Body cavity drug delivery with thermoreversible gels containing polyoxyalkylene copolymers

Claim 2

A process for treating a condition requiring a medical device or the application of a medicament, which comprises administering to a body cavity of a mammal a hyperosmotic, iso-osmotic, or hypo-osmotic aqueous composition, having a buffered pH, which is a liquid at room temperature or below and an aqueous gel with a desired osmolality at mammalian body temperature, said aqueous composition containing; (1) about 20% to about 80% by weight of water and (2) about 10% to about 50% by weight of a polyoxyalkylene block copolymer of formula Y[(A).sub.n --E--H].sub.x (I) wherein A is a polyoxyalkylene moiety having an oxygen/carbon atom ratio of less than 0.5, x is at least 1, Y is derived from water or an organic compound containing x reactive hydrogen atoms, E. is a polyoxyethylene moiety, n has a value such that the minimum molecular weight of A is between about 500 to about 900, as determined by the hydroxyl number of an intermediate of formula Y[(A).sub.n --H].sub.x (II) and the total average molecular weight of the polyoxyalkylene block copolymer is at least about 5000; wherein the osmolality of the composition in the liquid state is adjusted to achieve the desired value of the osmolality of the aqueous gel by assuming that the polyoxyalkylene block copolymer does not contribute to the osmolality in the aqueous gel.

Claim 3

The process of claim 1, wherein said y in said polyoxyalkylene block copolymer is derived from a water soluble organic compound having 1 to about 6 carbon atoms and wherein said aqueous composition further contains a pharmacologically effective amount of a drug selected from the group consisting of antiparsitics and antihistamines.

Claim 4

The process of claim 1 wherein said Y in said polyoxyalkylene block copolymer is derived from a water soluble organic compound having 1 to about 6 carbon atoms and wherein said aqueous composition further contains a pharmacologically effective amount of a drug selected from the group consisting of antibacterials, decongestants, anti-inflammatories, antivirals, local anesthetics, antifungels, amoebicidals, trichomonocidals, analgesics, antiarthritics, antiasthmatics, anticoagulants, anticonvulsants, antidepressants, antidiabetics, antineoplastics, antipsychotics, antihypertensives, antiprotozoals, spermicidals, and muscle relaxants.

Claim 5

The process of claim 1 wherein Y in said formulas I and II is a water soluble organic compound having 1 to 6 carbon atoms, wherein said polyoxyalkylene block copolymer is selected from the group consisting of a polyoxyethylene-polyoxybutylene block copolymer, a polyoxyethylene-polyoxypropylene block copolymer and mixtures thereof, wherein the polyoxyethylene moiety constitutes at least about 70% by weight of the polyoxyalkylene block copolymer and wherein the pH is maintained at 7.4±0.2 and the osmolality of the aqueous gel is maintained at about 290 mOsm/kg.

Claim 6

The process of claim 4 wherein said polyoxyalkylene block polymer is selected from block copolymers which form aqueous gels at a concentration of about 10-40% by weight of the total weight of said composition.

Claim 7

The process of claim 5 wherein said Y is a compound selected form the group consisting of propylene glycol, glycerin, pentaerythritol, trimethylolpropane, ethylenediamine, and mixtures thereof.

Claim 8

The process of claim 6 wherein Y is derived from propylene glycol, A is the residue of propylene oxide, and the intermediate of Formula II has an average molecular weight of at least about 900.

Claim 9

The process of claim 6 wherein Y is derived from butylene glycol, A is the residue of butylene oxide, and the intermediate of Formula II has an average molecular weight of at least about 500.

