KR101286624B1 - Spray Device containing Tissue adhesive composition - Google Patents

Abstract

The present invention relates to a spray device incorporating a bioadhesive composition, and by using the bioadhesive as a spray type, it is possible to spray a wider wound more effectively, and easily to a portion where a pouch type bioadhesive cannot be directly attached. It is intended to support the use. The spray device incorporating the bioadhesive composition according to the present invention is an exterior case, an injection rod provided on one side of the exterior case, a discharge passage connected to the injection rod and disposed inside the exterior case, and an argon gas layer provided in the exterior case, the exterior case It includes a bioadhesive layer provided inside.

Description

Spray device containing bioadhesive composition {Spray Device containing Tissue adhesive composition}

The present invention relates to a bioadhesive, and more particularly to a spray device comprising a bioadhesive configured for use in a spray device.

Tissue adhesives are very useful high-tech medical products that replace damaged tissue by simple manipulation on behalf of sutures. Generally, the tissue to be bonded is wetted by body fluid or blood, and thus it is difficult to obtain sufficient adhesive force, and also has to have characteristics such as fast adhesion and biocompatibility, so only limited materials are used. Double fibrin glue and cyanoacrylate adhesives are the closest practical materials. Fibrin glue is composed of fibrinogen, thrombin, and calcium chloride, and adhesion is expressed by a reaction between them. However, because fibrinogen is manufactured separately from human plasma, there is a possibility of virus infection. Fibrin glue is widely used in various sites because of its hemostatic properties and tissue regeneration, but its adhesive strength is lower than that of cyanoacrylate adhesive.

Cyanoacrylate adhesives are originally known as instant adhesives as cyanoacrylate ester monomers. Colorless liquid, instantaneous polymerization by anionic polymerization under weak base such as water or amine. Cyanoacrylates of long alkyl esters have better adhesion in the blood than methylcyanoacrylates, which are shorter molecular chains, and degradation occurs slowly. While methylcyanoacrylate is fast to hydrolyze and forms formaldehyde, causing toxic inflammation, octyl cyanoacrylate (trade name: Dermabond), recently approved by the FDA, has excellent tissue compatibility and is widely applied as a tissue adhesive. It is expected to be. However, octylcyanoacrylates have low production yields and are mostly sold at high prices, so there are many restrictions on their commercial use.

Meanwhile, octylcyanoacrylate, which is used in the related art, is hardened at high speed in air and developed for single use and sold in pouch form. However, such a pouch-type bioadhesive has a disadvantage in that it cannot be used in areas where the hands are not closed or invisible to the eyes, and the use of the pouch is limited to wounds larger than the size of the pouch.

In order to solve the conventional problems as described above, the present invention can be sprayed more effectively to a wide wound by enabling the use of the bio-adhesive as a spray type, and can be easily used even in the area where the bio-adhesive of the pouch form cannot be directly attached. To provide a spray device with a built-in bio-adhesive to support.

In order to achieve the above object, the present invention is an exterior case, the injection rod provided on one side of the exterior case, the discharge passage connected to the injection rod and disposed inside the exterior case, an argon gas layer provided inside the exterior case, Disclosed is a configuration of a spray device incorporating a bioadhesive composition including a liquid bioadhesive layer provided inside the outer case.

Here, the argon gas layer may be composed of a mixed gas of an argon gas ratio of 80% and a carbon dioxide gas ratio of 20%, and may be disposed on the bioadhesive layer.

Meanwhile, the bioadhesive layer may be composed of 2-octylcyanoacrylate, and a diluent may be mixed with the 2-octylcyanoacrylate as necessary.

In addition, the bioadhesive layer contains polyoctylcyanoacrylate as a thickener, and 3,5-diiodine-4-pyridone-1-acetic acid (3,5-diiodo-4-pyridone-1- as an anion stabilizer It may be composed of a cyanoacrylate-based bioadhesive composition containing actetic acid).

