Emulsions for treating mucous membrane infections

Abstract

The invention relates to an emulsion, e.g. in the form of a salve or a cream, with an aqueous phase and an oil phase, containing an NSAID, characterised in that: (a) the NSAID in the aqueous phase is in a concentration range that corresponds to half to a tenth of the standard concentration for these active substances; (b) the weight ratio of the water-to-oil phase in said emulsion is between the values 2.0 and 2.7; and (c) the pH value of the emulsion is not below the value 6.5 and not above 8.5, preferably in the region of between 7.0 and 8.0, particularly for application in the topical treatment of vaginal fungal infections.

Claims

1. An emulsion with an aqueous phase and an oil phase, comprising: an antimycotic and an NSAID, wherein (a) the NSAID is diclofenac in a concentration of 0.1 to 0.5 weight percent, indometacin in a concentration of 0.1 to 0.4 weight percent, naproxen in a concentration of 1 to 5 weight percent, ibuprofen in a concentration of 0.5 to 2.5 weight percent, dexibuprofen in a concentration of 0.25 to 1.25 weight percent, ketoprofen in a concentration of 0.25 to 1.25 weight percent, mefenamic acid in a concentration of 0.5 to 4 weight percent, or lornoxicam in a concentration of 0.02 to 0.04 weight percent, the NSAID is present in salt form; while (b) a weight ratio of the aqueous phase to the oil phase in the emulsion is between 2.0 and 2.7, and (c) a pH value of the emulsion is not less than 6.5 and not more than 8.5.

2. The emulsion according to claim 1, wherein the emulsion is in the form of a salve or a cream.

3. The emulsion according to claim 1, wherein the emulsion is semi- solid.

4. The emulsion according to claim 1, wherein the antimycotic is nystatin, ciclopirox or ciclopiroxolamine, or an antimycotic from a group of azoles.

5. The emulsion according to claim 1, wherein the antimycotic is clotrimazole.

6. The emulsion according to claim 1, wherein the NSAID is diclofenac and is contained in a concentration range of 0.2-0.4 weight percent of the emulsion.

7. The emulsion according to claim 1, further comprising a preservative active in the pH range of the emulsion.

8. The emulsion according to claim 7, wherein the preservative is phenoxyethanol, propylene glycol or a combination thereof.

9. The emulsion according to claim 7, wherein the preservative is dequalinium chloride.

10. The emulsion according to claim 1, further comprising an antibiotic which acts against bacterial germs.

11. The emulsion according to claim 1, further comprising an antiseptic.

12. The emulsion according to claim 11, wherein the antiseptic is selected from the group consisting of benzalkonium chloride; dequalinium chloride; and phenoxyethanol.

13. A method for treatment of a vaginal fungal infection, the method comprising: applying the emulsion according to claim 1 to a subject in need thereof.

14. The method according to claim 13, wherein the treatment is a topical treatment.

15. The method according to claim 13, wherein the vaginal fungal infection is a mixed vaginal infection by Candida albicans and bacteria.

16. The method according to claim 13, wherein the vaginal fungal infection is a candida mycosis.

17. A process for preparing the emulsion according to claim 1, the process comprising: introducing the NSAID into the aqueous phase.

18. A process for preparing the emulsion according to claim 1, the process comprising: introducing the N SAID as a finely crystalline or micronised salt into an emulsion comprising the antimycotic.

19. A process for preparing the emulsion according to claim 1, the process comprising: introducing the NSAID via a hydrogel into an emulsion comprising the antimycotic.

20. A process for preparing the emulsion according to claim 11, the process comprising: adding substances in such a way that a therapeutically effective antibacterial effect is obtained.

Description

FIGURES

(1) FIG. 1: Phase II clinical study. Pain diaries of patients with recurrent vulvovaginal candidiasis (RVVC) who were treated with emulsions according to the invention containing different concentrations of diclofenac Na (CP1: 0.2 wt. %, CP2: 0.3 wt. %, CP3: 0.4 wt. %) or with a control composition without diclofenac Na (“comparator”) according to the invention. The intensity of pain was recorded by the patients at the time of recording on a pain scale from 0 to 10. The diagram shows the mean values of the treatment groups during the course of treatment. At CP 1, there is a rapid decrease in pain intensity, but the healing curve flattens out as soon as the daily dose is halved (from day 4). CP 2 shows an optimal healing process. Already on day 2 the pain level has decreased to 50% of the initial value.

