GB2366726A - Pharmacologically active compounds extractable from the Cortinariaceae family or Crassulaceae family - Google Patents
Pharmacologically active compounds extractable from the Cortinariaceae family or Crassulaceae family Download PDFInfo
- Publication number
- GB2366726A GB2366726A GB0021287A GB0021287A GB2366726A GB 2366726 A GB2366726 A GB 2366726A GB 0021287 A GB0021287 A GB 0021287A GB 0021287 A GB0021287 A GB 0021287A GB 2366726 A GB2366726 A GB 2366726A
- Authority
- GB
- United Kingdom
- Prior art keywords
- pharmacologically active
- family
- therefrom
- cortinariaceae
- active compound
- 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.)
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/41—Crassulaceae (Stonecrop family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
A pharmacologically active compound extractable from a fungus of the <I>Cortinariaceae</I> family, formulations, processes of production is claimed, as its use in the manufacture of a medicament to treat cancer. Alternatively claimed is a pharmacologically active compound extractable from a plant of the <I>Crassulaceae</I> family, formulations, processes of production and its use in the manufacture of a medicament to treat cancer. A medicament or therapeutic combination comprising a fungus of the <I>Cortinariaceae</I> family or pharmacologically active compound thereof and a plant of the <I>Crassulaceae</I> family or pharmacologically active compound thereof is also claimed.
Description
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Composition and Method for the Treatment of Cancers This invention relates to a pharmaceutical formulation for the treatment of cancer. It also relates to a method for the treatment of cancer using the formulation.
Cancer remains a major cause of death in the United Kingdom and throughout the world. Although many treatments are now known, few are universally effective, and many exhibit serious and unpleasant side-effects.
There nevertheless remains the need for more effective treatments for all forms of cancer. The present inventor has surprisingly found that extracts from commonly available plant and fungal material display in vitro and in vivo activity against a wide range of human and mammalian cancer cell lines.
The invention therefore provides in one aspect a pharmacologically active compound extractable from fungi of the family Cortinariaceae, as well as the use of such a compound as a medicament.
The invention provides in another aspect a pharmacologically active extract from fungi of the family Cortinariaceae, as well as the use of such an extract as a medicament.
In a further aspect, the invention provides a pharmaceutical formulation containing as an active ingredient a fungus of the family Cortinariaceae, a pharmacologically active extract therefrom or a pharmacologically active compound extracted therefrom, in conjunction with a pharmacologically acceptable carrier or diluent.
In a yet further aspect, the invention provides a method for the treatment of cancer in a mammal comprising administering to a mammal in need of such treatment an effective amount of a fungus of the family Cortinariaceae, a pharmacologically active extract
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therefrom, a pharmacologically active compound extracted therefrom, or a pharmaceutical formulation containing such a fungus, extract or compound as an active ingredient. The invention provides in a still further aspect the use of a fungus of the family Cortinariaceae, a pharmacologically active extract therefrom or a pharmacologically active compound extracted therefrom, in the manufacture of a medicament for the treatment or the prophylaxis of cancers in a mammal. The invention provides in another aspect a process for the production of a pharmacologically active compound comprising extracting said compound from a fungus of the family Cortinariaceae. The invention also provides a pharmacologically active compound extractable from plants of the family Crassulaceae, as well as the use of such a compound as a medicament. In another aspect, the invention provides a pharmacologically active extract from plants of the family Crassulaceae, as well as the use of such as extract as a medicament. In a further aspect, the invention provides a pharmaceutical formulation containing as an active ingredient a plant of the family Crassulaceae, a pharmacologically active extract therefrom or a pharmacologically active compound extracted therefrom, in conjunction with a pharmacologically acceptable carrier or diluent. In a yet further aspect, the invention provides a method for the treatment of cancer in a mammal comprising administering to a mammal in need of such treatment an effective amount of a plant of the family Crassulaceae, a pharmacologically active extract therefrom, a pharmacologically active compound extracted therefrom or a pharmaceutical formulation containing such a plant or compound as an active ingredient.
