AU7560491A - Use of trinitrobenzenes or carminic acid in the treatment of cancer or viral diseases - Google Patents
Use of trinitrobenzenes or carminic acid in the treatment of cancer or viral diseasesInfo
- Publication number
- AU7560491A AU7560491A AU75604/91A AU7560491A AU7560491A AU 7560491 A AU7560491 A AU 7560491A AU 75604/91 A AU75604/91 A AU 75604/91A AU 7560491 A AU7560491 A AU 7560491A AU 7560491 A AU7560491 A AU 7560491A
- Authority
- AU
- Australia
- 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.)
- Granted
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
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)
- Molecular Biology (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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
USE OF TRINITROBENZENES OR CARMINIC ACID
IN THE TREATMENT OF CANCER OR VIRAL DISEASES
The present invention relates generally to compounds and therapeutic formulations based on trinitrobenzene and/or carminic acid (or their derivatives) which in certain low concentrations exhibit anti-cancer or anti-viral activity.
Traditional cancer treatments generally involve surgery, radiotherapy, chemotherapy, or some combination thereof. While these treatments are often effective in lengthening a patient's life or sometimes eradicating the cancer, they have well-known serious side effects. More recently, alternative attempts to treat certain cancers have been developed. One such technique, "immunotherapy," is designed to strengthen the innate ability of the patient's immune system to fight cancer.
While diagnostic and treatment techniques have improved significantly over the last decades, there has been very little improvement in the overal l survival rate in pat ient s , especi al ly those with solid tumours treated by these orthodox methods. And, although alternative techniques such as "immunotherapy" show promise, the treatments developed thus far can only help a limited nember of patients, still exhibit toxic side effects and/or are complex and expensive to perform.
In the area of anti-viral medicine, many anti-viral drugs are known, but therapy may involve high doses or be of limited effect. In HIV treatment, AZT is the only significantly effective drug found to date, but treatment results are variable and the drug is expensive.
The present invention approaches these problems through the low dose use of readily available trinitrobenzene compounds and/or carminic acid (either singularly or in combination). It has now been found, most surprisingly, that such compounds are efficacious as anti-cancer or anti-viral agents when administered at low concentrations, regardless of patient bodyweight. Toxicity and expense problems associated with the prior art thus do not apply.
Thus, in one aspect the invention provides for use in the therapy or prophylaxis of neoplasm or viral infection in human and non-human animals, a formulation comprising a compound dissolved or dispersed in an aqueous medium at a concentration of 10-3 to 10-15 moles per litre and having the general formula:
wherein X is selected from OH, NH2 halogen, a sulfo group, a carboxyl group, OCH3 or a substituted or unsubstituted hydrazyl group of the formula:
wherein A is hydrogen or an unpaired electron of the nitrogen atom, Y is hydrogen or an organic group and Z is an organic group, or Y and Z together with the adjacent nitrogen atom form a nitrogen-containing heterocycle; provided that when X is a substituted or unsubstituted hydrazyl group as aforesaid one of the NO2 groups may be replaced by a sulfo group. The sulfo group is preferably a sulphonate salt group, optionally, sodium or potassium sulphonate (SO3Na or SO3K) and the carboxyl group is preferably a carboxylate salt group, optionally, sodium or potassium carboxylate.
In another aspect the invention provides for use in the therapy or prophylaxis of neoplasm or viral infection in human and non-human animals, a formulation comprising:
(a) one or more compounds of the general formula:
X - P
wherein P is a nitrophenyl, and X is selected from OH, NH2 halogen, a sulfo group, a carboxyl group, OCH3 or a substituted or unsubstituted hydrazyl group of the formula:
wherein A is hydrogen or an unpaired electron of the nitrogen atom, Y is hydrogen or an organic group and Z is an organic group, or Y and Z together with the adjacent nitrogen atom form a nitrogen-containing heterocycle; provided that when X is a substituted or unsubstituted hydrazyl group as aforesaid one of the NO2 groups may be replaced by a sulfo group; and
(b) a quinone, such as carminic acid or its derivatives.
A further aspect of the invention is a pharmaceutical or veterinary formulation wherein a compound as defined above is dissolved or dispersed in an aqueous medium at a concentration of from about 10-3 to 10-15 moles per litre.
