JP6263305B1 - Medical sheet - Google Patents

Abstract

[PROBLEMS] To provide a medical sheet capable of distinguishing a surface (part) subjected to ion bombardment and a surface (part) not subjected to ion bombardment. When the difference between a certain b1 value and the b2 value that is the b value of the second surface 7 is Δb, the medical sheet having Δb of 2 or more and 11 or less, and the first of the sheet containing polytetrafluoroethylene A method of manufacturing a medical sheet including a roughening step of roughening the entire surface 5 by ion bombardment to form a roughened portion 5, wherein the ion bombardment is 10 −7 atm or more. A method which is continuously performed at a vacuum degree of 10-1 atm or less. [Selection] Figure 1

Description

  The present invention relates to a medical sheet. More specifically, the present invention relates to a medical sheet that can be used for biological repair materials, artificial membranes, and the like.

  Japanese Patent No. 4445697 and Japanese Patent No. 5505572 disclose a biological repair material.

Japanese Patent No. 4445697 Japanese Patent No. 5505552

  In the biomedical repair material described in the above publication, it is difficult to distinguish between the surface subjected to ion bombardment and the surface not subjected to ion bombardment. Living body repair materials and artificial membranes are embedded in the living body. For this reason, it is difficult to use colorants, and it is necessary to reapproval when the composition changes. Therefore, a medical sheet that can distinguish a surface (part) subjected to ion bombardment from a surface (part) not subjected to ion bombardment is desired. Furthermore, when an artificial blood vessel was created using a medical sheet, it was desired that a vascular endothelial cell is easily fixed.

  In the present invention, basically, the whole or a part of one surface of a resin sheet such as ePTFE (stretched polytetrafluoroethylene) is subjected to a surface treatment by ion bombardment and the like, and then a heat treatment is performed. This is based on the knowledge that only the roughened portion changes color without changing the physical properties. In addition, the present invention continuously maintains the degree of vacuum of the ion bombardment device at a constant value when performing ion bombardment, and continuously performs ion bombardment to enhance the effect of ion bombardment and achieve high surface roughness. Based on the knowledge that it can be achieved.

The present invention relates to a medical sheet. This medical sheet is a medical sheet 1 having a first surface 5 having a roughened portion 3 and a second surface 7 positioned opposite to the first surface 5 and containing polytetrafluoroethylene. .
The roughened portion 3 has a surface roughness Rz value of 8 or more and 14 or less, and an Ra value of 0.65 or more and 1.5 or less. The roughened portion 3 is preferably a portion modified by an ion bombardment portion. The roughened portion 3 may be a part of the first surface 5 or the entire first surface 5. B ₁ value and a b value of roughening unit 3, the difference between the b ₂ values is b value of the second surface 7 when the [Delta] b, [Delta] b are those preferably 2 to 11.

The present invention also provides a method for producing a medical sheet. In this method, all or part of the first surface 5 of the sheet containing polytetrafluoroethylene is roughened by ion bombardment to form a roughened portion 5. It is a manufacturing method. The ion bombardment is continuously performed at a vacuum degree of 10 ⁻⁷ atm or more and 10 ⁻¹ atm or less. This method preferably further includes a heating step of heating the sheet containing polytetrafluoroethylene that has undergone the roughening step to obtain a medical sheet. The roughened part 3 preferably has a surface roughness Rz value of 8 or more and 14 or less and a Ra value of 0.65 or more and 1.5 or less. The example of a heating process is a process of heating a sheet | seat for 10 second or more and 10 minutes or less at the temperature of 60 to 300 degreeC.

  ADVANTAGE OF THE INVENTION According to this invention, the medical sheet which can manufacture the medical sheet which can distinguish the surface (part) to which the ion bombardment was given, and the surface (part) which was not roughened, and the medical sheet which can be distinguished Can provide. In addition, when an artificial blood vessel was created using this medical sheet, vascular endothelial cells were likely to settle.

FIG. 1 is a conceptual diagram showing a medical sheet of the present invention. FIG. 1A shows the first surface, and FIG. 1B shows the second surface.

  Hereinafter, embodiments for carrying out the present invention will be described with reference to the drawings. The present invention is not limited to the embodiments described below, but includes those appropriately modified by those skilled in the art from the following embodiments.