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In a still further aspect, the invention provides the use of a plant of the family Crassulaceae, a pharmacologically active extract therefrom or a pharmacologically active compound extracted therefrom, in the manufacture of a medicament for the treatment or prophylaxis of cancers in a mammal. The invention provides in another aspect a process for the production of a pharmacologically active compound comprising extracting said compound from a plant of the family Crassulaceae. In preferred embodiments, both of the above ingredients are administered in combination. Therefore, in preferred aspects, the invention provides the use of a fungus of the family Cortinariaceae or a pharmacologically active compound extracted therefrom, in combination with a plant of the family Crassulaceae or a pharmacologically active compound extracted therefrom, in the manufacture of a medicament of treatment or prophylaxis of cancers in a mammal. The invention also provides in preferred aspects a pharmaceutical formulation containing as active ingredients a fungus of the family Cortinariaceae, a pharmacologically active extract therefrom or a pharmacologically active compound extracted therefrom, and a plant of the family Crassulaceae a pharmacoogically active extract therefrom or a pharmacologically active compound extracted therefrom in conjunction with a pharmacologically acceptable carrier or diluent. The invention further provides in preferred aspects a therapeutic combination comprising a fungus of the family Cortinariaceae,a pharmacologically active extract therefrom or a pharmacologically active compound extracted therefrom, together with a plant of the family Crassulaceae a pharmalogically active extract therefrom or a pharmacologically active compound extracted therefrom.
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The invention is further described in detail below.
The fungi from which the pharmacologically active compounds of the present invention are extracted are of the family Cortinariaceae, and are preferably of the species Cortinanus sp. Such fungi may be obtained, for example, from the Lebanon. The plants from which pharmacologically active compounds of the present invention are extracted are of the family Crassulaceae, and are preferable of the species Cotyledon intermedia bornum (Cotyledon pendulirus), commonly known as Kaak Bread. These plants may also be obtained in the Lebanon. The compound or compounds of the present invention may be administered in combination with all known pharmaceutically accepted additives known in the art to produce a suitable pharmaceutically acceptable formulation. Example of suitable formulations include any solid (tablets, pills, capsules, granules, etc.) or liquid (solutions, suspensions or emulsions) formulations which are suitable for oral, topical or parenteral administration, and they may contain the pure compound or in combination with any carrier or other pharmacologically active compounds. These compositions may need to be sterile when administered parenterally. However, it is especially preferred that a solution, more preferably a solution in water, ethanol or a mixture of the two is formulated for injection purposes. A combination therapy involving both the active ingredients referred to the above is preferred in this invention. The components may be administered in any ratio capable of producing the desired therapeutic effect, but are preferably in the ratio 0.5:1 to 5:1, more preferably 1:1 to 1.5:1, and most preferably 1.1:1 to 1.3:1 (the ratios being that of the fungal component to the plant component and are by weight). As noted above, the formulation may be administered as a solution in water, ethanol or a mixture of the two, preferably in the ratio (water:ethanol by volume) 1:2 to 2:1, more preferably 1:1.2 to 1.2:1.
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Iodine is preferably added to the solution, preferably in amount of 6 parts by volume based on 100 parts of solvent. Preferably, a 1 % solution of iodine in water is used. The dosage of formulation according to the invention will vary according to the pharmaceutical formulation, the mode of application, and the particular situs, host and tumour being treated. Other factors like age, body weight, sex, diet, time of administration, rate of excretion, condition of the host, drug combinations, reaction sensitivities and severity of the disease shall be taken into account. Administration can be carried out continuously or periodically within the maximum tolerated dose. A daily dosage of between 0.1 and 4 mg is preferred and a daily dosage between 0.2 and 3 mg is more preferred. For the first 9 days of treatment the following dosage regimen is especially preferred: Days 1 to 3: a daily dosage of 1 mg (0.5 mg in the morning and 0.5 mg in the evening). Days 4 to 6: a daily dosage of 1.5 mg (0.75 mg in the morning and 0.75 mg in the evening).
Days 7 to 9: a daily dosage of 2 mg (1 mg in the morning, and 1 mg in the evening). A Preparation Example is described below. The Preparation Example is intended to illustrate but not limit the scope of the invention. Preparation Example 500 g of mushrooms of the species Cortinanus sp. and 400 g of plant material of the species Cotyledon pendulirus were cut into chunks roughly 2-4 cm across. To this mixture was added 250 ml of 90% ethanol and 250 ml of water at 38 C. This mixture was left in a closed vessel at room temperature for 3 weeks, after which 30 ml of 1% aqueous iodine was added. The mixture was filtered through gauze to produce 500 ml of solution.
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The biological activity of the solution produced according to the above Preparation Example is described below with reference to the accompanying drawings, in which: Figure 1 is a graph showing the growth rate of various human cancer cell lines when treated with the Preparation Example in vitro; Figure 2 is a graph of tumour diameter in rats against time (rats treated with the Preparation Example being compared with controls); and Figure 3 is a further plot of external tumour diameter in two groups of rats when compared with controls.
