WO2022124797A1 - Nasal prosthesis and method for manufacturing same - Google Patents

Abstract

The present invention relates to a nasal prosthesis. The present invention provides a nasal prosthesis and a method for manufacturing same, wherein the nasal prosthesis is inserted into the nasal bridge so as to correspond to the longitudinal direction of the nasal bone during plastic surgery and comprises, when being inserted into the nose, an outer portion which is in contact with skin tissue and is rounded convexly, and a rear portion which is in contact with the nasal bone and cartilage and has a curved surface, the nasal prosthesis having an average surface roughness (Sa) value of 5 µm or more and 49 µm or less. According to the present invention, since the average surface roughness (Sa) value of the nasal prosthesis is within the specific range as described above, the nasal prosthesis prevents, after being inserted into the nose, excessive fibrosis of the surrounding tissue, can inhibit the occurrence of capsular contracture, can reduce the occurrence of side effects such as positional distortion, and can be easily removed when side effects occur and thus facilitates revision surgery.

Description

Nose implant and its manufacturing method

The present invention relates to a nose prosthesis and a method for manufacturing the same. More particularly, it relates to a nasal prosthesis that can be easily removed when a side effect occurs while improving the occurrence of side effects after being inserted into the nose by imparting roughness characteristics to the surface, and a method for manufacturing the same.

In modern times, various plastic surgeries are being performed. In recent years, with increasing interest in appearance, especially the face, plastic surgery is being performed on various parts of the face.

A typical example of plastic surgery for the face is nose plastic surgery. There are purely aesthetic surgery and surgery that considers the functional aspect of this nose plastic surgery. Pure aesthetic surgery includes rhinoplasty (plastic surgery to increase the nose), rhinoplasty (plastic surgery to reduce the nose), rhinoplasty, short nose correction, and long nose correction. There are surgery to correct the deformity or reconstruction of the nose caused by a malignant tumor.

Among these, rhinoplasty is an operation to raise the nose, which is lower than the face.

Accordingly, research for a more convenient and side-effect-free procedure is being conducted from various angles. In particular, various types of nose implants have been developed for nose implants for rhinoplasty.

Looking at the structure of the human nose, the part from the lower forehead to the middle 1/3 of the nose consists of a pair of nasal bones (tibia), and the lower 2/3 part consists of cartilage. This cartilage consists of the upper nasal cartilage (upper and outer cartilage) that is in contact with the nasal bone and the lower nasal tip cartilage (lower outer cartilage, nasal cartilage). And the cross section of the nasal bone (tibia) and cartilage region is round and round, and thin skin tissue covers the nasal bone (tibia) and cartilage.

During rhinoplasty surgery, the operator makes a space by exfoliating the inside of the skin of the nose, processes the nose implant to fit the person undergoing surgery, and then inserts the nose implant into the skin of the nose. For example, when raising the bridge of the nose, the nasal implant inserted into the skin of the nose covers the joint where the nasal bone and the upper nasal cartilage and the nasal bone and the upper nasal cartilage meet each other, and the nose bridge is raised by the thickness of the nose implant.

An artificial synthetic material or autologous tissue is used as a nose implant used in rhinoplasty. The most ideal material is autologous tissue, but it is difficult to process into a beautiful shape, and there are many fluctuations in the absorption rate in the body, so it is difficult to predict the design and final height of the nose line, and there are disadvantages that there is a risk of complications at the collection site, so its application is limited. is being done

The artificial synthetic material may include medical silicone, Gore-Tex (e-PTFE), or a combination thereof. However, these artificial synthetic materials can cause various side effects after being inserted into the body. In particular, when medical silicone is used, problems such as inflammation frequently occurs after rhinoplasty and the position of the implant are distorted or capsular contracture occurs.

The present invention has been made in view of the above problems. It is an object of the present invention to prevent excessive fibrosis of surrounding tissues after insertion into the nose, to suppress the occurrence of spherical contractures, and to improve the occurrence of side effects such as positional distortion, and at the same time, when side effects occur It is to provide a nose implant that can be easily removed and can be easily re-operated.

In addition, another object of the present invention is that the surrounding tissue does not become excessively fibrous after being inserted into the nose, it is possible to suppress the occurrence of spherical contracture, and it is possible to improve the occurrence of side effects such as position distortion, An object of the present invention is to provide a method for manufacturing a nose implant that can be easily removed when side effects occur and can be easily reoperational.

