KR20140073696A - Medical products with caffeic acid phenethyl ester and manufacturing method thereof - Google Patents

Abstract

The present invention is a technique for improving antibiotic property and the safety of a biodegradable or non-biodegradable medical product used in surgery, and is a technique for confirming biological safety of a medical product through a test on whether or not the toxicity is expressed in the body, as well as improving antibiotic and anti-inflammatory properties of the medical product, by containing, in the medical product, caffeic acid phenethyl ester (CAPE), which is an active component of propolis.

Description

TECHNICAL FIELD The present invention relates to a medical antibacterial product containing caffeic acid ester which is an active ingredient of propolis which is a natural antibiotic and has excellent biological safety,

The present invention relates to a technology for improving antimicrobial activity and safety of a biodegradable or non-biodegradable medical product used in surgery. The medical product contains caffeic acid phenethyl ester (CAPE), which is an active ingredient of propolis, It is a technology that not only increases the antibacterial and anti-inflammatory properties of medical products, but also confirms the biological safety by confirming the expression of toxicity in the human body through testing.

With the advancement of medicine and the improvement of living standards, the average life expectancy of humans is rapidly increasing. In Korea, the age of 65 or older is over 7% of the total population. It has been 10 years since the UN entered the age of aging. It is expected that the population aged 65 and over will be an aging society with more than 14% of the total population. As the lifespan of human being increases, various bio materials such as artificial joints, bone cement, dental implants and artificial blood vessels are being developed due to loss of body function due to aging or various disasters, and demand is also increasing. Biomaterials and medical devices require high safety because they are the subject of application. Therefore, proper evaluation of the material is important.

The above safety evaluation may vary depending on the composition, design and use of the biomaterial, but generally it should not ① stimulate the body tissue, ② cause no inflammation, ③ not cause allergy, ⑤ no toxicity, ⑥ no blood components should be destroyed or modified, and ⑦ thrombosis should not occur. The biological safety assessment methods currently in use are carried out in accordance with the standard notified by the KFDA according to the 'Common Criteria for Biological Safety Assessment of Medical Devices'. This is the test method described in most of the methods of ISO (International Organization for Standardization) 10993, and it is required to select the appropriate test method in consideration of the contact area, contact time, and characteristics of the medical biomaterial.

Propolis is known to contain about 149 compounds and 22 minerals. The major components are resin 50%, wax 30%, oil components 10%, pollen 5%, organic matter and minerals 5% . Contemporary people are suffering from various diseases such as rhinitis, atopy, sinusitis, cancer, gastrointestinal disease, etc. because of the immunity that keeps our body healthy from the disease due to contaminated environment and food with various harmful substances Many people are trying to use propolis, which is said to be good for immune enhancement. More precisely, we are looking at the efficacy of the Flavonoid ingredient in propolis and using propolis. Antibiotics frequently used by modern humans are only effective against some bacteria. They weaken the naturalness of the human body, which further deteriorates the immune system and causes many side effects and tolerance. But propolis extracted from honeycomb overcomes this limitation of antibiotics and sterilizes almost all bacteria (viruses, bacteria, fungi) directly. It is natural, so it has no resistance, no side effects, and strengthens the immunity of the human body. In addition, more than 18 flavonoids have excellent defense against viral infections, as Flavonoid acts as a barrier against germs, Dr. Benshabustin, of Germany, in May 1980 at the 5th International Propolis Symposium Dr. Bens also announced that this barrier has the same effect as immune status by disabling the action of bacteria and viruses and has reported flavonoids as the most important component of physiological activity of propolis.

The active ingredient of the present invention is a flavonoid-based ingredient known as vitamin P having an antibacterial effect with caffeic acid phenethyl ester (CAPE), and is mainly used in the propolis for antibacterial and anti-inflammatory actions . The molecular formula of CAPE is C ₁₇ H ₁₆ O ₄ and its chemical structure is shown in the following chemical formula 1.