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Cytotoxicity Test in vitro Four different malignant cell lines: 1 human oral squamous carcinoma: KB 2 human breast cancer: MCF-7 3 human ovarian cancer: CA OV-3 4 human endometrial adenocarcinoma: AN3-CA are grown in culture as monolayer, in Eagle's MEM. The growth rate of these cancer cell lines in vitro is measured by the concentration of DNA in ltg / flask. The Preparation Example solution is added in 4 different dilutions: 0.1 %; 0.5 %; 1 %; 2 to the cancer cell line cultures. Their growth rates are compared to the growth rate of the control culture. The results are shown in Fig 1. In the KB cell line cultures, growth inhibition appears only in those cultures treated with the 1 % and 2 % dilution of the Preparation Example solution. In the other cell line cultures, the growth inhibition increases with increasing concentration of the added Preparation Example solution. In the CA OV-3 cell line cultures and especially in the AN3-CA cell line cultures, the growth inhibition is extremely pronounced at the 0.5 %, 1 % and 2 % concentration of the Preparation Example solution. Short Term Toxicity Test in vivo Eight Wistar rats (4 females and 4 males), aged 4 weeks, are injected repeatedly during 38 days with the Preparation Example solution, previously sterilized by filtration on Micropore. The Preparation Example solution is injected in 3 ways: the subcutaneous, the intravenous and the intraperitoneal way, according to the following dosage:
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1 subcutaneous: up to 0.5 ml, not diluted or diluted 1/10 and 1/100. 2 intravenous: up to 0.6 ml, not diluted.
3 intraperitoneal: up to 4 ml, not diluted. The animals are examined every two days and sacrificed at the end of the experiment (38 days) for macroscopical examination. No rat has developed disease or showed microscopical alterations. Cytotoxicity Test in vivo Preliminary Approach Ten Wistar R rats/rnu rats (female and male), aged 4 weeks, are used for these experiments. Two malignant cell lines: KB and AN3-CA, in cell suspensions of 0.2 to 0.25 ml, with cell concentrations ranging from 1.0x 106 to 10x 106 / rat are transplanted to these immunodeficient rats by subcutaneous injection in the armpit of the right anterior paw. The animals are examined daily at the side of injection for cell growth. The treatment with the Preparation Example solution starts 2 to 5 days after cell transplantation, corresponding to an external tumour diameter of approximately 4 mm and is continued every 3 to 4 days. The undiluted Preparation Example solution is injected subcutaneously, into the tumour (0.2 to 0.5 ml) and /or around the tumour (0.25 to 0.8 ml). The control group receives a solvent injection at the same sides. The external tumour diameter is measured daily and carefully recorded. After treatment periods ranging from 15 to 27 days, the animals are killed by ether anaesthesia. The tumour growth rate curves, on which each point represents a triplicate experiment, show an evident inhibition induced by intra - and/or peritumoral administration of the Preparation Example solution, as shown in Fig. 2.
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Final Approach Twelve Wistar R rnu/rnu rats, aged 4 weeks, are used for these experiments. The AN' )- CA cell line in a 0.2 ml suspension with cell concentrations of either 1.0 x 106, either 5.0 x 106 / rat is transplanted to these immunodeficient rats by subcutaneous injections in the armpit of the right anterior paw. In group I, four rats receive only the cell line transplantation at a cell concentration 5.0 x 106 / rat and are used as controls. In group II, four rats receive the cell line transplantation at a cell concentration of 1.0 x 106 / rat and are treated, when the tumour reaches an external diameter of 2 to 4 mm, every day by peritumoral injection of 0.8 to 1 ml of the Preparation Example solution. In group III, four rats receive the cell transplantation line at a cell concentration of 5.0 x 106 / rat and are treated, when the tumour reaches and external diameter of 10 mm, every day by peritumoral injections of 0.8 to 1 ml of the Preparation Example solution. The growth rate curves (Fig. 3) suggest that the treatment of the transplanted AN3-CA cell line in the Wistar rat with the Preparation Example solution seems to be effective for tumour growth inhibition, only when the peritumoral injection is started early in the tumoural induction at a diameter less than 10 mm.
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Claims (23)
- CLAIMS: 1. A pharmacologically active compound extractable from a fungus of the family Cortinariaceae.
- 2. A compound according to claim 1, wherein the fungus is of the species Cortinanus SP.
- 3. A pharmacologically active extract from a fungus of the family Cortinariaceae.
- 4. An extract according to claim 3, wherin the fungus is of the species Cortinanus SP.
- 5. The use as a medicament of a compound according to claim 1 or claim 2 or an extract according to claim 3 or claim 4.
- 6. A pharmaceutical formulation containing as an active ingredient a fungus of the family Cortinariaceae, a pharmacologically active extract therefrom or a pharmacologically active compound extracted therefrom, in conjunction with a pharmacologically acceptable carrier or diluent.
- 7. A formulation according to claim 6, formulated so as to be administered by injection.
- 8. The use of a fungus of the family Cortinariaceae, a pharmacologically active extract therefrom, or a pharmacologically active compound extracted therefrom, in the manufacture of a medicament for the treatment or prophylaxis of cancers in a mammal.
