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EP0524212A1 - Utilisation trinitrobenzenes ou d'acide carminique pour le traitement du cancer ou de maladies virales - Google Patents

Utilisation trinitrobenzenes ou d'acide carminique pour le traitement du cancer ou de maladies virales

Info

Publication number
EP0524212A1
EP0524212A1 EP91907059A EP91907059A EP0524212A1 EP 0524212 A1 EP0524212 A1 EP 0524212A1 EP 91907059 A EP91907059 A EP 91907059A EP 91907059 A EP91907059 A EP 91907059A EP 0524212 A1 EP0524212 A1 EP 0524212A1
Authority
EP
European Patent Office
Prior art keywords
group
formulation
optionally
carminic acid
prophylaxis
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP91907059A
Other languages
German (de)
English (en)
Inventor
Washington Odur Ayuko
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.)
RADOPATH PHARMACEUTICALS INTERNATIONAL LIMITED
Original Assignee
RADOPATH Ltd
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
Priority claimed from GB909007453A external-priority patent/GB9007453D0/en
Priority claimed from GB909012166A external-priority patent/GB9012166D0/en
Priority claimed from GB919103075A external-priority patent/GB9103075D0/en
Application filed by RADOPATH Ltd filed Critical RADOPATH Ltd
Publication of EP0524212A1 publication Critical patent/EP0524212A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/04—Nitro compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/15—Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals

Definitions

  • such a formulation contains the active ingredients dissolved or suspended in an aqueous medium at a concentration in the range from 10 -3 to 10 -15 moles per litre, and may be administered orally or parenterally.
  • Carminic acid is especially useful for anti-viral treatment.
  • X is selected from OH, NH 2, halogen, a sulfo group, a carboxyl group, OCH 3, or a substituted or unsubstituted hydrazyl group.
  • X is the hydroxyl radical
  • the compound is picric acid.
  • X is chloride, picryl chloride is formed, and so forth.
  • the sulfo group is preferably a sulphonate salt group, optionally, sodium or potassium sulphonate (SO 3 Na or SO 3 K) and the carboxyl group is preferably a carboxylate salt group, optionally, sodium or potassium carboxylate.
  • the halogen is Cl, Br or F.
  • the hydrazyl group or derivative is a radical of the following general formula:
  • DDSH diphenyl dinitrosulfonate phenylhydrazyl
  • SO 3 K sulfonate potassium salt group SO 3 K (substituted for the 5-NO 2 group) and is preferably synthesized by the interaction of diphenylhydrazine with the potassium salt of 2-chloro-3, 5-dinitro-benzene sulfonic acid in dilute alcohol or dilute dioxane, with subsequent oxidation of the resulting hydrazine by lead dioxide. Additional details concerning the synthesis of the DDSH radical are set forth in Investigation ln The Field Of The Chemistry Of Free Radicals Of The
  • FIGURE 2 is a plot of the dose response of a GM892 cell line to diphenyl picrylhydrazyl (DPPZ) and diphenyl picrylhydrazine (DPPH). The figure represents an average of 3-6 different experiments, with a Coulter counter used to determine the cell count. As seen in FIGURE 2 , both agents provide significant in-vitro anti-tumor effects on this cell line when administered in a substantially pure aqueous solution/suspension ranging at dilutions between about 10 -3 - 10 -15 molar concentration.
  • DPPZ diphenyl picrylhydrazyl
  • DPPH diphenyl picrylhydrazine
  • one preferred composition is an admixture of one or more trinitrobenzene derivatives and an anthraquinone having a glycosidic moiety, optionally carminic acid.
  • one such composition is an admixture of picryl chloride (or picryl sulfonate) and carminic acid.
  • picryl chloride or picryl sulfonate
  • the preferred ratio of picryl chloride to carminic acid is preferably between 1:1 and 1:2 but with the concentration of the active ingredients being in a therapeutically-effective concentration of between about 10 -3 - 10 -15 molar concentration.
  • a therapeutically-effective amount of the pharmaceutically composition in solution or suspension is between 2.0-5.0 mis, and this amount is apparently substantially independent of the bodyweight of the host animal .
  • a pharmaceutical or veterinary composition may be formed by first dissolving the hydrazine derivative in double-distilled, deionized water in a clean glass container under sterile conditions. Thereafter, the carminic acid is added and mixed into the solution. The picric acid is then added and the solution throughly mixed. Serial dilution can then be used to obtain the desired molar concentration. Alternatively, the three constituents are mixed together prior to dissolution in the carrier.
  • trinitrobenzene derivatives useful in accordance with the present invention are picric acid, picryl chloride, picryl sulfonate, diphenyl picrylhydrazine and diphenyl picrylhydrazyl, other trinitrobenzene compounds are also suitable catalysts for the free radical mechanism. Such compounds are included within the above general formula.
  • the preferred hydrazine derivatives are diphenyl picrylhydrazine (DPPH) and derivatives thereof such as diphenyl picrylhydrazyl (DPPZ), phenyl picrylhydrazine (PPH), carbazyl picrylamine (CPZ) and 2-sulfophenyl, 2-sulfophenyl, picrylhydrazine.
  • DPPH diphenyl picrylhydrazine
  • DPPZ diphenyl picrylhydrazyl
  • PPH phenyl picrylhydrazine
  • CPZ carbazyl picrylamine
  • 2-sulfophenyl 2-sulfophenyl, 2-sulfophenyl, picrylhydrazine.
  • DDSH diphenyl dinitrosulfonate phenylhydrazyl
  • carminic acid has evidenced significant anti-viral effects when dissolved in an aqueous medium at low concentrations.
  • a thirty seven year old male was diagnosed as HIV positive by the standard ELISA test.
  • the patient had oral thrush, very severe herpes zooster of the left facial nerve with involvement of the left orbital region, hard bilateral cervical lymph nodes, and an enlarged liver and spleen.
  • the patient was treated with carminic acid, dissolved in double-distilled, deionized water at 10 -6 molar concentration, via subcutaneous injections. For five days, the patient received a single 2.0 ml. injection per day.
  • carminic acid in therapeutically-effective concentrations as described, appears to stimulate the immune system. It is believed that other quinones having side-chained sugars (and derivatives thereof) may also exhibit anti-viral activity when administered according to the teachings herein.
  • an important aspect of the invention is the use of carminic acid and its derivatives in the preparation of a medicament for the prophylaxis or therapy of viral disease such as AIDS.
  • Such derivatives have the following genaral formula:
  • R is COOH (carminic acid) or other organic or inorganic functional group such as NH 2 , SO 3 [K, H or Na], and the C-glycoside is any sugar.
  • the anthraquinone may optionally be a benzoguinone (single ring) or napthaquinone (double ring).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Composés de radicaux à base de trinitrobenzène, acide carminique et ses dérivés, utilisables comme agents anti-cancer et anti-virus. Ces composés et les formules basées sur ceux-ci, peuvent s'administrer par voie orale ou parentérale à un malade humain ou animal, en solution/suspension aqueuse pratiquement pure dans une plage de dilutions située entre 10-3 et 10-15 en concentrations molaires. Selon une application préférentielle de l'invention, on utilise un ou davantage desdits composés et un anthraquinone (comme l'acide carminique). L'acide carminique seul présente des effets anti-virus notoires.
EP91907059A 1990-04-03 1991-04-03 Utilisation trinitrobenzenes ou d'acide carminique pour le traitement du cancer ou de maladies virales Withdrawn EP0524212A1 (fr)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
GB9007453 1990-04-03
GB909007453A GB9007453D0 (en) 1990-04-03 1990-04-03 Tumour therapy
GB909012166A GB9012166D0 (en) 1990-05-31 1990-05-31 Hydrazine derivatives for cancer therapy
GB9012166 1990-05-31
GB9103075 1991-02-13
GB919103075A GB9103075D0 (en) 1991-02-13 1991-02-13 Trinitrobenzene derivatives and their therapeutic use

Publications (1)

Publication Number Publication Date
EP0524212A1 true EP0524212A1 (fr) 1993-01-27

Family

ID=27265028

Family Applications (1)

Application Number Title Priority Date Filing Date
EP91907059A Withdrawn EP0524212A1 (fr) 1990-04-03 1991-04-03 Utilisation trinitrobenzenes ou d'acide carminique pour le traitement du cancer ou de maladies virales

Country Status (11)

Country Link
EP (1) EP0524212A1 (fr)
JP (1) JPH06501449A (fr)
AU (1) AU662883B2 (fr)
BR (1) BR9106310A (fr)
CA (1) CA2079803A1 (fr)
FI (1) FI924475L (fr)
HU (1) HUT62785A (fr)
LV (1) LV10574B (fr)
MC (1) MC2246A1 (fr)
NO (1) NO923824L (fr)
WO (1) WO1991015200A2 (fr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9103075D0 (en) * 1991-02-13 1991-03-27 Washington Odur Ayuko Trinitrobenzene derivatives and their therapeutic use
US5412123A (en) * 1993-02-08 1995-05-02 Glycomed Incorporated Anthraquinone and anthracene derivatives as inhibitors of the cell-adhesion molecules of the immune system
GB2284153B (en) * 1993-05-21 1998-02-25 Radopath Ltd Substances for use in treatment of HIV-infection in HIV-infected patients
DZ1781A1 (fr) * 1993-05-21 2002-02-17 Radopah Ltd Agents d'arylation.
GB9310520D0 (en) 1993-05-21 1993-07-07 Radopath Ltd Arylating agents
EP0751768B1 (fr) * 1994-03-17 2000-12-27 Radopath Pharmaceuticals International Limited Agent antiviral et anticancereux
AU5115396A (en) * 1995-03-17 1996-10-08 Radopath Limited Anti-viral and anti-cancer agents
GB9615619D0 (en) * 1996-03-18 1996-09-04 Radopath Ltd Costimulation of TcR/CD3-induced T-Lymphocytes
AU1903699A (en) * 1997-12-08 1999-06-28 Glycomed Incorporated Disalicylate analog based sialyl lewisx mimetics
CN112424291A (zh) * 2018-07-17 2021-02-26 皮利公司 蒽醌衍生物及其作为着色剂的用途

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4032659A (en) * 1969-03-20 1977-06-28 American Home Products Corporation Method of viral chemoprophylaxis
CA1262864A (fr) * 1982-09-17 1989-11-14 Clarence D. Cone Methode de production d'une oncolyse
FR2622445B1 (fr) * 1987-10-30 1990-07-27 Pasteur Institut Application de groupes nitrophenyles a la stimulation des capacites d'incorporation d'un medicament dans les cellules sensibles de l'hote

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9115200A2 *

Also Published As

Publication number Publication date
LV10574A (lv) 1995-04-20
WO1991015200A3 (fr) 1992-03-05
FI924475A0 (fi) 1992-10-05
BR9106310A (pt) 1993-04-20
LV10574B (en) 1995-08-20
FI924475A7 (fi) 1992-10-05
HUT62785A (en) 1993-06-28
NO923824L (no) 1992-11-26
JPH06501449A (ja) 1994-02-17
FI924475L (fi) 1992-10-05
HU9203148D0 (en) 1992-12-28
WO1991015200A2 (fr) 1991-10-17
CA2079803A1 (fr) 1991-10-04
AU662883B2 (en) 1995-09-21
MC2246A1 (fr) 1993-03-25
NO923824D0 (no) 1992-10-01
AU7560491A (en) 1991-10-30

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Legal Events

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