Significantly, carminic acid has been found to exhibit anti-viral effects when used alone at low molar concentrations according to the invention. Thus, 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 general formula:
where R is COOH (i.e., carminic acid) or some other organic or inorganic functional group such as NH2, SO3[K, H or Na], and the C-glycoside is any sugar. The anthraquinone may optionally be a benzoquinone (single ring) or napthaquinone (double ring).
Without being tied to an exact mechanism, it is believed that the compounds referred to above function by initiating and propagating a free radical mechanism, thereby producing active chemical species that selectively attack abnormal cell structures. In Cancer Research 36 (1978), 1745-1750, Bachur et al describe possible free radical mechanisms in connection with the known biological actions of quinone-containing anti-cancer drugs. It is postulated that these drugs may generate oxygen-dependent free radicals such as superoxide or hydroxyl radicals. In the present invention, it is likely that the above mentioned compounds serve as catalysts for a redox-recycling mechanism which continuously generates free radicals such as superoxides. The free radicals, or their by-products, selectively attack cancer cells or viruses.
Preferred formulations according to the invention comprise a trinitrobenzene derivative (such as picryl chloride or diphenyl picrylhydrazine (DPPH)), an anthraquinone having a glycosidic moiety (such as carminic acid or a derivative thereof), or an admixture of one or more trinitrobenzene derivatives and an anthraquinone glycoside. Carminic acid has been used in the laboratory for staining nucleic acids and, interestingly, its effect on DNA is inhibited by, inter alia, free radical scavengers (Lown et al., Bioorganic Chem. 8 (1979), 17-24). Again, 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.
For a more complete understanding of the present invention and the advantages thereof, reference should be made to the following detailed description taken in connection with the accompanying figures in which:
FIGURE 1 is a plot of the average survival time in days of NMRI mice transplanted with MAC16 colon carcinoma cells after treatment with various therapeutically-effective concentrations of picryl chloride according to the teachings of the present invention; and
FIGURE 2 is a plot of the dose response of a GM892 cell line to diphenyl picrylhydrazyl (DPPZ) and diphenyl picrylhydrazine (DPPH) according to the teachings of the invention.
Turning now to the various specific aspects of the invention, a compound capable of initiating and propagating a free radical mechanism may be dissolved or dispersed in an aqueous medium at a therapeutically-effective concentration in the range of from about 10-3 - 10-15 moles per litre. Such compounds catalytically trigger free radical chain reactions, thereby producing active chemical species that selectively attack abnormal cells. One such set of compounds include derivatives of nitrobenzene of the following general formula:
wherein X is selected from OH, NH2, halogen, a sulfo group, a carboxyl group, OCH3, or a substituted or unsubstituted hydrazyl group. When X is the hydroxyl radical, the compound is picric acid. When X is chloride, picryl chloride is formed, and so forth. The sulfo group is preferably a sulphonate salt group, optionally, sodium or potassium sulphonate (SO3Na or SO3K) and the carboxyl group is preferably a carboxylate salt group, optionally, sodium or
potassium carboxylate. The halogen is Cl, Br or F. Preferably, the hydrazyl group or derivative is a radical of the following general formula:
wherein A is hydrogen or the unpaired electron of one nitrogen atom, Y is hydrogen or an organic group and Z is an organic group, or Y znd Z together with the adjacent nitrogen atom form a nitrogen-containing heterocycle (e.g., a carbazyl group); provided that when X is a substituted or unsubstituted hydrazyl group as aforesaid one of the NO2 groups may be replaced by a sulfo group. For example, where A is hydrogen and Y and Z are phenyl groups, the overall compound becomes diphenyl picrylhydrazine (DPPH). Where A is an unpaired electron and Y and Z are phenyl groups, the diphenyl picrylhydrazyl (DPPZ) radical is formed. Carbazyl picrylamine (CPZ) is formed when A is hydrogen and Y and Z are paired phenyl groups, thus forming a nitrogen-containing heterocycle. One particularly desirable water-soluble derivative has the following structural formula for the hydrazyl-derived group:
wherein Y and Z are phenyl groups, and potassium is optionally hydrogen or sodium.
