WO1995029670A1

WO1995029670A1 - Pharmaceutical composition and methods of treatment

Info

Publication number: WO1995029670A1
Application number: PCT/US1995/005113
Authority: WO
Inventors: William F. Cotter; Lester B. Weintraub; Joseph A. Matthias
Original assignee: Smithkline Beecham Corporation
Priority date: 1994-04-28
Filing date: 1995-04-24
Publication date: 1995-11-09

Abstract

This invention relates to a pharmaceutical composition which is pH-buffered, isotonic and which does not adversely affect or interfere with the normal vaginal microflora which are essential to maintaining the vaginal tract of a mammal in a healthy condition. In addition, this invention relates to methods of restoring and maintaining the pH of the vaginal tract within an optimal range. Further, this invention relates to a method for cleansing the vaginal tract with a pharmaceutical composition that is pH-buffered and isotonic, and which restores and maintains the pH of the vaginal tract within optimal ranges. Still further, this invention relates to methods for preventing and treating vaginal infections which comprise administering to a mammal in need thereof, an effective amount of the instant pH-buffered, isotonic pharmaceutical composition.

Description

PHARMACEUTICAL COMPOSITION AND METHODS OF TREATMENT

FIELD OF THE INVENTION

This invention relates to a pharmaceutical composition buffered to a pH of about 4.0 to about 4.5 for restoration of vaginal lumen pH to an optimal pH of about 4.0 to about 5.0. Further, this invention relates to a method for restoring vaginal pH by vaginally administering an effective amount of the pharmaceutical composition of the invention. This invention also relates to a method of maintaining a stable microenvironment in the human vagina which environment has a pH of about 4.0 to 5.0, by vaginally administering an effective amount of the pharmaceutical composition of the invention. In addition, this invention relates to a method for cleansing the vaginal tract by vaginally administering an effective amount of the pharmaceutical composition of the invention. Still further, this invention relates to a method for preventing vaginal infections by vaginally administering an effective amount of the instant pharmaceutical composition. Yet further, this invention relates to a method for treating vaginal infections by vaginally administering an effective amount of the instant pharmaceutical composition.

BACKGROUND OF THE INVENTION

The pH of the normal, healthy vaginal tract has been reported to be between 3.0 and 6.0. U.S. Patent Nos. 2,649,398, issued April 1, 1941, and 3,346,450, issued October 10, 1967. [See, also, The Human Vagina, edited by E.S.E. Hafez & T.N. Evans, Elsevier North-Holland Biomedical Press, Chapter 29, p. 411 (1978), which discloses that the average pH of the vagina in regularly menstruating women ranges from 3.7 to 6.3]. Specifically, in women of child-bearing age, the pH varies between 4.0 and 5.0 depending upon the stage of the menstrual cycle. A pH of 4.0 or less is found during pregnancy, whereas in the post-menopausal woman, neutral or alkaline values may be seen. The Human Vagina, edited by E.S.E. Hafez & T.N. Evans, Elsevier/North-Holland Biomedical Press, Chapter 7, pp. 109-110 (1978).

Numerous nonpathogenic aerobic and anaerobic bacteria inhabit the healthy vagina, including Staphylococci, Streptococci, Bacteroides, Gardnerella and Doderlein's bacillus, a strain of lactobacillus. Lactobacillus is considered to be particularly useful because it may metabolize vaginal glycogen to lactic acid, thus helping maintain the normal acid pH of the vaginal tract. Further, it is generally believed that acidity promotes a normal microflora environment and helps control the growth of pathogenic microbials. Gossel, T.A., US. Pharmacist, p. 24 (May 1992). In addition, it has been suggested that a quantitative change in the normal vaginal microflora may cause lower vaginal tract infections since such changes may allow rapid proliferation of potential pathogens during this altered state. Onderdonk et al., Obstetrics & Gynecology, Vol. 80, No. 3, Part 1, pp. 333-338 (Sept. 1992). Thus, a change in the pH of the vaginal tract which has a quantitative effect on the normal vaginal microflora may allow pathogenic microbes to flourish in or invade the vaginal tract thereby causing infection. Therefore, it is believed that the two critical factors in maintaining a healthy and stable environment in the vaginal tract are the existence of certain normal vaginal microflora and the existence of a particular pH in the vaginal tract.

