Surgical marking ink

Abstract

[Problem] To provide a novel ink which is composed of only biocompatible components, satisfies the required characteristics necessary for a surgical ink, and can be suitably used as an ink for a surgical pen. [Solution] An ink comprising at least a colorant, a dispersion medium, and a water-soluble polymer having a viscosity average molecular weight of 1,000-220,000, wherein the colorant is a carbon material, the pH of the ink is 4.0-11.0, the content of the water-soluble polymer is 20-200 parts by weight per 100 parts by weight of the colorant, and 50 wt% or more of the liquid constituting the ink is water serving as the dispersion medium.

Description

Technical Field

[0001] The present invention relates to a surgical ink that can be suitably used for performing surgical markings (surgical markings) on the surface or inner surface, cross-section, etc. of the skin epidermis, incised skin tissue, organs, muscles, oral cavity, tongue, bone, etc. in medical procedures such as surgery.

Background Art

[0002] In surgery, particularly in surgical operations, in order to confirm the positions of lesion parts, resection sites, blood vessels, nerves, etc., and for information transmission among doctors and nurses and recording and confirmation of surgical procedures, etc., markings of lines, dots, numbers, and characters are generally made on living bodies such as the skin epidermis, muscles, bones, and organs with surgical ink. As methods, there are methods of marking the target site using a bamboo skewer or pen dipped in ink, methods of writing using a pen-shaped surgical writing instrument (surgical pen) filled with ink, methods of injecting ink into the target site using a syringe, etc. For the ink and instruments therefor, for example, Patent Document 1, Patent Document 2, Patent Document 3, Patent Document 4, Patent Document 5, etc. are disclosed.

[0003] As surgical ink, fixability that can fix on the surface without flowing even on parts wrapped with oil and moisture such as blood, sweat, and body fluids, drying property that dries quickly after fixing and does not cause rubbing or bleeding, water resistance that is not easily dissolved or deteriorated by body fluids or physiological saline, etc., coloring property that realizes the visibility required for surgery, gamma-ray resistance that is not denatured by gamma rays irradiated for disinfection, low irritation adjusted to an optimal pH according to the application site, and biocompatibility composed only of non-toxic and safe materials and having no adverse effects on the human body are cited as the main required characteristics. There is a demand for surgical ink that satisfies as many of these required characteristics as possible. Among them, fixability, coloring property, and biocompatibility are particularly important. Also, for use in marking the skin epidermis etc. where the marking location appears on the appearance, it is required to satisfy the erasability that the pigment does not deposit and the coloring easily disappears by rubbing with gauze etc. and no trace remains after surgery. In addition, when used as surgical pen ink, it is necessary to satisfy the requirements of stable ink ejection that can be dispensed without clogging even in the narrow channels inside the pen, and long-term stability that the ink does not deteriorate, solidify, separate, or settle even during long-term storage, thus maintaining its ejection properties.

[0004] However, at present, there is no high-performance surgical ink that meets these requirements, can reliably mark the surface, interior, and cross-section of a wide range of areas such as the skin epidermis or incised skin tissue, organs, muscles, oral cavity, tongue, bone, etc., and is suitable for use as a surgical pen ink.

[0005] For example, conventional surgical inks, such as those described in Patent Documents 1 and 2, use methylrosalinine chloride and methylene blue as colorants due to their high color development and ejection properties. However, recent studies have pointed out that these materials may be carcinogenic or cause chromosomal abnormalities, and therefore their biocompatibility is not ensured. While surgical inks that do not use methylrosalinine chloride or methylene blue have been disclosed, such as surgical inks using food colorings as colorants (Patent Document 3), the colorants used are dyes, resulting in insufficient fixation and water resistance. They bleed, dissolve, or flow when applied to bones, muscles, organs, etc., which are covered in bodily fluids such as blood or saline solution, making proper marking impossible. Therefore, their use in surgical applications is limited to marking on dry surfaces such as skin and drapes.

[0006] Furthermore, inks primarily used by injecting them into the target area with a syringe, as exemplified by Patent Documents 4 and 5, are intended to remain within the tissues of living organisms. Because they do not contain components that form a film upon contact with the outside air, they have insufficient fixation, water resistance, and drying properties, and it has been found that the applied ink may easily flow or dissolve. Therefore, they are not suitable for marking areas where ink cannot be injected, such as bones and muscles. In addition, the dispersion state and particle size of the colorants are not adjusted to be suitable for surgical pens, and using them as pens may cause problems such as poor dispensing. Moreover, since it is not possible to draw fine lines or curves arbitrarily when injecting ink with a syringe, it is not possible to write letters or numbers, thus limiting its uses.

[0007] While inks intended for edible materials such as food products are biocompatible, these inks do not meet the required characteristics for surgical inks and cannot be used suitably. For example, printing inks for edible materials such as food are designed for printing on substrates whose surface condition is predetermined by surface treatments such as coating or baking. Therefore, they are unlikely to perform adequately in surgical ink applications where the surface condition of the application target is not uniform depending on the location and situation. In particular, inks primarily used for printing on dry substrates are difficult to apply for surgical markings because they dissolve and flow due to blood or saline solution used for washing. Furthermore, these edible inks are designed to be digested in the body, and erasability, water resistance, and low irritation on the printed substrate are not considered. While cosmetic inks meet biocompatibility and skin irritation requirements for use on the skin's epidermis, their use on incised muscles, organs, and bones is not considered and may have adverse effects on the body. Furthermore, they are designed to be highly water-resistant and durable, assuming they will be washed off vigorously with soap during cleaning. However, such cleaning is not possible on surgical sites, so surgical inks are considered to lack the erasability necessary for surgical use. [Prior art documents] [Patent Documents]

[0008] [Patent Document 1] Patent No. 5888658 [Patent Document 2] US2019 / 125483 Al [Patent Document 3] Special Publication No. 63-044788 [Patent Document 4] Japanese Patent Publication No. 2007-262062 [Patent Document 5] Patent No. 5099815 [Disclosure of the Invention] [Problems that the invention aims to solve]