  The present invention relates to a medical sheet. The medical sheet means a sheet that has a portion having high adhesion and adhesion to living tissue and a portion having low adhesion and can be used in medical treatment. This sheet can be used, for example, to adhere a specific tissue while the opposite surface does not adhere to the tissue. In addition, an artificial blood vessel can be obtained by rounding the medical sheet. Furthermore, this medical sheet can be used for artificial valves and various transplants by cutting into a predetermined shape. The medical sheet may be a living body repair material described in Japanese Patent No. 4445697 or a supplementary material having adhesion to an artificial dura mater or muscle described in Japanese Patent No. 5505572. These most preferred materials are elliptical in size ranging from 7.5 cm × 10.0 cm to 26.0 cm × 34.0 cm. Other planar shapes are also contemplated for use with the present invention, such as circles, squares, triangles, and shapes that are specifically tailored. Regardless of shape, suitable implantable sheet material sizes range from as small as 1.0 cm × 1.0 cm to as large as 50.0 cm × 50.0 cm, from 5.0 cm × 5.0 cm to 40 cm. A small piece having a size of 0.0 cm × 40.0 cm is preferable, and a small piece having a size of 7.0 cm × 7.0 cm to 20.0 cm × 20.0 cm may be used.

  As shown in FIG. 1, the medical sheet 1 has a first surface 5 having a roughened portion 3 and a second surface 7 positioned opposite to the first surface 5, and is made of polytetra This is a medical sheet 1 containing fluoroethylene. FIG. 1 is a conceptual diagram showing a medical sheet of the present invention. FIG. 1A shows the first surface, and FIG. 1B shows the second surface. The roughened portion 3 means a portion having a rougher surface roughness than the second surface. The roughened portion 3 may be a portion modified by ion bombardment. The rough surface portion 3 may be the entire first surface 5 or a specific portion of the first surface. When it is desired to roughen only a specific part of the first surface, for example, a roughening process may be performed in a state where a part that is not roughened is masked. The roughened portion 3 has a surface roughness Rz value of 8 or more and 14 or less (preferably 9 or more and 13 or less, or 9.5 or more and 12.5 or less, or 10 or more and 12 or less), and an Ra value. May be 0.65 or more and 1.5 or less (preferably 0.7 or more and 1.4 or less, or 0.8 or more and 1.3 or less). These values may be obtained in accordance with JIS B 0601-2001.

  Since the medical sheet having such a surface roughness is subjected to heat treatment, the degree of discoloration differs between the roughened portion and the portion that is not, so the medical sheet having the roughened portion and the portion that is not. A sheet can be obtained. As will be described later, when an artificial blood vessel is produced using a medical sheet having the above surface roughness, vascular endothelial cells are likely to be established.

  This medical sheet is preferably one that can visually distinguish a roughened portion and a portion that is not so based on a difference in color.

  The Lab colorimetric method is obtained from the following equation using tristimulus values X, Y, and Z defined in JIS Z8730.

L = 10Y ^1/2 (1)
a = 17.5 (1.02X−Y) / Y ^1/2 (2)
b = 7.0 (Y−0.847Z) / Y ^1/2 (3)
L: Lightness index in the color difference formula of Hunter (R. S. Hunter).
a, b: Color coordinates in Hunter's color difference formula.
X, Y, Z: Tristimulus values X, Y, Z in the X, Y, Z color display.

  Among the Lab color specifications, L represents lightness and is generally a value from 100 to 0. Lightness refers to the lightness or darkness of a color, that is, the degree of brightness. A larger L value means brighter.

  Further, a and b represent colors, the a value represents the red-green direction, and the b value represents the yellow-blue direction. Therefore, the red value becomes stronger as the value a becomes larger, the greenness becomes stronger when the value a becomes smaller, the yellowness becomes stronger as the value b becomes larger, and the blueness becomes stronger when the value a becomes smaller.

