FOAM WOUND DRESSING COMPRISING AN ANTISEPTIC

Abstract

An open-cell foam wound dressing comprising a formulation of an amphiphilic antiseptic and particular surfactants is provided.

Claims

1.-23. (canceled)

24. A wound dressing comprising a formulation of (a) an amphiphilic antiseptic and (b1) a non-ionic surfactant or (b2) a cationic surfactant or (b3) a zwitterionic surfactant; and an open-cell foam.

25. The wound dressing according to claim 24, wherein the non-ionic surfactant comprises a fatty acid monoester or fatty acid monoamide of a polyhydroxy compound.

26. The wound dressing according to claim 25, wherein the fatty acid monoester or fatty acid monoamide comprises a C2-C22 fatty acid moiety, a C4-C18 fatty acid moiety or a C6-C12 fatty acid moiety.

27. The wound dressing according to claim 26, wherein the polyhydroxy compound comprises glycerol, sorbitan, ethoxylated sorbitan, glucose, ethylene glycol, polyethylene glycol or amine derivatives thereof.

28. The wound dressing according to claim 24, wherein the non-ionic surfactant comprises a fatty alcohol monoether of a polyhydroxy compound.

29. The wound dressing according to claim 28, wherein the fatty alcohol monoether comprises a C2-C22 fatty alcohol moiety, a C4-C18 fatty alcohol moiety or a C6-C12 fatty alcohol moiety.

30. The wound dressing according to claim 29, wherein the polyhydroxy comprises glycerol, sorbitan, ethoxylated sorbitan, glucose, ethylene glycol, polyethylene glycol or amine derivatives thereof.

31. The wound dressing according to claim 24, wherein the non-ionic surfactant comprises a tri-block copolymer (A-B-A or B-A-B) or a di-block copolymer (A-B), wherein one block of the copolymer (A) is hydrophobic, and the other block (B) of the copolymer is hydrophilic.

32. The wound dressing according to claim 31, wherein the hydrophobic block (A) comprises a polypropylene oxide, a polypropylene ethylene oxide copolymer, a polysiloxane, a polystyrene, a polylactide, or a polycaprolactone.

33. The wound dressing according to claim 31, wherein the hydrophilic block (B) comprises a polyethylene oxide, a poly(ethylene oxide co-propylene oxide), a polyoxazoline or a poly(vmyl pyrrolidone).

34. The wound dressing according to claim 24, wherein the formulation comprises a solution of the components in water and/or alcohols.

35. The wound dressing according to claim 24, wherein the amphiphilic antiseptic comprises benzalkonium chloride, benzethonium chloride, chlorhexidine, polyhexanide (PHMB), octenidine or ethyl lauroyl arginate (LAE) or salts thereof.

36. The wound dressing according to claim 24, wherein the amphiphilic antiseptic comprises octenidine or salts thereof.

37. The wound dressing according to claim 24, wherein the formulation is coated on a surface of the open-cell foam and/or incorporated into pores of the open-cell foam.

38. The wound dressing according to claim 24, wherein the non-ionic surfactant is decyl glucoside and the amphiphilic antiseptic is octenidine or salts thereof.

39. The wound dressing according to claim 37, wherein the open-cell foam comprises a polyether-polyurethane foam or a polyester-polyurethane block copolymer foam.

40. The wound dressing according to claim 24, wherein the formulation comprises between 0.001 and 10% w/w of the amphiphilic antiseptic.

41. The wound dressing according to claim 40, wherein the formulation comprises between 0.05 and 10% w/w of the surfactant.

42. A method for manufacturing a wound dressing comprising the steps: a. providing a formulation comprising (a) an amphiphilic antiseptic and (b1) a non-ionic surfactant or (b2) a cationic surfactant, or (b3) a zwitterionic surfactant wherein the formulation further comprises an optional solvent; and b. applying the formulation to a pre-formed open-cell foam wound dressing, such that the formulation becomes coated on a surface of the open-cell foam wound dressing and/or impregnated into the pores of the open-cell foam wound dressing.

