the effect of a combination of 0.1% octenidine dihydrochloride and 2% 2-phenoxyethanol...

ORIGINAL ARTICLE

The effect of a combinationof 0.1% octenidinedihydrochloride and 2%2-phenoxyethanol(octenisept®) on woundhealing in pigs in vivoand its in vitro percutaneouspermeation through intactand barrier disrupted porcineskinJessica Stahl, Michael Braun, Joerg Siebert, Manfred Kietzmann

Stahl J, Braun M, Siebert J, Kietzmann M, The effect of a combination of 0.1% octenidine dihydrochloride and 2%2-phenoxyethanol (octenisept®) on wound healing in pigs in vivo and its in vitro percutaneous permeation through intactand barrier disrupted porcine skin. Int Wound J 2010; 7:62–69

ABSTRACTA combination of 0.1% octenidine dihydrochloride and 2% 2-phenoxyethanol (octenisept®) is a commonly useddisinfectant in human medicine. As porcine skin represents an adequate model for human skin, the effect of octenidinedihydrochloride and phenoxyethanol on wound healing is studied in pigs. Furthermore, the in vitro percutaneouspermeation of the test substances is studied. The impact of the test formulations on wound healing is examined(A) under non occlusive conditions and (B) in comparison to another disinfectant based on povidone-iodine underocclusive conditions, while wounds are treated daily with the test substances. The percutaneous permeation of octenidinedihydrochloride and phenoxyethanol is studied in Franz-type diffusion cells with intact skin as well as barrier disruptedafter tape stripping. Compared with povidone-iodine or vehicle treatment as well as untreated control wounds thetreatment of wounds with the test formulation has no influence on the healing rate in pigs and does not induceretardation of wound healing. The in vitro diffusion experiment reveals that octenidine dihydrochloride is only detectablein the acceptor chamber of three-barrier disrupted skin samples. Phenoxyethanol permeates through intact porcine skinin amounts of 11.3% and through barrier disrupted skin in amounts of 43.9%

Key words: In vitro permeation • Octenidine dihydrochloride • Octenisept • 2-Phenoxyethanol • Wound healing

Authors: Dr J Stahl, Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Foundation, Hannover,Germany; Dr M Braun, Schulke & Mayr GmbH, Norderstedt, Germany; J Siebert, Schulke & Mayr GmbH, Norderstedt, Germany; Professor, Dr MKietzmann, Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Foundation, Hannover, GermanyAddress for correspondence: Dr J Stahl, Bunteweg 17, 30559 Hannover, GermanyE-mail: [email protected]

62 © 2010 The Authors. Journal Compilation © 2010 Blackwell Publishing Ltd and Medicalhelplines.com Inc • International Wound Journal • Vol 7 No 1

Octenidine dihydrochloride in porcine wound healing

INTRODUCTIONAs antiseptics aim to kill or inactivatemicroorganisms by reducing their numberor inhibiting their multiplication after topicaladministration, they are used locally on thesurface of the body, in body cavities aswell as on surgically exposed tissues (1).To achieve best conditions in killing orinhibition of microbes, many studies wereconducted in the last decades to developnew antiseptic agents like chlorhexidine,iodine or iodophores (1,2). Out of thesestudies octenidine dihydrochloride (OCT)was designed as an alkanediylbis[pyridine]germicidal agent with optimal antisepticproperties (3). Stability is given in the pHrange 1·6–12·2, and under exposition to lightand in contrast to chlorhexidine chloride OCTis not sensitive to hydrolysis and shows noreduction in the effect as a result of albuminor mucin (protein error) (1). It is levurocidal,effective against resident skin microflora andeffects Gram positive and negative as well asplaque-forming bacteria (1,3–8). Antibacterialeffects of OCT on the oral microflora invivo and in vitro are comparable to those ofchlorhexidine gluconate and povidone-iodine(9). The comparison of its biocompatibility

with other disinfectants like PVP iodine orchlorhexidine digluconate showed that OCTrepresents an antiseptic with low cytotoxicityand high microbicidal effects (10,11). TodayOCT [in combination with 2-phenoxyethanol(PH)] is a licensed product in several Europeancountries (octenisept® with 0.1% OCT and 2%PH). It has been reported that the use of thiscombination of OCT and PH in prematurenewborn infants of 23–26 weeks gestationdoes not cause skin damage. Interestingly,PH permeates newborn’s skin but seemsto be inactivated effectively by oxidativemetabolisation to 2-phenoxyacetic acid (12).

