WO2018203327A1

WO2018203327A1 - Composition containing phenethyl alcohol for treatment of candida infection

Info

Publication number: WO2018203327A1
Application number: PCT/IL2018/050470
Authority: WO
Inventors: Shabtay Dikstein
Original assignee: Resdevco Research And Development Co. Ltd.
Priority date: 2017-04-30
Filing date: 2018-04-30
Publication date: 2018-11-08

Abstract

A novel composition for treatment of yeast infection, particularly infection by Candida, is disclosed. The composition comprises phenethyl alcohol and at least one polyol, preferably xylitol or a combination of xylitol and glycerol. Methods of prevention and treatment of yeast infections and of yeast infections accompanied by bacterial infection using the novel composition are also disclosed.

Description

COMPOSITION CONTAINING PHENETHYL ALCOHOL FOR TREATMENT OF

CANDIDA INFECTION

REFERENCE TO RELATED PUBLICATIONS

[0001] This application claims priority from U.S. Provisional Pat. Appl. No. 62/492,190, filed 30 April 2017, which is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

[0002] This invention rates in general to compositions and methods for prevention and treatment of infection by Candida. It relates specifically to compositions containing phenethylalcohol and polyols, and methods that incorporate the use of such compositions.

BACKGROUND OF THE INVENTION

[0003] Yeasts of the genus Candida are generally regarded as the most common cause of fungal infection worldwide. Candida infections are especially common in mucous membranes such as that of the vagina. The most common current treatment of Candida infection is the use of topical or systemic antifungal agents such as amphotericin B, clotrimazole, echinocandins, fluconazole, nystatin, or voriconazole to kill the fungus.

[0004] Phenethyl alcohol (2-phenylethan-l-ol) has been reported to inhibit growth of C. albicans in vitro; see Lingappa, B. T.; Prasad, M.; Lingappa, Y.; Hunt, D. F.; Biemann, K. Science 1983, 163, 192, and Han, T.-L.; Tumanov, S.; Cannon, R. D.; Villas-Boas, S. G. PLoS ONE 2013, 8, e71364. A family of patents assigned to Closure Medical, one example of which is U.S. Pat. No. 6585967, lists phenethyl alcohol as an anti-fungal compound without specifying the dosage or treatment conditions.

[0005] Xylitol is known to have antimicrobial activity and can prevent colonization by harmful bacteria; see, for example, Eros, G.; Korponyai, C; Szabo, K.; Behany, Z.; Szel, Edit; Kemeny, L. Borgyogy. Vener. Szle. 2014, 90, 152. U.S. Pat. Appl. Pub. No. 2006/0189701 discloses a method for treating bacterial infection by application of xylitol to an epithelial surface, thereby lowering its ionic strength and increasing its toxicity to bacteria. Similarly, U.S. Pat. Appl. Pub. No. 2006/0106117 discloses the treatment of vaginal infection by Gardnerella bacteria by application of xylitol. Treatment with xylitol was found to be ineffective against other bacteria, particularly Lactobacillus. U.S. Pat. Appl. Pub. No. 2015/0265517 discloses composition for topical treatment of skin or mucosa that comprises a combination of xylitol and alginate. [0006] Xylitol is also known to inhibit or eliminate growth of Candida. For example, Japanese Pat. Appl. No. 2000333973 discloses a dental adhesive that comprises 1.5 - 10% xylitol, which acts to prevent oral candidiasis. U.S. Pat. Nos. 7619008 and 7786176 disclose a composition for topical treatment of vaginal Candida infections. The composition comprises a xylitol-containing material that rapidly forms a gel upon contact with ions naturally found in the vaginal mucosa. Compositions containing 3 - 5% xylitol almost completely eliminated Candida from cultures in vitro.

[0007] U.S. Pat. No. 6414035 discloses the use of polyols such as xylitol to prevent growth of yeast such as Candida on mucosa of various orifices of the body. The patent additionally discloses that orally administered xylitol can increase the effectiveness of other antifungal drugs, but that the additional benefit of topically administered xylitol is only seen at xylitol levels sufficiently high to show antifungal activity alone.

