WO2023157953A1 - サージカルインク、同インクの作製方法、及び同インクを用いたサージカルペン - Google Patents

サージカルインク、同インクの作製方法、及び同インクを用いたサージカルペン Download PDF

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Publication number
WO2023157953A1
WO2023157953A1 PCT/JP2023/005806 JP2023005806W WO2023157953A1 WO 2023157953 A1 WO2023157953 A1 WO 2023157953A1 JP 2023005806 W JP2023005806 W JP 2023005806W WO 2023157953 A1 WO2023157953 A1 WO 2023157953A1
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WIPO (PCT)
Prior art keywords
ink
surgical
pen
weight
water
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Ceased
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PCT/JP2023/005806
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English (en)
French (fr)
Japanese (ja)
Inventor
豊 丸岡
俊寿 豊国
森 横山
慶 大本
剛 荒殿
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Yasui Co Ltd
Mikuni Color Ltd
Mitsubishi Pencil Co Ltd
National Center for Global Health and Medicine
Original Assignee
Yasui Co Ltd
Mikuni Color Ltd
Mitsubishi Pencil Co Ltd
National Center for Global Health and Medicine
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Yasui Co Ltd, Mikuni Color Ltd, Mitsubishi Pencil Co Ltd, National Center for Global Health and Medicine filed Critical Yasui Co Ltd
Priority to JP2024501453A priority Critical patent/JPWO2023157953A1/ja
Priority to CN202380022494.0A priority patent/CN119053663A/zh
Priority to US18/834,792 priority patent/US12472766B2/en
Publication of WO2023157953A1 publication Critical patent/WO2023157953A1/ja
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B43—WRITING OR DRAWING IMPLEMENTS; BUREAU ACCESSORIES
    • B43K—IMPLEMENTS FOR WRITING OR DRAWING
    • B43K8/00—Pens with writing-points other than nibs or balls
    • B43K8/02—Pens with writing-points other than nibs or balls with writing-points comprising fibres, felt, or similar porous or capillary material
    • B43K8/026—Pens with writing-points other than nibs or balls with writing-points comprising fibres, felt, or similar porous or capillary material with writing-points comprising capillary material
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/90—Identification means for patients or instruments, e.g. tags
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B43—WRITING OR DRAWING IMPLEMENTS; BUREAU ACCESSORIES
    • B43K—IMPLEMENTS FOR WRITING OR DRAWING
    • B43K8/00—Pens with writing-points other than nibs or balls
    • B43K8/02—Pens with writing-points other than nibs or balls with writing-points comprising fibres, felt, or similar porous or capillary material
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
    • C09D11/00—Inks
    • C09D11/16—Writing inks
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
    • C09D11/00—Inks
    • C09D11/16—Writing inks
    • C09D11/17—Writing inks characterised by colouring agents

Definitions

  • the present invention relates to a biocompatible surgical ink that can be safely used in surgical operations, a method for producing the same ink, and a surgical pen using the same ink.
  • the surgical purpose is to observe the follow-up part, the excision part, and the incision position.
  • colored ink is used to mark the target site.
  • the marking work on the target site using this colored ink is done by the so-called "dip pen method" using the dye ink stored in the ink pot and a dip pen such as a bamboo skewer as a surgical pen.
  • the ink dripping from the pen tip is applied so as to draw a line or mark on the target site.
  • the pen tip is put into the ink reservoir again to replenish the ink.
  • the pen tip is always held to the target area so as not to inadvertently damage the target area. It is necessary to float slightly from the surface and not to apply too much force, which makes the marking work complicated and difficult.
  • the target site to be marked is mostly wet with tissue fluid such as blood and saliva
  • the dye ink is basically water-soluble with crystal violet as the main component.
  • the dye ink immediately diffuses into the tissue fluid and bleeds, and as a result, the ink does not stay at the target site and accurate marking cannot be performed.
  • crystal violet which is the main component of dye ink, exhibits carcinogenicity in living organisms.
  • the surgical ink according to Patent Document 1 by mixing a resin material, a volatile agent, and a coloring agent, the volatilization effect of the ink at the target site is enhanced to improve the fixability of the ink.
  • Methylrosaniline chloride that is, crystal violet, is used as a coloring agent, and safety issues remain.
  • Patent Document 2 although a pigment ink using carbon powder is used as a surgical ink, it does not guarantee sterility in accordance with "sterilization validation", and furthermore, the relationship with the pigment ink It does not disclose a surgical pen that takes into account the writing ability.
  • the pigment ink according to Patent Document 2 discloses a general autoclave sterilization process, it is not produced in consideration of a gamma-ray irradiation sterilization process that guarantees a higher level of sterility. .
  • the properties of the ink such as the viscosity of the ink and the average particle size of the pigment, would change, and there is a risk that writing problems would occur.
  • Patent Document 2 it only discloses an aspect in which pigment ink is filled into a syringe and injected into a target site, and is not an aspect as a medical device, but is sterilized by ⁇ -ray irradiation in accordance with sterilization validation.
  • the problem of deterioration due to processing is not considered, and writing convenience such as stable ejection of pigment ink and improvement of writing operation are not taken into consideration.
  • the present invention has been made in view of such problems, and is a biocompatible and writable surgical ink that can be widely marketed as a medical device that ensures safety in accordance with sterilization validation. , a method for producing the same ink, and a surgical pen with improved writing convenience.
  • the surgical ink according to the present invention has the following features.
  • a biocompatible surgical ink containing activated carbon powder and a water-soluble organic solvent comprising 8 to 10% by weight of the activated carbon powder, 5 to 7% by weight of a water-soluble polymer, and sodium hydroxide. 60 to 80 parts by weight of a dispersion containing 0.01 to 1.00% by weight and water as the remainder; pH 4-11, average particle size 150-310 nm, viscosity 2.0-8.0 mPa ⁇ s.
  • the water-soluble polymer is polyvinylpyrrolidone
  • the water-soluble organic solvent is propylene glycol.
  • a surgical pen includes a cylindrical shaft portion having a storage portion for surgical ink, and a pen tip portion for ejecting the ink at the tip of the shaft portion, and has the following points. It has characteristics. (3)
  • the pen tip is made of synthetic resin and has a bending strength of 1.0 N or more after ⁇ -ray irradiation of 25 kGy to 70 kGy.
  • the surgical ink is the ink according to (1) or (2).
  • the surgical ink is stored in the storage part in a state in which the batting part is impregnated, and the batting part is communicated with the proximal end of the pen tip at the tip.
  • the shaft portion has a holder for writing operation at the tail end portion, and the holder has a bulging portion that bulges outward from the tail end of the shaft portion.
  • the holder has a second bulging portion that bulges out to cover the outer peripheral surface of the rear half of the shaft portion, and the bulging portion and the second bulging portion have a constricted shape.
  • a detachable cap body is provided at the tip of the shaft part, the shaft part has a pen tip receiving part formed at the tip part for attaching and fixing the pen tip part, The cap body encloses the pen tip portion when attached to the shaft portion, and has a pressure contact surface portion on the inner peripheral surface portion that is pressed against and engages with the outer peripheral wall portion of the pen tip receiving portion.
  • the cap body is composed of an outer cap and an inner cap disposed inside the outer cap, and the inner cap is a bottomed cylindrical cap body portion having the crimping surface portion on the inner peripheral surface portion. and a leaf spring portion that has a certain gap between itself and the outer peripheral surface of the cap body portion and that extends outwardly from the opening of the cap body portion by bending the leaf spring portion. It is inserted into the outer cap so that the opening direction is the same as that of the outer cap, and is crimped and fixed to the inner peripheral surface of the outer cap via the plate spring portion.
  • a sterilized ink-forming step for obtaining a surgical ink having a pH of 4 to 11, an average particle size of 150 to 310 nm, and a viscosity of 2.0 to 8.0 mPa s by subjecting the ink composition to ⁇ -ray irradiation of 25 kGy to 70 kGy.
  • a method for producing a surgical ink characterized by the following is also provided.