Nevertheless, only few are known about theeffects of the combination of OCT and PHon wound healing. Therefore, we investigatedthe impact of two antiseptic products onwound healing in a standardised porcinewound model simulating wound care in theclinical setting. To detect the influence ofocclusive conditions, an additional study wasconducted under occlusive conditions. Becauseintact and wounded skin gets in contact withthe two components during skin disinfection,percutaneous permeation of OCT and PH

through intact and wounded porcine skin was Key Points

• octenidine dihydrochloride(OCT) was developed as anew antiseptic agent with highantimicrobial effects and lowcytotoxicity

• OCT (in combination with 2-phenoxyethanol (PH)) is alicensed product in severalEuropean countries

• very little is known about theeffects of the combination ofOCT and PH on wound heal-ing. Therefore, we investigatedthe impact of two antisepticproducts on wound healing ina standardised porcine woundmodel under occlusive and nonocclusive conditions

• as intact and wounded skingets in contact with the twocomponents during skin disin-fection, percutaneous perme-ation of OCT and PH throughintact and wounded porcineskin was determined in vitro

• pigs were chosen for theexperiments, as pig skin iscomparable to human skinregarding skin morphology andbiochemical composition

determined in vitro. Pigs were chosen for thein vivo and in vitro experiments, as porcineskin is comparable to human skin regardingskin morphology and biochemical composition(13–18).

MATERIALS AND METHODSTrial preparationsOctenisept®, a combination of 0.1% OCT and2% PH, was provided by Schulke & MayrGmbH, Norderstedt, Germany. Vetsept®, acombination of 5% poly(1-vinyl-2-pyrrolidon)-iodine and 9% nonoxinol, was used asbrand medicinal product of AniMedica GmbH,Senden-Bosensell, Germany.

The study design of the wound treatment ofstudies A and B is described in Table 1.

AnimalsFor each study six male pigs with a weightof 10–15 kg (study A) respectively 20–25 kg(study design B) were used. They werefed restrictively, received water ad libitumand were kept on straw in single boxes(temperature in the stable: 22◦C) according tolegal requirements.

Study descriptionIn vivo wound healing studyThe study was conducted according to therequirements of good clinical practice (GCP)and the German animal welfare law. After7 days of acclimatisation, each pig was putunder general anaesthesia using a combinationof azaperon (Stresnil, Janssen-Cilag, Neuss,Germany) and ketamin (ketamin 10%, Wdt,Garbsen, Germany) and the wounds were set.

The following studies were carried out:Study design A (non occlusive conditions):

Six full thickness wounds with a diameterof 6 mm (= 28·3 mm2) each were set withbiopsy punches (Stiefel laboratories, Offen-bach, Germany) on the back skin of eachpig on day 0. To avoid cross-contaminationof the wounds, at least 4-cm distance weremaintained between the wounds. Directly afterwounding until day 3, 100 μl of the test formu-lations were applied once daily according toTable 1. Because there was no occlusive cover,the wounds got the possibility to get infectedwith environmental bacteria. On days 1–4, 7–10and 14 wound areas were measured planimet-rically (ScionImage 4.0.3.2; Scion Corporation,

© 2010 The Authors. Journal Compilation © 2010 Blackwell Publishing Ltd and Medicalhelplines.com Inc 63


Table 1 Wound treatment of the two in vivo studies; Ringer solution (Braun, Melsungen, Germany) was used for dilution of thetreatment of wound number 2–4 (study design A) and 2 and 3 (study design B)

Study design A Study design B

Wound number Treatment Occlusive bandage Treatment Occlusive bandage

1 Octenisept® No Octenisept® yes2 Octenisept®1:2 No Octenisept®1:5 yes3 Octenisept®1:5 No Octenisept®1:10 yes4 Octenisept®1:10 No Vetsept® yes5 Ringer solution No Ringer solution yes6 Untreated No Untreated no7 – – Untreated yes

Maryland, USA) and inflammation parameters(rubor and tumour) were documented.

Study design B (occlusive conditions):According to study design A, seven fullthickness wounds were inflicted on the backskin of each pig. Directly after wounding sixwounds were covered with occlusive patches(Hydrosorb, Hartmann, Heidenheim, Ger-many), which were fixed with adhesive tape(Leukoplast, BSN medical GmbH, Hamburg,Germany). Wound number 7 served as nonocclusive control. Wound area measurementwas conducted on days 1, 4, 7, 10 and 11 andwound treatment according to Table 1 startedon day 1 and was repeated once daily untilday 11. Therefore, new occlusive patches wereapplied on the wounds daily after treatment.