MEANS TO SOLVE THE PROBLEM The present inventors earnestly researched for the purpose of solving the said subject advantageously. As a result, if the average roughness (Sa) value of the surface of the nose implant inserted into the nose is within a predetermined range, the surrounding tissue does not become excessively fibrous after being inserted into the nose, and the occurrence of spherical contracture can be suppressed, It is possible to improve the occurrence of side effects such as positional distortion or implants being reflected, and at the same time, when side effects occur, it can be easily removed, thereby completing the present invention by finding out that reoperation is easy.

According to the present invention, as a nose prosthesis inserted into the bridge of the nose corresponding to the longitudinal direction of the nasal bone,

When inserted into the nose, it includes an outer part that is in contact with the skin tissue and convexly rounded, and a back part that is in contact with the nasal bone and cartilage and has a curved surface,

A nose implant having an average surface roughness (Sa) value of 5 μm or more and 49 μm or less is provided.

In addition, in this invention, "the average roughness (Sa) value of the surface" can be measured using the measuring method as described in an Example.

In addition, the nose prosthesis according to the present invention can be manufactured through an injection process. Specifically, it may be manufactured through an injection process of injection into a chemically corroded mold.

According to the present invention, after being inserted into the nose, the surrounding tissue is not excessively fibrous, it is possible to suppress the occurrence of spherical contracture, and it is possible to improve the occurrence of side effects such as position distortion, and at the same time, when side effects occur, A nose implant that can be easily removed for easy reoperation is provided.

In addition, according to the present invention, after being inserted into the nose, the surrounding tissue does not become excessively fibrous, it is possible to suppress the occurrence of spherical contracture, and it is possible to improve the occurrence of side effects such as positional distortion, and at the same time to reduce the side effects. Provided is a method for manufacturing a nose prosthesis, which can be easily removed when it occurs and can be easily re-operated.

BRIEF DESCRIPTION OF THE DRAWINGS It is explanatory drawing explaining the mean roughness (Sa) of a surface, and root mean square deviation (Sq).

2(a) to 2(c) are right side views schematically showing the shape of the nose prosthesis according to the present invention when viewed from the side.

3(a) is a cross-sectional view taken along line B-B' of FIG. 2(a), FIG. 3(b) is a cross-sectional view taken along line B-B' of FIG. 2(b), and FIG. 3(c) is a rear perspective view of FIG. 2(c).

4 is a cross-sectional view taken along line A-A' of FIG. 2(a).

5 shows the results of hematoxylin & eosin (H&E) staining of samples prepared using the test specimens of Example 1. FIG.

6 shows the results of H&E staining of samples prepared using the test specimens of Example 2.

7 shows the results of H&E staining of samples prepared using the test pieces of Example 3.

8 shows the results of H&E staining of samples prepared using the test pieces of Comparative Example 1.

9 shows the results of MT (Masson's trichrome) staining of a sample prepared using the test piece of Example 1.

10 shows the MT staining results of samples prepared using the test specimens of Example 2.

11 shows the MT staining results of samples prepared using the test pieces of Example 3.

12 shows the MT staining results of samples prepared using the test pieces of Comparative Example 1.

13 is a graph showing the capsule thickness measurement results of Examples and Comparative Examples according to the present invention.

14 shows the results of α-SMA IHC (immunohistochemistry) staining of samples prepared using the test specimens of Example 1. FIG.

15 shows the results of α-SMA IHC staining of samples prepared using the test specimens of Example 2. FIG.

16 shows the α-SMA IHC staining results of samples prepared using the test specimens of Example 3. FIG.

17 shows the results of α-SMA IHC staining of samples prepared using the test specimens of Comparative Example 1. FIG.

18 is a graph showing the results of Myofibroblast and Fibroblast proliferation in Examples and Comparative Examples according to the present invention.

19 is a graph showing the TGF-b1 secretion and expression results of Examples and Comparative Examples according to the present invention.

EMBODIMENT OF THE INVENTION Hereinafter, embodiment of this invention is described in detail.

The nose prosthesis according to the present invention is a nose prosthesis inserted into the bridge of the nose corresponding to the longitudinal direction of the nasal bone during rhinoplasty, and has roughness characteristics (hereinafter referred to as 'surface roughness characteristics') on the surface.