The major functions of the CAPE are as follows: CAPE has antibacterial, antifungal and antiviral effects in the human body. In addition, CAPE inhibits inflammation by blocking the secretion of enzymes that cause inflammation. Particularly, it is water-soluble, so its use range is wide and it is characterized by its non-toxicity even when consumed in excess.

The principle of anti-inflammatory action of CAPE is briefly described as follows. First, the process of inflammation is explained as follows: When the body becomes acidic, the body accumulates in the body, and when the waste accumulates in the body, wastes accumulate around the cells, the cells start to melt by the acidic residue, (LT), and prostaglandine (PG), which cause inflammation such as fever and pain. This would require enzymes such as lipoxygenase and cyclooxygenase to produce the cytotoxic components, LT and PG, which cause inflammation. The effect of CAPE, which is an active ingredient of propolis for such inflammation, is that it inhibits both LT and PG-producing enzymes, lipoxygenase and cyclooxygenase, at the same time.

Propolis is more powerful than analgesic anti-inflammatories because analgesic anti-inflammatory agents only inhibit cyclooxygenase among the two enzymes during inflammatory cytoxin production, while propolis suppresses both enzymes at the same time. Therefore, propolis has a much stronger anti-inflammatory action than the anti-inflammatory agent, and it can be said that it is an excellent anti-inflammatory drug with no side effects. In addition, the CAPE component has the effect of stopping the growth of malignant cells and the anticancer effect of restoring cells damaged by carcinogens.

The inventors of the present invention have developed a medical product and a method for manufacturing the same which have no problem that nanoparticles remain in the living body while having antibacterial and anti-inflammatory properties by applying CAPE, which is an active ingredient in propolis having various functions, 2011-122973, filed on November 24, 2011.

Accordingly, the present invention is based on the above patent, and aims to develop a product which not only has a problem of retaining nanoparticles in a living body while having antimicrobial and anti-inflammatory properties, but also has excellent safety.

It is an object of the present invention to provide a CAPE having an antibacterial and anti-inflammatory effect to a medical product so as to minimize infections that may occur during surgery and to prevent the inflammation that may develop after surgery, Which is one of the most important requirements of such medical products, as well as to provide a medical product and a method for producing the medical product which are confirmed to have biological safety.

To achieve the above object, a medical antimicrobial product containing caffeic acid ester as an active ingredient of propolis, which is a natural antibiotic of the present invention and having excellent biological safety, contains CAPE (caffeic acid phenethyl ester), which is an active ingredient of propolis , And the biological safety was evaluated through testing.

The production method of the present invention is characterized by comprising the step of impregnating a medical product into a solution containing CAPE, which is an active ingredient of propolis, and testing the impregnated medical product to evaluate biological stability .

Here, the solution containing CAPE, which is an active ingredient of the propolis, is characterized in that the solvent is methanol and the concentration is 500 to 3000 ppm.

Here, the test is characterized by being either one or both of the return mutation test and the micronucleus test.

Herein, the medical product is characterized in that it is a disinfectant cotton, a bandage, a cotton gauze, a cotton swab or a suture.

According to the present invention, CAPE, which is an active ingredient of propolis having antibacterial and anti-inflammatory properties, is contained in a medical product and its safety is tested, thereby enhancing the hygiene of the product, , It is possible to confirm the stability problems such as the return mutation and the micronucleus test which may occur upon administration into the human body.

FIG. 1 is a SEM photograph showing changes in time of suture impregnated with CAPE and Pinocembrin solution, which are active ingredients of propolis.
FIG. 2 is a photograph of decomposition of suture containing CAPE, which is an active ingredient of propolis, according to an embodiment of the present invention.
FIG. 3 is a graph showing the UV-Vis of CAPE, an active ingredient of propolis according to an embodiment of the present invention. Analytical spectrum.
FIG. 4 is a graph showing an amount of CAPE, which is an active ingredient of propolis contained in a suture according to an embodiment of the present invention, over time.
FIG. 5 is a graph showing a calibration curve for a CAPE solution as an active ingredient of propolis according to an embodiment of the present invention.
FIG. 6 is a graph showing the CAPE release of sutures containing CAPE, which is an active ingredient of propolis, according to an embodiment of the present invention.
7A and 7B are photographs showing the antibacterial activity of a suture according to an embodiment of the present invention.
Figure 8 is a photograph of a preparation sample for biological safety testing according to one embodiment of the present invention.

