GB1587638A - Iodophenoxyphenylalkenoic acid derivatives and pharmaceutical preparations containing them - Google Patents
Iodophenoxyphenylalkenoic acid derivatives and pharmaceutical preparations containing them Download PDFInfo
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- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4826—Trypsin (3.4.21.4) Chymotrypsin (3.4.21.1)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/4873—Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
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- 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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
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- 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
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
- A61K8/66—Enzymes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/06—Preparations for care of the skin for countering cellulitis
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Abstract
The active product corresponds to the formula <IMAGE> in which R is an aliphatic carboxylic acid group, preferably an acetic, propionic or butyric acid residue. The medicinal preparation displays therapeutic activity, in particular against hypercholesterolaemia and hyperlipidaemia. It is intended more especially for the treatment of excess lipid deposits and cellulite.
Description
(54) IODOPHENOXYPHENYLALKENOIC ACID DERIVATIVES
AND PHARMACEUTICAL PREPARATIONS CONTAINING
THEM
(71) We, BEREMA S. A., a body corporate organised and existing under the laws of Switzerland, of 7 Avenue de Delay 1110-Morges, Switzerland, do hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- The invention concerns new medicinal preparations with a therapeutic action particularly against hypercholesterolemia, hyperlipemia (hyperlipidemie) and certain forms of obesity with overweight fat and/or cellulitis.
Many active substances are already known for the treatment of lipidic excesses and cellulitis, the most recently disclosed substances including 3,5,3'triiodothyroacetic acid. However, this has a relatively short life since it is eliminated from the human blood in about 5 hours, and consequently has to be administered to the patient repeatedly, 4 to 5 times a day. This is a serious drawback, particularly for the patient, and especially considering that such treatments are generally of long duration (from 3 to 12 months). Research has therefore been carried out in an attempt to find substances which have a similar therapeutic action but a much longer life. This research has led to the discovery of a marked retarding action inherent in 3,5,3',5'-tetraiodothyroacetic, 3,5,3',5'tetraiodothyropropionic and similar acids and inorganic or organic salts thereof. It takes about 15 to 18 hours to eliminate these substances from the human blood stream, which means that the number of administrations can be reduced to I or 2 a day at the maximum.
The invention consequently comprises a new medicinal preparation with a therapeutic action particularly against hypercholesterolemia, hyperlipemia and obesity, containing as its active substance at least one compound represented by the general formula (I).
wherein R is a carboxy substituted aliphatic radical, or a pharmaceutically acceptable salt thereof, either alone or mixed with other active substances and/or with excipients.
The R group in the compound of formula (I) is preferably an acetic, propionic or butyric acid radical.
Depending on the treatment required and the method of administration chosen, the active substance of formula (I), preferably 3,5,3',5'tetraiodothyroacetic acid or its potassium or sodium salt, is thus used alone or mixed with other substances which may themselves be inactive or therapeutically active.
For oral administration the active substance of formula (I) is used preferably with clofibrate and/or a choleretic cholagogue, such as divanillidenecyclohexanone (DVCH), cyclobutyrol, sorbitol, triamcinolone, amferpramone, meprobamate, acetazolamide, alphachymotripsin, bromelains, a lipase, vitamin A, etc.
For administration by injection, the active substance of formula (I) is used preferably with hyaluronidase and/or mucopolysaccharidases, alphachymotrypsin, etc.
For rectal administration the active substance of formula (I) is used preferably with mucopolysaccharidases.
For transcutaneous administration, finally, the active substance of formula (I) is used preferably with a compound activating adenylate cyclase, such as catecholamine, e.g. adrenaline or noradenaline, bamethan, neosynephrine, salbutamol, etc. and/or with xanthine or derivatives thereof, hyaluronidase, mucopolysaccharidases, acetazolamide, etc.
The toxicity of formula (I) compounds and more particularly of 3,5,3',5'tetraiodothyroacetic acid is low. It has been measured in mice, 5 days after a single intraperitoneal administration of the above compound in solution, diluted 50% with propanediol, and also in rats, 5 days after a single intravenous administration of the same solution as for the mice, or 5 days after a single oral administration of the active compound suspended in a carboxymethylcellulose gel. Table I shows the DLso value in microgrammes per kilogramme live weight.