Here, the "surface roughness characteristic" refers to the degree of roughness or non-uniformity of the surface, for example, protrusions/peaks, concavities/valleys, irregularities, and/or gaps on the surface. Surface roughness properties can be characterized by, for example, peaks and valleys of the surface. If this change in the surface is relatively large, then the surface is characterized as "rougher" than a surface in which this change is relatively small. The surface roughness characteristic according to the present invention is mathematically described by the mean roughness (Sa) value and the root mean square deviation (Sq) value in three dimensions, as shown in Equation 1 and FIG. 1 below.

[Equation 1]

where A is the surface area of the area to be measured, and z(x,y) is the surface profile along the x-axis and the y-axis. The average roughness (Sa) represents the average of the absolute values of z(x,y) values in the measurement target area, and represents the arithmetic mean of the measurement target area in a state in which the valley part is converted to an absolute value and changed to a peak. . The root mean square deviation (Sq) represents the root mean square deviation of z(x,y) in the measurement target area, and represents the root mean square of the measurement target area in a state in which the valley portion is changed to a high peak portion by squaring. .

The roughness of the surface can be measured using, for example, a profilometer such as an optical 3D microscope, a contact profilometer, or a non-contact profilometer. Using such a measuring device, a three-dimensional profile of the surface can be obtained in which the roughness can be quantified.

The nose prosthesis according to the present invention has an average surface roughness (Sa) value of 5 μm or more and 49 μm or less, preferably 30 μm or more and 40 μm or less. If the average roughness (Sa) value of the surface of the nose implant is within the above range, it is possible to prevent the film from forming thick around the implanted implant, thereby preventing inflammation due to external reflection or liquid retention in the film. In addition, it is possible to prevent the surrounding tissue from becoming excessively fibrous, so that the tactile feel becomes hard and the shape is prevented from being deformed. In addition, if the average roughness (Sa) value of the surface of the nose implant is greater than or equal to the lower limit of the above range, the implant may be crooked due to frequent positional fluctuations after insertion, or side effects such as thinner skin due to continuous skin friction, or spherical contracture This can be prevented from occurring. In addition, if the average roughness (Sa) value of the surface of the nose implant is less than or equal to the upper limit of the above range, it is not excessively adhered to the tissue after insertion, so that it can be easily removed when side effects occur.

In addition, the nose implant according to the present invention preferably has a surface mean roughness (Sa) value within the predetermined range, and a surface root mean square deviation (Sq) value of 6 μm or more and 60 μm or less, particularly 35 μm It is more preferable that it is more than 45 micrometers. As such, when the average roughness (Sa) of the surface of the nose implant according to the present invention is within a predetermined range, and the root mean square deviation (Sq) value is within the above range, a thick film around the implanted implant is prevented from forming It can be done, and it is possible to more effectively suppress the excessive fibrosis of the surrounding tissues. In addition, if the root mean square deviation (Sq) value of the surface of the nose implant is equal to or greater than the lower limit of the above range, side effects such as distortion of the implant after insertion and occurrence of spherical contracture can be more effectively suppressed. In addition, if the root mean square deviation (Sq) value of the surface of the nose implant is less than or equal to the upper limit of the above range, it is not excessively adhered to the tissue after insertion and can be easily removed when side effects occur.

A nose implant having the above-mentioned average roughness (Sa) and root mean square deviation (Sq) values in the specific ranges on the surface is manufactured by the following method.

The nose implant having surface roughness characteristics according to the present invention is manufactured through an injection process in which medical silicone, Gore-Tex (e-PTFE), or a combination thereof is injected into a mold and molded. The surface roughness characteristic is transferred to the surface of the nose implant from the mold having the surface roughness characteristic, thereby imparting the surface roughness characteristic to the surface of the nose implant.

A mold having surface roughness characteristics is obtained by surface-treating a mold used for injection molding in advance. The surface treatment method of the mold may include a chemical corrosion treatment method or a sand/aluminum blasting method. Among them, the chemical corrosion treatment method is preferable from the viewpoint of easily imparting surface roughness characteristics in a desired range to the mold surface and controlling so that foreign substances do not remain on the surface of the mold to which the surface roughness characteristics are provided.