The medical product containing CAPE, which is an active ingredient of the propolis according to the present invention and having excellent biological safety, and a method for producing the same will be described in detail below with reference to the accompanying drawings.

The medical product of the present invention is characterized by containing CAPE, which is an active ingredient of propolis, and is characterized in that biological safety is evaluated through testing in particular.

The test may be either a return mutation test or a micronucleus test, and these tests may be performed according to ISO 10993-3 and ISO 10993-5 using an elution solvent after elution according to ISO 10993-12 Proceed with.

Examples of the medical products include a disinfectant cotton, a bandage, a cotton gauze, a cotton swab or a suture.

Here, the suture includes a biodegradable component, a non-absorbable component, or a mixture thereof

And the biodegradable suture may be made of polyglycolic acid (PGA), polylactic acid (PLA), polylactide-co-L-lactide (PLLA), poly (glycolideco-

L-lactide), PG (polyglycolide), PL (polylactide), and mixtures thereof. The non-absorbable component may be selected from the group consisting of polyester, nylon, PAN (polyacrylonitrile) ≪ / RTI > and mixtures thereof. In addition, the suture preferably has a multi filament shape, and the suture may further include a calcium stearate component as a coating agent. By using the coating, . ≪ / RTI >

It is preferable that the disinfectant cotton, bandage, cotton gauze, and cotton swab of the medical product have a multifilament shape, and as the suture, a calcium stearate component may be further included as a coating agent.

CAPE, which is a propolis active ingredient in the present invention, is a kind of flavonoid. In the following examples of the present invention, CAPE, which is an active ingredient of the propolis, is a product of Sigma Aldrich, a chemical company sold in the market.

Meanwhile, the manufacturing method of the present invention includes a step of preparing a medical product, impregnating it with a solution containing CAPE, which is an active ingredient of propolis, and testing the impregnated medical product to evaluate antibacterial and biological stability .

In the step of impregnating a medical product with a solution containing CAPE, which is an active ingredient of propolis, a medical product using a biodegradable suture or a biodegradable yarn has a property of being absorbed and decomposed in vivo. It is preferable to minimize the reaction with water by using methanol having a strong evaporation power as a solvent. If the concentration is less than 500 ppm, the antibacterial property is deteriorated. If the concentration is more than 3000 ppm, the solubility is lowered. At this time, the impregnation time of the medical product is not limited, but it is impregnated for 60 to 820 min, which is most preferably about 360 minutes.

In addition, the bandage and cotton gauze of the medical product may be impregnated after the production of the product, or may be impregnated with the yarn and dried, and then the product may be manufactured as an end product.

The medical product according to the present invention may be purchased and used in the market, and may be manufactured and used in accordance with the manufacturing method of Patent Application No. 10-2009-0121725, Do not.

Hereinafter, embodiments of a medical product manufactured according to the present invention will be described in detail. It should be noted, however, that the scope of the present invention is not limited to the following examples, but the suture is used as a medical product in the present invention.

[Example 1] Preparation of suture [Preparation of PGLA (polyglycolide-co-L-lactide)

The suture was largely completed through four processes. First, the polyglycolide and lactide are melted into a gel state and then mixed with the pigment. In this case, the pigment is injected into a separate melting and mixing tank to be mixed with the gel state, Respectively. Thereafter, the raw materials in the molten state are pressurized through respective pressurizing chambers to alternately open and open the valves provided in the respective pressurizing chambers. The raw material fed from the pressurizing vessel is discharged through the spinneret A spinning process in which the yarn is strongly extruded and a stretching process in which the yarn is stretched by using a stretching device to increase tensile strength and elasticity. This process is based on the preparation method of Application No. 10-2009-0121725 and was prepared according to the method of the earlier application.