  • the surgical ink of the present invention is a biocompatible surgical ink containing activated carbon powder and a water-soluble organic solvent, wherein 8 to 10% by weight of the activated carbon powder and 5 to 7 water-soluble polymers 60 to 80 parts by weight of a dispersion containing 0.01 to 1.00% by weight of sodium hydroxide, and water as the remainder; and 5 to 25 parts by weight of the water-soluble organic solvent.
  • pH 4-11 average particle size 150-310 nm, and viscosity 2.0-8.0 mPa s after gamma-ray irradiation of 25 kGy to 70 kGy. It is possible to improve the efficiency of the marking work.
  • the properties of the ink such as the stability of the ink over time and the dispersibility of the pigment powder, can be stabilized. Even if there is careless drug residue, adverse effects on the body such as toxicity can be suppressed as much as possible.
  • the water-soluble polymer is polyvinylpyrrolidone and the water-soluble organic solvent is propylene glycol, it not only exhibits biocompatibility but also exhibits good adhesion to the target site in a wet state. Furthermore, there is an effect that the dispersibility of the activated carbon powder can be improved and a good ink can be produced.
  • the surgical pen is a surgical pen having radiation resistance, and includes a cylindrical shaft portion having a storage portion for surgical ink, and the ink at the tip of the shaft portion. and a pen tip that ejects, and the pen tip is made of synthetic resin and has a bending strength of 1.0 N or more after ⁇ -ray irradiation of 25 kGy to 70 kGy.
  • the surgical ink stored inside the body can be stably discharged, and even if the pen tip is directly slid on the target site such as soft tissue or organ for writing operation, the target site will not be careless. It will not damage the product. Therefore, there is an effect that correct marking can be easily performed and writing convenience can be improved.
  • the surgical ink is the ink according to claim 1 or claim 2, it stabilizes the ejection and outflow properties of the ink even after the ⁇ -ray irradiation sterilization treatment, and it is in a wet state during writing operations. There is an effect that writing can be performed with good fixability on the surface of the living body.
  • the surgical ink is stored in the storage part in a state in which the batting part is impregnated, and the batting part communicates with the rear end part of the pen tip, it will not be affected by changes in the external environment such as atmospheric pressure and temperature. Along with this, it is possible to prevent the ink from accidentally leaking out of the shaft body, and there is an effect that the temporal stability of the surgical pen can be improved.
  • the holder can be It is possible to stably perform the pointing and writing operation by pinching the tail end of the pen with fingers and placing the tip of the pen on the target site on the surface of the living body. This has the effect of reducing the risk of damage without applying unnecessary writing pressure stress to the surface of the living body, as compared with the writing operation.
  • the holder has a second bulging portion that bulges out to cover the outer peripheral surface of the rear half of the shaft portion, and the bulging portion and the second bulging portion together have a constricted shape. 3, the constricted portion between the bulging portion and the second bulging portion is used as the gripping position, and there is an effect that the pointing and writing operation with the gripping position as the fulcrum can be further stabilized.
  • a detachable cap body is provided at the tip of the shaft part, the shaft part has a pen tip receiving part formed at the tip part for attaching and fixing the pen tip part, and the cap The body encloses the pen tip portion in a state of being attached to the shaft portion, and has a crimping surface portion on the inner peripheral surface portion that is pressed against and engages with the outer peripheral wall portion of the pen tip receiving portion.
  • the crimping surface portion engages with the pen tip receiving portion of the shaft portion so that the volume of the internal space of the pen tip portion closed and blocked from the outside can be reduced as much as possible.
  • the cap body is composed of an outer cap and an inner cap disposed inside the outer cap
  • the inner cap includes a bottomed cylindrical cap main body portion having the crimping surface portion on an inner peripheral surface portion. and a leaf spring portion which has a certain gap from the outer peripheral surface of the cap body portion and which is bent and extends outwardly from the opening of the cap body portion, wherein the outer cap is attached to the outer cap.
  • FIG. 1A and 1B are an external side view and an exploded perspective view showing the configuration of a surgical pen according to a first embodiment
  • FIG. 1A and 1B are a side sectional view and a partially enlarged sectional view showing the configuration of a surgical pen according to a first embodiment
  • FIG. 2 is a side sectional view and a partially enlarged sectional view showing the configuration of the surgical pen with the cap body according to the first embodiment attached.
  • FIG. 5 is an external side view showing the configuration of a surgical pen according to a second embodiment
  • FIG. 2 is a diagram showing the abdominal skin of rats immediately after writing with the surgical pen a and a comparative writing example.
  • FIG. 3 is a diagram showing the skull of a rat immediately after writing with the surgical pen a and a comparative writing example.
  • FIG. 3 is a diagram showing the thigh muscles of rats immediately after writing with the surgical pen a and a comparative writing example.
  • FIG. 10 is a diagram showing the abdominal skin of rats after 7 days of writing with the surgical pen a and Comparative Writing Example.
  • FIG. 10 shows the abdominal endothelium of rats after 7 days of writing with Surgical Pen a and Comparative Writing Example.
  • FIG. 10 is a diagram showing the thigh muscle of a rat after 14 days of writing with surgical pen a.
  • the surgical ink according to the present invention (hereinafter simply referred to as ink) is a biocompatible surgical ink containing activated carbon powder and a water-soluble organic solvent, wherein 8 to 10% by weight of the activated carbon powder and highly water-soluble 60 to 80 parts by weight of a dispersion containing 5 to 7% by weight of molecules, 0.01 to 1.00% by weight of sodium hydroxide, and water as the remainder; 5 to 25 parts by weight of the water-soluble organic solvent; and having a pH of 4 to 11, an average particle size of 150 to 310 nm, and a viscosity of 2.0 to 8.0 mPa ⁇ s after ⁇ -ray irradiation of 25 kGy to 70 kGy.
  • a surgical pen having radiation resistance comprises a cylindrical shaft portion having a storage portion for surgical ink, and a pen tip portion for ejecting the ink at the tip of the shaft portion.
  • the pen tip is made of a synthetic resin and has a bending strength of 1.0 N or more after 25 kGy to 70 kGy of ⁇ -ray irradiation.
  • ⁇ -ray irradiation sterilization can be performed at room temperature and is permeable. Even if there is a sealed part, the item to be sterilized can be sterilized while it is still wrapped, ensuring high sterility, making it ideal for medical devices on the market.
  • ⁇ -ray irradiation sterilization is excellent in that it can be applied to single-use medical devices (disposable products), which are mainstream in terms of hygiene management, and is applied to most disposable products on the market today.
  • the surgical ink according to the present invention and the surgical pen using it are biocompatible in order to quickly achieve the purpose of the medical industry as well as safety according to new sterilization validation standards that have changed in view of the current situation. It is a newly developed epoch-making invention that improves the visibility of the operative field of the target site on the surface of the living body by improving the writing performance and writing convenience.
  • Composition of surgical ink> ⁇ 2.
  • Method for making surgical ink> ⁇ 3.
  • This ink is a biocompatible ink containing activated carbon powder and a water-soluble organic solvent. is suppressed as much as possible while maintaining stable writability.
  • the dispersion liquid (A) of the ink is composed of activated carbon powder (a), water-soluble polymer (b), sodium hydroxide as a basic substance (c), and water (d) (for example, See Table 1 to be described later), and serves as a base material for inks that improve the biocompatibility, dispersibility, stability over time, writability, etc. of the ink after ⁇ -ray irradiation of 25 kGy to 70 kGy.
  • Activated carbon powder (a) is used as a pigment in the present ink, and by adopting powder that has been pulverized through a pulverization process using a pulverizer or the like, the color of the ink is darkened and good coloring properties are obtained. and the dispersibility in the dispersion becomes good.
  • the physical properties of the activated carbon powder (a) used in this ink are not particularly limited, but the average particle size is 5-70 ⁇ m, the specific surface area is 1000-2000 m 2 /g, the total pore volume is 0.5-3.0 ml/g, the average pore diameter is It is preferably between 2 and 10 nm. Further, the activated carbon powder (a) of the present ink preferably has a pH of 4.5 to 7.5 and an iron content of 0.01% by weight or less.
