KR20180136610A - Composition for Primary Tooth Crown, Antibacterial Primary Tooth Crown Using the Same, and Manufacturing Method Thereof - Google Patents

Abstract

The present invention relates to a composition for a primary tooth crown, an antibacterial primary tooth crown using the same, and a manufacturing method for the same. According to the present invention, the composition for a primary tooth crown includes: 30-50 wt% of poly lactic acid (PLA); 10-30 wt% of poly ε-caprolactone (PCL); 3-20 wt% of a compatibilizer; 0,5-2 wt% of zirconia (ZrO_2); and 10-30 wt% of an inorganic filler. According to the present invention, the composition for a primary tooth crown has a relatively excellent thermoform property, reduced brittleness, and relatively high rigidity while having excellent bio compatibility. The composition for a primary tooth crown has an excellent sustained-releasing property of an antibacterial substance and is useful for the formation of an antibacterial primary tooth crown. According to the present invention, the antibacterial primary tooth crown sustainably releases a natural antibacterial substance and suppresses proliferation of harmful bacteria in a mouth. So, the composition for a primary tooth crown effectively prevents oral cavity diseases and protects primary teeth. The composition for a primary tooth crown is harmless and has a high degree of bio compatibility, rigidity, and aesthetic impression, as well as reduced fragility. Also, the composition for a primary tooth crown can easily perform a shade guide that is actually the same color as that of a natural primary tooth.

Description

TECHNICAL FIELD The present invention relates to a composition for a toothbrush, an antibacterial toothbrush using the toothbrush, and a manufacturing method thereof.

More particularly, the present invention relates to a biodegradable polymer matrix resin having excellent biocompatibility and a biodegradable polymer matrix resin having relatively high strength and reduced brittleness, An effective antimicrobial composition comprising a plurality of fillers for imparting sustained-releasing properties, and an antimicrobial substance which is molded with the above-described host composition, To an antimicrobial tube that is effective for preventing primary teeth and preventing oral diseases, and an effective manufacturing method thereof.

Generally, a crown is defined as an anatomical crown, which means a clinical crown, which refers to a part of the tooth exposed in the mouth above the gingival line, or a part surrounded by enamel, and chewing and / It contributes to esthetic function and vocalization.

The dentition starts from 6 to 8 months of age and is completed for about 2 years. The dentition secures a space for the permanent teeth and guides the path of the permanent teeth. Therefore, Can cause malocclusion or depression of the face, as well as can cause imbalance of facial skeleton, pronunciation inaccuracy, tooth decay in permanent teeth, malnutrition due to problems in writing, and digestive disorders.

Recently, children who are exposed to the environment of instant food and sugar-containing foods tend to have cavities in the premature period before the permanent teeth are created, and the frequency of these teeth is increasing.

Particularly, in the case of such a bad tooth, when the tooth length is shortened due to tooth decay due to tooth decay, tooth decay occurs in the root tooth, or only root remains due to tooth decay, It is necessary to restore and maintain the weakened function or the lost function.

The crown prosthesis is performed when the tooth loss of the crown is large and the function of the tooth is difficult to be recovered by filling the crown. The crown prosthesis can be classified into the bifurcation and the local tube according to the area and shape to be covered, A metal tube made of gold alloy, silver alloy or nickel alloy, a ceramic tube made of ceramics, and a resin tube made of synthetic resin.

Most of the conventional artificial crown has been used as a simple restorative material, and antimicrobial crown using some inorganic coating material has been proposed. However, antibiotic substance curettage with antibiotic substance considering the health condition of childhood prone to carious disease has been proposed There is not.

In addition, the artificial crown has a problem that peripheral inflammation and calculus are apt to occur.

Typical conventional techniques for crown or boll tube include the following.

Korean Registered Patent No. 10-1071554 (registered on Apr. 4, 2011) discloses a method of mixing zirconia or alumina, a polymer for imparting softness during injection molding, and a colorant, heating and injection molding, And a barrel process is carried out for polishing and sintering after degreasing, degreasing, and polishing. Korean Patent Registration No. 10-1287812 (registered on Mar. 13, 2013) The present invention proposes a ceramic greenhouse having a base portion fitted in the removed exposed contour portion and provided with an outer shape portion that can be matched with a mandibular molar tooth conforming to the above-mentioned maxillary premolar tooth, and a through hole formed on the side of the molar However, these are all related to the ceramic tube, which has nothing to do with the emissive antibacterial resin crown.

Korean Patent Registration No. 10-1237103 (registered on Mar. 29, 2013) discloses a dental prosthesis having a protective layer made of an anodizing-coated titanium oxide film on the outer surface of a dental prosthesis, a buffer layer made of nanosilver and titanium, A dental prosthesis coated with antimicrobial coating composed of a silver-coated antimicrobial layer is disclosed in Korean Patent Publication No. 10-1477066 (registered on December 22, 2014), and a dental prosthesis having a coating layer of nitrogen-doped titania nanotubes Discloses a dental implant including an abutment and the nitrogen-doped titania nanotube coating layer comprises an antibiotic and a polylactic acid mixture. The former exhibits an antimicrobial effect by silver nano-coating as an inorganic material, After the antibiotic encapsulated with lactic acid was eluted from the inside of the nitrogen-doped titania nanotube, the polylactic acid was biodegraded and the antibiotic drug By the effect that the expression slowly and to prevent a bacterial infection of the peripheral region of planting the implant.

On the other hand, US 8,372,420 B2 and US 8,425,927 B2 disclose compositions and methods for medical implant coatings, but they are not limited to implantable medical implants such as poly (Foley) catheters, Which is capable of releasing various antibiotics to prevent bacterial colony formation by a catheter, such as a drainage tube, artificial blood vessel, endotracheal tube and tracheostomy tube, or angioplasty catheter, and is independent of dental implants.

WO 2012 096965 A1 (international publication on July 19, 2012) proposes prosthetic joints for use in shoulder arthroplasty in which various antibiotics are incorporated into a metal adhesive carrier coated on the surface of an artificial joint part, .

Considering the fact that the prevalence rate of premature tooth decay in domestic children is as high as 30% or more as the frequency of exposure to instant foods and sugar-containing foods increases, effective teeth that can be supplemented or replaced effectively until permanent teeth are normally produced There has been a long-felt need in the art for the development of artificial attracting tubes.

Patent Registration No. 10-1071554 (Registered on April 4, 2011) Patent Registration No. 10-1287812 (registered on July 15, 2013) Patent Registration No. 10-1237103 (registered on Feb. 19, 2013) Patent Registration No. 10-1477066 (registered on December 22, 2014)

Accordingly, a first object of the present invention is to provide a host composition useful for forming a tube having excellent biocompatibility, relatively high strength, reduced brittleness, and relatively good thermoforming properties.

A second object of the present invention is to provide a host composition having an excellent antibacterial substance sustained-releasing property in addition to the above first object.

A third object of the present invention is to provide an artificial antibacterial tube which is effective for protection of primary teeth and prevention of oral diseases and is harmless to human body by suppressing the growth of harmful bacteria in the oral cavity by sustained releasing the natural antibacterial substance .

A fourth object of the present invention is to provide an antibacterial tube having relatively high strength and satisfactory brittleness characteristics while using a biodegradable polymer resin having excellent biocompatibility in addition to the above third object.

A fifth object of the present invention is to provide an antibacterial tube having high esthetics and relatively good heat insulation.

A sixth object of the present invention is to provide an antibacterial attracting tube capable of easily realizing a shade guide which is substantially the same as the color of the natural attracting.

A seventh object of the present invention is to provide an effective manufacturing method of an antibacterial attracting tube according to the above objects.