Claim 10

The process of claim 6 wherein said polyoxyalkylene block copolymer has the formula HO(C.sub.2 H.sub.4 O).sub.b (C.sub.4 H.sub.8 O).sub.a (C.sub.2 H.sub.4 O).sub.b H (III) wherein a and b are integers such that the hydrophobe base represented by (C 4 H 8 O) a has an average molecular weight of at least 1000, as determined by hydroxyl number, the polyoxyethylene chain constitutes at least about 60% by weight of the polyoxyalkylene block copolymer, and the polyoxyalkylene block copolymer has a total average molecular weight of at least 5,000; or has the formula HO(C.sub.2 H.sub.4 O).sub.b (C.sub.3 H.sub.6 O).sub.a (C.sub.2 H.sub.4 O).sub.b H (IV) wherein a and b are integers such that the hydrophobe base represented by (C 3 H 6 O) a has an average molecular weight of at least about 1500, as determined by hydroxyl number, the polyoxyethylene chain constitutes at least about 60% by weight of the polyoxyalkylene block copolymer, and the polyoxyalkylene block copolymers has a total average molecular weight of at least 5,000; or has the formula ##STR4## wherein a and b are integers such that the polyoxyalkylene block copolymer has an average hydrophobe molecular weight of at least 2000, a hydrophile content of at least about 60% by weight, and a total average molecular weight of at least about 5,000.

Claim 11

The process of claim 9, wherein said total average molecular weight of said polyoxyalkylene block copolymer is at least about 15,000.

Claim 12

The process of claim 9, wherein said copolymer is ##STR5##

Claim 13

The process of claim 1 wherein said aqueous gel is hyperosmotic to mammalian body tissues.

Claim 14

The process of claim 1 wherein said aqueous gel is hypo-osmotic to mammalian body tissues.

Claim 15

A process for treating a condition requiring a medical device or the application of a medicament which comprises administering to a body cavity of a mammal a hypo-osmotic, hyperosmotic, or iso-osmotic aqueous composition having a buffered pH, which aqueous composition is an aqueous gel with a desired osmalality at mammalian body temperature, said aqueous composition containing. a surfactant and a polyoxyalkylene polyether said surfactant and said polyoxyalkylene polyether being present in a combined total amount not exceeding about 10 percent and having a molecular weight of about 10,000 to about 100,000 which is selected from the group consisting of (A) polyoxyalkylene polyethers prepared by reacting ethylene oxide and at least one lower alkylene oxide having 3 to 4 carbon atoms with at least one active hydrogen-containing compound having from 3 to 10 carbon atoms and from 3 to 6 active hydrogens to prepare a heteric or block copolymer intermediate and further reacting said copolymer intermediate with at least one alpha-olefin oxide having an average carbon chain length of about 20 to 45 aliphatic carbon atoms and wherein said alpha-olefin oxide is present in the amount of about 0.3 to 10 percent by weight based upon the total weight of said polyether and (a) polyoxyalkylene polyethers prepared by reacting ethylene oxide with at least one active hydrogen-containing compound having from 2 to 10 carbon atoms and from 2 to 6 active hydrogens to prepare a homopolymer intermediate and further reacting said homopolymer intermediate with at least one alpha-olefin oxide having an average carbon chain length of about 20 to 45 aliphatic carbon atoms and wherein said alpha-olefin oxide is present in the amount of about 0.3 to 10 percent by weight based on the total weight of said polyether; wherein the osmolality of the aqueous composition is adjusted to achieve the desired value of the osmolality of the aqueous gel by assuming that the polyoxyalkylene polyether does not contribute to the osmolality in the aqueous gel.

Claim 16

A process for treating a condition requiring a medical device or the application of a medicament which comprises administering to a body cavity of a mammal a hypo-osmotic, hyperosmotic, or iso-osmotic aqueous composition having a buffered pH, which aqueous composition is an aqueous gel with a desired osmalality at mammalian body temperature, said aqueous composition containing. a surfactant and a polyoxyalkylene polyether said surfactant and said polyoxyalkylene polyether being present in a combined total amount not exceeding about 10 percent and having a molecular weight of about 10,000 to about 100,000 which is selected from the group consisting of (A) polyoxyalkylene polyethers prepared by reacting ethylene oxide and at least one lower alkylene oxide having 3 to 4 carbon atoms with at least one active hydrogen-containing compound having from 3 to 10 carbon atoms and from 3 to 6 active hydrogens to prepare a heteric or block copolymer intermediate and further reacting said copolymer intermediate with at least one alpha-olefin oxide having an average carbon chain length of about 20 to 45 aliphatic carbon atoms and wherein said alpha-olefin oxide is present in the amount of about 0.3 to 10 percent by weight based upon the total weight of said polyether and (a) polyoxyalkylene polyethers prepared by reacting ethylene oxide with at least one active hydrogen-containing compound having from 2 to 10 carbon atoms and from 2 to 6 active hydrogens to prepare a homopolymer intermediate and further reacting said homopolymer intermediate with at least one alpha-olefin oxide having an average carbon chain length of about 20 to 45 aliphatic carbon atoms and wherein said alpha-olefin oxide is present in the amount of about 0.3 to 10 percent by weight based on the total weight of said polyether; wherein the osmolality of the aqueous composition is adjusted to achieve the desired value of the osmolality of the aqueous gel by assuming that the polyoxyalkylene polyether does not contribute to the osmolality in the aqueous gel.

Claim 17

The process of claim 14 wherein said polyether is polyether (B).

Claim 18

The process of claim 15 wherein said polyether is prepared using an alpha-olefin oxide having an average carbon chain length of about 20 to 30 carbon atoms, present in the amount of about 0.3 to 10 percent of the total weight of said polyether.

Claim 19

The process of claim 14 wherein said aqueous composition further contains a pharmacologically effective amount of a drug selected from the group consisting of antibacterials, decongestants, anti-inflammatories, antivirals, local anesthetics, antifungels, amoebicidals, trichomonocidals, analgesics, antiarthritics, antiasthmatics, anticoagulants, anticonvulsants, antidepressants, antidiabetics, antineoplastics, antipshychotics, antihypertensives, antiprotozoals, spermicidals, and muscle relaxants, wherein the surfactant is present at about 1% by weight or more, the polyoxyalkylene polyether is present at about 1% by weight of more, such that the combined amounts of surfactant and polyoxyalkylene polyether is less than about 10l% by weight, and the drug is present at about 0.01% to 60% by weight based on the total weight of the aqueous composition.

Claim 20

The process of claim 14, wherein said aqueous composition further contains a pharmacologically effective amount of a drug selected from the group consisting of antiparasitics and antipistamines.

Claim 21

The process of claim 14 wherein said polyether is prepared using a heteric copolymer intermediate and wherein the pH is maintained at 7.4±0.2 and the osmolality of the aqueous gel is maintained at about 290 mOsm/kg.

Claim 22

The process of claim 19 wherein said polyether is prepared using an alpha-olefin oxide having an average carbon chain length of about 20 to 30 carbon atoms, present in the amount of about 0.3 to 10 percent of the total weight of said polyether.

Claim 23

The process of claim 20 wherein said polyether contains a proportion of ethylene oxide residue to the residue of said lower alkylene oxide of about 70 to about 90 percent by weight of ethylene oxide residue to about 30 to about 10 percent by weight of the residue of said lower alkylene oxide.

Claim 24

The process of claim 21 wherein said polyether is prepared using propylene oxide as the lower alkylene oxide.

Claim 25

The process of claim 14 wherein said polyether is prepared using a block copolymer intermediate.

Claim 26

The process of claim 23 wherein said polyether is prepared using an alpha-olefin oxide having an average carbon chain length of about 20 to 30 carbon atoms, present in the amount of about 0.3 to 10 percent of the total weight of said polyether.

Claim 27

The process of claim 24 wherein said polyether is prepared using a proportion of ethylene oxide residue to the residue of said lower alkylene oxide of about 70 to about 90 percent by weight of ethylene oxide residue to about 30 to about 10 percent by weight of said lower alkylene oxide residue.

Claim 28

The process of claim 25 wherein said polyether is prepared using propylene oxide as the alkylene oxide.