According to Table 1 two puffs (210 μl) ofthe test solution were applied on the wounds.Inflammation parameters were documenteddaily (rubor and tumour). Pig number 6 waseuthanised on day 3, as an advanced stateof greasy pig disease was diagnosed (therewas no correlation between the wound healingexperiment and the disease).

In vitro percutaneous permeation studiesAll studies were conducted in accordance toOECD-guideline 428 (19). Skin samples wereobtained from the lateral abdominal skin of sac-rificed pigs of study design B and were storedat – 20◦C until use. After gentle defrosting ofthe skin hair was clipped off (hair clipper:Wahl GmbH, Unterkirnach, Germany). Splitskin with a thickness of 500 μm was obtainedby using a dermatom (Zimmer, Freiburg,Germany) and was incubated in phosphatebuffered saline (pH 7·4, disodiumhydro-genphosphate 1·44 g, sodiumchloride 8·0 g,potassiumdihydrogenphosphate 0·24 g, potas-siumchloride 0·2 g, aqua bidest. ad 1000 ml) for

30 min before starting the experiment. Visualexaminations were used to study the integrityof the skin.

To induce barrier disruption in six skin sam-ples, the skin surface was treated with tapes(Beiersdorf GmbH, Hamburg, Germany) upto 100 times. Permeation experiments wereconducted in Franz-type diffusion cells (Per-mgear, Bethlehem, USA). The skin sampleswere mounted dermal site down betweendonor (upper part) and acceptor (lower part)chamber (permeation area of 1·77 cm2). Theacceptor compartment was filled with 12 mlSoerensen phosphate buffer (pH 7·4, potas-siumdihydrogenphosphate 2·0, disodiumhy-drogenphosphate 9·2 g, sodiumchloride 4·2 g,aqua bidest. ad 1000 ml) and was stirred con-tinuously with a magnetic bar at 500 rpm.The donor compartment was filled with 2 mloctenisept® (1·13 ml/cm2) and was coveredwith parafilm (American Can Company, Balti-more, USA).

A water bath provided a constant temper-ature of 32◦C in each Franz-type diffusioncell. Samples were taken from the acceptorcompartment (2 × 400 μl) at each time pointand were filled up with the same amount ofSoerensen phosphate buffer (0, 1, 2, 3, 4, 5, 6,22, 24, 26, 28 h).

High-performance liquid-chromatography(HPLC) with the following HPLC conditionswas used to analyse the content of OCT andPH in each sample: autosampler (508, Beck-mann, Muenchen, Germany), column (Lichro-CART 125-4, 5 μm, 10 cm, Merck, Darmstadt,Germany), pre-column (LichroCART 4-A,5 μm, Merck, Darmstadt, Germany), heater(SpH 99, Spark Holland, Emmen, Nether-lands): 40◦C, UV-VIS-detector (168, Beckmann,Muenchen, Germany).

64 © 2010 The Authors. Journal Compilation © 2010 Blackwell Publishing Ltd and Medicalhelplines.com Inc


The flow rate was set up at 1.5 ml/min,the pressure was approximately 20 mPa. Hun-dred microlitres of each sample were injectedinto the HPLC. OCT was detected at 280 nmwith a mobile phase containing 80% methanoland 20% McIlvaine buffer (pH 2.2, citric acid(anhydrous) 20.8 g, disodiumhydrogenphos-phate 0.4 g aqua bidest. ad 1000 ml). PH wasdetected at 270 nm with a mobile phase consist-ing of 80% McIlvaine buffer and 20% methanol.

Quantitative analysis was based on compar-ison with the calibration curve. The area underthe curve were analysed using the methodof external standards. The concentration inthe acceptor chamber was used to calculatethe drug amount permeated through cm2 skinaccording to Niedorf et al. 2008 (20). The maxi-mum flux (Jmax) and the apparent permeabilitycoefficient Papp were calculated from the max-imum absorption after 28 h.

AnalysisAnalysis was done using the computer soft-ware Scion Image (Scion Corporation, Fred-erick, Maryland, USA). Significance of the invivo study was tested using a Friedman’s testwith a post hoc Dunn’s test at an error level of5% (P < 0·05).