[0009] The objective of the present invention is to resolve the above-mentioned problems of the prior art. Specifically, the objective is to provide a new ink that is composed only of biocompatible components, satisfies the required characteristics for surgical ink, and can be suitably used as an ink for surgical pens. [Means for solving the problem]

[0010] Therefore, the inventors diligently conducted research to achieve the above objectives and discovered that by using carbon materials and primarily using water as a dispersion medium, adding a specific polymer material, and adjusting the pH within a predetermined range, an excellent ink can be obtained that is composed only of biocompatible components and meets the required characteristics for surgical ink and surgical pen ink, leading to the present invention. Furthermore, they discovered that by appropriately adding specific basic substances or organic solvents, or by adjusting the dispersion particle size, an ink exhibiting even better performance as a surgical pen ink can be obtained.

[0011] In other words, the present invention is (1) A surgical ink comprising at least a colorant, a dispersion medium, and a water-soluble polymer having a viscosity-average molecular weight of 1,000 to 220,000, wherein the colorant is a carbon material, the pH of the ink is 4.0 to 11.0, the content of the water-soluble polymer is 20 to 200 parts by weight per 100 parts by weight of the colorant, and the dispersion medium contains 50% by weight or more of water of the liquid constituting the ink. (1) The ink according to (1), wherein the carbon material is activated carbon. (3) The ink according to (1) or (2) above, comprising 5% to 30% by weight of a water-soluble organic solvent in the ink solution. (4) The ink according to (3) above, wherein the water-soluble organic solvent comprises one or more of ethanol, isopropanol, polyethylene glycol, propylene glycol, and glycerin. (5) The ink according to any one of (1) to (4) above, characterized in that the average dispersed particle size of the carbon material is 50 nm to 1 μm. (6) An ink according to any of (1) to (5) above, containing 0.01 to 1.00% by weight of one or more of sodium carbonate and sodium hydroxide in the ink solution. (7) Ink for surgical pens as described in any of (1) to (6) above, (8) Cosmetic ink consisting of any of the inks described in (1) to (7) above, (9) Edible ink comprising any of the inks described in (1) to (7) above, (10) A method for producing ink according to any one of (1) to (9), characterized by adding 0.01 to 1.00% by weight of a basic substance relative to the total weight of the ink. (11) The manufacturing method according to (10) above, wherein the basic substance comprises one or more of sodium carbonate and sodium hydroxide. (12) The manufacturing method according to (11) above, wherein the basic substance is sodium hydroxide. It is located there. [Effects of the Invention]

[0012] Since the ink of the present invention satisfies the important required characteristics as surgical ink, it can be applied to the surfaces, inner surfaces, cross-sections, etc. of a wide range of sites such as the skin epidermis or incised skin tissue, organs, muscles, oral cavity, tongue, bone, etc., and can be suitably used for surgical marking in a wide range of surgeries. In addition, since it has suitable physical properties as ink for surgical pens, by filling it into a pen and using it, the line drawing width can be adjusted from a thin line to a thick line, and arbitrary line drawings, characters, numbers, symbols, etc. can be written smoothly and stably, which is highly convenient.

Brief Description of the Drawings

[0013] [Figure 1] Figure 1 is a view showing the gingiva on which writing was performed using pen a in an example. [Figure 2] Figure 2 is a view showing the gingiva on which writing was performed using pen b in an example. [Figure 3] Figure 3 is a view showing the gingiva on which writing was performed using pen c in an example. [Figure 4] Figure 4 is a view showing the gingiva on which writing was performed using pen d in an example. [Figure 5] Figure 5 is a view showing the buccal mucosa on which writing was performed using pen a in an example [Figure 6] Figure 6 is a view showing the buccal mucosa on which writing was performed using pen b in an example. [Figure 7] Figure 7 is a view showing the buccal mucosa on which writing was performed using pen c in an example. [Figure 8] Figure 8 is a view showing the buccal mucosa on which writing was performed using pen d in an example. [Figure 9] Figure 9 is a view showing the tongue on which writing was performed using pen a in an example. [Figure 10] Figure 10 is a view showing the tongue on which writing was performed using pen b in an example. [Figure 11] Figure 11 is a view showing the tongue on which writing was performed using pen c in an example. [Figure 12]Figure 12 shows a tongue that has been written on using pen d in the example. [Figure 13] Figure 13 shows the dry skin on which writing was performed in the example. [Figure 14] Figure 14 shows the wet skin on which writing was performed in the example. [Figure 15] Figure 15 shows the abdominal skin of rats immediately after writing with pens a and e in the example. [Figure 16] Figure 16 shows the skull of a rat immediately after writing using pens a and e in the example. [Figure 17] Figure 17 shows the thigh muscles of rats immediately after writing using pens a and e in the example. [Figure 18] Figure 18 shows the abdominal skin of rats that underwent writing using pens a and e in the example, 7 days later. [Figure 19] Figure 19 shows the abdominal endothelium of rats that underwent writing using pens a and e in the example, 7 days later. [Figure 20] Figure 20 shows the thigh muscle of a rat that wrote using pen a in the example 14 days later. [Modes for carrying out the invention]

[0014] The ink of the present invention is characterized by containing at least a colorant, a dispersion medium, and a water-soluble polymer, and using a carbon material as the colorant. [Carbon materials] This invention is characterized by the use of carbon materials. A wide range of biocompatible carbon materials can be used in this invention, and activated carbon, carbon black, graphite, graphene, fullerene, and the like are suitably used. These carbon materials have excellent visibility, enabling the color development necessary for surgery, and are also biocompatible. Furthermore, the inventors' research has revealed that using carbon materials as colorants can impart gamma-ray resistance to ink. Although the mechanism is not fully understood, it is presumed that the carbon material dispersed in the ink shields against gamma rays, preventing the deterioration of other components such as water-soluble polymers. This effect is particularly pronounced when the carbon material is activated carbon and the water-soluble polymer is polyvinylpyrrolidone. Among these carbon materials, activated carbon is particularly preferable because it has excellent colorability and dispersibility and is relatively inexpensive to obtain. Furthermore, one of these carbon materials can be used alone, or two or more can be used in combination.

