KR20230124821A - Wound healing composition comprising probiotics and metal ion-tannic acid - Google Patents

Abstract

The present specification relates to a composition for treating and/or improving wounds including metal ion-tannic acid and probiotics.

Description

Wound healing composition comprising probiotics and metal ion-tannic acid

The present specification relates to a pharmaceutical and / or cosmetic composition for treating and / or improving wounds containing probiotics, metal ions and tannic acid, and a dressing containing the composition.

Materials used in wound treatment should reduce the period of wound healing due to epithelialization, should not cause discomfort due to bleeding or pain during replacement, and should be capable of minimizing scar formation after epithelialization. In addition, the secondary infection rate (secondary infection rate) is low, and it should be easily available because it is easy to manufacture and store. Based on this, in order to promote wound healing, a wet dressing agent applying moist wound healing to the wound is used, and the effect of helping epithelial regeneration can be seen.

Probiotics are microorganisms that have a beneficial effect on the human body and have the ability to assist the body's immune system and reduce inflammatory responses. It has been reported that Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Enterococcus and Klebsiella, which show multi drug resistance, have excellent antibacterial activity. In addition, it reduces the risk of tissue infection during the wound regeneration process and helps in angiogenesis, showing good effects on wound recovery. However, probiotics have a property of rapidly decomposing when exposed to heat or organic solvents, so it is necessary to develop probiotics with improved stability by using strains with excellent heat resistance and methods such as coating for probiotics with improved stability.

Among various coating methods, tannic acid (TA) derived from secondary metabolites of plants has a galloyl group (1,2,3-trihydroxyphenyl group) and is used as a coating material. Tannic acid is a natural substance that can help heal wounds through its antibacterial effect. Coordination complexes of tannic acid and metal cations such as Fe(III) or Fe(II) can form a coating layer with controllable thickness for virtually any material, and each constituent material is a material generally recognized as safe. safe, GRAS) and is cytocompatible.

In order to solve the above limitations, the present inventors coated probiotics with ferric ion-tannic acid, developed a wound healing dressing containing the material, and confirmed the excellent shape, number of bacteria, elasticity and expansion rate of the dressing.

An example of this specification is,

Provided is a pharmaceutical and/or cosmetic composition for treating and/or improving wounds, including probiotics, metal ions and tannic acid.

Another example of this specification is,

It provides a dressing agent comprising the composition.

An example of this specification is

Provided is a pharmaceutical and/or cosmetic composition for treating and/or improving wounds, including probiotics, metal ions and tannic acid.

The composition may include a particle form in which the probiotics are coated with metal ions and/or tannic acid, but is not limited thereto.

The metal ion and tannic acid may be included in the form of a metal ion-tannic acid complex, but is not limited thereto.

The probiotics are Lactobacillus brevis, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus casei, lactobacillus It may be at least one selected from the group consisting of Lactobacillus bulgaricus, Lactobacillus fermentum and Lactobacillus salivarius, but is not limited thereto.

The metal ion is iron ion (Fe), aluminum (Al), vanadium (V), manganese (Mn), iron (Fe), zinc (Zn), zirconium (Zr), molybdenum (Mo), ruthenium ( It may be at least one selected from the group consisting of Ru), rhodium (Rh), cerium (Ce), europium (Eu), gadolinium (Gd), and terbium (Tb), but is not limited thereto.

The composition contains 10 ⁴ to 10 ¹² CFU, 10 ⁵ to 10 ¹² CFU, 10 ⁶ to 10 ¹² CFU, 10 ⁷ to 10 ¹² CFU, 10 ⁸ to 10 ¹² CFU, 10 ⁹ to 10 12 ^CFU per 10 g of the composition. CFU, 10 ¹⁰ to 10 ¹² CFU, 10 ⁴ to 10 ¹¹ CFU, 10 ⁵ to 10 ¹¹ CFU, 10 ⁶ to 10 ¹¹ CFU, 10 ⁷ to 10 ¹¹ CFU, 10 ⁸ to 10 ¹¹ CFU, 10 ⁹ to 10 ¹¹ CFU , 10 ¹⁰ to 10 ¹¹ CFU, 10 ⁴ to 10 ¹⁰ CFU, 10 ⁵ to 10 ¹⁰ CFU, 10 ⁶ to 10 ¹⁰ CFU, 10 ⁷ to 10 ¹⁰ CFU, 10 ⁸ to 10 ¹⁰ CFU, or 10 ⁹ to 10 ¹⁰ CFU It may be included in an amount of, for example, 10 ¹⁰ It may include an amount of CFU, but is not limited thereto.

The composition contains the probiotics in an amount of 10 ⁴ to 10 ¹² CFU ^, 10 ⁵ to 10 ¹² CFU, 10 ⁶ to 10 ¹² CFU, 10 ⁷ to 10 ¹² CFU, 10 ⁸ to 10 ¹² CFU, 10 ⁹ to 10 ¹² CFU, 10 ¹⁰ to 10 ¹² CFU, 10 ⁴ to 10 ¹¹ CFU, 10 ⁵ to 10 ¹¹ CFU, 10 ⁶ to 10 ¹¹ CFU, 10 ⁷ to 10 ¹¹ CFU, 10 ⁸ to 10 ¹¹ CFU, 10 ⁹ to 10 ¹¹ CFU, 10 ¹⁰ to 10 ¹¹ CFU, 10 ⁴ to 10 ¹⁰ CFU, 10 ⁵ to 10 ¹⁰ CFU, 10 ⁶ to 10 ¹⁰ CFU, 10 ⁷ to 10 ¹⁰ CFU, 10 ⁸ to 10 ¹⁰ CFU, or 10 ⁹ to 10 ¹⁰ CFU may be included in an amount, for example, it may be included in an amount of 10 ¹⁰ CFU, but is not limited thereto.

