KR101453219B1 - Compositions for bio-glue - Google Patents

Abstract

The present invention relates to a bio-adhesive composition. According to the present invention, the bio-adhesive composition contains a bio-adhesive component having a specific functional group which can be a covalently bonded with a protein residue of a surface of a skin or a hair, forms covalent bonding without damage to the skin or hair, and provides a desired bio-adhesive effect semi-permanently.

Description

Compositions for bio-glue < RTI ID = 0.0 >

TECHNICAL FIELD The present invention relates to a reactive bio-bonding component having a functional group bonded to a protein and a composition for bio-bonding.

In general, the wound on the skin is a state in which the continuity of the normal structure of the body tissue is destroyed by the external force, and depending on the cause, the capillary blood vessels of the subcutaneous tissue due to the external force are damaged, the abrasion due to the sharp outer force, Which is a wound scraped with ice, a nail, a twig, etc., which is a scar, a knife, a piece of glass, and a wound caused by surgery, a skin that is torn by a blunt external force, And so on.

In general, the method used to enhance the wound healing effect of the wound is to dry the wound by covering the wound with the initial drying treatment method, and it is a method of healing the wound, Non-woven gauze, non-sticky gauze, non-sticky absorbent pad, and the like. As a wet treatment method, typical therapeutic agents that can greatly contribute to the treatment of chronic intractable skin ulcers such as a pressure ulcer include films, filled beads, hydrocolloids, alginates, polyurethane foams, and hydrogels. Recently, a widely used drug delivery system is an effective method for treatment of chronic wounds that are difficult to heal. Growth factors can regulate the wound healing process and enable effective wound treatment. Typical biojoint components include growth factors, physiologically active substances, Antimicrobial coatings, and the like.

The object of the present invention is to provide a composition for bioadhesion for the treatment of skin damaged areas such as wounds, which effectively and rapidly treats the wound area, but does not leave a scar so as to beautify the wound area like the original skin and increase the attractiveness do.

The bioabsorbable composition can also be used for bonding the hair to be cracked.

The composition for bio-bonding, which is capable of bonding skin or hair, generally comprises a skin or hair bond such as a cleansing composition for care of the skin, a composition or base for functionally bonding skin or hair for foundation, And a composition of possible function. Compositions that are capable of joining skin or hair for scalp may first include a functional composition capable of joining skin or hair for scalp such as cleansing, treatment, regular hair, wool, hair dressing, and the like.

Common raw materials used to form a functional composition capable of bonding between skin or hair include oily materials such as oil, wax, hydrocarbon, higher fatty acid, higher alcohol, ester oil and silicone oil, anionic, cationic, amphoteric, Antioxidants, metal ion sequestrants, coloring materials including dyes and pigments, perfumes, preservatives, and the like, which are used in the present invention, as a nonionic surfactant, a moisturizer, a thickener and a film former.

However, when the composition is used for skin or hair using only the raw material and composition of a bioabsorbable composition capable of bonding between the skin or hair, it provides only a temporary effect until the next washing after the treatment. However, There is always a limit of.

Patent Document 1 discloses a non-aqueous personal care product for skin or hair, which comprises a non-water-based functional group capable of forming a covalent bond with a hair or a protein residue on the surface of a skin, such as carbonate, aldehyde, propionaldehyde, But are not limited to, butylaldehyde, nitrophenyl carbonate, aziridine, isocyanate, thiocyanate, epoxide, tresylate, succinimide, A hydroxysuccinimidyl ester, an imidazole, an oxycarbonylamidazole, an imine, a thiol, a maleimide, a vinylsulfone, For example, ethyleneimine, thioether, acrylonitrile, acrylic acid or methacrylic ester, (Wherein R is any one selected from the group consisting of alkyl, aryl, aralkyl, cyclic and unsaturated rings, and X is I, Br or Cl) represented by the following formula And a water-based part containing a conditioning component having at least one selected from the group consisting of the above-mentioned various kinds of functional groups, (1.9 to 3.1%) and skin keratin (3.1 to 6.9%) in the amino acids of the proteins constituting the hair or the skin, ~ 18%) and skin keratin (2.3 ~ 3.8%) are targeted and reacted, so that the reaction efficiency is lowered. There is a problem in that it must be synthesized.