[0015] [Activated carbon] Activated carbon is a black, porous powder that is generally used for deodorization, water purification, wastewater treatment, and catalyst support, taking advantage of its pores. Refined activated carbon, in particular, is taken orally as medicinal charcoal to adsorb gases and toxic substances in the intestines and expel them from the body. In this invention, activated carbon, which is not commonly used as a coloring agent, is used as a black coloring agent. Activated carbon is known as a carbon material with an extremely large specific surface area. By heating carbon materials such as wood, charcoal such as Binchotan is obtained (this process is called "carbonization"), but the specific surface area of ​​charcoal (including powdered charcoal) is generally 300-500 m². 2 It is said to be / g. In contrast, activated carbon is produced by further processing charcoal at a high temperature of nearly 1000°C, resulting in a specific surface area of ​​800-2000m². 2 / g, and even 500-3000m 2When the amount reaches / g (this process, where carbon materials are treated at high temperatures to increase their specific surface area and become activated carbon, is called "activation" or "activation reaction"), it is known to have extremely high adsorption performance.

[0016] Generally, activated carbon is produced by reacting carbon materials such as coal or coconut shells with gases or chemicals at high temperatures. Known methods include chemical activation, in which the raw material is impregnated with a zinc chloride solution and then heated and activated under certain conditions, and steam activation, in which the raw material is activated with heated steam at a temperature of 800-1000°C. However, in this invention, the method of producing activated carbon is not particularly limited. Activated carbon can be broadly classified into three types based on its raw materials: "coal-based," "plant-based," and "other." However, in this invention, it can be used without any particular limitation.

[0017] Furthermore, activated carbon can be broadly classified into powdered activated carbon and granular activated carbon based on its shape. Powdered activated carbon refers to powder with a particle size that can pass through a 100-mesh (0.15 mm opening) sieve, while granular activated carbon refers to particles that cannot pass through the same sieve. Other types include fibrous activated carbon and specially molded activated carbon (honeycomb-shaped, plate-shaped (sheet-shaped)). In this invention, it is preferable to use powdered activated carbon because it is finer and has superior dispersibility and colorability.

[0018] The physical properties of the activated carbon used in this invention are not particularly limited, but generally, the average particle size is 1 to 100 μm, and particularly preferably 5 to 70 μm. The specific surface area is also not particularly limited, but preferably 500 to 3000 m². 2 / g, particularly preferably 1000-2000m 2 The total pore volume is not particularly limited, but is preferably 0.3 to 5 ml / g, more preferably 0.5 to 4 ml / g, and most preferably 0.5 to 3 ml / g.

[0019] The average pore diameter is preferably 1 to 20 nm, and particularly preferably 2 to 10 nm. The pH of the activated carbon is preferably 3 to 8, and particularly preferably 4.5 to 7.5. The iron content in the activated carbon is preferably 0.03% by weight or less, and particularly preferably 0.01% by weight or less. pH, average particle size, specific surface area, total pore volume, average pore diameter, and iron content are measured according to the method of JIS K 1474-91.

[0020] Furthermore, the activated carbon used in this invention is preferably one that conforms to the methods described in JIS K 1474-91 and the Japanese Food Additives Standards, containing 0.53% or less chloride (as Cl), 0.48% or less sulfate (as SO4), 0.10% or less zinc, and 4.0 μg / g or less arsenic (as As2O3). Within these ranges, it conforms to food additive standards, is non-toxic to the human body, and prevents the influence of impurities on the ink's properties.

[0021] The amount of activated carbon added to the ink solution should be between 0.1% and 10% by weight, preferably between 0.5% and 8% by weight, and more preferably between 1% and 5% by weight. Below 0.1% by weight, the concentration as a colorant is too low, and the ink's color development may be insufficient. Above 10% by weight, poor stability over time due to activated carbon aggregation and reduced ink discharge from the marking pen may make stable writing difficult.

[0022] [Water-soluble polymer] The present invention is characterized by containing a water-soluble polymer with a viscosity-average molecular weight of 1,000 to 220,000. Generally, to prepare a liquid composition in which solid fine particles such as pigments are dispersed in a liquid medium, compounds called dispersants are added. These are compounds that have the function of stably dispersing solid fine particles such as pigments in a dispersion medium, and can be broadly classified into compounds called surfactants, which have relatively low molecular weights, and polymer compounds, which have higher molecular weights.

[0023] Among these, polymer compounds generally have many hydrophilic groups in their molecular chains, which allow water molecules to hydrate and dissolve them. Others have long-chain aminoamides, acrylic acid / polycarboxylic acids, or their salts as their main structure, and possess basic adsorbent groups such as amides and amines, or acidic groups such as carboxyl groups and phosphate groups, which are soluble as neutralized salts. In contrast to these general solid particle dispersion methods, the present invention is characterized by the stable dispersion of carbon material solid particles by incorporating a polymer that is water-soluble and has a viscosity-average molecular weight of 1,000 to 220,000. It is not limited to those known as dispersants.

[0024] The viscosity-average molecular weight of the water-soluble polymer is 1,000 to 220,000, preferably 2,000 to 100,000, more preferably 5,000 to 100,000, and most preferably 7,000 to 50,000. If the viscosity-average molecular weight is less than 1,000, the ink will not form a film during writing and will not be able to adhere to the writing surface. If the viscosity-average molecular weight is greater than 220,000, the adhesion to the writing surface becomes too strong, and the erasability required for surgical ink cannot be obtained. The viscosity-average molecular weight is basically measured according to the molecular weight measurement method described in the Journal of Polymer Science, Vol. 38, No. 7, pp. 457-463 (July, 1981). That is, the procedure is as follows.

