgift is connected to a new substance.
Dieser neue Stoff besteht aus Anti-A-Hellixagglutinine und Gallensäuren, wie z. B. dem Gallensäurederivat Desoxycholat. This new substance consists of anti-A-Hellixagglutinins and bile acids, such as B. the bile acid derivative deoxycholate.
Das Desoxycholat ist das durch den Schlepper, Anti-A-Helixagglutimine, herangescheppte Zellgrift. Es ist vorteilhaft, wenn die Beladung mit Desoxycholat drei bis zehn, vorzugsweise fünf Gewichtsprozent, des Anti-A-Hexilxaggluthins beträgt. Verwendet man nun diese mit Desoxycholat beladenen Anti-A-Helixagglutinine in Verbindung mit einer Labilisierung der Krebszellen durch gleichzeitige Haperthermie mit einer Temperatur von 40°C und einer optimierten Tumorübersäuerung mit einem pH-Wert von 6,3, welcher durch langzeitige intravenöse Infusion von Glucose mit einer Hate von 3,9 Gramm pro kg Körpergewicht des Patienten während einhundert Minuten erzielt wird, so ergibt sich eine hochwirksame und hochselektive immunochemische Attacke gegen die Krebszellen. Diese immunochemische Attacke löst einen Kettenreaktionsmechanismus der Krebszellenabtötung aus, bei dem durch Aktivierung lysosomaler Enzyme aus absterbenden Krebszellen neue Krebszellen abgetötet werden usw.The deoxycholate is the one made by the tug, anti-A-helix agglutimine, zipped cell handles. It is beneficial when loading with deoxycholate is three to ten, preferably five percent by weight of the anti-A-Hexilxaggluthin. If you now use these anti-A-helix agglutinins loaded with deoxycholate in conjunction with a labilization of the cancer cells by simultaneous haperthermia with a Temperature of 40 ° C and an optimized tumor hyperacidity with a pH value of 6.3, which is obtained by long-term intravenous infusion of glucose with a rate of 3.9 Grams per kg of body weight of the patient is achieved during one hundred minutes, this results in a highly effective and highly selective immunochemical attack against the cancer cells. This immunochemical attack triggers a chain reaction mechanism the killing of cancer cells, in which by activating lysosomal enzymes from dying Cancer cells new cancer cells are killed etc.
Das Verfahren zur Herstellung des Pharmakons besteht darin, daß erfindungsgemäß zunächst ein Teil Anti-A-Helixagglutinine in zehn Teilen einer phosphatgepufferten Kochsalzlösung mit einem pH-Wert von ca. 7,4 unter zweibis dreistündigem Rühren bei Zimmertemperatur gelöst werden. Auschließend werden die unlöslichen Überreste der Anti-A-Helixagglutinine abzentrifugiert. Danach wird in die so erhaltene Lösung Desoxyglucolsäure gegeben und mehrere Stunden bei Zimmertemperatur gerührt. Dieses oder andere Sallenssäure-Derivate sind vorgesehen, weil sie speziell bei den pH-Werten von kleiner als 7,0 der optimiert übersäurerten Tumore wirken und weil sie eine starke Beladung des Anti-AHP von z. B. fünf Gewichtsprozent möglichen. The process for the preparation of the drug is that according to the invention initially a part of anti-A-helix agglutinins in ten parts of a phosphate-buffered Saline solution with a pH of approx. 7.4 with stirring for two to three hours be dissolved at room temperature. The insoluble remains are excluded the anti-A-helix agglutinins centrifuged off. Thereafter, in the solution obtained in this way Given deoxyglucolic acid and stirred for several hours at room temperature. This or other sallic acid derivatives are provided because they are specific to pH levels of less than 7.0 of the optimized overacidified tumors act and because they are a heavy loading of the anti-AHP of z. B. five percent by weight possible.
Anschließend wird der nicht an die Anti-A-Helixagglutinine gebunden Teil der desoxyclorate in phosphate, offerter Kochsalzlösung im Durchfußverfahren abdialysiert. Then the is not bound to the anti-A-helix agglutinins Part of the deoxyclorate in phosphate, offered saline solution in the flow-through method dialysed.
Die Erfindung hat den Vorteil, das bei Patienten der Blutgruppe 6 und 8 ohne die schädigung gesunder Zellen @i@@menschlichen Körper befindliche Krebszellen in relativ kurzer Zeit hochselektiv abgetötet werden. Dies wird noch besonders durch die vorherige bzw. gleichzeitige Labilisierung der Krebszellen unterstützt. Die Labilisierung dann dabei so stark sein, daß schon eine relativ schwache cancerolytische Attacke beliebiger Natur ausreicht, um eine hochwirsame Kettenreaktion der Krebszellenschädigung in Tummeoren und Metastasen auszulösen. The invention has the advantage that in patients of blood group 6 and 8 cancer cells located without harming healthy cells @ i @@ human body in relative be killed highly selectively in a short time. this will especially due to the previous or simultaneous labilization of the cancer cells supports. The labilization then be so strong that it is already a relative weak cancerolytic attack of any nature is sufficient to produce a highly effective Triggering chain reaction of cancer cell damage in tumors and metastases.
An Hand eines Ausführungsbeispiels und der Zeichnung soll die Erfindung näher erläutert werden. In der Zeichneung zeigen: Fig. 1: die schematische Abdeutung einer Krebszelle mit dem durch Anti-AHP-Körper herangeschleppten Zellgift, Fig. 2: eine Kurvenschar über die Abtätung der Krebszellen in Abhä@@igkeit von der Zeit mit und ohne dem erfindungsgemäßen Pharmakon.The invention is to be based on an exemplary embodiment and the drawing are explained in more detail. The drawings show: FIG. 1: the schematic illustration a cancer cell with the cell poison dragged in by anti-AHP bodies, Fig. 2: a family of curves showing the ablation of cancer cells as a function of time with and without the pharmaceutical according to the invention.
Bei der Abtätung von Krebszellen besteht in erster Linie das Problem, die Zellmembranen, und hier insbesondere die Anwenmembran, zu zerstören. Die Voraussetzung dafür ist die bekannten Tastache, das Krebszellen immunologisch einen @-atigen sierflächentyp besitzen, also Anti-A-Körper wie z. B. vom Typ Anti-A- (Anti-A-arti@es Agglutinin aus der Eiweischrüsender Zeitserschenke) anlocken und binden. The main problem with the killing of cancer cells is to destroy the cell membranes, especially the application membrane. The condition for this is the well-known fact that cancer cells are immunologically a @ -atigen sierfläche type own, so anti-A bodies such. B. of the type anti-A- (anti-A-arti @ es agglutinin from the albumen of the time tavern) to attract and bind.
Es wurde und gefunten, daß die aus den Eiweißstoffen der Zeinbergschnecke (Helix pomati) gewonnennen Antikörper Anti-A-Eigenschaften und daher eine besonders hohe Affinität zu Krebszellen besitzen. werden nun diese Anti-A-Helixagglutinine (Abkrärzung: Anti-AHP) mit einenn Zell@iit beladen, d.h. mit ihn zu einem Neuen Stoff verbunden, so gelingt es, diesen hochselektiv an die krebszelle heranzubringen. ES wurde gefunden, daß sich als solcher Stoff besonders Gallen säuren, wie z.b. Desoxycholat, einet. Der neue stoff -mit Gallensäuren beladene Anti-A-Helixagglutinine - stellt alsdo ein hochwirksammes chemotherapeutisches Pharmakon gegen die Krebszellen dar. In Etizur 1 ist das prinzip des Heranbringens diese Stoffes an die Krebszelle schematisch dargestellt. Wenn man nun die Krebszelle gegen äußere Angriffe besonders labilisiert, wie dies mittels der bekannten Krebhs-Mehrschritt-Therapie möglich ist, indem beispeilsweise durch Verarbreichung von Glukose die Krebszelle optimal übersäuret wird (pH 6,3) und mittels Hyperthermie eine Erwärmung der Krebszelle auf 40°C erreicht wird, findet das Zellgift besonders günstige Bedingungen zur Vernichtung der Krebszellen vor.It was found out that those from the proteins of the Zeinberg snail (Helix pomati) obtained antibodies anti-A properties and therefore a special one have high affinity for cancer cells. now these anti-A-helix agglutinins become (Sketch: Anti-AHP) loaded with a cell @ iit, i.e. with it to a new one Fabric connected, this is how it succeeds this is highly selective to the cancer cell bring up. It was found that as such a substance, bile acids in particular, such as. Deoxycholate, one. The new substance - anti-A-helix agglutinins loaded with bile acids - alsdo is a highly effective chemotherapeutic drug against cancer cells In Etizur 1 is the principle of bringing this substance to the cancer cell shown schematically. If you now protect the cancer cell against external attacks especially labilized, as possible by means of the well-known Krebhs multi-step therapy is, for example, by administering glucose to the cancer cell optimally acidification (pH 6.3) and hyperthermia warming the cancer cell If the temperature reaches 40 ° C, the cytotoxin finds particularly favorable conditions for destruction of the cancer cells.