The first object of the present invention is to provide a polylactic acid composition which comprises 30 to 60% by weight of poly (lactic acid) (PLA), 10 to 40% by weight of polycaprolactone (PCL) (ZrO ₂ ) 0.5 to 2% by weight, and an inorganic filler 10 to 30% by weight, based on the total weight of the composition.

The compatibilizing agent may be selected from the group consisting of poly (methyl methacrylate) (PMMA), poly (methyl acrylate) PMA, poly (ethyleneglycol) PEG, Poly (lactic-co-glycolic acid): PLGA, poly (glycidyl methacrylate): GMA), or any mixture thereof.

In addition, the above-mentioned inorganic filler may be silica (SiO _2), hydroxide apatite, tricalcium phosphate, bio-glass, bio-crystallized glass, alumina, or any mixture thereof.

It is a second object of the present invention to provide a toothpaste composition according to the first aspect of the present invention, which further comprises 0.02 to 2% by weight of a nano-particle carrying naturally-occurring antibacterial substance, Can be achieved.

The above-mentioned natural antimicrobial substance-supported nanoparticles may be zeolite, clay, aluminosilicate, aluminophosphate, silicoaluminophosphate, silicon dioxide, titanium oxide, aluminum oxide, or any mixture thereof.

The nanoparticles may have an average particle diameter of 50 to 150 nm.

The natural antimicrobial material may also be propolis, berberine, rosmarinic acid, catechin, naringin, or any mixture thereof.

In particular, the natural antimicrobial substance may be a fat-soluble propolis, and the amount of the antimicrobial substance may be 0.006 to 1.6% by weight based on the total weight of the composition.

In addition, the above-described host composition may further comprise a pigment mixture of 0.01 to 0.09 phr (per hundred resin) and 0.01 to 0.09 phr of a red pigment for shade tinting.

In particular, the pigment mixture may be formulated to exhibit a shade guide A2 shade as a mixture of yellow pigment: red pigment = 0.08 phr: 0.02 phr.

The third to fifth objects of the present invention can be attained by an antibacterial attracting tube formed by injection molding of a toothpaste composition containing the above-mentioned natural antibacterial substance-bearing zeolite.

The sixth object of the present invention can also be achieved by an antibacterial attracting tube which is formed by injection molding of the above-mentioned yellow pigment and the red pigment.

The seventh object of the present invention is to provide a polylactic acid composition which comprises (A) 30 to 60% by weight of poly (lactic acid): PLA, 10 to 40% by weight of poly (竜 -caprolactone: PCL) A composition for a toothpaste comprising 3 to 20% by weight of zirconia (ZrO ₂ ), 0.5 to 2% by weight of zirconia (ZrO ₂ ) and 10 to 30% by weight of an inorganic filler is kneaded and extruded and cut with a cutter to form chips, pellets, (B) nanoparticles having an average particle diameter of 50 to 150 nm are dried and heat-treated, dispersed in an aqueous solution of a natural antimicrobial material and stirred, recovered and dried to prepare natural antimicrobial substance-supported nanoparticles And (C) forming an inlet tube by compounding the matrix resin and the natural antimicrobial substance-supported nanoparticles followed by injection molding to form an antibacterial inlet tube.

On the other hand, after the step (A), an electron beam irradiation step of 40 to 120 kGy may be further performed.

In addition, in the above step (A), it is possible to further include a pigment mixture of 0.01 to 0.09 phr of a yellow pigment and 0.01 to 0.09 phr of a red pigment.

The inventive composition according to the present invention has excellent biocompatibility, relatively high strength and reduced brittleness, relatively excellent thermoforming property, and excellent antibacterial substance sustained-releasing property The antibacterial tube according to the present invention is effective for preventing primary teeth and preventing oral diseases by inhibiting the growth of harmful bacteria in the oral cavity by sustained releasing the natural antibacterial substance, A shade guide having high biocompatibility, strength and aesthetics, reduced brittleness, and substantially the same as the color of a natural attractant can be easily realized.

1 is a photograph showing a matrix resin pellet of Example 1. Fig.
2 is a photograph showing the matrix resin pellets of Example 3. Fig.
3 and 4 are graphs showing the cell viability of berberine of Experimental Example 1, respectively.
5 and 6 are photographs of antibacterial test results of berberine oral bacteria in Experimental Example 1, respectively.
Fig. 7 is a photograph of an antibacterial test result of rosmarinic acid against oral noxious bacteria in Experimental Example 1, respectively.
8 to 12 are photographs of antibacterial test results of catechin EGCG of Example 1 against oral noxious bacteria.
13 and 14 are photographs of antibacterial test results of catechin ECG against oral noxious bacteria in Experimental Example 1, respectively.
15 is a photograph of an antibacterial test result of catechin EC in Experimental Example 1 against oral harmful bacteria.
16 is a photograph of an antibacterial test result of catechin EGC against oral noxious bacteria in Experimental Example 1. Fig.
17 to 20 are graphs showing biosafety results of cell survival rate for each of the four catechins of Experimental Example 1. Fig.
21 is a photograph of an antibacterial test result of naringin against oral noxious bacteria in Experimental Example 1. Fig.
Figs. 22 and 23 are photographs of antibacterial test results of oral probiotics of propolis of Experimental Example 1, respectively.
24 is a graph showing the biosafety results of the propolis according to the cell survival rate in Experimental Example 1. FIG.
Fig. 25 and Fig. 26 are photographs of antibacterial test results of the water-soluble and fat-soluble propolis of Example 2 against oral noxious bacteria.
FIG. 27 and FIG. 28 are photographs of antibacterial test results for oral harmful bacteria according to the morphology and compounding concentration of propolis of Experimental Example 2, respectively.
29 and 30 are photographs of antimicrobial test results showing the antibacterial activity of propolis according to the heat treatment of Experimental Example 2, respectively.
31 and Fig. 32 are SEM photographs of the zeolite before and after CHx support of Comparative Example 1, respectively.
33 is an ATR-FTIR spectrum of pure zeolite, CHX, and CHX supported zeolite in Comparative Example 1. Fig.
34 is a photograph showing the bulk of zeolite nanoparticles before propolis loading (A) and after (B) prepared in Example 4. Fig.
35 is a HPLC spectrum of the propolis-containing carrier (A) and the after-treatment (B) of Example 4. Fig.
Fig. 36 is an SEM photograph of the zeolite nanoparticles before and after propolis deposition (Example 4). Fig.
37 is an ATR-FTIR profile of Example 4 before propolis loading (A) and after (B).
38 is a photograph showing the pellet of Example 5. Fig.
39 is a graph showing an analysis of the release behavior of CHX supported on the zeolite of Experimental Example 3 by HPLC.
40 is a photograph of an antibacterial test result of zeolite and acryl resin carrying CHX in Experimental Example 3. FIG.
41 is a graph showing propolis release behaviors of Example 4 and Example 5 in Experimental Example 3;
42 is a photograph showing the antibacterial effect of Example 5 of Experimental Example 3;
43 is a photograph showing the results of antibacterial test on oral microorganisms against the effluent of Example 5 of Experimental Example 3. Fig.
44 is a graph showing the result of pyrolysis analysis in Experimental Example 4. Fig.
45 is a graph showing the result of pyrolysis analysis using the thermogravimetric analyzer of Experimental Example 4. Fig.
46 is a process chart for manufacturing an antibacterial tube of Example 6. Fig.
47 and 48 are photographs of an example of the antibacterial attracting tube manufactured in Example 6, respectively.
49 is a photograph of a specimen for measuring bending strength in Experimental Example 5;
50 is a photograph of an antibacterial test result of zeolite-free pellets (control group) in Experimental Example 6;
51 is a photograph of an antibacterial test result of the zeolite-supporting pellet (control group) in Experimental Example 6. Fig.
52 is a graph showing the comparison of the biosafety (cytotoxicity) by the MTT assay of the zeolite-carrying pellets in Experimental Example 6. Fig.
53 is a diagram showing the result of the skin irritation test in Experimental Example 6. Fig.
FIG. 54 is an official report showing that the cytotoxic response grade 0 is in accordance with ISO 10993 for the prototype of Example 6. FIG.
FIG. 55 and FIG. 56 are visual and microscopic official report showing no oral mucous membrane stimulation according to ISO 10993-10 for the prototype of Example 6, respectively, and FIG. 57 is a microscopic photograph of the tissue specimen.
Fig. 58 is a report showing the results of the dissolution test for the prototype of Example 6. Fig.
FIGS. 59 and 60 are the official transcripts showing the results of the stress reduction test in accordance with ISO 10993 for the prototype of Example 6, respectively.
61 is an official report showing that the result of the genotoxicity test according to ISO 10993 for the prototype of Example 6 is negative.
62 is an official report showing the results of the antibacterial activity test based on ASIM E2149-13a for the prototype of Example 6. FIG.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will now be described in detail with reference to the accompanying drawings.