Wherein the polyoctylcyanoacetate reacts cyanoacetic acid with octane alcohol in a 1: 1 equivalent ratio to produce octylcyanoacetate, and in the presence of a solvent, the octylcyanoacetate and paraformaldehyde are 1: 1 equivalent ratio. After the reaction, the reaction is completed, the solvent may be removed and then the octylcyanoacrylate is separated and purified to obtain a polyoctylcyanoacrylate from the remaining by-product.

The bioadhesive layer may be a composition used as a wound coating agent, a cartilage adhesive, an organ bonding agent, a blood vessel bonding agent, a neuroadhesive agent, or an oral bonding agent.

According to the spray device incorporating a bioadhesive according to the present invention, the present invention can be easily applied to a wide range of wounds or invisible or unclosed wounds based on the method of spraying and spraying directly on the wound site. In addition, it can be used several times in succession to support more economical and efficient wound healing.

1 is a view schematically showing the configuration of a spray device according to an embodiment of the present invention.
2 is a view for explaining a method for manufacturing a spray device containing the bioadhesive composition of the present invention.
3 is a view for explaining a method for producing a bioadhesive that can be used in the bioadhesive of the present invention.

In the following description, only parts necessary for understanding the embodiments of the present invention will be described, and the description of other parts will be omitted so as not to obscure the gist of the present invention.

The terms and words used in the present specification and claims should not be construed as limited to ordinary or dictionary meanings and the inventor is not limited to the meaning of the terms in order to describe his invention in the best way. It should be interpreted as meaning and concept consistent with the technical idea of the present invention. Therefore, the embodiments described in the present specification and the configurations shown in the drawings are merely preferred embodiments of the present invention, and are not intended to represent all of the technical ideas of the present invention, so that various equivalents And variations are possible.

1 is a view schematically showing a spray device 100 integrated with a bioadhesive according to an embodiment of the present invention.

Referring to FIG. 1, the spray device 100 of the present invention includes an exterior case 10, a spray table 20, a discharge path 30, an argon (Ar) gas layer 40, and a bioadhesive layer 50. It may include.

In the spray device 100 of the present invention having such a configuration, the bioadhesive layer 50 is embedded in the exterior case 10 together with the argon gas layer 40, so that the injection hole provided in the spray table 20 is opened. In this case, the bioadhesive constituting the bioadhesive layer 50 is sprayed through the injection hole along the discharge path 30 by the pressure of the argon gas layer 40. The spray device 100 can support the user to continuously spray the bioadhesive through the spraying rod 20 while performing the operation of the spraying rod 20 so that the bioadhesive can be easily applied to a wide range of wounds. Can be.

The exterior case 10 may be formed of various materials such as steel, aluminum, or an alloy having strength corresponding thereto. The exterior case 10 may be manufactured in a hemispherical shape in which the bottom surface is bent upward to support the internal pressure, and the upper end may have a structure that is entirely sealed by the injection table 20. In addition, the discharge case 30, the argon gas layer 40, and the bioadhesive layer 50 described below may be provided in the exterior case 10. The exterior case 10 may be manufactured in a cylindrical shape for internal pressure distribution, and may also be manufactured in the shape of a hexahedron according to storage or a special purpose. The upper end of the exterior case 10 may be manufactured in a protruding shape for the placement of the injection rod 20, so that the area around the area on which the injection rod 20 is mounted may be sealed after the placement of the injection rod 20. Certain structures may be further provided, such as rubber or special plastic structures.

The spraying rod 20 is mounted on the upper end of the exterior case 10, and sprays the bioadhesive disposed inside the exterior case 10 to the outside in the form of a spray by external pressure such as a user's pressing pressure. This configuration is supported. The spray rod 20 may be formed of a material having a certain strength, for example, a plastic material to support the user's finger pressing, the size is smaller than the size of the groove provided in the upper end of the exterior case 10 Can be prepared. The spray table 20 may further provide an additional structure to adjust the amount of spray or spray rate. Here, the additional structure may be provided in a form that can substantially adjust the size of the injection hole provided in the injection table (20). In addition, the spray table 20 may be mounted on the upper end of the exterior case 10 in a replaceable form in order to prevent the clogging of the injection hole due to the curing of the bio-adhesive sprayed by the bio-adhesive injection.