TABLE I
animal administration DLsn (llg/kg) mouse intraperitoneal 350 rat intravenous 300 rat oral 825 The toxicity of 3,5,3',5'-tetraiodothyroacetic acid has also been studied by observations of dogs, 4 months after oral administration of the active substance diluted with lactose, in doses of 150 ,ug in capsule form per kg per day. The observations were as follows: no abnormal reaction; food consumption, which was reduced for a time, returned to the same rate as that of the untreated control dogs; respiratory and cardiac rhythms normal; no disturbance of the electrocardiogram, which retains its normal basic sinusoidal movement; no discernable biological change. After autopsy a slight pallor of the thyroid glands was observed, whereas the liver, kidneys and spleen were normal, as was the weight of the heart. Nothing special was observed on histological examination of the thyroid, liver, bone medulla or on analysis of the blood formulation.
The suitability of 3,5,3',5'-tetraiodothyroacetic acid for percutaneous penetration was measured in rats. A cream containing 0.2% of compound, with part in radio-active form to provide a tracer, was applied to the animals. Rapid passage into the blood was noted, the appearance of radio-activity in the blood being observed less than 10 minutes after application.
The therapeutic effect of a treatment based on 3,5,3',5'-tetraiodothyroacetic acid on induced cholesterolemia was then studied in chickens in the following manner: 50 chickens were subjected to an atherogenic diet for 30 days, designed to create a high concentration of cholesterol in the blood; this brought the average total quantity of cholesterol (average for 50 chickens) from 125 mg per 100 ml of blood (normal quantity) to 340 mg per 100 ml (induced cholesterolemia). 30 chickens were then given 500 ,ug of the above active substance orally per kg per day, the other 29 chickens (1 chicken having died following the atherogenic diet) being used as a control group. The atherogenic diet was maintained both for the 19 'control' chickens and throughout the treatment of the 30 'treated' chickens. The results obtained are set out in Table II below.
TABLE 11
Duration of treatment - 36 days 57 days Total cholesterol (in mg/100 ml) Control chickens 340 315 330 Treated chickens 340 145 145 The above Table shows that 3,5,3',5'-tetraiodothyroacetic acid has an effective therapeutic action against hypercholesterolemia, since the quantity of cholesterol in the blood returns to an almost normal level after 36 days of treatment, bearing in mind that the atherogenic diet is maintained.
The clinical effect of some medicinal preparations according to the invention has been studied, particularly with regard to therapeutic action against hypercholesterolemia, hyperlipemia and obesity. The conditions of administration and results obtained are described in the following examples 1 to 5:
Example 1
3,5,3',5'-tetraiodothyroacetic acid alone is administered 3 times a day at 350 yg a time to 3 men (subjects 1 to 3) and 4 women (subjects 4 to 7) of ages ranging from 35 to 52 years. The results obtained are set out in Table III.
TABLE III
Subject 1 2 3 4 5 6 7 Duration of treatment (weeks) 3 3 4 3 4 5 3 Cholesterol Before 3.40 3.50 3.90 4.15 4.2 3.20 3.80 (mg/ml) After 2.20 2.20 2.60 3.20 3.10 2.50 2.40 Total lipids Before 7.0 8.0 6 8.2 9 10.2 8 (mg/ml) After 6.0 6.0 5.4 7.9 7.5 8.0 6.5 Weight of subject (kg) Before 71 97 84 65 62 70 48 After 63 92 79 60 59 64 47 Height of subject (m) 1.62 1.75 1.76 1.54 1.60 1.53 1.55 Reduction in measurement (cm) 72 Waist 3 5 5 7 3 Hips 4 6 5 5 4 Thighs 2 2 3 4 2 3 ~ Example 2
A preparation in capsule form containing 350 ,ug of 3,5,3',5'tetraiodothyroacetic acid, 25 mg of amfepramone and 100 mg of meprobamate are administered at the rate of 2 capsules a day to 4 male patients aged 45 to 55 years.
The results obtained are shown in Table IV.
