GB2140686A - Drugs containing a psoralene derivative - Google Patents
Drugs containing a psoralene derivative Download PDFInfo
- Publication number
- GB2140686A GB2140686A GB08315070A GB8315070A GB2140686A GB 2140686 A GB2140686 A GB 2140686A GB 08315070 A GB08315070 A GB 08315070A GB 8315070 A GB8315070 A GB 8315070A GB 2140686 A GB2140686 A GB 2140686A
- Authority
- GB
- United Kingdom
- Prior art keywords
- drugs
- treatment
- active substance
- methoxypsoralene
- cancerous
- 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
- 229940079593 drug Drugs 0.000 title claims description 12
- 239000003814 drug Substances 0.000 title claims description 12
- 150000003194 psoralenes Chemical class 0.000 title description 3
- BGEBZHIAGXMEMV-UHFFFAOYSA-N 5-methoxypsoralen Chemical compound O1C(=O)C=CC2=C1C=C1OC=CC1=C2OC BGEBZHIAGXMEMV-UHFFFAOYSA-N 0.000 claims abstract description 26
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 19
- 238000011282 treatment Methods 0.000 claims abstract description 15
- 230000035755 proliferation Effects 0.000 claims abstract description 11
- 239000013543 active substance Substances 0.000 claims abstract description 7
- 230000000699 topical effect Effects 0.000 claims abstract description 6
- 235000019271 petrolatum Nutrition 0.000 claims description 6
- 230000005855 radiation Effects 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- 230000035515 penetration Effects 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 229960001760 dimethyl sulfoxide Drugs 0.000 claims description 3
- 239000000969 carrier Substances 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- 239000002480 mineral oil Substances 0.000 claims description 2
- 239000008158 vegetable oil Substances 0.000 claims description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 claims 1
- 230000001476 alcoholic effect Effects 0.000 claims 1
- 229910052500 inorganic mineral Inorganic materials 0.000 claims 1
- 235000010755 mineral Nutrition 0.000 claims 1
- 235000015112 vegetable and seed oil Nutrition 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 15
- 102000053602 DNA Human genes 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 208000000453 Skin Neoplasms Diseases 0.000 description 5
- 201000009030 Carcinoma Diseases 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 238000011200 topical administration Methods 0.000 description 4
- 201000004681 Psoriasis Diseases 0.000 description 3
- 201000005962 mycosis fungoides Diseases 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 201000000849 skin cancer Diseases 0.000 description 3
- 206010014970 Ephelides Diseases 0.000 description 2
- 208000003351 Melanosis Diseases 0.000 description 2
- QXKHYNVANLEOEG-UHFFFAOYSA-N Methoxsalen Chemical compound C1=CC(=O)OC2=C1C=C1C=COC1=C2OC QXKHYNVANLEOEG-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- PCWZKQSKUXXDDJ-UHFFFAOYSA-N Xanthotoxin Natural products COCc1c2OC(=O)C=Cc2cc3ccoc13 PCWZKQSKUXXDDJ-UHFFFAOYSA-N 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 210000004207 dermis Anatomy 0.000 description 2
- 208000010932 epithelial neoplasm Diseases 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 210000002751 lymph Anatomy 0.000 description 2
- 229960004469 methoxsalen Drugs 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 231100000760 phototoxic Toxicity 0.000 description 2
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 2
- -1 -isopropyl myristate Chemical compound 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 206010020648 Hyperkeratoses Diseases 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 206010038111 Recurrent cancer Diseases 0.000 description 1
- 206010047642 Vitiligo Diseases 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 208000030381 cutaneous melanoma Diseases 0.000 description 1
- 210000001339 epidermal cell Anatomy 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000001373 regressive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 201000003708 skin melanoma Diseases 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
- A61K31/37—Coumarins, e.g. psoralen
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Compositions for topical and oral application contain as an active substance 5-methoxypsoralene of the formula: <IMAGE> are useful for the treatment of epidermal proliferation tumours.
Description
SPECIFICATION
Drugs containing a psoralene derivative
This invention relates to new compositions of drugs containing as an active substance 5methoxypsoralene of the formula:
French Patent No. 77.31719 filed on October 21, 1977 in the name of the present applicant disclosed these new drugs as having a very high therapeutic index due to the very low toxicity of 5methoxypsoralene compared to that of other psoralenes. The Patent made clear that one could use therapeutic doses of 5-methoxypsoralene up to five times greater than those used for the 8methoxypsoralene and advocated the administration of oral doses of 20 mg to 300 mg of 5-methoxypsoralene per day, followed by a daily exposure to ultraviolet A, at a rate of 1.5 to
10 joules/cm2.
For topical administration, the patent advocated 5-methoxypsora lene concentrations between 100 ppm and 1000 ppm. Trials concerning the therapeutic activity of the new drugs had been carried out in the treatment of psoriasis, vitiligo, atypical eczema and mycosis fungoides.