The composition may further include a biocompatible polymer, and the biocompatible polymer may include polyacrylic acid, polyvinyl pyrrolidone, hydroxyalkyl cellulose, carbomer , Polyvinyl alcohol, Chitosan, Alginate, Carboxymethyl Cellulose, Poly(hexamethylenebiguanide), Carrageenan, Polyethylene oxide oxide), polysaccharide, collagen, gelatin, hyaluronic acid, xanthan gum, acacia gum, arginic acid, agar ( Agar), Gum arabic, Tragacanth, Karaya gum, Pectin, Mannitol, Poloxamer, Guar gum, Polyethylene glycol (polyethylene glycol; PEG) (eg, polyethylene glycol 6000), dextran, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose. It is not limited.

The composition contains 0.1 to 50 g, 0.1 to 30 g, 0.1 to 20 g, 0.1 to 15 g, 0.1 to 12 g, 0.1 to 10 g, 0.1 to 5 g, 0.1 to 4 g, 0.1 to 3 g per 10 ¹⁰ CFU of probiotics in the composition. , 0.1 to 2 g, 0.1 to 1 g, 0.5 to 50 g, 0.5 to 30 g, 0.5 to 20 g, 0.5 to 15 g, 0.5 to 12 g, 0.5 to 10 g, 0.5 to 5 g, 0.5 to 4 g, 0.5 to 3 g, 0.5 to 2 g, 0.5 to 1 g, 0.8 to 50 g, 0.8 to 30 g, 0.8 to 20 g, 0.8 to 15 g, 0.8 to 12 g, 0.8 to 10 g, 0.8 to 5 g, 0.8 to 4 g, 0.8 to 3 g, 0.8 to 2 g, 0.8 to 1 g, 1 to 50 g , 1 to 30 g, 1 to 20 g, 1 to 15 g, 1 to 12 g, 1 to 10 g, 1 to 5 g, 1 to 4 g, 1 to 3 g, 1 to 2 g, 2 to 50 g, 2 to 30 g, 2 to 20 g, 2 to 15 g, 2 to 12 g, 2 to 10 g, 2 to 5 g, 2 to 4 g, 2 to 3 g, 3 to 50 g, 3 to 30 g, 3 to 20 g, 3 to 15 g, 3 to 12 g, 3 to 10 g, 3 to 5 g , 3 to 4 g, 5 to 50 g, 5 to 30 g, 5 to 20 g, 5 to 15 g, 5 to 12 g, 5 to 10 g, 8 to 50 g, 8 to 30 g, 8 to 20 g, 8 to 15 g, 8 to 12 g, 8 to 10 g, 10 to 50 g, 10 to 30 g, 10 to 20 g, 10 to 15 g, or 10 to 12 g, and may include, for example, 1, 2, 3, or 10 g, but is not limited thereto.

Another example provided herein is,

It provides a dressing agent comprising the above composition.

Another example provided herein is,

Provides a wound treatment method and/or wound improvement method comprising the step of applying a pharmaceutical and/or cosmetic composition for wound treatment and/or improvement containing probiotics, metal ions and tannic acid to a wound or attaching it to a wound .

In the wound treatment method and/or wound improvement method, the composition may include a particle form in which the probiotics are coated with metal ions and/or tannic acid, but is not limited thereto.

It may be in the form, but is not limited thereto.

The metal ion and tannic acid may be included in the form of a metal ion-tannic acid complex, but is not limited thereto.

In the wound treatment method and/or wound improvement method, probiotics include Lactobacillus brevis, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus rhamnosus, It may be at least one selected from the group consisting of Lactobacillus casei, Lactobacillus bulgaricus, Lactobacillus fermentum and Lactobacillus salivarius, and is limited thereto no.

In the wound treatment method and/or wound improvement method, the metal ion is iron ion (Fe), aluminum (Al), vanadium (V), manganese (Mn), iron (Fe), zinc (Zn), zirconium (Zr) , molybdenum (Mo), ruthenium (Ru), rhodium (Rh), cerium (Ce), europium (Eu), gadolinium (Gd), and terbium (Tb). it is not going to be

In the wound treatment method and/or wound improvement method, the composition contains the probiotics in an amount of 10 ⁴ to 10 ¹² CFU, 10 ⁵ to 10 ¹² CFU, 10 ⁶ to 10 ¹² CFU, 10 ⁷ to ^{10 12} CFU, 10 ⁸ per 10 g of the composition. to 10 ¹² CFU, 10 ⁹ to 10 ¹² CFU, 10 ¹⁰ to 10 ¹² CFU, 10 ⁴ to 10 ¹¹ CFU, 10 ⁵ to 10 ¹¹ CFU, 10 ⁶ to 10 ¹¹ CFU, 10 ⁷ to 10 ¹¹ CFU, 10 ⁸ to 10 ¹¹ CFU, 10 ⁹ to 10 ¹¹ CFU, 10 ¹⁰ to 10 ¹¹ CFU, 10 ⁴ to 10 ¹⁰ CFU, 10 ^{5 to 10 10 CFU, 10 6 to 10 10} CFU, 10 ⁷ to 10 ¹⁰ CFU, 10 ⁸ to 10 ¹⁰ CFU, or 10 ⁹ to 10 ¹⁰ CFU may be included in the amount, for example, 10 ¹⁰ CFU may be included in the amount, but is not limited thereto.