The composition according to the present invention comprises 30 to 60% by weight of poly (lactic acid) (PLA), 10 to 40% by weight of polycaprolactone (PCL), 3 to 20% by weight of compatibilizer 0.5 to 2 wt% of zirconia (ZrO ₂ ), and 10 to 30 wt% of an inorganic filler.

The polylactic acid used in the present invention is a medical polymer having excellent biocompatibility and has a relatively excellent thermal processing property and strength property but is inferior in brittleness property and is fragile and has a problem that the polylactic acid In order to improve inferior brittleness characteristics, the present invention uses polycaprolactone having excellent flexibility as another medical polymer.

Since the polylactic acid and polycaprolactone are immiscible and form an incompatible blend that lacks the interfacial adhesion between the separated two phases, the host composition according to the present invention can be prepared by mixing a suitable polymer alloy (PMMA), polymethyl acrylate (PMA), polyethylene glycol (PEG), lactic acid-glycolic acid copolymer (PLGA), glycidyl methacrylate (GMA) 3 to 20% by weight of a compatibilizer of any of these mixtures is used.

Among the above compatibilizing agents, glycidyl methacrylate has a double bond or a condensable epoxy group capable of radical reaction, so that graft polymerization is performed at the interface between polylactic acid and polycaprolactone to form a copolymer. Therefore, polylactic acid and polycarboxylic acid It is more preferable because the compatibility of the roll lactone can be effectively enhanced.

If the content of the compatibilizing agent is less than 3% by weight based on the weight of the entire composition, the compatibilizing effect may be excessively lowered. Conversely, when the content of the compatibilizing agent exceeds 20% by weight, swelling may occur at the interface between polylactic acid and polycaprolactone If the content of the polylactic acid is less than 30% by weight based on the total weight of the composition, the strength and thermal processing characteristics may be deteriorated. On the other hand, if the content of the polylactic acid exceeds 60% by weight, If the content of polycaprolactone is less than 10% by weight based on the total weight of the composition, the effect of improving brittleness characteristics may be insufficient, and conversely, the content of polycaprolactone is preferably 40% by weight or less, , There is a possibility that the strength is lowered, which is not preferable.

In addition, the present invention provides a composition for a dental implant, which, when modified by high energy ionizing radiation such as gamma-ray, x-ray, electron beam, etc., is used to produce a polymer blend exhibiting high compatibility by chain cleavage, .

Polylactic acid has a remarkable increase in polymer chain cleavage at a high irradiation dose and crosslinking of polycaprolactone is remarkable. By irradiating with an electron beam of 40 to 120 kGy, the interface of two phases is filled, May be useful for forming a good blend that appears.

In addition, in order to improve the attraction tolerance composition strength and wear resistance and corrosion resistance according to the present invention, the silica as the inorganic filler (SiO _2), hydroxide apatite, tricalcium phosphate, bio-glass, bio-crystallized glass, alumina, or any mixture thereof And 10 to 30% by weight based on the total composition.

When the content of the inorganic filler is less than 10% by weight, there is a possibility that the effect of improving the strength, abrasion resistance and corrosion resistance may be insufficient. Conversely, if it exceeds 30% by weight,

Of the above-mentioned inorganic fillers, silica may be more preferable from the viewpoint of economic efficiency, strength, abrasion resistance and corrosion resistance improving effect.

Zirconia (ZrO ₂ ) used in the present invention composition is a biocompatible material free from corrosion and toxicity, but also imparts high strength and hardness to the inlet tube, thereby increasing the durability and increasing the heat insulating property. In particular, If the addition amount is less than 0.5% by weight, the effect of improving the aesthetics may be insufficient. On the other hand, if the added amount is more than 2% by weight, it is difficult to expect an increase in aesthetic effect due to the increase of the added amount.

The inventive adhesive composition according to the present invention may further optionally comprise 0.02 to 2% by weight of a nano-particle carrying naturally-occurring antimicrobial substance based on the total weight of the composition.

Examples of the nano-particles supported on the natural antimicrobial material include zeolite, clay, aluminosilicate, aluminophosphate, silicoaluminophosphate, silicon dioxide, titanium oxide, aluminum oxide or any mixture thereof. Zeolites are particularly preferred in terms of the amount of natural antimicrobials supported and the sustained release.

The above-mentioned natural antimicrobial substance-supported nanoparticles have an average particle diameter of 50 to 150 nm, and when it is less than 50 nm, it may be undesirable from the viewpoint of process efficiency and economical efficiency. If it exceeds 150 nm, And may be undesirable.

On the other hand, examples of the natural antimicrobial substance that can be supported on the nanoparticles include propolis, berberine, rosmarinic acid, catechin, naringin, or any mixture thereof. Preferably, the antimicrobial substance has thermal stability, antibacterial effect, May be a propolis, especially a fat soluble propolis.

However, the present invention is not limited to this, and the present invention is not limited to this, and it is possible to provide a method for inhibiting proliferation of oral disease-causing microorganisms, It is also possible to use extracts of Peppermint, Chunmun-dong, Gosam, Pepper, Rhubarb, Push, Yellow, White, Dehydrated, Omija, Gaza, Jinpum, Ankyo, White mulberry, Mulberry, Mulberry, Mulberry and Seixin.

In particular, the loading amount of the natural antimicrobial substance may be in the range of 30 to 80% of the weight of the nanoparticles, specifically 0.006 to 1.6% by weight of the total composition.

The inventive composition according to the invention may also contain a pigment mixture of 0.01 to 0.09 phr (per hundred resin) and 0.01 to 0.09 phr of a yellow pigment for the same or very similar shade coloring as the original tooth shade , And in particular a mixture of yellow pigment: red pigment = 0.08 phr: 0.02 phr to develop the shade guide A2 shade, which is the most common tooth color of the Korean.

The antimicrobial induction tube according to the present invention is formed by injection molding the inventive host composition containing the above-mentioned natural antimicrobial substance-bearing zeolite with a tooth mold of a specific kind.

Next, a method of manufacturing an antibacterial attracting tube according to the present invention will be described.

The method for producing an antibacterial attracting tube according to the present invention includes the following steps.

(A) Matrix resin forming step:

30 to 60 wt% of poly (lactic acid) (PLA), 10 to 40 wt% of polycaprolactone (PCL), 3 to 20 wt% of compatibilizer, zirconia (ZrO ₂ ) 0.5 To 2% by weight of an inorganic filler and 10 to 30% by weight of an inorganic filler is kneaded and extruded, followed by cutting with a cutter to produce chips, pellets or grains.