43. A method for manufacturing a wound dressing comprising the steps: a. providing a formulation comprising (a) an amphiphilic antiseptic and (b1) a non-ionic surfactant or (b2) a cationic surfactant, or (b3) a zwitterionic surfactant wherein the formulation further comprises an optional solvent; b. blending the formulation with a foamable matrix; and c. foaming the foamable matrix together with the formulation, to provide an open-cell foam wound dressing in which the formulation is comprised within the matrix of the open-cell foam wound dressing.

Description

EXAMPLES

[0054] As an amphiphilic molecule, octenidine has shown to associate to surfaces and thereby reduce mobility in a matrix such as foam. Previous studies have indicated that Octenidine did not diffuse freely in the foam matrix, indicating a high degree of interactions between octenidine and foam matrix.

[0055] To address this, we have investigated formulations to increase the mobility of octenidine by co-formulating different surface active compounds. Solubility and stability (evidenced by lack of precipitation when interacting with e.g. salts or proteins) were tested in a solution, while release was tested by infiltrating the solution into a plain foam sample, drying the foam and following carrying out release studies.

[0056] 1. Octenidine in foam, no surfactant

[0057] Discs of hydrophilic polyurethane foam were impregnated by applying a known volume of octenidine-containing solution to the surface of the foam and letting it soak into the foam matrix in a liquid:foam ratio which allowed the foam to be saturated with liquid. Afterwards, the impregnated foam was dried at RT overnight.

[0058] The dried foam disc was immersed in the extraction media for 24 h and the extracted octenidine concentration was determined by UV at 285 nm

TABLE-US-00001 TABLE 1 These results show that when octenidine is impregnated into a plain foam matrix only relatively low amounts of octenidine were freely extractable. % Octenidine extractable Release % after being impregnated into phosphate plain foam w % OCT in Release % buffer impregnation solution water (23 mM) 0.1 w %   5%  7% 0.5 w % 1.5% 13% 1.0 w % 1.5% 20%

[0059] 2. Solubility of Octenidine with/without Surface Active Compounds.

[0060] In these experiments, octenidine dihydrochloride was dissolved in different solutions to determine the solubility with/without the presences of surface active compound (surfactant).

[0061] To investigate the interaction between the dissolved octenidine and isotonic salt concentrations (0.9%), 0.9% NaCl was co-formulated with glycerol (A4), tween (A5), or both combined (A6).

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[0062] The solutions used were as follows: [0063] A1: 3 w % Tween-20 [0064] A2: 5 w % glycerol [0065] A3: 3 w % tween-20, 5 w % glycerol [0066] A7. MQ water [0067] A8: PBS buffer 23 mM [0068] A9: 2% Benzalkonium chloride [0069] A10: 5% Plantacare 2000 UP (50% decyl glucoside solution)

[0070] Two concentrations of Octenidine were tested: 1% and 3% [0071] Conc. 1%: 1.00 g Octenidine+100 ml solution [0072] Conc. 3%: 3.00 g Octenidine+100 ml solution

[0073] All solutions were prepared in conical glass bottles, sealed with plastic film at room temperature and stirred. The solutions were inspected every 15 min. and observations were recorded.

[0074] The results from the solubility tests are shown in Table 2:

TABLE-US-00002 TABLE 2 overview of solubilities of 1% Octenidine co-formulated with different surfactant compounds. 1% Total time to Dissolved after Octenidine pH dissolution 1 week at RT A1 3.23 1 h Yes A2 5.06 1 h 05 min Yes A3 3.28 1 h 15 min Yes A7 4.99 1 h 20 min Yes A8 6.82 41 min Yes A9 6.45 1 h 15 min Yes A10 10.14 51 min Yes

[0075] All of the used solvent systems (H.sub.2O, Glycerol, Phosphate, Tween20, Benzalkonium Cloride, and Plantacare(50% Decyl glucoside)) were able to dissolve 1%Octenidine. The solubility of 3% Octenidine was also tested and only Plantacare (solution A10) was able to fully dissolve 3% Octenidine and keep it in the dissolution without precipitation (results not shown).

