US 20150374641A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2015/0374641 A1 KM et al. (43) Pub. Date: Dec. 31, 2015

(54) FILM-FORMING PHARMACEUTICAL Publication Classification COMPOSITION FOR WOUND HEALING AND METHOD FOR PREPARING THE SAME (51) Int. Cl. A69/70 (2006.01) A619/00 (2006.01) (71) Applicant: DONG-A PHARMACEUTICAL CO., A647/36 (2006.01) LTD, Dongdaemun-gu, Seoul (KR) A638/2 (2006.01) (72) Inventors: Soon Hoe KIM, Gyeonggi-do (KR); Mi A613 L/567 (2006.01) (52) U.S. Cl. Won SON, Gyeonggi-do (KR); Sun CPC ...... A61 K9/7015 (2013.01); A61K 38/12 Woo JANG, Seoul (KR); Joon Ho JUN, (2013.01); A61 K3I/567 (2013.01); A61 K Gyeonggi-do (KR); Sang Dug HAN, 47/36 (2013.01); A61 K9/0014 (2013.01) Gyeonggi-do (KR); Sung Rak CHOI, Incheon (KR); Dae Hwan KIM, (57) ABSTRACT Gyeonggi-do (KR); Yong Sung SOHN, The present invention relates to a pharmaceutical composi Seoul (KR); Yong Sam KWON, tion for forming a film directly on a wound to accelerate Gyeonggi-do (KR) wound healing, a use for the same, a treatment method using the same, and a method for preparing the same. The film forming composition according to the present invention (21) Appl. No.: 14/765,318 forms a film directly on the wound to increase the adhesion to the wound. The formed thin hydrophilic film protects the (22) PCT Filed: Feb. 11, 2014 wound surface to prevent infection of the wound surface, retains the physiologically active Substance useful for wound (86). PCT No.: PCT/KR2O14/OO1103 healing on the wound Surface to promote the wound healing, S371 (c)(1), and allow drugs to be continuously delivered to the wound (2) Date: Jul. 31, 2015 Surface. Therefore, the composition according to the present invention has excellent wound healing effect and has excel (30) Foreign Application Priority Data lent usability as it is notabsorbed into clothing, bandage, etc., thus effectively replacing conventional gel or ointment for Feb. 13, 2013 (KR) ...... 10-2013-OO154OO mations for delivering physiologically active Substances. Patent Application Publication Dec. 31, 2015 US 2015/0374,641 A1

Fig. 1

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rootsoeveremonsoreau Time (days) - N: P40. Q.5 as T-Test result coalpared to non-treated group T: PKC. 05 as T-Test result compared to Tyrosur-treated group F: P40.05 as T-Test result compared to Fucidin-treated group US 2015/0374641 A1 Dec. 31, 2015

FILM-FORMING PHARMACEUTICAL myofibroblasts. When the levels of collagen production and COMPOSITION FOR WOUND HEALING AND degradation equalize, the maturation and rearrangement METHOD FOR PREPARING THE SAME phase of wound repair is started. During maturation, type III collagen is gradually replaced with type I collagen, and fibro TECHNICAL FIELD blasts are rearranged and cross-linked, resulting in increased tissue tension. This phase can last for a year or longer as the 0001. The present invention relates to a pharmaceutical wound type. composition for forming a film directly on a wound to accel 0004 Wound treatment methods have been studied for a erate wound healing, a use for the same, a treatment method long time and a variety of products have been sold in the using the same and a method for preparing the same. market. Disinfecting products containing oxygenated water, poVidone-iodine, ethyl alcohol, isopropyl alcohol, etc. used BACKGROUND ART to disinfect the wound Surface and dressing products such as 0002. A wound is a type of injury and can be divided into gauze, bandage, etc. which facilitate hemostasis and protect an open wound where skin is torn, punctured or cut and a the wound Surface to prevent secondary infections, etc. have closed wound Such as a bruise, contusion, etc. caused by blunt been sold. Moreover, products containing , such as force. There are various methods for treating wounds. When , and salts thereof, tyrothricin, etc., the wound is slight, it is healed naturally only by cleaning; used for a wound that may concern infection or be infected however, when the wound is a serious open wound, it needs from Such wound, or products containing a titrated extract of treatment such as cleaning, disinfection, Suture and dressing. Centella asiatica alone or in combination with steroid or In the case of most clean open wounds, they do not require antibiotics have been sold usually in the form of a gel or treatment, but a wound that may be infected with ointment. Representative products include Fucidinr) oint bacteria or an infected wound requires antibiotic treatment. ment, Tyrosur R gel, Madecassol(R), etc. 0003. The wound healing process involves a hemostasis 0005. The use of these gel or ointment formulations has phase including vasoconstriction and hemostatic chain reac the following several problems. Upon application to the tion, an inflammatory phase in which immune-related cells wound, the formulation on the wound Surface is not present are activated, a proliferation phase in which damaged blood for a long time due to external contact with gauze, clothing, vessels are newly formed and fibroblasts are formed, and a etc. Therefore, the drug is not in constant contact with the maturation and rearrangement phase in which disorganized wound surface and thus is not continuously delivered to the collagen fibers are rearranged and cross-linked. When a wound. Moreover, when the wound is exposed to the outside wound occurs, blood comes in contact with collagen to pro through the area from which the drug is removed, the prob mote platelet aggregation and secretion of inflammatory Sub ability of re-infection will increase. Further, the exposed stances. Fibrin and fibronectin are cross-linked to form a sort wound causes the patient to feel pain by other external physi of plug, preventing further blood loss. Within an hour after the cal stimuli. Therefore, many patients use disposable bandage, wound occurs, polymorphonuclear neutrophils arrive at the gauze or bandage in combination with the use of these for wound site and become predominant cells in the wound after mulations to cope with these drawbacks, but it is very incon two days. These neutrophils phagocytize debris and bacteria Venient to replace these dressings for each application. In in the wound. Macrophages are essential for wound healing addition, typical products containing antibiotics alone exhibit and replace polymorphonuclear neutrophils the predominant antibiotic activity in infected wound sites and thus they only cells in the wound by two days after injury. The main role of prevent infection in infected wound sites. However, the effect these macrophages is to phagocytize bacteria and damaged of promoting wound healing that make a Swift recovery is not tissue and they also debride damaged tissue by releasing yet known. proteases. These macrophages also secrete growth factors 0006. Therefore, the present inventors have conducted involved in the proliferation phase after post-wounding, con continuous research to overcome the drawbacks of the above tributing to pushing the wound healing process into the next described preparations. As a result, they invented a wound phase. About two or three days after the wound occurs, fibro healing gel, which is usually in the form of a gel during blasts begin to enter the wound site, marking the onset of the storage and usage, converted into the form of a film upon proliferative phase. Angiogenesis, which is important for this application to a wound site to protect the wound site, continu period, occurs concurrently with