[Example 2] Preparation of solution of CAPE, which is an active ingredient of propolis

CAPE solution was prepared and its concentration was made from 100 ppm to 1000 ppm. In order to prevent decomposition of the suture due to moisture when the suture was impregnated in the CAPE solution, Methanol of high degree was used.

[Example 3] Impregnation in a CAPE solution of a composite yarn

First, 1 g of the suture prepared as described above was placed in 30 mL of the 1000 ppm concentration CAPE solution prepared in Example 2, and the suture was impregnated in a unit of 6 hours. The results are shown in Fig. The SEM analysis image of FIG. 1 is a photograph before and after the immersion of the suture, the left is a photograph before immersion, and the right is a photograph after immersion. As can be seen in FIG. 1, it can be seen that there is almost no change in the thickness of the suture due to the suture containing CAPE. Therefore, it was confirmed that even when impregnated with CAPE through the above-described test, inconvenience was not caused in using the suture.

2 shows the degradation behavior of 0.1 g of the PGLA suture in a 0.01 M solution of PBS (phosphate buffered saline monobasic monohydrate: 1.1832 g, Dibasic ACS reagent: 8.1572 g) similar to human body, , And that the degradation of the suture progressed considerably faster as the photographs were taken over a period of two months. The short decomposition period of the suture means that the biodegradation effect is high, so that the secondary infection due to the residual suture is reduced And it was confirmed that there was no influence of CAPE, which is an active ingredient of propolis.

1 g of the suture prepared in Example 1 and 30 mL of the CAPE solution having a concentration of 1000 ppm prepared in Example 2 were added to the vial and incubated at 0, 60, 120, 180, 360, 480, and 600 minutes , 660 min, 720 min, 780 min, 820 min, 1300 min, the suture was taken out and vacuum dried. The remaining solution was UV-Vis at a wavelength of 330 nm, which is the wavelength of CAPE, in order to check the activity of propolis in the suture. Analysis was performed, and the amount of active ingredient of propolis contained in the suture was shown in the graph of FIG. 4 according to the impregnation time.

As can be seen from FIG. 4, it was confirmed that the amount of CAPE contained in the suture was the largest at around 360 minutes, and that the content did not increase any more after 720 minutes. As a result, it was confirmed that the maximum impregnation time was 720 min and the experiment was conducted using 820 min.

On the other hand, the wavelength of the CAFE is determined by UV-Vis. The analytical spectra were obtained using a JASCO V-550 UV-Vis Spectrophotometer (Wavelength Range: 200 to 900 nm, Bandwidth Selectable: 0.5 nm, Scanning Speed: 400 nm / min, Data Pitch: 1 nm) , And the results are shown in Fig. That is, as can be seen from FIG. 3, it was confirmed that the intrinsic wavelength of CAPE was 330 nm.

[Example 4] Measurement of drug release

Tests were conducted to confirm the degree of in vivo drug release of the suture containing CAPE by impregnation for 820 minutes prepared in Example 3 above. 0.01M of PBS (Monobasic monohydrate: 1.1832g, Phosphate Buffer Calculator: Dibasic ACS reagent: 8.1572g) was prepared as the solvent for this release test and the pH was adjusted to 7.4. The standard curve of FIG. 5 was drawn with CAPE, and the test was performed according to the respective concentrations. The calibration curve for the CAPE was obtained by measuring absorbance using a JASCO V-550 UV-Vis Spectrometer (Wavelength Range: 200 to 900 nm; Bandwidth Selectable: 0.5 nm; Scanning Speed: 400 nm / min; Data Pitch:

lost. The calibration curves shown in FIG. 5 are as follows. x is the concentration of CAPE, and y is the absorbance.

                       y = 0.063x + 0.022

1 g of the suture was impregnated in 30 mL of CAPE solution of 1000 ppm of active ingredient of propolis under stirring for 820 min, and then filtered. The filtered suture was dried, and 1 g of the dried suture was added and 5 mL of 0.01 M PBS solution was pipetted. Each sample was added to a shaker and extracted with a pipette every 5 hours for 100 hours, and the time was 6 hours. Then, 5 mL of PBS solution was added and placed in a shaker. At this time, the temperature was adjusted to 36.5 ° C. and the experiment was performed under conditions similar to the temperature in the body.

