Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-11-07
1997-11-04
Henley, III, Raymond
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
A61K 3135
Patent
active
056840403
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to novel compositions in the form of solid solutions, containing alkoxycoumarins with a heterocyclic substituent or of hydroxycoumarins esterified with a sulfonic acid as active substance and substance.
The invention additionally relates to a process for the production of these compositions and to their use as drugs.
Compositions in which the active substance is present homogeneously dispersed in a water-soluble polymer are generally known in numerous embodiments. For example, EP-A 240 773, EP-A 462 066, EP 521 310 and Drug Development and Industrial Pharmacy, 6 (2) (1980) 137-160 describe compositions containing hydroxypropylmethylcellulose or polyvinylpyrrolidone as carrier substance.
Alkoxycoumarins with a heterocyclic substituent ##STR1## R.sup.I, R.sup.II, R.sup.III, R.sup.IV =substituents Het=N, S and O containing heterocyclic radical and sulfonic esters of hydroxycoumarins ##STR2## R.sup.I, R.sup.II, R.sup.III =Substituents
as well as pharmaceutical compositions containing these substances as active substances are known and are proposed in U.S. Pat. No. 5,073,563 for the treatment of disorders of the central nervous system, especially of neurodegenerative disorders and parkinsonism, and in EP-B 111 746 for the treatment of psychological disturbances, especially of depressions. The disadvantage of these active substances and their pharmaceutical compositions described therein is that they are unsatisfactory in respect of their bioavailability because of their low solubility in water. It is therefore possible for these coumarin derivatives which are in crystalline form to be absorbed only very slowly and incompletely after intake.
It is an object of the present invention to provide compositions in the form of solid solutions with good solubility and bioavailability as well as rapid absorption of the coumarin derivatives A.
We have found that this object is achieved by the compositions defined at the outset.
The invention furthermore relates to a process for their production, their use as drugs and their dosage forms.
The compositions according to the invention contain from the group of alkoxycoumarins with a heterocyclic substituent or hydroxycoumarins esterified with a sulfonic acid as active substance and water-soluble polymer B as carrier substance.
Suitable alkoxycoumarins A' with a heterocyclic substituent are the compounds specified in U.S. Pat. No. 5,073,563, and those which are preferably suitable here have a thiadiazole residue as heterocyclic substituent and are claimed in the cited publication. Particularly suitable are
Suitable hydroxycoumarins A" esterified with sulfonic acid are the compounds described in EP-B 111 746.
The principle according to the invention is very particularly suitable for compositions with 3,4-dimethyl-7-(2-isopropyl-1,3,4-thiadiazol-5-yl)methoxycoumarin A'/1 ##STR3## from the group of alkoxycoumarins A' with a heterocyclic substituent, and with 7-hydroxy-3,4-dimethylcoumarin ethanesulfonic ester A"/1 ##STR4## from the group of hydroxycoumarins A" esterified with sulfonic acid as active substance.
The following water-soluble polymers B may be mentioned: hydroxypropyl- and hydroxybutylcellulose hydroxypropylmethylcellulose carboxymethylcellulose well as copolymers of ethylene oxide and propylene oxide carrageenans, galactomannans, tragacanth, agar-agar, gum arabic, guar gum and xanthan gum
Preferred polymers B are methylcelluloses, hydroxypropylmethylcelluloses, hydroxypropylcellulose, polyvinylpyrrolidone and N-vinylpyrrolidone/vinyl acetate copolymers, especially polyvinylpyrrolidone and copolymers of 40-70% by weight of N-vinylpyrrolidone and 30-60% by weight of vinyl acetate.
The term water-soluble means that at least 0.5 g, preferably 2 g, of the polymer dissolve, possibly colloidally or with gel formation, in 100 g of water at 20.degree. C.
A solid solution is present when the active substance is essentially in the form of a molecular dispersion in the polymer matrix (J. Pharm. Sci. 60 (1971) 1281-1302).
The compositions according t
REFERENCES:
patent: 4618622 (1986-10-01), Schlecker et al.
patent: 5073563 (1991-12-01), Frickel et al.
Derwent Abstract, DE 830355 (1990).
Binder Rudolf
Grabowski Sven
Mueller Winfried
Rosenberg Joerg
Sanner Axel
BASF - Aktiengesellschaft
Henley III Raymond
LandOfFree
Compositions in the form of solid solutions does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compositions in the form of solid solutions, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compositions in the form of solid solutions will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1833398