[0008] Despite these advances in the field, there remains a need for improved topical treatments for Candida infections that overcome the weaknesses of those compositions and treatments known in the art.

SUMMARY OF THE INVENTION

[0009] The present invention provides topical compositions that are effective for the prevention, treatment, or alleviation of yeast infection, particularly infection by Candida (candidiasis). The primary active ingredients in the composition are phenethyl alcohol and xylitol. In preferred embodiments of the invention, the xylitol is present at a concentration that is too low to treat yeast or bacterial infection on its own. The combination of the effects of these two components provides an effective treatment for, and prevention of, infection by yeast such Candida, particularly when the yeast infection is accompanied by bacterial infection.

[0010] It is a therefore an object of this invention to disclose a topical composition for treatment, alleviation, or prevention of yeast infection, wherein said composition comprises phenethyl alcohol, no more than 5% (w/v) xylitol, and optionally a preservative; and, said composition contains no additional antifungal agent other than said preservative. In some embodiments of the invention, said composition is for treatment, alleviation, or prevention of candidiasis. In some embodiments of the invention, said composition is for treatment, alleviation, or prevention of yeast infection accompanied by bacterial infection. [0011] It is a further object of this invention to disclose the composition as defined in any of the above, wherein said composition is characterized by a phenethyl alcohol concentration of between 0.2% and 1.2% (w/v). In some preferred embodiments of the invention, said composition is characterized by a phenethyl alcohol concentration of 1% (w/v). In some preferred embodiments of the invention, said composition is characterized by a phenethyl alcohol concentration of 0.5% (w/v).

[0012] It is a further object of this invention to disclose the composition as defined in any of the above, wherein said composition is characterized by a xylitol concentration of no more than 3% (w/v). In some preferred embodiments of the invention, it is characterized by a xylitol concentration of between 0.5% and 3%. In some preferred embodiments of the composition, it is characterized by a xylitol concentration of between 1% and 3% (w/v). In some preferred embodiments of the composition, it is characterized by a xylitol concentration of no more than 1.5% (w/v).

[0013] It is a further object of this invention to disclose the composition as defined in any of the above, wherein said solution comprises glycerol. In some preferred embodiments of the invention, said composition is characterized by a glycerol concentration of between 1% and 5% (w/v). In some particularly preferred embodiments of the invention, the composition is characterized by a xylitol concentration of between 1% and 3% (w/v) and a glycerol concentration of between 1% and 5% (w/v).

[0014] It is a further object of this invention to disclose the composition as defined in any of the above, wherein said composition comprises an isotonic aqueous solution.

[0015] It is a further object of this invention to disclose the composition as defined in any of the above, wherein said composition is characterized by a pH that is within a normal pH range of the tissue for which the use is intended.

[0016] In some embodiments of the invention, the composition is characterized by a pH of between 6.5 and 7.6, and topical application of said composition to an eye is an effective treatment for infection of said eye by yeast that is accompanied by bacterial infection.

[0017] In some embodiments of the invention, the composition is characterized by a pH of between 4.0 and 7.0, and topical application of said composition to skin is an effective treatment for a skin infection by yeast that is accompanied by bacterial infection.

[0018] In some embodiments of the invention, the composition is characterized by a pH of between 3.5 and 4.5, and topical application of said composition to vaginal mucosa is an effective treatment for infection of said vaginal mucosa by yeast that is accompanied by bacterial infection.

[0019] It is a further object of this invention to disclose the composition as defined in any of the above, wherein said solution is characterized by an inorganic salt concentration of less than 0.1%.

[0020] It is a further object of this invention to disclose the composition as defined in any of the above, comprising at least one polymer characterized by a molecular weight of at least 10,000 Dalton. In some preferred embodiments of the invention, said at least one polymer is characterized by a molecular weight of at least 100,000 Dalton. In some preferred embodiments of the invention, said at least one polymer is present in a concentration chosen to bring said composition to a predetermined viscosity. In some preferred embodiments of the invention, wherein said at least one polymer is present in a concentration sufficient to produce a gel. In some preferred embodiments of the invention, said at least one polymer is anionic. In some particularly preferred embodiments of the invention in which said at least one polymer is anionic, said polymer is selected from the group consisting of hyaluronates, carbomers, and anionic polysaccharides. In some embodiments, said polymer is a sulfated polysaccharide.

