WO2019225948A1 - Patch for alleviation and prevention of acne - Google Patents

Abstract

The present invention relates to a patch for alleviation and prevention of acne in which anti-acne bacteria activity is identified for a biodegradable metal represented by Mg_aZn_bX_c (wherein, a, b, and c are the weight percent of each component, a + b + c = 100 weight percent, a or b is the largest among 0 ≤ a ≤ 100, 0 ≤ b ≤ 100, and 0 ≤ c ≤ 10, and X is at least one selected from the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce, and P), and a new use as a patch for alleviation and prevention of acne is proposed.

Description

Acne Relief and Prevention Patch

The present invention relates to a patch for alleviating and preventing acne, and more particularly, to a new use of a biodegradable metal containing magnesium as a main component.

Many researches have been actively conducted since the microneedles were proposed in 1998 by the Frausnits Group of Georgia Institute of Technology to make microneedle arrays of silicon devices using semiconductor process technology. When the microneedles are inserted into the skin, the microneedles must maintain a sufficiently high physical strength so that the microneedles can be inserted without being bent or broken. In order to satisfy these characteristics, stainless steel was used as the material of the microneedle, but inflammation occurred when small particles remained in the body, and polymers (PLA, PGA, and biodegradable copolymer) were used. There was a problem of not being penetration.

Korean Unexamined Patent Publication No. 2016-0058261 is a water-soluble microorganism based on polyglycolide (PGA), polylactide-glycolide copolymer (PLGA), hyaluronic acid, alginic acid, pectin and the like. A needle and a manufacturing method thereof are disclosed, and Korean Patent No. 1622388 discloses a silicon micro needle stamp and a manufacturing method thereof, and Korean Patent Publication No. 2015-0121053 discloses a silicon, silicon dioxide, ceramic, metal (stainless steel, titanium, Nickel, molybdenum, chromium, cobalt and the like) and synthetic or natural resins have been disclosed for microneedle coated with Japanese encephalitis vaccine antigen.

As described above, the microneedle up to now is an alternative drug administration means that can replace the drug delivery method through oral administration or injection method, and penetrates the epidermis without stimulating pain sensory nerves distributed in the skin. It has been used as a device capable of delivering drugs, a kind of drug carrier.

Meanwhile, Korean Patent Application Publication No. 2017-0115449, previously filed by the present applicant, discloses a microneedle using a biodegradable metal and a patch including the same. It has been confirmed that the effect is also expressed in wrinkle improvement.

The present invention seeks to provide a novel use of biodegradable metals, which are the main component of microneedles that have been developed as conventional drug delivery means.

The present invention is confirmed that the biodegradable metal itself, which was used as a main component of the microneedle, expresses antimicrobial activity against acne causing bacteria, and does not include a separate drug. We want to provide a new use.

The present invention is a biodegradable metal represented by the formula (1), and has an anti acne bacterium effect, provides a patch for acne relief and prevention.

[Formula 1]

Mg _a Zn _b X _c

In Formula 1, a, b, and c are weight percents of each component, and a + b + c = 100 wt%, where a or b is in a range of 0 ≦ a ≦ 100, 0 ≦ b ≦ 100, and 0 ≦ c ≦ 10. X is the one or more selected from the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce and P.

In such acne relief and prevention patches, the biodegradable metal may be included in the form of microneedles or in the form of a thin plate.

In the patch for acne relief and prevention according to an embodiment of the present invention, the biodegradable metal is a, b and c in the formula (1) as the weight percent of each component, a + b + c = 100 weight percent, i) 90≤a≤100, 0≤b≤10, 0≤c≤10 or ii) 0≤a≤10, 90≤b≤100, 0≤c≤10, and X is Ca, Fe, Mn, Si , Na, Zr, Ce and P may be one or more selected from the group consisting of.

In the patch for preventing and preventing acne according to the most preferred embodiment, the biodegradable metal may be Mg of 95% or more pure purity including inevitable impurities.

In the patch for acne alleviation and prevention according to an embodiment of the present invention, the biodegradable metal may be one or more metal phases to generate a galvanic circuit to accelerate the decomposition rate. Such biodegradable metal may be one comprising an Mg ₂ Ca phase, one comprising an MgZn phase, or one comprising a Ca ₂ Mg ₆ Zn ₃ phase.