Another particularly suitable water soluble derivative is diphenyl dinitrosulfonate phenylhydrazyl (DDSH), which includes a sulfonate potassium salt group SO3K (substituted for the 5-NO2 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
Hydrazine Series No. VIII, by M.A. Ikrina et al, Zhurnal Obschei Khimii, Volume 32, No. 12 at 3952-3957, December, 1962, incorporated here by reference.
It has been shown that trinitrobenzene derivatives as above, e.g., diphenyl picrylhydrazine, are effective when administered to a host in a substantially pure aqueous solution/suspension ranging at dilutions between about 10-3 - 10-15 molar concentration (i.e., "therapeutically-effective concentrations"). FIGURE 1 is a plot of the average survival time in days of NMRI mice transplanted with MAC16 colon carcinoma cells after treatment by subcutaneous injection with various therapeutically-effective concentrations of picryl
chloride according to the teachings of the present invention. As seen in FIGURE 1, the untreated control animals lived an average of less than 10 days, whereas animals treated with the various specified concentrations of picryl chloride had significant survival rates. The best results were obtained at 10-12 molar concentration when the animals were injected subcutaneously for five (5) days (one injection per day). At this concentration, most of the treated animals were tumor-free on day 60.
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.
Significant therapeutic results are obtained using pharmaceutical or veterinary compositions based on the above compounds, singularly or in combination, dissolved or dispersed in an aqueous medium in the concentrations previously described. For example, carminic acid alone (or a derivative thereof) is especially useful as an anti-viral
agent. Carminic acid has a C-glycoside (C6H11O5) side-linked to a polyhydroxyanthraquinone as evidenced by the following formula:
In combination form, one preferred composition is an admixture of one or more trinitrobenzene derivatives and an anthraquinone having a glycosidic moiety, optionally carminic acid. For example, one such composition is an admixture of picryl chloride (or picryl sulfonate) and carminic acid. Although not meant to be limiting, 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 .
If desired, more than one trinitrobenzene can be advantageously incorporated into the admixture. For example, when picric acid and DPPH are used, these trinitrobenzenes may act synergistically in generating free radicals and a free
radical chain reaction mechanism. The quinone, if used, can also be a source of OH free radicals. In one embodiment, predetermined amounts of picric acid, DPPH and carminic acid are mixed in a substantially pure aqueous solution/suspension ranging at dilutions giving between about 10-3 - 10-15 molar concentration. The DPPH has the highest dilution, followed by the carminic acid and then the picric acid. While not meant to be limiting, 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.
According to other features of the invention, the efficacy of a free radical chain reaction mechanism may be enhanced through administration of iron or any other transitional metal, especially copper. Although not described in detail, it is also envisioned that the anti-tumor agents described above can be administered to the host subcutaneously, intravenously or using an acceptable carrier or excipient. Also, while double-distilled, deionized water is the preferred solution/suspension liquid, other dilutants,
such as a dimethylsulfoxide/water solution, arachis oil, olive oil, vegetable oil or corn oil, may be useful as well. Yet another useful catalyst for the free radical mechanism is a (low concentration) polyunsaturated fatty acid, which is a long chain free carboxylic acid typically found in a lipid.
It should be appreciated that while the preferred 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.
In the above general formula, when A is hydrogen and Y is a phenyl group, Z may be, for example, any aromatic group such as shown in appendix Table I or an aliphatic group as shown in appendix Table II. Alternatively, Y and Z may be any of the aromatic compounds shown in appendix Table III. Another set of "phenyl" derivatives is derived from the compounds shown in appendix Table IV and a set of "carbazyl" derivatives is defined by the formulae set forth in appendix Table V. Although not meant to be limiting, 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.
Moreover, while the emphasis in the above discussion has been on novel anti-cancer and anti-viral therapies, it should be appreciated that the active chemical species generated by the trinitrobenzene and carminic acid derivatives according to the invention may also evidence significant anti-fungal and anti-bacterial effects. Use of such low concentration therapies is also being investigated in connection with treatment of genetic and autoimmune disorders.
In one pilot study of the invention, a sixty four year old female with advanced cervical cancer was treated with diphenyl dinitrosulfonate phenylhydrazyl (DDSH). On systematic examination, the patient presented with lower abdominal pain, anaemia, and vaginal bleeding. On gynecological examination, a large mass was located protrubing from the birth canal and extending to the lateral pelvic wall. The patient was diagnosed with stage 3 cervical cancer (squamous cell carcinoma), a finding later confirmed during exploratory surgery in which extensive metastatic masses throughout the abdomen were also discovered. After diagnosed as terminal, the patient was treated with a single 2.0 ml. subcutaneous injection of DDSH dissolved in double-distilled, deionized water at 10-9 molar concentration. No other
treatment was undertaken. Upon recent clinical examination, the patient was found to be free from the cancer, with no evidence remaining of the metastatic masses.
In another pilot study a sixteen year old male, diagnosed with metastatic pheochromocytoma involving the liver and jawbone, was also treated with DDSH by subcutaneous injection at 10-9 molar concentration. When first examined, the patient had extremely high blood pressure, 180/160, an abnormal heart rate, and extensive pain in the jaw area. A first subcutaneous injection was given in April, 1990, with a follow-up injection provided in November, 1990. Upon recent investigation, the patient's blood pressure is normal, the extensive jawbone pain has subsided, and general health is considered good.
Based on ongoing pilot studies, carminic acid has evidenced significant anti-viral effects when dissolved in an aqueous medium at low concentrations. In one pilot study, a thirty seven year old male was diagnosed as HIV positive by the standard ELISA test. When first examined in November, 1990, 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. Thereafter, 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. After five days, a similar five day course (one injection per day for five days) was repeated. After the fourth course (20 injections), the patient was in good general condition, was no longer anaemic, and the oral thrush, cervical lymph nodes and herpes zooster infection had cleared. The spleen and liver were normal and the patient had gained weight. Significantly, the patient's white blood count (WBC) had increased from 2,000 cells/mm3 to 12,400 cells/mm3, with a corresponding increase in hemoglobin (Hb) from 11.8 to 14.7 grams per deciliter.
These findings are significant and indicate that 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. Thus, 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:
where R is COOH (carminic acid) or other organic or inorganic functional group such as NH2, SO3[K, H or Na], and the C-glycoside is any sugar. The anthraquinone may optionally be a benzoguinone (single ring) or napthaquinone (double ring).
While the invention has been described in part by reference to various preferred embodiments, those skilled in the art will appreciate that various modifications, substitutions, omissions and changes may be made without departing therefrom.
Claims (15)
1. For use in the therapy or prophylaxis of neoplasm or viral infection in human and non-human animals, a formulation comprising a compound dissolved or dispersed in an aqueous medium at a concentration in the range from 10-3 to 10-15 moles per litre and having the general formula:
wherein X is selected from OH, NH2 halogen, a sulfo group, a carboxyl group, OCH3 or a substituted or unsubstituted hydrazyl group of the formula:
wherein A is hydrogen or an unpaired electron of the nitrogen atom, Y is hydrogen or an organic group and Z is an organic group, or Y and Z together with the adjacent nitrogen atom form a nitrogen-containing heterocycle; provided that when X is a substituted or unsubstituted hydrazyl group as aforesaid one of the NO2 groups may be replaced by a sulfo group.
2. For use in the therapy or prophylaxis of neoplasm or viral infection in human and non-human animals, a formulation comprising:
(a) one or more compounds of the general formula:
X - P
wherein P is trinitrophenyl and X is selected from OH, NH2 halogen, a sulfo group, a carboxyl group, OCH3 or a substituted or unsubstituted hydrazyl group of the formula:
wherein A is hydrogen or an unpaired electron of the nitrogen atom, Y is hydrogen or an organic group and Z is an organic group, or Y and Z together with the adjacent nitrogen atom form a nitrogen-containing heterocycle; provided that when X is a substituted or unsubstituted hydrazyl group as aforesaid one of the NO2 groups may be replaced by a sulfo group; and
(b) a quinone, optionally an anthraquinone having a glycosidic moiety, preferably, carminic acid.
3. A formulation as claimed in Claim 1 or Claim 2 wherein the sulfo group is a sulphonate salt group, optionally, sodium or potassium sulphonate.
4. A formulation as claimed in Claim 1 or Claim 2 wherein the carboxyl group is a carboxylate salt group, optionally, sodium or potassium carboxylate.
5. A formulation as claimed in Claim 1 or Claim 2 wherein halogen in Cl, Br or F.
6. A formulation as defined in any one of Claims 1 through 5 including picric acid, picryl chloride, picryl sulfonate or diphenyl picrylhydrazine or any two or more thereof.