In addition, it is preferable that the chemical corrosion treatment method for implementing roughness properties on the mold surface includes the following steps:

i) performing a masking operation with a separate film on a portion that does not require chemical corrosion (A);

ii) as a pretreatment process so that the etchant (nitric acid and photoresist) is well absorbed, the first sanding process (B);

iii) transferring the predetermined pattern design to the mold and etching the pattern on the mold using an etchant (C);

iv) performing secondary sanding to smooth the surface roughened by chemical corrosion (D); and

v) cleaning the mold surface using a cleaning solution (E);

According to the chemical corrosion treatment including steps (A) to (E), it is possible to efficiently impart roughness characteristics to the mold surface. In addition, since roughness characteristics can be uniformly applied to the surface of the mold as a whole, the roughness characteristics can be uniformly implemented on the entire surface of the nose implant obtained by using the mold.

According to the degree of chemical corrosion exhibited by the chemical corrosion treatment, the surface of the mold is given a roughness characteristic. When transferring roughness characteristics to the surface of the nose implant through injection molding using a mold with surface roughness characteristics, the average roughness (Sa) value and root mean square deviation (Sq) value realized on the surface of the mold are generally higher, The average roughness (Sa) value and the root mean square deviation (Sq) value transferred to the surface of the nose implant are measured to be equal to or less than the same. A person skilled in the art may set chemical corrosion treatment conditions in consideration of this point.

For example, during the chemical corrosion treatment step, the time of the first sanding in step (B), the pressure, the pattern design in the step (C), the concentration of the etchant, the contact time with the etchant, the step (D) By appropriately adjusting conditions such as the time and pressure for secondary sanding in the present invention, it is possible to adjust the roughness characteristics provided to the surface of the mold. Thereby, the average roughness (Sa) value and the root-mean-square deviation (Sq) value of the surface of the nose prosthesis obtained by using the mold can be within the predetermined ranges.

In addition, in the chemical corrosion treatment, after the step (D) and before the step (E), the steps (B) to (D) may be suitably adjusted one or more times and may be further carried out. In this way, by performing steps (B) to (D) one or more times after step (D) and before step (E), it is possible to more uniformly impart roughness characteristics to the surface of the mold, and also use the mold The mean roughness (Sa) value and the root mean square deviation (Sq) value of the surface of the nose implant obtained by performing the above procedure can be easily adjusted within the predetermined ranges. In particular, the average roughness (Sa) value of the surface of the nose implant can be more easily adjusted in the range of 30 µm or more and 40 µm or less, and the root mean square deviation (Sq) value is in the range of 35 µm or more and 45 µm or less.

On the other hand, in the case of manufacturing a nose implant having an average roughness (Sa) and root mean square deviation (Sq) in a specific range on the surface by the method of injection into the injection mold as described above, the shape of the nose implant is determined according to the shape of the injection mold. You can do it differently.

Hereinafter, specific embodiments related to the shape of the nose prosthesis according to the present invention will be described in detail with reference to the accompanying drawings. However, this invention is not limited to this embodiment.

The same reference numerals are used throughout the drawings to refer to parts having similar functions and functions.

In addition, "including" a certain component does not exclude other components, unless otherwise stated, means that other components may be further included.

2(a) to 2(c) are right side views schematically showing the appearance of the nose implant according to an embodiment of the present invention as viewed from the side, and FIGS. 3(a) to 3(b) are views Of the nose prosthesis according to the embodiment of the present invention, a cross-sectional view taken along the line B-B' in FIGS. 2(a) and 2(b) is shown, and in FIG. 3(c), a rear perspective view of FIG. 4 is a cross-sectional view taken along line A-A' of FIG. 2( a ).

2, 3, and 4, the nose prosthesis 10 according to the embodiment of the present invention includes an outer part 110 and a rear part 120.

More specifically, the nose prosthesis 10 according to the embodiment of the present invention is inserted into the bridge of the nose corresponding to the longitudinal direction of the nasal bone, and includes an outer part 110 in contact with the skin and a rear part 120 in contact with the nasal bone and cartilage. .

In the nose prosthesis according to the present invention, the outer part 110 in contact with the skin tissue is convexly rounded. Thereby, it is possible to utilize the natural line of the bridge of the nose and give volume to the nose.