While commercial douche products used for cleansing the vaginal tract overwhelmingly have a pH in the range of about 3.2 to about 3.9, it has now been discovered that the optimum pH for the vaginal tract is between about 4.0 and about 5.0. Often, after menstruation or the application of contraceptive foams, jellies, etc., the pH of the human vaginal tract increases significantly above the optimal pH range disclosed herein, creating an environment which is receptive to pathogenic microbes.

However, by vaginally administering the instant composition, the pH of the vaginal lumen is restored to about 4.0 to about 5.0. Further, vaginal administration of the instant composition maintains the pH of the vaginal lumen within the optimal range. This pH range is considered optimal because once the pH of the vaginal tract is outside this range, the levels of normal vaginal microflora decrease and pathogenic microbes have an opportunity to invade the healthy vagina, potentially causing infection. Ross et al., J. Clin. Microbiol., Vol. 32, No. 4, pp. 871-875 (1994). See, for example, Onderdonk et al., Obstetrics & Gynecology, Vol. 80, No. 3, Part 1, p. 337, (Sept. 1992) which suggests that the nature of a composition applied to the vaginal tract has a correlation to the existence of a healthy microenvironment therein.

Thus, if a vaginal infection is present in the vaginal tract, or, if the pH of the vaginal tract exists outside the optimal range, restoration of the pH thereof, to be within the optimal range is desirable. Furthermore, once the pH of the vaginal tract is restored to within the optimal range, maintenance of the vaginal pH within this optimal range is important in preventing future invasion by pathogenic microbes.

One method of restoring the desired vaginal pH is to vaginally administer a pharmaceutical composition, including, but not limited to a douche system, to a vaginal tract which has a pH existing outside the optimal pH range of about 4.0 to about 5.0. Similarly, a method for maintaining the desired vaginal pH is to vaginally administer a pharmaceutical composition, including, but not limited to a douche system, to the vaginal tract which has a pH existing within the optimal pH range. Therefore, it is important that the pharmaceutical composition be capable of both establishing and maintaining the desired optimal pH. Further, it is important that the pharmaceutical composition be free from components which would destroy the microbes that are normally and desirably present in the vaginal tract. It is also desirable in the case of a pharmaceutical composition that is to come in contact with a permeable membrane such as that of the vaginal surface, that the composition be isotonic so that the composition has a balanced electrolyte concentration equivalent to the normal body electrolyte composition. Furthermore, the ingredients should be non-toxic and free from irritating and other deleterious properties, and be chemically and physically stable so that the composition may be stored over a relatively long period of time without deteriorating.

The pharmaceutical composition of the present invention meets these criteria. Specifically, the pharmaceutical composition of this invention, upon application to the vaginal tract, restores the pH of the vaginal tract to within optimal ranges for a healthy system, i.e., between 4.0 and 5.0. In addition, the instant composition maintains the vaginal pH within the optimal pH range of about 4.0 to about 5.0. Furthermore, the buffer agent of this invention is present in amounts which make the pharmaceutical composition isotonic, thereby making it compatible with the physiology of the epithelial membranes of the vaginal tract. In addition, the pharmaceutical composition of this invention is effective for cleansing vaginal surfaces of the vaginal tract, especially when the preparation is used as a douche. Since the composition of this invention is effective for both restoring and maintaining the pH of the vaginal tract within normal and healthy ranges, it may be used as a therapeutic agent for treating both Trichomonas vaginalis vaginitis and non-specific vaginitis. By restoring and maintaining the vaginal pH to within normal ranges, the instant composition re-establishes a healthy microenvironment in the vaginal tract, promotes the growth of normal vaginal microflora and maintains the healthy environment free from the pathogenic microbes which caused the initial infection. In addition, the instant pharmaceutical composition may be used even if the pH of the vaginal tract is within the optimal range, i.e., the composition may be used in order to maintain the pH within this optimal range, thereby preventing potential invasion by pathogenic microbes.

The instant pharmaceutical composition differs from known vaginal preparations in that the buffering agent contained therein comprises an amount of a pharmaceutically acceptable acid and an amount of a pharmaceutically acceptable base which are effective to restore the vaginal pH to a pH of about 4.0 to about 5.0. Further, the buffering agent in the instant composition is used as the electrolyte which establishes the isotonicity of the composition. This is in contrast to the combination of multiple electrolytes, in order to establish isotonicity required by the disclosure in U.S. Patent No. 4,788,060 (see, for example, column 1, lines 46-51). Therefore, since the instant composition requires only one agent which acts as both a buffering agent and an electrolyte which establishes isotonicity, this invention provides a unique pharmaceutical composition that comprises a buffering agent in amounts effective to reach the highest buffering capacity of the composition, i.e., the ability to establish a pH of the composition in the range of about 4.0 to about 4.5, without disturbing the environment to which it is applied. Further, since the instant composition is buffered to the highest buffering capacity, upon vaginal administration, the pH of the vaginal tract is either restored to or maintained at a pH of about 4.0 to about 5.0.