Alternatively, an electron beam of 40 to 120 kGy may be irradiated during the kneading process to form a polymer blend exhibiting higher compatibility.

(B) Step of preparing nanoparticles carrying natural antibacterial substance:

The nanoparticles having an average particle size of 50 to 150 nm are heat-treated at 500 to 700 ° C for 0.5 to 2 hours to completely remove moisture and dried. The nanoparticles are then dispersed in an aqueous solution of a natural antimicrobial material and stirred, and recovered by appropriate means such as centrifugation , And lyophilized.

(C) Blow tube manufacturing step:

The matrix resin and the natural antimicrobial substance-supported nanoparticles are compounded and injection-molded to form an inlet tube.

Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples.

Example 1: Preparation of pellets using an inlet tube composition

50% by weight of poly (lactic acid) (PLA), 20% by weight of polycaprolactone (PCL), 3% by weight of polymethylmethacrylate (PMMA) , 2 wt% of polyethylene glycol (PEG), 3 wt% of lactic acid-glycolic acid copolymer (PLGA), 1 wt% of zirconia (ZrO ₂ ) and 20 wt% of silica were extruded and cut to obtain a matrix resin The pellets were prepared and the pellets produced were shown in Fig.

Example 2: Preparation of pellets using an inlet tube composition

, 50 wt% of poly (lactic acid) (PLA), 20 wt% of polycaprolactone (PCL), 8 wt% of glycidyl methacrylate (GMA), zirconia (ZrO ₂ ) 2 wt%, and 20 wt% of silica were kneaded, extruded and cut to prepare a matrix resin pellet. The pellets produced exhibited the same hue as that shown in Fig.

Example 3: Preparation of pellets using the parent tube composition

45 wt% of poly (lactic acid) (PLA), 15 wt% of polycaprolactone (PCL), 8 wt% of glycidyl methacrylate (GMA), zirconia (ZrO ₂ ) 2% by weight, and 30% by weight of silica were kneaded, extruded and cut to prepare a matrix resin pellet. The pellet produced was shown in FIG.

Experimental Example 1: Inhibitory effect of natural antibacterial substance on oral bacteria

(1) Cell survival rate of Berberine and its inhibitory effect on oral bacteria

We investigated whether berberine, an isoquinoline alkaloid, is safe for normal oral tissues and analyzed its inhibitory effect against oral bacteria.

Cell viability analysis of human oral keratinocytes (NHOKs)

The optimal concentration of berberine was determined by the treatment with berberine (1 mg / mL ~ 100 ng / mL).

The results of the first experiment showed no effect on cell survival at the concentration of 5 ug / mL to 100 ng / mL. As a result of the second experiment, there was.

FIG. 3 is a graph showing the results of the first experiment on cell viability in a concentration range of 100 ng to 1 mg, and FIG. 4 is a graph showing a second experimental result on cell viability in the range of 1 ug to 0.01 ug concentration.

② Analysis of inhibition against 3 kinds of oral bacteria:

Berberine was tested twice against C. albicans, S. mutans, and S. sobrinus, and the results were as follows. In the first experiment, strong inhibitory activity against S. sobrinus was observed at 100 μg / mL, and 250 to 500 μg / mL inhibited S. mutans and S. sobrinus. In the 500 μg / mL concentration group, the inhibition was observed in three strains. In the second experiment, in order to confirm that the powdered berberine to be loaded on the zeolite nanoparticle exhibits antibacterial activity by powder itself, the powder was applied to the lawn for 12 hours or more, The antimicrobial zygote was confirmed.

The results of the first experiment are shown in the following Table 1 and FIG. 5, and the results of the second experiment are shown in the following Table 2 and FIG. 6, respectively.

The first experiment on the inhibitory effect of berberine on three kinds of oral bacteria Inhibition zone ( Dia , mm) C. albicans S. mutans S. sobrinus Control - - - 100 μg / mL 0.0 mm 0.0 mm 3.0 mm 250 μg / mL 0.0 1.0 3.0 500 μg / mL 1.0 2.0 4.5

The first experiment on the inhibitory effect of berberine on three kinds of oral bacteria Inhibition zone ( Dia , mm) C. albicans S. mutans S. sobrinus Control - - - Liquid phase 5 mg / mL 3.0 mm 4.0 mm 4.0 mm Liquid 15 mg / mL 4.0 5.0 5.0 Liquid phase 50 mg / mL 5.0 5.0 6.0 Powder - 3.0 3.0

(2) Antimicrobial activity analysis of rosemarinic acid against S. oralis strain S. sobrinus

Rosemarinic acid is a caffeic acid ester, a phenolic active compound containing 3,4-dihydroxyphenylacetic acid as a natural ingredient derived from domestic wild-caustic rye (Agastache rugosa) and rosemary, and its antimicrobial activity against S. pneumoniae S. sobrinus was analyzed .

      As a result, the inhibitory effect on S. sobrinus was observed, and the concentration was in the range of 500 ug / mL to 2 mg / mL. As a result, the inhibitory effect was not observed at 1 mg / mL and 2 mg / mL The results are shown in Table 3 and FIG.

Inhibition of rosmarinic acid on S. sobrinus Inhibition zone ( Dia , mm) S. sobrinus Control - 500 μg / mL 3.0 mm 1 mg / mL 4.0 2 mg / mL 4.0

(3) Antimicrobial activity analysis of catechin against oral harmful bacteria

Four major components (EGCG, ECG, EC, EGC) were analyzed for catechin, a tea-derived natural product with anti-cavitation, anti-oxidative, carcinogenic, antiviral, antibacterial,

Effects of catechin EGCG on the inhibition of S. mutans, S. sobrinus, and C. albicans:

* Inhibition of EGCG against three kinds of oral harmful bacteria: As a result of treating EGCG with two high concentrations (1, 10 mg / mL) for three different organisms, a clear inhibition of about 1.8 mm of S. mutans and S. sobrinus was observed at a concentration of 1 mg / mL, and C. albicans , A zipper of 3 mm or more was shown. In addition, at 10 mg / mL, S. mutans, S. sobrinus, and C. albicans showed more than 10 mm of zonation.

The results are shown in Table 4 below.

Inhibition of 1 mg / mL and 10 mg / mL EGCG against S. mutans, S. sobrinus, and C. albicans Inhibition zone ( Dia , mm) S. mutans S. sobrinus C. albicans Control - - - 1 mg / mL 1.8 mm 1.8 mm > 3.0 mm 10 mg / mL 10.0 11.0 11.0

The antimicrobial test results for the inhibitory effect of 1 mg / mL of S. mutans and S. sobrinus are shown in FIGS. 8 and 9, and the antibacterial test results for the inhibitory effect of C. albicans are shown in FIG. 10, and the results of 10 mg / mL EGCG The results of antibacterial tests on the inhibitory activity of C. albicans, S. mutans and S. sobrinus are shown in Fig.

* Inhibition of low-concentration EGCG against S. mutans and S. sobrinus :

EGCG was treated with two low concentrations (15, 15, and 100 ug / mL) for two strains, respectively. As a result, a transparent inhibition of 1.0 mm for S. mutans and 4.0 mm for S. sobrinus at a concentration of 15 ug / , And 15 and 100 ug / mL, respectively.

The results are shown in Table 5 and Fig.

Inhibition of low-concentration EGCG against S. mutans and S. sobrinus Inhibition zone ( Dia , mm) S. mutans S. sobrinus Control - - 15 μg / mL 1.0 mm 4.0mm 50 μg / mL 1.5 4.5 100 μg / mL 2.5 4.5

② Effect of catechin ECG (Epicatechin gallate) on S. sobrinus inhibition:

As a result of treatment with S. sobrinus, which is a major pathogen of periodontal disease, in the concentration range of 15, 50 and 100 μg / mL, transparent inhibition of 3.0, 4.0 and 4.0 mm was obtained. I did not see it.