The discharge path 30 may be provided in a tubular shape in which one end thereof is connected to the injection rod 20 and the other end thereof is connected to a predetermined height of the bottom of the exterior case 10. The discharge path 30 is provided for discharging the bioadhesive layer of the bioadhesive layer 50 which is encapsulated from the bottom of the exterior case 10 to a predetermined height. That is, when the injection port of the injection table 20 is opened, if pressure is applied internally to the bioadhesive layer 50 in proportion to the pressure of the exterior case 10 relative to the atmospheric pressure, the discharge path 30 is the bioadhesive layer 50. Guide the inflow of the bio-adhesive located in the) and the movement inside the tube to support the movement in the direction of the injection hole of the injection table (20). The discharge path 30 may be formed of various materials such as rubber or plastic, for example.

The argon gas layer 40 is a layer in which argon gas, which is an inert gas, is disposed, and is positioned above the bioadhesive layer 50 in the exterior case 10. Such argon material may be sprayed by mixing with other materials, such as carbon dioxide gas. When carbon dioxide is mixed with argon gas, the argon gas layer 40 may be formed by mixing 80% argon gas and 20% carbon dioxide gas. In addition, the argon gas layer 40 acts as a shield gas of the bioadhesive layer 50 to change a material provided in the bioadhesive layer 50, for example, 2-octylcyanoacrylate or polyoctylcyanoacrylate. It can play a role of preventing. In particular, the argon gas provided in the argon gas layer 40 may serve to prevent solidification of the bioadhesive provided in the bioadhesive layer 50 so as not to solidify itself even after a long time.

The bioadhesive layer 50 is a liquid suture, and is provided in the lower portion of the argon gas layer 40 as a region where the bioadhesive is distributed, while the injection hole of the injection table 20 is opened by the comparative pressure inside and outside the exterior case 10. The bioadhesive material is introduced along the discharge path 30 to be sprayed through the injection hole. Here, the bioadhesive may be 2-octylcyanoacrylate, or may be polyoctylcyanoacrylate, which is a byproduct of octylcyanoacrylate used as a thickener described below. In addition, the bioadhesive and the diluent may be mixed together as necessary to form the bioadhesive layer 50. The diluent is used for the purpose of diluting the concentration or viscosity of the bioadhesive and the diluent may be mixed to prevent self-coagulation of the bioadhesive. The diluent is preferably composed of a material for which a bioadhesive is applied, that is, a human body. The production of the polyoctylcyanoacrylate as the bioadhesive will be described in more detail with reference to the drawings to be described later.

As described above, the spray apparatus 100 for the bioadhesive according to the embodiment of the present invention may support the bioadhesive as a spray type by encapsulating the bioadhesive together with the argon gas and the diluent in the exterior case 10. Accordingly, the spray device 100 of the present invention supports the use of the bio-adhesive having a limited number of uses more easily, and can be easily supported for carrying and storing.

Figure 2 will be described with respect to the manufacturing method of the spray device containing a bioadhesive composition according to an embodiment of the present invention.

Referring to FIG. 2, the method for manufacturing the spray device 100 of the present invention first prepares an exterior case 10 in which the discharge path 30 is disposed in step S101.

Next, a predetermined amount of argon gas is injected into the spray container through the discharge path 30 in step S103. Here, the argon gas may be mixed with another material, for example carbon dioxide gas, to be injected to support the spray function. In particular, the material injected into the spray container may be injected by mixing 80% argon gas to 20% carbon dioxide gas. Accordingly, an argon gas layer 40 may be formed in the spray container.