In the wound treatment method and/or wound improvement method, the composition contains the probiotics in an amount of 10 ⁴ to 10 ¹² CFU or 10 ⁵ to 10 ¹² CFU per 10 cm ² of the composition (eg, in the case of a semi-solid or solid formulation such as a patch or patch). , 10 ⁶ to 10 ¹² CFU, 10 ⁷ to 10 ¹² CFU, 10 ⁸ to 10 ¹² CFU, 10 ⁹ to 10 ¹² CFU, 10 ¹⁰ to 10 ¹² CFU, 10 ⁴ to 10 ¹¹ CFU, 10 ⁵ to 10 ¹¹ CFU, 10 ⁶ to 10 ¹¹ CFU, 10 ⁷ to 10 ¹¹ CFU, 10 ⁸ to 10 ¹¹ CFU, 10 ⁹ to 10 ¹¹ CFU, 10 ¹⁰ to 10 ¹¹ CFU, 10 ⁴ to 10 ¹⁰ CFU, 10 ⁵ to 10 ¹⁰ CFU, 10 ⁶ to 10 ¹⁰ CFU, 10 ⁷ to 10 ¹⁰ CFU, 10 ⁸ to 10 ¹⁰ CFU, or 10 ⁹ to 10 ¹⁰ CFU may be included in an amount, for example, it may be included in an amount of 10 ¹⁰ CFU, limited thereto. it is not going to be

In the wound treatment method and/or wound improvement method, the composition may further include a biocompatible polymer, and the biocompatible polymer includes polyacrylic acid, polyvinyl pyrrolidone, and hydroxyalkyl cellulose. (Hydroxyalkyl cellulose), Carbomer, Polyvinyl alcohol, Chitosan, Alginate, Carboxymethyl Cellulose, Poly(hexamethylenebiguanide) , Carrageenan, Polyethylene oxide, polysaccharide, Collagen, Gelatin, Hyaluronic acid, Xanthan gum, Acacia gum , Alginic acid, Agar, Gum arabic, Tragacanth, Karaya gum, Pectin, Mannitol, Poloxamer , guar gum (polyethylene glycol; PEG), dextran (dextran), hydroxypropyl cellulose (hydroxypropyl cellulose) and hydroxypropyl methyl cellulose (hydroxypropyl methyl cellulose) can be one or more selected from the group consisting of Yes, but not limited thereto.

In the wound treatment method and/or wound improvement method, the composition contains the biocompatible polymer in an amount of 0.1 to 50g, 0.1 to 30g, 0.1 to 20g, 0.1 to 15g, 0.1 to 12g, 0.1 to 10g, 0.1 to 10g per 10 ¹⁰ CFU of probiotics in the composition. to 5 g, 0.1 to 4 g, 0.1 to 3 g, 0.1 to 2 g, 0.1 to 1 g, 0.5 to 50 g, 0.5 to 30 g, 0.5 to 20 g, 0.5 to 15 g, 0.5 to 12 g, 0.5 to 10 g, 0.5 to 5 g, 0.5 to 4 g , 0.5 to 3 g, 0.5 to 2 g, 0.5 to 1 g, 0.8 to 50 g, 0.8 to 30 g, 0.8 to 20 g, 0.8 to 15 g, 0.8 to 12 g, 0.8 to 10 g, 0.8 to 5 g, 0.8 to 4 g, 0.8 to 3 g, 0.8 to 2 g, 0.8 to 1 g, 1 to 50 g, 1 to 30 g, 1 to 20 g, 1 to 15 g, 1 to 12 g, 1 to 10 g, 1 to 5 g, 1 to 4 g, 1 to 3 g, 1 to 2 g, 2 to 50 g , 2 to 30 g, 2 to 20 g, 2 to 15 g, 2 to 12 g, 2 to 10 g, 2 to 5 g, 2 to 4 g, 2 to 3 g, 3 to 50 g, 3 to 30 g, 3 to 20 g, 3 to 15 g, 3 to 12 g, 3 to 10 g, 3 to 5 g, 3 to 4 g, 5 to 50 g, 5 to 30 g, 5 to 20 g, 5 to 15 g, 5 to 12 g, 5 to 10 g, 8 to 50 g, 8 to 30 g, 8 to 20 g , 8 to 15 g, 8 to 12 g, 8 to 10 g, 10 to 50 g, 10 to 30 g, 10 to 20 g, 10 to 15 g, or 10 to 12 g, such as 1, 2, 3, or 10 g Yes, but not limited thereto.

Hereinafter, the present invention will be described in more detail.

In this specification, "wound" means damage to a living body, and is also referred to as a wound (創傷). Symptoms of injury include pain, bleeding, and functional disorders.

As used herein, "treatment" means alleviation or improvement of symptoms (eg, wounds, etc.), delay or alleviation of disease progression, amelioration, alleviation or stabilization of disease states or symptoms, partial or complete recovery or elimination, or other beneficial treatment results. etc. can be used in the meaning including all. "Improvement" may be used to mean all things such as alleviation or improvement of (eg, wounds, etc.), delay or alleviation of disease progression, improvement, alleviation or stabilization of disease states or symptoms.

In the present specification, “probiotics” may refer to living microorganisms that are considered to provide health benefits, and may be used as a meaning commonly used in the art.

