Company Catalog

(20150210)

IntuitiveMediCorp,Inc’s products are manufactured using our patented BIOFIT™ Technology. This unique formulation and process provides the optimal balance of the properties that matter most to physicians – strength to preserve the integrity of the wound closure and unmatched flexibility for patient comfort and physician control.

BIOFIT™ Product Info

DESCRIPTION High viscosity BIOFIT™ Topical Skin Glue is a sterile, liquid topical skin Glue containing a monomeric (2-octyl cyanoacrylate) formulation and the colorant . It is provided in a single use applicator packaged in a blister pouch.

The applicator is comprised of a crushable plastic ampule contained within a plastic vial with attached applicator tip. The product is also available with a pen applicator. As applied to skin, the liquid is syrup-like in viscosity and polymerizes within minutes. In vitro studies have shown that high viscosity BIOFIT™ Glue acts as a barrier to microbial penetration as long as the Glue film remains intact.

High viscosity BIOFIT™ Glue is different from the regular, or low viscosity BIOFIT™ Glue due to the increased viscosity of the liquid Glue formulation. Low viscosity BIOFIT™ Glue has a viscosity slightly greater than water, while high viscosity BIOFIT™ Glue has a syrup-like viscosity. The increased viscosity of high viscosity BIOFIT™ Glue is intended to reduce the risk of unintended placement of the Glue during application due to migration of the liquid Glue from the wound site.

INDICATIONS High viscosity BIOFIT™ Topical Skin Glue is intended for topical application only to hold closed easily approximated skin edges of wounds from surgical incisions, including punctures from minimally invasive surgery, and simple, thoroughly cleansed, trauma-induced lacerations. High viscosity BIOFIT™ Glue may be used in conjunction with, but not in place of, deep dermal stitches. INDICATIONS BIOFIT™ Topical Skin Glue is intended for topical application only to hold closed easily approximated skin edges of wounds from surgical incisions, including punctures from minimally invasive surgery, and simple, thoroughly cleansed, trauma-induced lacerations. BIOFIT™ Glue may be used in conjunction with, but not in place of,

For information on availability on IntuitiveMediCorp,Inc’s products in your area or how to order IntuitiveMediCorp,Inc’s products, please contact [email protected]

Clinical Education

IntuitiveMediCorp,Inc’s researchers are working closely with wound care specialists to develop a program to train doctors and clinicians in the proper use of IntuitiveMediCorp,Inc’s cyanoacrylate-based Glue products. Please check this our site(www.intuitivemedicorp.com) periodically for updates on our training programs and literature.

Description Product Code Fill Volume(ml) Packaging Remarks

BIOFIT™ BFCB001 0.5 10Applicators Topical Skin per Box Glue

BiOFiT Topical Skin Adhesive Manual

DESCRIPTION High viscosity BiOFiT Topical Skin Adhesive is a sterile, liquid topical skin adhesive containing a monomeric (2-octylcyanoacrylate) formulation. It is provided in a single use applicator packaged in a blister pouch. The applicator is comprised of HDPE applicator contained within a plastic vial with attached applicator tip. As applied to skin, the liquid is syrup-like in viscosity and polymerizes within minutes. In vitro studies have shown that high viscosity BiOFiT adhesive acts as a barrier to microbial penetration as long as the adhesive film remains intact. Clinical studies were not conducted to demonstrate microbial barrier properties.

INDICATIONS High viscosity BiOFiT Topical Skin Adhesive is utilized for topical application only to hold closed easily approximated skin edges of wounds from surgical incisions, including punctures from minimally invasive surgery, and simple, thoroughly cleansed, trauma-induced lacerations. High viscosity BiOFiT adhesive may be used in conjunction with, but not in place of deep dermal stitches. CONTRADITIONS • Do not use on any wound with evidence of active infection, gangrene, or wounds of decubitis etiology. • Do not use on mucosal surfaces or across mucocutaneous junctions (e.g., oral cavity, lips), or on skin which may be regularly exposed to body fluids or with dense natural hair,(e.g.,scalp). • Do not use on patients with a known hypersensitivity to cyanoacrylate or

formaldehyde.

WARNINGS Solvents such as acetone should be avoid. BiOFiT should not be applied to wet wounds. BiOFiT should not be applied to eye. When it occurs : flush the eye with saline or water. BiOFiT should not be used below the skin due to non absorption by skin or eliciting a foreign body reaction. BiOFiT should not be used in high skin tension. BiOFiT should not be used on wound sight that is to be subjected to repeated or continual moisture or friction. BiOFiT should be used after wounds have been cleaned. BiOFiT should be packaged and utilized for single use only. Discard remaining opened material. Do not resterilize BiOFiT adhesive. Do not apply liquid or ointment medication or other substances to the wound after close with BiOFiT adhesive. If unintended bonding of intact skin occurs ‘Petroleum jelly or acetone may help loosen the bond. Other agents such as water, saline’. Keep away from children. Check the adhesive validation time. (recommendable two years after production) Do not swallow adhesive. Keep the adhesive below room temperature.

Keep away from the direct sunlight. To use applicator, hold the body without gripping the cap and twist the cover Keep refrigerated to use longer period Multiple and thin application to proceed polymerization

Manufacturer : IntuitiveMediCorp, Inc. 105, Saneopdanji-gil, Pungsan-eup, Andong-si, Gyeongsangbuk-do, Rep of Korea

KFDA License Number 14-506

Picture can be changeable according company’s decision at any time.

To Place An Order:

E-mail: [email protected] Phone: +82(0)548235250 Fax: +82(0)548235251

BIOFIT™ Atomic Force Microscope picture

Product under the sales

PRODUCT 2-OCA* Hydroxy B-TCP GELATIN Apatite ` Dental Filler 50% 40% 10% Anti Adhesion 50% 50% Barrier Bone Cement 70% 30% Hemostat 80% 20% Synthetic 50% 40% 10% Bone

Patent_Registered(http://kpa.kipris.or.kr/kpa/search/search_kpa.do)

시아노아크릴레이트계 생체 접착제 조성물(Cyanoacrylate-based tissue adhesive composition)

CYANOACRYLATE-BASED TISSUE ADHESIVE COMPOSITION, WHICH USES POLY OCTYL CYANOACRYLATE AND 3,5-DIIODINE-4-PYRIDONE-1-ACETIC ACID

PURPOSE: A cyanoacrylate-based tissue adhesive composition is provided to enhance biodegradation property and antimicrobial efficiency.

CONSTITUTION: A cyanoacrylate-based tissue adhesive composition comprises poly octyl cyanoacrylate and 3,5-diiodine-4-pyridone-1-acetic acid. The poly octyl cyanoacetate is prepared as follows. The octyl cyanoacetate is prepared by reacting cyanoacetic acid and octane alcohol at 1:1 equivalence ratio. The octyl cyanoacetate and paraformaldehyde are reacted at 1:1 equivalence ratio. The octyl cyanoacrylate is separated and refined after eliminating solvent if the reaction is completed. The poly octyl cyanoacrylate is obtained from by-product in which octyl cyanoacrylate is refined.

The present invention relates cyano-acrylate adhesive composition vivo using biodegradable poly-octyl Montepulciano that is generated as a by-product during the manufacture acrylate Ano than as a thickener when octyl acrylate, as anionic stabilizers increase By using 3,5-die-iodine, 4-flute money-1-acetic acid (3,5-diiodo-4-pyridone-1-actetic acid) excellent antimicrobial efficacy, cyano acrylate adhesive composition vivo.

Damaged tissue by a simple operation on behalf of the suture, tissue adhesive bonding is very useful state-of-the-art medical supplies. Generally want to join the organization because it is wet in the blood or body fluids, and difficult to obtain sufficient adhesion only in limited, so possess characteristics such as fast adhesive properties and biocompatibility has been used. Double fibrin glue (fibrin glue) and cyanoacrylate glue (cyanoacrylate) is closest to the practicality ofFibrinogen (fibrinogen), fibrin glue and thrombin (thrombin) and calcium chloride (calcium chloride) is composed of the expression of adhesion by the reaction between them. Separation are manufactured from human plasma fibrinogen However, there are disadvantages that are likely to be infected with the virus. The fibrin glue used in many different areas but excellent hemostatic properties and tissue regeneration compared with cyanoacrylate glue, adhesive strength decreases,

Cyanoacrylate adhesive cyanoacrylate ester monomer as the original superglue known. Instantaneous polymerization of the anionic polymerization under a weak base, such as water or an amine as a colorless liquid. The long alkyl ester cyanoacrylate compared to a short molecular chain the Montepulciano methyl acrylate, exploded views, and excellent adhesion of the blood Gunn On the other hand, no Shia recently gained FDA approval octyl acrylate (trade name: Dermabond), the hydrolysis of the Montepulciano methyl acrylate, causing inflammation, toxic formaldehyde generated by fast expanding applied as a tissue adhesive has excellent histocompatibility is expected to be However, when octyl Ano acrylate production yield is low and most expensive, and sold them for commercial use, there are many restrictions.