Next, in step S105, a predetermined amount of cyanoacrylate-based bioadhesive composition including 2-octylcyanoacrylate or polyoctylcyanoacrylate, which is a bioadhesive, is injected into the spray container through the discharge passage 30. Wherein said bioadhesive contains polyoctylcyanoacrylate as a thickener and 3,5-diiodine-4-pyridone-1-acetic acid (3,5-diiodo-4-pyridone-1-actetic) as an anion stabilizer acid) -containing cyanoacrylate-based bioadhesive composition. The bioadhesive may be mixed and injected with a diluent to prevent self-solidification in the exterior case 10. The bioadhesive injected along the discharge path 30 may form the bioadhesive layer 50 while pushing the argon gas layer 40 injected thereon upward. To this end, the preparation may be performed to prepare 2-octylcyanoacrylate, which is previously used as the bioadhesive, or to prepare polyoctylcyanoacrylate. The polyoctylcyanoacrylate preparation will be described in more detail with reference to FIG. 3.

The argon gas layer 40 injected in step S103 may be injected in a predetermined amount in consideration of the gas injection pressure, and the capacity may be adjusted according to the size of the spray container and the injection hole shape of the spray table 20.

As described above, the spray device according to the embodiment of the present invention is a cyanoacrylate-based bioadhesive that is rapidly cured in the air is encapsulated in a predetermined case with a suitable ratio of diluent and argon gas and configured in the form of a spray I can make it. Accordingly, the spray device of the present invention allows the bioadhesive to be applied in a spray form, thereby supporting the use and storage of the bioadhesive more easily in a wider area.

Figure 3 is a flow chart for explaining the production of polyoctylcyanoacrylate according to an embodiment of the present invention.

Referring to FIG. 3, in the method for preparing polyoctylcyanoacrylate of the present invention, a method of preparing octylcyanoacetate by reacting cyanoacetic acid and octane alcohol in a 1: 1 equivalent ratio in the presence of a solvent [S201] ], Reacting the octylcyanoacetate and paraformaldehyde in a 1: 1 equivalent ratio in the presence of a solvent [S203], removing the solvent and separating and purifying the octylcyanoacrylate after the reaction is completed [S205] and Purifying octylcyanoacrylate and obtaining polyoctylcyanoacrylate from the remaining by-product [S207].

At this time, the solvent used in each reaction process may include an organic solvent commonly used in the art, for example, benzene, toluene or xylene may be used, but is not limited thereto. In addition, the polyoctylcyanoacrylate can be obtained by purifying by-products with silica gel, the content of which is preferably 0.001 to 4% by weight based on the total weight of the composition.

The 3,5-diiodine-4-pyridone-1-acetic acid used as an anion stabilizer in the present invention is characterized by having an antibacterial effect as well as an anion stabilizing function. The anion stabilizer is preferably added in an amount of 0.8 to 2.9% by weight based on the total weight of the composition.

In addition, the cyanoacrylate-based bioadhesive composition according to the present invention contains at least one polymerizable cyanoacrylate monomer as a main component and, in addition to the thickener and anion stabilizer, any component commonly used in the manufacture of bioadhesives in the art. It may further include them. For example, the cyanoacrylate-based bioadhesive composition according to the present invention may be applied to one or more polymerizable cyanoacrylate monomers, thickeners and anion stabilizers, free radical stabilizers, anionic gas phase stabilizers, polymerization initiators, plasticizers, It may further contain one or more of colorants, preservatives, heat dispersants, thixotropes and biocompatible agents, more specifically 90-95% by weight of one or more polymerizable cyanoacrylate monomers relative to the total weight of the composition, glass 0.01 to 0.2% by weight of a radical stabilizer, 0.01 to 2% by weight of a polymerization initiator and 0.001 to 2% by weight of other additives (such as plasticizers, colorants, preservatives, heat dispersants, or biocompatible agents).