TABLE IV
Subject 1 2 3 4 Duration of treatment (weeks) 3 3 8 8 Cholesterol Before 3.10 4.50 4.50 3.20 (mg/ml) After 2.60 2.50 3.10 2.50 Total lipids Before 7.5 9.0 9.5 7.8 (mg/ml) After 6.5 7.5 8.2 6.0 Weight of subject (kg) Before 72 87 81 00 After 68 81 77 90 Height of subject (m) 1.70 1.75 1.65 1.80 Reduction in measurement ( cm) Waist 4 6 1 5 8 Hips 3 5 1 4 6 Thighs 2 2 3 2 Example 3
A cream containing 100 ml of 3,5,3',5'-tetraiodothyroacetic acid, 15,000 TRU of mucopolysaccharidases and an excipient (e.g. containing 12 g of cetomacrogol, 5 g of lauric acid hexylester, 0.05 g of methyl p-oxybutyrate and 0.05 g of propyl poxybutyrate, the remainder being water) qsq 100 g, is applied locally to 5 women suffering from obesity with cellulitis. The results are summarised in Table V.
TABLE V
Subject 1 2 3 4 5 Duration of treatment (weeks) 4 6 6 6 6 Cutaneous suppleness Before nil average nil nil nil After good fairly good fairly good good good Orange peel effect Before yes yes yes yes yes After improved much much d little much improved improved improved improved Reduction in measurements (cm) Waist 4 6 3 5 4 Hips 3 4 3 6 4 Thighs 2 3 2 4 2 Tolerance G G G G G NB. Improved = appearance of skin improved
Much improved = appearance of skin much improved
Little improvement = little improvement in appearance of skin
G = Good
Good tolerance is taken as meaning that no discern able side effects were found in the women to whom the above cream was applied.
Example 4
3,5,3',5'-tetraiodothyroacetic acid is applied in the form of a 0.2% solution in dilute propane diol, by ionisation (electrode - 15 mA), at the rate of 20 minutes twice a week, alternating with application of the cream described in Example 3.
A clear decrease in rolls of fat is observed, also a clear decrease in subcutaneous infiltration of the cellulitic type and hence an improvement in measurements; tolerance for the treatment is found to be excellent.
Example 5
Two subjects are treated for 8 weeks with a preparation containing 0.350 mg of 3,5,3',5'-tetraiodothyroacetic acid and 0.5 mg of triamcinolone. They show a marked decrease in weight and a simultaneous reduction in obesity as well as an improvement in biological parameters.
Example 6
A preparation in capsule form containing 0.5 mg of 3,5,3',5'tetraiodothyroacetic acid, 200 mg of divannillidone cyclohexanone and 25000 I.U.
of axerophtol acetate (vitamin A) is administered to 4 male patients at the rate of 3 capsules per day. The treatment is carried out for 2 to 3 weeks and repeated 2 to 3 times, with one week's therapeutic rest between each treatment. The results obtained are set out in Table IV.
TABLE VI
Subject | 1 | 2 | 3 1 4 Duration of treatment (weeks) 2 x 2 2 x 3 3 x 2 2 x 3 Total cholesterol Before 3.10 3.05 2.80 3.60 (mg/ml) After 2.40 2.50 2.10 2.70 Total lipids Before 6.9 6.1 6.0 7.05 (mg/ml) After 8 5.9 5.4 5.6 The above Examples demonstrate that, whatever embodiments and methods of administration are adopted, the medicinal preparations according to the invention are valuable therapeutic agents for the treatment of hypercholesterolemia, hyperlipemia, localised lipodystrophia and certain forms of obesity with excess weight and/or sub-cutaneous infiltration of the cellulitic type.
The following compositions A to D may further be mentioned as examples to illustrate the invention. The dosing ranges given for these compositions represent the total daily dosage.
