US 4,346,709 A · Drug delivery devices comprising erodible polymer and erosion rate modifier

A device for delivering a beneficial drug at a controlled rate over a prolonged period, said device shaped, sized and adapted for delivering a drug to an animal environment of use, the device comprising:

(A) an erodible released rate controlling polymer of the formula:
##STR6## wherein (I) R.sub.1 is a member selected from the group consisting of divalent, trivalent and tetravalent radicals consisting of alkylene of 1 to 10 carbons;
alkenylene of 2 to 10 carbons;
alkyleneoxy of 2 to 6 carbons;
cycloalkylene of 3 to 7 carbons;
cycloalkylene of 3 to 7 carbons substituted with an alkyl of 1 to 7 carbons, alkoxy of 1 to 7 carbons, an alkenyl of 2 to 7 carbons, and an alkylene of 1 to 10 carbons;
cycloalkylene of 4 to 7 carbons;
cycloalkenylene of 4 to 7 carbons substituted with an alkyl of 1 to 7 carbons, an alkoxy of 1 to 7 carbons, alkenyl of 2 to 7 carbons, and an alkylene of 1 to 10 carbons;
arylene of 6 to 12 carbons;
arylene of 6 to 12 carbons substituted with an alkyl of 1 to 7 carbons, alkyloxy of 1 to 7 carbons, alkenyl of 2 to 7 carbons, and alkylene of 1 to 10 carbons;
wherein (II) R.sub.2 and R.sub.3 are selected from the grop consisting of alkyl of 1 to 7 carbons, alkenyl of 2 to 7 carbons, aryl or 6 to 12 carbons, an oxygen atom covalently bonded to the dioxycarbon atom, and when an oxygen atom R.sub.2 and R.sub.3 are a member selected from the group consisting of alkyloxy of 1 to 7 carbons;
alkenyloxy of 2 to 7 carbons;
and aryloxy of 6 to 12 carbons;
and when only one of R.sub.2 and R.sub.3 is selected from said member the other R.sub.2 and R.sub.3 is selected from the group consisting of alkyl of 1 to 7 carbons;
alkenyl of 2 to 7 carbons;
and aryl of 6 to 12 carbons;
wherein (III) R.sub.2 and R.sub.3 are intramolecularly covalently bonded to each other and to the same dioxycarbon atom, with at least one of R.sub.2 and R.sub.3 a ring oxygen atom forming a heterocyclic ring of 5 to 8 carbon and oxygen atoms when R.sub.2 and R.sub.3 are selected from the group consisting of alkylene of 2 to 6 carbons;
alkenylene of 2 to 6 carbons;
alkyleneoxy of 2 to 6 carbons;
alkenyleneoxy of 2 to 6 carbons;
alkylenedioxy of 2 to 5 carbons;
alkenylenedieoxy of 2 to 5 carbons;
oxa;
and a heterocyclic ring of 5 to 8 carbon and oxygen atoms substituted with an alkyl of 1 to 7 carbons, an alkyloxy of 1 to 7 carbons, an alkenyl of 2 to 7 carbons, and an alkenyloxy of 2 to 7 carbons;
wherein (IV) R.sub.2 and R.sub.3 are intramolecularly covalently bonded to each other and to the same dioxycarbon atom with at least one of R.sub.2 and R.sub.3 is a ring oxygen atom forming a fused polycyclic ring of 8 to 12 carbon and oxygen atoms when R.sub.2 and R.sub.3 are a member selected from the group consisting of aralkylene of 8 to 12 carbons;
aralkenylene of 8 to 12 carbons, aryloxy of 8 to 12 carbons;
aralkyleneoxy of 8 to 12 carbons;
aralkenyleneoxy of 8 to 12 carbons, aralkylenedioxy of 8 to 12 carbons;
aralkenylenedioxy of 8 to 12 carbons;
oxa;
and a fused polycyclic ring of 8 to 12 carbon and oxygen atoms substituted with an alkyl of 1 to 7 carbons, an alkyloxy of 1 to 7 carbons, an alkenyl of 2 to 7 carbons and an alkenyloxy of 2 to 7 carbons;
wherein (V) R.sub.2 and R.sub.3 are intramolecularly covalently bonded to each other and to the same dioxycarbon atom to form a 5 to 6 member carbocyclic ring;
(B) a beneficial drug in the device;
(C) an erosion rate modifier in the device in an amount that effects the period of time the device erodes and effects the amount of drug released as the device erodes over time;
and wherein n is greater than 10.

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A device for delivering a beneficial drug at a controlled rate over a prolonged period of time, which device is sized, shaped and adapted for delivering a drug to an animal, the device comprising (a) a polymer of the formula:

##STR7## wherein R.sub.1 is a member selected from the group consisting of divalent, trivalent and tetravalent radicals consisting of alkylene of 1 to 10 carbons;
alkenylene of 2 to 10 carbons;
alkyleneoxy of 2 to 6 carbons;
cycloalkylene of 3 to 7 carbons;
cycloalkylene of 3 to 7 carbons substituted with an alkyl of 1 to 7 carbons, alkoxy of 1 to 7 carbons, an alkenyl of 2 to 7 carbons, and an alkylene of 1 to 10 carbons;
cycloalkenylene of 4 to 7 carbons;
cycloalkenylene of 4 to 7 carbons substituted with an alkyl of 1 to 7 carbons, an alkoxy of 1 to 7 carbons, alkenyl of 2 to 7 carbons, and an alkylene of 1 to 10 carbons;
arylene of 6 to 12 carbons;
arylene of 6 to 12 carbons substituted with an alkyl of 1 to 7 carbons, alkyloxy of 1 to 7 carbons, an alkenyl of 2 to 7 carbons and an alkylene of 1 to 10 carbons;
wherein R.sub.2 and R.sub.3 are taken together to form a 5 to 8 member heterocycyclic ring selected from the group consisting of dioxolanyl;
dioxanyl;
dioxepanyl;
dioxocanyl;
dioxonanyl;
tetrahydrofuranyl;
dihydrofuranyl;
furyl;
pyranyl;
ocanyl;
and oxepanyl;
(b) an erosion rate modifier dispersed in the device, said erosion rate modifier is a member selected from inorganic metals and compounds that decrease rate of erosion of the polymer, and inorganic metals and compounds that increase the rate of erosion of the polymer;
(c) a dosage unit amount of a drug in the device, said drug a member selected from the group consisting of locally and systemically acting drugs;
and wherein n is greater than 10.

20 more elements

A method for administering a contraceptive steroid to a warm-blooded animal, which method comprises:

A. Admitting to the animal a bioerodible device, the device comprising:
1. a bioerodible polymer of the general structure:
##STR14## wherein R.sub.1 is a member selected from the group consisting of divalent, trivalent, and tetravalent radicals consisting of alkylene of 1 to 10 carbons;
alkenylene of 2 to 10 carbons;
alkyleneoxy of 2 to 6 carbons;
cycloalkylene of 3 to 7 carbons;
cycloalkylene of 3 to 7 carbons substituted with an alkyl of 1 to 7 carbons, alkoxy of 1 to 7 carbons, alkenyl of 2 to 7 carbons, and alkylene of 1 to 10 carbons;
cycloalkylene of 4 to 7 carbons;
cycloalkylene of 4 to 7 carbons substituted with an alkyl of 1 to 7 carbons, an alkoxy of 1 to 7 carbons, alkenyl of 2 to 7 carbons, and alkylene of 1 to 10 carbons;
arylene of 6 to 12 carbons;
arylene of 6 to 12 carbons substituted with an alkyl of 1 to 7 carbons, alkoxy of 1 to 7 carbons. alkenyl of 2 to 7 carbons and alkylene of 1 to 10 carbons;
wherein R.sub.2 and R.sub.3 are taken together to form a 5 to 8 member heterocyclic ring with at least one of R.sub.2 and R.sub.3 a ring oxygen atom, said ring selected from the group consisting of dioxolanyl, dioxanyl, dioxepanyl, dioxonanyl, tetrahydrofuranyl, dihydrofuranyl, furyl, ocanyl, and oxepanyl;
and n is greater than 10;
2. an effective amount of an erosion rate modifier that assists in regulating the rate of erosion of the polymer over time mixed with the polymer;
3. a dosage amount of a contraceptive steroid mixed with the polymer;
and,
B. administering a contraceptively effective amount of the steroid to the animal by the device bioeroding at a controlled rate over a prolonged period of time.

14 more elements

A method for administering a beneficially effective amount of a steroid to a warm-blooded animal, which method comprises:

A. placing on the animal a bioerodible device, the device comprising:
1. A bioerodible polymer of the following structure:
##STR19## wherein R.sub.1 is a member selected from the group consisting of divalent, trivalent, and tetravalent radicals consisting of alkylene of 1 to 10 carbons;
alkenylene of 2 to 10 carbons;
and alkyleneoxy of 2 to 6 carbons;
wherein R.sub.2 and R.sub.3 are taken together to form a 5 to 8 member heterocyclic ring with at least one of R.sub.2 and R.sub.3 a ring forming oxygen atom, said ring selected from the group consisting of dioxolanyl, dioxanyl, dioxepanyl, dioxonanyl, tetrahydrofuranyl, dihydrofuranyl, furyl, ocanyl and oxepanyl, and n is greater than 10;
2. an erosion rate modifier in an effective amount that assists in regulating the rate of erosion of the bioerodible polymer over time mixed with the polymer;
3. a steroid selected from the group consisting of cortical, androgenic, estrogenic, and progestational steroids, and mixtures thereof mixed with the polymer;
and
B. administering an effective amount of the steroid to the animal by the device bioeroding at a controlled rate over a prolonged period of time.

7 more elements

A device for delivering a beneficial drug at a controlled rate over a prolonged period of time, when the device is sized, shaped and adapted for delivering a drug to a drug receptor site, said device comprising (a) a polymer of the formula:

##STR20## wherein R.sub.1 is a member selected from the group consisting of alkylene of 1 to 10 carbons and alkenylene of 2 to 10 carbons;
R.sub.2 and R.sub.3 are taken together forming a heterocyclic ring selected from the group consisting of dioxolanyl;
dioxanyl;
dioxepanyl;
dioxocanyl;
dioxonanyl;
furyl, tetrahydrofruanyl;
dihydrofuranyl;
pyranyl;
ocanyl;
and oxepanyl;
a nontoxic erosion rate modifier admixed with the polymer in an effective amount that cooperates with the polymer for regulating the rate of erosion of the polymer over time;
a drug admixed with the polymer and the erosion rate modifier, which drug is released from the device to produce a beneficial therapeutic effect;
and n is greater than 10.

11 more elements

Drug delivery devices comprising erodible polymer and erosion rate modifier

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Drug delivery devices comprising erodible polymer and erosion rate modifier

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Abstract

Claims100