KR20190106127A - Topical gel comprising fusidicacid with enhanced skin-permeability forming a film on a skin - Google Patents

Abstract

The present invention relates to a skin external gel forming a film when applied to the skin and a manufacturing method thereof, wherein the skin external gel contains: fusidic acid or salts thereof; polyvinyl alcohol and hydroxypropyl cellulose as hydrophilic polymers for film formation; glycerin as a skin permeation enhancer; and water and/or lower alcohol as a solvent as active components.

Description

Topical gel comprising fusidicacid with enhanced skin-permeability forming a film on a skin}

The present invention as an active ingredient fucidinic acid or a salt thereof; Hydrophilic polymers for film formation include polyvinyl alcohol and hydroxypropyl cellulose; Polyethylene glycol as a plasticizer; Glycerin as a skin permeation enhancer; And a pharmaceutical composition for forming a film upon application to the skin, including water and / or a lower alcohol as a solvent, such as a skin external gel, a method for preparing the same, and a method for treating a wound using the same.

A wound is a state in which the anatomical continuity of a human tissue has lost its original continuity by external action. Wounds can be classified in various ways depending on their cause and / or size. In particular, the skin is exposed, so there is a lot of contact with the outside, so large and small wounds are likely to occur, and if the wound is not treated immediately, there is a high risk of secondary infection. Usually, to treat wounds, disinfection, dressings and external antibiotics can be used. If the wound is infected with bacteria, the use of external antibiotics is essential.

This wound healing process can be explained by dividing into hemostasis stage, inflammation stage, proliferation stage, and maturation stage. In the hemostasis stage, damaged blood vessels contract quickly, thrombotic mechanism is activated and bleeding stops. It is responsible for loading the cells. In the inflammatory stage, the foreign body or necrotic tissues in the wound are removed to clean the wound before the wound is repaired. Neutrophils and macrophages play a major role in this stage, preventing infection from the outside, and damaging or dead in the wound. Remove tissue. In the subsequent proliferation phase, cells and extracellular matrix proliferate, and blood vessels begin to form and restore the epithelial layers of the various layers of the skin. In the final stage of maturation, the maturation of the wound occurs with the onset of collagen synthesis by fibroblasts.

Various products have been introduced for a long time to treat wounds and are commercially available. Hydrogen peroxide and povidone iodine used to disinfect wounds, alcohols and various dressing products, and antibiotics and centella asiatica quantitative extracts such as mupirosine, fusidic acid and its salts, tyrotricin, etc. Examples are various gel or ointment products containing.

Conventional gels or ointments can be carried out by a simple method of application to the wound site without the help of a specialist, but the treatment is simple, but due to the nature of the formulation, they do not remain on the wound for a long time and can be applied to the skin and / or into the wound. There is a problem of low transmittance and most of all, it is very likely to be removed by clothes or foreign materials. Accordingly, when applied to the wound, but also using a band, etc. due to this is low breathability, there is a problem that the intra-permeability of the drug is still low.

Therefore, in order to solve this disadvantage, the present inventors have invented a film-forming external gel that has excellent skin permeability and can protect the wound by forming a film when applied to an external gel formulation or wound and skin. For example, Korean Patent No. 10-1457789 discloses a film-forming external gel composition using a polymer base and an organic solvent together with an active material. However, most of these compositions have a high specific gravity of the organic solvent, and may be irritating to the wound surface due to the formulation directly applied to the skin of the wound site, which is not suitable for the external gel for wound treatment. Alternatively, the elasticity of the formed film is difficult to apply to the curved area, or the drug contained therein has a problem of poor permeability into the skin.