SUMMARY OF INVENTION

The objectives, features, and advantages of the present invention are achieved by a pharmaceutical composition for the restoration of vaginal pH to an optimal pH of about 4.0 to about 5.0.

Accordingly, an object of the present invention is to provide a pharmaceutical composition buffered to a pH of about 4.0 to about 4.5, which comprises a unique buffering agent that serves as an agent to restore the pH of the vaginal tract to an optimal pH of about 4.0 to about 5.0, as well as being the electrolyte which establishes the isotonicity of the composition. Another object of the invention is to provide a buffering agent which comprises a salt selected for its ability to establish the highest buffering capacity of the pharmaceutical composition, without disturbing the microenvironment of the vaginal tract. A further object of the invention is to provide a method for maintaining the optimal pH of the vaginal tract at a pH of about 4.0 to about 5.0 by vaginally administering the instant pharmaceutical composition. A further object of this invention is to provide a method for cleansing exposed or readily accessible epithelial membrane surfaces of the vaginal tract by vaginally administering an effective amount of the instant pharmaceutical composition to a mammal, preferably a human, in need thereof. Yet a further object of this invention is to provide a method for restoring the vaginal tract pH to an optimal pH of about 4.0 to about 5.0 by vaginally administering, to a mammal in need thereof, an effective amount of the pharmaceutical composition of the invention. Another object of the invention is to provide a method for preventing vaginal infections, specifically vaginal infections which are mediated by a variation in the pH of the vaginal tract outside the optimal ranges (such that the levels of deleterious bacteria within the vaginal tract are increased, or the levels of normal bacteria within the vaginal tract are decreased so that deleterious bacteria are allowed to flourish), which comprises administering to a mammal in need thereof, an effective amount of the instant pharmaceutical composition. Another object of the invention is to provide a method for treating vaginal infections which comprises administering to a mammal in need thereof, an effective amount of the instant pharmaceutical composition. Other objects of the invention will be in part obvious and in part pointed out hereafter. DETAILED DESCRIPTION OF THE INVENTION

It has now been discovered that the optimal pH for the vaginal tract ranges between 4.0 and 5.0. The present invention relates to a pharmaceutical composition in the form of a pH-adjusted and isotonic formulation. The buffering agent contained in the instant composition serves a dual purpose of buffering the composition and establishing isotonicity of the composition.

In one aspect, the composition of the invention comprises an effective amount of a buffering agent such that the composition is buffered to a pH of between about 4.0 and about 4.5. A more preferable buffering range of the composition is to a pH of between about 4.2 and about 4.3. This is a preferable range for the composition because it restores, as well as maintains, the vaginal lumen pH to optimal levels if the pH has been altered by, e.g., menstruation (pH levels increase) or use of contraceptive foams, jellies, etc. (pH levels increase). Thus, the instant pharmaceutical composition may be used to restore the pH of the vaginal tract of a mammal, preferably a human, to within the optimal ranges disclosed herein. Further, the instant pharmaceutical composition may be used to maintain the pH of the vaginal tract of a mammal, preferably a human, within the optimal ranges. In addition, the instant pharmaceutical composition may be used in order to cleanse the vaginal tract of a mammal, preferably a human. Still further, this pharmaceutical composition may be used as a delivery vehicle for therapeutic agents. The terms "vaginal tract" or "vaginal lumen" are used herein at all occurrences to mean the canal or cavity in a female mammal that leads from the uterus to the external orifice of the genital canal, including the vulva which is the external portion of the female genital organ.

The terms "normal microflora" or "normal vaginal microflora" are used herein at all occurrences to mean microorganisms which inhabit and replicate in the vaginal tract and do no harm to that area, and may even serve a beneficial role.

The term "buffering agent" is used herein at all occurrences to mean a mixture of materials, in particular, a pharmaceutically acceptable conjugate acid and a pharmaceutically acceptable conjugate base, which when in solution, enable that solution to withstand the addition of moderate amounts of either a strong acid or base without causing a large change in pH value. Buffering agents usually comprise: (a) a weak acid and the salt of the weak acid; (b) a mixture of the acid salt with the normal salt; or (c) a mixture of two acid salts.