In the patch for acne alleviation and prevention according to an embodiment of the present invention, the biodegradable metal may be coated with a second kind of second metal on the metal surface to form a galvanic circuit. At this time, the second metal is selected from the group consisting of sodium, magnesium, potassium, iron, nickel, zinc, gallium, selenium, strontium, zirconium, molybdenum, niobium, tantalum, titanium, silicon, silver, gold, manganese and calcium It may be one or more metals.

Another embodiment of the present invention provides a method for attaching and using the aforementioned acne relief and prevention patch on acne skin.

In a method according to a more preferred embodiment, the water supply step or the skin soothing step may be performed before the acne relief and prevention patch is attached to the acne skin.

The patch to which the biodegradable metal of the present invention is applied is useful for alleviating and preventing acne by having antimicrobial activity against acne causing bacteria on its own, without the need for a separate drug, and by using a simple method of applying it to the skin by making it in various forms. You can prevent acne or relieve the acne caused.

1 is an exploded view of microneedles in which microneedles are processed into sheets composed of biodegradable metals.

2 is a schematic view of a microneedle bent over the processed microneedles.

3 is a schematic view of a microneedle and microneedle holder in the form of a tip.

4 is a prototype (A) of the microneedle of the present invention and a photograph (B) showing its bending characteristics.

5 is a photograph of the microneedle patch of the present invention (A: before use, B: after use).

Figure 6 is a photograph of the specimen of the present invention microneedle provided in the antimicrobial test.

7 to 9 are antimicrobial to antifungal test result photographs, FIG. 7 is a test result for Propionibacterium acnes ATCC 6919, FIG. 8 is a test result for Staphylococcus epidermidis ATCC 12228, and FIG. 9 is a test for Trichophyton rubrum ATCC 28188. The result is.

10-11 are schematic diagrams illustrating various shapes of the microneedle patch of the present invention.

12 is a photograph showing the results of sensory evaluation by applying the microneedle patch of the present invention, showing the skin condition (right side) before attachment (left), attachment state (center), and 8 hours after attachment.

Figure 13 is a photograph showing an example attached to the test subject in the clinical trial applying the microneedle patch of the present invention.

FIG. 14 is an image showing a test site divided into six sections of a face area in an evaluation through a global acne grading system (GAGS) in a clinical trial. FIG.

FIG. 15 is a table showing intrinsic factors and global scores of each section shown in FIG. 14 in the evaluation through the acne severity system (GAGS) in clinical trials.

FIG. 16 is a table of classification and status of adverse reactions in skin irritation evaluation in clinical trials.

17 is a photograph showing the results of the photographing with the progress of the test period by attaching a magnesium microneedle patch to a test subject in a clinical trial.

Acne is a chronic inflammatory disease of the sebaceous gland of the hair sebaceous gland, and various skin changes such as cotton (Comedone, hardened sebum in hair follicles), papules (rising skin lesions less than 1 cm in size), pus blisters, nodules, and false cysts This may result in concave scars or enlarged scars. It occurs in the face, neck, chest, etc. where sebaceous glands are gathered, and inflammation of the sebaceous glands attached to hair follicles that make hair.

The exact cause of acne is not known, but several causes work in combination, rather than one cause.The excess of male hormone during puberty stimulates the secretion of sebaceous glands, and the epithelium of hair follicles is dyskerosis (incomplete and immature keratinization). Abnormal keratinization) can cause hair follicles to be blocked, forming the scleroderma, the primary lesion of acne.

Among these bacteria, acne rash is known to be caused by propionibacterium acnes among the bacteria that reside in the hair follicles. This acne-causing bacterium is the main cause of trouble when eating and growing sebum.In normal people, even if the bacteria are present on the skin, they do not cause any problems.However, since the hair follicles become clogged and sebum accumulates in the hair follicles, it grows quickly.

The acne-causing bacteria also eat fat (triglycerides) and then excrete butter-like substances, or fatty acids. This chemical change causes healthy weak acidic skin to alkalinize as the pH balance of oil breaks down, which in turn degrades the skin's own function and causes a vicious cycle of the skin. In order to prevent and alleviate the acne caused by Propionibacterium acne, it is a matter of course that a treatment method of a commonly used medicine or a medicine has been proposed.

On the other hand, the applicant has developed a microneedle using a biodegradable metal and has already applied for this (Korea Patent Publication No. 2017-0115449).