EXAMPLES

(2) Preliminary Remark

(3) Changes in the preparation method and in the percentage composition of an oil-in-water mixture corresponding to base formulation A showed surprising changes in clinical efficacy away from the usual dose-effect relationships. The significantly improved or possibly also reduced efficacy can be derived from a particularly rapid onset of action (local pain relief) or a delay in the onset of action or the intensification of existing pain.

Example 1—Basic Formulation

(4) TABLE-US-00003 TABLE 1 Basic formulation A Composition of the emulsion Clotrimazole 1.00 Diclofenac Na 0.20 Sorbitan monostearate 2.00 Polysorbate 60 1.50 Cetylpalmitate 3.00 2-octyldodecanol 13.50 Cetostearyl alcohol 10.00 Benzyl alcohol 1.00 Purified water Ph. Eu. 67.80 Total 100.00 Ph 7.8

(5) If the concentration of the NSAID changes, it is exchanged in each case for purified water; the content of lipid components remains the same, unless otherwise stated. The clinical efficacy in the following preparations is related to a clinically effective basic formulation A.

Example 2: Variations of the pH Range and Clinical Efficacy

(6) Changes with respect to preservatives are associated with changes in the pH value. The stated examples were prepared according to general preparation instructions 1. The adjustment of the pH value to achieve the optimum effect of the preservative in question was carried out by adding suitable buffer solutions by which the relevant amount of purified water had been replaced.

(7) The pH value has a significant influence on the locally bioavailable amount of active substance by shifting the free active substance proportion compared to the proportion present as salt. Depending on the pKa values of the non-steroidal antiphlogistics used, this results, in accordance with the present invention, in a pH optimum of the combination preparations according to the invention.

(8) TABLE-US-00004 TABLE 2 pH dependence of clinical efficacy Composition Conc. wt. % Conc. wt. % Clotrimazole 1 1 Diclofenac Na 0.25 0.25 Sorbitan monostearate 2 2 Polysorbate 60 1.5 1.5 Cetylpalmitate 3 3 2-octyldodecanol 13.5 13.5 Cetylstearyl alcohol 10 10 Phenoxyethano1 1 0 Bronopol 0.1 0 Sorbic acid 0 0.2 Buffer solution 0.2201 0.0874 Purified water Ph. Eur. 67.4299 68.4626 Total 100 100 Ph 7.5 5.6 Clin. efficacy conforms reduced Microbiol. stability conforms conforms

Example 3: Influence of the Aqueous Phase/Oil Weight Ratio

(9) Surprisingly, changes in viscosity show clear influences on clinical efficacy even with a small range of variation. The stated examples were prepared according to general preparation instructions 1 by varying the content of fatty components and the water content.

(10) An increase in the water content and thus a decrease in viscosity leads to local irritation and reduced clinical efficacy through increased release and increased wetting of the mucosas.

(11) TABLE-US-00005 TABLE 3 Influence of the aqueous phase/oil weight ratio on the clinical efficacy Fat component/ Basic Fat component/ Phase viscosity reduced formulations viscosity increased Clotrimazole (oil) 1 1.0 1.0 1.0 1.0 1.0 Diclofenac Na (water) 0.3 0.3 0.3 0.3 0.3 0.3 Sorbitan monostearate (—) 2.0 2.0 2.0 2.0 2.0 2.0 Polysorbate 60 (—) 1.5 1.5 1.5 1.5 1.5 1.5 Cetylpalmitate (oil) 3.0 3.0 3.0 3.0 3.0 3.0 2-octyldodecanol (oil) 13.5 13.5 13.5 13.5 13.5 14.5 Cetylstearyl alcohol (oil) 7.5 5 10 10 14 16 Benzyl alcohol (oil) 1.0 1.0 1.0 1.0 1.0 Phenoxyethanol (oil) 1.0 Propylene glycol (water) 7 Water (water) 70.2 72.7 67.75 60.7 63.7 60.7 Total 100 100 100 100 100 100 Clinical efficacy irritating irritating conforms conforms reduced reduced Water phase total 70.5 73.0 68.0 68.0 64.0 61.0 Fat phase total 26 23.5 28.5 28.5 32.5 35.5 aqueous phase/fat 2.7 3.1 2.4 2.4 2.0 1.7