[0021] It is a further object of this invention to disclose the composition as defined in any of the above, comprising a pharmaceutically effective amount of a pharmacologically active agent.

[0022] It is a further object of this invention to disclose the composition as defined in any of the above, comprising a substance selected from the group consisting of stabilizers, preservatives, antioxidants, and buffers.

[0023] It is a further object of this invention to disclose the composition as defined in any of the above, wherein said preparation is in the form of an aqueous solution. In some preferred embodiments of the invention, said preparation is in the form of a water-based gel.

[0024] It is a further object of this invention to disclose the use of the composition as defined in any of the above in a method of treatment of a yeast infection, wherein said method of treatment comprises applying said composition topically to affected tissue. In some embodiments, said yeast infection is candidiasis.

[0025] It is a further object of this invention to disclose the use as defined in any of the above, wherein said yeast infection is accompanied by bacterial infection. [0026] It is a further object of this invention to disclose the use as defined in any of the above, wherein said method of treatment comprises applying said composition to an affected at least once weekly. In some embodiments of the invention, said method of treatment comprises applying said composition to an affected area 1 - 3 times daily. In some embodiments of the invention, said treatment comprises applying said composition to an affected area at least until a statistically significant reduction in yeast infection is observed.

[0027] It is a further object of this invention to disclose the use of the composition as defined in any of the above, subject to the limitation that said composition is characterized by a pH of between 6.5 and 7.6, in a method of treatment of a yeast infection accompanied by bacterial infection, wherein said yeast infection accompanied by bacterial infection is an infection of an eye and said method of treatment comprises applying said composition topically to said eye.

[0028] It is a further object of this invention to disclose the use of the composition as defined in any of the above, subject to the limitation that said composition is characterized by a pH of between 4.0 and 7.0, in a method of treatment of a yeast infection accompanied by bacterial infection, wherein said yeast infection accompanied by bacterial infection is a skin infection and said method of treatment comprises applying said composition topically to said skin.

[0029] It is a further object of this invention to disclose the use of the composition as defined in any of the above, subject to the limitation that said composition is characterized by a pH of between 3.5 and 4.5, in a method of treatment of a yeast infection accompanied by bacterial infection, wherein said yeast infection accompanied by bacterial infection is an infection of vaginal mucosa; and said method of treatment comprises applying said composition topically to said vaginal mucosa.

[0030] It is a further object of this invention to disclose the use of the composition as defined in any of the above in a method of prevention of yeast infection, wherein said method of prevention comprises applying said composition topically at least once weekly. In some embodiments of the invention, said method of prevention comprises applying said composition topically 1 - 3 times daily.

[0031] It is a further object of this invention to disclose the use of the composition as defined in any of the above, subject to the limitation that said composition is characterized by a pH of between 6.5 and 7.6, in a method of prevention of yeast infection of an eye, wherein said method of prevention comprises applying said composition topically to an eye at least once weekly.

[0032] It is a further object of this invention to disclose the use of the composition as defined in any of the above, subject to the limitation that said composition is characterized by a pH of between 4.0 and 7.0, in a method of treatment for prevention of yeast infection of skin, wherein said method of prevention comprises applying said composition topically to said skin at least once weekly.

[0033] It is a further object of this invention to disclose the use of the composition as defined in any of the above, subject to the limitation that said composition is characterized by a pH of between 3.5 and 4.5, in a method for prevention of yeast infection of vaginal mucosa, wherein said method of treatment comprises applying said composition topically to vaginal mucosa at least once weekly.

[0034] It is a further object of this invention to disclose a method for treatment or prevention of yeast infection, wherein said method comprises applying said composition as defined in any of the above topically to affected tissue.

