# US 4,381,001 A · IUD Arrangement

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- Number: US 4,381,001 A
- Document ID: US4381001A
- Status: Granted
- Kind: A
- Application number: 06/165,187
- Filed: 1980-07-01
- Granted: 1983-04-26
- Earliest claimed: 1978-07-25
- Inventors: Seth T. Shaw, Jr.
- Web page: https://patentgrep.com/patent/US4381001A

## CPC

- A61K 9/0039: {Devices retained in the uterus for a prolonged period, e.g. intrauterine devices for contraception}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

A medicated intrauterine device insertable in and retained in the uterus for a predetermined time period and having a drug with a controlled release rate and said drug comprising a guanidine such as an aromatic monoguanidine, an aromatic diguanidine, a non-aromatic monoguanidine or a non-aromatic diguanidine to provide anti-fibrinolytic, anti-proteolytic and/or anti-conceptive action. The drug is one or a mixture of more than one of such guanidines, or a mixture of one or more of such guanidines with one or more amidines.

## Claims

### Claim 1

A medicated intrauterine device of the type insertable into the uterus for retention therein for a predetermined time period and comprising, in combination, a uterus insertable body member comprising a polymer matrix having an external surface contacting the uterus, a coating on a first portion of said external surface of said body member comprising a drug, and said drug compromising at least a guanidine in one of a non-biodegradable monomer, non-biodegradable dimer, non-biodegradable oligomer and non-biodegradable, cross-linked polymer form and said drug chemically bonded to said surface of said polymer matrix.

### Claim 2 (depends on 1)

The arrangement defined in claim 1 wherein:
said at least a guanidine of said drug selected from the class consisting of:
(a) aromatic monoguanidines;
(b) aromatic diguanidines;
(c) non-aromatic monoguanidines; and
(d) non-aromatic diguanidines.

### Claim 3 (depends on 1)

The arrangement defined in claim 1 wherein:
said at least a guanidine of said drug selected from the class of aromatic monoguanidines of the group: ##STR19## wherein R is selected from the class consisting of: (a) a carbon chain free of other elements;
(b) a carbon chain with at least one other element;
(c) an aromatic group free of additional carbon atoms, carbon chains and other elements;
(d) an aromatic group with at least one addition selected from the class consisting of carbon atoms, carbon chains and other elements;
(e) a cyclic non-aromatic group free of additional carbon atoms, carbon chains and other elements;
(f) a cyclic non-aromatic group with at least one addition selected from the class consisting of carbon atoms, carbon chains, and other elements; and
(g) a combination of at least two of (a), (b), (c), (d), (e) and (f); and
wherein: ##STR20## represents the benzene ring.

### Claim 4 (depends on 1)

The arrangement defined in claim 1 wherein:
said at least a guanidine of said drug selected from the class of aromatic diguanidines of the group: ##STR21## and wherein each guanidine group ##STR22## is in one of a meta or para position with respect to R.sub.1, and in which:
R.sub.1 is selected from the class consisting of:
(a) a hydrocarbon chain free of ether and ester bonds to the benzene ring; and
(b) a hydrocarbon chain having at least one bond selected from the class of ether bonds and ester bonds to the benzene ring;
R.sub.2 and R.sub.3 are selected from the class consisting of:
hydrogen, chlorine, bromine, iodine, hydroxyl group and alkyl group; and ##STR23## represents the benzene ring.

### Claim 5 (depends on 1)

The arrangement defined in claim 1 wherein:
said at least a guanidine of said drug selected from the class of non-aromatic monoguanidines of the group: ##STR24## wherein R is selected from the class consisting of: (a) a carbon chain free of other elements;
(b) a carbon chain with at least one other element;
(c) a cyclic non-aromatic group free of additional carbon atoms, carbon chains and other elements;
(d) a cyclic non-aromatic group with at least one addition selected from the class consisting of carbon atoms, carbon chains and other elements;
(e) a combination of at least two of (a), (b), (c), and (d).

### Claim 6 (depends on 1)

The arrangement defined in claim 1 wherein:
said at least a guanidine of said drug selected from the class consisting of non-aromatic diguanidines of the group: ##STR25## wherein R is selected from the class consisting of: (a) a carbon chain free of other elements;
(b) a carbon chain with at least one other element;
(c) a cyclic non-aromatic group free of additional carbon atoms, carbon chains and other elements;
(d) a cyclic non-aromatic group with at least one addition selected from the class consisting of carbon atoms, carbon chains and other elements;
(e) a combination of at least two of (a), (b), (c), and (d).

### Claim 7 (depends on 1)

The arrangement defined in claim 1 wherein:
said at least a guanidine of said drug selected from the class consisting of: ##STR26## ethyl-p-guanidinobenzoate, ##STR27## p-nitrophenyl-p'-guanidinobenzoate (commonly named NPGB), ##STR28## p-guanidinophenyl-p'-guanidinobenzoate, ##STR29##
1. 3 bis (2-bromo-4-guanidinophenoxy) propane, ##STR30## guanidinocyclohexane, and ##STR31##
1. 4 -di(2-guanidinovinyl)cyclohexane.

### Claim 8 (depends on 1)

The arrangement defined in claim 1 and further comprising:
a coating of copper on a second portion of said external surface of said body member.

### Claim 9

A medicated intrauterine device of the type insertable in the uterus for retention therein for a predetermined time period and comprising, in combination;
a uterus insertable body member having an external surface contacting the uterus, and said body member comprising a polymer matrix and at least one drug with said polymer matrix and said at least one drug providing an anti-fibrinolytic effect, a reversible anti-fertility effect, and an anti-proteolytic effect, and said at least one drug comprising at least a guanidine, and said at least one drug and said polymer matrix selected to provide said at least one drug releasable at a predetermined rate from said body member to the uterus;
a coating on a first portion of said external surface of said body member comprising one of a biodegradable cross-linked polymer and biodegradable cross-linked copolymer form of a second drug, and said second drug comprising at least a guanidine, and said second drug covalently bonded to said surface of said polymer matrix;
said second drug selected from the class consisting of:
(a) a mixture of an amidine and a guanidine;
(b) a mixture of more than one amidine and a guanidine;
(c) a mixture of an amidine and more than one guanidine;
(d) a mixture of more than one amidine and more than one guanidine;
(e) a guanidine; and
(f) a mixture of more than one guanidine; and
said one drug selected from the class consisting of:
(a) a mixture of an amidine and a guanidine;
(b) a mixture of more than one amidine and a guanidine;
(c) a mixture of an amidine and more than one guanidine;
(d) a mixture of more than one amidine and more than one guanidine;
(e) a guanidine; and
(f) a mixture of more than one guanidine.

### Claim 10

A medicated intrauterine device of the type insertable in the uterus for retention therein for a predetermined time period and comprising, in combination:
a uterus insertable body member having an external surface contacting the uterus, and said body member comprising a polymer matrix and at least one drug with said polymer matrix and said at least one drug providing an anti-fibrinolytic effect, a reversible anti-fertility effect, and an anti-proteolytic effect, and said at least one drug comprising at least a guanidine, and said at least one drug and said polymer matrix selected to provide said at least one drug releasable at a predetermined rate from said body member to the uterus; and
wherein said at least one drug comprises a soft hydrogel coating on a first portion of said external surface of said body member, and said at least one drug is in the form of one of a biodegradable cross-linked polymer and biodegradable copolymer covalently bonded to said body member.

### Claim 11 (depends on 10)

The arrangement defined in claim 10 wherein said at least one drug is selected from the class consisting of:
(a) a mixture of an amidine and a guanidine;
(b) a mixture of more than one amidine and a guanidine;
(c) a mixture of an amidine and more than one guanidine;
(d) a mixture of more than one amidine and more than one guanidine;
(e) a guanidine; and
(f) a mixture of more than one guanidine.

### Claim 12 (depends on 10)

The arrangement defined in claim 10 wherein said guanidine of said at least one drug is selected from the class consisting of:
(a) aromatic monoguanidines;
(b) aromatic diguanidines;
(c) non-aromatic monoguanidines; and
(d) non-aromatic diguanidines.

### Claim 13 (depends on 10)

The arrangement defined in claim 10 wherein
said at least one drug is selected form the class of aromatic monoguadines of the group: ##STR32## wherein R is selected from the class consisting of: (a) a carbon chain free of other elements;
(b) a carbon chain with at least one other element;
(c) an aromatic group with at least one addition selected from the class consisting of carbon atoms, carbon chains and other elements;
(e) a cyclic non-aromatic group free of additional carbon atoms, carbon chains and other elements;
(f) a cyclic non-aromatic group with at least one addition selected from the class consisting of carbon atoms, carbon chains, and other elements; and
(g) a combination of at least two of (2) (b), (c), (d), (e) and (f); and
wherein: ##STR33## represents the benzene ring.

### Claim 14 (depends on 10)

The arrangement defined in claim 10 wherein
said at least one drug is selected form the class of aromatic diguanidines of the group: ##STR34## and wherein each guanidine group ##STR35## is in one of a meta or para position with respect to R.sub.1, and in which:
R.sub.1 is selected from the class consisting of:
(a) a hydrocarbon chain free of ether and ester bonds to the benzene ring; and
(b) a hydrocarbon chain having at least one bond selected from the class of ether bonds and ester bonds to the benzene ring;
R.sub.2 and R.sub.3 are selected from the class consisting of:
hydrogen, chlorine, bromine, iodine, hydroxyl group and alkyl group; and ##STR36## represents the benzene ring.

### Claim 15 (depends on 10)

The arrangement defined in claim 10 wherein
said at least one drug is selected from the class of non-aromatic monoguanidines fo the group: ##STR37## wherein R is selected from the class consisting of: (a) a carbon chain free of other elements;
(b) a carbon chain with at least one other element;
(c) a cyclic non-aromatic group free of additional carbon atoms, carbon chains and other elements;
(d) a cyclic non-aromatic group with at least one addition selected from the class consisting of carbon atoms, carbon chains and other elements;
(e) a combination of at least two of (a), (b), (c), and (d).

### Claim 16 (depends on 10)

The arrangement defined in claim 10 wherein
said at least one drug is selected from the class consisting of non-aromatic diguanidines of the group: ##STR38## wherein R is selected from the class consisting of: (a) a carbon chain free of other elements;
(b) a carbon chain with at least one other element;
(c) a cyclic non-aromatic group free of additional carbon atoms, carbon chains and other elements;
(d) a cyclic non-aromatic group with at least one addition selected from the class consisting of carbon atoms, carbon chains and other elements;
(e) a combination of at least two of (a), (b), (c), and (d).

### Claim 17 (depends on 10)

The arrangement defined in claim 10 wherein
said at least one drug is selected from the class consisting of: ##STR39## ethyl-p-guanidinobenzoate, ##STR40## p-nitrophenyl-p'-guanidinobenzoate (commonly named NPGB), ##STR41## p-guanidinophenyl-p'-guanidinobenzoate, ##STR42##
1. 3 bis (20bromo-4-guanidinophenoxy) propane, ##STR43## guanidinocyclohexane, and ##STR44##