In addition, as shown in FIG. 3 , the rear surface portion 120 is concavely rounded so that the rear surface of the nose prosthesis has a predetermined depth and curvature along the longitudinal direction, and is in close contact with the nasal bone and cartilage. That is, it is preferable that the rear portion 120 extends along the longitudinal direction of the nasal bone, and the portion in contact with the nasal bone and cartilage is concave, so that it is completely in close contact with the nasal bone and the upper and outer cartilage.

In addition, as shown in Figs. 2 and 3, it is preferable that the concave portion 130 is formed in a slightly concave shape in accordance with the shape of the nasal bone in the central portion of the rear surface of the nose prosthesis 10.

In this way, it is possible to minimize the occurrence of seroma, hematoma, etc. by preventing an empty space from being formed between the nasal implant and the nasal bone and cartilage. In addition, it is possible to prevent the surgical site from appearing conspicuously.

In addition, when the upper end of the nose prosthesis 10 is inserted into the nose, it is preferable that a curve is formed with a predetermined curvature in the portion extending to the forehead.

As described above, the upper end of the nose prosthesis 10 extends to the forehead when inserted, thereby extending the length of the nose while creating a natural curve in the area where the forehead and the nose contact.

At this time, as shown in FIG. 2(c), an imaginary line L1 connecting the central point on the outer surface of the nose prosthesis 10 and the end of the upper end of the nose prosthesis 10, and the nose prosthesis 10 When the angle between the imaginary lines L2 extending the straight line portion where no curve is formed is defined as θ, the angle θ is not particularly limited, but is generally set to a value of 10° to 20°. By setting the angle θ within the above range, it is possible to form a natural curve in the glabellar part after molding.

In addition, as shown in FIGS. 2(b) and 2(c), the lower end of the nose prosthesis 10 is extended so that it touches the tip of the nose upon insertion, and the corresponding part is more convex than the other parts of the outer part 110 you can do it In this case, the bridge of the nose and the tip of the nose can be raised at the same time.

In addition, the nose implant 10 is formed of a material made of medical silicone, Gore-Tex (e-PTFE), or a combination thereof, which is harmless to the human body as a whole.

In addition, the nose implant according to the present invention has an average surface roughness (Sa) value within the specified range as described above. For this reason, it is possible to suppress the formation of an excessively thick film, excessive fibrosis of the surrounding tissue, and the occurrence of spherical contracture, and it is possible to suppress side effects such as distortion or reflection of the implant.

On the other hand, although not shown, the nose prosthesis 10 may be configured in a conventional substantially L-shape. As described above, since the nose implant 10 according to the present invention has roughness characteristics on the surface, even if it is approximately L-shaped as in the prior art, the coating film is excessively thick, or the surrounding tissue is excessively fibrous and spherical construction is not possible. It can suppress the occurrence and side effects such as crooked or protruding implants can be suppressed.

Example

Hereinafter, the present invention will be specifically described with reference to Examples. However, the present invention is not limited to the following examples, and can be arbitrarily changed and implemented within the scope not departing from the scope of the claims of the present invention and its equivalents.

In order to evaluate safety and biocompatibility according to the surface roughness characteristics, using a nose implant with various surface roughness characteristics in a mouse model, histological analysis of the tissue surrounding the test specimen according to the surface roughness characteristics, and the formed capsule thickness (Capsule thickness), myofibroblast and fibroblast proliferation, and TGF-b1 secretion and expression were measured.

If specific experimental methods and conditions are not mentioned below, conventional experimental methods and conditions may be used.

[Method for measuring surface roughness characteristics]

The surface roughness characteristics were evaluated using 3D Laser Confocal (model name: OLS5000, manufactured by Olympus). Specifically, the test specimens obtained in Examples and Comparative Examples were washed with isopropyl alcohol and dried, and then the dried test specimens were placed in a 3D Laser Confocal. The size of the area to be measured was set to (4.0 ± 0.1) mm ² . Subsequently, the average roughness (Sa) value and the root mean square deviation (Sq) value were measured 5 times (5 areas) on the surface of the test piece by using a measuring device, respectively, and the average value was obtained.

[Method for evaluating safety and biocompatibility]

The test specimens prepared in each Example and Comparative Example were cut to 10mm (width) × 30mm (length) × 3mm (thickness) and transplanted into the dorsal skin of a total of 48 (12 per group) Sprague-Dawley rats. After transplantation, after 4 weeks and 8 weeks, respectively, test specimens and surrounding tissues were collected and analyzed according to the evaluation criteria below. Details of transplantation of test specimens and collection of test specimens and surrounding tissues are as follows.