The results are shown in Table 6 below.

Inhibition of ECG on S. sobrinus Inhibition zone ( Dia , mm) S. sobrinus Control 2.0 mm 15 μg / mL 3.0 50 μg / mL 4.0 100 μg / mL 4.0

Antibacterial results at concentrations of 15 [mu] g / mL and 100 [mu] g / mL are shown in FIGS. 13 and 14, respectively

③ Effect of catechin EC (Epicatechin) on the inhibition of oral harmful bacteria (S. mutans, S. sobrinus, C. albicans)

EC was applied to 3 different organisms at a concentration of 10 mg / mL, respectively. As a result, 4 mm of translucency was observed in S. mutans, 7 mm of translucency was restored in S. sobrinus and 6 mm in C. albicans.

The results are shown in Table 7 and Fig.

The inhibitory effect of catechin EC on oral noxious bacteria Inhibition zone ( Dia , mm) S. mutans S. sobrinus C. albicans Control - - - 10 mg / mL 4.0 mm 7.0 mm 6.0 mm

④ Inhibition of oral antibiotics (S. mutans, S. sobrinus, C. albicans) of catechin EGC (Epigallocatechin)

The effect of EGC 15, 50 and 100 ug / mL on the inhibition of growth of S. mutans, S. sobrinus and C. albicans was not observed. The proliferation inhibition of sobrinus was stronger than that of the other two species.

The results are shown in Table 8 and FIG.

Inhibition of EGC against C. albicans, S. mutans, and S. sobrinus Inhibition zone ( Dia , mm) C. albicans S. mutans S. sobrinus Control - - - 15 μg / mL 1.5 mm 1.0 mm 4.0 mm 50 μg / mL 1.5 2.0 4.5 100 μg / mL 1.5 2.0 4.5

⑤ Verification of biosafety through analysis of cell survival rate of catechin:

Treatment of Raw 264.7 cells with four different catechins (EGCG, EGC, EC, and ECG) by concentration (1 ~ 100 ug / mL) resulted in an effect on cell viability in the concentration range of 1 ~ 10 ug / mL for EGCG EGC treatment did not affect cell viability at all concentration ranges (1 ~ 100 ug / mL). EC treatment significantly affected cell viability in the range of 1 ~ 50 ug / mL. And ECG cells showed cell viability below 80% at all concentration ranges (1 ~ 100 ug / mL), indicating slight toxicity.

In conclusion, the three concentrations of catechins (EGCG, EGC, and EC) did not affect the cells in the concentration range of 1 ~ 50 ug / mL. Therefore, I could confirm.

EGCG, EGC, EC, and ECG are shown in Figs. 17 to 20, respectively.

(4) Naringin (Naringin) inhibitory effect on two kinds of oral bacteria

(S. mutans, S. sobrinus) at 500, 700 μg / mL and 1 mg / mL, respectively. In all concentrations, S. sobrinus was more strongly inhibited than S. mutans, and 700 μg / mL and 1 mg / mL, there was no significant difference in inhibition of the two strains.

The results are shown in Table 9 and Fig.

Inhibition of Naringin against S. mutans and S. sobrinus Inhibition zone ( Dia , mm) S. mutans S. sobrinus Control - - 500 μg / mL 1.0 mm 2.5 mm 700 μg / mL 1.5 3.0 1 mg / mL 1.5 3.0

(5) Analysis of inhibitory activity and cell survival rate of three kinds of oral pest bacteria of Propolis

① The results of the first and second experiments of treating 0.5% and 1% of propolis with three kinds of bacteria (C. albicans, S. mutans, S. sobrinus) are shown in the figure below. And the antimicrobial activity was analyzed.

The results are shown in Table 10, FIG. 22, and FIG. 23, respectively.

Inhibition of Propolis by C. albicans, S. mutans, and S. sobrinus Inhibition zone ( Dia , mm) C. albicans S. mutans S. sobrinus Control - - - 0.5% 5.0 mm 6.0 mm 4.0 mm One% 5.0 6.5 4.0

Cell viability analysis:

As shown in the lower graph, cell viability was confirmed by treating cells at 24 hours, 48 hours, and 72 hours in three concentration ranges (1.25 ~ 10 ug / mL). When treated for 24 hours, cell viability was not affected at all concentration groups, and cell survival rate was 80% or more in all concentration groups when treated for 48 hours, and 10ug / mL when treated for 72 hours (Survival rate 60%), all of the cells showed cell viability of 80% or more.

The results of cell viability by MTT analysis of propolis are shown in Fig.

Experimental Example 2: Optimum conditions for mixing propolis as a natural antimicrobial substance

(1) Comparative analysis of antibacterial activity between water-soluble propolis and liposoluble propolis

As a result of the comparative analysis of the antibacterial activity of water - soluble and lipid - soluble propolis using C. albicans as a target strain, the water - soluble propolis showed no or very weak antibacterial activity against bacteria at all concentration groups (0.137 ~ 1.10%) , And lipid soluble propolis showed excellent antimicrobial activity at all concentrations (0.137 ~ 1.10%).

The results are shown in Tables 11 and 12 and Figs. 25 and 26, respectively.

Antibacterial activity of C. albicans by concentration of water-soluble propolis receptivity propolis ① 0.137% ② 0.275% ③ 0.55% ④ 1.10% Control (EtOH) - - - - C. albicans - - 0.1 mm 0.5 mm

Antibacterial activity of liposoluble propolis on C. albicans Liposuction propolis  [Inhibition zone ( Dia , mm)] ① 0.137% ② 0.275% ③ 0.55% ④ 1.10% Control (EtOH) - - - - C. albicans 1.5 to 2.0 mm 2.0 to 2.5 mm 2.5 to 3.0 mm 4.0 mm

(2) Optimum concentration of liposoluble propolis

In order to determine the compounding concentration of the lipid soluble propolis to be carried on the zeolite, three antibacterial strains (C. albicans, S. mutans, S. sobrinus) were cultured in 0.125, 0.25, 0.5 and 1.0% As a result, there was no significant difference between 0.5% and 1.0% of antimicrobial activity. Therefore, the optimum concentration to be supported on the zeolite was determined to be 0.5%.

In order to determine the type of propolis to be carried on the zeolite, the powdered propolis was loaded on a bacterial lawn (at 8 o'clock in FIG. 27) to confirm the presence or absence of the antimicrobial activity.

The results of the comparison of the antimicrobial activity between liquid propolis and powder propolis are shown in Tables 13 and 27, and the results of the comparison of the antimicrobial activity by liquid propolis concentration are shown in Tables 14 and 28, respectively.

Comparison of Antibacterial Activity between Liquid Propolis and Powdered Propolis Unit (mm) Inhibition zone ( Dia , mm) C. albicans S. mutans S. sobrinus Control 0 0 0 0.5% 4.0 4.5 5.0 One% 4.0 5.0 5.0 powder 3.0 3.0 5.0

Comparison of Antimicrobial Activity of Liquid Propolis by Concentration Unit (mm) Inhibition zone ( Dia , mm) C. albicans S. mutans S. sobrinus Control - - - 0.125% 2.0 1.0 1.0 0.25% 2.0 1.0 1.5 0.5% 2.0 2.5 2.5 One% 3.0 4.0 4.5

(3) Analysis of change in antibacterial activity of propolis due to heat treatment

Propolis was treated at 120 ℃ and 150 ℃, respectively. As a result, the antimicrobial activity was slightly decreased, but the antimicrobial activity was maintained.

The results of the heat treatment at 120 占 폚 are shown in the following Tables 15 and 29, and the results of the heat treatment at 150 占 폚 are shown in the following Table 16 and Fig. 30, respectively.