Accordingly, the present inventors have studied diligently to provide an external gel formulation containing an antibiotic component, fucidinic acid as an active ingredient, to improve skin permeability of the drug, and to form a film when applied to the skin, which can be used without a support or an adhesive. As a result of the efforts, the external gel prepared by adding hydrophilic polymer polyvinyl alcohol and hydroxypropyl cellulose in a predetermined content and proportion as a film forming material, and adding glycerin as a skin permeation accelerator, has a predetermined elasticity within an appropriate time. The film was able to form, the skin permeability of the drug contained therein was confirmed to show excellent wound healing effect compared to commercially available fucidin in the form of gel, and completed the present invention.

One object of the present invention is a pharmacologically active substance of fusidic acid or a salt thereof; Hydrophilic polymers for film formation include polyvinyl alcohol and hydroxypropyl cellulose; Polyethylene glycol as a plasticizer; Glycerin as a skin permeation enhancer; And it provides a pharmaceutical composition for treating wounds, which forms a film when applied to the skin, including water, C _1-4 alcohol or a mixed solution thereof as an active ingredient as a solvent.

Another object of the present invention is a hydrophilic polymer for film formation, 5 to 15 parts by weight of polyvinyl alcohol and 1 to 10 parts by weight of hydroxypropyl cellulose, based on 1 part by weight of fucidinic acid or a salt thereof as an active ingredient; 0.3 to 1 part by weight of polyethylene glycol as a plasticizer; 0.5 to 5 parts by weight of glycerin as a skin permeation enhancer; And it is to provide a skin external gel to form a film when applied to the skin, comprising a solvent, water, C _1-4 alcohol or a mixed solution thereof 100 parts by weight of the total composition.

Still another object of the present invention is 5 to 15 parts by weight of polyvinyl alcohol, 1 to 10 parts by weight of hydroxypropyl cellulose, 0.3 to 1 part by weight of polyethylene glycol, 0.5 to 5 parts by weight of glycerin, based on 1 part by weight of fucidinic acid or a salt thereof. To provide a method for producing a skin external gel to form a film when applied to the skin, and the step of mixing the water, C _1-4 alcohol or a mixed solution thereof in a reaction vessel so that the total composition is 100 parts by weight will be.

Still another object of the present invention is to apply the pharmaceutical composition or the skin external gel to cover the wound on the site of the wound of the individual; And a second step of maintaining the gel applied to the skin by drying to form a film.

As one embodiment for achieving the above object, the present invention is a pharmacologically active material, a film-forming hydrophilic polymer; Plasticizers; Skin permeation enhancers; And it provides a pharmaceutical composition for treating wounds comprising a solvent as an active ingredient, forming a film when applied to the skin.

For example, the present invention relates to fusidic acid or a salt thereof; Polyvinyl alcohol and hydroxypropyl cellulose; Polyethylene glycol; glycerin; And water, C _1-4 alcohol, or a mixed solution thereof as an active ingredient, to provide a pharmaceutical composition for wound treatment, which forms a film when applied to the skin.

Specifically, the present invention is a pharmacologically active substance of fusidic acid or a salt thereof; Hydrophilic polymers for film formation include polyvinyl alcohol and hydroxypropyl cellulose; Polyethylene glycol as a plasticizer; Glycerin as a skin permeation enhancer; And water, C _1-4 alcohol, or a mixed solution thereof as an active ingredient, and may provide a pharmaceutical composition for treating wounds, wherein the film is formed upon application to the skin.

Fucidinic acid included as an active ingredient in the pharmaceutical composition of the present invention may be present in the form of salts thereof, particularly pharmaceutically acceptable salts. As the salt, salts conventionally used in the art may be used without limitation, such as acid addition salts formed by pharmaceutically acceptable free acid. The term "pharmaceutically acceptable salt" of the present invention is any non-organic or organic of any of the above compounds in which concentrations having relatively nontoxic and harmless effective action in the patient do not cause side effects due to this salt to degrade the beneficial efficacy of fusidic acid. It means inorganic addition salt.