  • the composition of activated carbon powder (a) conforms to food additive standards as follows: chloride (Cl) 0.5% or less, sulfate (SO4) 0.5% or less, zinc 0.1% or less, arsenic (As2O3) 4.0 ⁇ g/g or less. Adopt the one that matches. As a result, the physical properties of the ink are prevented from being adversely affected without exhibiting toxicity to the human body.
  • Various parameters of the activated carbon powder (a) described above are measured according to the methods specified in JIS K 1474-91.
  • the content of the activated carbon powder (a) in the dispersion (A) is 8 to 10 parts by weight/100 parts by weight of the dispersion. That is, the concentration of the activated carbon powder (a) in the dispersion is 8-10% by weight. If the amount is less than 8% by weight, the color density of the finally prepared ink may be low, and the marking performance on the writing object may be insufficient. On the other hand, if it exceeds 10% by weight, aggregation of the activated carbon powder occurs in the finally prepared ink, which may deteriorate the stability of the ink over time and the ejection property from the marking pen.
  • the amount of activated carbon powder (a) in the ink is 0.1% to 10% by weight, preferably 1% to 5% by weight, to ensure the color development of the ink. If it is less than 0.1% by weight, the concentration is low, and if it exceeds 10% by weight, the aggregation reaction is promoted.
  • Water-soluble polymer (b) The water-soluble polymer (b) of this ink is used as a dispersant that can stabilize the activated carbon powder (a) in the ink as a pigment in a finely dispersed state.
  • a material that exhibits adhesion to the surface of a living body and biocompatibility under certain conditions is used.
  • water-soluble polymer (b) examples include non-polar polymers such as hydroxypropyl cellulose (hereinafter also referred to as HPC), hydroxypropyl methyl cellulose (hereinafter also referred to as HPMC), polyvinylpyrrolidone (hereinafter also referred to as PVP). is preferred.
  • HPC hydroxypropyl cellulose
  • HPMC hydroxypropyl methyl cellulose
  • PVP polyvinylpyrrolidone
  • the water-soluble polymer (b) preferably has a viscosity-average molecular weight of 1,000 to 220,000.
  • the measurement of the viscosity-average molecular weight of the water-soluble polymer (b) is basically carried out according to Kobunshi Ronbun vol. 38, No. 7, pp. 457-463 (July, 1981) for molecular weight determination. Specifically, the following procedures (1) and (2) are followed.
  • (1) Precipitation purification is performed by adding the water-soluble polymer (b) sample to excess acetone. After repeating this operation twice, it is dried under reduced pressure until the smell of acetone disappears.
  • the content of the water-soluble polymer (b) in the dispersion (A) is 5-7 parts by weight/100 parts by weight of the dispersion. That is, the concentration of the water-soluble polymer (b) in the dispersion is 5-7% by weight. If the amount is less than 5% by weight, it becomes difficult to disperse the activated carbon powder (a) in the finally prepared ink, and the diameter of the dispersed particles increases, which may cause clogging in the surgical pen. On the other hand, if it exceeds 7% by weight, the viscosity of the finally prepared ink becomes too high, and there is a possibility that the ejection property from the surgical pen may deteriorate.
  • the blending amount of the water-soluble polymer (b) is 20-200 parts by weight, preferably 30-150 parts by weight, per 100 parts by weight of the activated carbon powder (a). If it is less than 20% by weight, the dispersibility of the carbon powder deteriorates, while if it exceeds 200 parts by weight, the ink jetting property deteriorates.
  • a basic substance (c) can be present in the ink in order to adjust the pH within a predetermined range.
  • the activated carbon powder (a) tends to cause the ink to exhibit acidity. Therefore, if neutralization with the basic substance (c) is not performed, depending on the site, the ink may be highly irritating to the body.
  • the suitable pH range of the living body varies depending on the site, but in the present invention, by appropriately adjusting the amount of the basic substance added, the pH can be adjusted to the appropriate range according to the site to be marked, and the irritation can be reduced. can.
  • the basic substance (c) of the present invention is not particularly limited as long as it is biocompatible among substances exhibiting basicity according to the definition of Arrhenius. Furthermore, basic substances (c) such as sodium carbonate, sodium hydroxide, potassium carbonate, sodium hydrogen carbonate, etc., which are approved for use as food additives, are preferred.
  • sodium hydroxide is most suitable as the basic substance (c).
  • the dispersed state of particles in the ink is stabilized even for difficult-to-disperse pigments such as activated carbon. It is possible to prevent solidification, grain increase, viscosity increase, and the like.
  • the mechanism by which sodium hydroxide contributes to the stabilization of the dispersed state is not clear, it is believed that the effect of stabilizing the surface activity of the carbon material particles and preventing aggregation is exhibited. Furthermore, it is easily degraded in vivo and can be safely used on the surfaces of tissues and organs such as skin, bones and organs. In addition, it is possible to stabilize the viscosity of the ink and suppress the reaggregation of the pigment powder, thereby improving the dispersibility.
  • the basic substance (c) is preferably contained in an amount of 0.01 to 1.00 parts by weight, more preferably 0.05 to 0.50 parts by weight, based on 100 parts by weight of the ink. If the amount of the basic substance is less than 0.01 parts by weight, the change in pH is insufficient, and when sodium hydroxide is used, the effect of stabilizing the dispersed state cannot be fully exhibited. If the amount added is more than 1.00 parts by weight, the pH may rise beyond the range appropriate for living organisms, resulting in strong irritation.
  • Water (d) is used as a dispersion medium when preparing dispersion liquid (A). ink.
  • Water (d) is preferably distilled water, water for injection, or the like, which is appropriately quality-controlled for medical use.
  • the content of water (d) in dispersion (A) is preferably 70 to 90 parts by weight/100 parts by weight of dispersion A. If it is less than 70 parts by weight, the concentration of the other components will be relatively high, and if it is more than 90 parts by weight, the concentrations of the other components will be relatively low. There is a possibility that the dispersion liquid A may not function properly as the base material of the ink.
  • this ink is mainly composed of water with a final water content of 50% by weight or more, preferably 60% by weight or more. That is, in the present ink, liquid components other than the specific water-soluble organic solvent (B) described below are substantially water. As a result, not only biocompatibility can be ensured, but also the degree of denaturation such as cross-linking of the water-soluble polymer in the ink can be suppressed as much as possible even after ⁇ -ray irradiation.
  • Water-soluble organic solvent (B) The water-soluble organic solvent (B) is used to improve the viscosity of the ink after ⁇ -ray irradiation and the fixability on the surface of the living body, and is not particularly limited as long as it exhibits a specific viscosity and biocompatibility. .
  • Water-soluble organic solvents (B) include methanol, ethanol, n-propanol, isopropanol, n-butanol, iso-butanol, t-butanol, trimethylolpropane, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, monoethylene glycol. , diethylene glycol, triethylene glycol, and polyethylene glycol.
  • ethanol, isopropanol, glycerin, and polyethylene glycol hereinafter also referred to as food additives.
  • the water-soluble organic solvent (B) in the ink should be 5 to 25 parts by weight per 100 parts by weight of the ink to improve the fixability of the ink on the surface of the body after ⁇ -ray irradiation and the ejection from the surgical pen. . If the amount is less than 5 parts by weight, the ink becomes less viscous and may cause accidental ink leakage from the surgical pen. On the other hand, when the amount is more than 25 parts by weight, the viscosity becomes too large, and there is a possibility that the ejection property from the surgical pen may be deteriorated.
  • the water-soluble organic solvent (B) is not necessarily an essential component of the ink composition, but is selectively added according to the type of surgical pen described below. Therefore, it is possible to make the water-soluble organic solvent (B) less irritant by making it ethanol-free, in which ethanol is not added.
  • the surface tension modifier (C) is a component that functions to improve ejection from the pen core and to adjust the surface tension.
  • anionic, nonionic, silicone, fluorine-based surfactants and water-soluble organic solvents such as ethanol and isopropanol
  • anionic surfactants include alkylbenzenesulfonates, higher alcohol sulfates, higher fatty acid salts, higher alkyldicarboxylates, alkylnaphthalenesulfonates, alkylsulfosuccinates, naphthalenesulfonic acid formalin condensate salts
  • examples include polyoxyethylene alkyl ether sulfates and polyoxyethylene alkyl phosphates.