The terms "buffering capacity" or "highest buffering capacity" are used herein at all occurrences to mean the ability of the buffering agent to maintain the pH of the composition in which it is used in the range of about 4.0 to about 4.5. The term "alkali metal salt" is used herein at all occurrences to mean an alkali salt made from the metals comprising Group IA of the periodic chart, including: potassium, sodium, lithium, rubidium, cesium and francium.

The term "alkali earth metal salt" is used herein at all occurrences to mean a salt made from the metals comprising Group II of the periodic chart, including: beryllium, magnesium, calcium, strontium, barium and radium.

The term "vaginal douche" is used herein at all occurrences to mean a liquid composition to irrigate the vaginal tract and includes powders that must be dissolved in water, liquid concentrate formulations, and the like. The term "vaginal suppository" is used herein at all occurrences to mean a small globular mass which liquifies at body temperature or dissolves in the vaginal secretions.

The term "optimal range(s)" is used herein at all occurrences to mean the desired pH of the vaginal tract, i.e., between about 4.0 and about 5.0.

The term "treating" is used herein at all occurrences to mean either prophylactic or therapeutic therapy.

The terms "restores", "restoring" and "restore" are used herein at all occurrences to mean the ability of the instant composition to bring back or put back the vaginal tract into its original, healthy state, i.e., to establish a vaginal pH of about 4.0 to about 5.0.

The terms "maintains", maintaining" and "maintain" are used herein at all occurrences to mean the ability of the instant composition to keep the vaginal tract in an existing state free from the invasion of pathogenic microbes.

The term "cleanse" is used herein at all occurrences to mean the ability of the instant composition to remove from the vaginal tract impurities which might cause deleterious effects thereto. The term "mediated" is used herein at all occurrences to mean caused by or exacerbated by.

The terms "prevent" or "preventing" are used herein at all occurrences to mean the ability of the instant composition to hinder or to keep pathogenic microbes from invading the vaginal tract and causing an infection thereof. In one embodiment, the instant invention is in a pharmaceutical composition comprising an amount of a pharmaceutically acceptable conjugate acid and a pharmaceutically acceptable conjugate base, in a pharmaceutically acceptable carrier or diluent, effective to restore the pH of the vaginal tract to the optimal levels, i.e., about 4.0 to about 5.0, disclosed herein. In addition, the effective amount of the buffering agent comprised in the instant composition also establishes the isotonicity of the instant composition. In another embodiment, the instant invention is in a method for restoring vaginal lumen pH to optimal levels, in a human in need thereof, by vaginally administering an effective amount of the instant composition. In yet another embodiment, the instant invention is in a method for maintaining a stable microenvironment in the human vaginal tract which environment has a pH of about 4.0 to about 5.0, by vaginally administering to a human in need thereof, an effective amount of the instant composition. In still another embodiment, the instant invention is in a method for cleansing the human vaginal tract by vaginally administering to a human in need thereof, an effective amount of the instant composition. In another embodiment, the instant invention is in a method for preventing human vaginal tract infections by vaginally administering an effective amount of the instant composition to a human in need thereof. In yet another embodiment, the instant invention is in a method for treating infections of the human vaginal tract by vaginally administering an effective amount of the instant composition to a human in need thereof.

Conjugate bases which may be incorporated into the instant pharmaceutical composition include, but are not limited to, sodium bicarbonate, sodium hydroxide, potassium bicarbonate, potassium hydroxide, and the like. A preferred conjugate base for use in this invention is sodium bicarbonate. It will be obvious to one of ordinary skill in the art, given the disclosure herein, which other alkali metal salts or alkali earth metal salts may be used as the conjugate base according to this invention.