[0035] It is a further object of this invention to disclose such a method, wherein said method is a method for treatment or prevention of candidiasis.

[0036] It is a further object of this invention to disclose the method as defined in any of the above, wherein said yeast infection is accompanied by bacterial infection.

[0037] It is a further object of this invention to disclose the method as defined in any of the above, wherein said method comprises applying said composition topically to an affected area 1 - 3 times daily.

[0038] It is a further object of this invention to disclose the method as defined in any of the above, comprising applying said composition at least until a statistically significant reduction in yeast infection is observed.

[0039] It is a further object of this invention to disclose the method as defined in any of the above, wherein said method is a method for treating a yeast infection of an eye, said yeast infection accompanied by bacterial infection; said composition is characterized by a pH of between 6.5 and 7.6; and said step of applying comprises applying said composition topically to an affected eye. [0040] It is a further object of this invention to disclose the method as defined in any of the above, wherein said method is a method for treating a yeast infection of skin, said yeast infection accompanied by bacterial infection; said composition is characterized by a pH of between 4.0 and 7.0; and said step of applying comprises applying said composition topically to affected skin.

[0041] It is a further object of this invention to disclose the method as defined in any of the above, wherein: said method is a method for treating a yeast infection of vaginal mucosa, said yeast infection accompanied by bacterial infection; said composition is characterized by a pH of between 3.5 and 4.5; and said step of applying comprises applying said composition topically to affected vaginal mucosa.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0042] In the following description, various aspects of the invention will be described. For the purposes of explanation, specific details are set forth in order to provide a thorough understanding of the invention. It will be apparent to one skilled in the art that there are other embodiments of the invention that differ in details without affecting the essential nature thereof. The examples presented herein are therefore not to be considered limiting, but only descriptions of specific embodiments of the invention that are provided in order to assist a person of ordinary skill in the art to make and use the invention. Rather, the invention disclosed herein is defined solely by the claims according to their broadest reasonable interpretation.

[0043] In some cases, for clarity or conciseness, individual elements of the invention may be discussed separately in the following detailed description. Any combination of these individual elements that is not self-contradictory is considered by the inventor to be within the scope of the invention.

[0044] Unless stated otherwise, all concentrations are given as percent w/v (grams per 100 ml).

[0045] As used herein, with reference to numerical quantities, the term "about" refers to a range of +25% of the nominal value.

[0046] As used herein, the acronym "PEA" and the term "phenethyl alcohol" are used interchangeably to refer to 2-phenylethan-l-ol (CAS number 60-12-8; EC number 200-456- 2). [0047] As used herein, the term "inorganic salt" is used to refer to a salt that comprises only inorganic ions. For example, salts of organic acids are not considered "inorganic salts" within the meaning of the term as it is used herein.

[0048] As used herein, the term "high molecular weight polymer" is used to refer to a polymer having an average molecular weight of greater than 10⁴ Dalton.

[0049] As used herein, the term "effective treatment" refers to a treatment that produces a statistically significant reduction in the concentration of infectious agent in or on the affected tissue.

[0050] The invention disclosed herein provides a composition and method for treatment and prevention of yeast infection, particularly Candida infection. The composition and method are particularly useful for treatment and prevention of yeast infection when the yeast infection is accompanied by bacterial infection. The composition comprises a solution containing phenethyl alcohol and <5% (w/v) xylitol. Xylitol is known to be a good moisturizer and to prevent bacterial colonization. In some embodiments of the invention, it additionally comprises a preservative. Any preservative known in the art that is compatible with the other components of the composition and with the tissue to which the composition is to be applied may be used. While the preservative may itself have antifungal activity, in preferred embodiments, the composition does not include any antifungal agents other than PEA, polyol, or the preservative.

[0051] In preferred embodiments of the invention, the solution comprises an aqueous solution containing between 0.2% and 1.2% phenethyl alcohol. In more preferred embodiments of the invention, the solution comprises 0.5% phenethyl alcohol (w/v).