fibroblast proliferation ously deliver drugs to the wound site, and is not removed from when endothelial cells migrate to the wound site. Simulta the wound site by clothing, gauze, etc. neously with angiogenesis, fibroblasts begin accumulating in 0007. Several formulations containing pharmaceutical the wound site. Fibroblasts begin to increasing as the inflam ingredients as active ingredients and forming films upon matory phase is ending between two and five days after the application to the skin have been known in the art. Korean wound. Their numbers peak between one and two weeks after Patent No. 0551930, Korean Patent Publication No. 2008 wound. While one of the most important functions of such 0049797 and Korean Patent No. 1996-0009415 disclose com fibroblasts is the production of collagen, the production of positions comprising active Substances as well as hydrophilic collagenase and other factors degrading collagen is also one thickeners, hydrophobic polymers such as octylacrylamide of their functions, and the production occurs more rapidly acrylate copolymer, aminoalkyl methacrylate copolymer, than the degradation in the wound. Granulation tissue con ammonio methacrylate copolymer, ethyl acrylate methyl sists of fibroblasts, inflammatory cells, endothelial cells, new methacrylate, and volatile solvents such as ethanol. However, blood vessels, etc. The formation of granulation tissue in an these compositions are separated with exudates after the for open wound allows the reepithelialization phase to take place, mation of films on the wounds due to the high content of as epithelial cells migrate and form a barrier between the hydrophobic polymers and stimulate the wound Surfaces due wound and the environment. Contraction is a key phase of to the high content of organic solvents and thus these com wound healing and begins as fibroblasts differentiate into positions are not suitable for wound healing. Moreover, US 2015/0374641 A1 Dec. 31, 2015

Korean Patent No. 0979347 discloses an antifungal compo DISCLOSURE OF INVENTION sition comprising terbinafine or a salt thereof and trimethy loxysilicate for forming a film after application to the skin. Technical Problem However, this composition is not also suitable for wound 0015. An object of the present invention is to provide a healing due to the above-described problems such as the high pharmaceutical composition, a use for the same, a treatment content of hydrophobic Substance and organic solvent. method using the same, and a method for preparing the same, 0008 Korean Patent No. 0748390 discloses a sustained which comprises an active Substance, maintains the form of a release film formulation for wound healing comprising epi gel before application to a wound, forms a film directly after dermal growth factor as well as chitosan, glycerin, etc. How application to protect the wound, continuously delivers drugs, ever, this technology reduces the adhesion between the prevents the formulation from being lost by physical contact wound and the formulation, because it does not form a film with gauze, bandage, etc., and prevents re-infection by bac directly on the wound surface. Therefore, the drug delivery teria. Therefore, it overcomes the drawbacks of conventional and the protection of the wound Surface are not complete. In preparations (such as gels, ointments, etc) for wound healing particular, in the case of an irregular wound which a portion of and improves the wound healing effect. the skin is taken away, the adhesion is further reduced. 0009 Korean Patent Publication No. 2011-0027434 dis Solution to Problem closes a composition for forming a water-repellent film with 0016 To achieve the above objects, the present invention Sustained drug delivery ability, comprising sodium fusidate, provides a composition which forms a film on a wound after ethyl cellulose, soybean oil and ethanol. As mentioned above, application thereto and maximizes the wound healing effect. the preparation having a high content of organic Solvent 0017. The present invention provides a pharmaceutical causes pain upon application to the skin and reduces the rate composition for wound healing, which forms a film upon of wound healing. application to the skin, the pharmaceutical composition for 0010 Korean Patent Publication No. 2002-0066024 dis woundhealing comprising: (a) a pharmaceutically active Sub closes an ointment composition and film comprising water stance; (b) a chitosan or a salt thereof as a film-forming soluble chitosan, chemically modified with water, and hep Substance; and (c) a solvent for dissolving the chitosan, arin as active Substances. wherein the film-forming Substance is contained in an amount of 0.3 wt % or higher, preferably 0.4 to 20 wt % and more 0011 Korean Patent No. 0440239 discloses a method for preferably 0.5 to 15 wt % with respect to the total weight of the preparation of hydrogels comprising polyvinyl alcohol, the composition, and wherein the composition further com polyvinylpyrrolidone and chitosan. The composition has a prises a cream base component and the weight ratio of the high content of polymer and thus the water in the gel is not film-forming Substance to the cream base component is 1:70, evaporated. Therefore, it cannot form a film. 1:60, 1:50, 1:40, 1:30, 1:25 or more. 0012 Korean Patent Nos. 0608192 and 0644369 disclose 0018. In one embodiment, the wound is an incised wound, technologies for producing sponges by freeze-drying dis a lacerated wound, a penetrating wound, a perforated wound, Solved chitosan. These technologies also do not form a film a puncture wound, an open wound, a subcutaneous wound, a directly on the wound surface and thus the adhesion to the closed wound and a combination thereof. In another embodi wound is reduced. Therefore, these technologies have the ment the wound is a consequence of a disease or disorder, same problems as described above. Surgery, accident and a combination thereof. In yet another embodiment, the wound is external wound, internal wound 0013 Korean Patent Publication Nos. 2012-0023.653 and and a combination thereof. 2012-0022930 disclose medicinal creams comprising fusidic 0019 Conventional chitosan-containing formulations acid, Sulphadiazine and chitosan as active Substances as well contain a small amount of chitosan, contain chitosan at levels as at least one of primary and secondary emulsifiers, wax, that do not form a film upon application to the skin, or contain acid and water. These compositions contain a large amount of a large amount of cream base component, etc., which makes non-volatile, lipophilic and semi-solid materials such as par it impossible to form a film upon application to the skin. affin, cetostearyl alcohol, etc. to give appropriate Viscosity. However, in the present invention, the composition contains However, the compositions disclosed in the above inventions chitosan in an amount Suitable to form a film, i.e., in an have poor film formation properties, and even if the film is amount of 0.3 wt % or higher, preferably 0.4 to 20 wt % and formed, it is easily destroyed by external mechanical stimuli. more preferably 0.5 to 15 wt % with respect to the total weight 0014. The present inventors have intensively studied to of the composition, so as to form and maintain a film having overcome the drawbacks associated with the conventional a suitable strength, preferably a strength of 10 N or higher preparations containing the above-described antibiotics. As a upon