Acid addition salts are prepared by conventional methods, for example by dissolving a compound in an excess of aqueous acid solution and precipitating the salt using a water miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. Equivalent molar amounts of the compound and acid or alcohol (eg, glycol monomethyl ether) in water can be heated and the mixture can then be evaporated to dryness or the precipitated salts can be suction filtered.

In this case, organic acids and inorganic acids may be used as the free acid, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc. may be used as the inorganic acid, and methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, and maleic acid may be used as the organic acid. (maleic acid), succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid (gluconic acid), galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanic acid, hydroiodic acid, etc. It is not limited to these.

Bases can also be used to make pharmaceutically acceptable metal salts. Alkali metal salts or alkaline earth metal salts are obtained, for example, by dissolving a compound in an excess of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and then evaporating and drying the filtrate. In this case, as the metal salt, it is particularly suitable to prepare sodium, potassium, or calcium salt, but is not limited thereto. Corresponding silver salts can also be obtained by reacting an alkali or alkaline earth metal salt with a suitable silver salt (eg silver nitrate).

Pharmaceutically acceptable salts of the compounds of the invention include salts of acidic or basic groups which may be present in fusidic acid, unless otherwise indicated. For example, pharmaceutically acceptable salts may include sodium, calcium and potassium salts of the hydroxy group, and other pharmaceutically acceptable salts of the amino group include hydrobromide, sulfate, hydrogen sulphate, phosphate, hydrogen phosphate , Dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts, and the like. It can be prepared through the method. Specifically, the pharmaceutical composition of the present invention may include, but is not limited to, fusidic acid sodium salt.

The pharmaceutical composition of the present invention includes both polyvinyl alcohol and hydroxypropyl cellulose as hydrophilic polymers, and includes 5 to 15 parts by weight and 1 to 10 parts by weight with respect to 1 part by weight of fucidinic acid or a salt thereof. It is characteristic. The polyvinyl alcohol and hydroxypropyl cellulose are both polymers used in cosmetic compositions and the like, which are approved as harmless substances to the human body. Since the pharmaceutical composition of the present invention contains both of these polymers, the time required for film formation is significantly shorter than that of one component such as polyvinyl alcohol, even though the total high molecular weight thereof is the same. Was increased (Example 3 vs. Comparative Example 1).

However, it is preferable that the total content of the polyvinyl alcohol and hydroxypropyl cellulose does not exceed 20 parts by weight with respect to 1 part by weight of fusidic acid or a salt thereof. For example, film formation may be difficult when the total content of the hydrophilic polymer exceeds 20 parts by weight. In other words, even after 30 minutes of application to the skin, the film still can not be formed and the gel form can be maintained. In a specific embodiment of the present invention, the external gel composition containing only 18 parts by weight of polyvinyl alcohol or 12 parts by weight of polyvinyl alcohol and hydroxypropyl cellulose, and a total of 24 parts by weight of hydrophilic polymer does not form a film. It was confirmed.

For example, the pharmaceutical composition of the present invention may include polyethylene glycol as a plasticizer, and the polyethylene glycol may be included in an amount of 0.3 to 1 part by weight based on 1 part by weight of fusidic acid or a salt thereof, but is not limited thereto. However, when the content of the plasticizer in the composition is lower than the above range, if the film formation is delayed or severe, it may not be possible to form the film at all, and when the content of the plasticizer exceeds the above range, the film formation time may be shortened. As a result, the physical properties of the formed film may be poor, and thus, the tensile strength may be weakened, and thus it may not be used for a desired purpose.