As used herein, “mannitol” refers to a naturally occurring alcohol found in fruits and vegetables that can be used as an osmotic diuretic.

In this specification, "metal ion" means an ion generated from a metal atom.

In the present specification, “Lactobacillus brevis; L. brevis” may have accession number KCTC3498, but is not limited thereto.

In the present specification, “Lactobacillus plantarum; L. plantarum” may have accession number KCTC3105, but is not limited thereto.

In this specification, "dressing agent" means a material that covers a wound in order to protect the wound surface, and the material can be in any form. In addition, it may be used for the purpose of absorbing and removing secretions from internal wounds, preventing the intrusion of foreign substances from the outside, or protecting from physical shock or stimulation, but is not limited thereto.

The pharmaceutical composition, cosmetic composition, and/or dressing agent provided herein may be applied to a wound in the form of coating, spraying, and/or attachment.

Water, purified water, or phosphate buffered saline (PBS) may be used as the solvent used in the preparation of the pharmaceutical and/or cosmetic composition for wound healing and/or improvement containing the probiotics and metal ion-tannic acid of the present specification. , but is not limited thereto.

The pharmaceutical and/or cosmetic composition for treating and/or improving wounds containing probiotics and metal ion-tannic acid of the present specification uses the Young's modulus evaluation method to fix the test agent to a probe and applies a constant force to a texture analyzer (Micro systems). G) The elastic force can be measured by Equation 1 below.

[Equation 1]

E = Tensile strength / Elongation at break

The Young's modulus value (10 ^-2 N/mm ² ) of the composition obtained by Equation 1 is 2.3 or less, 2.2 or less, 2.1 or less, 2 or less, 1.9 or less, 1.8 or less, 1.7 or less, 1.6 or less, 1.5 or less, 1.4 1.3 or less, 1.2 or less, 1.1 or less, 1.0 or less, 0.9 or less, 0.8 or less, 0.7 or less, or 0.67 or less, such as 1.5053 or less, 1.0423 or less, 0.6531 or less, 0.6965 or less, or 0.6641 or less, and 0.001 or more, 0.01 or more, or 0.1 or more, but is not limited thereto.

The pharmaceutical and/or cosmetic composition for treating and/or improving wounds containing probiotics and metal ion-tannic acid of the present specification is immersed in PBS (Phospahte buffered saline), weighed (We), and dried in an oven for 8 hours. After measuring the weight (Wo) of the sample, the expansion rate can be measured by Equation 2 below.

[Equation 2]

Expansion rate (%) = (We/Wo) x 100

The expansion rate of the composition obtained by Equation 2 is 120% or more, 130% or more, 140% or more, 150% or more, 160% or more, 170% or more, 180% or more, 190% or more, 195% or more, 200% or more , 205% or more, 210% or more, 215% or more, 220% or more, 225% or more, or 230% or more, such as 190.4% or more, 200.7% or more, 220.4% or more, 230.1% or more, or 225.3% or more. It may be 1000% or less, 500% or less, 400% or less, 300% or less, or 250% or less, but is not limited thereto.

The pharmaceutical and/or cosmetic composition for treating and/or improving wounds containing probiotics and metal ion-tannic acid of the present specification induces wounds in animals, dressings with the composition, and measuring the size of the wound over time. The wound recovery rate can be measured by Equation 3 below.

[Equation 3]

Wound recovery rate = ((first wound size - later wound size) / first wound size) X 100

In the case of wound dressing with a pharmaceutical and/or cosmetic composition for treating and/or improving wounds containing probiotics and metal ion-tannic acid provided in the present specification, the wound recovery rate at day 13 is that of dressing with gauze. 1.1 to 2 times, 1.1 to 1.8 times, 1.1 to 1.6 times, 1.1 to 1.5 times, 1.1 to 1.45 times, 1.1 to 1.42 times, 1.2 to 2 times, 1.2 to 1.8 times, 1.2 to 1.6 times the wound healing rate at day 13 1.2 to 1.5 times, 1.2 to 1.45 times, 1.2 to 1.42 times, 1.3 to 2 times, 1.3 to 1.8 times, 1.3 to 1.6 times, 1.3 to 1.5 times, 1.3 to 1.45 times, 1.3 to 1.42 times, 1.4 to 2 times times, 1.4 to 1.8 times, 1.4 to 1.6 times, 1.4 to 1.5 times, 1.4 to 1.45 times, or 1.4 to 1.42 times, for example, it may be 1.409 times or 1.412 times, but is not limited thereto.

In the present specification, the composition may be a pharmaceutical composition, cosmetic composition, skin external application composition, health functional food, or quasi-drug composition, which is a solution, ointment, external ointment, cream, essence, foam, lotion, nutrient lotion, softening water, softening lotion , pack, emulsion, makeup base, soap, cleanser, bath additive, sun cream, sun oil, suspension, emulsion, paste, gel, lotion, powder, soap, cleansing with surfactant, oil, foundation, powder foundation, emulsion foundation , may have a formulation selected from the group consisting of a wax foundation, a patch, and a spray.

The present specification relates to a pharmaceutical and/or cosmetic composition for treating and/or improving wounds, including probiotics, metal ions and tannic acid.

The pharmaceutical composition, cosmetic composition, and/or dressing may be one or more formulations selected from the group consisting of patches, patches, ointments, creams, gels, lotions, sprays, foams, and sprays. It is not limited.

The pharmaceutical composition may further include a pharmaceutically acceptable carrier.