application to the skin. result, the present inventors invented a formulation which 0020. In particular, the composition of the present inven comprises an active Substance, maintains the form of a gel tion does not contain a cream base component that interferes during storage period, and forms a film upon application to a with the film formation. Preferably, the composition of the wound. We found that the composition of the present inven present invention contains a small amount of the cream base tion has a simpler configuration than the prior art, has excel component, and the weight ratio of the film-forming Sub lent film-forming effect and high mechanical strength, and stance to the cream base component is 1:70, 1:60, 1:50, 1:40, has excellent properties that form a film directly on a wound 1:30, 1:25 or more. If the weight ratio of the film-forming Surface upon application to a wound site to provide high substance to the cream base component is lower than 1:70, it adhesion to the wound and to be easily removed from normal is impossible to form a film having a sufficient strength upon tissue of healed wound, thus completing the present inven application of the composition to the skin. Therefore, the tion. composition of the present invention, which contains the US 2015/0374641 A1 Dec. 31, 2015 cream base component in a predetermined ratio with respect the total weight of the composition; and (c) at least one to the chitosan, can form a film useful for wound healing on a Solvent selected from the group consisting of water ethanol, wound Surface as the solvent is evaporated or Volatilized upon isopropyl alcohol and mixtures thereof, wherein the compo application to the skin. sition further comprises a cream base component and the 0021. These cream base components are fully described in weight ratio of the film-forming Substance to the cream base “Handbook of Pharmaceutical Excipients, 6th edition, Phar component is 1:70, 1:60, 1:50, 1:40, 1:30, 1:25 or more. maceutical Press'. The cream base components that interfere 0025. According to still another embodiment of the with the film formation by the film-forming substances in the present invention, the present invention provides a pharma composition of the present invention are well known in the ceutical composition for wound healing, comprising: (a) at art. In general, the cream formulations are in the form of an least one pharmaceutically active Substance selected from the emulsion, in which an oil phase is dispersed in water, the group consisting of tyrothricin, fusidic acid or a salt thereof, emulsion comprising an oil phase, an emulsifier and a water Sulfate or a salt thereof, hydrocortisone, titrated phase. The cream base components mentioned in the speci extract of Centella asiatica and combinations thereof in an fication refer to the oil phase and the emulsifier, and those amount of 0.1 to 10 wt %, with respect to the total weight of skilled in the art can easily understand the meaning and the composition; (b) a chitosan or a salt thereof as a film examples of the cream base components. These cream base forming substance in an amount of 0.4 to 20 wt % and pref components include any materials, which interfere with the erably 0.5 to 15 wt % with respect to the total weight of the film formation by chitosan upon application of the composi composition; and (c) at least one solvent selected from the tion of the present invention to the skin and form a formula group consisting of water, ethanol, isopropyl alcohol and tion in the form of a cream when it is present in a predeter mixtures thereof in an appropriate amount, preferably in the mined amount, and are not limited to those described in this residual amount other than the main component and other specification. Examples of the cream base component may components, wherein the composition further comprises a include isopropyl palmitate, cetyl palmitate, paraffin, trio cream base component and the weight ratio of the film-form ctanoin, soybean oil, sesame oil, olive oil, liver oil, oleic acid, ing Substance to the cream base component is 1:70, 1:60. Stearic acid octyldodecanol, octyldodecyl myristate, Silicone 1:50, 1:40, 1:30, 1:25 or more. compound as dimethicone or Simethicone, Stearyl alcohol, 0026. According to yet another embodiment of the present Stearyl glycyrrhetinate, polyoxyl Stearate, squalane, ceto invention, the present invention provides a pharmaceutical Stearyl alcohol, cetomacrogol, cetanol, Sorbitan sesquioleate, composition for wound healing, comprising: (a) a pharma Vaseline, white beeswax, yellow beeswax, myristyl alcohol, ceutically active substance such as tyrothricinin an amount of isopropyl myristate, Sorbitan monooleate, Sorbitan 0.1 to 10 wt % with respect to the total weight of the compo monostearate, glycerin monostearate, lecithin, hydrogenated sition; (b) a chitosan or a salt thereofas a film-forming Sub castor oil, caprylic-capric triglyceride, lanolin, oleoyl mac stance in an amount of 0.4 to 20 wt %, preferably 0.5 to 15 wt rogolglycerides, etc., but not limited thereto. The film-form % and more preferably 1 to 10 wt % with respect to the total ing composition of the present invention is different from the weight of the composition; (c) at least one solvent selected conventional chitosan-containing formulations in that it con from the group consisting of water, ethanol, isopropyl alcohol tains the cream base component in a ratio that does not inter and mixtures thereof in an appropriate amount, preferably in fere with the film formation by chitosan. the residual amount other than the main component and other 0022. The film-forming composition of the present inven components; (d) an acid, preferably lactic acid, in an amount tion may further comprise at least one additive selected from of 0.20 to 20 wt %, preferably 0.25 to 10 wt % and more the group consisting of an acid, a plasticizer, a thickener, a preferably 0.5 to 7.5 wt % with respect to the total weight of Surfactant, a preservative, a flavoring agent and a humectant. the composition; and (e)a thickener, preferably poloxamer, in Here, the amount of each additive used in the present inven an amount of 0.2 to 10 wt % with respect to the total weight of tion is 30 wt % or less, preferably 0.1 to 20 wt %, more the composition, wherein the composition further comprises preferably 0.1 to 16 wt % and still more preferably 0.25 to 10 a cream base component and the weight ratio of the film wt % with respect to the total weight of the composition. forming substance to the cream base component is 1:70, 1:60. 