(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 29 March 2012 (29.03.2012) WO 2012/039887ft Al (51) International Patent Classification: (72) Inventors; and A61L 15/58 (2006.01) A61L 26/00 (2006.01) (75) Inventors/Applicants (for US only): ZHANG, Jinzhong [US/US]; 7 Soho Circle, Pittsford, NY 14534 (US). (21) International Application Number: WARD, Keith, W . [US/US]; 5340 Lincoln Road, On PCT/US201 1/049266 tario, NY 145 19 (US). LOPEZ, Francisco, J. [ES/US]; (22) International Filing Date: 70 Barchan Dune Rise, Victor, NY 14564 (US). 26 August 201 1 (26.08.201 1) JONASSE, Matthew [US/US]; 1190 Scandia Drive, Webster, NY 14580 (US). (25) Filing Language: English (74) Agents: VO, Toan, P. et al; BAUSCH & LOMB IN (26) Publication Language: English CORPORATED, One Bausch & Lomb Place, Rochester, (30) Priority Data: NY 14604-2701 (US). 61/384,754 2 1 September 2010 (21 .09.2010) US (81) Designated States (unless otherwise indicated, for every 13/217,336 25 August 201 1 (25.08.201 1) US kind of national protection available): AE, AG, AL, AM, (71) Applicant (for all designated States except US): AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, BAUSCH & LOMB INCORPORATED [US/US]; One CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, Bausch & Lomb Place, Rochester, NY 14604-2701 (US). DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, [Continued on next page] (54) Title: COMPOSITION AND METHOD FOR PROMOTING WOUND HEALING (57) Abstract: A composition for promoting wound healing comprises a bioadhesive polymer and a pharmaceutically ac 2400 ceptable liquid medium. Such a composition is applied to a wound to promote healing of the wound. The bioadhesive polymer can be selected from the group consisting of natural O or synthetic hydrophilic polymers and hydrogels. 0 FIG. 6 w o 2012/039887 Ai III III II II III III I llll III II I lllll II I II ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, NO, NZ, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, GW, ML, MR, NE, SN, TD, TG). TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. Declarations under Rule 4.17: — as to the identity of the inventor (Rule 4A7(i)) (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, Published: GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, — with international search report (Art. 21(3)) ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, COMPOSITION AND METHOD FOR PROMOTING WOUND HEALING BACKGROUND The present invention relates to a composition and method for promoting wound healing. In particular, the present invention relates to a composition comprising a bioadhesive polymer, and a method using such composition, for healing wounds. The process of wound healing involves a highly orchestrated series of biological responses to tissue injury, including proliferation, migration, and extracellular matrix 1-5 deposition . In the cornea, wound recovery begins with epithelial cell migration, which 6 occurs independent of epithelial cell proliferation until the wounded area is closed . Thereafter, the thickness of the epithelial layer is recovered with a combination of new cell proliferation and movement of cells into the new epithelial layer from the basal layer. While in vitro models can recapitulate most of these individual processes, and can be informative in the study of wound healing from a mechanistic point of view, such a complex process can best be studied in vivo, and there are numerous available 7-9 literature examples of relevant corneal wound healing models . Antimicrobial agents have been used to help the wound healing process have been used. However, there is still a need to provide simple, non-toxic, easy-to-use materials to assist wound healing. SUMMARY In general, the present invention provides a composition comprising a bioadhesive polymer for use to promote wound healing, and a method for healing wound by applying such a composition to a wound. A bioadhesive polymer is a natural or synthetic polymer that has a property of adhering to a biological surface upon being applied thereto. In one aspect, a composition of the present invention comprises a bioadhesive polymer and a pharmaceutically acceptable vehicle. In another aspect, a composition of the present invention comprises a bioadhesive polymer and a pharmaceutically acceptable vehicle, wherein the bioadhesive polymer comprises a mucoadhesive adhesive, and the pharmaceutically acceptable vehicle comprises a liquid medium. The term "mucoadhesive polymer" means a natural or synthetic polymer that has a property of adhering to a mucosal surface upon being applied thereto In