Korean Patent Publication No. 2008-0064467

It is an object of the present invention to provide a composition for bioadhesion which can continuously impart a semi-permanent biojunction effect without damaging hair or skin.

As a means for solving the above problems, the present invention provides a composition for bioadhesion comprising a carbodiimide compound and a bioadhesive component.

As another means for solving the above-mentioned problems, the present invention provides a method for producing a bioadhesive composition which comprises adding a bioadhesive component to a bioadhesive component comprising a carbodiimide, an imidoester, an aryl azide, a diazirine, a hydroxymethylphosphine, a pentafluorophenyl ester, a pyridyl disulfide, At least one hair selected from the group consisting of hydroxysuccinimide ester, alkoxyamine, hydrazide, haloacetyl, and azide, or a functional bonding agent capable of covalently bonding with a protein on the skin surface.

As another means for solving the above problems, the present invention provides a composition for bioadhesion comprising the above reactive bio-bonding component.

The composition for bio-bonding according to the present invention contains a reactive bio-bonding component and / or a carbodiimide compound into which a specific functional group capable of covalent bonding with a hair or skin protein residue is introduced, Thereby providing a semi-permanent bio-bonding effect.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a photograph showing the state of hair before and after treatment of hair with a composition for bio-bonding according to Example 4 of the present invention. Fig.

The present invention relates to a composition for bioadhesion comprising a carbodiimide compound and a bioadhesive component.

The composition for bioadhesion according to the present invention can be prepared by, for example, reacting a carbodiimide compound with a known bioadhesive component to form a covalent bond with a hair or skin protein through a reactive bioadhesive component to which a carbodiimide group is bonded The bio junction effect can be maximized.

The carbodiimide compound may be used in an amount of 0.001 to 10 parts by weight, 0.01 to 7 parts by weight, or 0.1 to 5 parts by weight based on 100 parts by weight of the total composition. When the content is less than 0.001 part by weight, there is a problem that the biojointing effect is not continuously exhibited. When the content exceeds 50 parts by weight, the carbodiimide compound existing excessively above the reaction site existing in the skin is present in a state There is a problem that it can act as a lost component.

In the present invention, the term "bio-bonding effect" refers to a function of preventing or improving skin damage or hair cracking by effectively regenerating or bonding damaged parts of living tissue such as skin or hair in an original state.

The biojoint component used in the present invention may include fibrin, albumin, glucosamine, n-acetylglucosamine, alginate, hydrogel, growth factor, physiologically active factor, necrotic tissue remover, glutinous adhesive agent, Examples of the growth factor include FGF (Fibroblast Growth Factor), Keratinocyte Growth Factor (KGF), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), Platelet Derived Growth Factor AA -AB (Platelet Derived Growth Factor AB), PDGF-BB (Platelet Derived Growth Factor BB), TGF-alpha (Transforming Growth Factor-?), TGF-beta, Insulin-like Growth Factor (IGF), Tumor Necrosis Factor ), GM-CSF (Granulocyte Macrophage Colony Stimulating Factor), NGF (NGF (Nerve Growth Factor)), etc. The physiologically active factors include interferon, erythropoietin, 1L- , IL-6, IL-8, etc. The glue conjugate may be N- (4-carboxy-3-hydroxy-phenyl) maleimide, TRANSGLUTAMINASE, etc. Antibacterial coating agents include benzalkonium chloride Trichloroacetic acid, trichloroacetic acid, trichloroacetic acid, isopropylmethylphenol, p-toluenesulfonic acid, p-toluenesulfonic acid, One, allantoin, ε- amino caproic acid and the like, glycidyl chili parent acids.