[0025] (1) Add the sample to excess acetone and precipitate it. Repeat this procedure twice, then dry under reduced pressure until the acetone odor disappears. (2) Prepare an aqueous solution of the purified sample and use an Ubbelohde viscometer (water, 120 seconds) to determine the viscosity-average molecular weight using the Mark-Kuhn-Houwink equation (Mark-Houwink-Sakurada equation). The coefficients M and α in the Mark-Kuhn-Houwink equation should be those listed in the above-mentioned polymer science paper. However, any other method that can obtain equivalent results is acceptable.

[0026] Please note that molecular weight values ​​may vary by about 10% due to measurement errors. Therefore, values ​​within approximately 10% above or below the aforementioned range are acceptable.

[0027] In this invention, it is preferable to use a nonionic water-soluble polymer. The acid value is an indicator of polarity, and in this invention, the acid value is preferably 30 mgKOH / g or less, more preferably 20 mgKOH / g or less, even more preferably 5 mgKOH / g or less, and most preferably no acid value is detected at all (substantially 0 mgKOH / g). Within this range, the dispersion performance of carbon materials and the water resistance of the ink are particularly excellent.

[0028] The acid value is measured according to the method specified in DIN 53402, more specifically as follows: (1) Place 0.9 to 1.3 g of the sample into a beaker and weigh it. (2) Add 50 ml of acetone. (3) Measure using an automated potentiometric titrator with a 0.1N NaOH aqueous solution. The results will be the same regardless of which automated potentiometric titrator is used. (4) The amine value can be determined by the following formula.

[0029] Acid value = [(ab)×5.61] / E (mgKOH / g)

[0030] a: Number of ml of 0.1N NaOH required for titration b: Number of ml of 0.1N NaOH required for the titration of the blank. E: Weight of the sample (g) (5) Display: Display to one decimal place.

[0031] Specifically, the water-soluble polymers mentioned above include casein, water-soluble cellulose derivatives, polyvinylpyrrolidone, acrylic polymers with acid values ​​such as styreneacrylic, and water-soluble polymers having carboxylic acid groups, which can be appropriately selected depending on the writing material.

[0032] The above water-soluble cellulose derivatives include cellulose ethers substituted with alkyl groups and hydroxyalkyl groups, or cellulose ethers substituted with hydroxyalkyl groups. This is preferably used.

[0033] Of the water-soluble polymers mentioned above, non-polar water-soluble polymers such as hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), and polyvinylpyrrolidone are particularly preferred. These polymers have excellent adhesion to the surface to which they are applied, excellent drying properties because they form a film upon contact with the outside air, and excellent erasability because the formed film is water-soluble. In addition, they have excellent dispersion properties, and when used as ink for surgical pens, they can provide an ink with excellent dispersion stability and discharge properties.

[0034] These water-soluble polymers exhibit good adhesion to the skin epidermis, incised subcutaneous tissue, organ surfaces, muscles, bones, oral cavity, tongue, etc., and can be suitably used. Among them, polyvinylpyrrolidone is the most preferred because it has excellent adhesion, is widely recognized as biocompatible as a food additive, exhibits resistance to gamma rays through interaction with activated carbon, and has high dispersibility.

[0035] In this invention, the amount of water-soluble polymer added is characterized by containing 20 to 200 parts by weight per 100 parts by weight of carbon material. More preferably, it is 25 to 180 parts by weight, and most preferably, 30 to 150 parts by weight. If it is less than 20% by weight, it is difficult to sufficiently disperse the colorant, the particle size of the dispersed carbon material in the dispersion medium will be large, and when used as a surgical pen, it may cause clogging inside the pen and lead to poor dispensing. If it exceeds 200 parts by weight, the viscosity of the ink will be high, making it difficult for the ink to be dispensed from the pen tip, and reducing writing performance.

[0036] In the present invention, it has been found that by incorporating the specific water-soluble polymer described above, carbon materials can be dispersed stably and finely in the ink, making it suitable for use as a surgical ink. Moreover, by incorporating this specific water-soluble polymer, it is possible to achieve excellent color expression of the carbon material, improved adhesion when writing on the surgical site, good fixation to the writing surface, and the ability to write in a superior black color that does not rub off during surgery and can be erased by wiping with a damp gauze. Although the mechanism by which such excellent effects are obtained is not fully clear, it is presumed that the good affinity with the porous fine powder carbon material, and the interaction with the polarity of the carbon material particle surface, prevent aggregation in the ink and stabilize the particle state, contribute to the effect.

[0037] [Dispersion medium] This invention is characterized by using water as the main dispersion medium. By using water as the main medium, an ink with superior biocompatibility, safety, and operability can be produced. In the ink composition of this invention, even when water is used as the main dispersion medium, the dispersion state remains stable, and the dispensing performance when writing with a surgical pen can be reliably maintained. The water used in this invention is not particularly limited, but distilled water or water for injection that has been appropriately quality-controlled for medical use is preferred. In this context, "primarily water" means that 50% or more by weight, and more preferably 60% or more by weight, of the liquid components constituting the ink is water. In other words, in this invention, 50% or more by weight of the liquid components constituting the ink is water. Particularly preferable is a composition in which the liquid components other than the specific water-soluble organic solvents described below are substantially water. In this invention, in addition to water and water-soluble organic solvents, a dispersion medium may also be included, as long as it contains water in amounts greater than those specified above. In this case, the liquid is not particularly limited as long as it can disperse the carbon material, and can be appropriately selected according to the application.