120 ℃ Antibacterial activity of propolis Concentration (mg / mL) Inhibition zone ( Dia , mm) C. albicans S. mutans S. sobrinus Control - - - 5 - - - 10 - - - 50 1.0 0.7 1.0 100 1.0 1.5 1.5

Antibacterial activity of propolis treated at 150 ℃ Concentration (mg / mL) Inhibition zone ( Dia , mm) C. albicans S. mutans S. sobrinus Control - - - 5 - - - 10 - - - 50 1.5 1.5 1.0 100 1.5 2.5 2.0

Comparative Example 1: Support of CHX on zeolite

Previous studies have been conducted using chlorhexidine (CHX), which is generally used for oral treatment, for the support of natural antimicrobial materials against zeolite. Zeolite [H-beta, SiO ₂ : Al ₂ O ₃ = 98: 2 (w / w)] was heat-treated at 600 ° C for 1 hour to completely remove water that might be present in the zeolite pores.

In order to support CHX on zeolite, 30 mg of CHX was dissolved in 10 mL of distilled water to prepare a CHX aqueous solution. Then, 30 mg of zeolite was added and stirred for 24 hours. Then, the zeolite was recovered by centrifugal separation and washed three times with distilled water And lyophilized.

Figs. 31 and 32 show the results of observing the morphological characteristics of zeolite particles before CHX loading and the prepared CHX supported zeolite using a scanning electron microscope (SEM), respectively.

The zeolite particles having an average particle size distribution of 100 nm were used. The water molecules contained in the pores of the zeolite were completely removed through a high-temperature heat treatment and then pulverized using a mortar bowl. The prepared CHX-supported zeolite was converted into pure zeolite And it was judged that zeolite lumps or CHX powder and lumps were not observed by the CHX, so that the zeolite pores or the surface supported the CHX well.

The attenuated total reflectance-fourier transform infrared (ATR-FTIR) spectra of the CHX supported on the zeolite was measured. The results are shown in FIG.

FIG. 33 shows the ATR-FTIR spectrum of the pure zeolite (a), CHX (b) and CHX supported zeolite (c).

In pure zeolite, vibrations due to H ₂ O were observed at 3,620 and 3,420 cm ^-1 in the spectrum, peaks due to stretching were observed at 1,640 cm ^-1 in HOH, and vibrations due to Si-O stretching were found at 969 -461 cm < ^{-1 &} gt ;.

In the case of CHX, CN stretching was observed at 1,640 cm ^-1 , peaks due to aromatic CC bending were observed at 1,500 cm ^-1 , peaks due to NH stretching and bending at 2,540 and 1,520 cm ^-1 were confirmed.

And it was confirmed that the case of the CHX-supported zeolite, ^1000-1, observed both a peak caused by the zeolite and CHX at 600 cm ^-1 CHX successfully supported on the zeolite.

Example 4: Preparation of supported zeolite of propolis

Propolis was supported on zeolite nanoparticles based on the design of carrying the CHX on zeolite nanoparticles.

First, zeolite nanoparticles (average 100 nm) were heat-treated at 600 ° C for 1 hour to completely remove moisture that might be present in the zeolite pores. Then, 20 g of zeolite was dispersed in 150 mL of an aqueous solution containing 10 g of propolis, Lt; / RTI >

Then, the zeolite was recovered by centrifugation and then lyophilized to prepare zeolite nanoparticles loaded with propolis.

34 shows the zeolite nanoparticle bulk before (A) and after (B) propolis deposition.

The supported ratio of the prepared propolis-supported zeolite nanoparticles was measured by HPLC. The zeolite was dispersed in an aqueous propolis solution as described above, and after stirring for 24 hours, the zeolite was recovered by centrifugation and the residual solution The amount of propolis carried on the zeolite was analyzed by quantifying propolis.

The peak of propolis using HPLC is p-coumaric acid, quercetin and cinnamic acid which are one kind of flavonoids. Among them, the propolis aqueous solution before and after carrying zeolite is analyzed by HPLC using area ratio of Qurecetin, Polys amount was quantified.

The HPLC conditions were mobile phase (water: methanol = 70:30), acetic acid (0.1%), flow rate (1 mL / min) and injection volume (10 μL) at a wavelength of 275 nm.

As a result of measuring the supporting ratio using the area ratio of the thus measured HPLC, it was confirmed that 78.58% by weight was supported on the zeolite.

FIG. 35 shows HPLC spectra of (A) and (B) before and after propolis administration.

The morphological characteristics of the prepared propolis-supported zeolite were analyzed by SEM. The shape and size of the zeolite particles before and after the propolis loading were not significantly changed. However, in the case of propolis-loaded zeolite, Was adsorbed and uniformly dispersed in nanometer size.

FIG. 36 shows an SEM photograph of the zeolite nanoparticles before and after propolis-supporting (A) and (B).

ATR-FTIR was measured to confirm propolis in propolis-loaded zeolite nanoparticles. In the case of zeolite bearing propolis, characteristic peaks attributed to propolis were observed in addition to pure zeolite characteristic peaks.

FIG. 37 shows the ATR-FTIR profile of (A) and (B) before propolis administration.

The propolis characteristic peaks include OH stretching at around 3310 cm ^-1 , CH bending of the aromatic compound at around 2920 cm ^-1 , C = C stretching of the aromatic ring around 1600 cm ^-1 , 1200-1400 cm ^-1 It was confirmed that the propolis was supported on the zeolite by observing the COC stretching, CH wagging, CH + OH bending, and vibration of the aromatic ring at about 861 cm ^-1 in the range.

Example 5: Preparation of natural antimicrobial substance-releasing antimicrobial seedling tube composition

The propolis-supported zeolite prepared in Example 4 was added in an amount of 2.6787% by weight (1.5% by weight of zeolite and 1.1787% by weight of supported propolis) to the matrix resin pellets of Example 2 by a twin-screw extruder Compounding was carried out using the Twin screw extruder (Korea EM, Φ = 32, L / D = 40) as shown in Table 17 below and extrusion molding was conducted to prepare a natural antimicrobial substance- To prepare pellets.

 PLA Composite-Zeolite Compounding Conditions Zone C1 C2 C3 C4 C5 C6 C7 C8 C9 Adapter Die Temperature (℃) 120 135 135 140 145 145 150 150 160 160 160 Melt pressure = 1 kg / cm3 Temperature = 161 ° C Main motor = 15 amp Exturder-speed = 99.5 r / min Screw feeder = 10 rpm

The result of the production is shown in Fig.

EXPERIMENTAL EXAMPLE 3 Evaluation of Antimicrobial Release Behavior and Antimicrobial Activity from Zeolite Containing Antimicrobial Substance

(1) Evaluation of release behavior and antibacterial property of CHX supported zeolite

The release behavior of CHX supported on zeolite was analyzed as follows.

First, CHX-supported zeolite was dispersed in a light-cured acrylic resin and then prepared into a disk form. The acrylic resin thus prepared was immersed in a phosphate buffered saline (PBS, pH 7.4) for 20 days, And analyzed by liquid chromatography. A graph of the release behavior is shown in Fig. 39

In the case of sample (a) in which pure CHX powder was directly mixed with acrylic resin, 38% of CHX released for 20 days was released, and in case of sample (b) in which CHX was mixed with acrylic resin, It was confirmed that CHX was slowly released from the polymer matrix when zeolite was used.

That is, when the zeolite is used as the support, it is confirmed that the antimicrobial substance supported on the zeolite is gradually released, so that the development of the functional induction tube capable of releasing the antimicrobial substance for a long time is expected.