The present invention was obtained as a result of continuous research on the microneedle developed as described above, and it was found that the biodegradable metal expresses antimicrobial activity against Propionibacterium acnes , an acne causing bacterium. By doing so, new applications of such biodegradable metals have been devised.

In the present invention, a substrate related to a biocompatible metal, a substrate related to a method of manufacturing the same in the form of a microneedle, and a related substrate related to a series of metallic reactions occurring in the skin are according to the contents described in Korean Patent Application Publication No. 2017-0115449. Of course.

However, in the present invention, the biodegradable metal is not limited to the microneedles proposed as drug carriers, but it is clarified that the biodegradable metal acts alone as a functional composition having antibacterial activity against acne causing bacteria.

In the present invention, a biodegradable metal made of magnesium or zinc alone and a biodegradable metal mixed with other metals such as calcium in the form of a thin plate or a microneedle are prepared and their antibacterial activity against acne-causing bacteria Was evaluated. As a result, it was confirmed that the biodegradable metal prepared by using magnesium, calcium, or zinc as a single material, or an alloy in which the metal is mixed in a specific range, has its own antimicrobial activity without additional drug encapsulation.

Accordingly, the present invention provides a patch for acne alleviation and prevention, which is, in one aspect, a biodegradable metal represented by Formula 1 and having an antiacne bactericidal effect.

[Formula 1]

Mg _a Zn _b X _c

In Formula 1, a, b, and c are weight percents of each component, and a + b + c = 100 wt%, where a or b is in a range of 0 ≦ a ≦ 100, 0 ≦ b ≦ 100, and 0 ≦ c ≦ 10. X is the one or more selected from the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce and P.

The biodegradable metal preferably contains the most magnesium or zinc. Accordingly, in Formula 1, a, b and c are weight percent of each component, and a + b + c = 100 wt%, i) 90 ≦ a ≦ 100, 0 ≦ b ≦ 10, 0 ≦ c ≦ 10 or ii) 0≤a≤10, 90≤b≤100, 0≤c≤10, and X is preferably at least one selected from the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce and P. Can be.

The biodegradable metal according to the present invention is a metal having the property of being attached or inserted into the subcutaneous or epithelium, and absorbed and decomposed to release metal ions and decomposition products in the body, and includes magnesium (Mg), calcium (Ca), and zinc ( Zn) and the like is an alkaline earth-based biodegradable metal, and has a mechanism for releasing hydrogen gas by reacting with water, as shown in Schemes 1 to 3 below.

Scheme 1

Mg + 2H ₂ O → Mg (OH) ₂ + H ₂ (gas)

Scheme 2

Ca + 2H ₂ O → Ca (OH) ₂ + H ₂ (gas)

Scheme 3

Zn + 2H ₂ O → Zn (OH) ₂ + H ₂ (gas)

In the present invention, the biodegradable metal may be preferably made of magnesium (Mg), zinc (Zn), or the like as a single material, and particularly in terms of excellent biocompatibility and no toxicity in normal cells or tissues. Most preferably, it may be a biodegradable metal that is magnesium alone. Herein, the term magnesium single material or zinc single material means pure magnesium or zinc with a purity of 95% or more, in addition to including unavoidable impurities generated during metal production.

On the other hand, biodegradable metals can be made from two or more metals as a material in order to accelerate the rate of degradation in the subcutaneous or epithelium, ie to produce a galvanic circuit. In the present invention, the biodegradable metal may be coated with another type of second metal on the surface of the biodegradable metal represented by Formula 1 to produce a galvanic circuit. In this case, the second metal may include sodium, magnesium, potassium, iron, nickel, zinc, gallium, selenium, strontium, zirconium, molybdenum, niobium, tantalum, titanium, silicon, silver, gold, manganese, calcium, and the like. It is not limited. In this case, in the case of containing the iron (Fe), in particular, it should not contain cron or nickel.

In the patch for acne alleviation and prevention of the present invention, the biodegradable metal may be included in the form of a thin plate or a microneedle. For example, the microneedle may be a conventional soluble microneedle in the industry such as laser cutting, sheet metal processing, casting method, and etching method. It can be prepared by a method for producing, the manufacturing method is not particularly limited. For example, after manufacturing the thin sheet 10 made of a biodegradable metal as shown in Figure 1 and then molded in a certain shape using a laser cutting machine (marking machine), the microneedle can be manufactured by bending in a jig press.

In the present invention, a patch containing such a biodegradable metal can be used for the purpose of acne relief and prevention by itself, without a separate drug coating or supporting.