Cyano-acrylate adhesive, cost-effective efforts to manufacture the biodegradable and antibacterial activity with excellent results, the inventors of the present invention using biodegradable acrylate as a thickener, which is generated as a by-product of octyl City Ano acrylate manufacturing poly-octyl Montepulciano increased 3,5-die-iodine -4 flute Don -1 - by using acetic acid as the anionic stabilizers, antimicrobial efficacy and excellent bio-cyanoacrylate glue compositions that can be prepared the present invention and discovery. has been completed.

Therefore, an object of the present invention is to provide a biodegradable and antibacterial efficacy and economic bio-cyano-acrylate adhesive composition.

To achieve the above objects, poly-octyl acrylate containing Montepulciano, in the present invention, as a thickener, containing acetic acid, 3,5-die-iodine -4 flute Don -1 - as the anionic stabilizers cyano-acrylate-based bio- the adhesive composition.

Cyano-acrylate-based bio-adhesive composition according to the present invention, wherein the poly-octyl acetate, Montepulciano cyano-acetic acid and octane alcohol is reacted with a 1:1 equivalence ratio in the presence of a solvent, octyl acetate Montepulciano, manufacturing steps, the presence of solvent refining the octyl, isooctyl acrylate, Montepulciano and Montepulciano acetate reacting paraformaldehyde equivalence ratio of 1:01, after the reaction is complete, the solvent was eliminated, separation, purification steps, and octyl Montepulciano acrylate under the remaining It can be manufactured through the steps to obtain a poly-octyl acrylate Montepulciano byproduct.

And in the cyano-acrylate-based bio-adhesive composition according to the present invention, the composition window epithelial replication, long-term cartilage adhesive, bonding agent, binder, vascular nerve junctions first or zero junction oral, can be prepared.

Separation, octyl cyanoacrylate bio-adhesive composition according to the present invention to increase the biodegradability was purified and the remaining by-product of poly-octyl Montepulciano acrylate is used as a thickener, iodine, 3,5-die-4-flute money -1 - by using the antibacterial efficacy of acetic acid anion stabilization agent was excellent.

Poly-octyl Montepulciano isooctyl acrylate Montepulciano and acrylate used in the present invention is a schematic diagram showing the process of manufacturing.

Only what you need to understand the embodiment of the present invention will be described in the following description, it should be noted that the description of the other parts will be omitted to avoid, scatter the gist of the present invention.

Less than that described in the specification and claims, the terms or words used are limited to common or dictionary meaning is not to be construed, to the best explanation of his own invention, the inventor of the concept of the term appropriate should be interpreted based on the meanings and concepts corresponding to technical aspects of the present invention can be defined based on the principle that Thus, the configuration that is shown in the drawings and embodiments described herein to only a preferred embodiment of the present invention only, and does not represent all of the technical idea of the present invention, as in effect at the time of filing this can replace them equivalents It should be understood that there may be a modified example.

-1-acetic acid, 3,5-die-iodine, 4-flute money as that is generated as a by-product during the manufacture Ano acrylate, poly the Montepulciano octyl acrylate, octyl when using the present invention as a thickener and a biodegradable anionic stabilizers By using cyano-acrylate economic bio-adhesive composition having excellent antimicrobial efficacy.

, Which is produced as a by-product in the manufacturing process Ano acrylate, when used as a thickener in the present invention, the poly octyl Montepulciano acrylate, octyl until now has been discarded.

As used in the present invention, the manufacturing process of poly-octyl acrylate Montepulciano is shown in Figure 1. Look at this in more detail, that manufactures octyl acetate, Montepulciano, the solvent in the presence of the cyano acetic acid (cyannoacetic acid) and octane alcohol is reacted with a 1:1 equivalence ratio 1: the octyl the Montepulciano acetate and the paraformaldehyde in the presence of the solvent phase; steps to obtain a poly-octyl acrylate Montepulciano, and octyl acrylate Montepulciano octyl acrylate Montepulciano, separation and purification of; After removing the solvent, was purified from the remaining byproducts After completion of reaction, reacting to the equivalence ratio; include: At this time, the solvent used in the reaction process, and the organic solvents commonly used in the art, such as benzene, toluene or xylene, for example, can be used, but is not limited thereto. Can be obtained byproduct was purified by silica gel and the poly acrylate, octyl Montepulciano, the content is preferably about 0.001 to 4% by weight based on the total weight of the composition.

In the present invention is used as the anion stabilized iodine, 3,5-die-4-flute money-1-acetic acid has the structure of formula, and the anion stabilization as well as the ability to have antibacterial efficacy. The anionic stabilizers to be added to 0.8 to 2.9% by weight based on the total weight of the composition is desirable.

Formula 1

The thickeners and stabilizers anion addition to any of the ingredients commonly used in the art during the manufacture of bio-adhesive cyano-acrylate-based bio-adhesive composition according to the present invention containing the active ingredient and one or more polymerizable cyanoacrylate monomer. It may further include. For example, the cyano-cyanoacrylate-based bio-adhesive composition according to the present invention, at least one polymerizable acrylate monomer, a thickener, and anionic stabilizers, free radical stabilizer, an anionic weather stabilizers, polymerization initiators, plasticizers, a colorant, a trough first tikso, and biocompatible first of one or more preservatives, heat dispersant, and may contain one or more polymerization based on the total weight of the composition, and more particularly cyano acrylate monomer, 90 to 95% by weight of glass radical stabilizers 0.01 to 0.2 wt% and a polymerization initiator, 0.01 to 2 wt% and other additives (plasticizers, colorants, preservatives,, heat dispersing agent, or biocompatible first) from 0.001 to 2 wt% may contain.

In one embodiment of the present invention, the one or more polymerizable cyanoacrylate monomers, octyl in Montepulciano acrylate, dodecyl in implementation Ano acrylate, 2- ethylhexyl conducted Ano acrylate, methoxyethyl in Montepulciano acrylate, 2 - ethoxyethyl in Montepulciano acrylate, butyl in Montepulciano acrylate, ethyl in Montepulciano acrylate, methyl acrylate, Montepulciano, Montepulciano 3-methoxy-butyl acrylate, 2-butoxy ethyl Montepulciano acrylate, 2-isopropoxy ethyl cyano acrylate, 1-methoxy-2-Time Lactobacillus Ano profile Montepulciano acrylate, butyl acrylate, butyl glycol Boliviano pause pause piano glycol acrylate, isopropyl acrylate, ethyl Montepulciano temporary lactose acrylate, at least one member selected from the group consisting of pause piano acrylate, iso-oxy-ethyl propionate Montepulciano methoxy acrylate, butyl in Montepulciano acrylate, and mixtures thereof may be used, ethyl glycol, preferably octyl acrylate-Ano is used.

The radical stabilization agents, hydroquinone, hydroquinone monomethyl ether, hydroquinone, methoxy catechol, fatigue galrol, and Benzoquinone, 2-hydroxy-Benzoquinone, p-methoxy phenol, t-butyl catechol, butylated hydroxy anisole, butylated hydroxy toluene, t-butyl hydroquinone, and mixtures thereof, or compounds may be used.

Weather the anionic stabilizers, sulfur dioxide, Boron trifluoride, hydrogen fluoride, and the like.

The polymerization initiator Reel Booty quaternary ammonium salt, for example, sea bream pen bromide, choline chloride, benzalkonium bromide, benzalkonium chloride or acetylcholine chloride, etc. may be used.

The plasticizer, acetyl tributyl citrate, dibutyl Sheba dimethyl-Sheba, Kate, Kate, triethyl phosphate, tri (2-ethylhexyl) phosphate, tree (p-Creston quality) phosphate, glyceryl triacetate, glyceryl butyrate tree mixture of diethyl the Sheba Kate, dioctyl adipate, isopropyl myristate, butyl stearate, lactic acid, Tree Jade tilt Lee Tate Melilla the diok rates of doubles tilgeul, polydimethylsiloxane, and of these, can be

Above, methyl paraben, sodium methyl paraben, ethyl paraben, Propylparaben, Propylparaben sodium, butyl paraben, cresol, chloro cresol as a preservative.