For example, the pharmaceutical composition of the present invention may include glycerin as a skin permeation enhancer. The glycerin may be included in an amount of 0.5 to 5 parts by weight based on 1 part by weight of fusidic acid or a salt thereof, but is not limited thereto. Glycerin (e) is a simple polyol compound, also called glycerol, which is a viscous liquid with a colorless, odorless sweet taste and nontoxic. It is also used as a sweetener in the food industry, and is widely used as a moisturizer or humectant in pharmaceutical compositions or cosmetic compositions. It has three hydroxyl groups in the molecule, so that it is water-soluble and hygroscopic. As described above, glycerin is a substance used as a moisturizer or humectant in the pharmaceutical composition, but the pharmaceutical composition of the present invention is characterized by including it as a skin permeation enhancer. In a specific embodiment of the present invention, while maintaining the content of the other components and a series of external gels were prepared while varying the content of water and glycerin and the skin permeability thereof was measured, as a result of increasing the content of glycidyl fusidic acid It was confirmed that the skin permeability of the increase (Fig. 1).

The solvent may be a solution in which water and C _1-4 alcohol are mixed at a weight ratio of 8: 1 to 12: 1, but are not limited thereto. However, if the content of alcohol is lower than the above range, it may require a long time until the film formation is delayed and completely dried when applied to the skin, if the alcohol content is higher than the above range is volatilized even under normal storage conditions It can be difficult to store and use for a long time because it can be solidified without maintaining the external gel state.

As the C _1-4 alcohol, ethanol having a low toxicity and / or irritation to the human body may be used, but is not limited thereto. Conventional film-forming external gels use other volatile organic solvents for faster drying, but most organic solvents can be harmful or irritating to the human body. It is desirable to avoid.

The pharmaceutical composition of the present invention is a formulation that is attached to the skin by directly applying to the wound site without the aid of any support or adhesive to form a film, in order to prevent peeling or tearing easily due to bending or movement of the body. It is preferable that the film formed at the time of application has predetermined elasticity and / or adhesiveness. For example, the film formed when applied to the skin is 0.00015 to 0.00038 It may have a Young's modulus of N / mm ² . Specifically, the film is 0.00016 to 0.00037 N / mm ² or 0.000163 to 0.000365 It may have a Young's modulus of N / mm ² , but is not limited thereto. If the Young's modulus is out of the above range, it can be easily peeled off or torn by the body's movement.

By applying a pharmaceutical composition according to the invention (brush-bur, abrasion or scratch); Burn; Bite; Cartilage window; It can not only heal wounds caused by stabs, wounds, lacerations, or stitches or sutures thereof; and / or skin diseases such as impetigo, folliculitis, swelling, purulent adenitis In addition, it is possible to prevent secondary infections that may occur in the wound site.

Infections that can be prevented using the pharmaceutical composition according to the present invention include Staphylococcus, Staphylococcus, Streptococcus, Corynebacterium, and Clostridium (Staphylococcus aureus). It may be due to gram positive bacteria such as Clostridium and gram negative bacteria such as Pseudomonas, but is not limited thereto.

When applied to the wound, it can be achieved by forming a film to block the access of external foreign substances and at the same time percutaneous absorption of the active ingredient contained therein. The pharmaceutical composition of the present invention can physically block the foreign body including bacteria from contacting the wound site by forming a film upon skin application. Furthermore, since fusidic acid or a salt thereof, which is an active ingredient contained in the pharmaceutical composition of the present invention, exhibits antimicrobial activity, the infection is reduced by the antibacterial action of percutaneously absorbed fusidic acid even if it is infected by a strain. You can block.

Treatment of wounds or prevention of secondary infection thereof by the pharmaceutical composition of the present invention can be achieved by blocking the infection of Pseudomonas aeruginosa or Staphylococcus aureus, but is not limited thereto. In a specific embodiment of the present invention, animal wounds, causing wounds, showing a higher wound recovery rate than the commercially available fucidin gel when applied to the wound skin infected with Pseudomonas aeruginosa and Staphylococcus aureus on the site, It was confirmed (Fig. 2).

In addition, the pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier, diluent or excipient in addition to the active ingredient. It can be used in various forms such as powder, granules, tablets, capsules, suspensions, oral formulations such as emulsions, syrups, aerosols, injections of sterile injectable solutions, etc. Administration may be through a variety of routes including intravenous, intraperitoneal, subcutaneous, rectal, topical, and the like. Examples of suitable carriers, excipients or diluents that may be included in such compositions include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like. In addition, the compositions of the present invention may further include fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers, preservatives and the like.