The bio-bonding component is preferably used in an amount of 0.001 to 50 parts by weight, 0.001 to 30 parts by weight, 0.01 to 10 parts by weight, or 0.1 to 5 parts by weight based on 100 parts by weight of the total composition. When the content is less than 0.001 part by weight, the effect of the active ingredient is limited. When the content exceeds 50 parts by weight, there is a problem that it acts as a component that can not be stabilized and reacted with time in formulation and formulation.

Particularly, in the present invention, the bioadhesive component can increase the reaction efficiency with the carbodiimide compound by including a carboxyl group or an amine group in the molecule.

In addition, in the present invention, the bio-bonding component may be one having a functional group capable of covalently bonding to hair or a protein residue on the skin surface.

The functional groups covalently bonded to the protein include carbodiimide, imidoesters, aryl azides, diazylines, hydroxymethylphosphines, pentafluorophenyl esters, pyridyl disulfides, sulfo-hydroxysuccinimide esters, alkoxy amines, The present invention also relates to a process for the preparation of a medicament for the treatment and / or prophylaxis of a disease or condition selected from the group consisting of hydrazide, haloacetyl, azide, carbonate, aldehyde, propionaldehyde, butylaldehyde, nitrophenylcarbonate, aziridine, isocyanate, thiocyanate, epoxide, May be at least one selected from the group consisting of imidazole, oxycarbonylamidazole, imine, thiol, maleimide, vinylsulfone, ethyleneimine, thioether, acrylonitrile, acrylic acid or methacrylic acid ester, disulfide and ketone , But is not limited thereto.

In addition, the protein may comprise reactive residues of thiol, hydroxyl, carboxyl or amine.

The carbodiimide compound is generally referred to as a compound containing a structure represented by the following formula (1) in the molecule.

[Chemical Formula 1]

-N = C = N-

The carbodiimide compound preferably has at least 1 to 1000 structures represented by the formula (1), more preferably 1 to 100 structures represented by the formula (1) It is more preferable that the structure includes 1 to 10 structures in the molecule.

In this case, if the number of the carbodiimide groups represented by the formula (1) exceeds 1,000 in one molecule, the viscosity of the starting material is too large, the molecular weight is excessively large, the reaction position where the reaction can be performed becomes excessively large, The molecule having the bodymide group becomes too large, and the efficiency is lowered by blocking the portion showing the functional effect of the molecule having the substantial function.

In the present invention, a specific example of the carbodiimide compound may be a compound represented by the following formula (2), wherein n is 4 and m is 11 in the following formula (2): benzene, 1,3, Isocyanato-1-methylethyl) -, homopolymer, polyethylene glycol mono-ether-block (benzene, 1-isocyanato- Me-ether-blocked (hereinafter referred to as polymeric carbodiimide compound of formula (2)).

(2)

In the above formula (2), n is 1 to 100 and m is 1 to 100.

Another example of the carbodiimide compound in the present invention is 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide, which is a compound represented by the following formula (3) carbodiimide or 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide.HCl may be used.

(3)

In one preferred embodiment of the composition for bioadhesion according to the present invention, the bio-bonding component having a carboxyl group is directly made into a bioactive reactive ester bio-bonding component, or the hair (17.5 to 21.9%) or the skin keratin (Ex, aspartic acid, and glutamic acid) existing in an excessive amount in a reaction mixture (e.g., 23.5%, 23.5%) is reacted with a carbodiimide compound capable of targeting a biojunction component including an amine group, ) Can be made to increase the reaction efficiency, thereby remarkably increasing the effect. In addition, it is also possible to use carbodiimides, imidoesters, aryl azides, diazylines, hydroxymethylphosphines, pentafluorophenyl esters, pyridyl disulfides, sulfo-hydroxysuccinimide esters, alkoxy The effect can be further enhanced by using a bio-bonding component containing a functional group such as amine, hydrazide, haloacetyl, or azide in the molecule.

