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
  • A61K31/33—Heterocyclic compounds
  • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
• • 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
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• • 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
  • A61P31/04—Antibacterial agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

• This invention relates to methods of treating humans afflicted with psoriasis by treatment with an antipsoriatic amount of tin protoporphyrin (SnPP) or tin mesoporphyrin (SnMP).
• SnPP tin protoporphyrin
• SnMP tin mesoporphyrin
• SnPP and SnMP are known compounds. Their utility in the treatment of hyperbilirubinemia has been described by Drummond and Kappas. The utility of SnPP for this purpose is described in Proc. Nat. Acad. Sci. USA 78 6466-6470 (1981). The use of SnMP is described in commonly owned copending patent application Serial No: 715,515 filed March 25, 1985.
• psoriasis vulgaris is characterized by erythematous, scaling plaques that often begin in the extensor aspects of the body. It may be extremely widespread, with occasional total skin involvement. It is frequently distressing to the patient and occasionally life threatening.
• psoriasis Other clinical types include generalized pustular psoriasis, localized pustular psoriasis of palms and soles, and exfoliative or erythrodermic psoriasis. Histologically, psoriasis is characterized by acanthosis (thickened epidermis) and parakeratosis (nucleated cells in stratum corneum) and has been described as showing benign hyperplasia. The dermal blood vessels are abnormally tortuous and dilated, and lymphocytic infiltration is frequently seen in the dermis and occasionally in the epidermis.
• antipsoriatic drugs act to slow cell proliferation primarily or to normalize keratinization.
• Some of the effective therapies appear to act as antiproliferative agents, and either reduce rates of epidermal KNA synthesis and/or mitosis, or both.
• topical corticosteroids, anthralin, methotrexate, topical 5-fluorouracil, psoralen plus long-wave ultraviolet light inhibit epidermal DNA synthesis and/or mitotic rate.
• Retinoids may act primarily partially to correct the abnormal differentiation seen in psoriasis.
• SnPP and SnMP have antipsoriatic activity when administered to humans.
• the active agents may be administered parenterally in solution or suspension, or topically in a suitable cream or ointment.
• the patient is exposed to ultraviolet light as an integral part of the treatment.
• parenteral administration any of a wide variety of pharmaceutically acceptable carriers currently in use for the preparation of therapeutically useful parenteral compositions may be employed. These include, for example, vegetable and mineral oils such as sesame oil, cottonseed oil and various mineral oil fractions. Aqueous media made isotonic by the addition of sodium chloride, glucose or other standard solutes are presently preferred.
• the compositions may be buffered to maintain a fixed pH, normally between 7 and 8. The preferred pH is from 7.4 to 7.5.
• an isotonic solution can be prepared by dissolving the selected amount of SnPP or SnMP in 0.2N aqueous sodium hydroxide solution, adjusting to the selected pH with 1N hydrochloric acid, and making up to volume with 0.9% aqueous sodium chloride solution.
• concentration of antipsoriatic agent in the parenteral compositions will normally be from about 1 mg/ml to 50 mg/ml, and the dosage per treatment will be from 0.5 to 5.0 mg/kg body weight.
• the SnPP or SnMP can be provided in the form of gels, lotions, oils, creams and the like and may contain thickening agents, surfactants, coloring agents, buffers, humectants or other components normally used in such compositions.
• These novel compositions may also be made isotonic with a selected solute such as sodium chloride, glucose, sodium tartrate or other selected inorganic or organic solutes.
• topical compositions will typically contain from about 1 to 50 mg/ml of active agent together with a pharmaceutically acceptable carrier. They may be utilized by application to the affected area with a gauze pad, as an aerosol spray or other selected mode.
• Treatment with SnPP or SnMP is utilized together with exposure to ultraviolet light.
• the exposure may be to ultraviolet light itself, sunlight or any artificial light which includes light in the ultraviolet region of the spectrum. Exposure may take place simultaneously with the administration of the therapeutic agent or subsequent thereto, and will be effective so long as unmetabolized SnPP or SnMP remains in systemic distribution.
• the total dose of ultraviolet energy to which the patient is exposed should be at least 2.5 joules/cm 2 . There is no particular upper limit to the dose, but it should remain below the level at which exposure to ultraviolet radiation becomes toxic which is normally about 60 joules/cm 2 .
• Polysorbate 80 USP 10.000g Methylcellulose (4000 CPS) USP 1.33g
• UVA doses given in this case were 3.5 J/cm 2 to start with, and at the end of the study 12 J/cm 2 . Prior to the study he had failed to respond to PUVA in doses much higher than these utilized in the actual study.
• Her psoriasis started in 1960. It has been wide spread and distributed to most parts of the body, arms, legs, back, chest and head. Her disease has often been hard to treat. She had earlier been treated with local steroids, tar, UVB, PUVA, and Methorexate. The only real effective modality in her case was Methotrexate. Prior to this study she had been treated for 2 months with Dithranol and UVB without success.
• the patient was given SnPP injections at a dosage level of 2 umol/kg and was treated 3 - 4 times a week with UVA, starting at
• the body of the patient was, while in a standing position, exposed to UVA light 4-5 times a week for three weeks using a Waldmann UV 1000 cabin equipped with 26 UVA lamps.
• the output of the lamps was measured weekly using a

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Veterinary Medicine (AREA)
• Chemical & Material Sciences (AREA)
• Public Health (AREA)
• Medicinal Chemistry (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• General Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Oncology (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Communicable Diseases (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Nitrogen Condensed Heterocyclic Rings (AREA)
• Medicinal Preparation (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

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Publications (1)

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Cited By (4)

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Citations (2)

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• 1987
  • 1987-12-02 US US07/125,011 patent/US4782049A/en not_active Expired - Lifetime
  • 1987-12-07 DE DE8888900434T patent/DE3770465D1/de not_active Expired - Lifetime
  • 1987-12-07 WO PCT/US1987/003248 patent/WO1988004174A1/en not_active Ceased
  • 1987-12-07 JP JP63500719A patent/JPH01501627A/ja active Granted
  • 1987-12-07 AT AT88900434T patent/ATE63815T1/de not_active IP Right Cessation
  • 1987-12-07 KR KR1019880700932A patent/KR920002330B1/ko not_active Expired
  • 1987-12-07 EP EP88900434A patent/EP0295280B1/en not_active Expired - Lifetime
  • 1987-12-07 AU AU10812/88A patent/AU597144B2/en not_active Ceased
  • 1987-12-07 CA CA000553714A patent/CA1302253C/en not_active Expired - Lifetime
  • 1987-12-08 IE IE332387A patent/IE63507B1/en not_active IP Right Cessation
  • 1987-12-08 PH PH36181A patent/PH25224A/en unknown
• 1988
  • 1988-08-08 DK DK443088A patent/DK443088D0/da not_active Application Discontinuation

Patent Citations (2)

Non-Patent Citations (1)

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