Vaginal ring

• US 4,155,991 A
• Filed: 03/03/1977
• Issued: 05/22/1979
• Est. Priority Date: 10/18/1974
• Status: Expired due to Term

• Current Assignee: Schering Ag (Merck & Co., Inc.)
• Original Assignee: Schering Ag (Merck & Co., Inc.)
• Inventors: Windt, Fred, Laudahn, Gerhard, Schopflin, Gisela, Hartmann, Heidemarie, Muhe, Barbara
• Primary Examiner(s): Rose, Shep K.
• Application Number:
  US05/774,170
• Time in Patent Office: 810 Days
• Field of Search: 128/260, 128/130, 424/15, 424/19-22, 424/28
• US Class Current: 424/432
• CPC Class Codes: A61F 6/08 Pessaries, i.e. devices worn in the vagina to support the uterus, remedy a malposition or prevent conception , e.g. combined with devices protecting against contagion
• CPC Class Codes: A61K 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• 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

A composite vaginal ring containing a safe and effective amount of a pharmaceutically active medicament, which comprises:

(a) a major supporting vaginal ring consisting essentially of a physiologically acceptable synthetic resin and having at least a portion of the annular surface thereof adapted to mate with corresponding minor, medicament-containing vaginal ring segment; and

(b) at least one minor, medicament-containing vaginal ring segment adapted to mate with the modified annular surface of said major supporting vaginal ring and consisting essentially of a safe and effective amount of a pharmaceutically active amount of a nonionic, lipophilic drug dissolved or uniformly suspended in an elastomeric, cross-linked LTV linear dimethylpolysiloxane resin.

Claims

1. A composite vaginal ring containing a safe and effective amount of a pharmaceutically active medicament, consisting essentially of:

(a) a supporting, medicament-free vaginal ring consisting essentially of a physiologically acceptable synthetic resin and having a continuous encircling pocket-like indentation along the inner edge of the annular surface along the central plane thereof adapted to mate with a corresponding smaller, medicament-containing inner encircling annular minor vaginal ring segment; and

(b) a smaller, vaginal medicament-containing inner encircling annular minor vaginal ring adapted to mate with the continuous encircling pocket-like indentation in the modified annular surface of said supporting, medicament-free vaginal ring along the central plane thereof and consisting essentially of a safe and effective amount of a pharmaceutically active nonionic, lipophilic vaginal drug dissolved or uniformly suspended in an elastomeric, crosslinked LTV linear dimethylpolysiloxane resin.

2. A vaginal ring according to claim 1, wherein said minor ring segment is vulcanized onto said major supporting ring.

3. A vaginal ring according to claim 1, wherein said LTV resin component consists essentially of a nontoxic pharmaceutical composition adapted for implantation into a human or animal body to provide a constant, uniform drug release rate over a time interval of several months or years, being substantially free of peroxide, acetic acid and metal salts of carboxylic acids and consisting essentially of a homogeneous mixture of:

(a) 85-95, preferably 89-91, parts by weight of an LTV linear dimethylpolysiloxane resin containing 0.05-0.5 molar percent of methylvinylsiloxane units, having a molecular weight of 20,000-50,000 and containing an average of 1.58-2.02 monovalent hydrocarbon residues per silicone atom;

(b) correspondingly 15-5, preferably 11-9, parts by weight of a cross-linking composition consisting essentially of a dimethylpolysiloxane cross-linking agent substantially free of methylvinylsiloxane units, having a molecular weight of 500-1000 and containing 1-3 Si--H bonds per molecule;

(c) a catalytic amount of a noble-metal based cross-linking catalyst; and

(d) a pharmaceutically active amount of a nonionic, lipophilic drug dissolved or uniformly suspended in said composition.

4. A vaginal ring according to claim 1, wherein said LTV resin component consists essentially of preferably 85-89 parts by weight of component (a) preferably 5-6 parts by weight of component (b);

together with 5-10 parts by weight of a dimethylpolysiloxane resin having a molecular weight of 10,000-40,000 and having 0.2-1.5 molar percent methylvinylsiloxane units as an auxiliary cross-linking agent.