The above "pharmaceutically acceptable carrier" refers to a carrier or diluent that does not stimulate living organisms and does not inhibit the activity and properties of treating and/or improving wound symptoms of the composition of the present invention. In the composition formulated as a liquid solution, acceptable pharmaceutical carriers are sterile and biocompatible, and include saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, and ethanol. And one or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added if necessary.

In addition, pharmaceutically acceptable carriers of the present invention may include non-natural carriers.

The pharmaceutical composition of the present specification may be administered singly or in multiple doses in a pharmaceutically effective amount.

As used herein, the term "pharmaceutically effective amount" means an amount sufficient to prevent or treat a disease with a reasonable benefit/risk ratio applicable to medical prevention or treatment, and the effective dose level is dependent on the severity of the disease and the activity of the drug. , Factors including the patient's weight, health, sex, sensitivity to the patient's drug, administration time of the composition of the present invention used, route of administration and excretion rate, treatment period, drug used in combination or simultaneous use with the composition of the present invention used and other factors well known in the medical field.

Another example of the present specification relates to a quasi-drug composition for treating and/or improving wounds, including probiotics, metal ions, and tannic acid.

As used herein, the term "quasi-drugs" refers to items that have a milder action than pharmaceuticals among items used for the purpose of diagnosing, treating, improving, mitigating, treating or preventing human or animal diseases. For example, according to the Pharmaceutical Affairs Act of the Republic of Korea Quasi-drugs are products excluding items used for pharmaceutical purposes, and include products used for the treatment or prevention of human or animal diseases, products with minor or no direct action on the human body, etc.

The quasi-drug composition of the present specification may be prepared in one or more forms selected from the group consisting of dressings, patches, pastes, body cleansers, foams, soaps, masks, ointments, creams, lotions, essences and sprays, but is limited thereto It is not.

When the probiotics, metal ions, and tannic acid of the present specification are used as quasi-drug additives, the probiotics, metal ions, and tannic acid of the present specification may be added as they are or used together with other quasi-drugs or quasi-drug ingredients, and may be appropriately used according to conventional methods. .

In addition, the quasi-drug composition and/or dressing agent is not particularly limited thereto, but specifically, a dressing agent, patch, patch, ointment, lotion, spray, patch, cream, powder, suspension, gel, foam Alternatively, it may be prepared and used in the form of a gel.

The composition for treating and/or improving wounds according to the present specification may be a cosmetic composition, but is not limited thereto. The cosmetic composition for treating and/or improving wounds of this embodiment may include probiotics, metal ions, and tannic acid, but is not limited thereto.

The cosmetic composition or cosmetics as an active ingredient

In addition to probiotics, metal ions and tannic acid, cosmetically acceptable carriers, excipients, and/or additives may be further included.

In the present specification, “cosmetics” or “cosmetic composition” may be in any form of formulation commonly prepared in the art, for example, dressings, patches, patches, capsules, solutions, suspensions, emulsions, pastes, and gels. , Cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation, pack, massage cream and spray, etc., but may be formulated, but are not limited thereto. Specifically, it may be prepared in the form of dressing softening lotion, nutrient lotion, nutrient cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder.

The cosmetic or cosmetic composition may be used alone or in combination with other cosmetic compositions. In addition, the cosmetic composition of the present invention can be used according to the usual method of use, but the number of times of use can be varied according to the user's skin condition or taste.

The cosmetic or cosmetic composition may be used for humans, primates such as monkeys, rodents such as mice, rats, and rabbits, other mammals including dogs, cats, cows, pigs, sheep, horses, goats, chickens, ducks, geese, etc. It may be applied to a target selected from vertebrates such as reptiles, amphibians, and fish, including birds, snakes, lizards, turtles, and crocodiles.

The present invention includes probiotics coated with metal ion-tannic acid to enhance the stability of probiotics during manufacture and contains probiotics capable of enhancing wound healing, resulting in a wound healing effect that enhances the convenience of wound application due to excellent physical properties. provides an enhanced dressing

Figure 1 is a result of observing the coating layer of the coated probiotics cells with a field emission transmission electron microscope (FE-TEM, JEM-2100F, JEOL).
Figure 2 is a photograph confirming wound recovery when treating a wound dressing containing probiotics coated on a wound or when treating a general commercially available wound dressing formulation, when treating a general gauze. A is a case of processing a general gauze, B is a case of processing a general commercially available wound dressing formulation (Duoderm ^TM ), and C is a case of processing Example 10.
Figure 3 is a photograph confirming wound recovery when treating a wound dressing containing probiotics coated on a wound or when treating a general commercially available wound dressing formulation, when treating a general gauze. A is a case of processing a general gauze, B is a case of processing a general commercially available wound dressing formulation (Duoderm ^TM ), and C is a case of processing Example 18.
4 and 5 are graphs showing the reduction in the size of wounds when treating wound dressings containing probiotics coated on wounds or general commercially available wound dressing formulations, when treating general gauze. Control is the case of processing general gauze.

Hereinafter, the present invention will be described in detail through the following examples. The following examples are intended to illustrate the present invention, but the present invention is not limited by the following examples.

Example 1. Preparation of coated probiotics

Among the probiotic species, small amounts of Lactobacillus brevis (L. brevis, accession number: KCTC3498) and Lactobacillus plantarum (L. plantarum, accession number: KCTC3105) were collected with a sterilized kolle handle, and respectively MRS agar ( DifcoTM Lactobacilli MRS Broth + BactoTM agar, Becton, Dickinson and Company, USA) solid medium was cultured by the streak plate method. One colony was obtained with a pipette from each of the cultured media, put into 3ml MRS broth (DifcoTM Lactobacilli MRS Broth, Becton, Dickinson and Company, USA) liquid medium, and cultured for 16 hours at 37°C with moderate agitation.