2 is a schematic diagram of the microneedles 11 bent to process the microneedles into the skin.

The microneedle according to the present invention may be formed in one piece or may be composed of the microneedle 20 and the microneedle holder 21 as shown in FIG. 3. The microneedle utilizing the form of the microneedle holder 21 may be twisted after the needle is inserted to artificially allow the needle to remain subcutaneously.

Figure 4 is a prototype photograph (A) of the microneedle manufactured according to an embodiment of the present invention and a photograph (B) showing its bending characteristics.

According to the present invention, such a microneedle can be manufactured in a patch form in terms of facilitating application to the skin.

As shown in FIG. 5, the microneedle patch is for fixing the microneedle to the skin, and is composed of a microneedle and a patch portion formed on an opposite side of the microneedle. The size, shape and material of the patch can be used without particular limitation. As shown in FIG. 5B, the microneedles used may be ionized and discolored subcutaneously.

When the patch containing the biodegradable metal of the present invention is applied to the skin, it exhibits an anti-acne effect by itself without the inclusion or application of other drugs, but in the sense of doubling the effect or shortening the time of effect expression, It may be desirable to involve a hydration step or skin soothing step prior to applying the patch of the invention. Here, the moisture supply step may be performed through the application of various moisturizing cosmetics, for example, toner or moisture supply mist, the skin soothing step is to apply a functional cosmetics or medicines known to calm skin redness or acne The method may be performed by, but is not limited to.

This water supply step or skin soothing step simply serves to assist the anti-acne effect of the patch containing the biodegradable metal of the present invention, and the effect of the patch of the present invention is not realized only when the step is preceded. .

The present invention has been developed a new use of the biodegradable metal applied in the form of microneedles for acne alleviation and prevention, the use is present in the skin using the above-described biodegradable metal as a specimen through the embodiments described below The purpose of this study is to evaluate the activity of various bacteria, and to identify that it is only active against acne-causing bacteria.

Hereinafter, the present invention will be described in detail with reference to Examples, of course, the present invention is not limited to these Examples.

<Example 1>

In order to evaluate the anti-acne bacterium activity against the biodegradable metal of the present invention, a sample was provided to the Korea Institute of Chemical Convergence Testing and the antimicrobial and antifungal test was performed in the following manner.

At this time, the sample provided is a sheet made of pure Mg (magnesium of 95% or more purity) containing inevitable impurities generated during manufacture (thickness of 100 μm), and cut to a predetermined standard as shown in FIG. Used as

<Test equipment and materials>

(1) test device

Autoclave (COATEC, South Korea)

Dry oven (Jisico, south korea)

Water bath (Polyscience, USA)

Incubator (Memmert, Germany)

pH meter (Thermo Orion, USA)

Stop watch (Time Art, Japan)

Vortex mixer (Thermolyne, USA)

Container (Iwaki Pyrex, Japan)

Sterile pipette (Falcon, USA)

Petri dish (SPL, South Korea)

Volumetric flask (Myung Sung, South Korea)

Mechanical shaker (Jisico, south korea)

Clean bench (Suyang, South Korea)

Colony counter (Dukwoo Science, South Korea)

Anaerobic container (DIFCO, USA)

(2) test material

1) Test strain

Received from Korea Microbial Conservation Center

Propionibacterium acnes ATCC 6919

Staphylococcus epidermidis ATCC 12228

Trichophyton rubrum ATCC 28188

2) Medium and Reagent

Reinforced clostridial medium broth (DIFCO, USA)

Brain heart infusion broth (DIFCO, USA)

Sabouraud dextrose broth (DIFCO, USA)

Reinforced clostridial medium agar (DIFCO, USA)

Tryptic soy agar (DIFCO, USA)

Sabouraud dextrose agar (DIFCO, USA)

GaspakTM EZ (DIFCO, USA)

0.05% polysorbate 80 solution

-Sterile liquid paraffin

(3) Test method

1) Test method

a. Preculture and Preparation of Test Bacteria

P. acnes were inoculated in Reinforced clostridial medium (RCM) broth and incubated at 35 ± 1 ° C for 3 days. The cultured bacterial solution was inoculated in fresh RCM broth and incubated under the same conditions as above, and this process was repeated one more time. All cultures of the strain were maintained in anaerobic conditions using sterile liquid paraffin. Then used as test bacteria.