The thermal dispersant potassium nitrate, sodium acetate trihydrate (sodium acetate trihydrate), sodium sulfate 10 hydrate (sodium sulfate decahydrate), barium hydroxide hydrate 8 (barium hydroxide octahydrate), calcium oxalate dihydrate (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 and zinc; carbon black (carbon black), carbides (carbides) elements; urea, paraffin wax, fluorine resin (polyvinyl fluoride); 2-hydroxy-2-trimethyl Silas Neal, propionitrile, 2-fluoro- Malpensa the cycle [6.3.0.02,6.03,10.05,9 est Khan undecane, 6,7-Dia, the jabayi cycle (diazabicyclo) -6 - [3.2.1] octene, 5,5,6,6-tetramethyl-by-cycle [2.2.1] heptane-2-ol, dimethyl magnesium and of trimethyl aluminum complex, N-benzyl--2,2,3,3,4,4,4 - hepta fluoro butyric amide, 3-isopropyl-a -5,8-dimethyl-deca-hydro-naphthalene-2-ol, 2-hydroxy-methyl -1,7,7- trimethyl-by-cycle [2.2.1] heptane-2-ol, 3,5-dichloro-3-methyl-(5-methyl cycle, pentane-1 ,2- dione, -1-yl)-acetic acid, 2-oxo-by-cycle [3.3.1] non-3-yen Tetra-fluoro-Xhosa-tetra-deca-hydro- anthracene (anthracene), 4,5-dichlorobenzene-1 ,2-Decatur v formaldehyde (dicarbaldehyde), 8- deck cycle by [4,3.1] -3 - guanidine-tert-butyl-1 ,2-bis-(3,5-dimethyl-phenyl)-3-hydroxy-1-[2,6- dihydroxy-4-methoxy-3-methylphenyl] butane-1- come, 2,3,6,7-tetra-chloro-naphthalene, 2,3,6- trimethyl naphthalene, Dodecanese fluoro-cyclohexane, 2,2,6,6-tetramethyl-4-hepten-3- -2,2,2- trifluoro-ethane [5 - (9H-β-carbolines (carbolin) -1 - yl)-furan-2-yl] methanol, 1,1,1- trichloroethane, 5 - nitro-benzo [1,2,3] Tia Dia Sol (thiadiazole), 4,5-dichloro-thiophen-2- carboxylic acid, 2,6-dimethyl-iso-nitrile, Nico Tino na fluoro -2,6-bis 1-methyl-cyclohexane- trifluoro-Methyl-piperidine, the difluoro (dimethylamino) Robo is ohsanhwayi nitrogen (dinitrogen pentoxide) the Chloe wheat fluoride (fluoride chromyl) and chromium hexa-carbonyl (chromium hexacarbonyl); come methylcyclohexanol, diphenyl ether, na decane, 1-tetra-deca play, 4-ethyl phenol, benzophenone, maleic anhydride (maleic anhydride) the octanoate (octacosane Mt), iso-phthalate, dimethyl hydroxy butyl hydroxy toluene (butylated hydroxy toluene ), glycolic acid, vanillin (vanillin), magnesium nitrate hexahydrate (magnesium nitrate hexahydrate), and cyclohexanone oxime (cyclohexanone oxime), glutaric acid, D-sorbitol, and phenanthrene (phenanthrene), methacrylamide, fluorene, fatigue pyrogallol (galrol), or di diglycolic acid, glycolic acid, 4-hydroxy benzaldehyde, trans-stilbene (trans-stilbene), neopentyl glycol, neopentyl glycol, may be used alone or in combination of two or more kinds of

As a component of the biocompatible agent to reduce active formaldehyde concentration levels produced during the biodegradation of the polymer in vivo, for example, sulfite, bisulfite, or a mixture of sulfite and bisulfite, and the like.

Epithelial replication, windows, cartilage, glue, long-term bonding agent, vascular binder, nerve junction, or an oral binder, but it can be used as a bio-adhesive composition according to the present invention is not limited thereto.

Through the embodiment of the present invention will be described in more detail. These examples, the scope of the present invention, but are presented in order to understand the contents of the present invention is not limited to these embodiments, but not normally in the art can perform the transformation, substitution, and insertion for this are included in the scope of the present invention.

[Example 1] the octyl when Ano acetate and poly-octyl acetate Montepulciano manufacturing

Octane alcohol were mixed in a 1:1 equivalence ratio cyano-acetic acid and 3.5 L of raw materials to inject 3.5 L of toluene as a solvent, the reaction was placed in a glass flask. After completion of reaction, after removing the toluene was purified the Montepulciano octyl acetate. In this case, the yield was more than 80%.

Reacted by putting paraformaldehyde were mixed in a 1:1 equivalence ratio, the octyl at Ano acetate and 3.5 L of raw materials base catalyst in 3.5 L of toluene and placed in a glass flask. When the reaction is complete, remove the toluene and was then purified on octyl acrylate Ano And the remaining by-products from refining the above octyl acrylate Ano obtained was purified by a silica gel column, the poly-octyl acrylate, Montepulciano, and this time poly-octyl Montepulciano acrylate yield was 80%.

Example 2 Preparation of bio-adhesive composition

95% by weight of octyl Montepulciano acetate obtained in Example 1, poly-octyl acrylate Montepulciano 1.5% by weight of iodine, 3,5-die-4-flute money-1-methoxy-hydroquinone, acetic acid, 0.8% by weight, 0.3 wt % sulfur dioxide, 1.2% by weight, and benzalkonium chloride 1.2% by weight of the bio-adhesive composition was prepared by mixing

Test Example 1 bio-adhesive properties of the composition test

Way to bio-physical properties of the adhesive composition prepared in Example 2, respectively, were measured and the results are shown in Table 1.

Adhesion strength

24 bonded stainless steel in accordance with ASTM D1002 using the adhesive area of 1 cm2 to about 0.03 mL of Example 2 bio-adhesive tensile strength machine (Instron 4-4204) and 37 ° C, 75% relative humidity conditions. after a period of time measured adhesion strength between the metal-to-metal adhesion strength (stainless steel).

Flexibility <>

And then poured into a molder of Example 2 using biological glue Hardness Tester Hardness Tester D Type (Teclock four-GS 709N) in accordance with ASTM D3111 method and then cured for 72 h at 37 ° C, 75% relative humidity conditions, specimen thickness of 5 mm, width 2 cm, was measured under a load of 5 kgf conditions.

Viscosity <>

According to the method of ASTM D 2556 using a viscometer (Brookfield four-viscometer DV-II), was measured at 0.5 ℃ under the conditions of 23 Wh sp15, 100 rpm.

Adhesion that can withstand at least when I walked the two plates bonded to a load of 2 kgf load of 5 kg weight after administration of 0.03 mL of glue adhesion area of 1 cm 2 stainless steel plates to ensure that in accordance with JIS K6861. time was measured.

Table 1

Test Adhesive strength (kgf / Viscosity Adhesion time (in Longitude substance cm 2) (cP) seconds) Example 2 Of 145 Of 55 <25 Of 61

You can see from the results in Table 1 of Example 2 according to the present invention, the bio- adhesive properties, including adhesion strength, good.

Antimicrobial Test Test Example 2]

To evaluate the anti-microbial efficacy of a bio-adhesive composition prepared in Example 2, co- Coos Staphylococcus aureus(Staphylococcus aureus, ATCC 6538), Staphylococcus nose Coos epi stack display (Staphylococcus epidermidis, ATCC 51625), Enterococcus nose max par magnesium (Enterococcus faecium ATCC 700221); E. coli (Escherichia coli, ATCC 8739), Pseudomonas Oh Loogie labor (Pseudomonas aeruginosa ATCC 9027) and Candida albicans (Candida albicans,ATCC 10231) for antimicrobial efficacy test were

From 35 to 37 ° C. for 16 to 24 hours during the 20 ml sterile TSB (Tryptic Soy Broth) medium, the microorganisms were cultured.

TSA (Trypticase Soy Agar) plates were used in the course of this black, 0.85% saline solution was used for dilution. The medium was steam sterilized before they can be used. The agar plates were prepared, one-time sterile Petri dish (100 15mm ㅧ) pour about 20 ml of molten medium was solidified under the hood of the laminated flow.

Vortex the overnight cultures of each microorganism, manufacturing, and 1:100 dilution, the minimum amount of 10 4 colony-forming units (CFU) / ml were prepared. Was applied using a sterile cotton swab diluted inoculum on the surface of agar plates. At this time, be careful to cover the entire agar surface. The plate for 30 minutes and dried naturally.

Vivo adhesive composition 20 ㎕, in Example 2 was added to the plate in the center of the inoculated microorganisms. Two drops of the control samples was expressed in a separate TSA plates. Drop is applied by hand, without the test sample, formed by polymerizing a thin film from the plate. The plates 35 to 24 hours at 37 ° C, incubated, and then the plate out of the product obtained from the diffusion of surfactant inhibition and agar medium range [minimum inhibitory concentration (MIC: Minimum inhibitory concentration) and minimum bactericidal concentration (MBC: Minimum Bactericidal Concentration)] were examined. Films from the edge of the inhibition zones were measured to the edge of the transparent areas are terminated, and the results are shown in Table 2.

Table 2.

Microbial cultures DIMPTS (ppm) Minimum bactericidal concentration Minimum inhibitory concentration (MIC) (MBC)

S. aureus (ATCC 6538) Of 50 <150 S. epidermidis (ATCC 51625) 6 <100 E. faecium (ATCC 700221) 25, NA E. coli (ATCC 8739) Of 90 <150 P. aeruginosa (ATCC 9027) 100- NA C. albicans (ATCC 10231) 25, <100

From the results in Table 2 above, it was confirmed that the antimicrobial efficacy of Example 2 according to the present invention, the bio-adhesive.

On the other hand, not only present a specific example to help you understand what you want to limit the scope of the present invention, embodiments of the present invention disclosed in the present specification and drawings. Is carried out by other transformations, for example, based on the technical idea of the present invention, in addition to the embodiments disclosed herein, it is apparent to those of ordinary skill in the art to which this invention pertains.

