Emulsions for the topical treatment of dermal and mucosal infections

Abstract

The invention relates to an emulsion for the topical treatment of dermal infections and mucosal infections, in particular of urogenital infectious diseases, characterized in that an antimicrobial agent and an anti-adhesive agent, preferably an NSAID, are used in combination.

Claims

1. An emulsion, comprising: an antimicrobial active substance selected from the group consisting of an antibiotic and an antiseptic, and an NSAID, wherein (a) the NSAID is diclofenac in a concentration of 0.1 to 0.5 weight percent, indomethacin 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 an aqueous phase to an 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, and the emulsion is suitable for topical treatment of a dermal infection or a mucosal infection.

2. The emulsion according to claim 1, further comprises an antimycotic active substance.

3. The emulsion according to claim 1, wherein the emulsion is in the form of a salve, cream, shampoo, solution or stick, for the topical treatment of dermal infections.

4. The emulsion according to claim 1, wherein the antimicrobial active substance is an antibiotic.

5. The emulsion according to claim 4, wherein the antibiotic is phosphomycin, clindamycin, metronidazole, nitrofurantoin, nitrofurazone, nitrofurantoin, nifuratel, nifuroxacin, nitroxolin, trimethoprim, sulfadiazine, or cotrimoxazole.

6. The emulsion according to claim 1, wherein the antimicrobial active substance is an antiseptic.

7. The emulsion according to claim 6, wherein the antiseptic is selected from the group consisting of benzalkonium chloride; dequalinium chloride; and phenoxyethanol.

8. The emulsion according to claim 2, wherein the antimycotic active substance is nystatin, ciclopirox, ciclopiroxolamine, or an antimycotic selected from the group consisting of clotrimazole, fluconazole, miconazole, itraconazole, tioconazole, voriconazole, bifonazole, econazole, isoconazole, fenticonazole, sertaconazole, ketoconazole, nosaconazole, quilseconazole, and oteseconazole.

9. 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.

10. The emulsion according to claim 1, further comprising: an odorous substance.

11. A method for topical treatment of infectious disease, the method comprising: applying the emulsion according to claim 1 to a subject in need thereof.

12. The method according to claim 11, wherein the infectious disease is a mucosal infection.

13. The method according to claim 11, wherein the infectious disease is a microbial urogenital infection.

14. The method according to claim 13, wherein the microbial urogenital infection is a bacterial urogenital infection.

15. The method according to claim 11, wherein the infectious disease is a mixed vaginal infection by Candida albicans Candida albicans and bacteria.

16. The method according to claim 11, wherein the infectious disease is an asymptomatic or symptomatic bacterial vaginosis or an asymptomatic or symptomatic dysbiosis of glans penis and/or male urethra.

17. The method according to claim 11, wherein the infectious disease is a chronic infectious disease.

18. The method according to claim 11, wherein the infectious disease is a dermal fungal infection.

19. The method according to claim 11, wherein the infectious disease is acne.

20. The method according to claim 19, wherein the emulsion is processed into an acne stick.

21. The method according to claim 11, wherein the method is for topical treatment of female cystitis, and for local partner treatment (glans penis, initial third of the urethra).

22. The method according to claim 11, wherein the method is for treatment of hair loss.

23. The method according to claim 11, wherein the method is for topical treatment of atopic dermatitis, wherein the emulsion is in the form of a salve, cream, shampoo, solution or stick.

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

25. A process for preparing the emulsion according to claim 2, the process comprising: introducing the NSAID as a finely crystalline or micronised salt into an emulsion comprising the antimycotic.

Description

EXAMPLES

(1) Preparation of Basic Formulation A, General Preparation Instructions 1:

(2) The components sorbitan monostearate, polysorbate 60, cetyl palmitate, 2-octyldodecanol and cetostearyl alcohol are melted at a temperature of 70-75° C. Clindamycin (and optionally clotrimazole) and then phenoxyethanol 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

(3) cooling with further homogenisation of the w/o emulsion formed, a phase inversion takes place which results in a hydrophilic, homogeneous cream.