It should be recalled here that mycosis fungoides is a well known skin cancer of the lymphoma type which is characterised by the proliferation of lymphocyte cells which are abundant in the lymph, that is, the interstitiai liquid irrigating notably the dermis and epidermis.
The clinical trials and experiments which were the basis of Patent No. 77 31719 were, of course, conducted both on patients affected with psoriasis and patients affected with skin cancer, since both of these illnesses are characterized by a more rapid than normal proliferation phenomenon of the cutaneous cells. This rapid proliferation phenomenon of the cells occurs at the level of the deoxyribonucleic acid (DNA) molecules present in the cell nucleus.
It is known that 5-methoxypsoralene, under the energetic action of UV.A radiation, attaches to each of the two helixes of a DNA molecule and so blocks the transcription process. No messenger
RNA (ribonucleic acid) is manufactured, completely inhibiting protein synthesis and cell
multiplication. In normal cells, the blocking of the
DNA helixes is overcome by the faster action of the DNA self-repair systems. This is achieved either by excision or by replication.
But in the case of cells affected with psoriasis or cancer, that is cells where the multiplication
phenomena are very accelerated, the self-repair systems do not have time to set to work. In the same cells however the psoralene, by forming bridges between the two DNA helixes, stops the anarchical cellular multiplication. This explains why 5-methoxypsoralene does not in any way disturb the multiplication of normal cells but selectively blocks diseased cells which are undergoing accelerated proliferation such as psoriatic cells or cancerous cells.
After the satisfactory results obtained with the treatment of the mycosis fungoides iymphoma (cancer of the lymph cells) by administration of 5methoxypsoralene and UV.A exposure, the applicant had the idea of carrying on with investigations on other types of cancers or precancerous lesions of the skin, that is, proliferation tumours of epidermal cells and not the proliferation of cells of the interstitial fluid such as the baso-cellular epithelioma, the spino-cellular epithelioma, Hutchinson's freckles, actinic hyperkeratosis and cutaneous melanomas, etc.
Such an idea was contrary to the well established view that therapy combining the use of 5-methoxypsoralene and UV.A irradiation was totally inadvisable in the case of epidermal proliferation tumours, since it was the solar radiation itself which produced such tumours.
It is therefore quite unexpected that the applicant found that 5-methoxypsoralene could heal malignant epidermal proliferation tumours when administered under new and special conditions; notably as regards posology.
The pharmacological activity of the drug was brought to the fore by topical administration of 5methoxypsoralene on mice having cancerous tumours produced by ultraviolet radiation.
It appeared that the concentrations of 5methoxypsoralene necessary for topical preparation were very high; from 10 to 100 times more than the prior art concentrations, and this as a function of the excipient.
The general toxicity of topical preparations having 1,000 to 10,000 ppm of 5methoxypsoralene has been studied in mice with various excipients, and has shown that the active substance is well tolerated, even in such high doses. This corresponds to the fact that 5methoxypsoralene is far less toxic than 8methoxypsoralene.
For the topical administration of 5methoxypsoralene, various carriers have proven satisfactory. The following examples are given by way of illustrations and are not limiting: -pure petroleum jellies of various viscosities of Codex,
-modified petroleum jellies as the salycilated petroleum jelly,
-mineral oils, -vegetable oils, particularly ethylenic oils comprising a small number of double bonds,
-lanoline, -oily continuous phase emulsions, -alcoholic solutions, etc.
Due to the powerful barrier developed by the cancerous cells with regards to their environment, and notably the thickening phenomenon of the cellular membranes, the penetration of the drug by the topical route is slow and difficult.
According to the invention, it has been found that is was advantageous to introduce topical preparation penetration agents into the 5methoxypsoralene such as: -isopropyl myristate,
-dimethyl sulphoxide (DMSO), etc.
The following clinical trials have been carried out with preparations containing 10,000 ppm of 5-methoxypsoralene in pure petroleum jelly.
All voluntary patients (a hundred of them) had family histories and personal histories of a skin cancer. They had all previously had many ablations of skin cancers, and all the previous treatments had not checked the formation of recurrent cancers.
The types of cancers of pre-cancerous lesions of these patients, which had been histologically proven were the following: -baso-cellular epitheliomas, -spino-cellular epitheliomas, -Hutchinson freckles actinic hyperkeratoses.
Some of these patients showed bilateral effects on the body or limbs so allowing a control to be set up, that is one side of the body or one limb received treatment and the other remained untreated.
All the patients chosen had no other serious illness.
