Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
  • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
  • A61K8/463—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur containing sulfuric acid derivatives, e.g. sodium lauryl sulfate

Definitions

• This invention relates to radioprotective agents and more particularly, to a novel compound which is especially useful as a protective agent against the deleterious effects of ionizing radiation.
• radioprotective agents are useful in a number of different fields. For example, in connection with the current space exploration program it is contemplated that various forms of animal life will be projected through areas of concentrated radiation wherein either external or internal protection will be required. It is evident that to the extent that chemical radioprotective agents are available, the external shielding provided in the space vehicle and hence its weight can be materially reduced. Therefore, the development of such radioprotective agents is important to the space program.
• Radioprotective agents provide the radiotherapist with means for increasing the dosage tolerance of healthy tissue surrounding a diseased area, thereby making possible the use of higher and hence more effective radiation levels for treatment of the diseased tissue.
• the 2-N-methylammoniumethylthiosulfuric acid which is believed to be a new compound, can be conveniently prepared by reaction of nitrogen mustard (N-methyl-betachloroeth-yl amine hydrochloride) with an alkali metal thiosulfate according to the following equation.
• the product obtained is an internal salt of the organothiosulfuric acid, commonly known as a z-witterion. While the equation has been written in terms of sodium thiosulfate, other alkali metal thiosulfates can be used. In order to illustrate the mehod of preparation of this compound, two exemplary procedures which have been found satisfactory are given herein.
• Example 1 A one-liter flask equipped with a reflux condenser, mechanical stirrer and heating mantle was charged with 0.55 mol (137 grams) of sodium thiosulfate pentahydrate and 137 grams of ethylene glycol solvent, and the mixture in the flask was heated and agitated until the thiosulfate dissolved. Thereafter, 0.5 mol (65 grams) of N-methyl-beta-chloroethylamine hydrochloride was added to the solution in the flask with continued heat and agitation. A 10% molar excess of the thiosulfate was used.
• the reaction mixture was held at pH 6 and refluxed at a temperature ranging from to 113 C. for a period of 3.5 hours. Consumption of thiosulfate was followed by iodine titration of aliquots withdrawn from the reaction mixture at various time intervals. During the terminal portion of the reaction period, no further consumption of thiosulfate was noted.
• a total net weight of 26 grams of crystalline methylammoniumethylthiosulfuri'c acid was obtained having a molecular weight by non-aqueous titration of 177 as compared with a theoretical M.W. of 171.
• the yield of the product was 27.3% and its melting point 160 to 162 C.
• Microchemical analysis showed that the product contained 20.96% carbon, 5.38% hydrogen, 8.25% nitrogen, and 37.16% sulfur as compared with a theoretical content of these elements of 21.20% C, 5.28% H, 8.20% N and 37.4% S. Ignition of a sample of the crystals over an open flame left no inorganic residue.
• Example 2 Two reaction bombs were each charged with 0.74 mol (96 grams) of nitrogen mustard, 0.81 mol (129 grams-10% excess) of anhydrous sodium thiosulfate and 600 ml. of a mixture of equal volumes of ethanol and water. The bombs were placed in a 120 C. oven for four hours. The contents of the bombs were then combined and filtered. The filtrate was concentrated on a roto-dryer to remove most of the solvent, and then filtered hot to separate the salt precipitated during concentration.
• Example 1 A quantity of 2-N-methylammoniumethylthiosulfuric acid as prepared in Example 1 was tested for toxicity and radioprotective activity.
• toxicity tests adult male mice weighing between 20 and 25 grams were employed. Both the control and experimental animals were picked at random from the same lot in order that their age and weight would be comparable. Groups of five mice were injected intra-peritoneally with an aqueous saline solution at a pH of about 7. The quantity of the solution used in the toxicity tests (and also in the radiation tests) was somewhat less than 2% of the body weight of the animals. Dosage levels of 250 to 500 milligrams per kilogram of body weight were administered to different groups of animals and mortality was reported for a period of 10 days. It was found that no mortality occurred at dosages of 300 mg./kg., and this drug level was used as a maximum in the radiation tests.
• mice were injected with a solution of the type described above. Drug levels of 300, 150, 75 and mg./kg. were administered to different groups of mice. The animals were then inserted in individual 50 ml. plastic centrifuge tubes which were placed radially on a rotating turntable so that each animal received an equal exposure of 800 roentgens of Whole body X-radiation.
• the X-ray apparatus was operated at 250 kv., 15 ms.; the radiation was filtered by 0.25 mm. of copper and 1.0 mm. of aluminum; and the target-skin distance was 75 cm. Dose rate was 40 r. to 43 r. per minute.
• the present invention provides a novel radioprotective compound that is markedly superior to various closely related chemical compounds.
• Table I show that the monomethyl derivative of ammoniumthiosulfuric acid claimed herein is superior to the unsubstituted ammoniumethylthiosulfuric acid and is also superior to the dimethyl substituted ammoniumethylthiosulfuric acid.
• the product of the present invention is substantially less toxic than for example the mercapto compounds previously proposed as radioprotective agents.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Dermatology (AREA)
• Birds (AREA)
• Epidemiology (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

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Applications Claiming Priority (1)

Publications (1)

Family

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Family Applications (1)

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Cited By (2)

Citations (4)

• 1961
  • 1961-12-22 US US161370A patent/US3284297A/en not_active Expired - Lifetime
• 1962
  • 1962-12-07 FR FR917943A patent/FR2500M/fr not_active Expired
  • 1962-12-17 GB GB47523/62A patent/GB964239A/en not_active Expired

Patent Citations (4)

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