  In this medical sheet, when the difference between the b1 value that is the b value of the roughened portion 3 and the b2 value that is the b value of the second surface 7 is Δb, Δb is 2 or more and 11 or less. is there. Δb is normally obtained from the b1 value−b2 value. Δb may be 4 or more and 10 or less, Δb may be 5 or more and 9.5 or less, Δb may be 6 or more and 9.5 or less, Δb may be 6 or more and 9 or less, Δb may be 7 or more and 8.5 or less. As described above, the medical sheet of the present invention has a yellowish roughened portion, so that it can be distinguished from a surface having a roughened portion and a surface not having a roughened portion (both sides). Both may have a partially roughened portion and determine whether or not it is a roughened portion by the color of the roughened portion).

  This medical sheet can also be distinguished by the fact that the roughened portion exhibits a slightly reddish color. In particular, in order to determine the roughened surface under a yellow fluorescent lamp, it is possible to distinguish between a reddish hue and a greenish hue. Conventional medical sheets had a slightly greenish color. On the other hand, the medical sheet of the present invention exhibited a slightly reddish color. In this medical sheet, when the difference between the a1 value that is the a value of the roughened portion 3 and the a2 value that is the a value of the second surface 7 is Δa, Δa is 0.1 or more and 1 or less. Preferably there is. Δa is usually obtained from a1 value−a2 value. Δa may be 0.15 or more and 0.9 or less, and Δa may be 0.2 or more and 0.5 or less.

  An example of polytetrafluoroethylene is expanded polytetrafluoroethylene (ePTFE). An example of expanded polytetrafluoroethylene is expanded porous polytetrafluoroethylene made according to US Pat. Nos. 3,953,566 and 4,187,390. In the examples, experiments were basically performed using expanded polytetrafluoroethylene. On the other hand, the effects demonstrated in the examples are considered to be effective for all polytetrafluoroethylene-based sheets.

Next, the present invention relates to a method for manufacturing a medical sheet. This method
A roughening step of roughening all or part of the first surface 5 of the sheet containing polytetrafluoroethylene to form the roughened portion 5 is included. In the roughening step, ion bombardment is continuously performed at a vacuum degree of 10 ⁻⁷ atm or more and 10 ⁻¹ atm or less. This method may include a heating step of heating a sheet containing polytetrafluoroethylene that has undergone the roughening step to obtain a medical sheet. Conventionally, the surface of the sheet has been washed with an organic solvent. On the other hand, when the surface of the sheet was washed with an organic solvent, the organic solvent remained on the sheet surface, and a compound derived from the organic solvent adhered to the sheet surface. For this reason, in the present invention, it is preferable that the work of cutting the sheet or roughening the sheet is performed in a clean room and the sheet surface is not washed with an organic solvent. As described later, the ion bombardment is preferably performed continuously in a vacuum chamber.

Examples of the roughening treatment in the roughening step are ion implantation (ion bombardment), plasma treatment, corona treatment, UV treatment, chemical blasting and sandblasting. In this manufacturing method, the roughened portion 3 may have a surface roughness Rz value of 8 or more and 14 or less, and an Ra value of 0.65 or more and 1.5 or less. That is, it is preferable to perform the next processing step with the surface slightly rougher than the conventional medical sheet. With respect to ion implantation, for example, in the conventional ion implantation method, the degree of vacuum in the vacuum chamber (in the ion bombardment apparatus) during ion bombardment is kept within a certain range, and ion bombardment is performed continuously. A preferable surface roughness can be achieved by controlling the amount of ion bombardment in the y-axis direction. Examples of ion density (dose amount φ) are 1 × 10 ¹³ ions / cm ² or more and 1 × 10 ¹⁶ ions / cm ² or less, and 1 × 10 ¹⁴ ions / cm ² or more and 1 × 10 ¹⁵ ions / cm ² or less. But you can. An example of the ion acceleration voltage is 30 keV or more and 2000 keV or less, 70 keV or more and 300 keV or less, or 100 keV or more and 250 keV or less. The example of ion irradiation time is 1 minute or more and 5 hours or less, 10 minutes or more and 2 hours or less may be sufficient, and 30 minutes or more and 1 hour or less may be sufficient.