5. A vaginal ring according to claim 1, wherein said LTV resin component consists essentially of

(a) 20-100 parts by weight of an organopolysiloxane having a viscosity of 500-200,000 centistokes (at 25°

C.) and having the general formula ##STR2## wherein R is lower alkyl (preferably methyl) and/or aryl of up to 10 carbon atoms, and

n is an integer from 200-1600;

(b) 0-50 parts by weight of an organopolysiloxane copolymer consisting essentially of;

(i) (R'"'"')₃ SiO₀.5 units,

(ii) (R'"'"')₂ (Vi)SiO₀.5 units, and

(iii) SiO₂ units, wherein

Vi is a vinyl group and R'"'"' is a monovalent organic residue which does not contain any unsaturated groups, and at least 50% of R'"'"' is methyl, and

wherein the ratio of a+b/c is 0.4-1.5 (preferably 0.6-1.0) and the ratio of b/c is 0.02-0.5 (preferably 0.05-0.15);

(c) 5-15 parts by weight of an organohydrogen polysiloxane of the general formula

space="preserve" listing-type="equation">R".sub.a H.sub.b SiO.sub.(4-a-b/2)

wherein

R" is a monovalent organic residue which has no unsaturated groups, a and b are each positive numbers;

the ratio of a;

b is 0.5-10 (preferably 1.0-5);

the sum of a+b is 1-2.5; and

wherein at least three hydrogen atoms bound to different Si atoms are present per molecule;

which component contain 50-500 molar percent, based on the unsaturated end groups in components (a) and (b) of vinyl groups attached to SiH; and

(d) a catalytic amount of platinum or a platinum compound.

6. A vaginal ring according to claim 1, wherein said major supporting ring is composed of an elastomeric, cross-linked LTV linear dimethylpolysiloxane resin.

7. A vaginal ring according to claim 1, wherein said drug is a steroid hormone.

9. A vaginal ring according to claim 1, wherein the major supporting ring is a closed-cell foam.

11. A vaginal ring according to claim 1, wherein said drug is an antiprotozoal medicament.

12. A vaginal ring according to claim 1, wherein the exposed portion of said minor ring segment is circular in cross-section.

13. A vaginal ring according to claim 12, wherein the entire minor ring segment is circular in cross-section.

14. A vaginal ring according to claim 1, wherein supporting, medicament-free ring (a) also has a continuous encircling pocket-like indentation along the outer edge of the annular surface along the central plane thereof adapted to mate with a corresponding smaller, medicament-containing outer encircling annular minor vaginal ring segment;

and which also contains

(c) a smaller, vaginal medicament-containing outer encircling annular minor vaginal ring adapted to mate with the continuous encircling pocket-like indentation in the modified outer annular surface of said supporting, medicament-free vaginal ring along the central plane thereof and consisting essentially of a safe and effective amount of a pharmaceutically active nonionic, lipophilic vaginal drug dissolved or uniformly suspended in an elastomeric, crosslinked LTV linear dimethylpolysiloxane resin;

whereby the composite ring contains both inner and outer minor ring segments along the central plane of said major supporting ring.

15. A vaginal ring according to claim 14, wherein one of said minor ring segments contains a progestationally active steroid drug and the other of said ring segments contains an estrogenically active steroid drug.

16. A vaginal ring according to claim 15, wherein the major supporting ring is a closed-cell foam composed of an elastomeric, cross-linked LTV linear dimethylpolysiloxane resin.

17. A vaginal ring according to claim 16 dimensioned for insertion into a human female vagina.

18. A vaginal ring according to claim 17 further comprising an antiprotozoal drug in a portion of at least one of said minor rings.

19. A vaginal ring according to claim 18, wherein the exposed portion of said minor ring segments are circular in cross-section.

8. A vaginal ring according to claim 8, wherein said drug is at least one steroid hormone having progestational or estrogenic activity.

10. A vaginal ring according to claim 10, wherein said major supporting ring is composed of an elastomeric, cross-linked LTV linear dimethylpolysiloxane resin.