Conjugate acids which may be incorporated into the instant pharmaceutical composition include, but are not limited to, citric acid, tartaric acid, acetic acid, ascorbic acid, potassium acid phthalate, oxalic acid, lactic acid, maleic acid, and the like. A preferred conjugate acid for use in the instant invention is citric acid. It will be obvious to one of ordinary skill in the art, given the disclosure herein, which other acids may be used as the conjugate acid according to this invention. The amount of each member of the buffering agent is such that: (i) the composition is buffered to a pH ranging between 4.0 and 4.5; and (ii) when the pharmaceutical composition is applied to the vaginal tract, the pH thereof is either restored to and maintained, or simply maintained, in the optimal range. In addition, the composition comprises an amount of the buffering agent which is effective to establish isotonicity of the composition as well as serving as a buffering agent for the composition. Preferably, the conjugate acid member of the buffering agent comprises about 0.5 % by weight to about 3.0 % by weight of the instant pharmaceutical composition. More preferably, the conjugate acid member of the buffering agent comprises about 0.85 % by weight to about 2.7 % by weight of the instant pharmaceutical composition. Most preferably, the conjugate acid member of the buffering agent comprises about 0.95 % by weight to about 2.6 % by weight of the instant pharmaceutical composition. Preferably, the conjugate base member of the buffering agent comprises about 0.3 % by weight to about 2.0 % by weight of the instant pharmaceutical composition. More preferably, the conjugate base member of the buffering agent comprises about 0.45 % by weight to about 1.7 % by weight of the instant pharmaceutical composition. Most preferably, the conjugate base member of the buffering agent comprises about 0.55 % by weight to about 1.6 % by weight of the instant pharmaceutical composition.

In another embodiment of the composition of the invention, a salt comprising an anion of the conjugate acid and a cation of the conjugate base may be used in combination with sufficient citric acid to produce a pH of about 4.0 to about 4.5. A suitable conjugate base is selected from the alkali earth metals of Group II. A preferable conjugate base is selected from the alkali metals of Group LA. Suitable salts for use according to this embodiment of the invention, include, but are not limited to, sodium citrate, sodium tartrate, sodium acetate, sodium ascorbate, sodium oxalate, sodium lactate, sodium maleate, and the like. A preferred salt for use in this embodiment of the invention is sodium citrate. The instant pharmaceutical composition may be in the form of a douche that has an effective cleansing action on the vaginal surfaces to which it is applied. The douche formulations according to this invention may be solids (i.e., a powder concentrate) adapted to be dissolved in water to form a liquid douche formulation, or relatively concentrated solutions (i.e., a liquid concentrate) that must be diluted before use, or solutions that are sufficiently dilute so that they may be used without further dilution. The douche formulations are preferably packaged in a single unit disposable container that is discarded after one use. The instant douche formulations may also be used to restore the pH of the vaginal tract of a mammal to within the optimal ranges. In addition, the instant douche may be used to maintain the pH of the vaginal tract at a pH of about 4.0 to about 5.0.

When the pharmaceutical composition is in the form of a liquid formulation, water, acting as a diluent, comprises about 93 % by weight to about 98 % by weight, preferably, about 95 % by weight to about 97.5 % by weight of the total formulation. Since this composition is intended for use in mammals, preferably humans, the water must be free of pathogens, toxins or chemicals which can irritate the epithelial surfaces and/or mucosa, such as chlorine, and any other deleterious materials. Water purification systems are well known and can be purchased from many manufacturers. Examples of such systems are reverse osmosis, activated carbon filters, deionizing systems, bacterial filters, and filtration devices to removed suspended solids. Distillation techniques may produce sufficiently pure water as well. The following method may be used to prepare the douche according to this invention:

1. To a stainless steel tank equipped with suitable agitation equipment, the formula amount of water is charged.

2. With agitation, add in order conjugate acid and optional ingredients such as vinegar, disodium EDTA (chelate), GERMALL II (preservative) and TRITON X-100 (surfactant). Mix until all ingredients are dissolved and the batch is clear.

3. With moderate agitation, slowly add the conjugate base. 4. Mix for at least 15 minutes or until all ingredients are dissolved and the batch is clear.

5. Sample the batch and when approved, fill into approved containers. Various agents other than those previously described may also be included in the pharmaceutical composition of the instant invention. For example, the instant pharmaceutical composition may also contain at least one surfactant and at least one aromatic or fragrance agent, both of which are conventional in the art. In addition, the instant composition may contain a chelating agent and/or a preservative which are conventional in the art of pharmaceutical compositions. See, for example Martin, A., Physical Pharmacy, 4th Edition, (Lea & Febiger, Philadelphia, London) (1993); Martindale, The Extra Pharmacopoeia, 30th Edition (The Pharmaceutical Press) (1993); and Handbook of Pharmaceutical Excipients, (American Pharmaceutical Association) (1986), for other suitable agents that may be incorporated into the instant composition. Further, the instant composition may contain an organic acid, such as acetic acid as a cleanser. It is obvious that changes in these agents may be made without affecting the objectives of this invention.