After centrifuging the probiotics cultured in the liquid medium, the liquid medium, which is the supernatant, was removed, and a series of washing processes of adding deionized water equal to the amount of the removed liquid medium were repeated three times to disperse the probiotics in the deionized water. To the suspension (490 μL) in which the probiotic cells were dispersed in deionized water, 5 μL of each of a 40 mg/mL aqueous solution of tannic acid and a 10 mg/mL aqueous solution of FeCl ₃ 6H ₂ O were added without delay, and the tube was shaken vigorously. Mixed for 10 seconds using a vortexer.

After that, the washing process using deionized water was repeated twice, and through the process of dispersing in deionized water, Lactobacillus brevis probiotics cells and Lactobacillus plantarum probiotics cells nano-coated with iron ion-tannic acid complex were prepared, and the probiotics The cell coating layer was confirmed using a field emission transmission electron microscope (FE-TEM, JEM-2100F, JEOL), and the results are shown in FIG. 1 . A suspension containing the coated probiotics at a concentration of 10 ¹⁰ CFU per 1 g of the solution was obtained by measuring the concentration of the probiotics strain by Colony Forming Unit (CFU) in the prepared coated probiotics solution.

Example 2. Preparation of coated probiotics dressing

A coated probiotics-containing wound dressing comprising the coated probiotics prepared in Example 1, polyvinyl alcohol and a polymer was prepared.

Specifically, the probiotics suspension, polyvinyl alcohol and polymer prepared in Example 1 were prepared according to the compositions in Tables 1 and 2 below, and the materials were added to purified water, frozen at -20 ° C for 18 hours, and at 20 ° C The freeze-thaw method of freezing and thawing for 6 hours was repeated three times. The amount of purified water required for the addition was prepared so that 100 g was combined with the amount of the composition in Tables 1 and 2 below (eg, in Example 3, 1 g of the suspension, 4 g of polyvinyl alcohol, and 95 g of water were added). The composition information used in the preparation of the dressing is shown in Tables 1 and 2 below. The prepared dressing agent has an area of 9.62 cm ² and a weight of 10 g.

division Example 3 Example 4 Example 5 Example 6 Example 7 Example 8 Example 9 Example 10 Lactobacillus brevis suspension One One One One One One One One polyvinyl alcohol 4 5 10 15 20 10 10 10 mannitol - - - - - One 2 3 Purified water 95 94 89 84 79 88 87 86

(The unit of Table 1 above is g)

division Example 11 Example 12 Example 13 Example 14 Example 15 Example 16 Example 17 Lactobacillus brevis suspension One One One One One One - Lactobacillus Planterum Suspension - - - - - - One polyvinyl alcohol 10 10 10 10 10 10 10 mannitol - - - - - - 2 Poloxamer 2 - - - - - - guar gum - 2 - - - - - Polyethylene glycol 6000 - - 2 - - - - Dextran - - - 2 - - - Hydroxypropyl Cellulose - - - - 2 - Hydroxypropyl Methyl Cellulose - - - - - 2 - Purified water 87 87 87 87 87 87 87

(The unit of Table 2 is g) As a comparative example, Lactobacillus brevis probiotics and Lactobacillus plantarum probiotics that were not coated were used instead of each probiotic strain that was coated, and were substantially the same as in Examples 9 and 17, respectively. Comparative Examples 1 and 2 were prepared in which wound dressings were prepared using the same method and composition.

Example 3. Evaluation of the number of bacteria of coated probiotics

For the evaluation of the shape of the wound dressing containing the coated probiotics, each of the wound dressings prepared in Example 2 was cut into pieces, put into 200ml of PBS (phosphate buffer saline), stirred with a stirrer, and then 1ml was sampled into PBS. After properly diluting, 100 μl was spread on MRS agar medium and cultured at 37 ° C. The number of colonies was directly counted to confirm the viable cell count.

Among them, the number of probiotic bacteria in Examples 9 and 17 containing coated probiotics and Comparative Examples 1 and 2 containing uncoated probiotics was evaluated, and the results are shown in Table 3 below.

division Number of probiotics (colony forming jint, CFU x 10 ⁴ ) Example 9 6.5300 ± 1.5200 Example 17 2.9100 ± 0.2830 Comparative Example 1 0.4534 ± 0.0480 Comparative Example 2 0.5820 ± 0.0424

As shown in Table 3, the coated probiotics Lactobacillus brevis (Example 9) was 14.4 times larger than the uncoated Lactobacillus brevis (Comparative Example 1), and the coated probiotics Lactobacillus plantarum (Example 17) was coated It was confirmed that the coated probiotics were more stable in the manufacturing environment than the uncoated probiotics, showing a 5.0-fold increase in the number of bacteria compared to the uncoated Lactobacillus plantarum.

Example 4. Evaluation of elastic properties of coated probiotics

In order to confirm that the wound dressing containing the coated probiotics can be well applied to the curved wound, the physical properties were evaluated.