폴리옥틸시아노아크릴레이트를 이용하여 제조한 봉합사 및 그 제조방법(Suture produced by using polyoctylcyanoacrylate and the method for preparing thereof)

SUTURE AND A METHOD FOR FABRICATING THE SAME USING POLYOCTYL CYANOACRYLATE

PURPOSE: A method for fabricating a suture using polyoctyl cyanoacrylate is provided to maintain tensile strength and to obtain the suture absorbed into human body with problem.

CONSTITUTION: A method for fabricating a suture comprises: a step of preparing octyl cyanoacetate by reaction of cyanoacetic acid and octane alcohol under the presence of solvent; a step of reaction of octyl cyanoacetate and paraform aldehyde under the presence of solvent; a step of removing solvent after the reaction and purifying the octyl cyanoacrylate; a step of collecting polyoctyl cyanoacrylate from by-product; and a step of melt-spinning or extruding the polyoctyl cyanoacrylate. The solvent includes benzene, toluene or xylene.

TECHNICAL FIELD

The present invention relates to a suture manufactured using poly octyl cyanoacrylate and a method for manufacturing the same and, more particularly, to a suture which is manufactured using poly octyl cyanoacrylate produced as a byproduct during the preparation of octyl cyanoacrylate, maintains tensile strength at the time of a surgical procedure, and is absorbed into the body without causing any problems after the surgical procedure, and a method for manufacturing the suture.

BACKGROUND ART

Together with tissue adhesives and surgical staples, a suture is an important medical joining material used to stitch and join a surgical site. An absorbable (in-vivo resolvable) suture has been fabricated using collagen extracted from the guts of animal (so called catgut), and collagen is decomposed by enzyme. Although a catgut suture is still widely used, its consumption tends to decrease due to high tissue responsiveness, high infection rate and poor operability.

Biodegradable or bioabsorbable polymers refer to polymers which are decomposed and dissipated by simple hydrolysis or reaction of enzyme. Polypeptides, polysaccharides and polynucleotides, produced as natural polymers in the nature, and polyester, made from a microbe, are decomposed respectively by proper breakdown enzyme. While most synthetic polymers are not decomposed, some aliphatic polyester or polycarbonate is slowly decomposed by hydrolysis. Such characteristics of biodegradable polymers allow medical products to be extinct in the body after performing given functions. Therefore, any additional removal process is not required, and a foreign body reaction of nondegradable polymers is prevented. For these reasons, biodegradable polymers have been applied to an absorbable suture and a tissue adhesive, which are used to join a wound, osteosynthesis material which is used to support a broken bone, and a drug delivery agent which is used to deliver a drug. Recently, tissue engineering for rebuilding tissues and organs of human by means of a cell culture on biodegradable polymer scaffolds has been studied actively.

Normally biodegradable polymers were decomposed in the body (a decomposition process), causing a reduction in molecular weight and a decrease in strength, and then absorbed by various kinds of enzyme in the body (an absorption process). The former decomposition reaction is performed by water or enzyme. Medical in-vivo resolvable polymers should not cause any foreign body reaction in the body, should be decomposed into harmless substances, and should have proper processing characteristics and strength. Natural polymers are suitable for in-vivo resolvable materials in comparison with synthetic polymers, but may accompany tissue rejections by the immune system because of similarity with a body structure. Additionally, a degradation rate of natural polymers is difficult to control due to uneven mechanical properties. Therefore, applications of synthetic polymers have been developed actively.

In the early 1970's, American Cyanamid Company commercialized the world's first synthetic absorbable suture (brand name: Dexon) using polyglycolic acid (PGA), and then Ethicon Company in U.S.A. commercialized copolymer poly(glycolide-co-lactide) (brand name: Vicryl).

Since 1987, Medical Supply Company in Japan has released a PGA suture (brand name: Medifit), and also Samyang in Korea has commercialized and exported a PGA suture (brand name: Trisorb) in conjunction with KIST from 2000. A PGA absorbable suture is decomposed simply through a hydrolysis process, and Makino et al. reported that esterase, trypsin, chymotrypsin, etc. would accelerate such a hydrolysis process. A PGA suture shows circular cross-sections of a bundle of sutures at the third day after a transplant in the body, but completely disappears and is absorbed after three months. Additionally, it is observed at the time of ex-vivo decomposition that a suture is cut in a direction perpendicular to a thread and decomposed. The reason is that degradable polymers are decomposed first at amorphous portions and then decomposed at crystalline portions while polymer crystal is oriented in an elongation direction of fiber and amorphous portions are placed between crystalline portions. Another critical factor that affects the decomposition is the pH. In the body, gastric juice has a pH of 0.9˜1.5, pancreas has a pH of 8.2, and bladder has a pH of 4.5˜8.0. Since hydrolysis is accelerated in general by acid, biodegradable polymer should be properly selected in consideration of variations in hydrolysis rate according to applied parts in the body.

PGA which is a representative suture substitutes for conventional collagen catgut. A recent research has been focused on two issues, 1) the development of soft monofilament and 2) the control of decomposition period. Namely, due to strong and rigid properties, PGA is difficult to knot in a state of monofilament, and a knot thereof becomes easily untied. Therefore, PGA is braided by twisting several yarns. However, a braided suture may increase a possibility of infection due to bacteria caught in space between yarns. In contrast, a monofilament type suture has great advantages of little infection, soft surface, and reduced tissue responsiveness. Therefore, in order to develop polymers for a suture being softer than a monofilament type suture and PGA, more efforts was made to develop copolymer of PGA and PLA or new monomer.

DETAILED DESCRIPTION OF THE INVENTION Technical Problems

Accordingly, the present inventor tried to find suitable material for an absorbable suture that maintains tensile strength at the time of a surgical procedure and is absorbed into the body without causing any problems after the surgical procedure. As a result, the present inventor found that poly octyl cyanoacrylate which was left as a byproduct after octyl cyanoacrylate was isolated and refined at the preparation of octyl cyanoacrylate was suitable material for the manufacture of a suture, and then completed this invention.

Thus, an object of the present invention is to provide a suture manufactured using poly octyl cyanoacrylate and a method for manufacturing the same.

Technical Solutions

In order to accomplish the above-mentioned object, the present invention provides a method for manufacturing a suture. The method includes steps of preparing octyl cyanoacetate by reacting cyanoacetic acid and octane alcohol at an equivalence ratio of 1:1 under the existence of a solvent; reacting the octyl cyanoacetate and paraformaldehyde at an equivalence ratio of 1:1 under the existence of a solvent; isolating and refining octyl cyanoacrylate after removing the solvent when the reaction is completed; obtaining poly octyl cyanoacrylate from a byproduct left by refinement of the octyl cyanoacrylate; and manufacturing a suture by a braid process after fabricating a thread through melt spinning or extrusion molding of the obtained poly octyl cyanoacrylate.

In the method, the solvent may be selected from the group consisting of benzene, toluene, and xylan.

The method may further include step of coating the suture with a coating composition for a suture.

In the method, the coating composition for a suture may be composed of powder type lubricant, at least one surfactant, and polymeric material.

Additionally, the present invention provides a suture manufactured by the above-mentioned method.

Advantageous Effects

The suture of this invention is safer in the human body and more cost effective than conventional products since it is manufactured using poly octyl cyanoacrylate which is left as a byproduct after octyl cyanoacrylate is isolated and refined.

DESCRIPTION OF THE DRAWING

FIG. 1 is a flow diagram showing a method for manufacturing a suture in accordance with an embodiment of the present invention.

FIG. 2 is a flow diagram showing a method for coating a suture with a coating composition in accordance with an embodiment of the present invention.

MODE FOR CARRYING OUT THE INVENTION

Hereinafter, embodiments of the present invention will be described in detail. The following descriptions are provided to assist in a comprehensive understanding of the embodiments. Well known techniques will be omitted to avoid obscuring the subject matter of the present invention.

The meaning of specific terms or words used in the specification and the claims should not be limited to the literal or commonly employed sense, but should be construed in accordance with the spirit of the invention as described herein. The description of the various embodiments is to be construed as exemplary only and does not describe every possible instance of the invention. Therefore, it should be understood that various changes may be made and equivalents may be substituted for various elements of the invention.

The present invention relates to a suture which is manufactured using poly octyl cyanoacrylate.

Poly octyl cyanoacrylate used in this invention is a byproduct which is produced during the preparation of octyl cyanoacrylate and typically discarded.

A method for manufacturing a suture using poly octyl cyanoacrylate in this invention is shown in FIG. 1. Referring to FIG. 1, the manufacturing method includes a step of preparing octyl cyanoacetate by reacting cyanoacetic acid and octane alcohol at an equivalence ratio of 1:1 under the existence of a solvent; a step of reacting the octyl cyanoacetate and paraformaldehyde at an equivalence ratio of 1:1 under the existence of a solvent; a step of isolating and refining octyl cyanoacrylate after removing the solvent when the reaction is completed; a step of obtaining poly octyl cyanoacrylate from a byproduct left by refinement of the octyl cyanoacrylate; and a step of manufacturing a suture by a braid process after fabricating a thread through melt spinning or extrusion molding of the obtained poly octyl cyanoacrylate. A solvent used in each reaction process is organic solvent typically used in the art, including benzene, toluene, xylan, or the like, but not limited thereto. In the above reaction, the reaction yield of poly octyl cyanoacrylate is 80%, and poly octyl cyanoacrylate may be obtained by refining the byproduct with silica gel. By mixing the poly octyl cyanoacrylate with typically used calcium, phosphate, catalyst, etc. and then coagulating them, the suture may be manufactured.