(4) TABLE-US-00003 Constituents of the emulsion Clindamycin 2.00 2.00 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 Phenoxyethanol 1.00 1.00 Purified water Ph. Eur. 66.80 66.70 100.00 100.00

(5) Emulsions which Contain Phenoxyethanol as Antibacterial Agent

(6) TABLE-US-00004 TABLE F1 phenoxyethanol as antibacterial agent Composition of the emulsion wt. % Clotrimazole 1 Diclofenac Na 0.4 Sorbitan monostearate 2 Polysorbate 60 1.5 Cetylpalmitate 3 2-octyldodecanol 13.5 Cetylstearyl alcohol 10 Phenoxyethanol 4 Purified water Ph. Eur. 64.6 Total 100

(7) Case study: 24-year-old female patient (EH), almost constant complaints due to fungal infections for 3 years, intercourse hardly possible for years. For 1 week extreme complaints. Burning and itching in the introitus.

(8) Gynaecological examination (Gyn.E.): Vulva and vaginal mucosa massively reddened, solid creamy greenish vaginal contents, secretion smear native: masses of leukocytes adhering to the epithelial cells and to masses of fungal hyphae, mixed flora, few lactobacilli, dirty background—lytic cells, intermediate flora.

(9) Therapy: F1 over 2 weeks,

(10) 0-0-1 Hb applied vaginally, then F1 if required.

(11) Check-up after 3 years: free of complaints since last therapy;

(12) Gyn.E.: Mucosa bland, normal vaginal flora, lactobacilli flora.

Example: Emulsions Containing Dequalinium Chloride

(13) TABLE-US-00005 TABLE F2 Dequalinium chloride as antibacterial agent Composition of the emulsion wt. % Clotrimazole 1 Diclofenac Na 0.3 Sorbitan monostearate 2 Polysorbate 60 1.5 Cetylpalmitate 3 2-octyldodecanol 13.5 Cetostearyl alcohol 10 Phenoxyethanol 1 Dequalinium chloride 0.4 Purified water Ph. Eur. 67.3 Total 100

(14) Case study: 40-year-old female patient (AKS), almost monthly complaints due to fungal infections for years, in each case for about 1 week to 10 days, intercourse hardly possible for years. For 1 week additionally thin and malodorous vaginal secretion. Burning and itching in the introitus.

(15) Gynaecological examination: Mucosa strongly reddened, secretion thin, slightly greenish. Secretion smear native: abundant biofilm plaques on thick fungal hyphae, leukocytes +++, hardly any lactobacilli, intermediate flora.

(16) Therapy: F2 over 1 week, 0-0-1 Hb applied vaginally.

(17) Check-up after 2 years: free of symptoms for 2 years, only occasionally very slight fungal infection, treated with residual F2;

(18) Gyn.E.: Mucosa bland, lactobacilli flora

(19) TABLE-US-00006 TABLE F3 Dequalinium chloride as antibacterial agent Composition of the emulsion wt. % 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 Propylene glycol 7.00 Dequalinium chloride 0.40 Purified water Ph. Eur. 61.40 Total 100.00

(20) Case study: 31-year-old female patient (FJ), almost monthly premenstrual complaints for approx. 3 years, in each case for approx. 1 week to 10 days, due to recurrent fungal infections. For 1 week additionally thin and malodorous vaginal secretion. Burning and itching in the introitus.

(21) Gyn.E: Mucosa slightly reddened, secretion thin, odour. secretion smear native: bacterial vaginosis (RG III), additionally fungal hyphae, abundant leucocytes.

(22) Therapy: F3 over 1 week, 0-0-1 Hb applied vaginally.

(23) Check-up after 4 months: subjectively no more complaints since therapy. Gyn.E: mucosa bland, secretion smear native: normal vaginal flora (RG I)

Example: Emulsions Containing Clindamycin

(24) TABLE-US-00007 TABLE F4 Composition of the emulsion wt. % Clindamycin 2 Diclofenac Na 0.3 Sorbitan monostearate 2 Polysorbate 60 1.5 Cetylpalmitate 3 2-octyldodecanol 13.5 Cetostearyl alcohol 10 Propylene glycol 7 Phenoxyethanol 1 Purified water Ph. Eur. 59.70 Total 100

(25) Case study: 31-year-old female patient (EK), bacterial vaginosis resistant to therapy for months, malodorous discharge, especially postmenstrual. In

(26) the microbial smear result plenty of Gardnerella and Prevotella.

