IE55137B1 - Pharmaceutical compositions containing at least one polyfluorinated alcohol - Google Patents
Pharmaceutical compositions containing at least one polyfluorinated alcoholInfo
- Publication number
- IE55137B1 IE55137B1 IE1259/83A IE125983A IE55137B1 IE 55137 B1 IE55137 B1 IE 55137B1 IE 1259/83 A IE1259/83 A IE 1259/83A IE 125983 A IE125983 A IE 125983A IE 55137 B1 IE55137 B1 IE 55137B1
- Authority
- IE
- Ireland
- Prior art keywords
- composition according
- formula
- pharmaceutical composition
- parts
- weight
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 12
- 125000003158 alcohol group Chemical group 0.000 title 1
- 239000000203 mixture Substances 0.000 claims abstract description 19
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 15
- 239000008159 sesame oil Substances 0.000 claims abstract description 7
- 235000011803 sesame oil Nutrition 0.000 claims abstract description 7
- 235000012000 cholesterol Nutrition 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 4
- 239000004480 active ingredient Substances 0.000 claims abstract 2
- GUAMVMSOIYAUSK-UHFFFAOYSA-N 1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8-hexadecafluorononan-1-ol Chemical compound CC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(O)(F)F GUAMVMSOIYAUSK-UHFFFAOYSA-N 0.000 claims description 6
- KUGBQWBWWNPMIT-UHFFFAOYSA-N 1,1,2,2,3,3,4,4-octafluoropentan-1-ol Chemical compound CC(F)(F)C(F)(F)C(F)(F)C(O)(F)F KUGBQWBWWNPMIT-UHFFFAOYSA-N 0.000 claims description 6
- BYKNGMLDSIEFFG-UHFFFAOYSA-N 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoroheptan-1-ol Chemical compound OCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)F BYKNGMLDSIEFFG-UHFFFAOYSA-N 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 230000000118 anti-neoplastic effect Effects 0.000 abstract description 2
- 241001465754 Metazoa Species 0.000 description 8
- 230000001925 catabolic effect Effects 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000005303 weighing Methods 0.000 description 3
- 206010070863 Toxicity to various agents Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 230000001195 anabolic effect Effects 0.000 description 2
- 230000007665 chronic toxicity Effects 0.000 description 2
- 231100000160 chronic toxicity Toxicity 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 231100000915 pathological change Toxicity 0.000 description 2
- 230000036285 pathological change Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 231100000456 subacute toxicity Toxicity 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C31/00—Saturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C31/34—Halogenated alcohols
- C07C31/38—Halogenated alcohols containing only fluorine as halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Pharmaceutical compositions having antineoplastic activity comprise as the active ingredient component a) which is at least one polyfluoroalcohol of formula I: CHF2-(CF2)n-CH2OH (I> wherein n is 3, 5, 7 or 9; and optionally component b) cholesterol. Preferably the compositions containing two and still better at least three polyfluoroalcohols. A lipophilic solvent may be present, for instance sesame oil.
[GB2121280A]
Description
5513? The present invention relates to pharmaceutical compositions having antineoplastic activity which contain as the active components a) at least one polyfluorinated alcohol of formula 1: CHF2-(CH2)n - CHgOH (I) 5 in which n is the number 3, 5, 7 or 9 and optionally b) cholestrol, together with a lipophilic physiologically acceptable carrier.
Preferably, the compositions according to the invention contain at least two polyfluorinated alcohols of formula I and cholesterol.
It is even more advantageous to use a composiiton containing a) three polyfluorinated alcohols of formula I and in addition component b) cholestrol. The relative proportions, of the three polyfluorinated alcohols in the preferred compositions according to the invention may vary within wide limits, for example, each one constituting from 1 to 12 parts in a 15 total of 14 parts by weight, for instance between 12 parts of dodeca- fluoreheptanol, compound I in which n = 5, one part of octafluoropentanol, that is compound I in which n = 3, and one part of hexadecaflourononanol, compound I in which n = 7, up to one part of dodecafluoroheptanol plus one part of octafluoropentanol plus 12 parts hexadecafluorononanol.
The relative; proportions between component a) and b) may vary between 10: 1 and 1:10 by weight.
As stated, the composition according to the invention further contain a lipophilic carrier, for example a lipophilic solvent such as sesame oil or similar substances. All the components of the -2- 55137 pharmaceutical compositions according to the invention are well known and are commercially available. The following examples are given by way of Illustration of the compositions according to the invention.
Example 1 5 In 150 g of sesame oil are dissolved 3 g of octafluoropentanol, 5 g of dodecafluoroheptanol and 7.5 g hexadecafluorononanol. To the solution are added 2.5 g of cholesterol, while wanning for a short period of time at 35°- 40°C.
Example 2 10 To 100 g of sesame oil are added 2.5 g of dodecafluoroheptanol, 2.5 g of hexadecafluorononanol and 5 g of octafluoropentanol and 4 g of cholestrol while stirring up to complete dissolution.