In an embodiment of this invention, the suture may be manufactured through extrusion molding by using, for example, but not limited to, an extruder disclosed in Korean Patent Publication No. 2004-0002673.

In an embodiment of this invention, the suture may be monofilament or multifilament produced by twisting a number of yarns.

Additionally, in an embodiment of this invention, the suture may be manufactured in the form of being coated with a coating composition for a suture as shown in FIG. 2 so as to give knot slippage or knot stability. The coating composition for a suture may be composed of powder type lubricant, at least one surfactant, and polymeric material. Preferably, as the powder type lubricant, fatty acid salt having a carbon number of six or more, e.g., magnesium stearate, may be used. As the surfactant, at least one selected from the group consisting of copolymer of polyethylene oxide and fatty acid ester, and copolymer of polyethylene oxide and polypropylene oxide may be used preferably. Used as the polymeric material may be polycaprolactone. Also, the polymeric material may be used in the form of dissolving in an organic solvent such as methylene chloride, chloroform, 1,1,2-trichloroethane, acetone, acetonitrile, ethanol, benzene, toluene, xylan, or the like.

The coating composition for a suture may contain the powder type lubricant of 10˜40 weight %, the surfactant of 10˜40 weight %, and the polymeric material of 20˜50 weight %.

Hereinafter, the present invention will be more fully described through embodiments and experimental examples. These embodiments and experimental examples are provided only to assist in understanding of the present invention, and the scope of this invention is not to be limited by such embodiments and experimental examples. Various well-known modifications, substitutions and additions may be made and they are included in the scope of the present invention.

EMBODIMENT 1 Manufacture of Suture

A 3.5 L mixture in which cyanoacetic acid and octane alcohol were mixed at an equivalence ratio of 1:1 was put in a glass flask and then 3.5 L toluene was added as a solvent to react. After a reaction was completed, toluene was removed and octyl cyanoacetate was isolated and refined. At this time, the reaction yield was 80% or more.

A 3.5 L mixture in which the above octyl cyanoacetate and paraformaldehyde were mixed at an equivalence ratio of 1:1 was put in a glass flask and then 3.5 L toluene and base catalyst were added to react. After a reaction was completed, toluene was removed and octyl cyanoacrylate was isolated and refined. From a byproduct left after the octyl cyanoacrylate was refined, poly octyl cyanoacrylate was obtained and refined using a silica gel column. At this time, the yield of poly octyl cyanoacrylate was 80%.

By extrusion-spinning the above poly octyl cyanoacrylate in a manner using an extruder disclosed in Korean PatentPublication No. 2004-0002673, a thread was fabricated. Then a suture was manufactured by means of a braid process.

EMBODIMENT 2 Manufacture of Coated Suture

The suture manufactured in the above embodiment 1 was dipped in a coating solution which contains a mixture of 12% polycaprolactone among methylene chloride and polysorbate 80 (ICI, Inc.) (4:6 (w/w)) as the surfactant. Then an organic solvent was removed by evaporation, and a coated suture was obtained.

EXPERIMENTAL EXAMPLE 1

Strength, elongation and toughness of the sutures manufactured in the above embodiments 1 and 2 were measured, and Table 1 below shows the results. Specifically, tensile characteristics including fiber strength and elongation were measured with a standard length of 500 mm and strain of 720 mm/min using test equipment, Statimat (both model M and model ME of Statimat were used in connection with embodiments). Toughness was determined by calculating area under a stress-strain curve measured in the unit of gram-centimeter per denier (g-cm/d).

TABLE 1 Sample Strength (g/d) Elongation (%) Toughness (g-cm/d) Embodiment 1 7.6 25.4 52 Embodiment 2 7.9 26.8 54

As shown in Table 1, it was confirmed that the sutures of embodiments 1 and 2 had excellent properties. Particularly, it was confirmed that the coated suture manufactured in the embodiment 2 had more excellent properties. Additionally, the sutures of this invention had good treatability and were completely absorbed in the body within about 70 days.

EXPERIMENTAL EXAMPLE 2

Appearance, wetted knot slippage and knot stability of the sutures manufactured in the above embodiments 1 and 2 were evaluated according to the following basis, and Table 2 below shows the results.

⊚: Slipping up to a targeted point at a time

O: Slipping after stopping once during slipping

Δ: Slipping after stopping twice or more during slipping

X: Not slipping

⊚: Knot does not slip in the opposite direction.

O: Knot slips within 1 cm in the opposite direction.

Δ: Knot slips between 1 cm and 5 cm in the opposite direction.

X: Knot slips 5 cm or more in the opposite direction.

⊚: Very Good, O: Good, Δ: Normal, X: Bad

TABLE 2 Wetted Knot Synthetic

Sample Appearance Slippage Knot Stability Decision Embodiment 1 ◯ ◯ ◯ ◯ Embodiment 2 ⊚ ⊚ ◯ ⊚

As shown in Table 2, the sutures of embodiments 1 and 2 not only had good appearance, but also were good in wetted knot slippage and in knot stability.

While this invention has been particularly shown and described with reference to embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.

혈관 문합 장치 제조를 위한 블랜딩 조성물 및 이를 기반으로 제조된 혈관 문합 장치(Blending material For Anastomosis Apparatus For Blood vessel And Anastomosis Apparatus manufacturing the same)

BLENDING MATERIAL FOR MANUFACTURING A BLOOD VESSEL ANASTOMOSIS APPARATUS AND THE BLOOD VESSEL ANASTOMOSIS APPARATUS MANUFACTURED BASED ON THE SAME CAPABLE OF PROVING SUFFICIENT SUPPORTING FORCE

PURPOSE: A blending material for manufacturing a blood vessel anastomosis apparatus and the blood vessel anastomosis apparatus manufactured based on the same are provided to simply connect the ends of blood vessels.

CONSTITUTION: A blood vessel anastomosis apparatus comprises a outside coupler(100) for fixing a first blood vessel, and an inside coupler(200) which fixes a second blood vessel and is combined with the outside coupler. The outside coupler is prepared with a blending composition.

The inside coupler is prepared with a blending composition.

습기 경화형 깁스 재료 조성물 및 이를 내장한 스프레이 장치(Cast composition type of stiffening using a moisture and Spray Device containing the same)

CAST COMPOSITION CAPABLE OF BEING CURED BY MOISTURE IN THE AIR AND A SPRAY DEVICE CONTAINING THE SAME

PURPOSE: A cast composition and a spray device containing the same are provided to rapidly form the shape of a cast.

CONSTITUTION: A spray device with a cast composition comprises an outer case(11), a spray header(20) which is mounted in the upper end of the outer case and assists to spray plaster cast materials arranged inside the outer case to the outside, a plaster cast material container which is arranged within the outer case, a discharge path(30) which is connected to the spray header and is arranged to the inside of the outer case, and an argon gas layer(40) which is prepared inside the outer case.

고탄성 고분자 지지체 및 이의 제조 방법과, 이를 기반으로 하는 고분자 지지체-연골세포 복합체 구조

물, 연골 재건 수술 방법(High Exclamation Macromolecules Support and manufacturing method thereof, Structure of Macromolecules Support-Chondrocyte Complex based on the same, and Chondrocyte Restructuring Method using the same)

HIGH ELASTIC POLYMER SUPPORTER, A MANUFACTURING METHOD THEREOF, POLYMER SUPPORT - CHONDROCYTE COMPOUND STRUCTURE BASED ON THE SAME, AND A CARTILAGE RECONSTRUCTION METHOD

PURPOSE: A high elastic polymer supporter, a manufacturing method thereof, a polymer support - chondrocyte compound structure based on the same, and a cartilage reconstruction method are provided to enhance recovery properties and bio compatibility.

CONSTITUTION: A high elastic polymer supporter is manufactured with blending composition in which poly octyl cyano acrylate and poly-e-caprolactone are blended at the fixed rate. The poly octyl cyano acrylate has the weight-average molecular weight of 50,000 - 500,000. The poly-e- caprolactone has the weight-average molecular weight of 60,000-80,000. The molar ratio of the poly octyl cyano acrylate of the poly octyl cyano acrylate and poly-e-caprolactone blending supporter is in 30 - 70% range.

폴리옥틸시아노아크릴레이트를 포함하는 부직포 형태의 조직유착 방지재 및 그의 제조 방법(Tissue Adhesion preventer in the form of Nonwoven Fabric including Polyoctylcyanoacrylate and Manufacturing Method thereof)

TISSUE ADHESION PROTECTOR IN NONWOVEN TYPE INCLUDING POLY OCTYL CYANO ACRYLATE AND A METHOD OF MANUFACTURING THEREOF

PURPOSE: A tissue adhesion protector in nonwoven type including poly octyl cyano acrylate and a manufacturing method thereof are provided not to generate coalescing with skin or organic tissue.