[0076] Solvent systems containing salts (A4, A5, A6) did not dissolve 1% octenidine. Also, if octenidine is dissolved in respectively Tween20 or Tween20/glycerol, the same solubility/stability is indicated, while glycerol alone did not show any better solubilisation capacity than water alone. This indicates that glycerol does not have any significant effect on the solubility of octenidine, neither negative nor positive.

[0077] 3. Stability of Solutions Towards Salts.

[0078] The solutions with 1% Octenidine from experiment 2 that were totally dissolved (Al, A2, A3, A7, A8, A9, A10), were tested in a new experiment. The solutions were diluted with 0.9%

[0079] NaCl to different concentrations to observe whether the Octenidine precipitated in the solution. The ratios 2:1, 1:4 and 1:10 (test solution: 0.9% NaCl) were tested and all the solutions were heated to RT (37° C.) for 1 hour. To challenge the solubility, the samples were also cooled to 4° and possible precipitation was observed.

[0080] The results are shown in Table 3:

TABLE-US-00003 TABLE 3 Salt stability of octenidine solutions 1% Addition of 0.9% Addition of 0.9% Addition of 0.9% Octenidine Temp. NaCl solution 2:1 NaCl solution 1:4 NaCl solution 2:1 A1 37° C. No precipitation No precipitation No precipitation  4° C. Precipitation Precipitation Precipitation A2 37° C. Visible precipitation Visible precipitation —  4° C. — — — A3 37° C. No precipitation No precipitation No precipitation  4° C. Precipitation Precipitation Precipitation A7 37° C. Visible precipitation Visible precipitation —  4° C. — — — A8 37° C. No precipitation Visible precipitation —  4° C. Precipitation — — A9 37° C. No precipitation No precipitation No precipitation  4° C. Precipitation Precipitation Precipitation A10 37° C. No precipitation No precipitation No precipitation  4° C. — Less precipitation Precipitation than other solutions

[0081] If addition of salt is carried out after octenidine has been dissolved, the precipitating effect of NaCl is not seen at room temperature for solutions A1, A3, A9 and A10 (Table 3), indicating that an interaction between an amphiphile such as Tween20 or decyl glucoside and octenidine, protects octenidine from salt precipitation.

[0082] For all formulations except Plantacare precipitation was observed at octenidine: salt solution of 2:1 at increasing salt concentrations (1:4) slight precipitation was observed in the octentine:plantacare formulation and with even stronger precipitations at a ratio of 1:10. However, this show that decyl glucoside has the best capacity to stabilize octenidine in relation to salting out.

[0083] Overall, the 3 amphiphiles (Tween 20, benzalkonium and decyl glucoside) all dissolve 1% octenidine. But most importantly, indicated by the salt additions, they are able to stabilize octenidine in a salt-containing solution such as a wound bed and avoid precipitation upon contact with salt. Based on the temperature experiments it is indicated that decyl glucoside (Plantacare) has the best capacity to stabilize the octenidine.

[0084] 4. Extraction of Octenidine from Impregnated Foams

[0085] Release profiles of octenidine in foam were studied.

[0086] Impregnation of the foam was prepared using plain Biatain (polyurethane) foam, 3 mm thick, and the foam was punched at Ø20 mm.

[0087] The 1% Octenidine solutions used for impregnations were prepared in the solubility experiments, A1, A2, A3, A7, A8, A9 and A10 as above. The volumes used for impregnation were 2 ml for Ø20 mm foam. All foam samples were placed in a fume hood overnight to dry.

[0088] Extraction Eperiment 1

[0089] The impregnated dry foam samples were cut into 4 pieces and put in a 50 ml centrifuge tube.