still another aspect, a composition of the present invention comprises a bioadhesive polymer and a pharmaceutically acceptable vehicle, wherein the bioadhesive polymer comprises a mucoadhesive polymer, and the pharmaceutically acceptable vehicle comprises a liquid medium. In yet another aspect, a composition of the present invention comprises a bioadhesive polymer and a pharmaceutically acceptable vehicle, wherein the bioadhesive polymer comprises a mucoadhesive polymer, and the pharmaceutically acceptable vehicle comprises an aqueous medium. The term "aqueous medium" means a medium comprising water, and optionally other materials, which may be soluble in water or in another material included in such medium. In a further aspect, the present invention provides a method for promoting wound healing, the method comprising applying to a wound a composition that comprises a bioadhesive polymer and a pharmaceutically acceptable vehicle, wherein the pharmaceutically acceptable vehicle comprises an aqueous medium. Other features and advantages of the present invention will become apparent from the following detailed description and claims and the appended drawings. DESCRIPTION OF THE DRAWINGS Fig. 1. Representative images showing the process of corneal reepithelialization in the Besivance® group. Slit-lamp photographs were taken after instillation of topical fluorescein drops. Image acquired immediately following surgery (Left), 36 hours post- surgery (Middle), and 72 hours post-surgery (Right), respectively. The dotted ring (Left or Middle) surrounding the fluorescein-labeled area represents the wound area of the cornea. Fig. 2 . Representative histochemical sections of the rabbit cornea stained with hematoxylin and eosin. Image on the left shows a multilayered epithelium acquired from an unwounded area of the cornea from an animal in the saline group. The image in the middle shows an unclosed corneal defect at 72 hours from an animal in the Vigamox® group. The arrow points to the epithelial front as the wound is healing. The image on the ght shows the closed wound from an animal in the Besivance® group at 72 hours post- surgery, exhibiting a reduced number of corneal cell layers as compared with the intact epithelium shown in the left panel. Scale bar, 50 µητι . Fig. 3. Besivance® and other fluoroquinolones do not affect corneal wound area in a rabbit wound healing model. Data are means ± SEM, n=10 per group. Data were analyzed by a two-way ANOVA with repeated measures followed by the Tukey-Kramer test on data elevated to the power 0.6 prior to statistical analysis. Fig. 4 . Integrated effects of Besivance® and other fluoroquinolones on the corneal wound area in a rabbit wound healing model. Integrated responses were analyzed by calculating the areas under the curve using the trapezoidal rule for each treatment over the time course. Data are means ± SEM, n=10 per group. Data were analyzed by a one-way ANOVA followed by the Tukey-Kramer test on raw data. Fig. 5. DuraSite® reduces wound area in a rabbit wound healing model. Data are means ± SEM, n=10 per group. Data were analyzed by a two-way ANOVA with repeated measures followed by the Tukey-Kramer test on data elevated to the power 0.6 prior to statistical analysis. Represents time points at which the DuraSite® group was significantly different from the saline group. P < 0.05.. Fig. 6. Integrated effects of 100 ppm BAK, DuraSite®, Durasite® + 100 ppm BAK, and AzaSite®on wound area in a rabbit wound healing model. Integrated responses were analyzed by calculating the areas under the curve using the trapezoidal rule for each treatment over the time course. Data are means ± SEM, n=10 per group. Data were analyzed by a one-way ANOVA followed by the Tukey-Kramer test on raw data. * vs. Saline; P < 0.05. Fig. 7. BAK does not affect corneal wound area in a rabbit wound healing model. Data are means ± SEM. n=10 per group. Data were analyzed by a two-way ANOVA with repeated measures followed by the Tukey-Kramer test on data elevated to the power 0.6 prior to statistical analysis. Fig. 8. Integrated effects of BAK on wound area in a rabbit wound healing model. Integrated responses were analyzed by calculating the areas under the curve using the trapezoidal rule for each treatment over the time course. Data are means ± SEM, n=10 per group. Data were analyzed by a one-way ANOVA followed by the Tukey-Kramer test on raw data. DETAILED DESCRIPTION In one aspect, a composition of the present invention comprises a bioadhesive polymer and a pharmaceutically acceptable vehicle.
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