RESULTSIn vivo studiesStudy ADetermination of the wound areas: All woundswere covered with eschar from day 2 to day14 and independent of the wound treatmentall wound areas showed the same healingrate, which did not differ significantly in thedifferent treatments (Table 2).

Inflammation parameters of the wounds: Red-ness (rubor) and swelling (tumour) were foundin the wounds on day 1. While the untreatedwound showed inflammation parameters untilday 10, the wounds treated with Ringer solu-tion showed inflammation parameters untilday 8. Wounds treated with the combinationof OCT and PH showed inflammation param-eters until day 4, while higher dilutions ofthis combination of OCT and PH resulted in alonger appearance of inflammation parameters(until day 7 in the dilution 1:10).

Study BDetermination of the wound areas: Independentfrom the treatment all wounds showed

the same rate of reepithelialisation, withoutsignificant differences between the woundareas (Table 3).

Inflammation parameters of the wounds: Onlyredness (rubor) was found in some woundareas from day 1 to day 10, while no relation-ship was observed between wound treatmentand inflammation rate. The untreated and nonocclusive wound number 7 showed formationof eschar from day 1 till day 11.

In vitro percutaneous permeationstudiesOCT was only detectable in the acceptormedium of three-barrier disrupted skin sam-ples with amounts of 6.28 μg/cm2 (0.6%)of the applied 2000 μg OCT. PH permeatedthrough physiological skin samples as wellas barrier disrupted skin after tape strippingwith a 10.2-fold higher flux Jmax in skin aftertape stripping. After 28 h PH permeated inamounts of 9.87 mg/cm2 (43.7%) through bar-rier disrupted skin and of 2.54 mg/cm2 (11.3%)through physiological intact porcine skin. Alldata obtained in the in vitro diffusion experi-ment are shown in Table 4 and Fig. 1.

DISCUSSIONOCT has been developed as a potential broadspectrum topical antiseptic and is described tobe effective against skin flora (3) with goodeffects in the treatment of mild to moderateinflammatory acne lesions, Pseudomonas nailinfections as well as the antibacterial treat-ment of intravascular catheter insertion sites(21–24). Although the combination of OCT andPH is licensed in several European countriesas a skin antiseptic for humans (octenisept®),only few is known about the impact on woundhealing and skin permeability after topicalapplication.

Thus, the present studies are made inpigs, which represent an adequate model forhuman skin, to examine: (a) the influence ofa combination of OCT and PH on woundhealing under non occlusive conditions, (b) theinfluence of two commonly used topicalantiseptics (a combination of OCT and PHversus povidone-iodine) on wound healingunder occlusive conditions, and (c) the in vitropercutaneous permeation of a combination ofOCT and PH through intact as well as barrierdisrupted skin.



Table 2 Wound areas (mean and standard deviation: STD) of six pigs after topical treatment with different test formulations ondifferent days (study design A: non occlusive)

Wound area [%]

octenisept® octenisept®1:2 octenisept®1:5 octenisept®1:10 Ringer solution untreated

Day Mean STD Mean STD Mean STD Mean STD Mean STD Mean STD

1 100·0 13·6 100·0 10·6 100·0 10·0 100·0 14·9 100·0 14·5 100·0 19·22 91·4 7·8 97·2 10·6 92·8 6·3 93·8 8·3 91·2 8·0 99·7 10·23 84·3 11·2 93·8 9·5 91·5 10·7 97·3 5·8 95·0 4·3 95·5 14·04 81·6 9·5 86·5 11·7 84·8 8·5 92·0 13·0 80·7 8·7 98·1 14·37 85·5 8·6 85·4 9·2 84·3 9·3 94·5 15·2 87·3 11·1 105·4 11·58 95·7 13·0 83·1 13·5 90·2 8·0 99·5 18·5 86·1 9·8 104·1 9·19 85·4 10·8 92·5 10·3 82·1 9·2 86·7 7·4 91·1 15·9 97·1 9·9

10 85·9 8·1 84·5 7·9 93·2 14·6 94·1 13·1 88·8 7·7 99·5 13·114 71·9 8·4 61·8 6·9 64·1 12·9 67·3 6·3 72·1 13·3 72·3 9·8

Table 3 Wound areas (mean and standard deviation: STD) of six pigs after topical treatment with different aqueous solutions onday 1 and 14 (study design B: occlusive)

Wound area [%]

Ringersolution octenisept®1:10 octenisept®1:5 octenisept® Vetsept® untreated

untreated + uncovered(eschar till day 11)