All patients were treated for five weeks in the following manner:
Twice a week, a pure petroleum jelly based preparation containing 10,000 ppm of 5methoxypsoralene was applied to the tumour and to its periphery (1 to 2 cm beyond the clinically evaluated limit of the tumour). From one to three hours after this application, the patient was subjected to an UV.A exposure with an energy of 5 joules/cm2 to 1 0 joules/cm2 (at the end of the treatment) after having re-applied the product a quarter of an hour prior to the exposure. The irradiation was applied to the whole area to which the 5-methoxypsoralene preparation had been applied.
The results were as follows: The biopsies carried out at the end of the treatment, that is from the sixth week and later, showed a total necrosis of the tumour's cancerous cells (as well as healing of the normal tissues).
Biopsies were carried out every six months following the treatment and showed no sign of recurrent or residual illness over a period of three years.
The tolerance to the drug and irradiation was perfect, that is, without major phototoxic incident causing prolonged gaps in the treatment.
Localized actinic erythemas, which were rapidly regressive, appeared on some patients who had a high sensitivity.
It should be mentioned in this regard that the patients thus treated and for whom the treatment was totally successful generally had type I skin.
Type I skin is particularly prone to skin cancers and notably to phototoxic incidents.
In other clinical trials on the same types of epidermic proliferation tumours, the treatment consisted in a topical administration of 5methoxypsoralene in concentrations of 1,000 to
10,000 ppm, which was then doubled by an oral administration of tablets containing 5methoxypsoralene and UV.A exposure with an average energy of 5 joules/cm2. Once again the results were spectacular and there was total necrosis of the cancerous cells.
The daily posology for the oral treatment of the cancerous tumours may be as much as 400 to 800 mg of 5-methoxypsoralene due to the low toxicity of the latter. It is preferable to increase the dose of active substance rather than the quantity of energy distributed so that the UV.A exposure should always remain within the range of 10 joules/cm2.
In the case of malignant tumours of the mucous membranes accessible by the natural routes, treatment such as that described above is directly applicable, since UV.A radiation is able to penetrate to the very depth of the dermis. In the case of inner malignant tumours, the administration of 5-methoxypsoralene has to be followed by an exposure to a more penetrating radiation with an appropriate wave-length in order to bring the necessary energy to the deeper sites.
Claims (6)
1. Drugs for the treatment by the topical route of epidermic proliferation cancerous tumours, characterized in that they contain an active substance 5-methoxypsora lene at concentrations of 1,000 ppm to 10,000 ppm, in a therapeutically acceptable carrier.
2. Drugs according to claim 1, characterized in that they further contain penetration agents.
3. Drugs according to claim 2, wherein the penetration agent is dimethyl sulphoxide (DMSO).
4. Drugs according to claims 1 to 3, wherein the therapeutically acceptable carriers are petroleum jellies, mineral and vegetable oils, oily continuous phase emulsions, alcoholic solutions, etc.
5. Drugs for the treatment by the oral route of cancerous or pre-cancerous tumours, characterized in that they contain as active substance 5-methoxypsoralene in the form of tablets containing 200 to 400 mg of active substance per tablet.
6. Drugs according to any one of the preceding claims 1 to 5, characterized in that they are activated by UV.A exposure or by any other appropriate radiation.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8206262A FR2524801B1 (en) | 1982-04-09 | 1982-04-09 | DRUGS CONTAINING A PSORALENE DERIVATIVE |
| BE0/210731A BE896700A (en) | 1982-04-09 | 1983-05-09 | MEDICINAL PRODUCTS CONTAINING A PSORALENE DERIVATIVE. |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8315070D0 GB8315070D0 (en) | 1983-07-06 |
| GB2140686A true GB2140686A (en) | 1984-12-05 |
| GB2140686B GB2140686B (en) | 1986-09-17 |
Family
ID=36782343
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08315070A Expired GB2140686B (en) | 1982-04-09 | 1983-06-01 | Drugs containing a psoralene derivative |
Country Status (7)
| Country | Link |
|---|---|
| JP (1) | JPH0653664B2 (en) |
| AU (1) | AU559029B2 (en) |
| BE (1) | BE896700A (en) |
| CA (1) | CA1205386A (en) |
| CH (1) | CH656801A5 (en) |
| FR (1) | FR2524801B1 (en) |
