LU84827A1 - PHARMACEUTICAL COMPOSITIONS CONTAINING AT LEAST ONE POLYFLUORINATED ALCOHOL - Google Patents

Description

The present invention relates to pharmaceutical compositions pos sedating an antinioplastic activity and containing, as active ingredients, (a) at least one polyfluorl alcohol of formula I: CHV (Cr2> n-CH20H (I) 5 in which n is a number equal to 3, 5, T or 9 and optionally (h) cholesterol.

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Preferably, the compositions according to the invention contain at least two polyfluorinated alcohols of formula (i) and cholesterol. It is even more

It is advantageous to use a composition containing (a) three polyfluorinated alcohols of formula (i) and in addition (h) cholesterol. The relative proportions of the three polyfluorinated alcohols in the preferred compositions according to the invention can vary between wide limits, for example of 12 parts of dodé-cafluoroheptanol (compound I in which n = 5) + 1 part of octafluoropentanol; 15 (compound I in which n = 3) + 1 part of hexadecafluorononanol (compound I

I in which n = T), to 1 part of dodecafluoroheptanol + 12 parts of octafluoro- | pentanol + 1 part of hexadecafluorononanol, up to 1 part of dodecafluoro- i heptanol + 1 part of octafluoropentanol +12 parts of hexadecafluorononanol J The relative proportions between components (a) and (h) can vary between 10: 1 and 1:10.

The composition according to the invention may also contain vehicles | lipophiles such as sesame oil or the like. All the com | pharmaceutical compositions according to the invention are well known and | j commercially available.

The following 25 examples, in which all the proportions are by weight, serve to illustrate the invention without in any way limiting its scope.

EXAMPLE 1

In 150 g of sesame oil, gold. dissolves 3 g of octafluoropentanol, 5 g of dodecafluoroheptanol or 7.3 g of riexadecafluc-rononanol. 2.5 g of cholesterol are added to the solution while heating for a short time at 35 ~ ko ° c.

EXE ·? LE 2 To 100 g of oil this sesame "add 2.3 g of dodecafluoroheptanol, 2.5 g of hexadecafluorononanol and 5 g of octafluoropentanol as well as t g of t! '· I I 2 cholesterol, shaking until completely dissolved.

EXAMPLE 3 To 17¾ g of sesame oil, the following components are added while stirring until complete dissolution: dodecafluoroheptanol (I, n = 5) 12g hexadecafluorononanol (l, n = 7) ig octafluoropentanol (i, n = 3 ) Itg - cholesterol 6 g IOn distribute the solution thus obtained in vials with a capacity of 10 ο 3 0.2 cm, in vials with a capacity of 0.3 cm and in vials with a capacity 3 of 0.5 cm. The vials are sterilized by heating.

EXAMPLE

The composition is prepared in the same way as in Example 1 by] ^ adding 2 g of eicosafluorundecanol (I, n = 9).

j EXAMPLE 5; The procedure is as in Example 1 but by replacing the hexadecafluo-

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rononanol with an equal amount of octafluoropentanol.

EXAMPLE 6 The procedure is as in Example S, but no cholesterol is added.

! The composition according to Example 3 was studied to determine the acute toxicity, the subacute toxicity and the chronic toxicity.

i: 25 Easy toxicity: The subcutaneous injection of doses greater than 0.5 cm in u 1 1 'mouse weighing 30 g causes, as the only swmpucme, sleep after which; animals wake up after a few hours without any abnormal manifestation. The same phenomenon occurs in rats with higher doses; v N <- "* + t ~. r __ | vs. I 5 ^ · CiL "pOXL · 1 Ü'J g *; —i, Subacute toxicity: Subcutaneous administration at a rate of 0.3 cm-3 d, per day for a period of 5 days during one week, for three; ' _ consecutive weeks, these mice weighing 30 g do not cause any toxic symptoms, W * * i, have been sacrificed.

! Chronic toxicity: Mice weighing 30 g are subjected to these sub-injections. 0.2 cnf * skin daily, three times a week for three consecutive months. The animals did not show any abnormal reaction compared to the controls and there was no pathological change in the animals after they were sacrificed.

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5 Identical results are obtained by administering ¾ cnr per 100 g to rats. No toxic phenomenon is observed when the composition is administered to mice and rats orally using an O n catheter at the rate of 0.2 cnr per day or 0, ¾ cnr per 100 g per day in the extended treatment framework. There are also no toxic symptoms when adding 1% of this composition to the diet of some animals, although some animals show a certain reluctance to eat foods containing this additive.

Based on the above, it is demonstrated that the compounds according to the invention are practically free from toxicity.

115 Pharmacology: The concept of anabolic / catabolic duality and related definitions, which will be discussed below, are also widely illustrated from an experimental point of view, both in animals and in humans by E. Revici, Research in physiopathology, Van Kostrand, ed.

j Princeton, 1961. However, the originality of the invention does not depend on the exactitude of the theories studied in this treatise. The compositions according to the invention and in particular the composition object of Example 3, has a very favorable influence on the lesions thus developing a catabolic effect. This influence is clearly shown by the healing of wounds and burns. In the case of experimental cancer, there was a very clear difference in behavior depending on the anabolic or catabolic nature of the tumors. In fact, in the first case, the compositions according to the invention only delay the release of animals, but these same compositions exert a significant beneficial effect on tumors of catabolic character, with necrosis and accumulation of this fluid and cells in pycnosis.

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!; Clinical study: Also in the treatment of patients affected by h - ”‘ tumors | * catabolic, the composition according to the invention administered by intra-I ^ · * 3 s I muscular injection at a dose of 2 to 3 which develop a clearly favorable action [’by eliminating or annealing, suffering thinking for several hours.

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Claims (8)

1 * * β I. Pharmaceutical composition having an antineoplastic activity, characterized in that it comprises, as active ingredient, a component (a) consisting of at least one polyfluorinated alcohol of formula (i) 5 CHF2- (CF2) n-CH20H '(I) in which n = 3, 5, 7 or 9 · - 2. Composition according to claim 1, characterized in that the active ingredient additionally contains a component (h ) consisting of cholesterol. "J". 3. Composition according to claim 1 or 2, characterized in that the component (a) contains at least two polyfluorinated alcohols of formula (i). Composition according to Claim 1 or 2, characterized in that the component (a) contains at least three polyfluorinated alcohols of formula (i). 5- Composition according to claim H, characterized in that the three polyfluorinated alcohols of formula (i) are present in proportions varying between 12: 1: 1 - 1: 12: 1 and 1: 1: 12. 6. Composition according to any one of claims 2 to 5 "characterized in that the ratio of component (a) to component (h) are between 10: 1 and 1:10. 7. Composition according to any one of the preceding claims, characterized in that it also contains a lipophilic solvent. 8. Composition according to claim 75 characterized in that the lipophilic solvent is sesame oil. 9- Composition according to any one of the preceding claims, characterized in that it comprises, by weight, 6 parts of dcôécafluoroheptanol 25 _ (formula I, n = 5), 2 parts of hexaâéeafluoronoranoi (formula I, n = î ), 2 parts of octafluoropentanol (formula I, n = 3), 3 parts of cholesterol and 87 parts of sesame oil. 10. Composition according to any one of these previous reverâieations, characterized in that it is under iron this ûr .; arorinated urinary round 30 * ‘‘ oral administration. II. Composition according to any one of Claims 1 to 9, characterized in that it is in the form of urinary doses suitable for administration by the parenteral route. > ’” • \ X \ • V