Day Mean STD Mean STD Mean STD Mean STD Mean STD Mean STD Mean STD

1 100·0 39·4 100·0 38·7 100·0 38·6 100·0 60·2 100·0 44·5 100·0 40·2 100·0 39·93 122·9 52·8 96·8 43·6 92·3 42·4 126·6 53.3 100·8 43·5 95·7 38·8 91·8 36·17 76·3 33·6 65·4 29·4 75·3 39·5 104·0 45.8 64·9 31·1 82·5 44·0 77·4 35.5

10 82·0 34·6 72·8 43.8 64·3 33·4 110·3 51.8 70·3 31·8 68·2 31·8 81·3 37·511 80·3 35·3 56·8 35·0 63·5 35·1 92·8 42.4 67·1 31·8 66·0 27·4 85·3 39·814 42·1 25·6 39·0 17·9 28·2 16·5 36·4 30.7 28·4 35·1 37·3 35·2 85·1 30·1

Table 4 Flux Jmax and apparent permeability coefficient Papp of permeated 2-phenoxyethanol (PH) and octenidine dihydrochloride(OCT) per cm2 skin obtained in diffusion experiments with porcine split skin after 28 h (n = 6) calculated from the maximumabsorption according to Niedorf et al. 2008 (20)

PH OCT

Intact skin Skin after tape stripping Skin after tape stripping

Parameter Mean STD Mean STD Mean STD

Jmax [μg/cm2/h] 1·31E+02 3·39E+01 1·34E+03 2·06E+02 2·90E+00 2·28E+00Papp [cm/s] 1·82E−06 4·70E−07 1·86E−05 2·86E−06 8·05E−07 6·34E−07Amount of substance

permeated per cm2 skinafter 28 h [μg/ml]

2544·30 685·12 9865·41 993·25 6·28 10·44

Amount of substancepermeated per cm2 skinafter 28 h [%]

11·3 3·0 43·7 4·4 0·6 0·9

The summary of the effects observed underdifferent study designs is given in the followingsections.

In vivo experiment under non occlusiveconditionsWound treatment with a combination of OCT

Key Points

• the present in vivo study inpigs shows that topical woundtreatment with a combinationof OCT and PH leads to noretardation in wound healingno matter if under occlusiveor non occlusive conditions,but to faster decay of woundinflammation without occlusivecover and PH results in no significant increase

of the reepithelialisation and no woundhealing retardation compared with controlunder non occlusive conditions in a porcinewound model. The most remarkable resultconcerns the different occurrences of woundinflammation parameters. Although rednessand swelling are observed in all wounds,wound treatment with OCT and PH slightly



Figure 1. Permeation rate curve of PH obtained in diffusion experiments over 28 h with physiological intact and barrier disruptedporcine split skin (mean and standard deviation).

accelerates the reduction of inflammationparameters compared with untreated andvehicle treated controls.

In vivo experiment under occlusiveconditionsUnder occlusive conditions no differences arefound in the reepithelialisation of porcinewounds treated with a combination of OCTand PH compared with povidone-iodine andcontrol. Bennet et al. (25) described povidone-iodine to decrease wound reepithelialisationin rodent back wounds compared with othersolutions. The present study reveals neitheroctenisept® nor Vetsept® (povidone-iodinebased) to retard wound healing under occlu-sive conditions. Interestingly, compared withseptic wounds in study A, no alterationwas observed in the appearance of woundsbetween the different wound treatments instudy B.

Summary of the in vivo results underdifferent study designsThe wound healing rate after 14 days differsconsiderably between the two study designs,which can be explained by the occlusive ban-dage as well as the different wound treatments.Study A is conducted without occlusive cover,so the wounds can get infected. Furthermore,wounds are treated with the different solu-tions from day 1 to 3 while wounds in study Bare occlusive covered and wound treatment isperformed daily. As compared with all otherwounds the untreated uncovered wound instudy B shows retardation of wound healing, itcan be concluded, that occlusive cover acceler-ates wound reepithelialisation. This result is in

accordance with former reports, who describedKey Points

• the best reepithelialisation rateis observed in wounds withocclusive cover

wounds to heal faster with occlusive dressings(26–29).