[0052] In some preferred embodiments of the invention in which the composition is to be applied to mucous membranes, it comprises an isotonic solution comprising xylitol; in these embodiments, the xylitol concentration is preferably not greater than 3% (w/v). In some preferred embodiments of the invention in which the composition is to be applied to mucous membranes, the xylitol concentration is between 0.5% and 3% (w/v). In some more preferred embodiments of the invention in which the composition is to be applied to mucous membranes, the xylitol concentration is between 1% and 3% (w/v).

[0053] The composition may be in the form of a liquid (preferably aqueous) solution or in the form of a water-based gel. [0054] In some embodiments of the invention, the composition comprises at least one polyol in addition to xylitol. One non-limiting example of a polyol that can be included in the composition is glycerol, which is known to be a good moisturizer and prevents and/or diminishes irritation. In preferred embodiments of the invention in which the composition contains glycerol, the glycerol concentration is between 1% and 5% (w/v). In particularly preferred embodiments of the invention in which the composition contains glycerol, the xylitol concentration is between 1% and 3% (w/v) and the glycerol concentration is between 1% and 5%.

[0055] In particularly preferred embodiments of the invention, the polyol concentration in the composition is too low to provide an effective treatment on its own for yeast or bacterial infection, particularly infection by Candida. Thus, in some non-limiting embodiments of the invention in which the polyol concentration is too low to treat yeast or bacterial infection on its own, the xylitol concentration is <1.5%.

[0056] In preferred embodiments of the invention, the solution is characterized by an inorganic salt concentration of less than 2 mM. In some preferred embodiments of the invention, the solution is isotonic.

[0057] The viscosity of the solution may be controlled by addition of one or more high molecular weight polymers (MW > 10,000 Dalton). In preferred embodiments of the invention, the viscosity is controlled by a polymer selected from the group consisting of hyaluronate, carbomers, and anionic polysaccharides. If the polymer is anionic, then in the absence of added salt, the solution has the additional advantage of having a non-Newtonian viscosity profile.

[0058] In some embodiments of the invention, the composition additionally comprises a pharmaceutically effective concentration of at least one pharmacologically active agent. If necessary, any stabilizer, preservative, antioxidant, buffer or combination thereof appropriate for use with the pharmacologically active agent may be added to the solution in any concentration suitable for the intended use.

[0059] In some preferred embodiments of the invention, the composition consists of an aqueous solution of phenethyl alcohol and xylitol, and optionally one or more ingredients selected from the group consisting of additional polyols, preservatives, pharmaceutically active agents, and viscosity-controlling agents. In some particularly preferred embodiments of the invention, the additional polyol is glycerol. In some particularly preferred embodiments of the invention, the viscosity-controlling agent comprises one or more high molecular weight polymers (MW > 10,000 Dalton). Non-limiting examples of polymers that can be used in the composition include hyaluronate, carbomers, and anionic polysaccharides.

[0060] The composition may be prepared according to standard procedures and transferred to and stored in a container appropriate for storing and/or dispensing it.

[0061] Without being bound by theory, it appears that the effectiveness of the composition disclosed herein derives from the action of the phenethyl alcohol component to inhibit growth of Candida, and the simultaneous action of the polyol to inhibit bacterial growth. The topical composition disclosed herein thus provides an effective treatment for Candida infections even though the active components are present in low concentrations.

[0062] It is also within the scope of the invention to disclose a method for treatment, alleviation, or prevention of Candida infection. In the inventive method for treatment or alleviation of Candida infection, the topical composition disclosed herein is applied to the affected region until the infection is reduced to an acceptable level. In typical embodiments of the invention, the composition is applied to the affected region 1 - 3 times per day. Statistically significant reduction in Candida infection is typically observed within a month of the start of treatment.

[0063] In the inventive method for prevention of Candida infection, the topical composition disclosed herein is applied regularly to a region of the body (e.g. the vagina, eyes, other mucous membranes, or skin) susceptible to Candida infection. In preferred embodiments of the inventive method for prevention of Candida infection, the topical composition disclosed herein is applied at least once weekly to a region of the body susceptible to Candida infection.