6 shows the release profile of the suture as a result of which the CAPE contained in the suture was released within a certain period of time in the living body. As a result of checking the release of the drug in the suture for 0 to 100 hours, In almost the same environment, the drug release behavior was completed after about 60 hours. This suggests that the antimicrobial and antimicrobial properties of the suture entering the body can be expected to be maintained for about 2 days to 3 days, thereby reducing the damage caused by the bacteria in the suture during and after the procedure .

[Example 5]

The antibacterial activity of the suture containing CAPE, which is an active ingredient of the propolis of Example 3, was tested. The test method used was a cell growth in a shaker using a Shake flask method and the growth of the strain was measured by UV-Vis. The method was used as a test strain. Escherichia coli (ATCC 25922) DH5α, one of the strains, was used to measure the changes of the published strains after culturing at 37.1 ℃ for 24 hours.

As another test method, the antimicrobial activity was tested using agar diffusion method. Bacteria among the strains required for the test for antimicrobial activity were measured by UV-Vis. By cell growth on LB medium (peptone 10 g) (ATCC 6538), which is a representative strain of Gram-positive bacteria, was used to determine the growth of the isolates after incubation at 37.1 ℃ for 24 hours.

7A and 7B are graphs showing the antibacterial activity of suture containing CAPE. As shown in FIG. 7A, the antibacterial activity is shown even at a concentration much lower than the experimental concentration of 1000 ppm. Thus, even when the suture is impregnated with less than 1000 ppm, Was expected. The number of photographs shown in Fig. 7B is 1 for the control group, 2 to 6 for the samples containing the CAPE, 2: 0.71 mg, 3: 1.42 mg, 4: 2.13 mg, 5: 6: 3.55 mg. 7B shows that the treatment concentration of CAFE is based on the experimental concentration of 1000 ppm. As can be seen in the drawing, since the concentration of 1000 ppm which was intended to be tested in the suture is not completely included, And the inflammatory reaction due to high concentration can be avoided. In addition, when the antibacterial activity of the suture before and after the CAPE treatment were compared with each other, it was confirmed that the antibacterial activity was clearly demonstrated.

[Example 6] Biological safety test preparation step

Prepare samples for biological safety testing.

The sample was prepared by impregnating the suture of Example 1 with the CAFE solution of Example 2, and a sample of about 10 g or more was required for the safety test. The prepared sample was prepared with 0.036 mg CAPE / 8.7 mg Suture with minimum antimicrobial activity. Since CAPE used methanol as a solvent, the amount of CAPE can be confirmed by evaporation of methanol in the drying stage of the sample. Thus, the impregnation was performed in the same manner as in Example 3, followed by vacuum drying, and the content of CAFE was confirmed. As a result, a sample of 0.036 mg CAPE / 8.7 mg Suture was prepared. 8 is a photograph of the prepared sample.

First, elution conditions are calculated. Sample elution was carried out according to ISO 10993-12 "Sample preparation and reference materials" at the rate of 4 g / 20 ml for the mutation test and the micronucleus test at 37 ° C for 72 hours.

[Example 7] Biosafety test - return mutation test (AMES test)

In Example 7, the suture prepared in Example 6 was used.

Test methods are the Genotoxicity term for ISO 10993-3: 2003 Tests for genotoxicity, carcinogenicity and reproductive toxicity, and the OECD Guideline for testing of selected-chemicals (471).

To prepare the sample, polar (sterile saline, saline) and non-polar solvent (CSO) were added to the test material at a ratio of 4 g / 20 ml and the mixture was eluted at 37 ° C for 72 hours. Strain - Salmonella typhimurium TA98, TA100, TA1535, TA1537, tryptophan strains - Escherichia coli WP2uvrA were used. Sterile saline was used for solvent control and test (50 μl / plate) and nonpolar solvent was used for solvent control and elution stock (50 μl / plate).