In a more preferred embodiment, a bioadhesive component molecule having a carboxyl group is formed on the protein surface of the skin or hair by first mixing the polymeric carbodiimide compound of Formula 2 or 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide . A carbodiimide compound such as 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide.HCl is firstly reacted to form a reactive ester, and a bioadhesive component having an amine in the molecule in addition to the reactive ester functional group formed Or by reacting with an amine on the surface of hair or skin, an excellent biojunction effect can be obtained. The reaction is preferably carried out at a pH of 2 to 10, more preferably at a pH of 3 to 9, most preferably at an acidic to slightly acidic pH of about 4 to 5 The reaction efficiency can be increased most. The reaction is completed within 1 minute to 30 minutes.

The reaction of the carbodiimide compound with aspartic acid or glutamic acid of the skin and hair protein having a carboxylic acid terminal in the following Reaction Scheme 1 is firstly reacted to form a reactive ester and then reacted with lysine present in the skin and hair proteins having an amine residue Covalent bond is formed.

[Reaction Scheme 1]

A biocompatible material containing a skin and hair protein containing a cysteine amino acid in the following Reaction Scheme 2 and maleimide conjugated with a cysteine which is a biogenic amino acid at a pH of 7 to 8 with a carboxylic acid moiety and a bioreactor in one molecule Formation of reactive ester by primary reaction of carbodiimide compound 1-ethyl-3- (3-dimethyl laminopropyl) carbodiimide and schematic diagram of biojunction through amine reaction of hair lysine amino acid of reactive ester produced Respectively.

[Reaction Scheme 2]

The carbodiimide compound increases the reaction efficiency of the hair or the skin protein and the bioadhesive component so that the reactive bioadhesive component bound to the hair or the skin does not fall off well during general cleaning due to shampoo or soap, It can be kept attached to hair or skin.

The present invention also relates to a method for producing a biodegradable polymer, wherein the bioadhesive component comprises a carbodiimide group, an imidoester, an aryl azide, a diazirine, a hydroxymethylphosphine, a pentafluorophenyl ester, a pyridyl disulfide, a sulfo-hydroxysuccinimide ester, The present invention relates to a process for the preparation of a pharmaceutical composition which comprises administering an effective amount of a compound selected from the group consisting of an amine, hydrazide, haloacetyl, azide, carbonate, aldehyde, propionaldehyde, butylaldehyde, nitrophenylcarbonate, aziridine, isocyanate, thiocyanate, epoxide, At least one member selected from the group consisting of diesters, imidazoles, oxycarbonylamidazoles, imines, thiols, maleimides, vinylsulfones, ethyleneimines, thioethers, acrylonitriles, acrylic acid or methacrylic acid esters, disulfides and ketones May contain a reactive bio-bonding component with a functional group covalently bonded to the protein have.

For example, as shown in Reaction Scheme 1, a carbodiimide compound may be bonded to a carbodiimide group to form a bioadhesive component. In addition, the present invention may include a composition for bioadhesion comprising the above-mentioned reactive bio-bonding component.

In order to further enhance the effect of the present invention, it is preferred that the fatty acid such as palmitic acid and stearic acid, the fatty alcohol, and the long chain alkyl quaternary ammonium salt of the straight chain and the branched chain are cationized When mixed with a cationic polymer such as a surfactant, cationized cellulose, cationic guar, cationized polyvinylpyrrolidone, silicone, etc., formulation can be facilitated. In addition, for formulation, auxiliary ingredients such as a solvent, a surfactant, a thickener, a stabilizer, a preservative, a colorant, a pH adjuster, a sequestering agent, a colorant, a pearlizing agent, can do. The ingredients for the formulation may be used in an amount of 40 to 99 parts by weight based on 100 parts by weight of the total composition.