  • Nonionic surfactants include polyoxyethylene alkyl ethers, polyoxyethylene alkylphenyl ethers, fatty acid monoglycerides, sorbitan fatty acid esters, sucrose fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene fatty acid esters, glycerin fatty acid esters, Polyoxyethylene-added acetylene glycols may be mentioned.
  • the surgical ink according to the present invention is produced by mixing the components described above at a predetermined mixing ratio. That is, the present ink is prepared by mixing 60 to 80 parts by weight of the dispersion liquid (A) having the composition described above and 5 to 25 parts by weight of the water-soluble organic solvent (B) (for example, see Table 3 below).
  • the dispersion liquid (A) is less than 60 parts by weight or the water-soluble organic solvent (B) is less than 5 parts by weight, the dispersibility of the activated carbon powder (a) and the adhesion (fixing property) at the target site are poor. It may get worse.
  • the dispersion liquid (A) exceeds 80 parts by weight or the water-soluble organic solvent (B) exceeds 25 parts by weight, the viscosity becomes too high, causing clogging at the tip of the surgical pen. There is a risk that the continuous and stable writing convenience will be deteriorated, such as making ejection difficult.
  • the active carbon powder (a), the water-soluble polymer (b), the sodium hydroxide (c), the water (d), and the water-soluble organic solvent (B), which are components of the dispersion (A), are mixed and stirred. It is also possible to In preparing the ink, it is preferable to prepare the dispersion liquid (A) and then add the water-soluble organic solvent (B) and stir the mixture, so that the activated carbon powder (a) can be well dispersed in the ink.
  • the present ink preparation method includes a dispersion liquid preparation step S1 for obtaining a dispersion liquid (A) and an ink composition preparation step S2 for obtaining an ink composition.
  • a dispersion liquid preparation step S1 8 to 10 parts by weight of activated carbon powder (a), 5 to 7 parts by weight of water-soluble polymer (b), 0.01 to 1.00 parts by weight of basic substance (c), and 70 parts by weight of water as the remainder. 90 parts by weight are mixed and stirred to prepare a dispersion (A).
  • the active carbon powder (a) can be stably dispersed in water by using a dispersing machine (for example, paint shaker, roll mill, ball mill, sand mill, jet mill, etc.) for stirring.
  • a refinement enhancement step S0 for enhancing refinement of the activated carbon powder with a sand mill or the like may be included. That is, it is possible to obtain an activated carbon powder whose average particle size and average pore diameter are adjusted by fine processing time of a sand mill or the like.
  • the ink composition preparation step S2 60 to 80 parts by weight of the dispersion (A) obtained in the dispersion preparation step S1, 5 to 25 parts by weight of the water-soluble organic solvent (B),
  • the tension modifier (C) is added to make the total weight 100 parts by weight, and mixed and stirred to prepare an ink composition.
  • the amount of the surface tension modifier (C) to be added is 5 to 15 parts by weight.
  • a coarse particle removal step of removing coarse particles of the activated carbon powder (a) by filtering with a filter or the like or classifying with a centrifuge. S3 may be interposed. Furthermore, after the ink composition preparation step S2, an ink filling step S5 of filling the surgical pen of the present invention with the obtained ink composition can be carried out.
  • the method for producing this ink includes a sterilized ink production step S4 that is irradiated with ⁇ -rays to ensure sterility.
  • the sterilized ink forming step S4 the ink composition that has undergone the ink composition preparation step S2, the coarse particle removal step S3, and the ink filling step S5 is subjected to ⁇ -ray irradiation of 25 kGy to 70 kGy, and finally the surgical ink according to the present invention. It is a process of obtaining Note that the conditions for ⁇ -ray irradiation and the like will be described later in ⁇ 5. ⁇ -ray irradiation conditions>.
  • the ink composition undergoes the sterile ink conversion step S4 to ensure sterility and become a surgical ink that has good writability and dispersibility, and can be safely marketed as a specific medical device.
  • the sterilized ink forming step S4 is performed integrally with the surgical pen.
  • the sterilized ink forming step S4 is performed after the ink composition is prepared by the ink composition preparing step S2.
  • the ink composition obtained in the ink composition preparation step S2 may be stored in a ⁇ -ray-resistant container such as a plastic container and subjected to ⁇ -ray irradiation, or may be filled in an arbitrary pen and used as a surgical pen. good.
  • the ink composition is basically a surgical ink whose sterility is guaranteed as a medical device by being subjected to a ⁇ -ray irradiation treatment while being impregnated in the batting portion 3 of the surgical pen A1 and stored in the storage portion 10. becomes (see FIG. 1(b), which will be described later).
  • the present ink is characterized by pH of 4 to 11, average particle diameter of 150 to 310 nm, and viscosity of 2.0 to 8.0 mPa ⁇ s after 25 kGy to 70 kGy of ⁇ -ray irradiation.
  • Methods for measuring various parameters indicating physical properties before and after ⁇ -ray irradiation are as follows.
  • ⁇ Viscosity measurement Conditioning Undiluted solution Measuring equipment: Conical plate type rotational viscometer (“TVE-20L model” manufactured by Toki Sangyo Co., Ltd.) Measurement condition: 50rpm Measurement temperature: 25°C ⁇ pH measurement Conditioning: Undiluted solution Measuring equipment: pH measuring instrument ("MH-41X type” manufactured by Toa DKK Co., Ltd.) Measurement temperature: 25°C ⁇ Average particle size measurement Conditioning: Dilute the undiluted solution with deionized water so that it falls within the specified measurement concentration range. Measuring instrument: Dynamic Light Scattering Particle Size Distribution Analyzer (NIKKISO: Microlracwave-EX150) Measurement time: 120 seconds
  • the viscosity change rate before and after ⁇ -ray irradiation is about 1.0% to 10.0%.
  • the pH is 8.7-8.8 for the ink composition before ⁇ -ray irradiation and 4-11 for the ink after ⁇ -ray irradiation to maintain a stable pH.
  • the average particle size of the ink composition before ⁇ -ray irradiation is 240 to 285 nm, and the ink after ⁇ -ray irradiation is 150 to 310 nm, and maintains stable dispersibility.
  • the ink configured as described above can be stored in an ink pot as in the conventional art and can be safely used for so-called "dip pen type” marking work together with a dip pen such as a bamboo comb and bamboo skewer. make good Furthermore, by using the present ink in the surgical pen of the present invention, it is possible to improve the convenience of writing by improving the ejection property.
  • FIG. 1 is an external side view and an exploded perspective view showing the configuration of the surgical pen according to this embodiment
  • FIGS. 2(a) and 2(b) show the configuration of the surgical pen with the cap body removed according to this embodiment.
  • FIG. 2C is a side sectional view showing the configuration of the cap body according to the present embodiment
  • FIG. 3 is a surgical pen with the cap body according to the present embodiment attached. It is a side cross-sectional view and a partially enlarged cross-sectional view showing the configuration.
  • the surgical pen A1 has radiation resistance and is configured to be able to write by containing the surgical ink described above. As shown in FIGS. 1(a) and 1(b), the surgical pen A1 has a tubular shaft portion 1 having a storage portion 10 for surgical ink, and a distal end of the shaft portion 1. and a pen tip portion 2 for ejecting ink.
  • the material of the Surgical Pen A1 should be a radiation-resistant material that does not denature when exposed to ⁇ -rays at the specified sterilization dose of 25 kGy to 70 kGy and does not reduce its mechanical strength and make it vulnerable at an early stage. It is not particularly limited.
  • a radiation-resistant material may be, for example, a metal material or a resin material. By using a resin material, the mass productivity and economic efficiency of the surgical pen are improved.
  • resin materials include polypropylene (PP), high-density polyethylene (HDPE), polyethylene terephthalate (PET), polyetheretherketone (PEEK), and ABS.
  • Metal materials include copper, iron, aluminum, and the like.
  • a radiation-resistant material such as stainless steel can be appropriately selected and employed for each constituent member of the surgical pen A1.