0023. According to an embodiment of the present inven 1:50, 1:40, 1:30, 1:25 or more. tion, the present invention provides a pharmaceutical compo 0027. The composition of the present invention can be sition for wound healing, comprising: (a) a pharmaceutically effectively used for wound healing to treat a wound or infec active Substance; (b) a chitosan or a salt thereof as a film tious disease. forming Substance; (c) a solvent for dissolving the chitosan, 0028. Hereinafter, the present invention will be described and (d) an additive selected from the group consisting of an in more detail. acid, a plasticizer, a thickener, a Surfactant, a preservative, a 0029. The composition of the present invention comprises flavoring agent, a stabilizer, a defoamer, an analgesic agent, at least one physiologically or pharmaceutically active Sub an antioxidant, an adhesive, agellant, an emulsifier, an astrin stance. The physiologically or pharmaceutically active Sub gent, an opacifier, a humectant and mixtures thereof. stance is a drug useful for wound healing and includes those 0024. According to another embodiment of the present commonly used in the art. Examples of the physiologically or invention, the present invention provides a pharmaceutical pharmaceutically active Substance may include antibiotics, composition for wound healing, comprising: (a) at least one wound healing accelerants, disinfectants, local anesthetics or pharmaceutically active Substance selected from the group anti-inflammatory agents. consisting of tyrothricin, fusidic acid or a salt thereof, neo 0030. For example, the active substance used in the com mycin Sulfate or a salt thereof, hydrocortisone, titrated extract position of the present invention may include: anti of Centella asiatica and combinations thereof; (b) a chitosan biotics Such as , amplicillin, moxalactam, piper or a salt thereof as a film-forming Substance in an amount of acillin, , , or salts thereof; 0.4 to 20 wt % and preferably 0.5 to 15 wt % with respect to antibiotics Such as , , US 2015/0374641 A1 Dec. 31, 2015

, , , , , ceftriax in the form of a gel, Sol, etc. during storage and forms a film one, , , or salts thereof; betalactam antibi on a wound site upon application to the human body. otics Such as , , or salts thereof, ami 0037 Chitosan can be obtained by deacetylation of chitin noglycoside antibiotics such as , arbekacin, from crustaceans and is a linear polysaccharide composed of isepamicin, Sisomycin, tobramycin, , or salts randomly distributed B-(1-4)-linked D-glucosamine and thereof macrollide antibiotics such as azithromycin, N-acetyl-D-glucosamine. The properties of polysaccharide clarithromycin, erythromycin, midecamycin, roXithromycin, vary depending on the degree of deacetylation, and the spiramycin, or salts thereof, quinolone antibiotics such as desired degree of deacetylation is 80%. 82%, 84%. 86%, ciprofloxacin, enoxacin, gatifloxacin, levofloxacin, lom 88%, 90% or higher. In the present invention, the chitosan efloxacin, to Sufloxacin, or salts thereof, antibiot serves as a thickener that maintains the form of a gel formu ics such as doxycycline, methacycline, minocycline, tetracy lation and does not flow during use to conveniently apply to cline, or salts thereof, or any other antibacterial Substances the skin as well as the role of the film-forming substance. The having different mechanisms. Preferably, the active sub molecular weight of the chitosan used in the present invention stance may be , chloroxylenol, clindamycin, is not limited to any particular molecular weight, and in the , , , mupirocin, neomycin, case of a low molecular weight, the chitosan may contain a nitrofuraZone, , retapamulin, silver Sulfadiaz thickener to maintain the gel formulation or can be adminis ine, tyrothricin, fusidic acid, , nystatin, mupirocin, tered in the form of a thingel without containing an additional or salts thereof. thickener. Moreover, the chitosan of the present invention is 0031 Moreover, the composition of the present invention in the form of a free base or salt or derivatives and if the may contain a disinfectant or sanitizer for disinfection in the chitosan is in the form of a salt, an acid may not be required. early stage of the wound healing as an active Substance. In the present invention, the chitosan may be prepared by a Examples of the disinfectant or sanitizer may include any method known in the art or may be commercially available. main components, which are known for their wound disin The content of chitosan in the composition of the present fection, such as Glutaral Concentrate, benzalkonium, benze invention shall be an amount Sufficient to maintain a proper thonium, chlorohexidine, cresol, ethanol, isopropyl ethanol, Viscosity and to form a film having a sufficient strength upon povidone-iodine, silver nitrate, or salts thereof. application to the skin. The amount of chitosan may prefer 0032. Furthermore, the composition of the present inven ably be 0.3 wt % or higher with respect to the total weight of tion may contain a wound healing accelerant as an active the composition, more preferably 0.4 wt % or higher and does substance for accelerating the wound healing. Examples of not exceed 20 wt % and still more preferably 0.5 wt % or the wound healing accelerant may include water-soluble aZu higher and does not exceed 15 wt %. lene, policresulen, becaplermin, Centella asiatica extract, 0038. The composition of the present invention may con dexpanthenol, keratinocytes, , polydeoxyribo tain an acid for dissolving chitosan. Examples of the acid for nucleotide, Solcoseryl 120 concentrate, trafermin, or salts dissolving the chitosan may include Sulfuric acid, fluorosul thereof. furic acid, nitric acid, phosphoric acid, hydroboric acid, boric acid, ascorbic acid, acetic acid, citric acid, propionic acid, 0033. In addition, the composition of the present invention formic acid, gluconic acid, lactic acid, oxalic acid, tartaric may contain a local anesthetic as an active Substance for acid, malic acid, adipic acid, maleic acid, Succinic acid, etc., eliminating pain of the initial wound. Examples of the local and these acids may be used alone or in combinations. The anesthetic may include , bupivacaine, levobupiv amount of the acids may preferably be 0.2 to 20 wt % with acaine, , mepivacaine, procaine, ropivacaine, tetra respect to the total weight of the composition. Preferably, caine, prilocaine, or salts thereof. lactic acid is used. 0034 Additionally, the composition of the present inven 0039. The composition of the present invention may also tion may contain an anti-inflammatory agent as an active contain a solvent for dissolving chitosan. The solvent serves Substance for eliminating inflammation at the wound site. to maintain the preparation in the form of a fluid before Examples of the anti-inflammatory agent may include application to the skin and to Volatilize after application to the alclometasone, amcinonide, beclomethasone, budesonide, wound, thus forming a film on the wound Surface. clobetasol, desonide, desoxymethasone, dexaltin NK, dex 0040. In the composition of the present invention, the sol amethasone, diflucortolone, fluocinolone, fluocinonide, flu vent for dissolving the chitosan may preferably be selected ticasone, halcinonide, hydrocortisone, methylprednisolone, from the group consisting of water, lower alcohol having 1 to prednicarbate, prednisolon, triamcinolone, or salts thereof. 4 carbon atoms and mixtures thereof, more preferably be 0035. The composition of the present invention may con selected from the group consisting of ethanol, isopropyl alco tain at least one of the above-listed substances that can be used hol and mixtures thereof. These solvents are used in an for wound healing, but not limited thereto. Preferably, the amount suitable to control the active substance. Moreover, pharmaceutically active Substance may comprise at least one these solvents are evaporated or Volatilized upon application selected from the group consisting of tyrothricin, fusidic acid of the composition to the skin such that a film can be formed or a salt thereof, neomycin Sulfate or a salt thereof, hydrocor on the skin Surface to which the composition of the present tisone, titrated extract of Centella asiatica and combinations invention is applied. thereof. The amount of the active substance contained in the 0041. The composition of the present invention may con composition of the present invention is in a concentration tain a solvent for dissolving an active substance as well as the range with the Suggestion that their safety and effectiveness chitosan. The solvent serves to maintain the preparation in the have been proven, preferably in a range of 0.3 to 2 times the form of a fluid before application to the skin and to volatilize commercially available concentration of each component. after application to the wound, thus forming a film on the 0036. The composition of the present invention comprise wound surface. The solvent of the present invention may chitosanas a film-forming Substance, which is usually present preferably be isopropyl alcohol, ethyl alcohol, ethyl acetate, US 2015/0374641 A1 Dec. 31, 2015