[0038] [Water-soluble organic solvents] In this invention, it is desirable to include a specific water-soluble organic solvent as a liquid component other than water. The addition of these water-soluble organic solvents has the effect of preventing clogging of the pen tip when writing with surgical pens, especially marker-type surgical pens, and also allows the drying time of the ink to be adjusted according to the pen structure. Specific examples of such water-soluble organic solvents include methanol, ethanol, n-propanol, iso-propanol, n-butanol, iso-butanol, t-butanol, trimethylolpropane, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, monoethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, propylene glycol, butylene glycol, 1,2,6-hexanetriol, thioglycol, hexylene glycol, glycerin, diglycerin, 1,2-hexanediol, 1,6-hexanediol, 2-pyrrolidone, and N-methyl-2 - Selected from pyrrolidone, 1,5-pentanediol, monoethylene glycol monomethyl ether, monoethylene glycol monoethyl ether, monoethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol dimethyl ether, diethylene glycol monobutyl ether, triethylene glycol monoethyl ether, triethylene glycol dimethyl ether, triethylene glycol monobutyl ether, methyl lactate, ethyl lactate, and 1,3-dimethyl-2-imidazolidinone, these can be used individually or in combination of two or more. Particularly preferred as food additives are ethanol, isopropanol, polyethylene glycol, propylene glycol, and glycerin.

[0039] In the embodiment of the present invention, the amount of water-soluble organic solvent added to the ink solution is preferably 5% to 35% by weight. More preferably, it is 10% to 30% by weight. Adding more than 35% by weight results in high viscosity ink, which can reduce ink stability and discharge performance, as well as slow drying speed. Adding less than 5% by weight may result in unstable ink discharge from the pen tip when used as a surgical pen, potentially leading to streaking, clogging, and reduced writing performance.

[0040] [Surface tension modifier] In the present invention, a surface tension modifier may be used as needed. The surface tension modifier is a component that improves the dispensing performance from the pen tip and adjusts the surface tension. Specific examples of surface tension modifiers include nonionic and anionic surfactants, specifically anionic surfactants such as alkylbenzene sulfonates, higher alcohol sulfates, higher fatty acid salts, higher alkyl dicarboxylates, alkylnaphthalene sulfonates, alkyl sulfosuccinates, naphthalene sulfonic acid formalin condensate salts, polyoxyethylene alkyl ether sulfates, and polyoxyethylene alkyl phosphates; nonionic surfactants such as 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, and polyoxyethylene-added acetylene glycols; silicone surfactants; fluorine surfactants; and water-soluble organic solvents such as ethanol and isopropanol. The amount of surface tension modifier added can be appropriately selected according to the required surface tension, but preferably it is 0.5 to 30% by weight in the ink, and particularly preferably 1 to 20% by weight.

[0041] [Basic substances] In this invention, a basic substance can be present in the ink to adjust the pH to a predetermined range. In the ink composition of this invention, the ink tends to be acidic due to the carbon material, so if neutralization with a basic substance is not performed, it may be highly irritating to the body in some areas. The optimal pH range varies depending on the body part, but in this invention, by appropriately adjusting the amount of basic substance added, the pH can be adjusted to an appropriate range according to the area being marked, thereby reducing irritation. The basic substance of the present invention is not particularly limited as long as it is a biocompatible substance that exhibits basicity according to the Arrhenius definition, but pH adjusters such as sodium carbonate, sodium hydroxide, potassium carbonate, and sodium bicarbonate are preferred as they can significantly change the pH with the addition of a small amount and are also edible. Of these, sodium carbonate and sodium hydroxide are particularly preferred, and sodium hydroxide is the most preferred.

[0042] In particular, when used as ink for surgical pens, sodium hydroxide is the most suitable of these. By adding sodium hydroxide, even with difficult-to-disperse pigments such as activated carbon, the dispersion state of particles in the ink is stabilized, preventing problems such as clogging at the pen tip, deterioration, sedimentation, solidification, particle size increase, and viscosity increase during long-term storage. Although the mechanism by which sodium hydroxide contributes to the stabilization of the dispersion state is not clear, it is thought that it stabilizes the surface activity of the carbon material particles and prevents aggregation.

[0043] The basic substance is preferably present in an amount of 0.01 to 1.00 parts by weight, and more preferably 0.05 to 0.50 parts by weight, per 100 parts by weight of ink. If the amount of basic substance is less than 0.01 parts by weight, the change in pH will be insufficient, and if sodium hydroxide is used, the effect of stabilizing the dispersion state cannot be fully exhibited. If the amount added is more than 1.00 part by weight, the pH will become too high, exceeding the range appropriate for living organisms, and may be highly irritating.

[0044] Furthermore, water-soluble polymers and other components may be added as appropriate, within the limits that do not impair the performance of the present invention, for purposes such as adjusting the viscosity of the ink, improving adhesion, etc. For example, starches such as guar gum, locust bean gum, agar, and methyl starch, as well as nonpolar water-soluble polymers such as gelatin, pullulan, xanthan gum, tragacanth gum, dextrin, casein, water-soluble cellulose derivatives, polyvinyl alcohol, and polyvinylpyrrolidone, may be added.

[0045] Furthermore, while the ink of the present invention is characterized by containing a carbon material as a colorant, it is also permissible to include other colorants as long as they do not impair the performance of the present invention.

[0046] [Ink characteristics] The carbon material in the ink of the present invention has an average dispersed particle diameter of 50 nm to 1 μm, preferably 50 to 800 nm, more preferably 50 to 700 nm, even more preferably 50 to 600 nm, even more preferably 50 to 500 nm, even more preferably 100 to 450 nm, and most preferably 150 to 400 nm. Within the above preferred ranges, the coloring power, dispersion stability, fixation, and discharge properties are excellent, but in the ranges of 50 to 500 nm, 100 to 450 nm, and 150 to 400 nm, the above performances are particularly excellent regardless of whether it is a pen component or a pen tip. If the average dispersed particle diameter is less than 50 nm, aggregation is likely to occur due to van der Waals forces between particles, and the stability over time tends to decrease. If the average dispersed particle diameter exceeds 1 μm, the colorant in the liquid is likely to separate, and precipitation may occur.