(12) To calculate the weight ratio of the water phase to the oil phase, the individual proportions of the water and oil phases are added together as shown in the table. Since emulsifiers, for example sorbitan monostearate and polysorbate 60, are located at the interfaces between the two phases, they are not assigned to either the water or the oil phase.

(13) If the ratio of the aqueous phase to the oil phase of the concentrated emulsion (i.e. the intermediate product of components A, B, J, C, E, G, H and half of K) of example 2 of WO 02/0768648 A2 is calculated, a ratio of 3.1 is obtained (oil phase: terbinafine, butylhydroxytoluene, benzyl alcohol, isopropyl myristate, total 11.52 g/100 g; water phase: diclofenac sodium and water, total 35.94 g/100 g; ratio 3.1). Such an emulsion therefore has a water-to-oil ratio outside the scope of the invention and would therefore not be suitable in the context of the present invention.

(14) Alternatively, the weight ratio of the water phase to the oil phase could be calculated without including the substances dissolved in the phases (clotrimazole, diclofenac Na, benzyl alcohol, cetylstearyl alcohol). With this method of calculation, only water and propylene glycol would be attributed to the water phase in Table 3, and cetyl palmitate, 2-octyldodecanol and cetylstearyl alcohol to the oil phase. The water-to-oil ratios 2.7, 3.1, 2.4, 2.4, 2.0, 1.7 given in Table 3 would correspond to the values 2.9, 3.4, 2.6, 2.6, 2.1, 1.8 according to this calculation method. The range according to the invention of 2.0 to 2.7 would correspond to a range of 2.1 to 2.9 according to this calculation method.

(15) In the context of the present invention, however, the calculation of the weight ratio of the water phase to the oil phase shall be carried out as shown in Table 3, i.e. including the substances dissolved in the phases.

Example 4: Variation of the Non-Steroidal Antiphlogistic

(16) Instead of diclofenac, various other non-steroidal antiphlogistics were added to the basic formulation A and examined for their clinical efficacy.

(17) TABLE-US-00006 TABLE 4 Variations of non-steroidal antiphlogistics Formulation Non-steroidal Preparation no. antiphlogistic Preparation variant Efficacy 1.1 Mefenamic 1 g/100 g Basic conforms acid formulation A + mefenamic acid micronised 1.2 Indometacin 0.15 g/100 g   Basic conforms formulation A + indometacin micronised 1.3 Ibuprofen 1 g/100 g Basic conforms formulation A + ibuprofen hydrogel 1.4 Ibuprofen 0.5 g/100 g.sup.  Basic conforms formulation A + ibuprofen hydrogel 1.5 Naproxen 1 g/100 g Basic conforms formulation A + naproxen micronised

Example 5: Optimum Concentration

(18) According to the basic formulation A, emulsions with different concentrations of diclofenac Na were prepared and tested for their clinical efficacy.

(19) TABLE-US-00007 TABLE 5 Dependence of clinical efficacy on the concentration of NSAIDS Conc. Conc. Conc. Conc. wt. % wt. % wt. % wt. % Clotrimazole 1 1 1 1 Diclofenac Na 0.1 0.25 0.5 0.75 Sorbitan 2 2 2 2 monostearate Polysorbate 60 1.5 1.5 1.5 1.5 Cetylpalmitate 3 3 3 3 2-octyldodecanol 13.5 13.5 13.5 13.5 Cetylstearyl 10 10 10 10 alcohol Benzyl alcohol 1 1 1 1 Purified water 67.9 67.75 67.5 67.25 Ph. Eur. Total 100 100 100 100 Ph 7.6 7.8 8.1 8.1 Clin. efficacy slightly conforms conforms, irritating reduced slightly to the irritating mucosa

Example 6: Variation of Preservatives and Microbiological Stability

(20) The combined use of clotrimazole and NSAIDs changes both microbiological and chemical stability [Lit. Pharmacopoeia] compared to a comparable clotrimazole formulation due to the pH shifts in the emulsion system.