For example, the pharmaceutical composition of the present invention may be provided in the formulation of the external skin gel, but is not limited thereto.

As another aspect, the present invention is a hydrophilic polymer for film formation, 5 to 15 parts by weight of polyvinyl alcohol and 1 to 10 parts by weight of hydroxypropyl cellulose relative to 1 part by weight of fucidinic acid or a salt thereof as an active ingredient; 0.3 to 1 part by weight of polyethylene glycol as a plasticizer; 0.5 to 5 parts by weight of glycerin as a skin permeation enhancer; And it provides a skin external gel to form a film when applied to the skin, including a solvent, water, C _1-4 alcohol or a mixed solution thereof to 100 parts by weight of the total composition. At this time, the total amount of the hydrophilic polymer is preferably used does not exceed 20 parts by weight.

As another aspect, the present invention, 5 to 15 parts by weight of polyvinyl alcohol, 1 to 10 parts by weight of hydroxypropyl cellulose, 0.3 to 1 part by weight of polyethylene glycol, 0.5 to 5 parts by weight of glycidyl acid or salt thereof Provided is a method for producing a skin external gel to form a film upon application to the skin, comprising the step of mixing in a reaction vessel so that the total composition is 100 parts by weight of water, C _1-4 alcohol or a mixture thereof. do. At this time, the total amount of the hydrophilic polymer is preferably used does not exceed 20 parts by weight.

The reaction does not require demanding reaction conditions and can be achieved by simply mixing at room temperature.

In another aspect, the present invention is Applying the pharmaceutical composition or the external skin gel according to the present invention to cover the wound on the site where the wound of the individual has occurred; And a second step of maintaining the gel applied to the skin by drying to form a film.

The term "individual" of the present invention means all animals including monkeys, cows, horses, sheep, pigs, chickens, turkeys, quails, cats, dogs, mice, rats, rabbits or guinea pigs, including the wounded human. In addition, by administering the pharmaceutical composition of the present invention to the individual, not only can the wound caused thereon be effectively treated, but also the secondary infection which can be caused therefrom can be prevented.

The amount of the pharmaceutical composition or the external skin gel according to the present invention is not limited as long as it can sufficiently cover the wound, and may be appropriately changed depending on the size and / or depth of the wound. For example, the pharmaceutical composition or the skin external gel may be applied to a width and about 0.1 to 2 mm thick enough to cover the wound, but is not limited thereto. However, when applied too thin, it may be difficult to sufficiently protect and / or heal wounds due to easy wear or tear, and when applied too thick, it not only consumes a lot of drugs unnecessarily, but also takes a long time to form a film, requiring a long time waiting. Can get on clothing if it is inadvertently moved.

The drying can be carried out by holding for about 8 to 20 minutes. In addition, the drying can be achieved by natural drying, which does not require separate conditions, which are simply kept exposed to air for a predetermined time.

The skin external gel of the present invention includes a polyvinyl alcohol and hydroxypropyl cellulose as a hydrophilic polymer for film formation, and includes glycerin as a skin permeation enhancer to form a film within a suitable time when applied to the skin, as well as skin permeability of the drug. The improved external skin gel for wound treatment is provided, and due to the antimicrobial properties of fusidic acid as an active ingredient contained therein, it is possible to effectively prevent wound healing as well as secondary infection caused therefrom.

1 is a view showing the skin permeability of the external gels of Examples 3 to 5 and commercially available fucidin gel according to the present invention.
2 is a view showing the rate of wound treatment over time of the group treated with the external gel of Example 4 according to the present invention and the commercially available fucidin gel and the untreated group covering only the gauze on the wound without drug.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are intended to illustrate the present invention more specifically, but the scope of the present invention is not limited by these examples.