S. epidermidis was inoculated into Brain heart infusion broth and cultured at (35 ± 1) ° C for 18 to 24 hours before being used as test bacteria.

T. rubrum was inoculated in Sabouraud dextrose agar (25 ± 1) and incubated for 14 days at ℃. 0.05% polysorbate 80 solution was dispensed on the solid medium in which the test bacteria were grown, and spores were removed using a spreader, followed by gauze to remove mycelia. Spore solution prepared in this way was adjusted to (1 ~ 9) ㅧ 10 ⁷ CFU / mL was used as the test bacteria.

b. Test procedure

Each fungal culture was evenly inoculated with a sterile swab on a prepared Reinforced clostridial medium (RCM) agar, Tryptic soy agar, and Sabouraud dextrose agar, and a prepared sample (20 mm × 20 mm) was placed in the center of the medium. After that, P. acnes was incubated for 5 days at anaerobic condition (35 ± 1) ℃, S. epidermidis at (35 ± 1) ℃ (24 ± 2) hours, T. rubrum at (25 ± 1) ℃ Incubated for 7 days. Thereafter, the test was carried out by measuring the zone of inhibition around the sample.

2) read result

The width (W) of the growth stop was calculated according to the following Equation 1.

<Equation 1>

W =-(T-D) / 2

W: width of lowland (mm)

T: total diameter of sample and low zone (mm)

D: diameter of sample (mm)

Test strain	T	D	W
P. acnes	32	20	6.0
S. epidermidis	20	20	0.0
T. rubrum	20	20	0.0

As summarized in Table 1, as a result of the antimicrobial effect on P. acnes , the total diameter (T) of the sample and the low zone was 32 mm, the diameter (D) of the sample was observed to 20mm. Therefore, according to the above formula, the width W of the low zone was confirmed to be 6.0 mm (see FIG. 7).

As a result of antimicrobial effect on S. epidermidis , the total diameter (T) of the sample and lowland was 20 mm and the diameter (D) of the sample was 20 mm. Therefore, according to the above formula, the width W of the low land was confirmed to be 0.0 mm (see FIG. 8).

As a result of antifungal effect on T. rubrum , the total diameter (T) of the sample and lowland was 20 mm and the diameter (D) of the sample was 20 mm. Therefore, according to the above formula, the width W of the low zone was confirmed to be 0.0 mm (see Fig. 9).

Under this test condition, the lowlands of P. acnes , S. epidermidis and T.rubrum for the samples (named Mg Micro Carrier Multi Care) were 6.0 mm, 0.0 mm and 0.0 mm, respectively.

As a result, the biodegradable metal of the present invention has antimicrobial activity only against acne causing bacteria, the rest of the antibacterial to antifungal effect was not observed.

Example 2 Fabrication of Micro Needle and Patch

After producing the same biodegradable metal sheet as the sheet provided in the evaluation of the antimicrobial activity of Example 1, a microneedle was manufactured using a laser marker (JTY FIBER MA20, JT Y System). At this time, the tip angles of the microneedles were 15 °, 30 °, and 35 °, and the needle heights were 0.5 mm, 1.0 mm, and 1.5 mm.

The microneedle patch was prepared by attaching a hydrocolloid patch coated with an adhesive to the opposite side where the needle of the microneedle was produced. The prepared microneedle patch was packaged and sterilized.

Such a microneedle patch may be manufactured in various shapes in terms of acne relief and prevention, and examples thereof may include shapes such as those illustrated in FIGS. 10 to 11.

The microneedle patch obtained was 7 male 15-year-old students with acne skin, and the patch was applied to one of the acne areas of the face after cleansing.

The evaluation criteria are 5 points for the acne treatment effect is significant, that is, the acne skin area is clearly reduced and the acne inflammation is clearly reduced. Rather, acne was worsened and evaluated as one point, and then a comprehensive judgment was made as a total score, and the results are shown in Table 2 below.

	Subject 1	Subject 2	Subject 3	Subject 4	Subject 5	Subject 6	Subject 7	Total score
Invention microneedle patch	5	5	5	4	4	5	4	32

As can be seen in Table 2 above, the evaluation results of the majority of the subjects showed five points, which can be seen to have a substantial effect on acne relief.

On the other hand, Figure 12 is a photograph showing the skin condition (left), the state of attachment (center), and the skin state (right) after 8 hours after attachment of the microneedle patch of a subject having forehead acne, from which the micro of the present invention Immediately after applying the needle patch, you'll see an immediate acne relief.