CONSTITUTION: A tissue adhesion protector in nonwoven type includes poly octyl cyano acrylate and one or more antibiotic or antiphlogistic. The antibiotic is selected from a group consisting of gramicidin, naildixic acid, neomycin, scull NAK tin, norfloxacin, bacitracin, cephalosporin, streptomycin, aminoglycoside, vice tonneau mycin, ampicilin, kanamycin, quinolone, chloramphenicol, terramycin, tetracycline, patulin, and penicillin.

폴리옥틸시아노아크릴레이트를 포함하는 조직유착 방지용 필름 및 그의 제조 방법(Tissue Adhesion prevention film including Polyoctylcyanoacrylate and Manufacturing Method thereof)

TISSUE ADHESION PREVENTION FILM INCLUDING POLY OCTYL CYANO ACRYLATE AND A MANUFACTURING METHOD THEREOF

PURPOSE: A tissue adhesion prevention film including poly octyl cyano acrylate and a manufacturing method thereof are provided not to generate coalescing with skin or organic tissue.

CONSTITUTION: A tissue adhesion prevention film includes poly octyl cyano acrylate, antibiotic or antiphlogistic. The molecular weight of the poly octyl cyano acrylate is 100,000 to 300,000. The antibiotic is selected from a group consisting of gramicidin, naildixic acid, neomycin, scull NAK tin, norfloxacin, bacitracin, cephalosporin, streptomycin, aminoglycoside, vice tonneau mycin, ampicilin, kanamycin, quinolone, chloramphenicol, terramycin, tetracycline, patulin, and penicillin.

수술용 스테이플 및 그의 제조 방법(A staple for operation and manufacturing method thereof)

STAPLE FOR OPERATION USING POLY OCTYL CYANO ACRYLATE ABSORBED INTO HUMAN BODY AND A MANUFACTURING METHOD THEREOF

PURPOSE: A staple for operation using poly octyl cyano acrylate absorbed into human body and a manufacturing method thereof are provided to naturally decompose sealing part.

CONSTITUTION: A manufacturing method of staple for operation comprises the following steps: manufacturing octyl cyanoacetate by reacting cyanoacetic acid with octane alcohol at 1:1 equivalence ratio under the presence of solvents; reacting the octyl cyanoacetate with paraformaldehyde under the presence of solvents at 1:1 equivalence ratio; isolating and refining the octyl cyano acrylate; obtaining poly octyl cyano acrylate; and manufacturing the staple(20) for operation by molding the obtained poly octyl cyano acrylate.

슬관절에 적용되는 인공 인대와 이를 포함하는 인공 인대 구조물 및 이를 이용한 인대 재건 방법 (Artificial Ligament and Anchor, and Rebuilding Method using the same as part of knee joint)

ARTIFICIAL LIGAMENT APPLIED TO A KNEE JOINT, AN ARTIFICIAL LIGAMENT STRUCTURE AND A LIGAMENT REBUILDING METHOD USING THE SAME

PURPOSE: An artificial ligament applied to a knee joint, an artificial ligament structure and a ligament rebuilding method using the same are provided to reduce risk of rupture generation and to enhance wear resistance.

CONSTITUTION: An artificial ligament comprises a ligament part manufactured with polyether- ether-ketone(PEEK), and connection parts(130) which is prepared at both side ends. The ligament part comprises a porous ligament part(110) in which pores having more than the fixed size are arranged, and tightening ligament parts(120) having pores relatively densed in comparison with the porous ligament part. The porous ligament part is manufactured by mixed material of 90% of polyether-ether-ketone and 10% of 03b2# -TCP.

생체 접착제 조성물을 내장한 스프레이 장치(Spray Device containing Tissue adhesive composition)

SPRAY DEVICE CONTAINING A TISSUE ADHESIVE COMPOSITION FOR EFFECTIVE SPRAY ON A WIDE WOUND

PURPOSE: A spray device containing a tissue adhesive composition is provided to easily spread a tissue adhesive composition on a wide wound or a hidden wound a hand does not reach.

CONSTITUTION: A spray device containing a tissue adhesive composition comprises an outer case(10), a spray unit(20), a discharge passage(30), an argon gas layer(40), and a tissue adhesive layer(50). The spray unit is formed on one side of the outer case. The discharge passage is connected to the spray unit and arranged inside the outer case. The argon gas layer, consisting of 80% of argon gas and 20% of carbon dioxide, is formed above the tissue adhesive layer inside the outer case.

세척기능을 가지는 생체 접착제용 스프레이 장치(Spray Device for tissue adhesive including a Cleaning Function)

TISSUE ADHESIVE SPRAY APPARATUS HAVING A CLEANING FUNCTION FOR PREVENTING THE RESIDUAL ADHESIVE HARDENED INSIDE THE APPARATUS

PURPOSE: A tissue adhesive spray apparatus having a cleaning function is provided to clean a passage for discharging an adhesive immediately after operation using water stored in apparatus.

CONSTITUTION: A tissue adhesive spray apparatus having a cleaning function comprises an outer case(11), an adhesive container(13), a cleaning agent container(15), a discharge unit(200), and a spray header(100). The adhesive container is enclosed with an adhesive material and arranged inside the outer case. The cleaning agent container is enclosed with cleaning water and arranged inside the outer case. The discharge unit allows the adhesive material and/or cleaning water to flow therethrough. The spray header sprays the adhesive material and/or cleaning water transferred through the discharge unit.

Technical Data Sheet

Intuitive can manufacture OCA and 2-OCA at own technology. Octyl cyanoacrylate (OCA), a cyanoacrylate ester, is an octyl ester of 2-cyano-2-propenoic acid. It is a clear colorless liquid with a sharp, irritating odor. Its chief use is as the main component of medical cyanoacrylate glues. It can be encountered under various trade name including LiquiBand, BIOFIT™, FloraSeal, Dermabond, Nexaband, and others. In medical and veterinary applications, the related compounds n-butyl cyanoacrylate and isobutyl cyanoacrylate are commonly used. They are bacteriostatic and their use is usually painless. Butyl esters provide a stronger bond, but the glue is rigid. The octyl ester, while providing weaker bond, is more flexible.It polymerizes rapidly in presence of moisture.Heating to higher temperatures causes pyrolysis and depolymerization of the cured glue, producing gaseous products strongly irritant to lungs and eyes

2-Octyl cyanoacrylate

IUPAC name Octyl 2-cyanoprop-2-enoate Identifiers

CAS number 6701-17-3

PubChem 23167

SMILES N#CC(C(OCCCCCCCC)=O)=C

InChI InChI=1S/C12H19NO2/c1-3-4-5-6-7-8-9-15-12(14)11(2)10-13/h2- 9H2,1H3 Properties

Molecular C12H19NO2

formula −1 Molar mass 209.28 g mol Appearance Colorless liquid Solubility inwater Reacts Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)

2-Octyl cyanoacrylate

IUPAC name[hide] Octan-2-yl 2-cyanoacrylate

Other names[hide] 2-Octyl 2-cyanoacrylate; 1-Methylheptyl cyanoacrylate

Identifiers

CAS number 133978-15-1

ChemSpider 10632587

Properties

MATERIAL SAFETY DATA SHEET

Manufacturer’s name: IntuitiveMediCorp,Inc

Emergency Telephone Numbers: #82-(0)54-823-5250 105 Saneopddanji-gil,Poongsan-eop, Andong-si,Gyyeongbuk-do, , Republic of Korea

Chemical name and synonyms: 2-OCTYL CYANOACRYLATE Trade Name and synonyms: BIOFIT™ Chemical family: CYANOACRYLATE ESTER Formula: N/A Flammability: MEDIUM Health: MEDIUM Reactivity: MEDIUM Specific Hazard: SKIN BONDING & BURNING

HAZARDOUS INGREDIENTS N/A

Carcinogen: NO

PHYSICAL DATA

Boiling 104° C at 0.4 Specific 25° C: point: mm Hg Gravity: 1.4444 Vapor 28 mm @ Density at 0.9850 Pressure 125° 20° C: Viscosity @25° C 3.9 cP Solubility in Polymerized Odor: Sharp, Water: by water irritant Appearance: Clear Liquid, violet liquid

FIRE AND EXPLOSION HAZARD DATA

FLASH POINT: NA/ : METHOD USED, T.C.C. FLAMMABLE LIMITS: LEL: N/A, UEL: N/A EXTINGUISHING MEDIA: CARBON DIOXIDE, DRY CHEMICAL, FOAM SPECIAL FIRE FIGHTING SELF CONTAINED PROCEDURES: BREATHING APPARATUS UNUSUAL FIRE AND POSSIBLE EXOTHERMIC EXPLOSION HAZARDS: REACTION LEADING TO IGNITION AND GENERATION OF FUMES

HEALTH HAZARD DATA

THRESHOLD LIMIT VALUE: NO CRITERIA FOR MEASUREMENT. NOT YET ESTABLISHED

EFFECTS OF OVEREXPOSURE: VAPOR IS IRRITATING TO EYES AND MUCOUS MEMBRANES. PROLONGED AND REPEATED OVEREXPOSURE TO VAPORS MAY PRODUCE ALLERGIC REACTIONS WITH ASTHMA–LIKE SYMPTOMS IN SENSITIVE INDIVIDUALS.