Example 3 To 174 g of sesame oil are added the following components 15 while stirring up to complete dissolution. dodecafluoroheptanol (I, n = 5 ) 12g hexadecafluorononanol (I, n = 7) 4g octafluoronentanol (I, n = 3) 4g cholestrol 6g 20 The solution so obtained is distributed In 0.2 cc phials, 0.3 cc phials and 0.5 cc phials. The phials are sterilized by heating. Example 4 The composition is prepared in the same manner as in Example 1 adding 2 g of eicosafluoroundecanol (I, n = 9).
Example 5 The preparation is carried out in the same manner as in Example 1 substituting hexadecafluorononanol with equal amount of -3- 55137 octafluoropentanol , Example 6 The composition is prepared in the same manner as in Example 3, but the addition of cholesterol is omitted.
The composition according to Example 3 has been studied for acute toxicity, subacute toxicity and chronic toxicity.
Acute Toxicity - The subcutaneous Injection of doses higher than 0.5 cc in mice weighing 30 g causes, as the only symptom, sleep from which the animals wake up after a few hours without any abnormal manifestations.
The same phenomenon occurs in the case of rats in a dose higher than 1.5 cc per 100 g.
Subacute Toxicity - The administration by the subcutaneous route in the amount of 0.3 cc per day for a period of five days in one week, for three consecutive weeks, to mice weighing 30 g, causes no toxic symptoms 15 nor ϊί any pathological change noted in the animals after they have been killed.
Chronic Toxicity - Mice weighing 30g are subjected to subcutaneous injection of 0.2 cc per day, three times a week for three consecutive months. The animals did not exhibit any abnormal reactions with respect 20 to the controls nor was any pathological change noted in the animals after they were killed.
Equal results were obtained by administration of 0.4 cc per 100 g to rats. No toxic phenomena was noted by administering the composition to mice and rats by the oral route by means of a catheter 25 in the amount of 0.2 cc per day or 0,4 cc per 100 g per day in the case of rats for prolonged periods of time. No toxic symptom was noted also when 1% of the composition was added to the feed of the same animals although the animals manifested a certain reluctance to eat the feed -4- 55137 which contained this additive.
On the basis of the foregoing it is manifested that the compounds according to the invention are practically f*ee from toxicity. Pharmacology -The concept of anabolic/catabolic dualism and related 5 definitions as discussed hereinbelow are widely illustrated also from an experimental point of view both in animals and humans in E. Revici, Research in Physiopathology , Van Nostrand ed, Priceton, 1961. However, the novelty of the invention does not depend upon the correctness of the theories discussed in this treatise. The composition according to 10 the invention and particularly the composition according to Example 3 exhibit a very favorable effect on lesions thus exhibiting a catabolic effect. This effect is clearly shown by the healing of the wounds and bums. In the case of experimental cancer, a clear difference in effect has been noted depending whether the tumours are of anabolic or catabolic 15 character. If fact, in the first case the compositions according to the invention slow up only the death of the animals but the same compositions exert a substantial beneficial effect on the tumours which have a catabolic character, with necrosis, accumulation of fluid and cells in pyknosis.
Clinical Study - also 1n the treatment of patients affected by catabolic tumours, the composition according to the invention, administered by intramuscular injection in the dose of 2-3 cc develop a clearly favourable action eliminating or reducing the suffering for several hours.
Claims (6)
1. A pharmaceutic»! composition which contains as an active ingredient a component a) which is at least one polyfluoroalcohol of formula I: cHF2-(CF2)n - CH20H (I) wherein n is 3,5, 7 or 9; together with a lipophilic, physiologically acceptable carrier.
2. A pharamceutical composition according to claim 1 containing a second component b) comprising cholestrol.
3. A pharmaceutical composition according to claim 1 or 2 wherein said component a) contains at least two polyfluoroalcohols of formula I.