[0090] Samples made in triplication. As negative control a plain Biatain foam without impregnation (from the same batch) was used.

[0091] 7 ml extraction solution, MQ water, Phosphate buffer 23 mm or Solution A (142 mM NaCl, 3.3 mM CaCl in MiliQwater) was added, and the sample tubes were placed on a shaking-table at 100 rpm. As will be appreciated by the skilled person, “Solution A” is an acknowledged standard solution for testing wound care devices.

[0092] Samples were taken at: 3 hours, 24 hours, 48 hours and 96 hours. Extraction samples of 500 μl were removed from the tubes at the given time-points and replaced with 500 μl new extraction solution.

[0093] The extraction samples were measured by UV at 285 nm using a micro-plate reader, and quantification of the extractions samples were carried out against a calibration curve prepared in MQ water or phosphate buffer. The calibration standards could not be dissolved in Solution A because of precipitation of Octenidine, so the extraction samples in Solution A were measured against the calibration curve obtain from standards prepared in MQ water.

[0094] Responses from the negative control samples were also calculated and used for background subtraction. The extraction solution from tubes from each time point were measured by UV as described above.

TABLE-US-00004 TABLE 3 Overview of the % recovery of octenidine from impregnated foam patches using different solutions as extraction media (using extraction test 1, above). Solution Phosphate % recovery Water A buffer 1% Oct. in 3%  3 hours 46.8 18.2 36.4 Tween-20 24 hours 48.6 18.8 42.8 48 hours 51.4 19.0 38.7 96 hours 52.6 21.5 42.7 1% Oct. in 5%  3 hours 39.2 0.4 16.9 Glycerol 24 hours 42.3 0.5 20.7 48 hours 43.2 0.6 20.9 96 hours 44.7 0.5 20.5 1% Oct. in 3%  3 hours 44.8 14.8 30.0 Tween-20 + 24 hours 48.9 20.2 36.6 5% Glycerol 48 hours 50.0 20.0 39.1 96 hours 48.8 20.7 41.2 1% Oct. in MQ  3 hours 38.3 0.4 19.5 water 24 hours 43.2 0.5 21.8 48 hours 44.2 0.6 23.8 96 hours 45.4 0.5 24.7 1% Oct. in  3 hours 22.2 0.4 18.2 Phosphate 24 hours 24.1 0.7 19.1 buffer 23 mM 48 hours 25.9 0.7 19.3 96 hours 26.3 0.7 21.5 1% Oct. in 2%  3 hours 38.6 0.5 35.2 Benzalkonium 24 hours 41.5 0.5 37.1 chloride 48 hours 42.2 0.6 37.9 96 hours 43.4 0.5 39.6 1% Oct. in  3 hours 57.9 32.8 60.9 2.5% decyl 24 hours 55.2 31.8 67.9 glucoside 48 hours 54.6 29.5 67.1 (5% Platacare 96 hours 56.8 29.5 64.3 2000 UP)

[0095] In all extractions, the release profile indicated a burst release with “full release” at first datapoint (3h). In all extraction experiments, Plantacare (A10) showed the release concentration with a max around 65% when extracted in phosphate buffer followed by ˜55% in MiliQ and ˜30% when extracted with solution A (Table 3). Between the 3 different extraction medias Tween 20 showed the second best extraction potential, while benzalkonium chloride (as an example of a cationic surfactant) showed the 3rd best extractability. In Solution A, the extractability of the benzalkonium was almost zero. This does not mean that it will necessarily be useless in a wound care application, but it does show that the examples of non-ionic (Tween, decyl glucoside) perform better and may be preferable in some applications.

[0096] Extraction Experiment 2

[0097] As in Table 3, above, all release profiles showed a burst release within the first 3 h. To understand if this represents actually available octenidine, or if it is a result of an equilibrium between dissolved and non-dissolved octenidine, the experimental setup was changed so that the foam pad was transferred to a new volume extraction media at every measuring point. Thereby the equilibrium between dissolved and non-dissolved octenidine is shifted, thereby simulating a consumption of the released octenidine as it would be expected in the wound bed.