EYE CONTACT: FLUSH WITH WARM WATER AND APPLY GAUZE PATCH. EYE WILL OPEN WITHIN 1-4 DAYS.

EMERGENCY AND FIRST AID PROCEDURES: SKIN: IMMERSE BONDED SURFACE IN WARM SOAPY WATER. PETROLATUM OR VASOLINE MAY BE OF ASSISTANCE IN RELEASING THE BOND. PEEL OR ROLL SURFACE APART WITH AID OF BLUNT EDGE. DO NOT PULL APART WITH DIRECT OPPOSING ACTION. MOUTH: APPLY WARM WATER TO MOUTH. PEEL OR ROLL LIPS APART. BURNS: SHOULD BE TREATED NORMALLY AFTER THE LUMP OF CYANOACRYLATE IS RELEASED FROM THE TISSUE.

INHALATION: VAPORS MAY CAUSE IRRITATION OF NOSE AND BRONCHIAL PASSAGES. AVOID PROLONGED INHALATION. REMOVE TO FRESH AIR.

INGESTION: CAUTION: IT IS ALMOST IMPOSSIBLE TO SWALLOW CYANOACRYLATES, THE GLUE SOLIDIFIES AND ADHERES IN THE MOUTH. THE LIPS MAY BE STUCK TOGETHER.

OTHER: NO CARCINOGENICITY, MUTAGENICITY OR TERATOGENICITY EFFECTS ARE KNOWN. NO EFFECTS OF CHRONIC EXPOSURE OR TARGET ORGAN EFFECTS ARE KNOWN. NO EXPOSURE LIMITS HAVE BEEN ESTABLISHED FOR THIS PRODUCT.

STABILITY: STABLE (UNDER NORMAL CONDITIONS) CONDITIONS TO AVOID: AMINES, BASES

HAZARDOUS DECOMPOSITION PRODUCTS: NONE

HAZARDOUS POLYMERIZATION: MAY OCCUR

INCOMPATIBILITY (MATERIALS TO AVOID): BASES, COTTON, WOOL POLYMERIZED BY CONTACT WITH WATER, ALCOHOL, AMINES

SPILL OR LEAK PROCEDURES

STEPS TO BE TAKEN IN CASE MATERIAL IS RELEASED OR SPILLED: FLOOD WITH WATER TO POLYMERIZE. SOAK UP WITH AN INERT ABSORBENT TOWEL

WASTE DISPOSAL METHOD: POLYMERIZE AS ABOVE. INCINERATE IN ACCORDANCE WITH EPA AND LOCAL REGULATIONS.

SPECIAL PROTECTION INFORMATION

RESPIRATORY PROTECTION (TYPE): NONE NEEDED FOR NORMAL USE.

VENTILATION: POSITIVE DOWN-DRAFT EXHAUST VENTILATION SHOULD BE PROVIDED TO MAINTAIN VAPOR CONCENTRATION BELOW TLV.

PROTECTIVE GLOVES: POLYETHYLENE GLOVES, DO NOT USE COTTON GLOVES.

EYE PROTECTION: SAFETY GLASSES OR GOGGLES.

OTHER PROTECTIVE EQUIPMENT: POLYETHYLENE/POLYPROPYLENE COATS OR APRONS (NOT RUBBER OR COTTON).

SPECIAL PRECAUTIONS

RESPIRATORY PROTECTION NONE NEEDED FOR NORMAL (TYPE): USE VENTILATION: POSITIVE DOWN-DRAFT EXHAUST VENTILATION SHOULD BE PROVIDED PROTECTIVE GLOVES: POLYETHYLENE GLOVES, DO NO USE COTTON EYE PROTECTION SAFETY GLASSES OR GOGGLES OTHER PROTECTIVE POLYETHYLENE/POLYPROPYL EQUIPMENT ENE COATS OR APRONS (NOT RUBBER OR COTTON SPECIAL PRECAUTIONS

Precautions to be taken in handling and storage: Store at or Below 30° C. to maximize shelf life Other precautions: Avoid contact with skin and eyes. Avoid breathing vapor. Information presented herein has been compiled from sources considered to be dependable and is accurate and reliable to the best of our knowledge and belief but is not guaranteed to be so. Nothing herein is to be constructed as recommending any practice or any product in violation of any patent or is violation of any law or regulation. It is the user’s responsibility to determine for himself the suitability if any materials for a specific purpose and to adopt such safety precautions as may be necessary. We make no warranty as to the results to be obtained in using any material and, since conditions of use are not under our control, we must necessarily disclaim all liability with respect to the use of any material supplied by us.

Company

IntuitiveMediCorp,Inc is a shareholder own medical device company focused on the development and commercialization of highly differentiated cyanoacrylate based surgical, wound management and infection prevention technologies. Founded in 2010, the company is based in Andong city, Kyungsang Province, Republic of Korea.

The vision of the IntuitiveMediCorp,Inc’s team is to redefine the way cyanoacrylate based surgical Glues and sealants are used in medicine. Our mission is to provide technologies that achieve optimal patient outcomes. IntuitiveMediCorp,Inc currently is developing and commercializing cyanoacrylate‐based Glues and sealants for use in professional and consumer healthcare settings. We specialize in products that provide solutions for three distinct healthcare segments; Surgical, Wound Management and Infection Prevention. We have a robust product pipeline under development and several products that are to be commercialized in the Korea and overseas markets.

Company Biz Coverage

IntuitiveMediCorp,Inc has been kept electronic material technology in advance (Acrl Binder,Dielctric Ink,Silver/Carbon Ink,Protecting Ink/Inorganic E/L) and is to reshuffle to in medicine based upon base manufacturing technology.

Vision

IntuitiveMediCorp,Inc on producing the highest quality professional medical and consumer health products in an effort to provide the best possible patient clinical results. We will strive to provide superior service and products to professionals, patients and consumers alike, while building an innovative medical device company.

Our Vision is to create an exciting and successful biomedical company that develops exciting new wound closure, wound care and surgical drape sealant products. We will endeavor to explore new materials, formulations and technologies to produce new medical products that provide superior modalities to heal and close wounds, treat disease and prevent infection

Elastin-like polypeptides

MALDI-TOF MS Analysis Method The MALDI-TOF MS samples were prepared in an aqueous 50% acetonitrile solution containing 0.1% trifluoroacetic acid and were analyzed by Voyager-DE STR BioSpectrometry using a sinapinic acid matrix. Analysis result RGD-ELP size - 60Kda

Material Safety Data Sheet

SAFETY DATA SHEET according to Regulation (EC) No. 1907/2006 Revision Date 30.11.2012 GENERIC EU MSDS - NO COUNTRY SPECIFIC DATA - NO OEL DATA

1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE AND OF THE COMPANY/UNDERTAKING 1.1 Product identifiers Product name : Elastin, biomimetic

Elastin is a major component of elastic fibers found in the extracellular matrix of many tissues, for which elasticity is of great importance. Elastin is an insoluble molecule formed from many monomers of water-soluble tropoelastin. Tropoelastin is encoded by a single-copy gene, but alternative splicing of transcripts results in various isomeric forms of the protein,each with a molecular weight of approximately 70 kDa.

Brand : Biofit CAS-No. : 9007-58-3 1.2 Relevant identified uses of the substance or mixture and uses advised against Identified uses : Laboratory chemicals, Manufacture of substances 1.3 Details of the supplier of the safety data sheet Company : Intuitivemedicorp, Inc Telephone : +82 54-823-5250 Fax : +82 54-823-5251

E-mail address : [email protected]

2. HAZARDS IDENTIFICATION 2.1 Classification of the substance or mixture Not a hazardous substance or mixture according to Regulation (EC) No 1272/2008 This substance is not classified as dangerous according to Directive 67/548/EEC. 2.2 Label elements The product does not need to be labelled in accordance with EC directives or respective national laws. 2.3 Other hazards - none

3. COMPOSITION/INFORMATION ON INGREDIENTS 3.1 Substances

4. FIRST AID MEASURES 4.1 Description of first aid measures If inhaled If breathed in, move person into fresh air. If not breathing, give artificial respiration. In case of skin contact Wash off with soap and plenty of water. In case of eye contact Flush eyes with water as a precaution. If swallowed Never give anything by mouth to an unconscious person. Rinse mouth with water. 4.2 Most important symptoms and effects, both acute and delayed

4.3 Indication of any immediate medical attention and special treatment needed no data available

5. FIREFIGHTING MEASURES 5.1 Extinguishing media Suitable extinguishing media Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. 5.2 Special hazards arising from the substance or mixture Nature of decomposition products not known. 5.3 Advice for firefighters Wear self contained breathing apparatus for fire fighting if necessary. 5.4 Further information no data available

6. ACCIDENTAL RELEASE MEASURES 6.1 Personal precautions, protective equipment and emergency procedures Avoid dust formation. Avoid breathing vapors, mist or gas. 6.2 Environmental precautions Do not let product enter drains. 6.3 Methods and materials for containment and cleaning up Sweep up and shovel. Keep in suitable, closed containers for disposal. 6.4 Reference to other sections For disposal see section 13.