  • the shaft portion 1 has an elongated cylindrical shape, and as shown in FIGS.
  • a pen tip receiving portion 12 for attaching and fixing the pen tip portion 2 is formed in a tapered shape with an outer and inner diameter smaller than that of the body portion 11 .
  • the shaft part 1 of this embodiment is made of PP.
  • the storage portion 10 is a space portion that stores a certain amount of ink, and in the present embodiment stores the ink indirectly through the filling portion 3 .
  • the surgical pen A1 is stored in the storage part 10 in a state in which the filling part 3 is impregnated with surgical ink, and the filling part 3 is connected to the base end of the pen tip part 2 at the tip, so that it is configured as a so-called filling type pen. ing.
  • the surgical pen A1 may be configured as a direct liquid type pen by directly storing ink in the storage section 10 .
  • the filling portion 3 is in the shape of a cylindrical bar having approximately the same length as the trunk portion 11 of the shaft portion 1, and is composed of a cylindrical outer skin 30 and a resin-fiber-like cotton body 31 evenly accommodated in the entire inner portion of the outer skin 30.
  • the cotton main body 31 can be impregnated with ink and held.
  • the outer skin 30 is made of PP
  • the cotton main body 31 is made of PET.
  • the pen tip receiving portion 12 includes a tip support portion 120 having a smaller diameter than the barrel portion 11 and a tip support portion 120 having a smaller diameter than the tip support portion 120 toward the tip direction. and a leading end fitting portion 121 having a reduced diameter on the side.
  • the tip fitting portion 121 is a portion where the pen tip portion 2 to be described later is press-fitted and fixed. It is formed on the abutting engagement surface.
  • a cap stopper stepped portion 13 is formed on the boundary between the body portion 11 and the tip support portion 120 of the pen tip receiving portion 12 so as to face and abut against the opening edge portion of the cap body 4 described later.
  • a flange portion 14 for hooking a cap body 4 is formed on the peripheral wall of the tip support portion 120 of the pen tip receiving portion 12 so as to protrude radially outward.
  • a tail plug 5 for closing the tail end side opening 1a of the shaft portion 1 is provided at the tail end portion of the shaft portion 1.
  • the tail plug 5 has a cylindrical shape with a bottom, and as shown in FIG. A flange portion 50 in contact with the flange portion 50, an insertion portion 51 that is inserted into the shaft portion 1 on the distal end side of the shaft portion 1 in the axial direction with the flange portion 50 as a boundary, and a tail portion of the shaft portion 1 in the axial direction. A fitting protrusion 52 protruding outward from the end side and fitted to the cap body 4 is provided. It should be noted that the tail plug 5 of this embodiment is made of PP like the shaft portion 1 .
  • the engaging means includes an engaging recess provided on the outer peripheral surface of the fitting portion 51 of the tail plug 5 and an engaging protrusion provided on the inner peripheral surface of the shaft portion 1 corresponding to the engaging recess. , consists of
  • the tail plug 5 having such a configuration functions as a weight because it is relatively heavier than other members. That is, the surgical pen A1 is configured such that the tail plug 5 eccentrically shifts the center of gravity from the center in the axial direction to the tail end side.
  • the tail end of the pen is picked up by each fingertip, such as the belly of the thumb and index finger, or the belly of the thumb and middle finger. It is possible to stably perform pointing and writing operations by placing the device on the target site on the surface of the living body.
  • the pen tip portion 2 comprises a core 20 made of a flexible resin fiber bundle, and a front half halfway in the axial direction of the core 20 with the tip portion of the core 20 exposed. and a tip 22 that exposes the front end of the pipe 21 and covers the middle part of the front half in the axial direction of the core 20 together with the pipe 21 .
  • the core 20 is composed of fiber bundles in which fibers of polyethylene terephthalate (PET) or polyetheretherketone (PEEK) as a resin material are bound together with urethane as a binder while providing gaps between them.
  • PET polyethylene terephthalate
  • PEEK polyetheretherketone
  • the pen tip 2 (core 20) is made of a fiber bundle with a porosity of 52-60%. If the porosity of the center core of the nib is less than 52%, the ejection performance of the ink filled in the storage section 10 may be lowered, and the writing performance may be deteriorated. On the other hand, if the porosity exceeds 60%, ink may leak when the pen is not in use.
  • the tip of the core 20 is a pen tip main body 20a that contacts the surface of the living body and allows ink to flow out, and is configured to allow sliding writing according to the writing direction and writing angle.
  • the pen tip main body 20a is formed as an exposed portion of the core 20 on the tip side of the pipe 21 fitted and fixed.
  • the pipe 21 is externally fitted and fixed to the base end side of the pen tip main body 20a, and the tip strength of the pen tip main body 20a is improved as much as possible.
  • the pipe 21 of this embodiment is made of stainless steel (SUS).
  • the shape of the core 20 of this embodiment is a rod-like body, and the tip surface of the pen tip main body 20a corresponding to writing is formed into a hemispherical surface, so that an inadvertent sliding frictional force is generated during sliding writing according to the writing direction and writing angle. It is configured so that it does not occur.
  • the pen tip main body 20a may be formed as a fibrillated bundle-like brush part in which the fibers are not bound and each has a free end.
  • the surgical pen A can be used as a brush-type pen, and it is possible to reduce the sliding friction force on the surface of the living body during the writing operation and to improve the ejection property of the ink.
  • the core 20 may be a molded core formed by extrusion molding with a space communicated inside instead of a fiber bundle core.
  • the shape of the pen tip main body 20a can be a so-called chisel shape in which the tip is a flat surface slanted with respect to the center of the pen shaft and the tip is sharpened in order to allow selection of the drawing line width.
  • the pen tip 2 is configured to have a bending strength of 1.0 N or more after ⁇ -ray irradiation of 25 kGy to 70 kGy. Furthermore, it is preferable that the bending strength of the pen tip portion 2 decreases by less than 10% before and after sterilization by ⁇ -ray irradiation.
  • the pen tip main body 20a of the core 20 is prevented from being accidentally bent and plastically deformed or broken when pressed against a writing object.
  • the outer diameter of the pen tip main body 20a can be appropriately determined according to the desired drawing line width. This makes it easier to mark the target site on the surface of the living body.
  • the tip 22 is press-fitted into the tip fitting portion 121 of the pen tip receiving portion 12 at the tip of the shaft portion 1 from the tip side and fixed to the inside, so that the pen tip portion 2 can be integrally fixed to the shaft portion 1. .
  • the tip 22 is a mushroom-shaped or substantially spindle-shaped thin cylinder, and has a cylindrical press-fitting portion 220 extending parallel to the axial direction on the base end side, and a radially bulging portion more than the press-fitting portion 220 on the distal end side. and an exterior portion 221 that Note that the chip 22 of this embodiment is made of high density polyethylene (HDPE).
  • HDPE high density polyethylene
  • the press-fit portion 220 is a portion corresponding to press-fitting into the tip fitting portion 121 of the pen tip receiving portion 12, and the pen tip portion is inserted into the pen tip receiving portion 12. 2 is attached, it is pressed and fixed by the tip fitting portion 121 .
  • the exterior part 221 has a truncated cone shape whose diameter gradually decreases from the base end side to the tip end side.
  • the surface is formed to be a tapered surface connected to the peripheral wall of the tip fitting portion 121 of the pen tip receiving portion 12 and inclined toward the tip side.
  • a step portion between the press-fit portion 220 and the exterior portion 221, that is, the rear end surface of the exterior portion 221, is formed into a flat surface perpendicular to the axial direction. , and a contact surface portion that comes into surface contact with the opening end face of the pen tip receiving portion 12 (tip fitting portion 121). That is, the pen tip portion 2 is press-fitted and fixed to the shaft portion 1 via the pen tip receiving portion 12 and has a contact surface portion that comes into surface contact with the opening end face of the pen tip receiving portion 12 .
  • the base end of the core 20 is a batting inserting portion 20b formed to have a substantially sharp tip toward the base end side.
  • the batting inserting portion 20b is inserted so as to face the batting portion 3 along the axis of the batting portion 3, and sucks the ink impregnated in the batting portion 3 so that it can flow to the tip side.