4. A pharmaceutical composition according to claim 3 wherein said component a) contains at least three .polyfluoroalcohols of formula I. 5. A pharmaceutical composition according to claim 3 or 4 wherein three polyfluoroalcohols of formula I are present, each one constituting from 1 to 12 parts in a total of 14 parts by weight. 6. A pharmaceutical composition according to claim 2 wherein the proportions between component, a) and component b) are between 10:1 and 1:10 by weight. 7. A pharmaceutical composition according to any of claims 1 to 6 in which the carrier comprises a lipophilic solvent. 8. A pharamceutical composition according to claim 7 wherein the lipophilic solvent is sesame oil. 9. A pharmaceutical composition according to claim 2 which consists of 6 parts by weight of dodecafluoroheptanol (formula I, n = 5), 2 parts by weight of hexadecafluorononanol (formula I, n = 7) 2 parts by weight of octafluoropentanol (formula I, n = 3), 3 parts by 5513 weight of cholesterol and 87 parts by weight of sesame oil. 10. A pharmaceutical composition according to any of claims 1 to 9 in unit dosage form for administration by the oral route. 11. A pharmaceutical composition according to any of claims 1 to 9 in unit dosage form for administration by the parenteral route. 12. A pharmacetucial composition substantially as described in any of the Examples . Dated this day the 27th of May, 1983. TOMKINS & CO., Applicant's Agents. (Signed)
5. Dartmouth Road, Dublin
6. -7-
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT8221553A IT8221553A0 (en) | 1982-05-28 | 1982-05-28 | PHARMACEUTICAL COMPOSITIONS ANTINEOPLASTIC ADAPTIVITY. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE831259L IE831259L (en) | 1983-11-28 |
| IE55137B1 true IE55137B1 (en) | 1990-06-06 |
Family
ID=11183507
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE1259/83A IE55137B1 (en) | 1982-05-28 | 1983-05-27 | Pharmaceutical compositions containing at least one polyfluorinated alcohol |
Country Status (16)
| Country | Link |
|---|---|
| JP (1) | JPS591414A (en) |
| AU (2) | AU552557B2 (en) |
| BE (1) | BE896838A (en) |
| CH (1) | CH653890A5 (en) |
| DE (1) | DE3319304A1 (en) |
| FR (1) | FR2527439A1 (en) |
| GB (1) | GB2121280B (en) |
| IE (1) | IE55137B1 (en) |
| IL (1) | IL68796A0 (en) |
| IN (1) | IN157042B (en) |
| IT (1) | IT8221553A0 (en) |
| LU (1) | LU84827A1 (en) |
| NL (1) | NL8301899A (en) |
| NZ (1) | NZ204393A (en) |
| SE (1) | SE8302976L (en) |
| ZA (1) | ZA833871B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3836971C1 (en) | 1988-10-31 | 1990-05-17 | Weck, Wolfgang, Dr.Med., 6990 Bad Mergentheim, De |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3219004C1 (en) * | 1982-05-19 | 1984-03-01 | Philippine Dr. 8000 München Hartmann | Pharmaceutical compositions for the treatment of tumours |
-
1982
- 1982-05-28 IT IT8221553A patent/IT8221553A0/en unknown
-
1983
- 1983-05-20 CH CH2772/83A patent/CH653890A5/en not_active IP Right Cessation
- 1983-05-26 BE BE2/60100A patent/BE896838A/en not_active IP Right Cessation
- 1983-05-26 JP JP58093889A patent/JPS591414A/en active Pending
- 1983-05-26 GB GB08314540A patent/GB2121280B/en not_active Expired
- 1983-05-26 IL IL68796A patent/IL68796A0/en unknown
- 1983-05-26 SE SE8302976A patent/SE8302976L/en not_active Application Discontinuation
- 1983-05-26 AU AU15000/83A patent/AU552557B2/en not_active Expired - Fee Related
- 1983-05-27 DE DE19833319304 patent/DE3319304A1/en not_active Ceased
- 1983-05-27 ZA ZA833871A patent/ZA833871B/en unknown
- 1983-05-27 FR FR8308776A patent/FR2527439A1/en not_active Withdrawn
- 1983-05-27 IE IE1259/83A patent/IE55137B1/en unknown
- 1983-05-27 NZ NZ204393A patent/NZ204393A/en unknown
- 1983-05-27 LU LU84827A patent/LU84827A1/en unknown
- 1983-05-27 NL NL8301899A patent/NL8301899A/en not_active Application Discontinuation
- 1983-05-27 IN IN673/CAL/83A patent/IN157042B/en unknown
-
1988
- 1988-05-04 AU AU15570/88A patent/AU1557088A/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| NL8301899A (en) | 1983-12-16 |
| SE8302976D0 (en) | 1983-05-26 |
| CH653890A5 (en) | 1986-01-31 |
| GB8314540D0 (en) | 1983-06-29 |
| AU1557088A (en) | 1988-11-10 |
| IT8221553A0 (en) | 1982-05-28 |
| IE831259L (en) | 1983-11-28 |
| FR2527439A1 (en) | 1983-12-02 |
| GB2121280A (en) | 1983-12-21 |
| GB2121280B (en) | 1985-08-29 |
| NZ204393A (en) | 1986-03-14 |
| AU552557B2 (en) | 1986-06-05 |
| SE8302976L (en) | 1983-11-29 |
| BE896838A (en) | 1983-09-16 |
| LU84827A1 (en) | 1983-11-17 |
| IN157042B (en) | 1986-01-04 |
| IL68796A0 (en) | 1983-09-30 |
| AU1500083A (en) | 1983-12-01 |
| ZA833871B (en) | 1984-07-25 |
| DE3319304A1 (en) | 1983-12-01 |
| JPS591414A (en) | 1984-01-06 |
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