The composition for bioadhesion according to the present invention can be used for the formulation of a cosmetic composition for bioadhesion including a bioadhesive component having a functional group. Examples of the application of the hair product include a shampoo composition, shampoo, rinse treatment, wax, spray, mousse, hair lotion, essence, hair cream, permanent hair dye, temporary hair dye, (Skin lotion, cream, essence, lotion, cream, etc.), color cosmetics (makeup base, foundation, powder, eye shadow, lip gloss, (Cleansing oil, cleansing lotion, cleansing cream, cleansing gel, pack, mask, soap, cleansing tissue, etc.), make-up for hand and toenails (manicure, nutrient, Etc.), sun care cosmetics, body cosmetics (body lotion, shower gel, body cream, body oil, etc.).

More preferably, the composition for bioadhesion according to the present invention comprises a bioadhesive component containing a carbodiimide compound and a reactive functional group. When the activity of the bioadhesive composition is lowered in the aqueous system, It may be easier to maintain the activity in the buffer solution before the reaction, or may be mixed with a buffer for pH control just before use, or may be brought into contact with water during the washing process. Examples of non-aqueous formulations include liquid, sheet, powder, tablet, oil, wax, ampoule, gel and the like which are used as ordinary non-aqueous cosmetic preparations. In addition, the carbodiimide compound and the bioadhesive component can be formulated as a single agent in an encapsulated form or in two separate forms, respectively. In addition, a method of blocking a derivative in which a functional group having a reactivity and a component having a bio-junction function are combined through encapsulation from moisture may also be used.

In order to increase the bioadhesion effect with a functional group in the composition for bioadhesion according to the present invention, it is preferred to use a mixture of 2-basic acid ester oil such as dioctylsuccinate, dioctyl adipate, diethyl sebacate and the like, polyol, polyethylene glycol, , Hexylene glycol, butane diol and their isomers, glycerol, benzyl alcohol, ethoxydiglycol and derivatives thereof. The above-mentioned solvents increase the permeability of hair or skin and are used as a solvent of a poorly soluble substance. More preferably, the solvent used for enhancing the activity-maintaining effect of the bio-bonding component having a functional group is diethyl sebacate, ethoxy glycol, bis-ethoxy glycol cyclohexane 1,4-dicarboxylate and the like.

Hereinafter, the present invention will be described in detail by the following examples. However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.

Example  1 to 2 and Comparative Example  One

The hair-bonding compositions of Examples 1 and 2 and Comparative Example 1 were prepared by the compositions and contents shown in the following Table 1, and 3 g of each of the prepared compositions was applied to each of the cracks of each of the twenty ends of the hair, The reaction was induced by leaving for a minute, and the process of washing with running water and shampoo was repeated twice a day for 3 days, and then the number of hair bonded was compared.

Category (% by weight) Comparative Example 1 Example 1 Example 2 water 49.0 48.0 48.0 ? -aminocaproic acid 1.0 1.0 1.0 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride - 1.0 - Benzene, 1,3, -bis (1-isocyanato-1-methylethyl) -, homopolymers, polyethylene glycol mono-ether- - - 1.0 The buffer (pH 4.5) 50.0 50.0 50.0 Sum 100.0 100.0 100.0

Example  3 to 4 and Comparative Example  2

The two-piece hair bonding compositions of Examples 3 and 4 and Comparative Example 2 were prepared by the compositions and contents shown in Table 2 below. Three grams of the prepared composition of Example 1 was applied to each of the cracks of the 20- After washing with running water, 3 g of the composition 2 was applied evenly to the cleaved part of the hair, and then allowed to stand at room temperature for 30 minutes to induce the reaction. Then, washing with running water and shampoo was repeated twice daily for 3 days After that, the number of hairs bonded was compared.

Category (% by weight) Comparative Example 2 Example 3 Example 4 1 The buffer (pH 8.0) 97.0 97.0 97.0 N- (4-carboxy-3-hydroxy-phenyl) maleimide 3.0 3.0 3.0 Sum 100.0 100.0 100.0 2 The buffer (pH 4.5) 100.0 97.0 97.0 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride - 3.0 - Benzene, 1,3, -bis (1-isocyanato-1-methylethyl) -, homopolymers, polyethylene glycol mono-ether- - - 3.0 Sum 100.0 100.0 100.0

In Examples 1 and 2 and Comparative Examples 1 and 2 (Table 2), carbodiimide-containing and carbodiimide-containing Examples 1 and 2 were compared with Comparative Example 1 containing? -Aminocaproic acid The effect of the covalent bond formation of carbodiimide was shown to be superior to that of Example 2. In particular, the polymeric carbodiimide of Example 2 exhibited better splicing of cleaved hair.