(transplantation of test piece)

Each rat was anesthetized by intraperitoneal injection using zolazepam-tiletamine mixture (30mg/kg) and xylazine (10mg/kg), and 0.12 to 0.16ml of gentamicin aqueous solution (20mg/kg) was administered subcutaneously. After that, the skin was washed with Betadine (registered trademark) Surgical Scrub (manufactured by Purdue Pharm LP) and the skin was disinfected with a sterilizing agent (10% povidone iodine solution). After that, both sides of the back were transversely incised to 15 mm each, and the subpanniculus carnosa layer was incised in the head direction to form 10 mm × 30 mm pockets on both sides of the back. Hemostasis with a bipolar coagulator, and after inserting the test specimens prepared in each Example and Comparative Example into the formed pocket, 4-0 absorbable and non-absorbable nylon sutures (Polysorb (registered trademark) and Monosof (registered trademark)) Trademark), manufactured by Covidien) was sutured.

(Collection of test specimens and surrounding tissues)

After 4 weeks and 8 weeks after implantation of the test specimen, half (6 mice) of each group of mice were euthanized by CO ₂ inhalation anesthetic overdose (ie, 4 weeks after transplantation). Six animals were euthanized, and the remaining six animals were euthanized after 8 weeks). Thereafter, the test piece and surrounding tissues (capsule, skin, all surrounding tissues including carnosa and thoracodorsal skeletal muscle) were excised into one piece and collected as one sample.

< Histological analysis >

Each sample collected above was fixed with 10% formalin. After 24 hours, the test piece and surrounding tissues were cut in the thickness direction of the test piece and embedded in paraffin. Slides were made into 5 μm-thick sections and stained with hematoxylin & eosin (H&E) and Masson's trichrome (MT). The surface of the capsule in contact with the surface of each test piece was photographed using a microscope equipped with a digital camera system (Olympus Bx 40 microscope, DP70 camera and DP controller; manufactured by Olympus).

The H&E staining results of each Example and Comparative Example are shown in FIGS. 5 to 8, and the MT staining results of each Example and Comparative Example are shown in FIGS. 9 to 12 . 5 to 12, (a) shows the staining results of slides prepared using samples collected 4 weeks after transplantation, and (b) shows slides prepared using samples collected 8 weeks after transplantation. The staining result is shown. In addition, in FIGS. 5-12, the left image is taken at ×40 magnification, and the right side is photographed at ×100 magnification. In addition, in FIGS. 9-12, the arrow in (b) shows the boundary of a capsule.

< Measurement of Capsule Thickness >

The thickness of the capsule was measured using the slide stained with hematoxylin&eosin (H&E) obtained in the section of <Histological analysis>, and the average value was used as the capsule thickness.

The capsule thickness was measured using a microscope equipped with the digital camera system at ×200 magnification, and the thicknesses were measured at 5 different locations for each slide, and the average value was obtained. The measurement results are shown in FIG. 13 . In FIG. 13, 4w and 8w indicate 4 weeks after transplantation and 8 weeks after transplantation, respectively, and have the same meaning in FIGS. 18 and 19 .

< Measurement of Myofibroblast and Fibroblast Proliferation >

Myofibroblast and fibroblast proliferation was measured using α-SMA immunostaining method. Using a mouse monoclonal Anti-α smooth muscle actin antibody (α-SMA), each sample fixed by formalin and embedded in paraffin was subjected to measurements. A specific measurement method is as follows.

For each sample collected, the tissues around the test piece were fixed using formaldehyde, put in a citric acid buffer solution (pH 6.0), and heated to recover the antigen. Blocking was performed with 10% serum at RT for 1 hour. . Then, the blocked sample was transferred to 2% serum. The primary antibody (trade name: ab5694, manufactured by Abcam) was diluted 1/300 and incubated with a sample in 2% serum at 4°C for 15 hours. As a secondary antibody, a biotin-conjugated goat polyclonal to rabbit IgG antibody (trade name: ab6720, manufactured by Abcam) diluted at 1/500 was used to bind to the primary antibody and stained. The stained sample was photographed at ×400 magnification using a microscope equipped with a digital camera system (Olympus Bx 40 microscope, DP70 camera and DP controller; manufactured by Olympus). The results of α-SMA IHC (Immunohistochemistry) staining of Examples and Comparative Examples are shown in FIGS. 14 to 17 . 14 to 17, (a) shows the staining results of a sample prepared using a sample collected 4 weeks after transplantation, (b) is a sample collected 8 weeks after transplantation The staining results of samples prepared using