7. HANDLING AND STORAGE

7.1 Precautions for safe handling Provide appropriate exhaust ventilation at places where dust is formed.Normal measures for preventive fire protection. 7.2 Conditions for safe storage, including any incompatibilities Store in cool place. Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: 2 - 8 °C 7.3 Specific end uses no data available

8. EXPOSURE CONTROLS/PERSONAL PROTECTION 8.1 Control parameters Components with workplace control parameters 8.2 Exposure controls Appropriate engineering controls General industrial hygiene practice. Personal protective equipment Eye/face protection Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). Skin protection Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and the standard EN 374 derived from it. Body Protection Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place., The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. Respiratory protection Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

9. PHYSICAL AND CHEMICAL PROPERTIES 9.1 Information on basic physical and chemical properties a) Appearance Form: solid b) Odour no data available c) Odour Threshold no data available d) pH no data available e) Melting point/freezing point :no data available f) Initial boiling point and boiling range no data available g) Flash point no data available h) Evaporation rate no data available i) Flammability (solid, gas) no data available j) Upper/lower flammability or explosive limits no data available k) Vapour pressure : no data available l) Vapour density : no data available m) Relative density no data available n) Water solubility no data available o) Partition coefficient: noctanol/water :no data available p) Autoignition temperature no data available q) Decomposition temperature no data available r) Viscosity no data available s) Explosive properties no data available t) Oxidizing properties no data available 9.2 Other safety information no data available

10. STABILITY AND REACTIVITY 10.1 Reactivity no data available 10.2 Chemical stability no data available 10.3 Possibility of hazardous reactions no data available 10.4 Conditions to avoid no data available 10.5 Incompatible materials Strong oxidizing agents 10.6 Hazardous decomposition products Other decomposition products - no data available

11. TOXICOLOGICAL INFORMATION 11.1 Information on toxicological effects Acute toxicity no data available Skin corrosion/irritation no data available Serious eye damage/eye irritation no data available Respiratory or skin sensitization no data available Germ cell mutagenicity no data available Carcinogenicity IARC: No component of this product present at levels greater than or equal to 0.1% is identified as probable, possible or confirmed human carcinogen by IARC. Reproductive toxicity no data available

Specific target organ toxicity - single exposure no data available Specific target organ toxicity - repeated exposure no data available Aspiration hazard no data available Potential health effects Inhalation May be harmful if inhaled. May cause respiratory tract irritation. Ingestion May be harmful if swallowed. Skin May be harmful if absorbed through skin. May cause skin irritation. Eyes May cause eye irritation. Additional Information RTECS: Not available

12. ECOLOGICAL INFORMATION 12.1 Toxicity no data available 12.2 Persistence and degradability no data available 12.3 Bioaccumulative potential no data available 12.4 Mobility in soil no data available 12.5 Results of PBT and vPvB assessment no data available

12.6 Other adverse effects no data available

13. DISPOSAL CONSIDERATIONS 13.1 Waste treatment methods

Product Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging Dispose of as unused product.

14. TRANSPORT INFORMATION 14.1 UN number ADR/RID: - IMDG: - IATA: - 14.2 UN proper shipping name ADR/RID: Not dangerous goods IMDG: Not dangerous goods IATA: Not dangerous goods 14.3 Transport hazard class(es) ADR/RID: - IMDG: - IATA: - 14.4 Packaging group ADR/RID: - IMDG: - IATA: - 14.5 Environmental hazards ADR/RID: no IMDG Marine pollutant: no IATA: no 14.6 Special precautions for user no data available

15. REGULATORY INFORMATION This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006. 15.1 Safety, health and environmental regulations/legislation specific for the substance or mixture no data available 15.2 Chemical Safety Assessment no data available 16. OTHER INFORMATION

Further information The above information is believed to be correct but does not purport to be all inclusive and shall be used only as a guide. The information in this document is based on the present state of our knowledge and is applicable to the product with regard to appropriate safety precautions. It does not represent any guarantee of the properties of the product. Intuitivemedicorp,Inc shall not be held liable for any damage resulting from handling or from contact with the above product.

Production Facility

Name Manufacturing NO. Process (Facilities or Production Code Quantity Company or Country equipment)

Reactor 1 Zhengzhou Keda 1 Production F-100L 3 Machinery and (Intermediates) Instrument Equiment Co.,Ltd

Reactor 2 Zhengzhou Keda 2 F-50L 2 Machinery and (Intermediates) Instrument Equiment Co.,Ltd 3 Reactor 3 (Mixing) 100L 1 Korea

4 Reserve tank 6000L 1 Sambo companies

Automatic filling & SuzhouBTM Packing 5 SZBTMBZ 1 Capping Machine Macinery Co.,Ltd

Automatic Servo DPP-250 Haichina Machinery 6 Photocell Blister 1 TMP200B co.,Ltd Packing/machine

Automatic Cartoning Haichina Machinery 7 DZH-120 1 Machine co.,Ltd

Air compressor 8 STORM 1 5horsepower

9 Air compressor KAC-25 1 Keyang Electric

2.5horsepower Machinery Co., Ltd

JA-ASM02×2 10 Air shower 3 Jina engineering JA-ASM04×1

Airborne bacteria 11 Jina engineering control system

Heating vents 12 LG Electronics Air Cleaning system

13 Nano particle testor CW-HPC-200(A) 1 Chinaway

14 Dust Collector 1 Dasawa

Hand cleaner 15 1 Jina engineering UV sterilizer

16 Sterilization Sterilizer MS055L 2 MOMENS

17 Laboratory Fementer 120L 2 SEWON SYSTEM 18 and quality SDS Protein analyzer 5611551 EN 1 Pharmacia

control 002011/EPS600

19 Sonication Ultrasonic processor 1 Ultrasonics

FL-2200×1 Fuli 20 Liquid chromatography 2 Serise 1090×1 Hewlett Packard

GC-14B×1 Shimadzu 21 Gas chromatography 2 GC-9790 II×1 Fuli

MAP-5021L-01-98- Nuclear magnetic Spincore 22 0W/SATA PS 1 resonance analyzer Technologies,Inc(USA). BLAQCK

1101120908301/FG- 23 Tension Meter 1 Lutron(china) 5020

24 UV spectrometer 721G 1 Jinyibo (China)

Scanning for electron 25 1200B 1 AMRAY microscope

SR-S6750×2 LG Electronics 26 Refrigerator 3 Woo Sung×1 Woo Sung

27 Freezers F-A243GM 1 LG Electronics

XY-105MW/12214×1 XINGYUN 28 Centrifugal separator 2 UNICON 32R×1 Hanil Science Industrial

29 Freeze Dryer Freeze Dryer 4.5 1 LABCONCO

30 Loss on drying tester AA21106 Kett(Japan)

Atomic force The Anfatec Level 31 1 Anfatec(Germany) microscope AFM

32 Ice maker CB15665 1 BREMA

33 Dryer DUXLAB 1 Jeongho TR Co.,Ltd

Chang Sin Scientifice C-IN×1 34 Incubators 2 Co.2.VISION Scientifir K.M.C-8480SF×1 Co.Ltd

VISION scientific 35 Clean Benches KMC-1400 2 Co.,Ltd

36 electronic scale FG-20KBM-H 2 AND

37 UV-Sterilization Dryer JS-SAG 1 Jina engineering

Wenzhou Tripod Instrument 38 Hardness Tester 302505224/LAC-J 1 Manufacturing Co.,Ltd.

Name NO. Process Picture (Facilities or equipment)

1 Production Reactor 1 (Intermediates)

2 Reactor 2 (Intermediates)

3 Reactor 3 (Mixing)

4 Reserve tank

Automatic filling & 5 Capping Machine

Automatic Servo 6 Photocell Blister Packing/machine

Automatic Cartoning 7 Machine

Air compressor 8 5horsepower

Air compressor 9 2.5horsepower

10 Air shower

Airborne bacteria control 11 system

Heating vents 12 Air Cleaning system

13 Nano particle testor

14 Dust Collector

Hand cleaner 15 UV sterilizer

16 Sterilization Sterilizer

Laboratory 17 and quality Fementer control

18 SDS Protein analyzer

19 Sonication

20 Liquid chromatography Hewlett packard Fuli

GC-14B(Shimadzu) 9790 II(Fuli)

21 Gas chromatography

Nuclear magnetic 22 resonance analyzer

23 Tension Meter

24 UV spectrometer

Scanning for electron 25 microscope

26 Refrigerator

27 Freezers

XY-105MW/12214 UNICON 32R

28 Centrifugal separator

29 Freeze Dryer

30 Loss on drying tester

31 Atomic force microscope

32 Ice maker

33 Dryer

C-IN K.M.C-8480SR

34 Incubators

35 Clean Benches

36 electronic scale

37 UV-Sterilization Dryer

38 Hardness Tester