The antimicrobial effect of CHX-loaded zeolite mixed acrylic samples was confirmed by an agar diffusion test using S. mutans, and the results of experiments of CHX-loaded zeolite and acrylic resin are shown in FIG.

First, pure zeolite in the form of pure zeolite (c), CHX (a), and CHX-loaded zeolite in particle form was observed to have no antimicrobial effect, and CHX-loaded zeolite showed excellent antimicrobial effect .

(B), which is a mixture of zeolite containing CHX and zeolite, showed antimicrobial effect even though the inhibitory zone of S. mutans was smaller than that of acrylic resin (c) prepared by directly mixing CHX powder, and pure zeolite The antimicrobial effect of the acrylic resin prepared by mixing was not observed.

As a result, in the case of the zeolite carrying the antimicrobial substance and the polymer resin containing the zeolite, when the zeolite is used as the carrier instead of the pure antimicrobial substance directly mixed with the polymer resin, an appropriate concentration of the antimicrobial substance is stable for a long period of time And it was confirmed that excellent antimicrobial effect was exhibited.

(2) Release behavior of propolis-zeolite and evaluation of antibacterial activity

The release behavior of zeolite loaded propolis was analyzed as follows.

First, only the propolis-carrying zeolite of Example 4 was immersed in PBS at 37 占 폚 and left in a static state. Then, the eluate was recovered by time and analyzed by HPLC as described above to measure release behavior. At this time, the propolis emission amount analysis was performed using the area ratio of the propolis specific peak Qurecetin peak.

The release behavior of propolis from the composition pellets of Example 5 containing propolis-loaded zeolite was also measured by the same method as described above by immersing in PBS at 37 ° C.

result:

The release behavior of propolis from only the propolis-bearing zeolite of Example 4 was 50% released within 5 days of immersion and about 70% or more propolis was released within 7 days of immersion. From 7 days after immersion, the amount of release was greatly decreased, and in the case of propolis - loaded zeolite, most propolis was released within 7 days of immersion.

On the other hand, in the case of Example 5 in which the propolis-supported zeolite was dispersed in the PLA / PCL matrix resin, about 20% of the propolis was released within 5 days of immersion, and after about 40% Or more.

That is, the release of propolis from the propolis-supported zeolite contained in the PLA / PCL matrix resin was confirmed by the PLA / PCL polymer matrix to exhibit a sustained and stable sustained release behavior rather than a rapid release, % Or more of propolis was retained in the matrix resin.

41 shows a propolis release behavior graph, wherein (A) shows the propolis-bearing zeolite nanoparticles and (B) shows the propolis-bearing zeolite-containing PLA / PCL matrix resin.

The antimicrobial effect of Example 5 containing the propolis-containing zeolite was confirmed by an agar diffusion test using C. albicans, and the results are shown in FIG.

In the case of the CHX powder (A) used as the control, the inhibition zone was observed to be clear and large, and (B) of Example 5 including the propolis-supported zeolite showed a suppression similar to that of CHX Zone, but pure zeolite (C) did not have an antibacterial effect (left drawing of FIG. 42).

In the case of the antimicrobial effect using the eluate (2) of the PLA / PCL matrix resin containing the propolis-supported zeolite of Example 5, it was confirmed that the inhibitory zone against the aqueous CHX aqueous solution (1) as a control exhibited a small but obvious antimicrobial effect 42).

Then, the propolis supported on the zeolite in the PLA / PCL matrix resin containing the propolis-supported zeolite of Example 5 was eluted with ethanol, and the antibacterial activity against the three kinds of oral bacteria was analyzed. As a result, the normal antibacterial activity was maintained And the results are shown in Table 18 and Fig. 43 below.

Propolis Supported - Antimicrobial activity against three kinds of oral harmful bacteria of zeolite Concentration (mg / mL) Inhibition clear zone (diameter, mm) C. albicans S. mutans S. sobrinus Control - - - 5 - - - 10 - - - 50 2.0 1.0 1.0 100 3.5 1.5 2.0

Experimental Example 4: Establishment of mixing conditions of matrix resin and antimicrobial supported zeolite nanoparticles

As a result of pyrolysis analysis of the propolis-supported zeolite using a thermogravimetric analyzer (TGA), as shown in the following Table 19 and FIG. 44, about 3.8% weight loss was firstly occurred from room temperature to 120 ° C, It was found that the weight loss gradually increased from 120 ° C to 700 ° C and the total weight loss was 24.4%.

Pyrolysis of propolis-supported zeolite using thermogravimetric analyzer (TGA) Sample T _D ⁱ (° C) at air Residue (%) at air Zeolite 57.8 75.6

As a result of the thermal decomposition analysis of PLA compound using DSC (Differential Scanning Calorimeter), it was confirmed that PLA and PCL were blended (PLA Tm = 15 9 ° C) in Example 5, and that TC of PLA was increased when Zeolite was included Respectively.

The results are shown in Table 20 and FIG.

Pyrolysis analysis of PLA compound using DSC Sample Tg Tc Tm PLA composite material (top graph) - 87.7 55.30
159.6 PLA / zeolite (bottom graph) - 125.8 61.3
159.7

PLA composite matrix resin, and PLA composite matrix resin, the MI was improved after compounding zeolite as a result of measurement of the melting index (MI) of the zeolite compound carrying the antibacterial substance. The results are shown in Table 21 below.

PLA composite matrix resin and the melt index Sample 190 ℃ 210 ℃ PLA composite matrix resin Weight (g / min) 3.0217 5.8923 3.1392 4.4424 2.9967 4.2714 Average (g / min) 3.05 4.87 PLA composite matrix resin + Zeolite Weight (g / min) 3.4962 5.7071 3.2639 5.4250 3.4805 5.8644 Average (g / min) 3.41 5.67

Example 6: Preparation of antibacterial tube

The yellow and red pigments were mixed with the composition of Example 5 in the amounts shown in Table 22 below, and the antimicrobial seed tubes were injection molded according to the procedure as shown in Fig.

Yellow Red Yellow Red 0.02 phr 0.001 phr 0.02 phr 0.002 phr 0.04 phr 0.04 phr 0.06 phr 0.06 phr 0.08 phr 0.08 phr

The A2 shade, which is the optimal shade for most Koreans, was obtained at yellow pigment: red pigment = 0.08 phr: 0.002 phr.

Prototypes of the injection molded antimicrobial tube are shown in Figs. 47 and 48. Fig.

Experimental Example 5: Physicochemical characterization of antibacterial tube

(1) Measurement of Flexural Strength (Strength of Tube Material)

- Test standard: ISO 10477 (Flexural strength) Reference value: ≥ 50 MPa

      Dentistry - Polymer-based crown and bridge materials

- specimen (see FIG. 49)

(2 ± 0.1) mm × (2 ± 0.1) mm × (25 ± 2.0) mm using five specimens prepared from the composition of Example 5,

- Test method: Prepare the above specimens, store them in distilled water (37 ± 1) ℃ for 24 ± 1 hours before testing, and set the cross-head speed of the tensile and compression tester to (0.75 ± 0.25) mm / min The maximum load was measured by three-point bending test.

- Test result

(1) (59.4 MPa), 2 (58.9 MPa), 3 (56.5 MPa), 4 (56.7 MPa) and 5 (59.2 MPa)

② All of the measured values were more than 50 MPa required by ISO 10477: 2009.

③ The flexural strength of all specimens was confirmed to be suitable as a duct.

(2) Solubility

- Test standard: ISO 10477 (Solubility) ≤ 7.5 ug / ㎣

Dentistry - Polymer-based crown and bridge materials

- The Psalms

Five specimens (15 ± 1) mm diameter and (1.5 ± 0.1) mm thickness prepared from the composition of Example 5

- Test Methods:

The specimens were stored at (37 ± 1) ° C for 23 hours, then stored at (23 ± 1) ° C for 2 hours and then weighed. The specimens were placed in 10 ml of distilled water, After storage for one day, the water content on the specimen surface was removed, air was blown for 15 seconds, and then the weight was measured to calculate the solubility.