(21) TABLE-US-00008 TABLE 6 Variants with different preservatives Composition wt. % wt. % wt. % wt. % wt. % Clotrimazole 1 1 1 1 1 Diclofenac Na 0.4 0.3 0.3 0.25 0.25 Sorbitan monostearate 2 2 2 2 2 Polysorbate 60 1.5 1.5 1.5 1.5 1.5 Cetylpalmitate 3 3 3 3 3 2-octyldodecanol 13.5 13.5 13.5 13.5 13.5 Cetylstearyl alcohol 10 10 10 10 10 Propylene glycol 7 5 Phenoxyethanol 4 1 1 1 Bronopol 0.1 Sorbic acid 0.2 Buffer solution 0.2201 0.0874 Purified water 64.6 60.7 62.7 67.4299 68.4626 Ph. Eur. Total 100 100 100 100 100 Ph 7.9 7.6 7.9 7.5 5.6 Clin. efficacy conforms conforms conforms conforms reduced Microbiol. stability conforms conforms conforms conforms conforms

Example 7

Preparation of Basic Formulation A

General Preparation Instructions 1

(22) The components sorbitan monostearate, polysorbate 60, cetyl palmitate, 2-octyldodecanol and cetostearyl alcohol are melted at a temperature of 70-75° C. Clotrimazole and then benzyl alcohol are added to the clear melt while stirring at a temperature of 60° C.-70° C. At the same time, diclofenac sodium is dissolved in purified water while heating. The aqueous solution is added to the oil phase while stirring and homogenised. Under slow cooling with further homogenisation of the w/o emulsion formed, a phase inversion takes place which results in a hydrophilic, homogeneous cream.

(23) TABLE-US-00009 TABLE 8 Formulations based on Formulation A, preparation instructions 1 Constituents of the emulsion Clotrimazole 1.00 1.00 Diclofenac Na 0.20 0.30 Sorbitan monostearate 2.00 2.00 Polysorbate 60 1.50 1.50 Cetylpalmitate 3.00 3.00 2-octyldodecanol 13.50 13.50 Cetostearyl alcohol 10.00 10.00 Benzyl alcohol 1.00 1.00 Purified water Ph. Eur. 67.80 67.70 100.00 100.00

(24) The clinical efficacy of the formulations in Table 8 is identical.

General Preparation Instructions 2

(25) The components sorbitan monostearate, polysorbate 60, cetyl palmitate, 2-octyldodecanol and cetostearyl alcohol are melted at a temperature of 70-75° C. Clotrimazole is added to the clear melt while stirring at a temperature of 60° C.-70° C. and melted. At the same time, diclofenac sodium is dissolved in purified water while heating. After addition of phenoxyethanol and, if necessary, propylene glycol, the aqueous solution is added to the oil phase at a temperature of 60° C.-70° C. while stirring and homogenised. With slow cooling and further homogenisation of the w/o emulsion initially formed, a phase inversion to an o/w emulsion takes place, resulting in a hydrophilic, homogeneous cream. (For clinical results see Table 6)

(26) Instead of dissolving the NSAID in water, it can also be incorporated by stirring in an NSAID dissolved in a hydrogel or by stirring in the (micronised) NSAID as a solid during emulsion preparation.

Example 9: Preparation of Basic Formulation a by Incorporating the NSAID into the Oil Phase

(27) Creams with different concentrations of Diclofenac Na were prepared according to basic formulation A in accordance with general preparation instructions 2 and their clinical efficacy was tested. Purified water was exchanged for diclofenac Na; the content of the lipid components, the O/W emulsifier polysorbate 60 and the preservative benzyl alcohol was identical in the formulations.