7. A formulation as defined in any one of Claims 1 through 6 in unit dosage form, optionally each unit comprising between 2.0-5.0 mls. of the solution or dispersion.
8. A pharmaceutical or veterinary formulation wherein a radical or compound as defined in Claim 1 is dissolved or dispersed in an aqueous medium at a concentration in the range from 10-3 to 10-15 moles per litre.
9. A formulation as claimed in Claim 8 and in unit dosage form, optionally each unit comprising from 2.0-5.0 ml of the solution or dispersion.
10. A formulation as claimed in Claim 8 or Claim 9 also comprising an anthraquinone glycoside, optionally carminic acid.
11. The use of a radical or compound having a formula as defined in Claim 1, optionally together with an anthraquinone glycoside, e.g. carminic acid, in the preparation of a medicament for the prophylaxis or therapy of cancer or viral disease.
12- The use of Claim 11, wherein said radical or compound is in an aqueous medium at a concentration of from 10-3 to 10-15 moles per litre.
13. For use in the therapy of viral infection in human animals, a formulation comprising an anthraquinone glycoside, optionally carminic acid, dissolved in an aqueous medium at a concentration in the range from 10-3 to 10-15 moles per litre.
14. The use of an anthraquinone glycoside, optionally carminic acid, in the preparation of a medicament for the prophylaxis or treatment of a viral infection.
15. The use of Claim 14 wherein the medicament is for the prophylaxis or treatment of an HIV infection.
Applications Claiming Priority (7)
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 | ||
GB919103075A GB9103075D0 (en) | 1991-02-13 | 1991-02-13 | Trinitrobenzene derivatives and their therapeutic use |
GB9103075 | 1991-02-13 | ||
PCT/GB1991/000517 WO1991015200A2 (en) | 1990-04-03 | 1991-04-03 | Use of trinitrobenzenes or carminic acid in the treatment of cancer or viral diseases |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU27172/95A Division AU2717295A (en) | 1990-04-03 | 1995-07-25 | Use of trinitrobenzenes or carminic acid in the treatment of cancer or viral diseases |
Publications (2)
Publication Number | Publication Date |
---|---|
AU7560491A true AU7560491A (en) | 1991-10-30 |
AU662883B2 AU662883B2 (en) | 1995-09-21 |
Family
ID=27265028
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU75604/91A Ceased AU662883B2 (en) | 1990-04-03 | 1991-04-03 | Use of trinitrobenzenes or carminic acid in the treatment of cancer or viral diseases |
Country Status (11)
Country | Link |
---|---|
EP (1) | EP0524212A1 (en) |
JP (1) | JPH06501449A (en) |
AU (1) | AU662883B2 (en) |
BR (1) | BR9106310A (en) |
CA (1) | CA2079803A1 (en) |
FI (1) | FI924475A (en) |
HU (1) | HUT62785A (en) |
LV (1) | LV10574B (en) |
MC (1) | MC2246A1 (en) |
NO (1) | NO923824L (en) |
WO (1) | WO1991015200A2 (en) |
Families Citing this family (10)
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 |
DZ1781A1 (en) * | 1993-05-21 | 2002-02-17 | Radopah Ltd | Arylating agents. |
GB9310520D0 (en) | 1993-05-21 | 1993-07-07 | Radopath Ltd | Arylating agents |
GB2312375B (en) * | 1993-05-21 | 1998-02-25 | Radopath Ltd | Agents for treatment of cancer |
AU1900195A (en) * | 1994-03-17 | 1995-10-03 | Radopath Limited | Anti-viral and anti-cancer agents |
WO1996029067A1 (en) * | 1995-03-17 | 1996-09-26 | 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 |
WO1999029706A2 (en) * | 1997-12-08 | 1999-06-17 | Glycomed Incorporated | DISALICYLATE ANALOG BASED SIALYL LEWISx MIMETICS |
WO2020016245A1 (en) * | 2018-07-17 | 2020-01-23 | Pili | Anthraquinonic derivatives and their use as colouring agents |