Example 3 Clinical Trials

In order to evaluate the acne skin compatibility of the biodegradable metal of the present invention was commissioned to the Chungcheongbuk-do Cosmetic Clinical Research Support Center was carried out clinical evaluation in the following way.

(1) Test method

The study was performed on male and female adults aged 18 to 40 years. The test product was used once a day at the test site according to the prescribed method of use, and the effect was evaluated through visual evaluation. The evaluation was carried out in accordance with the Center's Internal Guidelines (SOP), and matters not specified in the Ministry of Food and Drug Safety Notice were referred to the references. The test site was carried out on the face area of the test subject.

The prescribed method of use is as follows.

① After cleansing, prepare the skin.

② Remove the stopper of the syringe containing high concentration Centella ampoule (moisture supply or sedation effect).

③ Drop a high concentration of Centella ampoule on the microcarrier of magnesium patch (made of 95% or more of magnesium).

④ Remove the protective film from touching the magnesium patch.

⑤ Before going to bed, close the patch to the place where care is needed and press it several times to feel the irritation.

⑥ Remove the patch the next morning.

⑦ Attach the hydrocolloid band to the spot where you removed the patch.

An example of applying a magnesium patch to a tester is shown in FIG. 13.

The test subjects met the selection criteria, and 20 persons were selected and tested without the exclusion criteria.

After selecting the test subjects suitable for the study according to the selection and exclusion criteria, confirming the skin condition of the test subjects, and performing visual evaluation and photographing (VISIA-CR) before using the product (0 days) and 1 day of using the product, respectively. Then, 3 days after product use, 4 days after product use, and 5 days after product use.

(2) measuring and evaluation method

1) Preparation Step

For evaluation, the test subjects were allowed to settle for 30 minutes in the waiting room under constant temperature and humidity (22 ± 2 ℃, RH40 ~ 60%) to adapt the skin surface temperature and humidity to the environment of the measurement space. For the purpose of objective measurement, the device was evaluated by one investigator and the same area was measured by each researcher.

2) Take a picture

Photographs were taken with full face photographs using facial cameras (VISIA-CR, Canfield, USA) equipped with cameras (Canon, EOS6D, JAPAN), and the standard 2 measurement mode was used. Facial cameras (VISIA-CR, Canfield) fix the forehead and the chin to minimize the subject's movement, and the gray card is photographed together to see the change of light when shooting. Measurements were made before product use (day 0), after product use 1 day, after product use 3 days, and after product use 5 days. The overlay function was used to capture the same area, and only images were used in this study.

3) Visual evaluation

Visual evaluation was performed by two experts on a double-blind test.

In the case of differences between the two experts, a low level of suitability and a high level of skin adverse reactions were evaluated.

Visual evaluation was performed using the Global Acne Grading System (GAGS). GAGS analyzed the facial, chest and back areas into six sections according to the surface area distribution and density of the pilosebaceous units, and assigned a unique factor to each section. Was given to the global score and evaluated by rating. The six sections are as shown in FIG.

In addition, the unique factor and the global score of each section are as shown in FIG.

4) Survey Evaluation

In the questionnaire, each subject was surveyed for the general evaluation (feeling) of the test product, evaluation of change after use, satisfaction with the product, and adverse reactions.

a. Global Assessment of Efficacy

The evaluation of the questionnaire by the test subjects answered the questionnaire directly in five stages (5), satisfaction (4), moderate (3), dissatisfaction (2), and very dissatisfaction (1) for the measured items after using the test product. To do so. The investigator determined the efficacy of the test product by obtaining a percentage of the number of subjects for each response.

b. Product symbol road survey

The subjects were asked to answer the questionnaire about the test product and the feeling of use after use. The evaluation items were evaluated in five stages: general satisfaction (feeling of use) and satisfaction with the product.

5) Compliance assessment

From the start date of use of the product to the end of the use, the compliance log was written to indicate whether the product was applied or not.

6) Skin irritation evaluation

Erythema, Edema, Scaling, Itching, Stinging, Burning, Tightness, Prickling or other abnormalities of the test product The presence or absence of a reaction was closely monitored and graded according to the severity of skin adverse reactions, and test findings were prepared. If you are no longer able to participate in the test, even if it is not on the day you visited, you must write a "Sign-up Agreement" with your signature.