The incubation time was 10 hours (the incubation was stopped at the early stage of the stopper). The shaking type used was a revolution number of 180 times / minute, a turning diameter of 2.54 cm, an Erlenmeyer flask volume of 50 ml, a culture volume of 15 ml and an inoculum amount of 30 μl.

This test was carried out according to ISO10993-3, Tests for genotoxicity, carcinogenicity and reproductive toxicity, and the method using the metabolic activation system as the preincubation method and the method using the metabolic activation system were performed in parallel.

The results of this test on strains TA100, TA1535, WP2uvrA, TA98 and TA1537 treated with the suture of the suture are shown in Table 1 (polar solvent) and Table 2 (non-polar solvent).

As can be seen in the above Tables 1 and 2, no increase in the number of returning colonies which can be judged positive in the test substance treatment group was observed regardless of whether or not the TA100, TA1535, WP2uvrA, TA98 and TA1537 metabolic active systems were applied . As a result of treatment with the test substance in this test, P.C. (pinpoint colony) due to cytotoxicity was observed in the TA98, TA100, TA1535 and TA1537 strains in the non-polar solvent (DMSO) direct method (-S9 mix) test group. In the case of the polar solvent and the non-polar solvent (DMSO) test group except for the above strains, the return colonies were judged to be positive compared with the cytotoxic and negative control groups regardless of whether the metabolic activation method (S9 mix) was applied or not There was no increase in the number of people. Based on the above results, it was judged that the test substance did not induce a return mutation in the five strains under the present test conditions.

[Example 8] Biological safety test - In vivo micronucleus test [

The test method was based on the Genotoxicity test item of ISO 10993-3: 2003 (E) Tests for genotoxicity, carcinogenicity and reproductive toxicity, and the OECD Guideline for testing of chemicals-selected assays (474).

The number of administrations and the duration of administration were limited to one per day. The dosage and the composition of the test group were as follows. In the test, the administration method was forced oral administration.

(1) Saline leaching test

The test group was tested with five mice per group for three groups consisting of the solvent control group 1, the administration group 1 (the eluting solution administration group) and the positive control group 1 (mitomycin C (MMC) 2.0 mg / kg) Respectively.

(2) CSO dissolution test

The test group was tested with five mice per group for three groups consisting of the solvent control group 1, the administration group 1 (the eluting solution administration group) and the positive control group 1 (mitomycin C (MMC) 2.0 mg / kg) Respectively.

The dissolution test method was observed by optical microscope at a magnification of 400 times or more by blind method through (1) saline leaching test and (2) CSO leaching test by collecting bone marrow cells, preparing samples and staining specimens, The micronuclei in red blood cells were observed with a fluorescence microscope equipped with a FITC filter.

In order to observe the proliferation of bone marrow cells, approximately 200 polychromatic erythrocytes (PCE) and necrotic erythrocytes (NCE) were observed, (PCE + NCE) were measured. To observe the frequency of micronuclei, cells with micronuclei were counted in about 2,000 polyglut erythrocytes. In Giemsa - stained specimens, erythrocytes, which showed pale blue light without nucleus, were multicolored erythrocytes. In the acridine - stained specimen, multicolored erythrocytes were observed in which the red fluorescence light was not observed in the observation field. In Giemsa-stained specimens, erythrocytes with pale red or pink color without nucleus were used as positive erythrocytes. In acridine-stained specimens, positive erythrocytes were classified as only shaded without fluorescent light. The criterion for micronuclei is the one with the largest diameter of red blood cells, the smallest one that can be identified, and the same as the nucleus of surrounding nucleated cells, with green fluorescent light, mainly circular or other donut type, semicircular And so on. The results are shown in Tables 3 to 6 below.