  • the ink impregnated into the batting portion 3 is the same as described in ⁇ 2.
  • Properties of Surgical Ink> the ink can be stably ejected and discharged after gamma-ray irradiation sterilization, and the fixability on the wet surface of the living body can be improved.
  • the surgical pen A1 has a detachable cap body 4 at the distal end of the shaft part 1, as shown in FIGS. 2(c), 3(a) and 3(b).
  • the cap body 4 is configured to cover the pen tip portion 2 and prevent the volatilization of the surgical ink when attached to the shaft portion 1 .
  • the cap body 4 encloses the pen tip portion 2 in a state where it is attached to the shaft portion 1, and the inner peripheral surface portion is crimped to the outer peripheral wall portion of the pen tip receiving portion 12 to correspond to engagement.
  • the volatilization prevention means is comprised.
  • the cap body 4 includes a bottomed cylindrical outer cap 41 and a bottomed cylindrical inner cap 42 that is inserted into the outer cap 41 and arranged in the center in the axial direction. And, it has a double tube structure. Also, the cap body 4 has an inner cylindrical hole formed by two caps 41 and 42 along the outer shape of the pen tip portion 2 .
  • the inner cap 42 has a bottomed cylindrical cap body portion 420 having the crimping surface portion 43 on its inner peripheral surface and a certain gap between the outer peripheral surface of the cap body portion 420 and the gap from the opening of the cap body portion 420. and a plate spring portion 421 that bends and extends outward.
  • the plate spring portion 421 has a cylindrical shape larger than the cap body portion 420 and covers the outside of the cap body portion 420 . That is, the inner cap 42 has a double tube structure with an inner cap body portion 420 and an outer leaf spring portion 421 .
  • the inner cap 42 is inserted into the outer cap 41 so that the opening direction of the outer cap 41 is the same as that of the outer cap 41 , and is crimped and fixed to the inner peripheral surface of the outer cap 41 via the plate spring portion 421 .
  • the inner peripheral wall of the outer cap 41 is formed along the outer shape of the tip support portion 120 of the shaft portion 1, and the inner peripheral wall portion is formed so as to be crimped to the outer peripheral surface of the tip support portion 120.
  • the inner peripheral wall portion on the opening side of the outer cap 41 is configured as a second pressure-bonding surface portion 44 that is pressure-bonded to the flange portion 14 of the tip support portion 120 of the pen tip receiving portion 12 .
  • a thick wall portion is formed on the inner bottom side of the outer cap 41 by protruding the peripheral wall inward toward the center of the shaft, so that the outer end surface of the inner cap 42 to be inserted into the outer cap 41 is increased. Abutting stepped portion 410 is formed.
  • the inner cap 42 has an inner peripheral wall of the cap main body 420 formed along the outer shape of the tip fitting part 121 of the shaft part 1 and the pen tip part 2 at the tip thereof, and can be crimped to the outer peripheral surface of the tip fitting part 121. is formed in That is, the inner peripheral wall portion of the cap main body portion 420 is formed as a crimping surface portion 43 corresponding to the outer wall surface portion of the tip fitting portion 121 of the pen tip receiving portion 12 by crimping.
  • the inner peripheral wall portion on the tip side of the crimping surface portion 43 is formed in a facing surface portion that faces parallel to the outer peripheral surface of the pen tip portion 2 and has a constant minimal gap therebetween.
  • the exposed portion of the pen tip portion 2 from the shaft portion 1 is the cap body portion of the inner cap 42 when the cap body 4 of the shaft portion 1 is attached.
  • 420 is housed close to the inner wall.
  • the pressure-bonding surface portion 43 formed on the inner cap 42 and the second pressure-bonding surface portion 44 formed on the outer cap 41 block and block the communication path between the pen tip portion 2 in the cap body and the outside in two stages to improve sealing performance. While improving it as much as possible, the gap between the pen tip portion 2 and the inner wall of the cap body 4 is made as small as possible to make the ink diffusion space as small as possible, thereby making it possible to prevent volatilization of the ink.
  • the cap body 4 is provided with a non-woven stuffing core 45 filled in the inner bottom of the inner cap 42 as volatilization preventing means.
  • the nib main body portion 20a arranged on the inner bottom portion of the inner cap 42 is buried and covered by the stuffing core 45, and the stuffing core 45 is covered with the pen tip. It absorbs the ink exuded from the body portion 20a and becomes wet.
  • the pen tip main body 20a is covered with the stuffing core 45 which is always wet with ink, suppressing further bleeding of the ink and reducing the contact area in the gap where the ink is exposed to the outside air, thereby preventing the ink from volatilizing unintentionally. can be reliably prevented.
  • the stuffing core 45 of the present embodiment is preferably made of polyethylene terephthalate (PET).
  • the surgical pen A1 according to the present embodiment can be widely marketed as a medical device that ensures safety in accordance with sterilization validation, and has good biocompatibility and writing operability. It is configured to
  • FIG. 4 is a side view showing the configuration of the surgical pen according to this embodiment.
  • the same reference numerals are used for the same configuration as in the first embodiment, and the description is omitted.
  • the handle of the writing instrument is held by the middle finger and thumb while pinching the barrel portion 11 of the pen, that is, the approximate front half barrel portion of the shaft portion 1 near the pen tip portion 2, with the index finger, and the second joint of the index finger is the second joint of the index finger. and the third joint.
  • the writing operation with the handle of an ordinary writing instrument is good when the object to be written is hard bone tissue, but when the object to be written is the soft surface of an organ or the like, the pen tip portion 2 may cause an inadvertent writing operation.
  • the writing pressure is transmitted as a pressing stress, which may cause damage.
  • the axis A holder 6 for writing operation is provided at the tail end of the body 1 .
  • the holder 6 has a bulging portion 60 that bulges outward from the tail end of the shaft portion 1, as shown in FIGS. 4(a) and 4(b).
  • the holder 6 shown in FIG. 4( a ) has a substantially ellipsoidal shape, is formed along the long axis direction, and is inserted into the tail portion of the trunk portion 11 of the shaft portion 1 so as to correspond to the insertion portion. It has a hole 61 and is detachably attached to the tail end of the shaft portion 1 .
  • the tip of the pen tip 2 (the pen tip main body 20a) is stably placed on the target site on the surface of the living body for pointing and writing operation. It can be carried out.
  • the bulging portion 60 bulges outward in the radial direction from the outer peripheral surface of the shaft portion 1 . Therefore, a pointing portion is formed at the boundary between the tail portion of the shaft portion 1 and the holder 6 .
  • the boundary portion between the tail end portion of the shaft portion 1 and the holder 6 is pinched between the tips of the thumb and the index finger, or the tail end portion is pinched between the tips of the thumb and the middle finger, and the pad surfaces of the fingers are bulged.
  • a handle form that is in surface contact with the curved surface 60a of the portion 60 is realized.
  • the tip of the pen tip 2 (pen tip main body 20a) is placed on the surface of the living body with the boundary between the tail end of the shaft 1 and the holder 6 as a fulcrum. There is no fear of applying careless writing pressure.
  • the finger pad surface abuts against the curved surface 60a of the bulging portion 60, so that the handle shape is stable and writing operability is improved.
  • the holder 6 of the mode shown in FIG. 4B further has a second bulging portion 62 that bulges out to cover the outer peripheral surface of the rear half of the trunk portion 11 of the shaft portion 1 . It is also possible to form a constricted shape with the second bulging portion 62 . In other words, the constricted portion 63 between the bulging portion 60 and the second bulging portion 62 can be made to function as a pinched portion to be pinched with the tip of the finger.
  • the constricted portion 63 between the bulging portion 60 and the second bulging portion 62 can be used as a gripping position, and the pointing and writing operation can be further stabilized with the gripping position as a fulcrum. It is possible to reduce the risk of damage without applying careless writing pressure stress to the surface.
  • ⁇ -ray irradiation conditions The surgical ink configured as described above and the surgical pen filled with it are irradiated with Co60 as a radionuclide, and conform to JIS/ISO standards (JIS T 0806-1/ISO 11137-1 and JIS T 0806-2 /ISO 11137-2) ⁇ -irradiation sterilization is applied.