Nonionic, anionic or cationic surfactants may be used in the pharmaceutical composition of this invention. Suitable nonionic surfactants include, but are not limited to, octylphenoxy polyether ethanols with three to thirty oxyethylene groups e.g., octoxynol-9, known commercially as TRITON X-100, which is a trademark of the Union Carbide Company. Suitable cationic surfactants include, but are not limited to, cetyl pyridinium chloride.

Suitable alcohols, including, but not limited to, ethanol and isopropanol, may also be used in the instant pharmaceutical composition in order to solubilize the fragrance agent optionally contained therein. In addition, colorants, including, but not limited to certified dyes and natural colorants may be used in the pharmaceutical composition of the invention. Preferred embodiments are FD&C and D&C certified dyes. A suitable chelating agent for use in this invention includes, but is not limited to, disodium ethylenediaminetetraacetic acid ("disodium EDTA"). Suitable preservatives for use herein include, but are not limited to, GERMALL II (diazolidinyl urea) which is a trademark of Sutton Labs, or benzoic acid. A preferred preservative is GERMALL π. In addition, the instant pharmaceutical composition may be formulated for topical application to a mammal in need thereof. The topical formulations of the present invention, for use in mammals, preferably humans, comprise an amount of a pharmaceutically acceptable conjugate acid and a pharmaceutically acceptable conjugate base and a pharmaceutically acceptable carrier effective to restore the pH of the vaginal tract to the optimal levels disclosed herein and optionally any other therapeutic ingredient(s). The carrier(s) must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.

Formulations suitable for topical administration include liquid or semi-liquid preparations suitable for application to the site such as: liniments, lotions, creams, ointments, gels or pastes.

Lotions according to the present invention include those suitable for application to the vaginal tract. Lotions or liniments for application according to this invention may also include a humectant/moisturizer such as propylene glycol or glycerol, or an oil such as mineral or petrolatum oil. Creams, ointments, gels or pastes according to the present invention are semi-solid formulations of the instant pharmaceutical composition for application to the vaginal tract. They may be made by mixing the buffering agent in finely-divided or powdered form, alone or in solution or suspension in an aqueous or non-aqueous fluid, with the aid of suitable machinery, with a greasy or non-greasy base. The base may comprise hydrocarbons such as hard, soft or liquid paraffin, glycerol, beeswax, a metallic soap, a mucilage, an oil of natural origin such as almond, corn, or olive oil, wool fat or its derivatives, or a fatty acid such as steric or oleic acid together with an alcohol such as cetyl or stearyl alcohol and a moisturizer or humectant such as propylene glycol or glycerin. The formulation may incorporate any suitable surface active agent such as an anionic, cationic, amphoteric or non-ionic surfactant such as sorbitan esters or polyoxyethylene derivatives thereof. Suspending agents such as natural gums, cellulose derivatives or inorganic materials such as silicaceous silicas, and other ingredients such as lanolin, may also be included.

A pessary according to this invention may be in the form of a hydrocolloid. The hydrocolloid is a water-soluble or water-swellable polymeric substance such as a cellulosic polymer and gum. Suitable cellulosic polymers for use herein include, but are not limited to, methylcellulose, carboxymethylcellulose or hydroxyethylcellulose. Suitable gums for use herein include, but are not limited to, guar gum, locust bean gum, or xanthan gum. The pessary base may be of any conventional material for application to the vaginal tract of a mammal. Preferably, the low-melting pessary base will have a melting point of less than 90° to 95°F so that after insertion, it will melt in the vaginal tract. Preferred pessary bases are glycerol/gelatin, glyco/gelatin, macrogels (polyethylene glycols), natural, synthetic hard fats or waxes and fractionated palm kernel oil, including, but not limited to, cocoa butter (theobroma oil). The pessaries may be manufactured by conventional methods, for example, by admixture of the various ingredients in the molten pessary base and pouring the resulting mixture into chilled molds.

According to this invention, in order to restore vaginal lumen pH to within the optimal range, the dosage of the instant composition is 1 to 10 times per week.