[0098] Foam impregnated with 1% Octenidine in MQ water (A7) and 5% Plantacare (A10) were prepared described as in extraction experiment 1 with the same negative control and extraction solutions. In this experiment the foam pieces in each tube were carefully removed to a new tube containing 7 ml of fresh extraction solution at each time point.

TABLE-US-00005 TABLE 4 Time points: 3 hours, 24 hours, 48 hours and 72 hours. Phosphate % recovery Water Solution A buffer 1% Oct. in  0 hours 0.0 0.0 0.0 MQ water  3 hours 39.8 0.7 20.2 24 hours 63.5 1.4 34.9 48 hours 77.3 2.0 46.8 72 hours 85.0 2.5 56.8 1% Oct. in  0 hours 0.0 0.0 0.0 2.5% decyl  3 hours 52.3 39.6 57.5 glucoside 24 hours 69.4 52.1 76.5 (5% Platacare 48 hours 79.5 54.8 83.5 2000 UP) 72 hours 85.0 55.4 85.1

[0099] When the balance is shifted as described, the release profile changed from burst release to a more sustained release profile. Also, the total amount released changed from around 55% to 85% for the Plantacare formulation (Table 4) illustrating that release of octenidine is a result of equilibrium between released and non-released octenidine. Solution A has a sodium concentration equal to the serum concentration and should as such better simulate the physiological conditions. In solution A, the difference between non-ionic surfactants such as

[0100] Tween 20 and Plantacare and cationic surfactants such as benzalkonium chloride is most significant.

[0101] Extranction Experiment 3

[0102] The same procedure for release test as described for experiment 1 was followed, except for the preparation of the release media. In this experiment the release media is prepared with

[0103] Plantacare in different concentrations in PBS buffer. The three different release media solutions are pH adjusted to pH 7.4 (Plantacare makes the pH increase).

TABLE-US-00006 Impregnation solution Octenidine Solution Surfactant Vol % mg/mL Release media S1 Plantacare 0.25% 1.00 Plantacare 0.25% in PBS S3 Plantacare 0.50% 1.00 Plantacare 0.50% in PBS S6 Plantacare 1.00% 1.00 Plantacare 1.00% in PBS

[0104] The results, measured as recovery of octenidine in percent of the total amount of octenidine present, were as follows.

TABLE-US-00007 Octenidine recovery (%) 0 hours 24 hours 48 hours 72 hours Sample Release media Average Average Average Average S1 0.25% Plantacare 2000 0 24 43 56 S3  0.5% Plantacare 2000 0 46 72 85 S6   1% Plantacare 2000 0 73 97 100

[0105] When carrying out release studies with same surfactant concentration, as used for impregnation, in the release media, significantly higher percentage release is obtained, reaching 100% for 1% Plantacare 2000 and around 56% and still rising when using 0.25% plantacare. When carrying out release without surfactants in the release media, there is a significant risk of diluting out the surfactant concentration into the release media (3×10 mL media per Ø20 mm foam disk), thereby reducing the “facilitator” for Octenidine release. By keeping the surfactant concentration constant around the octenidine molecule, better simulating the situation in the wound, the release and thereby utilization of Octenidine is becoming significantly higher. 5. Zone of Inhibition Tests

[0106] Zone of inhibition was investigated for the different formulations and at two different octenidine concentrations (0.1 and 1%). Impregnation of the foam was prepared using plain Biatain (polyurethane) foam, 3 mm thick, and the foam was punched at Ø10 mm.

[0107] The 1% Octenidine solutions used for impregnations were prepared in the solubility experiments, A1, A2, A3, A7, A8, A9 and A10 as above. The volumes used for impregnation were 0.5 ml for Ø10mm foam.

[0108] 0.6% agarose plates were used. The impregnated dry samples (1% Octenidine) were pre-wetted with 400 μl MQ water before placing on the plates.