[0047] Furthermore, it is preferable not only to control the average dispersed particle size but also to suppress the amount of coarse particles. Specifically, if the dispersed particle size of 90% or more of the total carbon material particles in the liquid is adjusted to be 1 μm or less, more preferably 500 nm or less, an ink with even better physical properties can be obtained. As for adjustment methods, it is conceivable to perform dispersion treatment until 90% or more of the total carbon material particles have a dispersed particle size of 1 μm or less, more preferably 500 nm or less. However, in order to prevent the generation of a large amount of excessively fine particles and subsequent re-aggregation, it is also preferable to perform dispersion treatment until the average dispersed particle size is 1 μm or less, more preferably 500 nm or less, and then remove coarse particles by known methods such as centrifugation or filter filtration.

[0048] The method for measuring the average dispersed particle diameter and the dispersed particle diameter of all particles in this invention is as follows, but is not limited to this method if similar results can be obtained. Conditioning: Dilute the stock solution with deionized water so that it falls within the measurement concentration range specified for each measuring instrument. Measuring equipment: Dynamic light scattering particle size distribution analyzer ("NIKKISO: Microlracwave-EX150") Measurement time: 120 seconds

[0049] The viscosity of the ink of the present invention is preferably 1.0 to 10.0 mPa·s. More preferably 1.5 to 9.0 mPa·s, and most preferably 2.0 to 8.0 mPa·s. If the viscosity is less than 1.0 mPa·s, too much ink may flow from the pen tip when used for surgical pens. Conversely, if the viscosity exceeds 10.0 mPa·s, the ink may not flow easily from the pen tip, causing skipping or uneven writing. Furthermore, when using pigment-based ink in a marker pen, if the pen is stored with the tip facing downwards for a long period of time, the pigment may settle and accumulate and solidify near the tip, potentially clogging the tip and causing streaking or fading, thus reducing writing performance. However, by increasing the ink viscosity within the preferred range described above, the rate of pigment settling can be reduced, thereby suppressing the deterioration of writing performance.

[0050] The viscosity measurement method in this invention is as follows, but is not limited to this method if similar results can be obtained. Conditioning: Undiluted solution Measuring instrument: Conical plate rotational viscometer (TVE-20L model, manufactured by Toki Sangyo Co., Ltd.) Measurement conditions: 50rpm Measurement temperature: 25℃

[0051] The ink of the present invention is characterized by having a pH value of 4.0 to 11.0. Outside this range, it cannot be used as a surgical ink due to its strong irritant properties to living organisms. While a pH of 6.0 to 9.0 is more preferable for many parts of the body, irritation can be reduced by adjusting the pH to an appropriate value according to the application site. The method for measuring pH is not particularly limited, but it can be done as follows. Conditioning: Undiluted solution Measuring instrument: pH meter (MH-41X model, manufactured by Toa DKK Co., Ltd.) Measurement temperature: 25℃

[0052] The ink of the present invention can be made resistant to gamma rays. That is, as shown in the examples described later, the physical properties of the ink of the present invention remain almost unchanged before and after gamma ray irradiation, and stable quality is maintained for a long period of time even after gamma ray irradiation. Specifically, even after gamma ray irradiation treatment with absorbed doses of 25 kGy to 70 kGy in accordance with JIS / ISO standards (JIS T 0806-1 / ISO 11137-1 and JIS T 0806-2 / ISO 11137-2), the average dispersed particle size, viscosity, and pH can be maintained within the above preferred range, and furthermore, the average dispersed particle size, viscosity, and pH can be maintained within the above most preferred range. As mentioned above, it is presumed that the carbon material acts as a shield against gamma rays, preventing the deterioration of other components such as water-soluble polymers. Our own research has shown that this effect is particularly pronounced when the carbon material is activated carbon and the water-soluble polymer is polyvinylpyrrolidone, and this is supported by the examples described later. Because it is resistant to gamma rays, the ink does not deteriorate even when irradiated with gamma rays for sterilization of surgical pens, maintaining suitable physical properties for surgical ink, and allowing for marking and writing without problems such as poor ink dispensing.

[0053] The absorbed dose of 25kGy to 70kGy is a dose that ensures sterility for both the surgical ink and the surgical pen using it according to the present invention, and was determined in accordance with the provisions of sterilization validation (JIS T 0806-1 / ISO 11137-1 and JIS T 0806-2 / ISO 11137-2) through (1) material testing, (2) bioburden measurement, (3) sterilization dose setting testing, (4) sterility testing, and (5) dose distribution evaluation. (1) Bioburden measurement and (4) sterility testing were performed in accordance with the JIS / ISO standards "Method for measuring microbial groups on products" (JIS T 11737-1 / ISO 11737-1) and "Sterility testing performed in the definition, validation and maintenance of sterilization processes" (JIS T 11737-2 / ISO 11737-2), respectively. In other words, the sterility assurance level (SAL) is set to 10⁻⁶, and the absorbed gamma ray dose at which the SAL is achieved is determined from the number of microorganisms surviving per unit area of ​​the irradiated object and their lethal rate (time required to reduce the number of microorganisms to one-tenth: D value) obtained from (1) bioburden measurement and (4) sterility testing. In other words, the gamma ray irradiation time required to ensure sterility is at least the time required to achieve the absorbed gamma ray dose at which the SAL is achieved (approximately 2-3 hours). In this invention, the absorbed dose 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 guaranteed, and if it is greater than 70 kGy, radiation degradation may be promoted, potentially altering the properties of the ink unintentionally. The absorbed dose range of 25 kGy to 70 kGy is an error that occurs depending on the relative distance between the radiation source and the position in which each sterilized object is stored and arranged within the tote box. For surgical pens filled with the surgical ink of the present invention, this range guarantees (4) sterility in sterility tests and (1) mechanical strength in material tests.