General Preparation Instructions 3

(28) The components sorbitan monostearate, polysorbate 60, cetyl palmitate, 2-octyldodecanol and cetostearyl alcohol are melted. Benzyl alcohol is added to the clear melt while stirring (lipid phase). Purified water is heated to boiling point and 70% of the required mass according to the formulation is added to the lipid phase while stirring (phase inversion and formation of an O/W pre-emulsion). About 30% of the pre-emulsion is removed from the vessel, and clotrimazole and diclofenac sodium are dispersed in it. The active substance-containing pre-emulsion is added to the active substance-free pre-emulsion in the vessel and filled up to the final mass with purified water (remaining 30%). The cream is stirred until room temperature is reached, and finally, for homogenisation, it is passed twice over a three roll mill (pH 6.99).

(29) TABLE-US-00010 TABLE 9 Formulations based on formulation A, preparation instructions 3. Composition Clotrimazole 2.00 2.00 Diclofenac Na 0.10 0.20 Sorbitan monostearate 2.00 2.00 Polysorbate 60 1.50 1.50 Cetylpalmitate 3.00 3.00 2-octyldodecanol 13.50 13.50 Cetostearyl alcohol 10.00 10.00 Benzyl alcohol 1.00 1.00 Purified water Ph. Eur. 66.90 66.80 100.00 100.00 Clin. efficacy reduced reduced

(30) From the examples according to preparation instructions 3, a significant influence of the preparation process results, which must be designed in such a way that the non-steroidal antiphlogistic is incorporated via the aqueous phase and is predominantly present in the aqueous phase.

Example 10: Preparation of Basic Formulation A

(31) Preparation of basic formulation A with incorporation of a non-steroidal antiphlogistic (diclofenac Na) according to general preparation instructions 4:

(32) The components sorbitan monostearate, polysorbate 60, cetyl palmitate, 2-octyldodecanol and cetostearyl alcohol are melted. Benzyl alcohol is added to the clear melt while stirring (lipid phase). Purified water is heated to boiling point and 70% of the required mass according to the formulation is added to the lipid phase while stirring (phase inversion and formation of an O/W pre-emulsion). About 30% of the pre-emulsion is removed from the vessel, and clotrimazole is dispersed in it. The active substance-containing pre-emulsion is added to the active substance-free pre-emulsion in the vessel and filled up to the final mass with purified water (remaining 30%). The cream is stirred with the addition of micronised diclofenac sodium in several portions until room temperature is reached, and finally, for homogenisation, it is passed twice over a three roll mill.

Example 11: Phase II Clinical Study

(33) The clinical efficacy of emulsions according to the invention for the treatment of chronic vaginal infections was investigated in a phase II clinical study.

(34) In accordance with general preparation instructions 1, three emulsions according to the invention with different concentrations of diclofenac Na were prepared. An emulsion without NSAID was used as a control: Emulsion CP1: 0.2 wt. % diclofenac Na Emulsion CP2: 0.3 wt. % diclofenac Na Emulsion CP3: 0.4 wt. % diclofenac Na Emulsion Comparator: 0 wt. % diclofenac Na

(35) 31 patients with chronic recurrent vaginal infections (chronic recurrent vulvovaginal candidiasis, RVVC) were treated. Patients with clinical symptoms of at least moderate severity were enrolled in the study after positive detection of fungal infection. In the first 3 days, 2.5 ml of cream were administered intravaginally twice daily by means of an applicator, and in the following 3 days 2.5 ml of cream were applied once daily. After 7-10 days a check-up examination was performed.

(36) Each of the three emulsions according to the invention led to a better healing success than the control, which did not contain NSAID. Emulsion 2, containing 0.3 wt. % diclofenac Na, proved to be particularly beneficial. A complete clinical cure (complete freedom from symptoms at check-up examination by the treating physician) was achieved in all patients in this group. In the control group only 40% of the patients were cured.