An example of the degree of vacuum in the chamber is 10 ⁻⁷ atm to 10 ⁻¹ atm, 10 ⁻⁶ atm to 10 ⁻² atm, or 10 ⁻⁵ atm to 5 × 10 ⁻³ atm. ^However , it may be 10 ⁻⁴ atm or more and 10 ⁻³ atm or less. The vacuum system itself is known, and a desired degree of vacuum can be achieved by using a vacuum system including a vacuum chamber and a pump connected to the vacuum chamber. By performing ion bombardment while properly evacuating, ion bombardment can be performed continuously. This is considered to have achieved good surface roughness. Further, it is preferable to control the ion irradiation amount to be uniform in the x-axis direction and the y-axis direction. For this purpose, the position and direction of the ion irradiation nozzle may be controlled. In this way, a preferable surface roughness can be achieved. For example, by controlling the surface roughness in such a state and then performing a heat treatment, the medical sheet can be made more yellowish.

Examples of surface modification of PTFE are methods of introducing functional groups on the surface of the substrate and etching the surface using O ₂ or Ar gas, polymerizing organic monomers under plasma, and forming a thin film on the surface of the substrate. This is a plasma polymerization method to be formed.

  The heating step may be a step of heating the sheet at a temperature of 60 ° C. or higher and 300 ° C. or lower for 10 seconds to 1 hour. The heating temperature may be, for example, 60 ° C. or more and 150 ° C. or less, or 100 ° C. or more and 130 ° C. or less. In particular, when performing ethylene oxide gas (EOG) sterilization, the temperature may be 60 ° C. or higher and 100 ° C. or lower, and may be 65 ° C. or higher and 80 ° C. or lower. The heating temperature may be 110 ° C. or higher and 140 ° C. or lower, or 110 ° C. or higher and 130 ° C. or lower. The heating time may be appropriately adjusted according to the heating temperature, may be 10 minutes or more and 45 minutes or less, 15 minutes or more and 30 minutes or less, 20 seconds or more and 5 minutes or less, or 40 seconds or more and 2 minutes. It may be the following. After cooling the sheet that has undergone the heating process, the difference between the b1 value that is the b value of the roughened portion 3 and the b2 value that is the b value of the second surface 7 located opposite to the first surface 5 is Δb. It is preferable to heat the sheet so that Δb is 2 or more and 11 or less.

In a clean room, Gore-Tex (registered trademark), which is Gore's ePTFE, was cut into 10 cm × 10 cm to obtain an ePTFE sheet. The surface of the ePTFE sheet was not washed with an organic solvent, and an ion bombardment was applied to the ePTFE sheet using an ion implantation apparatus to modify the surface. The ion bombardment conditions were as follows.
Ion: Ar ⁺
Energy: 150 KeV
Ion density: 5 × 10 ¹⁴ ions / cm ²

During the ion bombardment, the degree of vacuum in the ion implantation apparatus was maintained at 10 ⁻⁵ atm or more and 10 ⁻⁴ atm. Further, the ion irradiation amount was adjusted so that the ion bombardment was uniform in the x-axis direction and the y-axis direction of the sheet.

  The surface-modified ePTFE sheet was heat-treated in an autoclave (120 ° C.) for 20 minutes. The ePTFE sheet was allowed to stand until heating to normal temperature after heating with an autoclave. In this way, a medical sheet was obtained.

[Reference Example 1]
A medical sheet was obtained in the same manner as in Example 1 except that heating by an autoclave was not performed (Reference Example 1).

  The surface roughness of the obtained medical sheet was measured. For the surface roughness, a Olympus 3D measurement laser microscope OLYMPUS OLS4000 was used. The obtained results are shown in Table 1.

  The color tone of the obtained medical sheet was measured. A spectral colorimeter manufactured by Konica Minolta was used for the measurement of color tone. The obtained results are shown in Table 2.

  As a result of visual observation, the portion subjected to ion bombardment was clearly yellowish compared to that of Reference Example 1, and the presence or absence of ion bombardment was clearly distinguishable.

[Example 2]
A medical sheet was obtained in the same manner as in Example 1 except that the temperature of the autoclave was changed to 130 ° C.

[Example 3]
A medical sheet was obtained in the same manner as in Example 1 except that the autoclave time was 3 minutes.

[Example 4]
A medical sheet was obtained in the same manner as in Example 1 except that a PTFE sheet was used instead of the ePTFE sheet.