Example  1 to 8: Fucidinic acid  Containing film forming skin External gel  Produce

Sodium fucidate as an active ingredient, poly (vinyl alcohol; PVA) and hydroxypropyl cellulose (HPC) as a hydrophilic polymer for film formation, and polyethylene glycol as a plasticizer PEG) was prepared by dissolving glycerin as a skin permeation enhancer and water and ethanol as a solvent in a reaction vessel and completely dissolving using a mechanical mixer. Eight samples were prepared by varying the composition of each component. The composition of each sample is shown in Table 1 by weight percent. At this time, the amount of water was adjusted to 100% of the total composition.

ingredient Example One 2 3 4 5 6 7 8 Sodium fucidinate One One One One One One One One PVA 6 8 10 10 10 10 10 12 HPC 2 2 2 2 2 4 8 4 PEG 1500 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 glycerin 2.5 2.5 2.5 3.5 One 2.5 2.5 2.5 ethanol 8 8 8 8 8 8 8 8 water 80 78 76 75 77.5 74 70 72

Comparative example  1 to 4: Fucidinic acid  Preparation of Containing Pharmaceutical Compositions

The pharmaceutical compositions of Comparative Examples 1 to 4 were prepared by the composition shown in Table 2 by excluding some of the compositions or adjusting the contents from the compositions of the examples. Differences in the composition resulting from the absence of specific ingredients or changes in content were adjusted to the total weight by adjusting the amount of water used.

ingredient Comparative example One 2 3 4 Sodium fucidinate One One One One PVA 12 8 12 12 HPC - - 12 - PEG 1500 0.5 0.5 0.5 - glycerin 2.5 2.5 2.5 - ethanol 8 8 8 8 water 76 70 64 79

Experimental Example  1: Evaluate film formation time

0.1 g of the compositions of Examples 1 to 8 and Comparative Examples 1 to 4 were evenly applied to the skin in a size of 2 cm × 2 cm, respectively, and the time until the film was formed was measured. It was confirmed that the film was formed on the basis that the contents did not come out when contacted by hand.

division Film formation time (minutes) division Film formation time (minutes) Example 1 18.6 ± 3.1 Example 2 18.2 ± 3.3 Example 3 8.6 ± 1.1 Example 4 10.2 ± .15 Example 5 8.2 ± 1.2 Example 6 12.4 ± 1.7 Example 7 14.9 ± 1.7 Example 8 20.3 ± 1.1 Comparative Example 1 21.4 ± 2.3 Comparative Example 2 Unformed film Comparative Example 3 Unformed film Comparative Example 4 24.3 ± 2.9

As shown in Table 3, Comparative Examples 2 and 3 containing only PVA in a high content prepared by adjusting the content of the hydrophilic polymer, or the sum of PVA and HPC was found to fail to form a film . On the other hand, in the case of Comparative Example 1 containing only 12% by weight of PVA, but the film was formed, it was confirmed that takes a long time compared to Examples 1 to 8. In particular, in Example 3 containing PVA and HPC in the same weight percent, film formation was completed in 8.6 minutes, but in Comparative Example 1 including only PVA without HPC, about 2.5 times of the time was required. This indicates that including both PVA and HPC in the film-forming external gel but including them in an appropriate ratio and / or content is an important factor for film formation. Furthermore, although the film was formed in Comparative Example 4 including only PVA and not including a plasticizer, PEG and a skin permeation enhancer, glycerin, a longer time was required.