(27) Gyn.E: Mucosa strongly reddened, vaginal secretion thin and malodorous. Secretion smear native: plenty of clue cells, leucocytes +++, bacterial vaginosis (RG III)

(28) Therapy: F4 over 1 week, 0-0-1 vaginally applied, then Hylaktiv Vagilact.

(29) Check-up after 2 years: since above-mentioned therapy free of complaints, once very slight fungal infection; Gyn.E.: mucosa bland, normal lactobacilli flora (RG I)

Example: Emulsions Containing Phosphomycin-Trometamol

(30) TABLE-US-00008 TABLE F5 Composition of the emulsion wt. % Phosphomycin trometamol 2 Diclofenac Na 0.4 Sorbitan monostearate 2 Polysorbate 60 1.5 Cetylpalmitate 3 2-octyldodecanol 13.5 Cetylstearyl alcohol 10 Phenoxyethanol 1 Purified water Ph. Eur. 66.6 Total 100

(31) Case study: 69-year-old female patient (ET), recurrent urinary tract infections for about 2 years, repeatedly treated with Ciproxin. For 2 weeks increased urge to urinate and burning in the introitus.

(32) Gyn.E: Pressure pain over bladder; mucosa atrophic, bleeds on contact, cervix atrophic, soldered, opened with cervix brush, secretion: atrophy, aerobic mixed flora (RGIII), abundant leukocytes.

(33) Therapy: F5 over 1 week, 0-0-1 Hb vaginally applied, additionally Ovestin.

(34) Control examination after 2 weeks: subjectively no more complaints since therapy.

(35) Gyn.E: mucosa bland, no pressure pain over bladder and urethra; secretion smear native: beginning of normal vaginal flora (RG I), no leukocytes.

(36) TABLE-US-00009 TABLE F6 Composition of the emulsion wt. % Phosphomycin trometamol 2 Clotrimazole 1 Diclofenac Na 0.3 Sorbitan monostearate 2 Polysorbate 60 1.5 Cetylpalmitate 3 2-octyldodecanol 13.5 Cetostearyl alcohol 10 Propylene glycol 7 Phenoxyethanol 1 Purified water Ph. Eur. 58.7 Total 100

(37) Case study: 36-year-old female patient (CS), 2 years ago first UTI after vacation in Thailand with macrohaematuria and long-lasting burning sensation, for 2 months again pain in the lower abdomen and UTI (again after vacation in Thailand), burning sensation again and again especially after urination, for 2 weeks increased urge to urinate again, after AB-treatment (1 week) no improvement of bladder problems but now additionally itching and burning sensation in the introitus.

(38) Gynaecological examination: pressure pain over the bladder; vaginal mucosa rather inconspicuous, pronounced cervicitis with bloody erosion around the cervix measuring about 1 cm, secretion/native preparation: bacterial vaginosis, masses of leukocytes, these covered with bacteria, isolated lactobacilli, hyphae ++. Microbiol. smear—secretion culture: masses of E. coli.

(39) Therapy: F6 over 10 days, 0-0-1 vaginally applied, additionally 2 Btl Monuril at intervals of 3 days.

(40) Check-up after 4 weeks: subjectively no more complaints since therapy.

(41) Gyn.E.: mucosa bland, no pressure pain over bladder and urethra; secretion smear native: normal vaginal flora (RG I), no leukocytes.

(42) TABLE-US-00010 TABLE F7 Composition of the emulsion wt. % Phosphomycin trometamol 2 Diclofenac Na 0.3 Sorbitan monostearate 2 Polysorbate 60 1.5 Cetylpalmitate 3 2-octyldodecanol 13.5 Cetostearyl alcohol 10 Propylene glycol 7 Phenoxyethanol 1 Purified water Ph. Eur. 59.7 Total 100

Example: Influence of the Aqueous Phase/Oil Weight Ratio on the Clinical Efficacy of the NSAID

(43) 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.

(44) 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.