[0064] The following examples are presented in order to assist a person skilled in the art to make and use the invention, and are not to be considered in any way limiting.

EXAMPLE 1

[0065] The following composition, comprising an isotonic solution of phenethyl alcohol and xylitol, was prepared for treatment or prevention of ocular candidiasis:

[0066] Phenethyl alcohol 0.5 g

[0067] Xylitol 4.0 g

[0068] Carbomer 981 0.05 g

[0069] Water sufficient to bring to 100 ml [0070] The solution was buffered to pH of 7.2. Preservative was added to some batches.

EXAMPLE 2

[0071] The following composition was prepared for treatment or prevention of ocular candidiasis:

[0072] Phenethyl alcohol 0.5 g

[0073] Xylitol 3.0 g

[0074] Glycerol 1.0 g

[0075] Carbomer 981 0.05 g

[0076] Water sufficient to bring to 100 ml

[0077] The solution was buffered to pH of 7.2. Preservative was added to some batches.

EXAMPLE 3

[0078] The following composition was prepared for treatment or prevention of Candida infection on the skin:

[0079] Phenethyl alcohol 1.0 g

[0080] Xylitol 5.0 g

[0081] Glycerol 5.0 g

[0082] Carbomer 980 0.4 g

[0083] Water sufficient to bring to 100 ml

[0084] The solution was adjusted to a pH of about 5.0. Preservative was added to some batches.

EXAMPLE 4

[0085] The following composition was prepared for treatment or prevention of Candida infection of the vagina:

[0086] Phenethyl alcohol 0.5 g

[0087] Xylitol 2.1 g

[0088] Glycerol 1.2 g

[0089] High M.W. polymer or polymers 0.1 g

[0090] Water sufficient to bring to 100 ml

[0091] The solution was adjusted to a pH of about 4.5. Preservative was added to some batches. EXAMPLE 5

[0092] The following composition was prepared for treatment or prevention of Candida infection of vaginal mucous membranes:

[0093] Phenethyl alcohol 0.5 g

[0094] Xylitol 1.5 g

[0095] Glycerol 1.0 g

[0096] Lactic acid 0.45 g

[0097] Water sufficient to bring to 100 ml

[0098] The solution was adjusted to a pH of about 4.5. Preservative was added to some batches.

EXAMPLE 6

[0099] The following composition was prepared for treatment or prevention of Candida infection of vaginal mucous membranes:

[0100] Phenethyl alcohol 1.0 g

[0101] Xylitol 1.5 g

[0102] Glycerol 1.0 g

[0103] Lactic acid 0.4 g

[0104] Polymer 2.0 g

[0105] Water sufficient to bring to 100 ml

[0106] The solution was adjusted to a pH of about 4.5. Preservative was added to some batches.

EXAMPLE 7

[0107] The following composition was prepared for treatment or prevention of Candida infection of vaginal mucous membranes:

[0108] Phenethyl alcohol 0.5 g

[0109] Xylitol 2.1 g

[0110] Glycerol 1.2 g

[0111] Lactic acid 0.45 g

[0112] High M.W. polymer 0.1 g

[0113] Water sufficient to bring to 100 ml

[0114] The solution was adjusted to a pH of about 4.5. Preservative was added to some batches. EXAMPLE 8

[0115] The following composition was prepared for treatment or prevention of Candida infection of vaginal mucous membranes:

[0116] Phenethyl alcohol 1.0 g

[0117] Xylitol 1.5 g

[0118] Glycerol 1.0 g

[0119] Lactic acid 0.75 - 1.0 g

[0120] High M.W. polymer 2.1 g

[0121] Water sufficient to bring to 100 ml

The solution was adjusted to a pH of between 3.5 and 4.5. Preservative was added to some batches.

EXAMPLE 9

[0122] The effects of several compositions containing 1.5% xylitol, 1.0% glycerol, and 0.45% lactic acid and varying concentrations of phenethyl alcohol (PEA) on Candida albicans cultures were tested.