A. For oral administration total daily dosage
tetraiodothyroacetic acid 1 to 3 mg
and/or tetraiodothyropropionic acid I to 3 mg
and/or clofibrate l to 1.5 g
and/or cyclobutyrol 0.3 to 0.8 g
and/or DVCH 0.6 to Ig and/or sorbitol 3 to 5 g
and/or triamcinolone 0.05 to 2 mg
and/or amfepramone 50 to 100 mg
A. For oral administration total daily dosage
and/or meprobamate 0.05 to 0.02 g
and/or acetazolamide 50 to 300 mg
and/or alphachymotripsin 50 to 50,000 U.S. Hb
and/or bromelain (extracted from
sativus pineapple and comosus pineapple) 100,000 to 300,000 units
and/or lipase 10,000 to 30,000 units of
lipolytic activity
B. For administration by injection
tetraiodothyroacetic acid 0.5 to 1.5 mg
and/or tetraiodothyropropionic acid 0.5 to 1.5 mg
and/or hyaluronidase 5,000 to 20,000 TRU
and/or mucopolysaccharidases 10,000 to 20,000 TRU
and/or alphachymotrypsine 50,000 UC. Hb
C. Rectal administration
tetraiodothyroacetic acid 0.5 to 1.5 mg
and/or tetraiodothyropropionic acid 0.5 to 1.5 rng
and/or mucopolysaccharidases 10,000 to 15,000
D. Transcutaneous administration a) Cream, gel, ointment, liniment doses as percentages
tetraiodothyroacetic acid 0.1 to 0.2
and/or tetraiodothyropropionic acid 0.1 to 0.2
and/or adrenaline, noradrenaline, bamethan,
neosynephrine, salbutanal, xanthine and
xanthine derivatives.
and/or hyaluronidase 5,000 to 20,000 TRU
and/or mucopolysaccharidases 10,000 to 15,000 TRU
andior acetazolamine 3 to 10% b) solutions for ionisation
tetraiodoethyroacetic acid 0.05 to 0.2
and/or tetraiodothyropropionic acid 0.05 to 0.2
and/or mucopolysaccharidases 10,000 to 15,000 TRU
Furthermore, preparations with extensive diffusion, in the galenical form of microspheres, may be provided to make better use of the retarding action inherent in the active compounds of Formula (I).
Finally, the preparation of the active compounds of formula (I), which are used in the medicinal preparations according to the invention, will now be described with reference to the following example, which concerns the preparation of 3,5,3',5'-tetraiodothyroacetic acid.
3,5,3',5'-triiodothyroacetic and similar iodophenolic products may be prepared e.g. by the following successive reactions: a) formation of the compound of the formula
by reacting chlorodinitrobenzaidehyde and p-methoxyphenol in the presence of CH3-H2 or of a reducing agent such as bisulfite; b) replacement of the two nitro groups with two -NH2 groups by reduction
(Raney nickel) in an alcoholic medium; then diazotation of the non isolated
diamine and Sandmeyer reaction in the presence of an iodine-iode solution in
a sulphuric acid medium, to replace the two -NH2 groups with two iodo
groups; c) formation of the corresponding acid by treatment with PCl5 and obtaining ttie chlorine derivative, then treating the derivative with KCN, conversion into
nitrile and hydrolysis by HI in the presence of red phosphorus; d) iodisation by I2 is an ammoniacal medium to provide the desired tetraiodo
derivative, after recrystallisation in absolute alcohol, having a melting point of
241 C and the following spectral properties: - infra-red spectrometry (KBr
pellet) # OH 3460 cm-1
vC=O 1708 cm-1 # C-O-C ll47cm-1 - UV spectrometry maximum absorption at 300 mm + 1.5 (e196m= 590) nuclear magnetic resonance
(solvent: (CD3)2 CO; s in pprn; internal reference TMS)
s protons appearance integration (protons) 8.3-9.5 OH, COOH low 2 exchangeable with D2O 7.88 H2 and H6 singlet 2 7.15 H'2 and H'6 singtet 2 3.68 CH2 singlet 2 WHAT WE CLAIM IS:1. Compounds of the formula
where R is a carboxy substituted aliphatic radical, and non-toxic, pharmaceutically acceptable salts thereof with organic or inorganic bases.