In one embodiment of the invention the at least one polymerizable cyanoacrylate monomer is octylcyanoacrylate, dodecylcyanoacrylate, 2-ethylhexylcyanoacrylate, methoxyethylcyanoacrylate, 2-ethoxy Ethylcyanoacrylate, butylcyanoacrylate, ethylcyanoacrylate, methylcyanoacrylate, 3-methoxybutylcyanoacrylate, 2-butoxyethylcyanoacrylate, 2-isopropoxyethyl Cyanoacrylate, 1-methoxy-2-propylcyanoacrylate, butyllactoylcyanoacrylate, butylglycoylcyanoacrylate, isopropylglyloylcyanoacrylate, ethyl lactoylcyanoacrylate, ethyl Glyloylcyanoacrylate, isopropoxyoxycyanoacrylate, methoxybutylcyanoacrylate, and mixtures thereof It can be used at least one selected from the group eojin, and preferably uses dicyano-octyl acrylate.

As the free radical stabilizer, hydroquinone, hydroquinone monomethyl ether, methoxyhydroquinone, catechol, pyrogallol, benzoquinone, 2-hydroxybenzoquinone, p-methoxyphenol, t-butylcatechol, butylated Hydroxyanisole, butylated hydroxytoluene, t-butylhydroquinone and mixtures or combinations thereof can be used.

The anionic gaseous stabilizer may be sulfur dioxide, boron trifluoride or hydrogen fluoride.

The polymerization initiator may be used a quaternary ammonium salt, for example, domiphen bromide, butyrylcholine chloride, benzalkonium bromide, benzalkonium chloride or acetylcholine chloride.

Examples of the plasticizer include acetyl tributyl citrate, dimethyl sebacate, dibutyl sebacate, triethyl phosphate, tri (2-ethylhexyl) phosphate, tri (p-crezyl) phosphate, glyceryl triacetate, and glyceryl tributyrate. , Diethyl sebacate, dioctyl adipate, isopropyl myristate, butyl stearate, lactic acid, trioctyl trimellitate, dioctyl glutarate, polydimethylsiloxane and mixtures thereof.

Examples of the preservative include methyl paraben, methyl paraben sodium, ethyl paraben, propyl paraben, propyl paraben sodium, butyl paraben, cresol or chlorocresol.

The heat dispersant is potassium nitrate, sodium acetate trihydrate, sodium sulfate decahydrate, barium hydroxide octahydrate, calcium oxalate dihydrate, magnesium oxalate Dihydrate (magnesium oxalate dihydrate), aluminum hydroxide, zinc sulfate, aluminum oxide, barium oxide, titanium oxide, manganese oxide, calcium oxide; Copper, lead, nickel, aluminum, zinc; Carbon black, carbides; Urea, paraffin wax, polyvinyl fluoride; 2-hydroxy-2-trimethylsilanyl-propionitrile, 1-fluorophenacyclo [6.3.0.02,6.03,10.05,9] undecane, 6,7-diazabicyclo [3.2 .1] -6-octene, 5,5,6,6-tetramethylbicyclo [2.2.1] heptan-2-ol, a complex of dimethylmagnesium and trimethylaluminum, N-benzyl-2,2,3,3 , 4,4,4-heptafluoro-butyramide, 3-isopropyl-5,8a-dimethyl-decahydronaphthalen-2-ol, 2-hydroxymethyl-1,7,7-trimethyl-bicyclo [2.2.1] heptan-2-ol, 3,5-dichloro-3-methyl-cyclopentane-1,2-dione, (5-methyl-2-oxo-bicyclo [3.3.1.] Non-3 -En-1-yl) -acetic acid, 4b, 6a, 11,12-tetrahydro-indeno [2,1-a] fluorene-5,5,6,6-tetracarbonitrile, tetracosa Fluoro-tetradecahydro-anthracene, 4,5-dichlorobenzene-1,2-dicarbaldehyde, bicyclo [4,3.1] dec-3-en-8-one, 3-tert -Butyl-1,2-ratio S- (3,5-dimethylphenyl) -3-hydroxyguanidine, 1- [2,6-dihydroxy-4-methoxy-3-methylphenyl] butan-1-one, 2,3,6,7 Tetrachloronaphthalene, 2,3,6-trimethylnaphthalene, dodecafluoro-cyclohexane, 2,2,6,6-tetramethyl-4-hepten-3-one, 1,1,1-trichloro- 2,2,2-trifluoro-ethane, [5- (9H-β-carbolin-1-yl) -furan-2-yl] methanol, 5-nitro-benzo [1,2,3 ] Thiadiazole, 4,5-dichloro-thiophene-2-carboxylic acid, 2,6-dimethyl-isonicotinonitrile, nonafluoro-2,6-bis-trifluoromethyl-piperidine , (Dimethylamino) difluoroborane, dinitrogen pentoxide, chromyl fluoride, and chromium hexacarbonyl; 1-methylcyclohexanol, phenylether, nonadecane, 1-tetradecanol, 4-ethylphenol, benzophenone, maleic anhydride, octacosane, dimethylisophthalate, butylhydride Butylated hydroxytoluene, glycolic acid, vanillin, magnesium nitrate hexahydrate, cyclohexanone oxime, glutaric acid, D-sorbitol, phenanthrene, metaanthene Single or two or more of krillamide, fluorene, 4-hydroxybenzaldehyde, trans-stilbene, neoopentyl glycol, pyrogallol, or diglycolic acid Can be used in combination.