Further, even when N- (4-carboxy-3-hydroxy-phenyl) maleimide having a carboxyl group and a maleimide group is used in the molecule, excellent carbons The bonding effect was confirmed.

The state of hair before and after treatment with respect to the above composition is shown in Fig.

(N = 20, pieces) Comparative Example 1 Comparative Example 2 Example 1 Example 2 Example 3 Example 4 Number of shaved hairs 0 2 5 7 7 10

Formulation example : For bio junction Cosmetic  Produce

According to the conventional cosmetic preparation method, cosmetic compositions for bio-bonding were prepared with the ingredients and contents shown in Table 4 below.

division Component (% by weight) Lotion for splinting 1 Formulation Lotion 2 for grooming 1 The buffer (pH 8.0) - Balance ? -aminocaproic acid 1.0 - N- (4-carboxy-3-hydroxy-phenyl) maleimide - 1.0 glycerin 3.0 3.0 Polysorbate 60 1.5 1.5 Sorbitacecequioleate 1.5 1.5 Triethanolamine 0.1 0.1 Cetearyl alcohol 2.0 2.0 Wax 5.0 5.0 antiseptic Suitable amount Suitable amount Spices Suitable amount Suitable amount The buffer (pH 4.5) Balance - Sum 100 100 2 The buffer (pH 4.5) - Balance N- (4-carboxy-3-hydroxy-phenyl) maleimide - 1.0 glycerin - 3.0 Polysorbate 60 - 1.5 Sorbitacecequioleate - 1.5 Triethanolamine - 0.1 Cetearyl alcohol - 2.0 Wax - 5.0 antiseptic - Suitable amount Spices - Suitable amount Sum - 100

Claims (9)

A carbodiimide compound represented by the following formula (2); And a bio-bonding component.
(2)

In the above formula (2), n is 1 to 100 and m is 1 to 100.
The method according to claim 1,
Wherein the bio-bonding component comprises a carboxyl group or an amine group in the molecule.
The method according to claim 1,
Wherein the biojoint component is at least one selected from the group consisting of fibrin, albumin, glucosamine, n-acetylglucosamine, alginate, hydrogel, growth factor, physiologically active factor, necrotic tissue remover, glue bonding agent and antibacterial coating agent.
The method according to claim 1,
Wherein the biojunction component has a functional group capable of being covalently bonded to a hair or a protein residue on the skin surface.
5. The method of claim 4,
The functional groups covalently bonded to the protein include carbodiimide, imidoesters, aryl azides, diazylines, hydroxymethylphosphines, pentafluorophenyl esters, pyridyl disulfides, sulfo-hydroxysuccinimide esters, alkoxy amines, The present invention also relates to a process for the preparation of a medicament for the treatment and / or prophylaxis of a disease or condition selected from the group consisting of hydrazide, haloacetyl, azide, carbonate, aldehyde, propionaldehyde, butylaldehyde, nitrophenylcarbonate, aziridine, isocyanate, thiocyanate, epoxide, At least one selected from the group consisting of imidazole, oxycarbonylamidazole, imine, thiol, maleimide, vinylsulfone, ethyleneimine, thioether, acrylonitrile, acrylic acid or methacrylic acid ester, disulfide and ketone / RTI >
The method according to claim 1,
Wherein the carbodiimide compound is 0.001 to 10 parts by weight based on 100 parts by weight of the total composition.
The method according to claim 1,
A carbodiimide-based compound and a bioadhesive component are formulated into a single preparation in an encapsulated form; Wherein the carbodiimide compound and the bioadhesive component are separated from each other.
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