(45) TABLE-US-00011 TABLE Influence of the aqueous phase/oil weight ratio on the clinical efficacy Fat component/ Basic Fat component/ Phase viscosity reduced formulations viscosity increased Clotrimazole 1 1.0 1.0 1.0 1.0 1.0 (oil) Diclofenac Na 0.3 0.3 0.3 0.3 0.3 0.3 (water) 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 3.0 3.0 3.0 3.0 3.0 3.0 (oil) 2-octyldodecanol 13.5 13.5 13.5 13.5 13.5 14.5 (oil) Cetylstearyl alcohol 7.5 5 10 10 14 16 (oil) Benzyl alcohol 1.0 1.0 1.0 1.0 1.0 (oil) Phenoxyethanol 1.0 (oil) Propylene glycol 7 (water) Water 70.2 72.7 67.75 60.7 63.7 60.7 (water) 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

(46) 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.

(47) 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.

(48) 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,

(49) 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.

(50) 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.

(51) Further examples of the influence of the aqueous phase/oil weight ratio on clinical efficacy:

(52) TABLE-US-00012 Fat component/ Basic Fat component/ viscosity reduced formulations viscosity increased Clotrimazole oil 1.00 1.00 1 1 1 1.00 1.00 Diclofenac Na water 0.30 0.30 0.25 0.3 0.4 0.30 0.30 Sorbitan monostearate 2.00 2.00 2 2 2 2.00 2.00 Polysorbate 60 1.50 1.50 1.5 1.5 1.5 1.50 1.50 Cetylpalmitate oil 3.00 3.00 3 3 3 3.00 3.00 2-octyldodecanol oil 13.50 13.50 13.5 13.5 13.5 13.50 14.50 Cetylstearyl alcohol oil 7.50 5.00 10 10 10 14.00 16.00 Benzyl alcohol oil 1.00 1.00 1 1.00 1.00 Phenoxyethanol oil 1 4 Propylene glycol water 7 Purified water Ph. Eur. water 70.20 72.70 67.75 60.7 64.6 63.70 60.70 Total 100.00 100.00 100.00 100.00 100.00 100.00 100.00 Clinical efficacy irritating irritating conforms conforms conforms reduced reduced aqueous phase/fat 2.7 3.1 2.4 2.4 2.1 2.0 1.7 Water phase 70.50 73.00 68.00 68.00 65.00 64.00 61.00 Fat phase 26.00 23.50 28.50 28.50 31.50 32.50 35.50

Example: Influence of the pH Value on the Clinical Efficacy of the NSAID

(53) Using emulsions with clotrimazole and NSAIDs, the influence of pH value on the clinical efficacy of the NSAID was investigated. Emulsions with different concentrations of diclofenac Na were prepared and examined for their clinical efficacy.

(54) TABLE-US-00013 TABLE Dependence of clinical efficacy on the concentration of the NSAID 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

(55) 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.

(56) TABLE-US-00014 TABLE 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 Ph.Eur. 64.6 60.7 62.7 67.4299 68.4626 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: Shampoo for the Treatment of Fungal Hair Loss

(57) TABLE-US-00015 TABLE F8 Composition of the emulsion wt. % Ketoconazole 2 Diclofenac Na 0.3 Ammonium lauryl sulfate 15.00 Lauramide 4.00 Sodium chloride 1.00 Farnesol 1 Disodium EDTA 0.2 Methylparaben 0.08 Propylparaben 0.05 Purified water Ph. Eur. 76.37 100

(58) Structural Formula of Ibrexafungerp (SCY-078).

(59) ##STR00001##

(60) Structural Formula of Oteseconazole (VT-1161).

(61) ##STR00002##

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

(63) 1. An emulsion for the topical treatment of dermal infections and mucosal infections, in particular of urogenital infectious diseases, characterised in that an antimicrobial active substance and an anti-adhesive active substance, preferably an NSAID, are used in combination.

(64) 2. An emulsion according to embodiment 1, which additionally contains an antimycotic active substance.

(65) 3. An emulsion according to embodiment 1 or 2, preferably in the form of a salve or a cream, with an aqueous phase and an oil phase, containing an antimicrobial active substance 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 used for these active substances in approved dermal formulations, 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, preferably for the treatment of urogenital infectious diseases, in particular for use in the topical treatment of vaginal infections and female cystitis, and for local partner treatment (glans penis, initial third of the urethra).