[0054] The ink of the present invention is preferably subjected to gamma irradiation treatment after ink preparation. Specifically, it is preferable to perform gamma irradiation treatment with an absorbed dose of 25 kGy to 70 kGy in accordance with JIS / ISO standards (JIS T 0806-1 / ISO 11137-1 and JIS T 0806-2 / ISO 11137-2) after ink preparation, and more preferably with an absorbed dose of 25 kGy to 45 kGy. By performing gamma irradiation treatment within the above range, the ink is sterilized, ensuring safety for surgical use, and preventing deterioration of the ink's physical properties due to radiation degradation and a decrease in the mechanical strength of the surgical pen it is filled into. It's difficult. The methods and conditions used for gamma-ray irradiation are not particularly limited as long as they conform to the above standards, but gamma-ray irradiation can be performed as follows. • Gamma ray irradiation treatment: Radioactive nuclide: Co60 Irradiation facility: Located within the Tokai Center of Japan Irradiation Service Co., Ltd. Irradiation container: Tote box (78 x 50 x 150 cm) Irradiation device: (Model) JS10000HD, IR-199, (Manufacturer) MDS Nordion Target absorbed dose: 50 kGy (Actual measured value: 54.0 kGy ~ 67.6 kGy) Irradiation time: 26,000 seconds

[0055] The ink of the present invention can be made so that its physical properties do not deteriorate even when stored for a long period of time. Specifically, when stored at room temperature, the average dispersed particle size, viscosity, and pH can remain within the above preferred range after preferably 30 days or more from the time of manufacture, more preferably after 60 days or more, and most preferably even after 90 days or more. Because the above physical properties can be maintained within a desirable range even during long-term storage, stable writing can be performed without compromising the dispenser, writing feel, or low irritation properties, even when the ink is filled into a pen and stored.

[0056] [Ink preparation] The method for manufacturing the ink of the present invention is not particularly limited, and the ink can be made by mixing the aforementioned components. For example, the carbon material, water-soluble polymer, and water are mixed and stirred, then dispersed using a commercially available disperser, such as a paint shaker, roll mill, ball mill, sand mill, or jet mill, and then various additives such as the water-soluble organic solvent and surface tension modifier described above are added as appropriate to produce the ink. Furthermore, the quality of the ink produced as described above can be further improved by subjecting it to known methods such as filtering, magnetic separation, and removal of impurity ions. In addition, adding a step to remove coarse particles after mixing, stirring, and dispersing the carbon material, water-soluble polymer, and water in the above manufacturing method is also effective in producing ink that maintains a stable and good dispersion state. When adding basic substances, the method and timing are not particularly limited. For example, they can be added together with the water, carbon material, and water-soluble polymer when mixing and stirring, or they can be added after the dispersion treatment together with additives such as water-soluble organic solvents or surface tension modifiers. If gamma ray irradiation is to be performed, it should be done after the ink has been prepared as described above. The ink can be irradiated with gamma rays in a gamma-ray resistant container such as a plastic container, or it can be filled into a pen and used as a surgical pen before being irradiated.

[0057] [How to use and its applications] The ink of the present invention, as described above, can be applied to and used for writing on various objects. For example, surgical marking can be performed by applying the ink of the present invention to the tip of a bamboo skewer, cotton swab, brush, spatula, etc., and applying it to the area to be marked. Furthermore, by filling a surgical pen with the ink and writing, more precise marking can be performed by adjusting the width of the lines and the size of the dots. When used with a surgical pen, there are no particular restrictions on the type of pen or writing method, and writing instruments such as markers, felt-tip pens, and plastic pens that have been used as stationery can be disinfected and used. However, from the standpoint of writing performance, it is preferable to use a pen in which the pen components do not deteriorate even after gamma ray irradiation treatment and maintain sufficient mechanical strength and dispensing performance. Among pens, marker pens have particularly fine ink channels, and writing performance such as dispensing performance tends to be a problem with pigment-based inks. However, the present invention exhibits physical properties suitable for writing due to the combination of the above-mentioned components, so it can be used suitably. Since the ink of the present invention is composed only of biocompatible components that can be safely ingested into the body, it can be suitably used in applications other than surgical inks that require biocompatibility, such as writing, decorating, and printing on cosmetics, hygiene products, food, toys, infant products, pharmaceuticals, etc. Furthermore, due to its excellent colorability and fixation properties, it can be used for various purposes in the above applications, such as preventing counterfeiting, recording traceability, displaying warnings to prevent accidental ingestion, improving identifiability, and adding design and amusement value. [Examples]

[0058] The present invention will be described in detail below with reference to examples. In the examples, "parts" all refer to parts by weight.

[0059] [Example 1] • Preparation of dispersion The following ingredients were mixed and stirred at room temperature for 1 hour using a propeller agitator. Ingredient Quantity (Weight portion (hereinafter referred to as "port")) activated carbon 10.0 (Average particle size: 35 μm, average pore diameter: 3.4 nm) Polyvinylpyrrolidone 7.22 (Viscosity average molecular weight; 50,000) Wednesday 82.78

[0060] Next, 150g of 0.5mm diameter zirconia beads were added to the resulting mixture in a paint shaker pot, and the mixture was shaken for 3 hours. The coarse particles contained in this dispersion were removed, and the dispersion was adjusted so that more than 90% of the particles had a diameter of 500 nm or less and a solid content concentration of 10% by weight, and this was designated as "Dispersion 1".

[0061] • Ink Next, the following mixture was stirred in a propeller agitator at room temperature for 30 minutes to obtain the ink. Ingredient amount (parts) Dispersion 1 (solid content 10%) 68.03 Propylene glycol 5.0 Wednesday 26.97 The obtained ink had an average dispersed particle size of 274 nm, a viscosity of 2.5 mPa·s, and a pH of 5.1. Furthermore, the ink exhibited a uniform black appearance. The above ink was then tested and evaluated for its long-term stability, writing properties, fixation, and water resistance according to the following method. The results are shown in Table 1.