| GB (1) | GB2140686B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0756477A4 (en) * | 1994-03-15 | 1999-05-19 | Gen Hospital Corp | METHODS OF PHOTOTHERAPEUTIC TREATMENT OF PROLIFERATIVE SKIN DISEASES |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9106365D0 (en) * | 1991-03-26 | 1991-05-15 | Bioglan Lab Ltd | An emollient for use with ultraviolet light |
| FR2695036B1 (en) * | 1992-09-03 | 1994-10-28 | Goupil Jean Jacques | Oil containing 5-methoxypsoralen at a concentration of 60 to 100 PPM and its use for the treatment of psoriasis. |
| CN116102713A (en) * | 2022-09-07 | 2023-05-12 | 江苏三木化工股份有限公司 | A kind of multi-arm structure amine epoxy curing agent and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2406444A1 (en) * | 1977-10-21 | 1979-05-18 | Goupil Jean Jacques | 5-Methoxy-psoralen for psoriasis treatment - prepd. from phloroglucinol via mono-methyl ether, 6-hydroxy-4-methoxy-coumaran-3-one and coumaran |
| LU80347A1 (en) * | 1977-10-21 | 1979-03-16 | Goupil J | 5-METHOXY-PSORALENE AS A NEW MEDICINAL PRODUCT AND SYNTHESIS |
-
1982
- 1982-04-09 FR FR8206262A patent/FR2524801B1/en not_active Expired
-
1983
- 1983-05-09 BE BE0/210731A patent/BE896700A/en not_active IP Right Cessation
- 1983-05-19 CH CH2751/83A patent/CH656801A5/en not_active IP Right Cessation
- 1983-05-24 AU AU14905/83A patent/AU559029B2/en not_active Ceased
- 1983-05-26 CA CA000428960A patent/CA1205386A/en not_active Expired
- 1983-06-01 JP JP58097768A patent/JPH0653664B2/en not_active Expired - Lifetime
- 1983-06-01 GB GB08315070A patent/GB2140686B/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0756477A4 (en) * | 1994-03-15 | 1999-05-19 | Gen Hospital Corp | METHODS OF PHOTOTHERAPEUTIC TREATMENT OF PROLIFERATIVE SKIN DISEASES |
Also Published As
| Publication number | Publication date |
|---|---|
| AU1490583A (en) | 1984-11-29 |
| JPH0653664B2 (en) | 1994-07-20 |
| JPS59222413A (en) | 1984-12-14 |
| GB8315070D0 (en) | 1983-07-06 |
| AU559029B2 (en) | 1987-02-19 |
| FR2524801B1 (en) | 1985-08-30 |
| CA1205386A (en) | 1986-06-03 |
| FR2524801A1 (en) | 1983-10-14 |
| CH656801A5 (en) | 1986-07-31 |
| BE896700A (en) | 1983-09-01 |
| GB2140686B (en) | 1986-09-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4826830A (en) | Topical application of glyciphosphoramide | |
| Abdel-Fattah et al. | An approach to the treatment of vitiligo by khellin | |
| ES2308810T3 (en) | USE OF AN INGENAN COMPOUND FOR THE PREPARATION OF A MEDICINAL PRODUCT FOR THE TREATMENT OF CANCER. | |
| Devi | Withaferin A: a new radiosensitizer from the Indian medicinal plant Withania somnifera | |
| CN103458882B (en) | Bakuchiol compositions for treating post-inflammatory hyperpigmentation | |
| Mullen et al. | Carcinogenic Effects of Monofunctional and Bifunctional Furocoumarins 1, 2 3 | |
| Grimaitre et al. | Topical colchicine therapy for actinic keratoses | |
| US7220438B2 (en) | Pharmacological activities of Curcuma longa extracts | |
| WO2001021185A1 (en) | Novel pharmacological activities of curcuma longa extracts | |
| JPH01501627A (en) | Composition for treating psoriasis | |
| US4970230A (en) | Drugs containing a psoralene derivative | |
| CN105030864B (en) | A kind of percutaneous dosing has the pharmaceutical composition and its application and preparation method of antalgic and inflammation relieving effect | |
| GB2140686A (en) | Drugs containing a psoralene derivative | |
| US5200425A (en) | Drugs containing a psoralene derivative | |
| JP7758770B2 (en) | Methods for treating basal cell carcinoma and glioblastoma | |
| US20130202540A1 (en) | Method for repair of acute and chronic injury, such as burned and photodamaged skin | |
| US10369170B1 (en) | Methods of treating basal cell carcinoma and glioblastoma | |
| Kumar et al. | Anti-cancer efficacy and mechanisms of usnic acid | |
| Pathak et al. | Photochemotherapeutic, photobiological, and photochemical properties of psoralens | |
| RU2088247C1 (en) | Method for enhancing effectiveness of radiation therapy | |
| Ramdhiani et al. | Mechanism of action, efficacy, and safety of propolis for the management of oral mucositis: A systematic review | |
| US10058611B2 (en) | Use of α-(8-quinolinyloxy) mono-substituted phthalocyanine zinc for treatment of psoriasis | |
| JP2527757B2 (en) | Compounds and compositions for reducing skin inflammation | |
| Zhong et al. | Photodynamic effects of Can-Sha photosensitizer on transplanted tumors in mice | |
| Mullen et al. | Carcinogenic Effects of Monofunctional and Bifunctional Furocoumarins 1, 2 3 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19960601 |