DE2507974A1 - Copper orotate for treatment of rheumatism and cancer - by oral or rectal admin. in humans - Google Patents
Copper orotate for treatment of rheumatism and cancer - by oral or rectal admin. in humansInfo
- Publication number
- DE2507974A1 DE2507974A1 DE19752507974 DE2507974A DE2507974A1 DE 2507974 A1 DE2507974 A1 DE 2507974A1 DE 19752507974 DE19752507974 DE 19752507974 DE 2507974 A DE2507974 A DE 2507974A DE 2507974 A1 DE2507974 A1 DE 2507974A1
- Authority
- DE
- Germany
- Prior art keywords
- copper
- rheumatism
- oral
- cancer
- treatment
- 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.)
- Granted
Links
- WKQFGWKSVRJAMI-UHFFFAOYSA-L copper;2,4-dioxo-1h-pyrimidine-6-carboxylate Chemical compound [Cu+2].[O-]C(=O)C1=CC(=O)NC(=O)N1.[O-]C(=O)C1=CC(=O)NC(=O)N1 WKQFGWKSVRJAMI-UHFFFAOYSA-L 0.000 title claims abstract description 10
- 206010028980 Neoplasm Diseases 0.000 title abstract description 5
- 201000011510 cancer Diseases 0.000 title abstract description 3
- 239000010949 copper Substances 0.000 claims abstract description 17
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 14
- 229910052802 copper Inorganic materials 0.000 claims description 14
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
- 230000001684 chronic effect Effects 0.000 abstract description 4
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 abstract 1
- 229940050410 gluconate Drugs 0.000 abstract 1
- OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical compound [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 4
- 229940108925 copper gluconate Drugs 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000005749 Copper compound Substances 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000003356 anti-rheumatic effect Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- QKMGIVQNFXRKEE-UHFFFAOYSA-L sodium;copper(1+);3-[(n-prop-2-enyl-c-sulfidocarbonimidoyl)amino]benzoate Chemical compound [Na+].[Cu+].[O-]C(=O)C1=CC=CC(NC([S-])=NCC=C)=C1 QKMGIVQNFXRKEE-UHFFFAOYSA-L 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 241000282412 Homo Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 150000001880 copper compounds Chemical class 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 229960005010 orotic acid Drugs 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- -1 penicillin amines Chemical class 0.000 description 1
- 230000001373 regressive effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
- C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/557—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. orotic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
- C07F1/005—Compounds containing elements of Groups 1 or 11 of the Periodic Table without C-Metal linkages
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Kupfer-orotat Die Erfindung betrifft aen neuen chemischen Stoff Kupfer-orotat gemäß der Strukturformel insbesondere zur therapeutischen Verwendung bei der Kupfer-Therapie in oraler oder rektaler Verabreichung. Es handelt sich dabei um das Kupfer-Salz der Orotsäure gemäß der Bruttoformel: Cu-(C5H3O4N2)2 Es wurde gefunden, daß sich Kupfer-orotat in besonders wirksamer Weise für die Behandlung von menschlichen Erkrankungen eignet, die mit einer krankheitstypischen Mobilisierung von Kupfer aus Zelisystemen einhergehen, insbesondere die Behandlung des chronischen Rheumatismus.Copper orotate The invention relates to a new chemical substance copper orotate according to the structural formula especially for therapeutic use in copper therapy in oral or rectal administration. It is the copper salt of orotic acid according to the gross formula: Cu- (C5H3O4N2) 2 It has been found that copper orotate is particularly effective for the treatment of human diseases that result in the mobilization of copper that is typical of the disease Zelisystems go hand in hand, especially the treatment of chronic rheumatism.
Es ist an sich seit langem bekannt, daß Kupfer-Verbindungen eine interessante Wirkung gegen Rheuma-Erkrankungen entfalten können (so z. B. EBESAL Hoechst, eine Harnstoff-Kupfer-Verbindung, und Cupro-Detoxin, ein Kupfer-Caseinhydrolysat-Konplex). Diese bekannten Präparate mußten jedoch im Laufe der Zeit aufgegeben werden, weil ihre Giftigkeit, z. B. auf die Nieren, zu groß war.It has long been known that copper compounds are an interesting Can develop an effect against rheumatic diseases (e.g. EBESAL Hoechst, a Urea-copper compound, and Cupro-Detoxin, a copper-casein hydrolyzate complex). However, these known preparations had to be abandoned in the course of time because their toxicity, e.g. B. on the kidneys, was too big.
Es ist aus Untersuchungen des Blutserums bekannt, daß insbesondere bei Rheuma, aber auch bei Krebs, der Spiegel des Kupfers im Serum erhöht ist, während gleichzeitig der Spiegel des Eisens abfällt. Man hat vermutet, daß der hohe Kupferspiegel im Serum mit der ursächlichen Entstehung des P.heumas zu tun habe. Es wurden daher Kupfer-bindende Komplexbildner zur Rheumatherapie eingesetzt (Metallcaptatse, Penicillinamin). Die Wirkung dieser Therapieform gegen Rheuma ist jedoch wenig verläßlich und beruht nach vom Erfinder vor allem mit Vollblutbilanzen durchgeführten Untersuchungen nicht auf der Verminderung des 'freien" Kupfers im Blutserum, sondern auf einer Abflachung des Gradienten gegenüber dem zellulären Kupferspiegel.It is known from studies of the blood serum that in particular in rheumatism, but also in cancer, the level of copper in the serum is increased while at the same time the mirror of iron falls off. It has been suggested that the high copper level have to do with the causative development of P.heumas in the serum. There were therefore Copper-binding complexing agents used for rheumatism therapy (metal captates, penicillin amines). However, the effect of this form of therapy against rheumatism is not very reliable and is based not according to investigations carried out by the inventor, especially with whole blood balances on the decrease of the 'free' copper in the blood serum, but on a flattening of the gradient versus the cellular copper level.
Ausgehend von dieser Erkenntnis entstand die erfindungsgemäße Überlegung, das Kupfer mit einem Trägermolekül auszustatten, das eine hohe Affinität zu Zellsystemen hat, die im Zuge der Rheuma-Erkrankung an Kupfer verarmte. Bei in dieser Richtung durchgeführten orientierenden Untersuchungen zeigte sich bereits, daß Kupfer-Gluconat in sehr geringen Dosen (z. B. von 1,5 mg Cu als ATluconat pro Tag bei einer er.achsenen Menschen) von interessanter antirheumatischer Wirkung ist.Based on this knowledge, the consideration according to the invention arose, to equip the copper with a carrier molecule that has a high affinity for cell systems who became depleted of copper in the course of rheumatism. In this direction carried out Orientation studies have already shown that copper gluconate is very low Doses (e.g. of 1.5 mg Cu as ATluconate per day in an adult human) has an interesting anti-rheumatic effect.
Weitere Untersuchungen mit dem Ziel einer gerichteten bzw. gezielten Kupfer-Pufladung von entzündlich veränderten Zellsystemen führten dann zum erfindungsgemäßen Kupfer-orotat. Es ergab sich, daß seine entzündungshemmende Wirkung im Pfotentest der Ratte, bezogen auf die Äauiffzienz der Dosen, etwa 100 mal stärker als die von Kupfer-Gluconat ist.Further investigations with the aim of a directed or targeted Copper charge of inflammatory changed cell systems then led to the invention Copper orotate. It was found that its anti-inflammatory effects in the paw test of the rat, based on the efciency of the cans, about 100 times stronger than that of Is copper gluconate.
Bei daraufhin am Menschen (16 Patienten) durchgeführten Versuchen mit primär chronischem Gelenkrheumatismus (PcP) ergab sich, daß Kupfer-crotat, bezogen auf die Äquieffizienz der Dosen etwa 160 mal wirksamer als Kupfer-Gluconat ist. Im Vergleich zu noch verfügbaren Chargen des eingangs erwähnten Präparats EBESAL Hoechst ist die Wirkung von Kupfer-orotat 600 bis 800 mal stärker, die Toxizität entsprechend geringer.In tests subsequently carried out on humans (16 patients) with primary chronic rheumatoid arthritis (PcP) it was found that copper crotate was related on the equi-efficiency of the doses is about 160 times more effective than copper gluconate. Compared to the batches of the EBESAL preparation mentioned at the beginning that are still available Hoechst the effect of copper orotate is 600 to 800 times stronger, the toxicity correspondingly lower.
Außerdem wurde bei weiteren Tierversuchen an Impftumoren der Ratte und Spontantumoren der Maus festgestellt, daß Kupferorotat stark regressiv, Kupfer-Gluconat dagegen nur wenig (im statistischen Grenzbereich) wirkt.In addition, in further animal experiments on vaccine tumors of the rat and mouse spontaneous tumors found that copper orotate is highly regressive, copper gluconate on the other hand, only has little effect (in the statistical limit range).
Aufgrund dieser Erkenntnisse stellt sich Kupfer-orotat als ein hochwirksamer, allen bisher bekannten Kupfer-Verbindungen weit überlegener Stoff von antirheumatischer, entzündungsbemmender Wirkung dar, der bei hauptsächlich oraler Verabreichung für die Behandlung von menschlichen Erkrankungen, die mit einer Krankheitstypischen Mobilisierung von Kupfer aus Zellsystemen einhergeben, insbesondere dem chronischen Rheumatismus, besonders geeignet erscheint.Based on these findings, copper orotate turns out to be a highly effective, all known copper connections far superior fabric of anti-rheumatic, anti-inflammatory effect, which is mainly oral Administration for the treatment of human diseases associated with a disease typical Mobilization of copper from cell systems, especially the chronic one Rheumatism, seems particularly suitable.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19752507974 DE2507974C3 (en) | 1975-02-25 | Copper orotate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19752507974 DE2507974C3 (en) | 1975-02-25 | Copper orotate |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2507974A1 true DE2507974A1 (en) | 1976-09-02 |
| DE2507974B2 DE2507974B2 (en) | 1977-04-14 |
| DE2507974C3 DE2507974C3 (en) | 1977-12-01 |
Family
ID=
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003510363A (en) * | 1999-10-04 | 2003-03-18 | カーター、ジョン | Pharmaceutical composition and use thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003510363A (en) * | 1999-10-04 | 2003-03-18 | カーター、ジョン | Pharmaceutical composition and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| DE2507974B2 (en) | 1977-04-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C3 | Grant after two publication steps (3rd publication) | ||
| E77 | Valid patent as to the heymanns-index 1977 | ||
| 8327 | Change in the person/name/address of the patent owner |
Owner name: PERMICUTAN-KG DR. EULER, 4790 PADERBORN, DE |
|
| 8339 | Ceased/non-payment of the annual fee |