(37) As a further clinical parameter—in addition to the healing effect—the development of pain in chronic patients (pain diary) was used. The intensity of pain was entered by the patients at the time of recording on a pain scale from 0 to 10. The mean values of the treatment groups during the course of treatment are shown in FIG. 1. With a constant concentration of the antimycotic, it was found that in the highest concentration of the NSAID (emulsion 3), the course of healing was better compared to the control, but the decrease in pain intensity showed no significant difference as compared to the control group. The optimal concentration (emulsion 2), at which all patients were cured, quickly led to a complete reduction in pain. The clear dose dependence was also evident in the patients with the lowest concentration (emulsion 1), where the pain decreased significantly until the dosage was changed from twice-a-day to a once-a-day dosage, whereupon the healing process slowed down accordingly (see FIG. 1).

(38) Microbiological tests carried out in parallel showed that none of the patients were infected with resistant candida strains, but the majority of RVVC patients did not respond to antifungal therapy.

(39) Accordingly, the invention relates to the following preferred embodiments:

(40) 1. An emulsion with an aqueous phase and an oil phase, containing an NSAID, characterised in that (a) the NSAID in the aqueous phase is in a concentration range that corresponds to half to a tenth of the standard concentration for these active substances, in that (b) the weight ratio of the water phase to the oil phase in this emulsion is between the values 2.0 and 2.7, and in that (c) the pH value of the emulsion is not less than the value 6.5 and not more than 8.5, preferably in the range 7.0 to 8.0.

(41) 2. An emulsion with an aqueous phase and an oil phase, containing an antimycotic and an NSAID, characterised in that (a) the NSAID in the aqueous phase is in a concentration range that corresponds to half to a tenth of the standard concentration for these active substances, in that (b) the weight ratio of the water phase to the oil phase in this emulsion is between the values 2.0 and 2.7, and in that (c) the pH value of the emulsion is not less than the value 6.5 and not more than 8.5, preferably in the range 7.0 to 8.0.

(42) 3. An emulsion according to embodiment 1 or 2, characterised in that the weight ratio of the water phase to the oil phase in this emulsion is between the values 2.1 and 2.6, preferably between the values 2.2 and 2.55.

(43) 4. An emulsion according to one of the embodiments 1 to 3, characterised in that the pH value of the emulsion is in the range 7.0 to 8.5, preferably in the range 7.5 to 8.0

(44) 5. An emulsion according to one of embodiments 1 to 4, characterised in that it is in the form of a salve or a cream.

(45) 6. An emulsion according to one of embodiments 1 to 5, characterised in that the emulsion is semi-solid.

(46) 7. An emulsion according to one of embodiments 1 to 6, characterised in that the antimycotic is nystatin, ciclopirox or ciclopiroxolamine, or an antimycotic from the group of azoles, preferably clotrimazole, fluconazole, miconazole, itraconazole, tioconazole, voriconazole, bifonazole, econazole, isoconazole, fenticonazole, sertaconazole, ketoconazole, posaconazole, quilseconazole, oteseconazole (VT-1161) or ibrexafungerp (SCY-078).

(47) 8. An emulsion according to one of embodiments 1 to 7, characterised in that the antimycotic is clotrimazole.

(48) 9. An emulsion according to one of embodiments 1 to 8, characterised in that the NSAID is diclofenac, preferably in a concentration of 0.2 to 0.5 weight percent, ibuprofen, preferably in a concentration of 0.5 to 2.5 weight percent, bufexamac, dexibuprofen, flurbiprofen, ketoprofen, piroxicam, meloxicam, lornoxicam, flufenamic acid, mefenamic acid, indometacin, preferably in a concentration of 0.1 to 0.4 weight percent, or naproxen, preferably in a concentration of 0.5 to 2.5 weight percent.

(49) 10. An emulsion according to one of embodiments 1 to 9, characterised in that the NSAID is diclofenac and this is contained in a concentration range of 0.2-0.4 weight percent of the emulsion.

(50) 11. An emulsion according to one of embodiments 1 to 10, in which a preservative active in the pH range of the emulsion is contained.

(51) 12. An emulsion according to embodiment 11, in which the preservative is phenoxyethanol or propylene glycol or a combination of the two.

(52) 13. An emulsion according to embodiment 11, in which the preservative is dequalinium chloride.

(53) 14. An emulsion according to one of embodiments 1 to 13, characterised in that it further contains an antibiotic which acts against bacterial germs.