[0109] Different control samples were used for this experiment: [0110] Positive control: standard silver (Ag) foam, Biatain [0111] Negative control: Plain Biatain foam without PU backing film.

[0112] Control samples impregnated with solutions without Octenidine: Impregnated samples with solution A1, A2, A3, A7, A8, A9 and A10 without Octenidine added. These were prepared as per the solubility experiments above.

[0113] The foam disk (Ø10mm) was incubated with the different formulations, dried and re-wetted and placed on an agarose plate. Then, the diameter of the inhibition zone was measured after 1 day of incubation. The results are shown in Table 5 (staph. aureus) and Table 6 (pseudomonas Aeruginosa).

TABLE-US-00008 TABLE 5 Zone of inhibition data for staph. Aureus. Positive control is Biatain Ag Staf. Aureus Staf. Aureus Controls ZOI 1% solutions 0.1% solutions without Oct. (average results) Average Stdev Average Stdev Average Stdev Positive control 7 0.0 6 0.0 5 0.6 Negative control 0 0.0 0 0.0 0 0.0 Oct. in 3% 30 3.5 29 3.5 1 1.2 Tween-20 Oct. in 5% 18 4.2 15 3.8 0 0.0 Glycerol Oct. in 3% 36 2.1 32 1.7 0 0.0 Tween-20 + 5% Glycerol Oct. in MQ water 18 3.6 18 1.0 0 0.0 Oct. in Phosphate 15 0.6 21 2.6 0 0.0 buffer 23 mM Oct. in 2% 26 1.7 25 1.0 29 2.5 Benzalkonium chloride Oct. in 5% 50 5.1 53 2.9 20 1.0 Platacare 2000 UP

TABLE-US-00009 TABLE 6 Zone of inhibition data for pseudomonas Aeruginosa. Positive control is Biatain Ag Pseudomonas Pseudomonas Controls ZOI 1% solutions 0.1% solutions without Oct. (average results) Average Stdev Average Stdev Average Stdev Positive control 8 0.6 12 1.0 5 0.6 Negative control 0 0.0 0 0.0 0 0.0 Oct. in 3% 9 2.1 7 0.6 1 1.2 Tween-20 Oct. in 5% 7 0.6 2 0.6 0 0.0 Glycerol Oct. in 3% 15 1.0 10 1.2 0 0.0 Tween-20 + 5% Glycerol Oct. in MQ 7 1.0 2 0.0 0 0.0 water Oct. in 6 0.6 2 0.0 0 0.0 Phosphate buffer 23 mM Oct. in 2% 9 1.7 8 0.6 29 2.5 Benzalkonium chloride Oct. in 5% 13 1.5 5 0.6 20 1.0 Platacare 2000 UP

[0114] Previous studies (not shown) have found that pure octenidine impregnated into foam without surfactants produces small or no zones in a zone of inhibition study.

[0115] In relation to Staph. Aureus, octenidine samples show significant larger zones than for

[0116] Biatain Ag and with a clear trend that the non-ionic detergents (Tween and Decyl glycoside) increase the size of the zones. This illustrates that co-formulating with non-ionic detergents increases the mobility of octenidine in the agarose matrix. Benzalkonium is classified as an antimicrobial component in itself, which explains the signal from the negative background. Decylglucoside has in this experiment a pH above 10, most probably explaining the signal from the negative control in A10. Other experiments have shown that the antimicrobial effect of the positive control is similar at pH 10 and pH 7 (data not shown). For pseudomonas Aeruginosa the signal is not as clear mainly due to higher noise level. However, the trend is still the same; that octenidine show higher mobility when formulated with non-ionic surfactants. 6. Protein Binding and Precipitation

[0117] The purpose of this experiment is to investigate the capability of surfactant to protect Octenidine from precipitation when mixed with a protein/salt media, such as simulated wound fluid (SWF), to further understand how Octenidine and the co-formulation with detergents will respond to being released into a wound bed environment.