acetone, water or mixtures thereof, more preferably isopropyl servatives may include, but not limited to, quaternary ammo alcohol, ethyl alcohol, water or mixtures thereof, which are nium compounds such as , less irritating to the wound Surface. An appropriate amount of , cetrimide, dequalinium chloride and the solvent may be one that can maintain the active Substance ; alcohol compounds such as chlo at a constant concentration. robutanol, phenylethyl alcohol and benzyl alcohol; parabens 0042. The composition of the present invention may also Such as methylparaben, ethylparaben, propylparaben and comprise a plasticizer. The plasticizer serves to facilitate the butylparaben; antibacterial esters such as ester of parahy production of preparations and prevent precipitation of the droxybenzoic acid; and other antibacterial agents such as active Substances from the preparations by assisting the dis chlorohexidine, chlorocrosol, benzoic acid, polymixine and Solution of the active substances in the composition of the phenoxyethanol. Preferably, the preservative may comprise present invention. Moreover, after the formation of the film on at least one selected from the group consisting of Sodium the wound Surface, the plasticizer serves to soften the strength benzoate, phenoxyethanol, benzyl alcohol, methylparaben, of the film formed so as to prevent destruction of the film due imidazolidinyl urea and diazolidinyl urea. The preservatives to contraction of the skin and maintain the film. Therefore, it may preferably be contained in an amount of 0.1 to 10 with provides functional and aesthetic excellence. Examples of the respect to the total weight of the composition. plasticizer that can be used in the present invention may be 0046. The composition of the present invention may fur selected from the group consisting of propylene glycol, poly ther comprise other additives typically added to usual phar ethylene glycol, propylene carbonate, Labrasol, Transcutol, maceutical preparations for external application. For Labrafac, Plurol Oleidue, Lauroglycol, Capryol, Labrafil. example, the additives may include preservatives, flavoring Miglyol, glycerin and mixtures thereofand may preferably be agents, bases, humectants, stabilizers, defoamers, analgesic contained in an amount of 0.2 to 10 wt % with respect to the agents, antioxidants, thickeners, gallants, emulsifiers, astrin total weight of the composition. gents, opacifiers, etc., and their examples are fully described 0043. The composition of the present invention may fur in “Handbook of Pharmaceutical Excipients, 6th edition, ther comprise a thickener. The thickener may be selected from Pharmaceutical Press'. Those skilled in the art can select the group consisting of hydroxypropyl cellulose, hydrox these additives and use them in the formulation of the present ypropylmethyl cellulose, hydroxyethyl cellulose, Xanthan invention without any technical difficulties. Moreover, these gum, locust bean gum, arabic gum, guar gum, carbomer, additives are typically added to pharmaceutical preparations polyethylene oxide, poloxamer and mixtures thereof, and the for external application, and those that do not interfere with thickener may preferably be contained in an amount of 0.2 to the film formation upon application of the composition of the 10 wt % with respect to the total weight of the composition, present invention can be appropriately used. Even when these which can maintain the Viscosity to a degree that can Supply additives correspond to the cream base components described the insufficient thickening ability of the chitosan. in this specification, these additives can be used in an amount 0044) The composition of the present invention may fur that is preferably adjusted within the range described in this ther comprise a surfactant. When the active substance is specification. poorly water soluble, the surfactant improves the solubility of 0047. The composition of the present invention is in the the active Substance in the preparation to prevent precipita form of a semi-solid such as a liquid, gel, or ointment before tion. Moreover, the surfactant increases the miscibility of use, but forms a film after application to the skin. The form of other hydrophobic materials in the preparation to maintain the active Substance present in the formulation may be a the formulation stable. Furthermore, in the case of a poor Suspension in which fine particles are Suspended in a solid water-soluble active Substance, the Surfactant increases the state or an emulsion in which fine particles are dissolved in an penetration of drugs into the wound. For example, in the case oil phase. Moreover, when the active substance itself is well of tyrothricin used as an antibiotic, its solubility in water is dissolved or solubilized, it may be present in the form of a significantly reduced and thus precipitates are formed in a liquid. The formulations for the composition of the present preparation containing excess water phases. However, in the invention may be prepared by a typical pharmaceutical pro case of an ethylene oxide?propylene oxide copolymer (poloX duction method such as a method described in “Remington's amer) used as a surfactant, it maintains the dissolved state. Pharmaceutical Science, Mack Publishing Co..”. Examples of the surfactant that can be added to the compo 0048 Moreover, the present invention provides a method sition of the present invention may include nonionic Surfac of wound healing, comprising treating to a subject a thera tants such as polysorbate 20, polysorbate 40, polysorbate 60, peutically effective amount of a pharmaceutical composition. polysorbate 80, polyethylene hydroxystearate (e.g., Solutol The wound healing method of the present invention com HS15), polyethoxylated castor oil (e.g., Cremophor EL, Cre prises alleviative and curative treatment. Preferably, the mophor RH40, Cremophor RH60), ethylene oxide?propylene method is used for treatment of humans. oxide copolymer (e.g., poloxamer 124, poloxamer 188, 0049. The term “pharmaceutically effective” means poloxamer 407), Stearoyl macrogol-32 glycerides, lauroyl approved by a regulatory agency of the government or listed macrogol-32 glycerides, propylene glycol monocaprylate, in Pharmacopeia or other generally recognized pharmacopeia caprylocaproyl macrogol-8 glycerides, etc. or ionic Surfac for use in animals, and more particularly in humans. tants such as sodium lauryl Sulfate, sodium docusate, benza 0050. The composition of the present invention is intended Ikonium chloride, benzethonium chloride, etc. The amount of to be applied topically and directly to the wound. In one the Surfactant used in the present invention may be an amount embodiment, the composition is in the form of an ointment, a that is sufficient for the above objectives and may preferably liquid or a gel which is spread directly onto the wound (e.g. be 0.1 to 10 wt % with respect to the total weight of the skin, etc) and forms a film upon application to the wound. composition. 0051. Furthermore, the present invention relates to a use of 0045. The composition of the present invention may fur the pharmaceutical composition of the present invention for ther comprise a preservative. Examples of appropriate pre wound healing. US 2015/0374641 A1 Dec. 31, 2015