  • the ⁇ -ray irradiation facilities are as follows. Irradiation facility: Japan Irradiation Service Co., Ltd. Tokai Center Irradiation device: Gamma ray irradiation device tote box type (JS10000HD manufactured by Nordion) Irradiation container: Tote box (78 x 50 x 150 cm: internal volume approx.
  • Irradiation source Co60 Set target absorbed dose: 50 kGy (Actual value 54.0 kGy to 67.6 kGy) Irradiation time: 26,000 seconds Maximum source capacity: 111PBq (3MCi) Tote box ( ⁇ -ray irradiation container):
  • the absorbed dose of ⁇ -rays for surgical ink and surgical pens using this is 25 kGy to 70 kGy.
  • Such absorption dose is the dose that ensures sterility in common for surgical inks and surgical pens that use this, and sterilization validation (JIS T 0806-1/ISO 11137-1 and JIS T 0806-2/ISO 11137 -2), determined by the following procedures (1) to (5).
  • Material test (2) Bioburden measurement
  • Sterilization dose setting test (4) Sterility test (5)
  • bioburden measurement and (4) sterility test are based on the JIS/ISO standard "Method for measuring microorganisms on products" (JIS T 11737-1/ISO 11737-1) and "Definition of sterilization process", respectively. , Sterility test performed in validation and maintenance” (JIS T 11737-2/ISO 11737-2).
  • the sterility assurance level is set to 10 -6 , and the number of living microorganisms per unit of irradiation obtained from (1) bioburden measurement and (4) sterility test and its From the lethal rate (the time required to reduce the number of bacteria to one-tenth: D value), the absorbed dose of ⁇ -rays at which the SAL is achieved is determined.
  • the ⁇ -ray irradiation time for ensuring sterility is the time (approximately 2-3 hours) required to achieve the absorbed dose of ⁇ -rays that achieves the SAL.
  • the absorbed dose to achieve SAL in the present invention is 25 kGy to 70 kGy, more preferably 25 kGy to 45 kGy. If the absorbed dose is less than 25 kGy, sterility cannot be ensured, and if it is greater than 70 kGy, radiation deterioration will be accelerated, and there is a risk that the properties of the ink will be changed unintentionally and the mechanical strength of the surgical pen will be reduced.
  • the absorbed dose range of 25 kGy to 70 kGy is an error caused by the relative distance between the position where each item to be sterilized is stored and arranged in the tote box and the radiation source. and (1) the mechanical strength in the material test.
  • Dispersion Liquid and Comparative Liquid Dispersion liquid A1 as a base material of surgical ink according to the example includes activated carbon powder (a), water-soluble polymer (b), and sodium hydroxide as basic substance (c). and water (d) as the remainder.
  • dispersion liquid A1 was replaced with 0.1 parts by weight of sodium carbonate, and the activated carbon powder (a) was replaced with red iron oxide.
  • Comparative liquid R2 was replaced with a water-soluble black dye, which was designated as comparative liquid R3. Specific procedures for preparing dispersion liquid A1 and comparative liquids R1 to R3 are as follows.
  • (Dispersion A1) 9.00 parts by weight of activated carbon powder (a), 6.30 parts by weight of polyvinylpyrrolidone as a water-soluble polymer (b), 0.13 parts by weight of sodium hydroxide as a basic substance (c), and water ( d) 84.57 parts by weight were added and mixed by stirring with a propeller stirrer at room temperature for 1 hour.
  • the activated carbon powder (a) had an average particle diameter of 35 ⁇ m and an average pore diameter of 3.4 nm
  • the polyvinylpyrrolidone used as the water-soluble polymer (b) had a viscosity-average molecular weight of 25,000.
  • Comparative liquid R1 10.00 parts by weight of red iron oxide as a coloring material, 8.50 parts by weight of polyvinylpyrrolidone as a water-soluble polymer (b), 0.10 parts by weight of sodium hydroxide as a basic substance (c), and 81.40 parts by weight of water as the balance so that the total amount is 100 parts by weight. and were mixed by stirring with a propeller stirrer at room temperature for 1 hour.
  • Comparative liquid R2 A comparative liquid R2 was prepared in the same manner as the comparative liquid R1 except that the coloring material of the comparative liquid R1 was changed to 10.00 parts by weight of black iron oxide.
  • Comparative liquid R3 A comparative liquid R3 was prepared in the same manner as the comparative liquid R1 except that the coloring material of the comparative liquid R1 was changed to 10.00 parts by weight of a water-soluble black dye. Table 2 shows the composition of each of the comparative liquids R1 to R3.
  • comparative compositions 1 to 3 were prepared by replacing dispersion liquid A1 with comparative liquids R1 to R3, respectively. Specific preparation procedures for each of Compositions 1 to 5 and Comparative Compositions 1 to 3 are as follows.
  • Ink composition 1 69.42 parts by weight of Dispersion A1, 5.00 parts by weight of propylene glycol and 15.00 parts by weight of ethanol as a water-soluble organic solvent (B), and 10.58 parts by weight of water were added to the remainder to make a total amount of 100 parts by weight. Ink composition 1 was obtained by stirring for 30 minutes.
  • Ink composition 2 66.12 parts by weight of Dispersion A1, 20.00 parts by weight of propylene glycol and 5.00 parts by weight of ethanol as water-soluble organic solvent (B), and 8.88 parts by weight of water were added to the remainder to make a total amount of 100 parts by weight. Ink composition 2 was obtained by stirring for 30 minutes.
  • Ink composition 3 Ink composition 3 was obtained by removing ethanol from ink composition 2. Specifically, 66.12 parts by weight of dispersion A1, 25.00 parts by weight of propylene glycol as a water-soluble organic solvent (B), and 8.88 parts by weight of water were added to the remainder to make a total amount of 100 parts by weight, and the mixture was stirred at room temperature with a propeller stirrer. Ink composition 3 was obtained by stirring for 30 minutes.
  • Ink composition 4 was obtained by classifying ink composition 2 using a centrifuge to remove coarse particles.
  • Ink composition 5 (Ink composition 5) Ink composition 5 was obtained by classifying ink composition 3 using a centrifuge to remove coarse particles.
  • compositions 1 to 5 exhibited a uniform black color in appearance.
  • Table 3 shows the components of each composition 1-5.
  • Comparative composition 1 50.00 parts by weight of comparative liquid R1 containing red iron oxide, 10.00 parts by weight of propylene glycol as a water-soluble organic solvent (B), and 30.00 parts by weight of water were added to the remainder, and stirred at room temperature for 30 minutes with a propeller stirrer to obtain a comparative composition. Item 1.
  • Comparative composition 2 50.00 parts by weight of comparative solution R2 containing black iron oxide, 10.00 parts by weight of propylene glycol as a water-soluble organic solvent (B), and 30.00 parts by weight of water were added to the remainder, and the mixture was stirred at room temperature for 30 minutes with a propeller stirrer. Comparative composition 2 was used.
  • Comparative composition 3 50.00 parts by weight of comparative liquid R2 containing a water-soluble black dye, 10.00 parts by weight of propylene glycol as a water-soluble organic solvent (B), and 30.00 parts by weight of water were added to the remainder, and the mixture was stirred at room temperature for 30 minutes with a propeller stirrer. was designated as Comparative Composition 3.
  • Comparative Compositions 1 to 3 exhibited a uniform black color in appearance.
  • Table 4 shows the composition of each of Comparative Compositions 1 to 3.
  • Comparative composition 3 used a water-soluble black dye as a coloring material, so its dispersibility could not be determined.
  • the rate of change in various parameters that indicate the properties of the ink before and after ⁇ -ray irradiation tends to be low, and it can be evaluated that the ink properties are stable. It is presumed that this is because the carbon material shields ⁇ -rays and functions to prevent deterioration of other constituents such as water-soluble polymers.
  • the present inventors have also found that this effect is particularly remarkable when the carbon material is activated carbon powder and the water-soluble polymer is polyvinylpyrrolidone.