[0123] The initial and the surviving microbial counts (means of the colony counts) of the solutions inoculated with the suspension (containing ~2 x 10⁵ microorganisms/ 100 μΐ) after incubation for 0 and 24 hours on the basis of the microbial count assessment are summarized in Table 1 (initial counts) and Table 2 (counts after 24 h) for compositions containing no PEA (control, 2 independent measurements), 0.1% PEA (3 independent measurements, 0.5% PEA (3 independent measurements), and 1.0% PEA (3 independent measurements).

TABLE 1 dilution control 0.1% PEA 0.5% PEA 1.0% PEA

10 ¹ many many many many many many many many many many

10² 88.8 102.3 81.3 75.3 79.6 73.6 60.3 63 76.6 68.3 !0³ 18.3 18.6 12 17 14.6 16 11 6 15.6 6.3

TABLE 2 dilution control 0.1% PEA 0.5% PEA 1.0% PEA

10 ¹ many many many many many 0 0 0 0 0 0 w² many many 38 41.3 42.6 0 0 0 0 0 0 io-³ 53.6 58.6 4 4 5.3 0 0 0 0 0 0

Claims

CLAIMS What is claimed is:

1. A topical composition for treatment, alleviation, or prevention of yeast infection, wherein said composition comprises:

phenethyl alcohol;

xylitol; and,

optionally, a preservative,

and further wherein:

said composition contains no more than 5% (w/v) xylitol; and,

said composition contains no additional antifungal agent.

2. The composition according to claim 1, wherein said composition is for treatment, alleviation, or prevention of candidiasis.

3. The composition according to claim 1, wherein said composition is for treatment, alleviation, or prevention of yeast infection is accompanied by bacterial infection.

4. The composition according to claim 1, wherein said composition is characterized by a phenethyl alcohol concentration of between 0.2% and 1.2% (w/v).

5. The composition according to claim 4, wherein said composition is characterized by a phenethyl alcohol concentration of 1% (w/v).

6. The composition according to claim 4, wherein said composition is characterized by a phenethyl alcohol concentration of 0.5% (w/v).

7. The composition according to claim 1, wherein said composition is characterized by a xylitol concentration of no more than 3% (w/v).

8. The composition according to claim 7, wherein said composition is characterized by a xylitol concentration of between 0.5% and 3%.

9. The composition according to claim 7, wherein said composition is characterized by a xylitol concentration of between 1% and 3% (w/v).

10. The composition according to claim 7, wherein said composition is characterized by a xylitol concentration of no more than 1.5% (w/v).

11. The composition according to claim 1, wherein said solution comprises glycerol.

12. The composition according to claim 11, wherein said composition is characterized by a glycerol concentration of between 1% and 5% (w/v).

13. The composition according to claim 11, wherein said composition is characterized by a xylitol concentration of between 1% and 3% (w/v) and a glycerol concentration of between 1% and 5% (w/v).

14. The composition according to claim 1, wherein said composition comprises an isotonic aqueous solution.

15. The composition according to claim 1, wherein said composition comprises a hypertonic aqueous solution.

16. The composition according to claim 1, wherein said composition is characterized by a pH that is within a normal pH range of tissue to which said composition is to be applied topically.

17. The composition according to claim 16, wherein said composition is characterized by a pH of between 6.5 and 7.6, and said tissue is eye tissue.

18. The composition according to claim 16, wherein said composition is characterized by a pH of between 4.0 and 7.0, and said tissue is skin tissue.

19. The composition according to claim 16, wherein said composition is characterized by a pH of between 3.5 and 4.5, and said tissue is vaginal mucosa.

20. The composition according to claim 19, wherein said composition comprises lactic acid.

21. The composition according to claim 20, wherein said composition comprises between 0.75% and 1.0% (w/v) lactic acid.

22. The composition according to claim 20, wherein said composition comprises between 0.4% and 0.45% (w/v) lactic acid.

23. The composition according to claim 1, wherein said solution is characterized by an inorganic salt concentration of less than 0.1%.

24. The composition according to claim 1, comprising at least one polymer characterized by a molecular weight of at least 10,000 Dalton.