[0118] The results show that surfactants can significantly reduce the interaction between a protein pool and Octenidine by reducing the agglomeration of octenidine and proteins/salts. This means that the surfactants will prevent unwanted precipitation, thereby making sure that a large portion of the Octenidine is available for acting in the wound environment.

[0119] The following surfactants were tested:

TABLE-US-00010 Solution no. Surfactant: INCI name Batch no. A 1% Tween 20 Polysorbate 20 Batch #094K0052 B 1% Tween 80 Polysorbate 80 Lot #BCBV7863 C 1% Plantacare Caprylyl/Capryl lot. 17483268 810 UP Glucoside D 1% Plantacare Decyl Glucoside lot. 0019096298 2000 UP E 1% Benzalkonium Benzalkonium Lot #BCBV7858 chloride chloride F 1% Empigen BB Lauryl Betaine Lot #BCBQ6967 G 1% Decanesulfonate Decane-sulfonate Lot #BCBT6967 H 1% Plantacare Lauryl glucoside lot. 19090815 1200 UP I Water — —

[0120] The experiment was done as follows: [0121] i) 2 ml of solution A, B, C etc., each containing 1 mg/ml Octenidine, were mixed with 2 ml SWF or water. The mix of solutions were done twice (one for each filter type). [0122] ii) The mix of solutions were incubated for 1 hour at room temp. on a shaking table at 100 rpm. [0123] iii) The mix of solutions were filtrated through a 0.22 μm filter. iv) The filtrated solution was diluted ten times in eluent. The Octenidine conc. should be 0.05 mg/ml (to be within detection area) if 100% was recovered after incubation and filtration. [0124] v) Controls were prepared by diluting the formulation solution in eluent (50% Mcllvaine buffer/50% Methanol) to conc. 0.05 mg/ml (dilution x20). [0125] vi) The samples and controls were analysed using HPLC.

[0126] The results were as follows.

TABLE-US-00011 Recovery Recovery Solution in SWF in water no. Surfactant: Octenidine (%) (%) A 1% Tween 20 1 mg/ml 99 100 B 1% Tween 80 1 mg/ml 100 100 C 1% Plantacare 810 UP 1 mg/ml 71 100 D 1% Plantacare 2000 UP 1 mg/ml 69 100 E 1% Benzalkonium 1 mg/ml 47 100 chloride F 1% Empigen BB 1 mg/ml 97 100 G 1% Decanesulfonate 1 mg/ml 7 n.a. H 1% Plantacare 1200 UP 1 mg/ml 54 99 I Water 1 mg/ml 26 100

[0127] The results show that Octenidine is precipitated by mixing with protein and salt containing solutions as well as when formulated with anionic surfactants, such as decanosulfonate. However, when co-formulated with nonionic (plantacare, Tween), cationic (Benzalkonium chloride) or zwitterionic (Empigen) surfactants, Octenidine is protected against precipitation, most probably by hydrophobic-hydrophobic interaction between octenidine and detergents, scavenging the octenidine molecule from interacting with salts and/or proteins.

CONCLUSIONS

[0128] Formulating octenidine with non-ionic or cationic surfactants, preferably non-ionic surfactants—increases the mobility and stability of the octenidine. Formulating with decyl glucoside (plantacare) resulted in the highest amount of total release octenidine with a total amount of released octenidine reaching 85% at 72 h together with an increased stability to salts. The results show that amphiphilic compounds can interact with octenidine and increase its mobility in foam and also increase stability of octenidine. Highest mobility and stability increase was seen when using decyl glucoside (Plantacare) followed by Tween 20. Glycerol did not have any effect on octenidine mobility or stability, while NaCl caused precipitation, if octenidine had not been stabilized by amphiphiles before adding salts.

[0129] Although the invention has been illustrated with reference to a number of embodiments, aspects and examples, the skilled person can combine such embodiments, aspects and examples within the scope of the appended claims.