Biocompatible agents are ingredients that reduce the active formaldehyde concentration levels produced during the biodegradation of the polymer, such as, for example, sulfite, bisulfite, or mixtures of sulfite and bisulfite.

The bioadhesive composition according to the present invention may be used as a wound coating agent, a cartilage adhesive agent, an organ bonding agent, a blood vessel bonding agent, a neuroadhesive agent or an oral bonding agent, but is not limited thereto.

It should be noted that the embodiments of the present invention disclosed in the present specification and drawings are only illustrative of specific examples for the purpose of understanding and are not intended to limit the scope of the present invention. It will be apparent to those skilled in the art that other modifications based on the technical idea of the present invention are possible in addition to the embodiments disclosed herein.

10: appearance case 20: jet
30: discharge furnace 40: argon gas layer
50: bioadhesive layer 10: spray device

Claims (8)

Appearance case;
A spraying bar provided on one side of the exterior case;
A discharge passage connected to the injection rod and disposed inside the outer case;
An argon gas layer provided inside the outer case;
A liquid bioadhesive layer provided inside the outer case;
/ RTI >
The bioadhesive layer is
Containing polyoctylcyanoacrylate as a thickener and containing 3,5-diiodine-4-pyridone-1-acetic acid as an anion stabilizer A spray device incorporating a bioadhesive composition, which is a cyanoacrylate-based bioadhesive composition. The method of claim 1,
The argon gas layer
A spray device incorporating a bioadhesive composition, comprising a mixture of argon gas at 80% and carbon dioxide at 20%. The method of claim 2,
The argon gas layer
Spray device embedded with a bioadhesive composition, characterized in that disposed on the bioadhesive layer. delete delete The method of claim 1,
The polyoctylcyanoacrylate is
Octylcyanoacetate was prepared by reacting cyanoacetic acid and octane alcohol in a 1: 1 equivalent ratio in the presence of a solvent, and the reaction was completed after reacting the octylcyanoacetate and paraformaldehyde in a 1: 1 equivalent ratio in the presence of a solvent. When the solvent is removed, and the octyl cyanoacrylate is separated and purified while obtaining a poly octyl cyanoacrylate from the remaining by-products, the spray device containing the bioadhesive composition. The method of claim 1,
The bioadhesive layer is
A spray device incorporating a bioadhesive composition, which is a composition used as a wound coating agent, a cartilage adhesive agent, an organ bonding agent, a blood vessel bonding agent, a neuroadhesive agent or an oral bonding agent. The method of claim 1,
The bioadhesive layer is
A spray device with a built-in bioadhesive composition, characterized in that the bioadhesive is mixed with a predetermined amount of diluent.

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