(54) 15. An emulsion according to embodiment 14, characterised in that the antibiotic is phosphomycin, clindamycin, metronidazole, nitrofurantoin, nitrofurazone, nitrofurantoin, nifuratel, nifuroxacin, nitroxolin, trimethoprim, sulfadiazine, or cotrimoxazole.

(55) 16. An emulsion according to one of embodiments 1 to 15, characterised in that it further contains an antiseptic, preferably in an amount sufficient for an acute antimicrobial effect.

(56) 17. An emulsion according to embodiment 16, characterised in that the antiseptic is a quaternary ammonium salt.

(57) 18. An emulsion according to embodiment 16 or 17, characterised in that the antiseptic is selected from the group consisting of: benzalkonium chloride, preferably in a concentration of at least 0.2 weight percent; dequalinium chloride, preferably in a concentration of at least 0.2 weight percent; and phenoxyethanol, preferably in a concentration of at least 2 weight percent.

(58) 19. An emulsion according to one of embodiments 1 to 18 for use in the treatment of dermal and vaginal fungal infections.

(59) 20. An emulsion according to one of embodiments 1 to 19 for use in the topical treatment of vaginal fungal infections.

(60) 21. Emulsion according to one of embodiments 1 to 20 for use in the treatment of chronic infections of the urogenital tract.

(61) 22. Emulsion according to one of embodiments 1 to 21 for use in the treatment of chronic vaginal fungal infections.

(62) 23. Emulsion according to one of embodiments 1 to 22 for use in the treatment of infectious diseases, in particular vaginal infections by Candida albicans.

(63) 24. Emulsion according to embodiments 1 to 23 for use in the treatment of infectious diseases, in particular mixed vaginal infections by Candida albicans and bacteria such as Enterobacter, E. coli, Klebsiella pneumoniae, Gardnerella vaginalis, and Prevotella spp.

(64) 25. Emulsion according to one of embodiments 1 to 24 for use in the treatment of bacterial vaginosis.

(65) 26. Emulsion according to embodiments 1 to 25 for use in the treatment of dermal or mucosal fungal infections, preferably of Candida mycoses, in particular vulvovaginal candidiasis, oropharyngeal candidiasis (oral thrush), nappy dermatitis (nappy rash), anal eczema, intertriginous eczema, and Malassezia mycoses.

(66) 27. Emulsion according to one of embodiments 1 to 26 for use in the treatment of mucosal inflammation, in particular chronic mucosal inflammation.

(67) 28. Emulsion according to one of embodiments 1 to 27 for use in the treatment of mucosal infections, in particular chronic mucosal infections.

(68) 29. Emulsion according to one of embodiments 1 to 28 for use in the post-treatment of mucosal infections, in particular vaginal inflammation.

(69) 30. Emulsion for use according to embodiment 29, characterised in that the vaginal inflammation are chronic.

(70) 31. Emulsion according to one of embodiments 1 to 30 for use in the treatment of inflammation of mucosas and the immediately adjacent tissues.

(71) 32. Emulsion according to one of embodiments 1 to 31 for use in the post-treatment of chronic cystitis.

(72) 33. Emulsion according to one of embodiments 1 to 32 for use in the treatment of atrophic vaginitis.

(73) 34. Emulsion according to one of embodiments 1 to 33 for use in the treatment of inflammation of the anal mucosa.

(74) 35. A process for preparing an emulsion according to one of embodiments 1 to 34, characterised in that, during preparation of the emulsion, the NSAID is introduced via the aqueous phase.

(75) 36. A process for preparing an emulsion according to one of embodiments 1 to 35, characterised in that the NSAID is introduced as a finely crystalline or micronised salt into the emulsion containing the antimycotic.

(76) 37. A process for preparing an emulsion according to one of embodiments 1 to 36, characterised in that the NSAID is introduced via a hydrogel into the emulsion containing the antimycotic.

(77) 38. A process for preparing an emulsion according to one of embodiments 1 to 37, in which the substances are added in such a way that a therapeutically effective antibacterial effect is obtained.