25. The composition according to claim 24, wherein said at least one polymer is characterized by a molecular weight of at least 100,000 Dalton.

26. The composition according to claim 24, wherein said at least one polymer is present in a concentration chosen to bring said composition to a predetermined viscosity.

27. The composition according to claim 24, wherein said at least one polymer is present in a concentration sufficient to produce a gel.

28. The composition according to claim 24, wherein said at least one polymer is anionic.

29. The composition according to claim 28, wherein said polymer is selected from the group consisting of hyaluronates, carbomers, and anionic polysaccharides.

30. The composition according to claim 28, wherein said anionic polysaccharide is a sulfated polysaccharide.

31. The composition according to claim 1, comprising a pharmaceutically effective amount of a pharmacologically active agent.

32. The composition according to claim 1, comprising a substance selected from the group consisting of stabilizers, preservatives, antioxidants, and buffers.

33. The composition according to claim 1, wherein said preparation is in the form of an aqueous solution.

34. The composition according to claim 1, wherein said preparation is in the form of a water- based gel.

35. The use of the composition according to any one of claims 1 - 34 in a method of treatment of a yeast infection, wherein said method of treatment comprises applying said composition topically to affected tissue.

36. The use according to claim 35, wherein said yeast infection is candidiasis.

37. The use according to claim 35, wherein said yeast infection is accompanied by bacterial infection.

38. The use according to claim 35, wherein said method of treatment comprises applying said composition to an affected at least once weekly.

39. The use according to claim 38, wherein said method of treatment comprises applying said composition to an affected area 1 - 3 times daily.

40. The use according to claim 35, wherein said treatment comprises applying said composition to an affected area at least until a statistically significant reduction in yeast infection is observed.

41. The use of the composition according to any one of claims 1 - 17 or 23 - 34 in a method of treatment of a yeast infection accompanied by bacterial infection, wherein:

said yeast infection accompanied by bacterial infection is an infection of an eye;

said composition is characterized by a pH of between 6.5 and 7.6; and,

said method of treatment comprises applying said composition topically to said eye.

42. The use of the composition according to any one of claims 1 - 16, 18, or 23 - 34 in a method of treatment of a yeast infection accompanied by bacterial infection, wherein:

said yeast infection accompanied by bacterial infection is a skin infection;

said composition is characterized by a pH of between 4.0 and 7.0; and,

said method of treatment comprises applying said composition topically to said skin.

43. The use of the composition according to any one of claims 1 - 16 or 19 - 34 in a method of treatment of a yeast infection accompanied by bacterial infection, wherein:

said yeast infection accompanied by bacterial infection is an infection of vaginal mucosa;

said composition is characterized by a pH of between 3.5 and 4.5; and,

said method of treatment comprises applying said composition topically to said vaginal mucosa.

44. The use of the composition according to any one of claims 1 - 34 in a method of treatment for prevention of yeast infection, wherein said method of treatment comprises applying said composition topically at least once weekly.

45. The use according to claim 44, wherein said method of treatment comprises applying said composition topically 1 - 3 times daily.

46. The use of the composition according to any one of claims 1 - 17 or 23 - 34 in a method of treatment for prevention of yeast infection of an eye, wherein:

said composition is characterized by a pH of between 6.5 and 7.6; and,

said method of treatment comprises applying said composition topically to said eye at least once weekly.

47. The use of the composition according to any one of claims 1 - 16, 18, or 23 - 34 in a method of treatment for prevention of yeast infection of skin, wherein:

said composition is characterized by a pH of between 4.0 and 7.0; and,

said method of treatment comprises applying said composition topically to said skin at least once weekly.

48. The use of the composition according to any one of claims 1 - 16 or 19 - 34 in a method of treatment for prevention of yeast infection of vaginal mucosa, wherein:

said composition is characterized by a xylitol concentration of no more than 3% (w/v); said composition is characterized by a pH of between 3.5 and 4.5; and,

said method of treatment comprises applying said composition topically to said vaginal mucosa at least once weekly.