Family Cites Families (3)
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 (en) * | 1982-09-17 | 1989-11-14 | Clarence D. Cone | Method for producing oncolysis |
FR2622445B1 (en) * | 1987-10-30 | 1990-07-27 | Pasteur Institut | APPLICATION OF NITROPHENYL GROUPS TO STIMULATE THE CAPACITIES OF INCORPORATION OF A DRUG IN SENSITIVE HOST CELLS |
-
1991
- 1991-04-03 JP JP3506514A patent/JPH06501449A/en active Pending
- 1991-04-03 MC MC91GB9100517D patent/MC2246A1/en unknown
- 1991-04-03 BR BR919106310A patent/BR9106310A/en not_active Application Discontinuation
- 1991-04-03 HU HU923148A patent/HUT62785A/en unknown
- 1991-04-03 WO PCT/GB1991/000517 patent/WO1991015200A2/en not_active Application Discontinuation
- 1991-04-03 AU AU75604/91A patent/AU662883B2/en not_active Ceased
- 1991-04-03 CA CA002079803A patent/CA2079803A1/en not_active Abandoned
- 1991-04-03 EP EP91907059A patent/EP0524212A1/en not_active Withdrawn
-
1992
- 1992-10-01 NO NO92923824A patent/NO923824L/en unknown
- 1992-10-05 FI FI924475A patent/FI924475A/en not_active Application Discontinuation
- 1992-10-05 LV LVP-92-149A patent/LV10574B/en unknown
Also Published As
Publication number | Publication date |
---|---|
BR9106310A (en) | 1993-04-20 |
LV10574B (en) | 1995-08-20 |
JPH06501449A (en) | 1994-02-17 |
NO923824L (en) | 1992-11-26 |
HUT62785A (en) | 1993-06-28 |
CA2079803A1 (en) | 1991-10-04 |
WO1991015200A3 (en) | 1992-03-05 |
NO923824D0 (en) | 1992-10-01 |
MC2246A1 (en) | 1993-03-25 |
FI924475A0 (en) | 1992-10-05 |
AU662883B2 (en) | 1995-09-21 |
WO1991015200A2 (en) | 1991-10-17 |
HU9203148D0 (en) | 1992-12-28 |
LV10574A (en) | 1995-04-20 |
EP0524212A1 (en) | 1993-01-27 |
FI924475A (en) | 1992-10-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2001230977B2 (en) | Combinations for treating neoplasms | |
Kennedy | Hydroxyurea therapy in chronic myelogenous leukemia | |
NZ240487A (en) | Formulations comprising trinitrobenzene derivative and optionally a quinone | |
AU2001230977A1 (en) | Combinations for treating neoplasms | |
TW201500046A (en) | Use of sodium meta arsenite for the treatment of cancer pain and inflammation | |
AU662883B2 (en) | Use of trinitrobenzenes or carminic acid in the treatment of cancer or viral diseases | |
US6720011B1 (en) | Injectable composition for cancer treatment | |
US5891454A (en) | Anti-cancer drug and special tumor necrotizing agent | |
NL194430C (en) | Non-injectable pharmaceutical preparation with anti-cancer effect. | |
EP0938900A1 (en) | Preventives/remedies for stomatitis | |
Mouridsen et al. | Mitoxantrone as first line cytotoxic therapy in advanced breast cancer: preliminary results of a phase II study | |
CN102470146A (en) | Angiogenesis-regulating composition and angiogenesis regulation method | |
US6306901B1 (en) | Agent for prophylaxis and therapy of diseases | |
JPH01313433A (en) | Anti-hiv agent | |
JP2004315470A (en) | Pharmaceutical preparation containing sodium iodide | |
JP2003507334A (en) | Plasma substitute composition | |
LT3173B (en) | Use of trinitrobenzenes or carminic acid in the treatment of cancer or viral diseases | |
RU2211035C1 (en) | Anti-tuberculosis preparation | |
HRP920891A2 (en) | Quinone preparation | |
JPS6337767B2 (en) | ||
JP2004522775A (en) | Anticancer drug | |
JPH05229939A (en) | Therapeutic agent for thrombocytopenia and/or leukopenia | |
JPH03120216A (en) | Composition for suppression of bone marrow | |
JPH0672896A (en) | Improver for renal function | |
JPH0517351A (en) | Leukocyte decrease-preventing agent containing 3-oxygermylpropionic acid as main ingredient |