Adverse reaction status and classification table is shown in FIG.

(3) Result Analysis

1) Visual evaluation

The visual evaluation result was conducted by comparing the difference before and after using the product, and the evaluation method was evaluated using the method described in item 3) of the above (2).

2) statistical analysis

For the evaluation results, the paired t-test method was used for changes before and after the use of the product, and the statistical results were statistically significant when the significant difference of 5% (p <0.05) used in the biological statistical analysis. Considered.

3) Survey evaluation

The survey results and product preferences were also evaluated based on the survey results.

4) SPSS version 10.0 software was used for statistical analysis program.

(4) results

The subjects who participated in this study were selected from 20 healthy adult male and female subjects with an average age of 21.9 ± 2.9. The 20 subjects completed the final test without dropping out.

1) Visual Evaluation

As a result of visual evaluation, it was confirmed that the grade of global score decreased from moderate to mild in some test subjects, and the grade of global test score was mild.

On the other hand, the test product showed statistically significant difference after 1 day of test product use, 3 days after product use, and 5 days after product use compared to before product use (day 0).

No adverse events occurred due to the test product during the evaluation period, and the analysis results are shown in Table 3 below.

Measuring point	Before using the product (0 days)	After 1 day of product use	After 3 days of product use	5 days after product use
Grade	Mild	Mild	Mild	Mild
Visual evaluation (mean ± standard deviation, unit: score)	17.7 ± 3.3	16.3 ± 4.0	15.9 ± 3.6	15.4 ± 4.2
p -value	-	0.005 ( p <0.05)	0.012 ( p <0.05)	0.003 ( p <0.05)

2) Survey Results

a. Effectiveness Survey Results

The results of the survey conducted on the measured items after using the test product are shown in Table 4 below.

	Number of test subjects (%)					Average	Standard Deviation
	* 5	*4	* 3	*2	*One
Acne improvement	6 (30.0)	14 (70.0)	0 (0.0)	0 (0.0)	0 (0.0)	4.3	0.5

* 5: very satisfied, 4: satisfied, 3: moderate, 2: dissatisfied, 1: very dissatisfied

As a result of the questionnaire evaluation, 100% of the test subjects rated the acne improvement effect items as more than satisfied.

b. Favorability Survey Results

After using the product, the satisfaction level of the product, the feeling of use, and the degree of change after the use were examined. The results of the survey are shown in Table 5 below.

	Number of test subjects (%)					Average	Standard Deviation
	* 5	*4	* 3	*2	*One
Product color	12 (60.0)	7 (35.0)	1 (5.0)	0 (0.0)	0 (0.0)	4.6	0.6
Product viscosity	12 (60.0)	7 (35.0)	1 (5.0)	0 (0.0)	0 (0.0)	4.6	0.6
Stimulation degree	6 (30.0)	9 (45.0)	5 (25.0)	0 (0.0)	0 (0.0)	4.1	0.8
Skin absorption degree	6 (30.0)	8 (40.0)	5 (25.0)	1 (5.0)	0 (0.0)	4.0	0.9
Adhesion	6 (30.0)	7 (35.0)	6 (30.0)	1 (5.0)	0 (0.0)	3.9	0.9
Softness	5 (25.0)	12 (60.0)	3 (15.0)	0 (0.0)	0 (0.0)	4.1	0.6
Moist	7 (35.0)	6 (30.0)	7 (35.0)	0 (0.0)	0 (0.0)	4.0	0.9
Sebum improvement effect	4 (20.0)	14 (70.0)	2 (10.0)	0 (0.0)	0 (0.0)	4.1	0.6

* 5: very satisfied, 4: satisfied, 3: moderate, 2: dissatisfied, 1: very dissatisfied

Results of the survey, subjects were tested for the color and viscosity of the satisfaction part of the product.

100% of people rated above average. In terms of feeling, 100% of the test subjects rated above the average level for the stimulus level, and 95% of the test subjects rated above the average level for the skin absorption level and the adhesion level. In the post-use change part, 100% of the test subjects were evaluated to be above normal for the softness, moistness and sebum improvement effect items.

3) Skin irritation evaluation

The skin irritation evaluation (self-evaluation) results of the test subjects are shown in Table 6 below.