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (8)
- **WARNING** start of CLMS field may overlap end of DESC **.3,5,3',5'-triiodothyroacetic and similar iodophenolic products may be prepared e.g. by the following successive reactions: a) formation of the compound of the formulaby reacting chlorodinitrobenzaidehyde and p-methoxyphenol in the presence of CH3-H2 or of a reducing agent such as bisulfite; b) replacement of the two nitro groups with two -NH2 groups by reduction (Raney nickel) in an alcoholic medium; then diazotation of the non isolated diamine and Sandmeyer reaction in the presence of an iodine-iode solution in a sulphuric acid medium, to replace the two -NH2 groups with two iodo groups;c) formation of the corresponding acid by treatment with PCl5 and obtaining ttie chlorine derivative, then treating the derivative with KCN, conversion into nitrile and hydrolysis by HI in the presence of red phosphorus; d) iodisation by I2 is an ammoniacal medium to provide the desired tetraiodo derivative, after recrystallisation in absolute alcohol, having a melting point of 241 C and the following spectral properties: - infra-red spectrometry (KBr pellet) # OH 3460 cm-1 vC=O 1708 cm-1 # C-O-C ll47cm-1 - UV spectrometry maximum absorption at 300 mm + 1.5 (e196m= 590) nuclear magnetic resonance (solvent: (CD3)2 CO; s in pprn; internal reference TMS)s protons appearance integration (protons) 8.3-9.5 OH, COOH low 2 exchangeable with D2O 7.88 H2 and H6 singlet 2 7.15 H'2 and H'6 singtet 2 3.68 CH2 singlet 2 WHAT WE CLAIM IS:1. Compounds of the formulawhere R is a carboxy substituted aliphatic radical, and non-toxic, pharmaceutically acceptable salts thereof with organic or inorganic bases.
- 2. A compound according to claim 1, where R is -CH2COOH,-CH2CH2COOH or -CH2CH2CH2COOH.
- 3. The alkali and alkaline earth metal salts of the compound claimed in claim 2.
- 4. A pharmaceutical preparation comprising a compound or salt according to any one of the preceding claims in admixture with a pharmaceutically acceptable carrier or diluent and/or with one or more other pharmaceutically active ingredients.
- 5. A preparation according to claim 4, in orally administrable form and which comprises said compound or salt in admixture with one or more of the following: a choleretic cholagogue, cyclobutyrol, sorbitol, triamcinolone, amfepramone, meprobamate, acetazolamide, alphachymotripsin, a bromelain, a lipase or Vitamin A.
- 6. A preparation according to claim 4, in parenterally administrable form and which comprises said compound or salt in admixture with a mucopolysacchridase, a hyaluronidase or alphachymotripsin.
- 7. A preparation according to claim 4 in transcutaneously administrable form and which comprises said compound or salt in admixture with a catchecholamine, bamethan, neosynephrine, salbutamol, xanthine or a xanthine derivative, hyaluronidase, a mucopolysacchridase or acetazolamide.
- 8. A preparation according to claim 7, comprising said compound or salt in admixture with adrenaline or noradrenaline.
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB23722/77A GB1587638A (en) | 1977-06-03 | 1977-06-03 | Iodophenoxyphenylalkenoic acid derivatives and pharmaceutical preparations containing them |
CH564078A CH630803A5 (en) | 1977-06-03 | 1978-05-24 | Medicinal preparations, for the treatment of hypercholesterolaemia in particular |
FR7815888A FR2433943A1 (en) | 1977-06-03 | 1978-05-29 | DRUG PREPARATIONS ESPECIALLY FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA |
FR8219398A FR2515962B1 (en) | 1977-06-03 | 1982-11-19 | DRUG PREPARATIONS CONTAINING A TETRAIODOTHYROCARBOXYLIC ACID DERIVATIVE IN PARTICULAR FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA |
FR8219401A FR2515961B1 (en) | 1977-06-03 | 1982-11-19 | DRUG PREPARATIONS CONTAINING A TETRAIODOTHYROCARBOXYLIC ACID DERIVATIVE, PARTICULARLY FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA |
FR8219399A FR2520230B1 (en) | 1977-06-03 | 1982-11-19 | DRUG PREPARATIONS CONTAINING A TETRAIODOTHYRO-CARBOXYLIC ACID DERIVATIVE IN PARTICULAR FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB23722/77A GB1587638A (en) | 1977-06-03 | 1977-06-03 | Iodophenoxyphenylalkenoic acid derivatives and pharmaceutical preparations containing them |
Publications (1)
Publication Number | Publication Date |
---|---|
GB1587638A true GB1587638A (en) | 1981-04-08 |
Family
ID=10200238
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB23722/77A Expired GB1587638A (en) | 1977-06-03 | 1977-06-03 | Iodophenoxyphenylalkenoic acid derivatives and pharmaceutical preparations containing them |
Country Status (3)
Country | Link |
---|---|
CH (1) | CH630803A5 (en) |
FR (4) | FR2433943A1 (en) |
GB (1) | GB1587638A (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1990007329A1 (en) * | 1989-01-06 | 1990-07-12 | The Regents Of The University Of California | Selection method for pharmacologically active compounds |
EP1398024A3 (en) * | 1995-06-07 | 2004-12-15 | Karo Bio Ab | uses for thyroid hormones compounds |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5284971A (en) * | 1992-07-16 | 1994-02-08 | Syntex (U.S.A.) Inc. | 4-(3-cyclohexyl-4-hydroxy or-methoxy phenylsulfonyl) 3,5 dibromo phenyl acetic thyromimetic cholesterol-lowering agents |
US5643586A (en) * | 1995-04-27 | 1997-07-01 | Perricone; Nicholas V. | Topical compositions and methods for treatment of skin damage and aging using catecholamines and related compounds |
AU4625901A (en) * | 2001-03-19 | 2001-10-03 | Topic Empreendimentos E Participacoes S/C Ltda. | Pharmaceutical composition of carrier substance for products based on vitamin-E,bromeline and hyaluronidase |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE566423A (en) * | ||||
US3985892A (en) * | 1971-04-15 | 1976-10-12 | Jouveinal S.A. | Pharmaceutical preparation for percutaneous treatment of local edemas employing acetazolamide |
CH622703A5 (en) * | 1976-06-10 | 1981-04-30 | Berema Sa | Therapeutic compositions for treating deposits of excess fat and infiltrates causing cellulite |
FR2356427A2 (en) * | 1976-07-02 | 1978-01-27 | Ana Laboratoires | Compsn. for treatment of cellulitis and lipidic excess - contains mucopolysaccharidases opt. with hyaluronidase and active cpds. such as triiodo-thyroacetic acid, acetazolamide and aescin |
-
1977
- 1977-06-03 GB GB23722/77A patent/GB1587638A/en not_active Expired
-
1978
- 1978-05-24 CH CH564078A patent/CH630803A5/en not_active IP Right Cessation
- 1978-05-29 FR FR7815888A patent/FR2433943A1/en active Pending
-
1982
- 1982-11-19 FR FR8219399A patent/FR2520230B1/en not_active Expired
- 1982-11-19 FR FR8219401A patent/FR2515961B1/en not_active Expired
- 1982-11-19 FR FR8219398A patent/FR2515962B1/en not_active Expired
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1990007329A1 (en) * | 1989-01-06 | 1990-07-12 | The Regents Of The University Of California | Selection method for pharmacologically active compounds |
WO1990007330A1 (en) * | 1989-01-06 | 1990-07-12 | The Regents Of The University Of California | Selection method for specific useful pharmaceutical compounds |
EP1398024A3 (en) * | 1995-06-07 | 2004-12-15 | Karo Bio Ab | uses for thyroid hormones compounds |
Also Published As
Publication number | Publication date |
---|---|
FR2515961A1 (en) | 1983-05-13 |
FR2520230A1 (en) | 1983-07-29 |
FR2515962A1 (en) | 1983-05-13 |
CH630803A5 (en) | 1982-07-15 |
FR2515961B1 (en) | 1986-07-18 |
FR2520230B1 (en) | 1986-07-18 |
FR2515962B1 (en) | 1986-07-18 |
FR2433943A1 (en) | 1980-03-21 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PS | Patent sealed | ||
732 | Registration of transactions, instruments or events in the register (sect. 32/1977) | ||
PCNP | Patent ceased through non-payment of renewal fee |