In addition, the general symptoms were observed on the day of administration and once each observation on the animals to which the test substance was administered, and the occurrence of the used animals and abnormality indications were observed. In the case of body weight measurement, . The results are shown in Tables 7 and 8 below.

As shown in Table 3, the frequency of induction of MNPCE observed in about 2,000 PCE per individual in the saline-eluting group was significantly higher than that in the negative control group (Saline), test substance administration group (eluate, 10 ml / kg) And positive control group in the order of 0.12, 0.10 and 7.48, respectively. In other words, the frequency of erythrocytes with micronucleus in polychromatic erythrocytes was not significantly different from that of solvent control group in each group to which test substance eluted with polar solvent (Saline) was administered. The incidence of micronuclei in the positive control group, Mitomycin C, was statistically significant (P <0.01) compared to the negative control group.

As shown in Table 4, the percentage of polychromatic erythrocytes (PCE) observed in about 200 total red blood cells (PCE + NCE) per individual, which is an indicator of cytotoxicity, was significantly higher in the negative control group (Saline) In the order of 0.43, 0.41 and 0.42, no cytotoxicity was observed.

As shown in Table 5, the incidence frequency of MNPCE observed in about 2,000 PCE per individual in the group administered with the non-polar solvent (CSO) eluent was significantly higher than that in the negative control group (CSO), the test substance administration group (elution stock solution, 10 ml / kg) 0.10, 0.10 and 7.48, respectively. In other words, in each group administered test substance eluted with non-polar solvent (CSO), the frequency of the presence of micronucleated erythrocytes among the polychromatic erythrocytes did not show a statistically significant difference in the test substance administration group compared to the solvent control group. The incidence of micronuclei in the positive control group, Mitomycin C, was statistically significant (P <0.01) compared to the negative control group.

As shown in Table 6 above, the ratio of polychromatic erythrocytes (PCE) observed in about 200 total red blood cells (PCE + NCE) per individual, which is an index of cytotoxicity, was determined by using the negative control (CSO), the test substance administration group and the positive control group The mean cytotoxicity was 0.42, 0.41 and 0.42, respectively.

And no general symptoms were observed in the test substance administration group as compared with the solvent control group in both the polar solvent eluent administration group and the nonpolar solvent eluent administration group. In addition, no statistically significant change in body weight was observed after the administration of the polar solvent eluent and the non-polar solvent eluent as shown in Tables 7 and 8.

Taken together, these results suggest that the test substance does not affect the micronucleus formation of mouse bone marrow cells under the conditions of this test.

As described above, the medical product of the present invention contains CAPE, which is an active ingredient of propolis having antibacterial and anti-inflammatory properties, to thereby impart antibacterial and anti-inflammatory functions to medical products, thereby preventing pathogenic infections caused by medical products As well as being able to evaluate the biological safety of the human body can be used safely.

The present invention is not limited to the above-described specific embodiments and descriptions, and various modifications can be made to those skilled in the art without departing from the gist of the present invention claimed in the claims. And such modifications are within the scope of protection of the present invention.

Claims (7)

A medical antibacterial product characterized by containing a caffeic acid phenethyl ester (CAPE), which is an active ingredient of propolis, and evaluating biological safety through testing. The method according to claim 1,
Wherein the test is either a return mutation test or a micronucleus test or both. 3. The method according to claim 1 or 2,
Wherein said medical product is a disinfectant cotton, bandage, cotton gauze, cotton swab or suture. Impregnating the medical product with a solution containing CAPE, which is an active ingredient of propolis,
And testing the impregnated medical product to assess biological stability. &Lt; Desc / Clms Page number 20 &gt; 5. The method of claim 4,
Wherein the solution containing CAPE, which is an active ingredient of the propolis, is methanol and the concentration is 500 to 3000 ppm. 5. The method of claim 4,
Wherein the test is one or both of a return mutation test and a micronucleus test. 7. The method according to any one of claims 4 to 6,
Wherein the medical article is a disinfectant cotton, a bandage, a cotton gauze, a cotton swab or a suture.

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