0052 Moreover, the present invention relates to a use of 0062 FIG. 2 shows the wound recovery rate in burned composition for manufacturing a pharmaceutical composi animal models treated with Example 1 and commercially tion for wound healing. available preparations such as Tyrosurr) and Fucidin R. 0053. The details mentioned in the use, composition and method of the present invention are equally applied unless MODE FOR THE INVENTION they are contradictory. 0063. The present invention will be described in more Advantageous Effects of Invention detail with reference to the following Examples. However, the following Examples are intended to illustrate the present 0054 The present invention provides the following invention, and the present invention is not limited by the effects: following Examples. 0055. First, upon application of the composition in a typi cal form to the skin, it forms a film to prevent the formulation EXAMPLES 1 TO 6 being separated from the wound Surface by physical contact, thus reducing the use of bandage orgauze and the number of Preparation of Film-Forming Gels Containing USS. Tyrothricin and Water 0056 Second, the film directly forms on the wound sur face and increases the adhesion to the wound. In particular, in 0064 Tyrothricin, ethanol, propylene glycol, cetylpyri the case of an irregular wound, the adhesion is further dinium chloride and a flavoring agent were mixed in amounts increased. described in the following Table 1 and completely dissolved 0057 Third, the formed film allows drugs to be continu using an overhead mixer, thus preparing liquid 1. Apart from ously delivered to the wound Surface, thus increasing the above liquid 1, water was placed in a Homo-Agi Mixer, wound healing effect. chitosan was added and dispersed, and lactic acid was further 0.058 Fourth, the film formed on the wound surface can added and dissolved. To the dissolved liquid, poloxamer 407 protect the wound from being infected by external bacteria, (and polysorbate 80) was further added and dissolved. Liquid etc. 1 containing tyrothricin was added to the resulting Solution 0059 Fifth, it prevents both edges of an incised wound, and completely dissolved, thus preparing film-forming gels Such as a wound cut by a knife, from being opened, thus containing tyrothricin. improving the treatment of the incised wound. 0065. When the preparations of the following Examples 0060 Lastly, the composition of the present invention were applied to the skin, transparent films were formed in all tends to adhere to the wound surface only in a humid envi cases after 10 to 20 minutes. TABLE 1. Ingredients Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Tyrothricin O.1 O.1 O.1 O.1 O.1 O.1 Chitosan, low 4 10 molecular weight* Chitosan, high 4 O.S 4 molecular weight** Chitosan 4 chloride:*** Poloxamer 407 2.5 5 2.5 8 O.1 Polysorbate 80 1 Lactic acid 2 2 2 6 2 Propylene glycol 1 1 1 1 1 Cetylpyridinium O.OS O.OS O.OS O.OS O.OS O.OS chloride Flavoring agent Quantum Quantum Quantum Quantum Quantum Quantum satis satis satis satis satis satis Ethanol 1 1 1 1 1 1 Purified water Balance Balance Balance Balance Balance Balance up to up to up to up to up to up to 100 g 100 g 100 g 100 g 100 g 100 g *Molecular weight of 100,000 or less **Molecular weight of 100,000-2,000,000 or less ***Prepared by treating chitosan with hydrochloric acid and solubilizing in the water ronment and thus it is selectively separated from the healing EXAMPLES 7TO 9 site as the wound healing process continues. Preparation of Film-Forming Gels Containing BRIEF DESCRIPTION OF DRAWINGS Tyrothricin in Different Concentrations and Water 0061 FIG. 1 shows the wound contraction ratio in abra sion animal models treated with Examples 1 and 13 and 0.066 Film-forming gels having different chitosan con commercially available preparations such as TyroSur R and centrations as described in the following Table 2 were pre Fucidin(R). pared by the same method as Example 1. When the prepara US 2015/0374641 A1 Dec. 31, 2015 tions of the following Examples were applied to the skin, and completely dissolved, thus forming film-forming gels transparent films were formed in all cases after 10 to 20 containing tyrothricin. When the preparations of the follow minutes. ing Examples were applied to the skin, transparent films were formed in all cases after 8 to 15 minutes. TABLE 2 TABLE 4 Ingredients Example 7 Example 8 Example 9 Example Tyrothricin O.1 O.1 O.1 Ingredients Example 11 Example 12 Example 13 14 Chitosan, high O.S 1 2 molecular weight Tyrothricin O.1 O.1 O.1 O.1 Poloxamer 407 2.5 2.5 2.5 Chitosan, low 2 2 3 2 Lactic acid O.25 O.S 1 molecular weight Propylene glycol 1 1 1 Hydroxypropyl 1.5 2 Cetylpyridinium O.OS O.OS O.OS cellulose HF chloride Hydroxypropyl 2 2.5 Flavoring agent Quantum Quantum Quantum cellulose MF satis satis satis Lactic acid 1.33 1.33 1.33 1.33 Ethanol 1 1 1 Propylene glycol 1 1 1 1 Purified water Balance up Balance up Balance up Benzyl alcohol O.1 O.1 to 100 g to 100 g to 100 g Cetylpyridinium O.OS O.OS chloride Flavoring agent Quantum Quantum Quantum Quantum satis satis satis satis EXAMPLE 10 Ethanol 46 46 46 46 Purified water Balance up Balance up Balance up Balance Preparation of Film-Forming Liquid Containing to 100 g to 100 g to 100 g up to Tyrothricin and Water 100 g 0067 Tyrothricin, ethanol, propylene glycol, cetylpyri dinium chloride and a flavoring agent were mixed in amounts described in the following Table 3 and completely dissolved EXAMPLES 15 AND 16 using an overhead mixer, thus preparing liquid 1. Separately, water and chitosan were placed and dispersed in another Preparation of Film-Forming Gels Containing overhead mixer, and lactic acid was further added to dissolve Sodium Fusidate the chitosan. Liquid 1 containing tyrothricin was added to the chitosan Solution and completely dissolved, thus preparing a 0069. Sodium fusidate or sodium fusidate and hydrocor film-forming liquid containing tyrothricin. When the prepa tisone, water (20g), polysorbate 80, propylene glycol, etha ration of the following Example 10 was applied to the skin, a nol and a flavoring agent were mixed in amounts described in transparent film was formed after 10 to 20 minutes. the following Table 5 and completely dissolved or dispersed using an overhead mixer, thus preparing liquid 1. Separately, TABLE 3 the rest of water was added to a Homo-Agi mixer, chitosan was added and dispersed, and then lactic acid was added to Ingredients Example 10 dissolve the chitosan. To the resulting solution, poloxamer Tyrothricin O.1 407 was further added and dissolved by stirring. Liquid 1 was Chitosan, low 4 placed in the Homo-Agi Mixer and stirred, and then liquid 2 molecular weight was added and completely dissolved, thus forming film Lactic acid 2.5 Propylene glycol 1 forming gels containing sodium fusidate, etc. When the Cetylpyridinium O.OS preparations