In addition, using a computer-assisted image analysis device (Image-Pro (registered trademark) Plus), the average value of the area stained by α-SMA was obtained in a high-power field, and the degree of Myofibroblast and Fibroblast proliferation was quantified. The analysis results of each Example and Comparative Example are shown in FIG. 18 .

It indicates that the lower the number of myofibroblast and fibroblast proliferation can suppress the occurrence of clinical side effects such as localization and spheroid contracture.

< TGF-b1 secretion and expression >

Measurement of TGF-b1 secretion and expression was performed through quantitative real-time PCR on tissues surrounding the test specimen for each sample collected. A specific measurement method is as follows.

First, 30 mg of tissue around each test piece was put into a cell storage reagent (trade name: RNAlater (registered trademark), manufactured by Ambion) and stored for 1 day to obtain a mixture. The mixture was pulverized with a tungsten carbide bead of 5 mm at a frequency of 27 Hz using a mixer mill grinder for 2 minutes. The pulverized solution was centrifuged at 10,000×g for 3 minutes to collect pulverized debris and the supernatant was removed. Then, total RNA (total RNA) was extracted using an RNA purification kit (trade name: RNeasy Mini Kit, manufactured by Qiagen). 1 μg of total RNA was reverse transcribed using High-Capacity RNA-to-cDNA Master Mix (manufactured by Applied Biosystems) to obtain cDNA.

Next, real-time PCR analysis was performed using a quantitative real-time PCR system (7900HT Fast Real-Time PCR System equipped with SYBR-Green I gene expression assay, manufactured by Applied Biosystems). Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as an endogenous control. The temperature profile used in the quantitative real-time PCR system was 40 cycles of 37°C for 60 min, 95°C for 5 min, 95°C for 30 sec, 60°C for 30 sec, and 72°C for 30 sec for reverse transcription. All reactions were performed twice, and the data amplified by the quantitative real-time PCR system was analyzed using Applied Biosystems Sequence Detection Software version 1.3.1 (manufactured by Applied Biosystems).

A standard curve was prepared by measuring the transcription level of mRNA obtained as a specific primer set from cDNA samples of TGF-b1 diluted to concentrations of 1, 0.5, 0.25, 0.125, and 0.0625. A standard curve was prepared by diluting GAPDH, a housekeeping gene, in the same manner as above. mRNA transcription levels for GAPDH at each dilution concentration (Ct) were normalized. TGF-b1 secretion and expression were assessed based on normalized data. The evaluation results in each Example and Comparative Example are shown in FIG. 19 .

Lower levels of TGF-b1 secretion and expression indicate that fibrosis of the surrounding tissue can be inhibited and it is safer from clinical side effects such as spheroid contracture.

[Example 1]

(Surface treatment of mold for injection molding)

The surface of the mold that does not require chemical corrosion (the part that does not come in direct contact with the raw material for injection molding) was masked with a film, and then the etchant (nitric acid and photoresist) was first sanded so that it was well absorbed. Next, the pattern design was transferred to the mold, and the pattern was etched on the mold using an etchant. After that, secondary sanding was performed to smooth the roughened surface, and the surface of the surface-treated mold was washed using a cleaning solution.

(Production of test specimens)

A test specimen was prepared by injection molding a medical silicone raw material using the mold.

The roughness characteristics of the surface of the obtained test specimen were measured, and histological analysis and capsule thickness, Myofibroblast and Fibroblast proliferation, TGF-b1 secretion and expression were measured according to the above evaluation method. The measured surface roughness characteristics are shown in Table 1, and each evaluation result is shown in FIGS. 5, 9, 13, 14, 18, 19.

[Example 2]

In the same manner as in Example 1, except that the concentration of the etchant was increased in the surface treatment of the injection molding mold and the contact time with the etchant was increased so that the roughness characteristics of the surface of the test specimen obtained were the values shown in Table 1, Surface treatment of the mold for injection molding and production of test specimens were performed.