	Erythema	Edema	Scaling	Itching	Stinging	Burning	Tightness		Prickling
1 day after use	none	none	none	none	none	none	none		none
3 days after use	none	none	none	none	none	none	none	none
5 days after use	none	none	none	none	none	none	none	none

Subjects were advised to report to the investigator as soon as adverse events occurred. In addition, the questionnaire was to indicate whether the skin irritation. As a result of a survey of subjects during the trial, no skin adverse reactions were observed for all test subjects.

In addition, in the visual evaluation by the researcher, no skin adverse reaction was observed.

4) Photo Shoot Results

Photographs were taken for all the test subjects, but not all of them are shown in FIG. 17.

From Fig. 17, it is possible to confirm the shape of the magnesium patch and the form of adhesion used as the test material, and of course, the basis of visual observation of the acne relief effect can be confirmed.

Skin irritation evaluation and skin invasion effect on the micro-needles and micro-needles patch for acne relief and prevention of the present invention has been identified through the experiment of Korean Patent Application No. 2017-0115449 published and published by the present applicant, thereby The patch containing the biodegradable metal of the present invention may invade without irritation on the skin without inducing toxicity in normal cells or tissues, thereby expressing antimicrobial activity against acne causing bacteria, thereby contributing to simple and safe acne relief and prevention. Can be.

On the other hand, the selective anti-acne bactericidal activity of the patch containing the non-toxic biodegradable metal having excellent biocompatibility is mainly due to the increase of the local pH due to OH ^- ions generated during the decomposition of the metals shown in Schemes 1 to 3. It is expected that, if the pure magnesium or pure zinc metal containing the components according to the formula (1) to accelerate the decomposition rate, a faster antibacterial effect is expected.

The patch to which the biodegradable metal of the present invention is applied is useful for alleviating and preventing acne by having antimicrobial activity against acne causing bacteria on its own without carrying a separate drug, and by using a simple method of applying it to the skin by manufacturing it in various forms It may be useful as a patch to prevent acne or to alleviate the caused acne.

Claims (13)

1. The following acne relief and prevention patch, comprising a biodegradable metal represented by the formula (1) having an anti-acne effect.

   [Formula 1]

   Mg _a Zn _b X _c

   In Formula 1, a, b, and c are weight percent of each component, and a + b + c = 100 wt%, and a or b is in a range of 0 ≦ a ≦ 100, 0 ≦ b ≦ 100, and 0 ≦ c ≦ 10. X is the one or more selected from the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce and P.
2. According to claim 1, wherein the biodegradable metal acne palliation and prevention patch, characterized in that included in the form of a microneedle.
3. According to claim 1, wherein the biodegradable metal acne palliation and prevention patch, characterized in that included in the form of a thin plate.
4. According to claim 1, wherein in Formula 1 a, b and c are the weight percentage of each component, a + b + c = 100% by weight, i) 90≤a≤100, 0≤b≤10, 0≤ c ≦ 10 or ii) 0 ≦ a ≦ 10, 90 ≦ b ≦ 100, 0 ≦ c ≦ 10, and X is one selected from the group consisting of Ca, Fe, Mn, Si, Na, Zr, Ce, and P Acne relief and prevention patch, characterized in that above.
5. According to claim 1, wherein the biodegradable metal is a patch for acne alleviation and prevention, characterized in that the purity of 95% or more pure purity containing inevitable impurities.
6. The patch of claim 1, wherein the biodegradable metal has two or more metal phases to generate a galvanic circuit to accelerate the decomposition rate.
7. 7. The patch of claim 6, wherein the biodegradable metal comprises a Mg ₂ Ca phase.
8. 7. The patch of claim 6, wherein the biodegradable metal comprises a MgZn phase.
9. 7. The patch of claim 6, wherein the biodegradable metal comprises a Ca ₂ Mg ₆ Zn ₃ phase.
10. The method of claim 1, wherein the biodegradable metal is a patch for acne relief and prevention, characterized in that the second surface of the metal is coated with a different type of metal.
11. The method of claim 10, wherein the second metal is sodium, magnesium, potassium, iron, nickel, zinc, gallium, selenium, strontium, zirconium, molybdenum, niobium, tantalum, titanium, silicon, silver, gold, manganese and calcium. Acne relief and prevention patch, characterized in that at least one metal selected from the group consisting of.
12. Use of the acne alleviation and prevention patch of any one of claims 1 to 11 attached to the acne skin.
13. 13. The method of claim 12, wherein the step of moisturizing or soothing the skin is performed prior to attaching the acne relief and prevention patch to the acne skin.

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