of the following Examples were applied to the chloride skin, transparent films were formed in all cases after 10 to 20 Flavoring agent Quantum satis minutes. Ethanol 1 Purified water Balance up to 100 g TABLE 5 ngredients Example 15 Example 16 EXAMPLES 11 TO 14 sodium fusidate 2 2 Hydrocortisone 1 Preparation of Film-Forming Gels Containing Chitosan, high 4 4 Tyrothricin, Water and Ethanol molecular weight Poloxamer 407 2 2 0068 Tyrothricin, ethanol (1 g), propylene glycol, Polysorbate 80 1 2 cetylpyridinium chloride, benzyl alcohol and a flavoring Lactic acid 2 2 Propylene glycol 1 1 agent were mixed in amounts described in the following Table Cetylpyridinium O.OS O.OS 4 and completely dissolved using an overhead mixer, thus chloride preparing liquid 1. Separately, chitosan was dispersed in Flavoring agent Quantum Quantum satis satis water (40 g) using an overhead mixer and then lactic acid was Ethanol 1 1 added to dissolve the chitosan, thus preparing liquid 2. Etha Purified water Balance up Balance up nol (45 g) was placed in a Homo-Agi Mixer, and hydroxypro to 100 g to 100 g pyl cellulose was added and dissolved. Liquid 1 was placed in the Homo-Agi Mixer and stirred, and then liquid 2 was added US 2015/0374641 A1 Dec. 31, 2015

EXAMPLES 17 TO 20 -continued

Preparation of Film-Forming Gels Containing Sulfadiazine silver 1% + Chitosan cream Titrated Extract of Centella asiatica Content 0070 A titrated extract of Centella asiatica (Example 17), Sample No. Ingredients % (w.fw) the titrated extract of Centella asiatica and neomycin Sulfate 6 Cetomacrogol 1000 2.5 (Example 18), or the titrated extract of Centella asiatica, 7 Methylparaben O.2 neomycin sulfate and hydrocortisone (Example 19) were 8 Propylparaben O.O2 9 Light liquid paraffin 5 mixed with propylene glycol, ethanol, ethylene glycol Stear 10 Propylene glycol 10 ate, a flavoring agent and polysorbate 80 in amounts 11 Disodium EDTA O.1 described in the following Table 6 and dissolved or dispersed. 12 Disodium hydrogen phosphate O.S Cetylpyridinium chloride was added thereto and homoge 13 Purified water 63SO neously mixed by heating, thus preparing liquid 1. Separately, water was placed in a Homo-Agimixer, and then chitosan was added and dispersed. Lactic acid was added thereto and dis EXPERIMENTAL, EXAMPLE1 Solved, and then liquid 1 was added and stirred, thus prepar ing film-forming gels containing the respective active ingre Comparison of Strengths of Films Prepared dients. When the preparations of the following Examples According to the Examples of the Present Invention were applied to the skin, transparent films were formed in all and Comparative Example 1 cases after 10 to 20 minutes. 0072 Each 0.5g was taken from the formations according TABLE 6 to Examples 1, 7 to 9, and 20 of the present invention and the cream formulation according to Comparative Example 1. Example Samples applied to 1.5 cm x 1.5 cm PE plastic bag and dried at Ingredients Example 17 Example 18 Example 19 2O 37.5°C., thus forming films. The breaking strength of each Titrated extract of 1 1 1 1 film was measured using a texture analyzer (Stable Micro Centella asiatica Systems, UK), and the results are shown in Table 7. It could be Neomycin sulfate 1 1 Hydrocortisone 1 seen that the strengths of the films formed of the compositions Chitosan, high 4 4 4 1 of the present invention were significantly increased at least molecular weight 10 times compared to Comparative Example 1. Cetostearyl 8.5 alcohol TABLE 7 Ethylene glycol 5 5 5 8.5 Stearate Polysorbate 80 5 5 5 7 Breaking Strength of Film (N) Lactic acid 2 2 2 2 Comparative Example 1 1.3 Propylene glycol 5 5 5 5 Example 1 78.7 Cetylpyridinium O.OS O.OS O.OS O.OS Example 7 13.8 chloride Example 8 22.1 Flavoring agent Quantum Quantum Quantum Quantum Example 9 46.8 satis satis satis satis Example 20 14.1 Ethanol 1 1 1 1 Purified water Balance up Balance up Balance up Balance to 100 g to 100 g to 100 g up to 100 g EXPERIMENTAL, EXAMPLE 2 Comparison of Wound Healing Effect of COMPARATIVE EXAMPLE1 Compositions According to the Present Invention and Commercially Available Products in Abrasion Preparation of Cream Formulation Containing Models Chitosan 0073. SD rats with diabetes induced by intravenous injec 0071. A cream formulation containing 0.25% (w/w) chi tion of Streptozocin (40 mg/kg) were anesthetized and an tosan and was prepared from the ingredi abrasion with a diameter of 40 mm was created in each rat. ents of Example 1 disclosed in Korean Patent Publication No. The preparations of Examples 1 and 13 and commercially 2012-OO2293O. available Tyrosur R gel 1 (Engelhard Co., Ltd.) and Fucidin R ointment (DONG WHA Pharmaceutical Co., Ltd.) in Com parative Examples were used as the test materials. The experi Sulfadiazine silver 1% + Chitosan cream mental groups were divided into a non-treated group, a Content treated group of Example 1, a treatment group of Example 13, Sample No. Ingredients % (w.fw) a TyroSur gel-treated group, and a Fucidin ointment-treated group, and the treated groups were treated with 0.5g of each 1 Silver sulfadiazine 1 2 Chitosan O.25 test material once a day. The evaluation of wound healing was 3 Lactic acid O.1 performed by calculating the wound contraction ratio, which 4 White soft paraffin 8.5 represents the ratio of the initial wound size to the wound size 5 Cetostearyl alcohol 8.5 after two days from the wound healing (Wound contraction ratio=(Initial wound size-Wound size after two days in each US 2015/0374641 A1 Dec. 31, 2015

group)/Initial wound sizex100(%)). The results are shown in 3. The pharmaceutical composition of claim 1, further FIG. 1. As can be seen from FIG. 1, the compositions of the comprising at least one additive selected from among an acid, present invention exhibited significant effects on the reduc a plasticizer, a thickener, a Surfactant, a preservative, a flavor tion in wound area (P<0.05) in the abrasion, compared to the ing agent and a humectants, non-treated group and the commercially available prepara wherein the at least one additive is present in an amount of tion Such as TyroSurgel and Fucidin ointment. 30 wt % or less with respect to the total weight of the composition. EXPERIMENTAL, EXAMPLE 3 4. The pharmaceutical composition of claim3, wherein the acid is selected from among lactic acid, acetic acid, citric Comparison of Wound Healing Effects of acid, ascorbic acid, gluconic acid, malic acid, adipic acid, Compositions According to the Present Invention maleic acid, Succinic acid, tartaric acid and mixtures thereof and Commercially Available Products in Burn and is present in an amount of 0.2 to 20 wt % with respect to Models the total weight of the composition. 