Measurements and evaluations were carried out in the same manner as in Example 1 using the obtained test specimens. The measured surface roughness characteristics are shown in Table 1, and each evaluation result is shown in FIGS. 6, 10, 13, 15, 18, 19.

[Example 3]

After the secondary sanding in the surface treatment of the injection molding mold, before cleaning the surface of the surface-treated mold using a cleaning solution, the primary sanding process, pattern design is transferred to the mold, and the etchant is used in the mold The process of etching the pattern and the secondary sanding process were performed once more.

Except for the above, a test piece was prepared in the same manner as in Example 1. Measurements and evaluations were carried out in the same manner as in Example 1 using the obtained test specimens. The measured surface roughness characteristics are shown in Table 1, and each evaluation result is shown in FIGS. 7, 11, 13, 16, 18, 19.

[Comparative Example 1]

As a product of MegaDerm Nasal (manufactured by L&C BIO), a test specimen was prepared using an acellular allogeneic dermal product, and was measured and evaluated in the same manner as in Example 1. The measured surface roughness characteristics are shown in Table 1, and each evaluation result is shown in FIGS. 8, 12, 13, 17-19.

	Example 1	Example 2	Example 3	Comparative Example 1
Average Roughness (Sa/㎛)	5.03	11.70	37.50	49.53
Root Mean Square Deviation (Sq/μm)	6.42	14.75	43.39	58.87

According to the measurement results shown in FIGS. 5 to 19, the nasal implants (Examples 1 to 3) having an average surface roughness (Sa) value within a specific range (5 μm or more and 49 μm or less) of the present invention had excessive film after insertion. It was found that it can suppress the formation of thick skin, suppress the excessive progression of fibrosis and the occurrence of spherical contracture, and improve clinical side effects such as position change of the implant. In addition, it was found that it was not excessively adhered to the surrounding tissues and could be easily removed when side effects occurred.

On the other hand, when the average roughness (Sa) value of the surface is out of the specific range of the present invention (Comparative Example 1), the film is formed thickly, fibrosis is excessively progressed, and it is excessively adhered to the surrounding tissue, which is the purpose of the present invention. The effect was not obtained.

Claims (9)

1. As a nose implant to be inserted into the bridge of the nose corresponding to the longitudinal direction of the nasal bone,

   When inserted into the nose, it includes an outer portion that is in contact with the skin tissue and convexly rounded, and a rear portion that is in contact with the nasal bone and cartilage and has a curved surface,

   A nose implant having an average surface roughness (Sa) value of 5 μm or more and 49 μm or less.
2. The method of claim 1,

   A nose implant having a root mean square deviation (Sq) of the surface of 6 μm or more and 60 μm or less.
3. 3. The method of claim 1 or 2,

   A nose implant having an average roughness (Sa) value of the surface of 30 μm or more and 40 μm or less.
4. 4. The method of claim 3,

   A nose implant, wherein the root mean square deviation (Sq) value of the surface is 35 μm or more and 45 μm or less.
5. 3. The method of claim 1 or 2,

   A nose implant made of medical silicone, Gore-Tex (e-PTFE), or a combination thereof.
6. 3. The method of claim 1 or 2,

   A nose prosthesis further having a concave portion in the middle portion of the rear portion.
7. A method for manufacturing the nose prosthesis according to claim 1 or 2, comprising:

   Chemical corrosion treatment of the mold used in the injection process; and

   A method of manufacturing a nose prosthesis comprising; injecting a raw material into the chemically corroded mold.
8. 8. The method of claim 7,

   The chemical corrosion treatment comprises the following steps,

   i) performing a masking operation with a separate film on a portion that does not require chemical corrosion (A);

   ii) as a pretreatment process so that the etchant (nitric acid and photoresist) is well absorbed, the first sanding process (B);

   iii) transferring the predetermined pattern design to the mold and etching the pattern on the mold using an etchant (C);

   iv) performing secondary sanding to smooth the surface roughened by chemical corrosion (D); and

   v) cleaning the mold surface using a cleaning solution (E);

   The raw material is medical silicone, Gore-Tex (e-PTFE), or a combination thereof.
9. 9. The method of claim 8,

   After the step (D) and before the step (E), the method for manufacturing a nose prosthesis in which the steps (B) to (D) are performed one or more times.

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