Das erfindungsgemäße Pharmakon läßt sich beispielsweise nach folgendem Verfahren herstellen.The pharmaceutical according to the invention can be, for example, according to the following Process.
Die in fester Form vorliegenden Anti-A-Helixagglutinine (ein Teil) werden in zehn Teilen einer phosphatgepufferten Kochsalzlösung gelöst. Diese Kochsalzlösung besitzt eine pH-Wert vor. ca. 7,4. Zur Lösung der Anti-A-Helixagglutinnine wird bei Zimmertemperatur zwei bis drei stunden terührt. Anschließend werden die unlöslichen bzw. ungelösten Anti-A-helixagglutinine abzentrifugiert. Zu der so erhaltenen Lösung wird Desoxycholsäure gegeben und wiederum mehrere Stunden bei Zimmertemperatur gerührt. Der Proteingehalt (Eiweißgehalt) der Lösung wird vor der Zugabe der Desoxychlosäure bestimmt. ihr soll ca. 3 g pro 100 ml betragen.The solid anti-A-helix agglutinins (a part) are dissolved in ten parts of a phosphate-buffered saline solution. This saline solution possesses a pH value before. approx 7.4. To solve the Anti-A-Helixagglutinnine is stirred at room temperature for two to three hours. Subsequently, the insoluble or undissolved anti-A-helix agglutinins centrifuged off. To the solution thus obtained deoxycholic acid is added and the mixture is again stirred for several hours at room temperature. The protein content (protein content) of the solution is determined before the addition of the deoxychlosic acid certainly. you should be about 3 g per 100 ml.
Die Desoxycholsäure wird in einer Menge von 15 mg pro ml der Proteinlösung zugegeben. Abschließend wird der nicht an die Anti-A-Hellixaggklutinine gebundene Teil des Desoxycholats in phosphatgepufferter Kochsalzlösung im Durchflußverfahren abdialysiert.The deoxycholic acid is used in an amount of 15 mg per ml of the protein solution admitted. In the end, the will not turn on the Anti-A-Hellixaggklutinin Bound part of the deoxycholate in phosphate-buffered saline in a flow-through process dialysed.
In Figur 2 ist die in vitro gemessene Abtötungsrate ij der Krebszellen bei pb = 6,S und 40°G in Prozent in Abhängigkeit von der Zeit t wiedergegeben. Aus der Kurve 1 ist ablesbar, daß bei Verwendung des Pharmakons in Kombination mit optimierter Tumorübersäuerung plus 40°C Hyperthermie nach 300 Minuten eine 100 %ige Abtötung der Krebszellen erreicht ist. Hierbei wurden als Modellkrebszellen Ehrlich-Mäuse-Ascites-Krebszellen verwendet. Zum Nachweis der tatsächlichen Abtötung der Krebszellen wurde der Trypanblaufärbetest verwendet. Kurve 2 zeigt im Vergleich dazu die Abtötungsrate der Krebszellen bei optimierter tummorsäurung plus hyperthermie ohne das erfindungsgemäße Pharmakon.FIG. 2 shows the killing rate ij of the cancer cells measured in vitro at pb = 6, S and 40 ° G in percent as a function of time t. the end the curve 1 can be seen that when using the drug in combination with optimized Overacidification of the tumor plus 40 ° C hyperthermia after 300 minutes a 100% kill of cancer cells is reached. Ehrlich mouse ascites cancer cells were used as model cancer cells used. The trypan staining test was used to demonstrate that the cancer cells were actually killed used. In comparison, curve 2 shows the killing rate of the cancer cells optimized tumor acidification plus hyperthermia without the drug according to the invention.
Auf Grund der Anti-A-Eigenschaften der Anti-A-Helixagglutinine ist dieses Pharmakon auf die anwendung bei den Dlutgruppen 0 und B beschränkt.Due to the anti-A properties of the anti-A helix agglutinins this drug is restricted to use with blood groups 0 and B.
Claims (4)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DD13805069 | 1969-02-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2003914A1 true DE2003914A1 (en) | 1970-09-10 |
Family
ID=5480928
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19702003914 Pending DE2003914A1 (en) | 1969-02-24 | 1970-01-29 | Immunochemical product for killing cancer cells |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE2003914A1 (en) |
-
1970
- 1970-01-29 DE DE19702003914 patent/DE2003914A1/en active Pending
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