007.4 SD rats were anesthetized and their back hair was 5. The pharmaceutical composition of claim3, wherein the removed. A burn wound was induced by contacting a cylin plasticizer is selected from among propylene glycol, polyeth drical metal having a diameter of 1.5 cm and heated at 80°C. ylene glycol, propylene carbonate, Labrasol(R) PEG-8 with the back of each rat. The epidermis of the wound was caprylic/capric glycerides, Transcutol R. 2-(2-ethoxyethoxy) excised to the fascia. The preparations of Example 1 and ethanol, LabrafacTM propylene glycol gicaprylate dicaprate, commercially available Tyrosur R gel 1 (Engelhard) and Fuci Plurol Oleidue(R) polyglyceryl-6 dioleate, LauroglycolTM pro din R) ointment (DONG WHA Pharmaceutical Co., Ltd.) in pylene glycol laurate, CapryolTM propylene glycol caprylate, Comparative Examples were used as the test materials. The Labrafil R lauroyl, linoleoyl and oleoyl polyoxylglycerides, experimental groups were divided into a non-treated group, a Miglyol(R) fractionated coconut oil or caprylic/capric triglyc treated group of Example 1, a TyroSurgel-treated group, and erides, glycerin and mixtures thereof and is present in an a Fucidin ointment-treated group, and the treated groups were amount of 0.2 to 10 wt % with respect to the total weight of the treated with 0.5 g of each test material once a day. The composition. evaluation of wound healing was performed by calculating 6. The pharmaceutical composition of claim3, wherein the the wound recovery rate, which represents the rate of wound thickener is selected from among hydroxypropyl cellulose, recovery from the initial wound size after 1, 2, 4 and 6 days hydroxyethyl cellulose, Xanthan gum, locust bean gum, ara from the woundhealing (Wound recovery rate-Wound size at bic gum, guar gum, carbomer, polyethylene oxide, poloxamer 1, 2, 4 and 6 days in each group/Initial wound sizex100(%)). and mixtures thereof and is present in an amount of 0.2 to 10 The results are shown in FIG. 2. As can be seen from FIG. 2, wt % with respect to the total weight of the composition. the composition of the present invention exhibited a signifi 7. The pharmaceutical composition of claim3, wherein the cant effect on the reduction in wound area (P<0.05) in the Surfactant is selected from the group consisting of polysor burn wound at 1, 2, 4 and 6 days from the wound healing, bate, polyethylene hydroxyStearate, polyethoxylated castor compared to the non-treated group and the commercially oil, ethylene oxide?propylene oxide copolymer, Stearoyl mac available preparation Such as TyroSur gel and Fucidin oint rogol-32 glycerides, lauroyl macrogol-32 glycerides, propy ment. lene glycol monocaprylate, caprylocaproyl macrogol-8 glyc 1. A pharmaceutical composition for wound healing, com erides, sodium lauryl Sulfate, sodium docusate, prising: benzalkonium chloride, benzethonium chloride and mixtures (a) a pharmaceutically active Substance; thereof and is contained in an amount of 0.1 to 10 wt % with (b) a chitosan or a salt thereofas a film-forming Substance; respect to the total weight of the composition. and 8. A pharmaceutical composition for wound healing, com (c) a solvent for dissolving the chitosan, prising: wherein the film-forming Substance is presentinanamount (a) a pharmaceutically active Substance; of 0.4 to 20 wt % with respect to the total weight of the (b) a chitosan or a salt thereofas a film-forming Substance; composition, and (c) a solvent for dissolving the chitosan, and wherein: (d) an additive selected from among an acid, a plasticizer, the composition further comprises a cream base compo a thickener, a Surfactant, a preservative, a flavoring nent and the weight ratio of the film-forming Substance agent, a stabilizer, a defoamer, an analgesic agent, an to the cream base component is 1:50 or more; and antioxidant, an adhesive, a gellant, an emulsifier, an the composition forms a film upon application to the skin. astringent, an opacifier, a humectant and mixtures 2. The pharmaceutical composition claim 1, wherein the thereof, cream base component is selected from among isopropyl wherein the film-forming Substance is present in an amount palmitate, cetyl palmitate, paraffin, trioctanoin, soybean oil, of 0.4 to 20 wt % with respect to the total weight of the sesame oil, olive oil, liver oil, oleic acid, Stearic acid octyl composition and the additive is present in an amount of dodecanol, octyldodecyl myristate, a silicone compound, 0.1 to 30 wt % with respect to the total weight of the Stearyl alcohol, Stearyl glycyrrhetinate, polyoxyl Stearate, composition. squalane, cetostearyl alcohol, cetomacrogol, cetanol, Sorbi 9. The pharmaceutical composition of claim 1, wherein the tan sesquioleate, VaselineR petroleum jelly, white beeswax, pharmaceutically active Substance comprises at least one yellow beeswax, myristyl alcohol, isopropyl myristate, Sor selected from among an antibiotic, a wound healing acceler bitan monooleate, Sorbitan monostearate, glycerin ant, a disinfectant or sanitizer and a local anesthetic or anti monostearate, lecithin, hydrogenated castor oil, caprylic-ca inflammatory agent. pric triglyceride, lanolin, oleoyl macrogolglycerides and 10. The pharmaceutical composition of claim 9, wherein mixtures thereof. the pharmaceutically active Substance comprises at least one US 2015/0374641 A1 Dec. 31, 2015 selected from among tyrothricin, fusidic acid or a salt thereof, 15. The pharmaceutical composition of claim 14, wherein neomycin Sulfate or a salt thereof, hydrocortisone, titrated (a) the pharmaceutically active Substance is present in an extract of Centella asiatica and combinations thereof. amount of 0.1 to 10 wt % with respect to the total weight of the 11. The pharmaceutical composition of claim 1, wherein composition, (b) the film-forming Substance is present in an the solvent for dissolving the chitosan is selected from among amount of 0.4 to 20 wt % with respect to the total weight of the water, a lower alcohol having 1 to 4 carbon atoms and mix composition, (d) the acid is present in an amount of 0.20 to 20 tures thereof. wt % with respect to the total weight of the composition, and (e) the thickener is present in an amount of 0.2 to 10 wt % with 12. The pharmaceutical composition of claim 1, wherein respect to the total weight of the composition. the composition is in the form of agel, an ointment, or a liquid 16. The pharmaceutical composition of claim 15, wherein before application to a wound or to skin. paragraphs 47 and (a) the pharmaceutically active Substance is tyrothricin, (b) 50 the film-forming Substance is chitosan, (c) the solvent is 13. A pharmaceutical composition for wound healing, water, (d) the acid is lactic acid, and (e) the thickener is comprising: poloxamer. (a) at least one pharmaceutically active Substance selected 17. A method of wound healing, comprising treating Sub from among tyrothricin, fusidic acid or a salt thereof, ject with a therapeutically effective amount of a pharmaceu neomycin Sulfate or a salt thereof, hydrocortisone, tical composition of claim 1 to protect the wound. titrated extract of Centella asiatica and combinations 18. The method of claim 17, wherein the wounds are thereof; selected from among an incised wound, a lacerated wound, a (b) a chitosan or a salt thereof as a film-forming Substance penetrating wound, a perforated wound, a puncture wound, in an amount of 0.4 to 20 wt % with respect to the total an open wound, a Subcutaneous wound, a closed wound and weight of the composition; and a combination thereof. (c) at least one solvent selected from among ethanol, iso 19. A method for treating a wound, comprising applying propyl alcohol and mixtures thereof, the pharmaceutical composition of claim 8 to a wound of a wherein the composition further comprises a cream base Subject, wherein the pharmaceutical composition forms a component and the weight ratio of the film-forming film after application to protect the wound and improve Substance to the cream base component is 1:50 or more. wound healing. 14. The pharmaceutical composition of claim 13, further 20. (canceled) comprising: 21. The pharmaceutical composition of claim 2, wherein (d) an acid; and the silicone compound is dimethicone or simethicone. (e) a thickener. k k k k k