  • Tables 11 to 13 show the rate of change over time of various parameters of ink compositions 1 to 5 at 50°C.
  • Tables 14 to 16 show the rate of change over time of various parameters of the inks of Examples 1 to 5 under the condition of 25°C.
  • Tables 17 to 19 show the temporal change rates of various parameters of the inks of Examples 1 to 5 at 50°C.
  • the ink of Example 5 it was confirmed that the average dispersed particle size, viscosity, and pH values were all within the above-mentioned most preferable ranges even after 3 months under storage conditions of 25°C and 50°C. was done. Therefore, it was shown that the ink of the present invention can be suitably used as a surgical ink even when it is filled in a pen and stored for a long period of time.
  • Core 20 described in Setting The core 20 is supported with a distance between fulcrums of 20 mm, and a load is applied from above to the middle point between the fulcrums of the core 20 until the core 20 breaks.
  • Other measurement conditions conformed to item 8.6 bending strength of JIS S6006 (pencils, colored pencils and leads used therefor).
  • the surgical pen used in this test had the same configuration as the surgical pen A1 according to the first embodiment except for the central core 20, and the respective materials were as shown in Table 20 below.
  • the core 20 (pen tip main body 20a) of the pen tip 2 was a fiber bundle core in which synthetic resin fibers made of PET were bound using urethane as a binder, and the material was made of PEEK.
  • Test sections 1 to 3 were obtained by extruding cores each having an outer diameter of ⁇ 1.3 mm, ⁇ 1.4 mm, and ⁇ 0.8 mm, and irradiating gamma rays. The air efficiencies of the cores in Test Groups 1 and 2 were 52% to 60%.
  • comparative zones 1 to 3 correspond to test zones 1 to 3, respectively, and are not irradiated with ⁇ -rays. Furthermore, the outer diameter was ⁇ 0.8 mm, the material was polyacetal (POM), and the core type was an extruded core.
  • POM polyacetal
  • the bending strength (MPa) before ⁇ -ray irradiation and the bending strength (N) after ⁇ -ray irradiation were measured for these Test Groups 1 to 3 and Comparative Groups 1 to 5.
  • the results are shown in Tables 21 and 22.
  • test plots 1-3 and comparative plots 1-3 exhibited stable bending strength before and after ⁇ -ray irradiation. Looking at the maximum withstand load of Test Areas 1 to 3, Test Area 1 was 2.25N, Test Area 2 was 2.94N, and Test Area 3 was 1.08N.
  • polyether ether ketone and polyethylene terephthalate showed stable strength before and after ⁇ -ray irradiation.
  • Comparative Groups 4 and 5 made of polyacetal as shown in Table 22, the bending strength tended to be significantly lower after ⁇ -ray irradiation than before ⁇ -ray irradiation.
  • the appearance of the pen tip main body 20a after gamma ray irradiation was deformed and fractured. It is presumed that the molecular structure of the polymer was cleaved and decomposed by the radical reaction generated by the ⁇ -ray irradiation.
  • the performance tests were (a) surgical pen mechanical writing test, (b) fixation drying test, (c) water resistance test, and (ii) color development test. Specific conditions for each test are as follows.
  • Example 3 was subjected to ⁇ -ray irradiation treatment in accordance with JIS/ISO standards (JIS T 0806-1/ISO 11137-1 and JIS T 0806-2/ISO 11137-2) to store the surgical ink of Example 3. I used a surgical pen. Experimental rats (male SD rats, weight 292g-346g, manufactured by Japan SLC) were used as objects for writing, and writing was performed on the following areas using the following method, and the writing ability was confirmed and the writing area was observed over time. Ta.
  • JIS/ISO standards JIS T 0806-1/ISO 11137-1 and JIS T 0806-2/ISO 11137-2
  • ⁇ Writing site Abdominal skin, skull, thigh muscle, tongue, buccal mucosa
  • ⁇ Writing method Abdominal skin was shaved under general anesthesia, and an ellipse with a width of 1 cm and a length of about 2 cm was written on the outer skin.
  • a dot-like tattoo was applied around the writing area using a blue pigment dispersion ("SA Blue 5636" manufactured by Mikuni Shiyo Co., Ltd.).
  • SA Blue 5636 manufactured by Mikuni Shiyo Co., Ltd.
  • FIGS. 5-10 Each writing section is shown in FIGS. 5-10.
  • the lower part of the two ellipses in the figure is a writing part with a surgical pen
  • the upper part is a writing part by Comparative Writing Example 4
  • the points around each are a position confirmation tattoo using a blue pigment dispersion. be.
  • the lower ellipse is the writing portion of the surgical pen
  • the upper ellipse is the writing portion of Comparative Writing Example 4.
  • FIG. 7 the thigh muscle drawn with a surgical pen is shown on the left side
  • the thigh muscle drawn by Comparative Writing Example 4 is shown on the right side.
  • FIG. 8 as well, the same portions as in FIG. 5 are written using the surgical pen and Comparative Writing Example 4, but both have disappeared as described below.

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PCT/JP2023/005806 2022-02-18 2023-02-17 サージカルインク、同インクの作製方法、及び同インクを用いたサージカルペン Ceased WO2023157953A1 (ja)

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JP2009011518A (ja) * 2007-07-04 2009-01-22 Shin Etsu Polymer Co Ltd 医療用ゴム部材、滅菌済医療用ゴム部材及びゴム組成物
JP2012126820A (ja) * 2010-12-15 2012-07-05 Sakura Color Products Corp 固形マーキングペン
US20140182480A1 (en) * 2011-10-20 2014-07-03 Endochoice Inc. Ink Formulation and Manufacture Thereof
CN204307216U (zh) * 2014-12-18 2015-05-06 陈林 具有笔尖调整功能的医用放疗标记笔
JP2016084417A (ja) * 2014-10-27 2016-05-19 紀州技研工業株式会社 インクジェットインク及びその印字方法
JP2019014912A (ja) * 2015-01-21 2019-01-31 クオリカプス株式会社 インク及びこれを用いた可食体の製造方法並びに可食体の印刷方法
JP2021187901A (ja) * 2020-05-27 2021-12-13 紀州技研工業株式会社 錠剤用インクジェットインク
KR102350083B1 (ko) * 2020-07-10 2022-01-10 이상주 레이저 시술용 마커 조성물 및 이를 이용한 레이저 조사방법
CN215662652U (zh) * 2021-06-15 2022-01-28 山东新华医疗器械股份有限公司 用于医疗灭菌的变色油墨书写笔

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JP3251186B2 (ja) 1997-01-10 2002-01-28 宗明 佐野 手術用生体マーキング製剤
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JPS62204754A (ja) * 1986-03-03 1987-09-09 株式会社ニツシヨ− 中空糸型血液処理器の放射線滅菌方法
JP2009011518A (ja) * 2007-07-04 2009-01-22 Shin Etsu Polymer Co Ltd 医療用ゴム部材、滅菌済医療用ゴム部材及びゴム組成物
JP2012126820A (ja) * 2010-12-15 2012-07-05 Sakura Color Products Corp 固形マーキングペン
US20140182480A1 (en) * 2011-10-20 2014-07-03 Endochoice Inc. Ink Formulation and Manufacture Thereof
JP2016084417A (ja) * 2014-10-27 2016-05-19 紀州技研工業株式会社 インクジェットインク及びその印字方法
CN204307216U (zh) * 2014-12-18 2015-05-06 陈林 具有笔尖调整功能的医用放疗标记笔
JP2019014912A (ja) * 2015-01-21 2019-01-31 クオリカプス株式会社 インク及びこれを用いた可食体の製造方法並びに可食体の印刷方法
JP2021187901A (ja) * 2020-05-27 2021-12-13 紀州技研工業株式会社 錠剤用インクジェットインク
KR102350083B1 (ko) * 2020-07-10 2022-01-10 이상주 레이저 시술용 마커 조성물 및 이를 이용한 레이저 조사방법
CN215662652U (zh) * 2021-06-15 2022-01-28 山东新华医疗器械股份有限公司 用于医疗灭菌的变色油墨书写笔

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TW202400236A (zh) 2024-01-01

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