(66) 4. An emulsion according to embodiment 1 or 2, preferably in the form of a salve, cream, shampoo, solution or stick, with an aqueous phase and an oil phase, containing an antimicrobial active substance and an NSAID, characterised in that (a) the NSAID in the aqueous phase is in a concentration range which, in the event of cutaneous application,

(67) corresponds to at most the standard concentration, and in the event of application to mucosas corresponds to half to a tenth of the standard concentration for these active substances, and in that (b) the pH value of the emulsion is not less than the value 5.5 and not more than 8.5, preferably for the topical treatment of dermal infections, in particular for use in the topical treatment of acne, hair loss, Pityriasis versicolor and atopic dermatitis.

(68) 5. An emulsion according to one of embodiments 1 to 4, characterised in that the NSAID is diclofenac, bufexamac, ibuprofen, dexibuprofen, flurbiprofen, ketoprofen, piroxicam, meloxicam, lornoxicam, flufenamic acid, mefenamic acid, indometacin or naproxen.

(69) 6. An emulsion according to one of embodiments 1 to 5, characterised in that the antimicrobial active substance is an antibiotic.

(70) 7. An emulsion according to embodiment 6, characterised in that the antibiotic is phosphomycin, clindamycin, metronidazole, nitrofurantoin, nitrofurazone, nitrofurantoin, nifuratel, nifuroxacin, nitroxolin, trimethoprim, sulfadiazine, or cotrimoxazole.

(71) 8. An emulsion according to one of embodiments 1 to 7, characterised in that the antimicrobial active substance is an antiseptic.

(72) 9. An emulsion according to embodiment 8, 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.

(73) 10. An emulsion according to one of embodiments 2 to 9, characterised in that the antimycotic active substance 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).

(74) 11. An emulsion according to one of embodiments 1 to 10, characterised in that the NSAID is diclofenac and this is contained in a concentration

(75) range of 0.2-0.4 weight percent of the emulsion.

(76) 12. An emulsion according to one of embodiments 1 to 11, characterised in that it further contains an odorous substance, preferably a terpene, in particular farnesol.

(77) 13. An emulsion according to one of embodiments 1 to 12 for use in the topical treatment of infectious diseases, in particular for use in the topical treatment of dermal and urogenital infectious diseases.

(78) 14. An emulsion for use according to embodiment 13, characterised in that the infectious disease is a mucosal infection, in particular a urogenital infection.

(79) 15. Emulsion for use according to embodiment 13 or 14, characterised in that the infectious disease is a microbial urogenital infection, in particular a microbial urogenital infection of the woman.

(80) 16. Emulsion for use according to embodiment 15, characterised in that the microbial urogenital infection is a bacterial urogenital infection.

(81) 17. Emulsion for use according to one of embodiments 13 to 16, characterised in that the infectious disease is a mixed vaginal infection by Candida albicans and bacteria such as Enterobacter, E. coli, Klebsiella pneumoniae, Gardnerella vaginalis, or Prevotella spp.

(82) 18. Emulsion for use according to one of embodiments 13 to 17, characterised in that the infectious disease is an asymptomatic or symptomatic bacterial vaginosis or an asymptomatic or symptomatic dysbiosis of the glans penis and/or the male urethra.

(83) 19. Emulsion for use according to one of embodiments 13 to 18, characterised in that the infectious disease is a chronic infectious disease.

(84) 20. Emulsion according to one of embodiments 1 to 12 for use in the treatment of acne.

(85) 21. Emulsion according to embodiment 20, characterised in that the emulsion is processed into an acne stick or an acne solution.

(86) 22. Emulsion according to one of embodiments 1 to 12 for use in the treatment of dermal fungal infections, preferably Candida mycoses and Malassezia mycoses.

(87) 23. Emulsion, preferably shampoos, according to one of embodiments 1 to 12 for use in the treatment of hair loss.

(88) 24. A process for preparing an emulsion according to one of embodiments 1 to 12, characterised in that, when preparing the emulsion, the NSAID is introduced via the aqueous phase.

(89) 25. A process for preparing an emulsion according to one of embodiments 1 to 12, characterised in that the NSAID is introduced as a finely crystalline or micronised salt into the emulsion containing the antimycotic.