Method and composition for prevention and treatment of female lower genital tract microbial infections

• US 5,667,817 A
• Filed: 08/28/1996
• Issued: 09/16/1997
• Est. Priority Date: 03/20/1992
• Status: Expired due to Term

• Current Assignee: Ecolab USA Incorporated (Ecolab, Inc.)
• Original Assignee: Alcide Corp (Ecolab, Inc.)
• Inventors: Kross, Robert D.
• Primary Examiner(s): PAK, JOHN D
• Application Number:
  US08/703,942
• Time in Patent Office: 384 Days
• Field of Search: 424/661, 424/662, 424/663, 424/664, 424/665, 514/931, 514/932, 514/933, 514/934, 514/967, 514/968
• US Class Current: 424/661
• CPC Class Codes: A61K 33/40 Peroxides

Abstract

Methods for preventing and treating microbial infections in the mammalian female lower genital tract such as vulvitis, vaginitis, cervicitis, and endometritis involve the intra-vaginal and/or intra-uterine infusion of a solution containing a pharmacologically acceptable carrier and chlorine dioxide in an amount ranging from about 5 ppm to 1000 ppm, and having a chlorine dioxide to chlorite ratio of at least 5:1. Typical solutions exhibit a pH compatible with the lower genital tract, e.g., a pH from about 5 to about 7.5. In many embodiments, chlorine dioxide in the solution is produced by reacting a chlorite with a mineral acid and adjusting the pH, by reacting a chlorite with an organic acid having a pK of about 2.8 to 4.2, or by reacting a chlorite at a pH below about 5.5 with a heat-activated saccharide in the presence of an organic acid having a pK of about 2.8 to about 4.2. Sodium chlorite is employed in preferred embodiments.

Claims

1. A method for treating or reducing susceptibility to a microbial infection in the lower genital tract of a female mammal comprising infusing into the lower genital tract of the mammal an effective amount of an aqueous composition comprising greater than about 125 ppm to about 1000 ppm chlorine dioxide and a pharmaceutically acceptable carrier, wherein the molar ratio of chlorine dioxide to chlorite in the composition is at least 5:

1 and the pH is compatible with the tract.

2. A method according to claim 1 wherein the composition contains from greater than about 125 ppm to about 600 ppm chlorine dioxide.

3. A method according to claim 1 wherein the mammal is post-parturient.

4. A method according to claim 1 wherein the chlorine dioxide in the composition is produced by the reaction of a chlorine dioxide generating compound and an acid.

5. A method according to claim 4 wherein the chlorine dioxide generating compound is a water-soluble chlorite selected from the group consisting of an alkali metal chlorite, an alkaline earth metal chlorite, and mixtures thereof.

6. A method according to claim 5 wherein the chlorine dioxide in the composition is produced by a process selected from the group consisting of:

(a) reaction of a chlorite with a mineral acid and adjustment of the pH to about 5 to about 7.5;

(b) reaction of a chlorite with an organic acid having a pK of from about 2.8 to about 4.2; and

(c) reaction of a chlorite with a saccharide, which has been heat-activated by heating the saccharide to a temperature of from about 50°

C. to about 150°

C. for at least about 1 minute, in a solution in the presence of an organic acid having a pK of from about 2.8 to about 4.2 and a pH below about 5.5.

7. A method according to claim 6 wherein the saccharide is selected from the group consisting of glucose, galactose, mannose, ribose, rhamnose, lactose, sucrose, maltose, and mixtures thereof.

8. A method according to claim 5 wherein the chlorite is sodium chlorite.

9. A method according to claim 1 wherein the mammalian female lower genital tract microbial infection is selected from the group consisting of vulvitis, vaginitis, cervicitis, endometritis and mixtures thereof.

10. A method according to claim 9 wherein the infection is equine endometritis.

11. A method according to claim 9 wherein the infection is caused by an organism selected from the group consisting of Candida, Trichomonas, Corynebacterium, Campylobacter, Pseudomonas, Streptococcus, Klebsiella, and Escherichia species.

12. A method according to claim 9 wherein the chlorine dioxide in the composition is produced by reaction of an acid with a water-soluble chlorite selected from the group consisting of alkali metal chlorites, alkaline earth metal chlorites, and mixtures thereof.

13. A method according to claim 12 wherein the composition is adjusted to a pH of about 5 to about 7.5 after the reaction.

14. A method according to claim 12 wherein the acid is a mineral acid selected from the group consisting of sulfuric acid, hydrochloric acid, and phosphoric acid.

15. A method according to claim 12 wherein the acid is an organic acid selected from the group consisting of citric acid, malic acid, lactic acid, mandelic acid, tartaric acid, and mixtures thereof.

16. A method according to claim 15 wherein the composition further comprises an isotonic solution of chloride salts.

17. A method according to claim 16 wherein the reaction is carried out in the presence of a heat-activated saccharide compound prepared by heating a saccharide selected from the group consisting of glucose, galactose, mannose, ribose, rhamnose, lactose, sucrose, maltose, and mixtures thereof, to a temperature of from about 50°

C. to about 150°

C. for at least about 1 minute.

18. A method according to claim 5 wherein the chlorite is sodium chlorite and the composition has a pH of about 5 to about 7.5.

19. A method for treating or reducing susceptibility to post-parturient microbial infections in the lower genital tract of mares or cows comprising infusing into the tract of the cow or mare after birth 1 to 5 liters of a solution that contains a chlorite selected from the group consisting of an alkali metal chlorite, an alkaline earth metal chlorite, and mixtures thereof, reacted with an acid in amounts sufficient to yield greater than about 125 ppm to about 1000 ppm chlorine dioxide, provided that the ratio of chlorine dioxide to chlorite in the solution is at least 5:

1, and the pH of the composition is compatible with the tract.

20. A method according to claim 19 wherein the chlorite is sodium chlorite and the composition has a pH of about 5 to about 7.5.