Experimental Example  2: evaluation of the physical properties of the formed film

Considering that the composition of the present invention is a skin external gel applied to the skin without the aid of a substrate or an adhesive, the film formed by applying to the skin to maintain it without being easily detached or damaged by the bending of the skin or the movement of the body has a predetermined elastic force. It is necessary to have Thus, Young's modulus of the film of the compositions of Examples 1 to 8 and Comparative Examples 1 to 4 was measured, and the results are shown in Table 4 below. Young's modulus is defined as the ratio of tensile strength to elongation at break, and the formed films were fixed to a probe and subjected to a constant force, measured by a texture analyzer (Micro systems).

division Young's modulus (N / mm ² ) division Young's modulus (N / mm ² ) Example 1 0.000231 Example 2 0.000225 Example 3 0.000206 Example 4 0.000165 Example 5 0.000304 Example 6 0.000293 Example 7 0.000331 Example 8 0.000363 Comparative Example 1 0.000387 Comparative Example 2 Not measurable Comparative Example 3 Not measurable Comparative Example 4 0.001028

As shown in Table 5, Examples 1 to 8 are 0.000363 N / mm ² Comparative Examples 1 and 4, except for Comparative Examples 2 and 3, which exhibited low values below, that is, relatively high elasticity, but failed to form films, had high Young's modulus of 0.000387 N / mm ² and 0.001028 N / mm ² , respectively. Value, that is, low elastic force. Further, Examples 1 to 8 exhibited various Young's modulus values in the range of at least 0.000165 N / mm ² to at most 0.000363 N / mm ² , indicating that the modulus of elasticity can be adjusted by adjusting the ratio of each component of the composition. .

Experimental Example  3: skin permeation evaluation

The composition of the present invention is applied to the skin to deliver a pharmacologically active substance through the percutaneous absorption into the skin to achieve a therapeutic effect, it is also important to enhance skin permeation. Thus, by using the compositions of Examples 3 to 5 showing the excellent effect from Experimental Examples 1 and 2 was evaluated by comparing the release characteristics with commercially available fucidin gel.

Specifically, the Franz diffusion cell method using the skin of a hairless mouse was used while maintaining the temperature of 37 ° C. and 600 rpm. Using 250 mg of each composition, drug release was measured by HPLC at 365 nm with 0.5 mL of PBS buffer at pH 7.4 at 1, 2, 4, 6, 9, 12 and 24 hours and the results are shown in FIG. 1. It was. As shown in Figure 1, the composition of Examples 3 to 5 according to the present invention increased cumulative release amount over time, that is, the continuous release of the drug, the high content of glycerin used as a skin permeation enhancer Example 4> Example 3> The high emission rate was shown in the order of Example 5. On the other hand, commercially available fucidin gel hardly released the drug. This indicates that the pharmaceutical composition of the present invention, such as the external gel preparation, has significantly improved skin permeation of fusidic acid, a pharmacologically active substance, and glycerin plays a role in promoting skin permeation.

Experimental Example  4: wound recovery evaluation

Using the composition of Example 4 showing the best drug release effect in Experimental Example 3 was confirmed whether the effect on the actual wound recovery. A commercially available fucidin gel was used for comparison, and a simple gauze was treated as a negative control group.

Specifically, SD rats having an average age of 6 to 8 weeks and a weight of 250 to 300 g were used for 1 week. General breeding room (temperature 23 ± 2 ℃, humidity 55-60%, lighting from 7 am to 7 pm) was raised until the end of the experiment, and the general feed and purified water were supplied. During the acclimation period, rats without any abnormality were anesthetized with ketamine and xylazine, depilated and disinfected skin, and cut off the skin with scissors to cause 10 mm × 10 mm wounds, thereby causing Pseudomonas aeruginosa and yellow Wounds were induced by infection with Staphylococcus. Example 4, after commercially available dressings with fucidin gel and a simple gauze, visually observed with time and at the same time measuring the wound area using a grid paper to obtain the size and the recovery rate is calculated by the following equation and the results are shown in FIG. Indicated.

As shown in Figure 2, the treatment of the composition of Example 4 showed the best wound recovery rate. On the other hand, the commercially available fucidin gel showed a lower wound recovery rate than the negative control group.