Specifically, the physical properties of Examples 5 to 17 and Comparative Examples 1 and 2 prepared in Example 2 were evaluated. Physical properties of wound dressings containing active ingredients such as probiotics were evaluated by Young's modulus. Young's modulus was measured with a texture analyzer (Micro Systems Co.) by fixing the test agent to the probe and applying a constant force, which was calculated by Equation 1 below, and the results are shown in Table 4 below. The lower the Young's modulus value, the better the elasticity, which means that a lot of stretching is achieved with a small amount of force.

[Equation 1]

Young's modulus (E) = Tensile strength / Elongation at break

(In Equation 1, Tensile strength represents uniaxial stress, that is, uniaxial force per unit surface, and Elongation at break means strain, that is, change in length divided by original length)

division Young's modulus (10 ^-2 N/mm ² ) Example 5 1.8774 ± 0.0858 Example 6 2.0241 ± 0.0741 Example 7 2.2211 ± 0.0987 Example 8 1.0423 ± 0.0433 Example 9 0.6531 ± 0.0699 Example 10 0.6965 ± 0.0871 Example 11 1.7081 ± 0.1337 Example 12 1.4428 ± 0.1187 Example 13 1.4995 ± 0.0639 Example 14 1.9003 ± 0.0604 Example 15 2.4480 ± 0.1599 Example 16 1.9715 ± 0.0924 Example 17 0.6641 ± 0.0658 Comparative Example 1 0.6489 ± 0.0625 Comparative Example 2 0.6583 ± 0.0689

As a result, it was confirmed that among Examples 5 to 17 containing coated probiotics, Examples 8 to 10 and Example 17 containing mannitol were relatively superior in elasticity compared to other wound dressings. In particular, Example 17, which includes other types of probiotics strains, also confirmed that the measured Young's modulus values were similar when mannitol was included, confirming that there was little change depending on the type of probiotics.

In addition, there was no difference in the measured Young's modulus values of Comparative Examples 1 and 2 and Examples 9 and 17 containing uncoated probiotics, so it was confirmed that there was no difference in elasticity depending on the presence or absence of coating.

Through the above results, it was confirmed that the elasticity can be adjusted in various ways according to the components used when preparing a wound dressing using the coated probiotics.

Example 5. Expansion rate evaluation of coated probiotics

In order to evaluate the effect on the absorbency of the exudate, which is important for maintaining a wet environment of the wound dressing containing the coated probiotics, the expansion rate was evaluated.

Specifically, the absorption rates of Examples 3 to 17 and Comparative Examples 1 and 2 prepared in Example 2 were measured by taking a size of 2 cm X 2 cm in a dried state and incorporating the prepared wound dressing in 37 ° C. PBS (Phospahte buffered saline). After immersing for 24 hours, the weight (We) was measured, and after drying in an oven at 60 ° C. for 8 hours, the weight (Wo) of the sample was measured and calculated by Equation 2 below. The results of this measurement are shown in Table 5 below.

[Equation 2]

Expansion rate (%) = (We/Wo) x 100

division Expansion rate (%) Example 3 124.3 ± 2.1 Example 4 151.3 ± 4.4 Example 5 182.6 ± 5.7 Example 6 164.2 ± 4.5 Example 7 151.1 ± 3.8 Example 8 200.7 ± 5.1 Example 9 220.4 ± 7.1 Example 10 230.1 ± 6.6 Example 11 200.4 ± 1.5 Example 12 220.8 ± 3.5 Example 13 200.4 ± 1.5 Example 14 190.9 ± 2.6 Example 15 190.2 ± 2.4 Example 16 195.5 ± 2.6 Example 17 225.3 ± 6.8 Comparative Example 1 220.1 ± 5.6 Comparative Example 2 226.7 ± 6.9

As a result, it was confirmed that polyvinyl alcohol and mannitol were included (Examples 8 to 10 and 17) exhibiting a better expansion rate. In addition, it was confirmed that Comparative Examples 1 and 2 including uncoated probiotics showed little difference in expansion rate when compared to Examples 9 and 17, which included coated probiotics and had the same remaining composition.

Through this, when the wound dressing was prepared by containing the coated probiotics, it was confirmed that the absorbency could be adjusted in various ways according to the components used, and among them, it was confirmed that polyvinyl alcohol and mannitol were excellent.

Example 6. Evaluation of wound healing ability of coated probiotics

In order to evaluate the wound healing ability of the wound dressing containing the coated probiotics, Examples 9 and 17 prepared in Example 2 and Duoderm ^TM (Convatec) (commercial preparation) and general gauze (sterile gauze; Suseongsa) (untreated) was prepared, and wound healing was evaluated.

Specifically, SD-based rats with an average age of 6 to 8 weeks and a body weight of 250 to 300 g were prepared by acclimatization for one week, and a general breeding room (temperature 23 ± 2 degrees, humidity 55 to 60%, lighting from 7 am to 60 pm) 7:00) in a breeding environment until the end of the experiment, and feed was supplied with normal feed, and normal purified water was used for water. Induction of wounds was anesthetized with Ketamine and Xylazine to rats without abnormalities during the acclimatization period to remove and disinfect the skin, and then cut the skin with scissors to induce a 10mm x 10mm wound or cut the skin with scissors to create a 10mm x 10mm wound. The induced wound was infected with Pseudomonas aeruginosa. After dressing with the prepared wound dressing, the area was measured using graph paper according to the time (day 0, 1, 3, 6, 9, or 13) to obtain the wound size, and the recovery rate by Equation 3 below The wound healing effect was measured by evaluation and visual observation, and the results are shown in FIGS. 2 and 3, and the measured wound recovery rates are shown in Tables 6, 7, and 4 and 5.