Kramer et al. 2004 described OCT to havea higher cytotoxicity compared with poly-hexanide and control in vitro which leadsto wound retardation without histologicalalterations compared with polyhexanide andcontrol in pigs in vivo (30), while anotherexamination revealed that OCT representsan antimicrobial agent with the highest bio-compatibility index compared to other dis-infectants like polyhexanide, povidone-iodineor chlorhexidine digluconate (11). Com-pared with povidone-iodine OCT, chlorhex-idine digluconate and polyhexamethylenebiguanide show a 20-fold lower tolerabilityin murine fibroblasts L929 in vitro (31). As inour studies on a porcine wound model neitherretardation of reepithelialisation nor increasedduration of inflammation parameters, whichargue for high cytotoxicity, were observedin octenisept® as well as Vetsept® treatedwounds, the present study shows a high in vivobiocompatibility of the combination of 0.1%OCT and 2% PH as well as povidone-iodine.Under experimental conditions five epidemicMRSA clones did not develop stable resistanceafter exposure to low concentrations of OCTand a strong inhibition of fungal phospholi-pase B1 was shown (3,32,33). Based on ourdata and because of the high antimicrobialeffects, OCT seems to be a promising agent fortopical antisepsis.

In vitro percutaneous permeationOCT is described to be neither absorbed dur-ing the usage on the vagina nor by topical



treatment of the skin for 24 h under occlusiveKey Points

• in vitro diffusion of OCT andPH under occlusive conditionsleads to a low permeation rateof PH in intact and a 3.8-foldhigher permeation of PH inbarrier disrupted skin; OCT onlypermeates three of six barrierdisrupted skin samples in lowamounts

• concerning its high antimicro-bial effect as well as its goodbiocompatibility the combina-tionof 0.1% OCT with 2% PHrepresents a promising antisep-tic for topical skin and woundtreatment

conditions in humans (1). The present studyillustrates, that after application of octenisept®

on physiological intact porcine skin no OCTcan be found in the acceptor compartment,while 11.3% of the topical applied PH per-meate per cm2. To get further information ofpercutaneous permeation of wounded skin,skin samples were treated with adhesive tapes100 times before application of the test solu-tion. Tape stripping is an effective method toremove stratum corneum layers from the skinsurface (19), therefore it can be used to weakenthe skin barrier, maintained by the horny layerand it is also used to detect drug amounts inthe stratum corneum after topical drug appli-cation (34). After removing the horny layerOCT could be found in three of six acceptorchambers (0.6% of the applied OCT), whilePH permeated 10.2-fold higher than throughintact porcine skin. It has to be considered thatthe study was conducted under extreme con-ditions regarding the amount of solution perskin area (1.14 ml/cm2) for 28 h and the resultsobtained in the in vitro diffusion study mayover-estimate percutaneous permeation underphysiological conditions in practice. Therefore,it can be assumed that under clinical conditionsthe absorption of OCT even after applicationon wounds is neglectible. Nevertheless, thepermeation of PH observed in the presentstudy confirms examinations conducted innewborn infants, in which after topical treat-ment of human infants with octenisept®, bothsmall amounts of PH and high amounts of itsmetabolite 2-phenoxyacetic acid but no OCTwere found in spot urine (12). And in vitrostudies in rat skin showed that PH perme-ates up to 99%, while first-pass metabolism inthe skin does not have any influence on sys-temic availability of topical applied PH (35).Although few is known about systemic toxicityof PH, Scortichini et al. 1987 could neither showembryotoxic, fetotoxic, nor teratogenic effectsof PH in rabbits after topical treatment (36).

In conclusion, the present in vivo study inpigs shows that topical wound treatment witha combination of OCT and PH leads to no retar-dation in wound healing no matter if underocclusive or non occlusive conditions, but tofaster decay of wound inflammation withoutocclusive cover. The best reepithelialisationrate is observed in wounds with occlusivecover. In vitro diffusion of OCT and PH under

occlusive conditions with high amounts of top-ically applied octenisept® onto porcine splitskin, leads to a low permeation rate of PH inintact and a 3.8-fold higher permeation of PHin barrier disrupted skin. OCT only permeatesthree of six barrier disrupted skin samples inlow amounts.

In summary, concerning its high antimicro-bial effect as well as its good biocompatibility(3,10,21–24), the combination of 0.1% OCTwith 2% PH represents a promising antisepticfor topical skin and wound treatment.

ACKNOWLEDGEMENTSThe present study was sponsored by Schulke& Mayr GmbH, Norderstedt, Germany. Braun,M. and Siebert J. are employees of Schulke &Mayr GmbH, Norderstedt, Germany.

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the effect of a combination of 0.1% octenidine dihydrochloride and 2% 2-phenoxyethanol...

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