Preferably, the dosage used for restoring the vaginal lumen pH is 2 to 5 times per week. Most preferably, the dosage used for restoring the vaginal lumen pH is 2 to 3 times per week. According to this invention, in order to maintain vaginal lumen pH to within the optimal range, the dosage of the instant composition is 1 to 7 times per week. Preferably, the dosage used for maintaining the vaginal lumen pH is 2 to 3 times per week. Most preferably, the dosage used for maintaining the vaginal lumen pH is 2 times per week. According to this invention, in order to cleanse the vaginal tract, the dosage of the instant composition is 1 to 5 times per week. Preferably, the dosage used for cleansing the vaginal tract is 1 to 3 times per week. Most preferably, the dosage used for cleansing the vaginal tract is 2 times per week. The quantity of the pharmaceutical composition to be administered, in all cases ranges between 50 and 250 ml, preferably between 80 and 200 ml, and most preferably between 100 and 190 ml. According to this invention, if the pharmaceutical composition contains an active ingredient for treatment of a particular vaginal disease state, the dosage and quantity of the composition to be administered depends upon the nature of the active ingredient and the disease state being treated, and is within the knowledge of the skilled artisan.

It will be recognized by one of skill in the art that the optimal quantity of the individual dosages of the compositions herein will be determined by the nature and extent of the condition being treated, the form, route and site of administration, and the particular patient being treated, and that such optimums can be determined by conventional techniques known by those skilled in the art. The dosage to be administered is obviously dependent upon species, body weight, age, individual condition and method of application. It will also be appreciated by one of skill in the art that the optimal course of treatment, i.e., the number of doses given per treatment, the frequency of such treatment and the eventual duration of use can be ascertained by those skilled in the art using conventional course of treatment determination tests. EXAMPLES

The following ingredients and their percent concentration, exemplify pharmaceutical preparations which are within the scope of the instant invention.

INGREDIENT % BY WEIGHT water 94.85 citric acid, anhydrous USP 2.47 vinegar, 100 grain 0.80 disodium EDTA 0.01

TRITON X-100 0.05

GERMALL π 0.20 sodium bicarbonate USP 1.60 cetylpyridinium chloride 0.02

INGREDIENT % BY WEIGHT water 94.93 citric acid, anhydrous USP 2.47 vinegar, 100 grain 0.80 sodium bicarbonate USP 1.60

The above description fully discloses the invention including preferred embodiments thereof. Modifications and improvements of the embodiments specifically disclosed herein are within the scope of the following claims. Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. Therefore, any examples are to be construed as merely illustrative and not a limitation on the scope of the present invention in any way. The embodiments of the invention, in which an exclusive property or privilege is claimed, are defined as follows.

Claims

What is claimed is:

1. A pharmaceutical composition for restoration of vaginal tract pH to a pH of about 4.0 to about 5.0 comprising a pharmaceutically acceptable carrier or diluent and a buffering agent, said buffering agent comprising an effective amount of a pharmaceutically acceptable conjugate acid and a pharmaceutically acceptable conjugate base.

2. The composition according to claim 1, wherein the pharmaceutically acceptable acid is citric acid.

3. The composition according to claim 1, wherein the pharmaceutically acceptable base is sodium bicarbonate.

4. The composition according to claim 1, wherein the pH of the composition range between about 4.0 to about 4.5.

5. The composition according to claim 1, wherein the composition is in the form o a liquid, solid or semi-solid preparation.

6. The composition according to claim 5, wherein the composition is a douche.

7. The composition according to claim 5, wherein the composition is in the form o a gel, or a cream or ointment.

8. The composition according to claim 1, wherein the pharmaceutically acceptable acid is present in an amount of about 0.95 % by weight to about 2.6 % by weight of the composition.

9. The composition according to claim 1, wherein the pharmaceutically acceptable base is present in an amount of about 0.55 % by weight to about 1.6 % by weight of the composition.

10. The composition according to claim 1, wherein isotonicity of the composition is maintained by buffering agent.

11. A method of restoring vaginal tract pH in a human in need thereof, by vaginally administering an effective amount of a composition according to claim 1.

12. A method of maintaining a stable microenvironment in the human vaginal tract which environment has a pH of about 4.0 to about 5.0, by vaginally administering an effective amount of a composition according to claim 1.

13. The method according to claim 12, wherein the composition is a douche.

14. A method of cleansing the human vaginal tract by vaginally administering a composition according to claim 1.

15. The method according to claim 14, wherein the composition is a douche.

16. A method of preventing infections of the human vaginal tract by vaginally administering a composition according to claim 1.

17. A method of treating infections of the human vaginal tract by vaginally administering a composition according to claim 1.