[Example 5]
A medical sheet was obtained in the same manner as in Example 1 except that the roughening treatment part was partially used.

[Example 6]
A medical sheet was obtained in the same manner as in Example 1 except that sandblasting was used instead of ion implantation.

[Example 7]
A medical sheet was obtained in the same manner as in Example 1 except that plasma etching was performed instead of ion implantation.

[Example 8]
A medical sheet was obtained in the same manner as in Example 1 except that 70 ° C. EOG sterilization was performed instead of the autoclave.

[Example 9]
A medical sheet was obtained in the same manner as in Example 1 except that Porelon (registered trademark) manufactured by Sumitomo Electric was used instead of Gore-Tex (registered trademark), which is ePTFE manufactured by Gore.

  In Examples 2 to 7 and 9, the closer to that in Example 1, the more yellowish, but in Example 1, the yellowish color was the strongest and the presence or absence of treatment could be clearly understood. The sample of Example 8 was slightly yellowish compared to the sample of Reference Example 1, and the presence or absence of treatment could be grasped by careful observation. Moreover, when the same experiment was conducted by changing various ion bombardment conditions in Example 1, the same tendency as in Examples 1 to 9 and Reference Example 1 was shown.

[Comparative Example 1]
About the Example of patent 4445697 gazette, the medical sheet was created according to the conditions actually performed.
The surface of expanded polytetrafluoroethylene (ePTFE) was washed with an organic solvent. Thereafter, irradiation with an ion beam was performed at 200 KeV (Ne ⁺ , 150 keV, 5 × 10 ¹⁴ ions / cm ² ). Every time ion bombardment is performed, the degree of vacuum drops. Also, the uniformity in the direction of ion bombardment was not adjusted. The color tone of the obtained medical sheet was measured. A spectral colorimeter manufactured by Konica Minolta was used for the measurement of color tone.

  As for the surface roughness of the medical sheet obtained in Comparative Example 1, the Rz value was an average value 5 (standard deviation 0.5), and the Ra value was an average value 0.52 (standard deviation 0.05). . This sheet could not distinguish the color of the surface irradiated with the ion beam and the surface not irradiated. The average b value of the roughened portion of the sheet is considered to be a negative value.

[Example 10]
The medical sheet obtained in Comparative Example 1 was heat-treated for 20 minutes in an autoclave (120 ° C.). The ePTFE sheet was allowed to stand until the temperature reached room temperature after heating with an autoclave. In this way, a medical sheet was obtained. As a result of visual observation, the portion subjected to ion bombardment was colored so that it could be distinguished slightly from that of Comparative Example 2. The b value of this sheet was about 2 to 3.

  Artificial blood vessels (medical tubes) having inner diameters of 4 mm and 6 mm were prepared using the sheets in the above-described Examples, Reference Examples and Comparative Examples. The blood coagulation component was observed when human whole blood flowed into the created artificial blood vessel for 1, 2, 4, 8, 24, 48 hours. As a result, in Example 1, a thrombus film was formed very early, and vascular endothelial cells were established on the thrombus film, which was a good artificial blood vessel. On the other hand, the sample of Comparative Example 1 did not leak blood and functioned as an artificial blood vessel, but it took a long time for vascular endothelial cells to settle. The other examples and reference examples exhibited the performance between Example 1 and Comparative Example 1.

  The present invention can be used in the field of medical devices.

  DESCRIPTION OF SYMBOLS 1 Medical sheet, 3 Roughening part, 5 1st surface, 7 2nd surface

Claims (3)

A medical sheet (1) having a first surface (5) having a roughened portion and a second surface (7) located opposite to the first surface (5) and comprising polytetrafluoroethylene There,
The roughened portion (3) has a surface roughness Rz value of 8 or more and 14 or less, a Ra value of 0.65 or more and 1.5 or less ,
Wherein b ₁ value and a b value of roughening portion (3), the difference between the b ₂ values is b value of the second surface (7) when the [Delta] b, [Delta] b is 2 to 11 , Medical sheet.   The medical sheet according to claim 1, wherein the roughened portion (3) is a portion modified by an ion bombardment portion.   The medical sheet according to claim 1, wherein the roughened portion (3) is a part of the first surface (5).

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