- 9. A process for the production of a pharmacologically active compound comprising extracting said compound from a fungus of the family Cortinariaceae.<Desc/Clms Page number 11>
- 10. A pharmacologically active compound extractable from a plant of the family Crassulaceae.
- 11. A compound according to claim 7, wherein the plant is of the species Cotyledon intermedia bornum (Cotyledon pendulirus).
- 12. A pharmacologically active extract from a plant of the family Crassulaceae.
- 13. An extract accorrding to claim 12, wherein the plant is of the species Cotyledon intermedia bornum (Cotyledon pendulirus).
- 14. The use as a medicament of a compound according to claim 10 or claim 11 or an extract according to claim 12 or claim 13.
- 15. A pharmaceutical formulation containing as an active ingredient a plant of the family Crassulaceae, a pharmacologically active extract therefrom or a pharmacologically active compound extracted therefrom, in conjunction with a pharmacologically acceptable carrier or diluent.
- 16. A formulation according to claim 15, formulated so as to be administrable by injection.
- 17. The use of a plant of the family Crassulaceae, a pharmacologically active extract therefrom or a pharmacologically active compound extracted therefrom, in the manufacture of a medicament for the treatment or prophylaxis of cancers in a mammal.
- 18. A process for the production of a pharmacologically active compound comprising extracting said compound from a plant of the family Crassulaceae.<Desc/Clms Page number 12>
- 19. The use of a fungus of the family Cortinariaceae, a pharmacologically active extract therefrom or a pharmacologically active compound extracted therefrom, in combination with a plant of the family Crassulaceae, a pharmacologically active extract therefrom or a pharmacologically active compound extracted therefrom, in the manufacture of a medicament for the treatment or prophylaxis of cancers in a mammal.
- 20. A therapeutic combination comprising a fungus of the family Cortinariaceae, a pharmacologically active extract therefrom or a pharmacologically active compound extracted therefrom, together with a plant of the family Crassulaceae, a pharmacologically active extract therefrom or a pharmacologically active compound extracted therefrom.
- 21. A pharmaceutical formulation containing as active ingredients a fungus of the family Cortinariaceae, a pharmacologically active extract therefrom or a pharmacologically active compound extracted therefrom, together with a plant of the family Crassulaceae, a pharmacologically active extract therefrom or a pharmacologically active compound extracted therefrom, in conjunction with a pharmacologically acceptable carrier or diluent.
- 22. A formulation according to claim 21, formulated so as to be administrable by injection.
- 23. A formulation according to claim 21 or claim 22 further including iodine.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB0021287A GB2366726A (en) | 2000-08-30 | 2000-08-30 | Pharmacologically active compounds extractable from the Cortinariaceae family or Crassulaceae family |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB0021287A GB2366726A (en) | 2000-08-30 | 2000-08-30 | Pharmacologically active compounds extractable from the Cortinariaceae family or Crassulaceae family |
Publications (2)
Publication Number | Publication Date |
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GB0021287D0 GB0021287D0 (en) | 2000-10-18 |
GB2366726A true GB2366726A (en) | 2002-03-20 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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GB0021287A Withdrawn GB2366726A (en) | 2000-08-30 | 2000-08-30 | Pharmacologically active compounds extractable from the Cortinariaceae family or Crassulaceae family |
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GB (1) | GB2366726A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106692257A (en) * | 2017-01-18 | 2017-05-24 | 上海理工大学 | Pectin composition, preparation method, and application thereof |
-
2000
- 2000-08-30 GB GB0021287A patent/GB2366726A/en not_active Withdrawn
Non-Patent Citations (5)
Title |
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BIOSIS ABS.PREV199598419512, KOREAN J.MYCOLOGY, 1995,23,37- 45, LEE KAP-DUK ET AL * |
BIOSIS ABS.PREV199800401277, MIKOLOGIYA I FITOPATOLOGIYA, 1996,30,37-42, BADALYAN ET AL * |
BIOSIS ABS.PREV200000086412, ALLIONIA (TURIN), 1998-1999, 89-92, BIANCO & LELLI * |
INTER. J. PHARMACOGNOSY, 1997,35,255-260, AMOROS ET AL * |
PARSITOL. RES., 1999, 85, 582-588, FRANCOIS ET AL * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106692257A (en) * | 2017-01-18 | 2017-05-24 | 上海理工大学 | Pectin composition, preparation method, and application thereof |
CN106692257B (en) * | 2017-01-18 | 2019-11-01 | 上海理工大学 | A kind of combination of pectins, preparation method and its usage |
Also Published As
Publication number | Publication date |
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GB0021287D0 (en) | 2000-10-18 |
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WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |