Intrauterine device having means for changing from uterine-retentive shape to nonuterine-retentive shape

• US 3,971,367 A
• Filed: 06/04/1975
• Issued: 07/27/1976
• Est. Priority Date: 12/27/1972
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Zaffaroni, Alejandro
• Primary Examiner(s): Trapp, Lawrence W.
• Application Number:
  US05/583,829
• Time in Patent Office: 419 Days
• Field of Search: 128/127-130, 128/260, 424/19, 424/14, 424/21, 424/22, 424/33, 424/37
• US Class Current: 128/833
• CPC Class Codes: A61F 6/144 with T-configuration
• CPC Class Codes: A61K 9/0039 Devices retained in the uterus for a prolonged period, e.g. intrauterine devices for contraception
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50

Abstract

An improved intrauterine device which delivers a predetermined therapeutically effective dosage of drug locally to the uterus over a defined period of time is disclosed. The device is initially of a uterine-retentive shape. The device is characterized by undergoing a structural biotransformation in the uterus such that at the completion of the defined period of drug delivery it has achieved a nonuterine-retentive configuration.

Claims

1. A drug dispensing intrauterine device, shaped and adapted for insertion and positioning in the uterine cavity, with the device comprising in combination:

a. a drug

b. a delivery means adapted for insertion into the uterine cavity and for dispensing a therapeutically effective amount of drug to the uterine cavity over a defined period of time, and

c. retention means for retaining the delivery means within the uterine cavity throughout the defined period of drug dispensing time, said retention means having an initial unit structural configuration sahped and adapted for insertion and positioning in the uterine cavity including means formed of a member selected from the group consisting of protein, collagen, elastin, keratin, resilin and fibrin that undergo biotransformation in the uterine cavity to a different and nonuterine-retentive configuration whereby at the completion of said defined period of drug dispensing time, said drug dispensing device is facilely removed or spontaneously eliminated from the uterine cavity.

2. The device according to claim 1 wherein the drug is a member selected from the group consisting of progestational and estrogenic steroids.

3. A drug dispensing intrauterine device, shaped and adapted for insertion and positioning into the uterine cavity, with the device comprising in combination:

a. a drug

b. a delivery means adapted for insertion into the uterine cavity and for dispensing a therapeutically effective amount of drug to the uterine cavity over a defined period of time, and

c. retention means for retaining the delivery means within the uterine cavity throughout the defined period of drug dispensing time, said retention means having an initial unit structural configuration shaped and adapted for insertion and positioning in the uterine cavity including means formed of a member selected from the group consisting of a noncross-linked polysaccharide, algin, pectin, carrageenin, chitin, chondrotin sulfate, agar-agar, guar, locust bean gum, gum arabic, gum karaya, tragacanth and gum ghatti that undergo biotransformation in the uterine cavity to a different and nonuterine-retentive configuration and shape whereby at the completion of said defined period of drug dispensing time, said drug dispensing device is facilely removed or spontaneously eliminated from the uterine cavity.

4. The device according to claim 3 wherein the drug is a member selected from the group consisting of progestational and estrogenic steroids.

5. A drug dispensing intrauterine device, shaped and adapted for insertion and positioning into the uterine cavity, with the device comprising in combination:

a. a drug

b. a delivery means adapted for insertion into the uterine cavity and for dispensing a therapeutically effective amount of drug to the uterine cavity over a defined period of time, and

c. retention means for retaining the delivery means within the uterine cavity throughout the defined period of drug dispensing time, said retention means having an initial unit structural configuration shaped and adapted for insertion and positioning in the uterine cavity including means formed of a member selected from the group consisting of starch, oxystarch, starch phosphate, carboxymethyl starch, sulfaethyl starch, aminoethyl starch, amidoethyl starch, starch esters, starch maleate, starch succinate, starch benzoate, starch acetate and mixtures of starch and gelatin that undergo biotransformation in the uterine cavity to a different and nonuterine-retentive configuration and shape whereby at the completion of said defined period of drug dispension time, said drug dispensing device is facilely removed or spontaneously eliminated from the uterine cavity.

6. The intrauterine dispensing device according to claim 5 wherein the drug is a member selected from the group consisting of progestational and estrogenic steroids.

7. A drug dispensing intrauterine device, shaped and adapted for insertion and positioning into the uterine cavity, with the device comprising in combination:

a. a drug

b. a delivery means adapted for insertion into the uterine cavity and for dispensing a therapeutically effective amount of drug to the uterine cavity over a defined period of time, and

c. retention means for retaining the delivery means within the uterine cavity throughout the defined period of drug dispensing time, said retention means having an initial unit structural configuration shaped and adapted for insertion and positioning in the uterine cavity including means formed of a member selected from the group consisting of cellulose, hydroxyethylated cotton, carboxymethylated cotton and mixtures thereof that undergo biotransformation in the uterine cavity to a different and nonuterine-retentive configuration and shaped whereby at the completion of said defined period of drug dispensing time, said drug dispensing device is facilely removed or spontaneously eliminated from the uterine cavity.

8. The drug dispensing device according to claim 7 wherein the drug is a member selected from the group consisting of progestational and estrogenic steroids and mixtures thereof.

9. A drug dispensing intrauterine device, shaped and adapted for insertion and positioning into the uterine cavity, with the device comprising in combination:

a. a drug

b. a delivery means adapted for insertion into the uterine cavity and for dispensing a therapeutically effective amount of drug to the uterine cavity over a defined period of time, and

c. retention means for retaining the delivery means within the uterine cavity throughout the defined period of drug dispensing time, said retention means having an initial unit structural configuration shaped and adapted for insertion and positioning in the uterine cavity including means formed of a member selected from the group consisting of poly(vinyl alcohol), poly(ethylene oxide), poly(vinyl pyrrolidone), poly(acrylamide), poly(vinyl imidazole), poly(glycolic acid), poly(lactic acid), poly(peptide), poly(methacrylamide), copolymers of acrylamide and methacrylamide, water soluble hydrophilic polymers of uncross-linked hydroxyalkyl acrylates and methacrylates, and copolymers of poly(glycolic acid) and poly(lactic acid) that undergo biotransformation in the uterine cavity to a different and nonuterine-retentive configuration and shape whereby at the completion of said defined period of drug dispensing time, said drug dispensing device is facilely removed or spontaneously eliminated from the uterine cavity.

10. The device according to claim 9 wherein the drug is a member selected from the group consisting of progestational and estrogenic steroids and mixtures thereof.

11. A drug dispensing intrauterine device, shaped and adapted for insertion and placement in the uterine cavity, with the device comprising in combination:

a. a drug

b. a delivery means adapted for insertion into the uterine cavity for dispensing a therapeutically effective amount of drug to the uterine cavity over a defined period of time, and

c. retention means for retaining the delivery means within the uterine cavity throughout the defined period of drug dispensing time, said retention means having an initial unit structural configuration shaped and adapted for insertion and placement in the uterine cavity including means formed of a polyester of the formula;

##EQU4## wherein W is a member selected from the group consisting of --CH₂ -- and ##EQU5## and Y has a value such that the molecular weight of the polymer is above 4,000, which polyester undergoes biotransformation in the uterine cavity to a different and nonuterine-retentive configuration and shape whereby at the completion of said defined period of drug dispensing time, said drug dispensing device is facilely removed or spontaneously eliminated from the uterine cavity.

12. The device for dispensing a drug according to claim 11 wherein the drug is a member selected from the group consisting of progestational and estrogenic steroids and mixtures thereof.

13. A drug dispensing device adapted and sized for insertion and placement in the uterine cavity comprising in combintion:

a. a drug

b. a delivery means for supplying a therapeutically effective amount of drug to said cavity over a period of time, said delivery means comprising a body of erodible material formed of a member selected from the group consisting of poly(vinyl alcohol), poly(ethylene oxide), poly(vinyl pyrrolidone), poly(acrylamide), poly(vinyl imidazole), poly(glycolic acid), poly(lactic acid), poly(peptide), poly(methacrylamide), copolymers of acrylamide and methacrylamide, water soluble hydrophobic polymers of uncross-linked hydroxyalkyl acrylates and methacrylates, and copolymers of poly(glycolic acid) and poly(lactic acid) having drug dispersed therethrough which upon erosion releases drug at a controlled rate, and

c. retention means for retaining said delivery means within the cavity throughout the period of time, with the retention means undergoing biotransformation by erosion in the cavity from a uterine retentive configuration to a nonuterine-retentive configuration whereby at the completion of the period of time, said device is facilely removed or spontaneously eliminated from said uterine cavity.

14. A drug dispensing device adapted, shaped and sized for insertion and placement in the uterine cavity comprising in combination:

a. a drug

b. a delivery means for supplying a therapeutically effective amount of drug to said cavity over a period of time, said delivery means comprising a body of erodible material formed of a member selected from the group consisting of protein, collagen, elastin, keratin, resilin and fibrin having drug dispersed therethrough which upon erosion releases drug at a controlled rate, and

c. retention means for retaining said delivery means within the cavity throughout the period of time, with the retention means undergoing biotransformation by erosion in the cavity from a uterine retentive configuration to a nonuterine-retentive configuration whereby at the completion of the period of time, said device is facilely removed or spontaneously eliminated from said uterine cavity.

15. A drug dispensing device adapted for insertion into the uterine cavity comprising in combination:

a. a drug

b. a delivery means for supplying a therapeutically effective amount of drug to said cavity over a period of time, said delivery means comprising a body of erodible material formed of a member selected from the group consisting of a noncross-linked polysaccharide, algin, pectin, carrageenin, chitin, chondrotin sulfate, agar-agar, guar, locust bean gum, gum arabic, grum karaya, tragacanth and gum ghatti having drug disprsed therethrough which upon erosion releases drug at a controlled rate, and

c. retention means for retaining said delivery means within the cavity throughout the period of time, with the retention means undergoing biotransformation by erosion in the cavity from a uterine retentive configuration to a nonuterine-retentive configuration whereby at the completion of the period of time, said device is facilely removed or spontaneously eliminated from said uterine cavity.

16. A drug dispensing device adapted for insertion into the uterine cavity comprising in combination:

a. a drug

b. a delivery means for supplying a therapeutically effective amount of drug to said cavity over a period of time, said delivery means comprising a body of erodible material formed of a member selected from the group consisting of starch, oxystarch, starch phosphate, carboxymethyl starch, sulfaethyl starch, aminoethyl starch, amidoethyl starch, starch esters, starch maleate, starch succinate, starch benzoate, starch acetate and mixtures of starch and gelatin having the drug dispersed therethrough which upon erosion releases drug at a controlled rate, and

c. retention means for retaining said delivery means within the cavity throughout the period of time, with the retention means undergoing biotransformation by erosion in the from a froma uterine retentive configuration to a nonuterine-retentive configuration whereby at the completion of the period of time, said device is facilely removed or spontaneously eliminated from said uterine cavity.

17. A drug dispensing device adapted for insertion into the uterine cavity comprising in combination:

a. a drug

b. a delivery means for supplying a therapeutically effective amount of drug to said cavity over a period of time, said delivery means comprising a body of erodible material formed of a member selected from the group consisting of cellulose, hydroxyethylated cotton, carboxymethylated cotton and mixtures thereof having drug dispersed therethrough which upon erosion releases drug at a controlled rate, and

c. retention means for retaining said delivery means within the cavity throughout the period of time, with the retention means undergoing biotransformation by erosion in the cavity from a uterine retentive configuration to a nonuterine-retentive configuration whereby at the completion of the period of time, said device is facilely removed or spontaneously eliminated from said uterine cavity.

18. A drug dispensing device adapted for insertion into the uterine cavity comprising in combination:

a. a drug

b. a delivery means for supplying a therapeutically effective amount of drug to said cavity over a period of time, said delivery means comprising a body of erodible material formed of a polyester of the general formula;

##EQU6## wherein W is a member selected from the group consisting of ##EQU7## and mixtures thereof, and y has a value such that the molecular weight is above 4,000 and having drug dispersed therethrough which upon erosion releases drug at a controlled rate, and

c. retention means for retaining said delivery means within the cavity throughout the period of time, with the retention means undergoing biotransformation by erosion in the cavity from a uterine retentive configuration to a nonuterine-retentive configuration whereby at the completion of the period of time, said device is facilely removed or spontaneously eliminated from said uterine cavity.

19. A drug dispensing device for insertion into a body cavity with the device comprising in combination:

a. a drug

b. a drug delivery means adapted for insertion into the cavity and for dispensing a therapeutically effective amount of drug to the cavity over a prolonged period of time, said delivery means comprising a wall enclosing said drug and permeable to the passage of said drug by diffusion and formed of a member selected from the group consisting of silicone rubbers, poly(dimethylsiloxane), ethylene vinylacetate copolymers, poly(isoprene), poly(isobutylene), poly(butadiene) and cross-linked hydrolyzed poly(vinylacetate), with passage of drug through the wall controlling the rate of release from the device, and

c. retention means for retaining the delivery means within the cavity throughout the prolonged period of time, said retention means having an initial unit structure shape adapted for insertion and positioning in the cavity, with the retention means undergoing biotransformation in the cavity to a second structure noncavity-retentive structure whereby at the completion of the prolonged period of time, said device is facilely removed or spontaneously eliminated from the cavity.

20. A drug dispensing device for insertion into a mammalian body cavity with the device comprising in combination:

a. a drug present in a dosage amount to produce a physiological or pharmacological effect,

b. a drug delivery means adapted and sized for insertion into the cavity and for dispensing a therapeutically effective amount of drug to the cavity over a prolonged period of time, said delivery means comprising a wall enclosing said drug and permeable to the passage of said drug by diffusion, with passage of drug through the wall controlling the rate of release from the device, and

c. retention means having a memory for retaining the delivery means within the cavity throughout the prolonged period of time, said retention means having an initial unit structural shape adapted for insertion, positioning and placement in the cavity, with the retention means and membory undergoing a gradual loss in the cavity to a different noncavity-retentive configuration whereby at the completion of the prolonged period of time, said device is facilely removed or spontaneously eliminated from the cavity.

21. The drug dispensing device according to claim 20 wherein the device dispenses a drug to a cavity selected from the group of cavities consisting of vagina and uterus.

22. A drug dispensing device adapted and sized for insertion into a mammalian body cavity comprising in combination:

a. a drug present in a unit dosage amount for producing a local or systemic effect,

b. a drug delivery means adapted for insertion into the cavity and for dispensing a therapeutically effective amount of drug to said cavity over a period of time, wherein said delivery means comprises an erodible material which upon erosion releases drug, and

c. retention means having a memory for retaining the delivery means within the cavity throughout the prolonged period of time, said retention means having an initial unit structural shape adapted for insertion, positioning and placement in the cavity, with the retention means and memory undergoing a loss throughout the prolonged period of time in the cavity to a different noncavity-retentive configuration whereby at the completion of the prolonged period of time, said device is facilely removed or spontaneously eliminated from the cavity.

23. The drug dispensing device according to claim 22 wherein the device dispenses a drug to a cavity selected from the group consisting of the vagina and uterus.