Claims (15)

As pharmacologically active substance, fusidic acid or a salt thereof; Hydrophilic polymers for film formation include polyvinyl alcohol and hydroxypropyl cellulose; Polyethylene glycol as a plasticizer; Glycerin as a skin permeation enhancer; And water, C _1-4 alcohol or a mixed solution thereof as a solvent as an active ingredient, a pharmaceutical composition for wound treatment forming a film when applied to the skin.
The method of claim 1,
The polyvinyl alcohol and hydroxypropyl cellulose, 5 to 15 parts by weight and 1 to 10 parts by weight with respect to 1 part by weight of fusidic acid or salts thereof, pharmaceutical composition for wound treatment.
The method of claim 2,
The total content of the polyvinyl alcohol and hydroxypropyl cellulose, does not exceed 20 parts by weight with respect to 1 part by weight of fusidic acid or salts thereof, pharmaceutical composition for wound treatment.
The method of claim 1,
The polyethylene glycol, it comprises 0.3 to 1 part by weight with respect to 1 part by weight of fucidinic acid or salts thereof, pharmaceutical composition for wound treatment.
The method of claim 1,
Wherein the glycerin, 1 to 5 parts by weight of fucidinic acid or a salt thereof, containing 0.5 to 5 parts by weight, pharmaceutical composition for wound treatment.
The method of claim 1,
Wherein the solvent is a mixed solution of 8: 1 to 12: 1 by weight ratio of water and C _1-4 alcohol, pharmaceutical composition for wound treatment.
The method of claim 1,
The C _1-4 alcohol is ethanol, pharmaceutical composition for wound treatment.
The method of claim 1,
The film formed when applied to the skin is 0.00015 to 0.00038 It has a Young's modulus of N / mm ² , pharmaceutical composition for wound treatment.
The method of claim 1,
The wound is a scratch, or wound, wound, laceration, or a suture portion thereof, pharmaceutical composition for treating a wound.
The method of claim 1,
When applied to the wound site to form a film to block the access of foreign foreign materials and at the same time achieved by the percutaneous absorption of the active ingredient contained therein, the pharmaceutical composition for wound treatment.
The method of claim 1,
What is achieved by blocking the infection of Pseudomonas aeruginosa or Staphylococcus aureus, pharmaceutical composition for wound treatment.
The method of claim 1,
Having a formulation of an external gel for skin, pharmaceutical composition for wound treatment.
5 to 15 parts by weight of polyvinyl alcohol and 1 to 10 parts by weight of hydroxypropyl cellulose as a hydrophilic polymer for film formation, based on 1 part by weight of fucidinic acid or a salt thereof as an active ingredient; 0.3 to 1 part by weight of polyethylene glycol as a plasticizer; 0.5 to 5 parts by weight of glycerin as a skin permeation enhancer; And a skin external gel for forming a film upon application to the skin, the solvent comprising water, C _1-4 alcohol or a mixed solution thereof so that the total composition is 100 parts by weight,
The total amount of the hydrophilic polymer does not exceed 20 parts by weight of the skin external gel.
5 to 15 parts by weight of polyvinyl alcohol, 1 to 10 parts by weight of hydroxypropyl cellulose, 0.3 to 1 part by weight of polyethylene glycol, 0.5 to 5 parts by weight of glycerin, and water, C ₁ with respect to 1 part by weight of fucidinic acid or a salt thereof. _A method for producing a skin external gel for forming a film upon application to the skin, the method comprising: mixing the alcohol or a mixed solution thereof in a reaction container so that the total composition is 100 parts by weight,
The total amount of the hydrophilic polymer used does not exceed 20 parts by weight.
Claim 1 to 12, wherein the pharmaceutical composition of any one of claims 1 to 12 or the topical skin gel of claim 12 to apply to cover the wound on the site of the wound of animals other than human; And
A method of treating a wound or a secondary infection thereof comprising a second step of maintaining the gel applied to the skin by drying to form a film.

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