[Equation 3]

Wound recovery rate = ((first wound size - later wound size) / first wound size) X 100

Date untreated Commercially available preparation Example 9 0 0 0 0 One 8 8 10 3 20 30 45 6 32 52 65 9 43 63 80 13 63 77 89

Day untreated Commercial preparation Example 17 0 0 0 0 One 8 23 27 3 24 47 63 6 40 63 75 9 55 76 83 13 66 91 93

As shown in Figures 2 and 3, the excellent wound healing effect of Examples 9 and 17, which are wound dressings containing coated probiotics, was visually confirmed. In addition, as shown in Table 6, Table 7, Figure 4 and Figure 5 showing the wound recovery rate, the wound dressings of Examples 9 and 17 containing probiotics coated similarly to the naked eye showed excellent wound recovery rates. Confirmed.

In addition, the commercially available formulation (Duoderm ^TM ) showed a superior wound healing effect than that of untreated (general gauze), but lower wound healing than the wound dressings of Examples 9 and 17 containing coated probiotics. was

Through this, it is judged that the wound dressing containing the coated probiotics is superior to general commercial products, and this is because the probiotics contained in the dressing have an effect of helping to heal the wound.

Claims (15)

A pharmaceutical composition for treating wounds containing probiotics, metal ions and tannic acid. According to claim 1, wherein the metal ion and tannic acid is in the form of coating the probiotics, a pharmaceutical composition for wound treatment. The method of claim 1, wherein the probiotics are Lactobacillus brevis, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus casei (Lactobacillus casei), Lactobacillus bulgaricus (Lactobacillus bulgaricus), Lactobacillus fermentum (Lactobacillus fermentum) and Lactobacillus salivarius (Lactobacillus salivarius) at least one member selected from the group consisting of, a pharmaceutical composition for wound treatment. The method of claim 1, wherein the metal ion is iron (Fe), aluminum (Al), vanadium (V), manganese (Mn), iron (Fe), zinc (Zn), zirconium (Zr), molybdenum (Mo), ruthenium (Ru), rhodium (Rh), cerium (Ce), europium (Eu), gadolinium (Gd) and at least one member selected from the group consisting of terbium (Tb), a pharmaceutical composition for treating wounds. According to claim 1, wherein the probiotics per 10g of the composition 10 ⁴ To 10 ¹² A pharmaceutical composition for wound treatment comprising an amount of CFU. According to claim 1, wherein the probiotics composition 10cm ² Per 10 ⁴ To 10 ¹² A pharmaceutical composition for wound treatment comprising an amount of CFU. The method of claim 1, polyacrylic acid, polyvinyl pyrrolidone, hydroxyalkyl cellulose, carbomer, polyvinyl alcohol, chitosan , Alginate, Carboxymethyl Cellulose, Poly(hexamethylenebiguanide), Carrageenan, Polyethylene oxide, Polysaccharide, Collagen ), Gelatin, Hyaluronic acid, Xanthan gum, Acacia gum, Alginic acid, Agar, Gum arabic, Tragacanth (Tragacanth), Karaya gum, pectin, mannitol, poloxamer, guar gum, polyethylene glycol (PEG), dextran, A pharmaceutical composition for treating wounds, further comprising at least one member selected from the group consisting of hydroxypropyl cellulose and hydroxypropyl methylcellulose. A dressing comprising the pharmaceutical composition for wound treatment according to any one of claims 1 to 7. A cosmetic composition for improving wounds containing probiotics, metal ions and tannic acid. [Claim 10] The cosmetic composition for improving wounds according to claim 9, wherein the metal ion and tannic acid are in the form of coating the probiotics. The method of claim 9, wherein the probiotics are Lactobacillus brevis, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus casei (Lactobacillus casei), Lactobacillus bulgaricus (Lactobacillus bulgaricus), Lactobacillus fermentum (Lactobacillus fermentum) and Lactobacillus salivarius (Lactobacillus salivarius) at least one member selected from the group consisting of, a cosmetic composition for improving wounds. 10. The method of claim 9, wherein the metal ion is iron (Fe), aluminum (Al), vanadium (V), manganese (Mn), iron (Fe), zinc (Zn), zirconium (Zr), molybdenum (Mo), ruthenium (Ru), rhodium (Rh), cerium (Ce), europium (Eu), gadolinium (Gd) and at least one member selected from the group consisting of terbium (Tb), a cosmetic composition for improving wounds. 10. The method of claim 9, wherein the probiotics per 10g of the composition 10 ⁴ To 10 ¹² CFU contained in an amount, a cosmetic composition for improving wounds. 10. The method of claim 9, wherein the probiotics per 10cm ² of the composition 10 ⁴ To 10 ¹² A cosmetic composition comprising an amount of CFU. The method of claim 9, polyacrylic acid, polyvinyl pyrrolidone, hydroxyalkyl cellulose, carbomer, polyvinyl alcohol, chitosan , Alginate, Carboxymethyl Cellulose, Poly(hexamethylenebiguanide), Carrageenan, Polyethylene oxide, Polysaccharide, Collagen ), Gelatin, Hyaluronic acid, Xanthan gum, Acacia gum, Alginic acid, Agar, Gum arabic, Tragacanth (Tragacanth), Karaya gum, pectin, mannitol, poloxamer, guar gum, polyethylene glycol (PEG), dextran, A cosmetic composition for improving wounds, further comprising at least one member selected from the group consisting of hydroxypropyl cellulose and hydroxypropyl methylcellulose.