- Test result

The results were as follows: 1 (1.7 ug / ㎣), 2 (1.4 ug / ㎣), 3 (1.7 ug / ㎣), 4 10477: 2009, which is less than 7.5 ug / 요구, all of which were found to be within the acceptable range of solubility.

Experimental Example 6: Analysis of antibacterial activity Light biosafety evaluation

(1) Comparison of antibacterial activity of zeolite-free pellets and zeolite-loaded pellets

The antimicrobial activity of zeolite-free pellets (control) and zeolite-loaded pellets (antimicrobial pellets, test group (Example 5)) were compared using a liquid shaking culture based on KS J 4206.

The control and test groups were each prepared in 3 replicates, Escherichia E. coli ATCC 25922 was inoculated on TSB medium, diluted with the bacterial culture to a concentration of (1 × 10 ⁵ ) (CFU) / ml, and then diluted with the test and control groups in sterilized TSB liquid medium (50 mL) E. coli culture was inoculated at 100 each and cultured at 37 째 C with shaking at 120 rpm for 24 hours. Subsequently, approximately 200 μL of the dilution culture was spread on TSA medium, and then colonies counted after culturing at 37 ° C. for 24 hours were counted.

On the other hand, at the time of inoculation, a certain amount was taken from the test group and the control group, diluted to a dilution range of (10 ¹ to 10 ³ ) times using physiological saline, and about 200 μL of the diluted culture was spread on TSA medium, After incubation, the number of bacteria was confirmed.

In the case of zeolite-free supported pellets (control group), it was confirmed that E. coli was normally proliferated as shown in FIG.

On the other hand, in the case of the zeolite-supported pellets (test group: Example 5), as shown in Fig. 51, unlike Fig. 50, it was confirmed that E. coli proliferation was significantly inhibited.

(2) Biosafety (cytotoxicity) analysis of zeolite-free pellets and zeolite-supported pellets

Preparation of eluate: In order to prepare an eluate of zeolite-free ferrets (control group) without antimicrobial substance (control group) and Example 5 (test group), 1 g each was added to 10 mL of DMEM / CM, And used as a sample for cytotoxicity analysis.

The survival rate of the normal cells (HaCaT cells) was analyzed by MTT assay, and the medium component (DMEM / CM) (left side) was used as a blank and the control pellet ). As a result of the analysis, as shown in FIG. 52, the cell survival rate was nearly 100% when the blank and the control group and the test group (right side) were compared, and it was confirmed that Example 5 was non-toxic.

(3) Skin test

Preparation of eluate: 1 g of each pellet was added to 10 mL of DMEM / CM, which is a cell culture medium, to obtain an eluate of the zeolite-free ferret having no antimicrobial substance (control group) and Example 5 (test group) And then used as a sample for cytotoxicity analysis.

Using the eluent of the pellet obtained by the above method as a test group, about 200 uL of distilled water (control group) and prototype eluate (test group) were applied to the gauze surface of the disposable band by applying the basic method of skin irritation test, And the skin condition was checked after 12 hours.

After 12 hours of attachment, the naked band was removed from the skin surface and visually examined whether the skin was erythema, pruritus, irritation, swelling or not. As a result, no difference was found between the control group and the test group, These results confirm that the prototype is non-toxic to the skin.

The skin irritation test results are shown in Fig.

In addition, FIG. 54 is an official report showing that the cytotoxic reaction grade 0 grade according to ISO 10993 for the prototype of Example 6, FIG. 55 and FIG. 56 show a visual report showing no oral mucosal irritation according to ISO 10993-10 57 is a microscope photograph of a tissue specimen, FIG. 57 is a microscope image of a dissolution test, and FIGS. 58 to 60 are an official report showing the results of a sensitization test according to ISO 10993 , Fig. 61 is an official report showing that the result of the genotoxicity test based on ISO 10993 is negative, and Fig. 62 is an official report showing the results of the antibacterial test based on ASIM E2149-13a. And a detailed description thereof will be omitted.

Claims (15)

30 to 60 wt% of poly (lactic acid) (PLA), 10 to 40 wt% of polycaprolactone (PCL), 3 to 20 wt% of compatibilizer, zirconia (ZrO ₂ ) 0.5 To 2% by weight of an inorganic filler and 10 to 30% by weight of an inorganic filler. The method of claim 1, wherein the compatibilizer is selected from the group consisting of poly (methyl methacrylate) (PMMA), poly (methyl acrylate) PMA, poly (ethyleneglycol) Which is at least one compatibilizer selected from the group consisting of poly (lactic-co-glycolic acid) (PLGA) and poly (glycidyl methacrylate) Composition. The host composition according to claim 1, wherein the inorganic filler is at least one inorganic filler selected from the group consisting of silica (SiO ₂ ), hydroxyapatite, calcium triphosphate, biological glass, biocrystalline glass and alumina. The host composition according to claim 1, wherein the host composition further comprises 0.02 to 2% by weight based on the total composition of the nano-particles. 5. The method of claim 4, wherein said natural antimicrobial carrier carrying nanoparticles are selected from the group consisting of zeolite, clay, aluminosilicate, aluminophosphate, silicoaluminophosphate, silicon dioxide, titanium oxide and aluminum oxide At least one support. The host composition according to claim 5, wherein the nanoparticles have an average particle size of 50 to 150 nm. The host composition according to claim 4, wherein the natural antimicrobial substance is at least one natural antimicrobial substance selected from the group consisting of propolis, berberine, rosmarinic acid, catechin, and naringin. [Claim 5] The composition according to claim 4, wherein the natural antibacterial substance is a fat-soluble propolis and the amount of the antibacterial substance is 0.006 to 1.6% by weight based on the total weight of the composition. 6. The process according to claim 4 or 5, wherein said host composition further comprises a pigment mixture of 0.01 to 0.09 phr of a yellow pigment for shade coloring and 0.01 to 0.09 phr of a red pigment, Composition. 10. The composition according to claim 9, wherein said pigment mixture is formulated to exhibit a shade guide A2 shade as a mixture of yellow pigment: red pigment = 0.08 phr: 0.02 phr. An antimicrobial induction tube formed by injection molding of the host composition according to any one of claims 4 to 8. 12. The antimicrobial induction tube according to claim 11, wherein said antimicrobial tube is a mixture of yellow pigment: red pigment = 0.08 phr: 0.02 phr to exhibit a shade guide A2 shade. (A) 30 to 60% by weight of polylactic acid (PLA), 10 to 40% by weight of polycaprolactone (PCL), 3 to 20% by weight of compatibilizer, zirconia ₂ ) 0.5 to 2% by weight of an inorganic filler and 10 to 30% by weight of an inorganic filler is kneaded and extruded and then cut with a cutter to prepare a matrix resin in the form of chips, pellets, or grains ,
(B) a step of heat-treating nanoparticles having an average particle size of 50 to 150 nm, drying the nanoparticles, dispersing the nanoparticles in an aqueous solution of a natural antimicrobial material, stirring the nanoparticles, recovering and drying the nanoparticles,
(C) a step of compounding the matrix resin and natural antimicrobial substance-supported nanoparticles followed by injection molding to form an inlet tube
A method for manufacturing an antibacterial tube. 15. The method according to claim 14, further comprising an electron beam irradiation step of 40 to 150 kGy following the step (A). The method according to claim 13, further comprising a pigment mixture of 0.01 to 0.09 phr of a yellow pigment and 0.01 to 0.09 phr of a red pigment in the above step (A).

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