[0062] (i) Stability test over time The ink was placed in a plastic bottle and left to stand in a constant temperature room at 25°C for one month. After that, the presence or absence of colorant separation, floating, and sedimentation was checked. Any separation, floating, or sedimentation of the colorant was considered abnormal. In Table 1, ○ indicates no abnormality, △ indicates an abnormality was observed but the separation, floating, and sedimentation improved to the same level as an abnormality after light stirring with a spoon, and × indicates an abnormality was observed and the separation, floating, and sedimentation did not improve to the same level as an abnormality even after light stirring with a spoon.

[0063] (b) Written examination A cotton-filled marker pen, with a fiber bundle core (12 mm in diameter) consisting of polyurethane resin-bonded PET resin fiber bundles with a roughly hemispherical tip, was filled with ink. Writing was then performed on dry skin on the back of the hand and on chicken bones. The ability to dispense ink from the pen tip, the visibility of the lines drawn, and the ability to rewrite 30 minutes after writing were investigated. In Table 1, a circle (○) indicates that ink could be dispensed immediately after filling, the lines were clearly visible, and rewriting was possible even after 30 minutes. A cross (×) indicates that any of these conditions were not met.

[0064] (h) Fixation / drying test The marker pens used in the above (b) writing performance test were filled with ink, and the pens were used to write on the skin of a dry hand. The writing area was then rubbed three times with a dry nonwoven fabric to investigate whether the ink spread or transferred to the nonwoven fabric. In Table 1, a circle (○) indicates that there was no ink spreading and no transfer to the nonwoven fabric, while a cross (×) indicates that either of these conditions was not met.

[0065] (ii) Water resistance test The marker pens used in the above (b) writing performance test were filled with ink, and the pens were used to write on the skin of a dry hand. After 10 minutes, the writing area was rinsed with running tap water for 1 minute to check the visibility of the lines and whether or not there was any bleeding. In Table 1, a circle (○) indicates that the writing line was clearly visible and no bleeding or spreading to the surrounding area was observed, while a cross (×) indicates that any of these conditions were not met. (e) Color development test (ii) After the written test, the drawn lines were visually inspected to confirm whether the lines were discernible and to check the color tone. In Table 1, items where the lines are clearly identifiable in black or dark gray are marked with ○, and items where they are identifiable are marked with ×.

[0066] [Example 2] In Example 1, the ink was prepared in the same manner as described below, except that the composition during ink formation was as follows. Ingredient amount (parts) Dispersion 1 (solid content 10%) 68.03 Propylene glycol 5.0 Ethanol 15.0 Wednesday 11.97 The obtained ink had an average dispersed particle size of 313 nm, a viscosity of 4.3 mPa·s, and a pH of 4.9. Furthermore, the obtained ink exhibited a uniform black appearance. The ink was then evaluated in the same manner as in Example 1. The results are shown in Table 1.

[0067] [Example 3] In Example 1, the ink was prepared in the same manner as described below, except that the composition during ink formation was as follows. Ingredient amount (parts) Dispersion 1 (solid content 10%) 75.83 Propylene glycol 5.0 Sodium carbonate 0.0064 Wednesday 19.16 The obtained ink had an average dispersed particle size of 352 nm, a viscosity of 2.8 mPa·s, and a pH of 6.1. Furthermore, the obtained ink exhibited a uniform black appearance. The ink was then evaluated in the same manner as in Example 1. The results are shown in Table 1.

[0068] [Example 4] In Example 1, the ink was prepared in the same manner as described below, except that the composition during ink formation was as follows. Ingredient amount (parts) Dispersion 1 (solid content 10%) 75.83 Propylene glycol 5.0 Ethanol 15.0 Sodium carbonate 0.0064 Wednesday 4.16 The obtained ink had an average dispersed particle size of 300 nm, a viscosity of 5.1 mPa·s, and a pH of 6.2. Furthermore, the obtained ink exhibited a uniform black appearance. The ink was then evaluated in the same manner as in Example 1. The results are shown in Table 1.

[0069] [Example 5] In Example 1, the dispersion was prepared using the following formulation, and otherwise in the same manner as in Example 1. The resulting dispersion was designated "Dispersion 2". Ingredient Quantity activated carbon 9.0 (Average particle size: 35 μm, average pore diameter: 3.4 nm) Polyvinylpyrrolidone 6.3 (Viscosity average molecular weight; 25,000) Sodium hydroxide 0.129 Water 84.571

[0070] Using the obtained dispersion 2, an ink was prepared in the same manner as in Example 1, except that the formulation for ink formation was as follows. Ingredient amount (parts) Dispersion 2 (solid content 10%) 62.5 Propylene glycol 25.0 water 12.5 The obtained ink had an average dispersed particle size of 290 nm, a viscosity of 6.1 mPa·s, and a pH of 8.9. Furthermore, the obtained ink exhibited a uniform black appearance. The ink was then evaluated in the same manner as in Example 1. The results are shown in Table 1.

[0071] [Example 6] In Example 5, the ink was prepared in the same manner as described below, except that the composition during ink formation was as follows. Ingredient amount (parts) Dispersion 2 (solid content 10%) 62.5 Propylene glycol 20.0 Ethanol 5.0 water 12.5 The obtained ink had an average dispersed particle size of 270 nm, a viscosity of 5.7 mPa·s, and a pH of 8.7. Furthermore, the obtained ink exhibited a uniform black appearance. The ink was then evaluated in the same manner as in Example 1. The results are shown in Table 1.

[0072] [Example 8] In Example 1, the dispersion was prepared using the following formulation, and otherwise in the same manner as in Example 1. The resulting dispersion was designated "Dispersion 3". Ingredient Quantity activated carbon 9.0 (Average particle size: 35 μm, average pore diameter: 3.4 nm) Polyvinylpyrrolidone 6.3 (Viscosity average molecular weight; 40,000) Sodium hydroxide 0.129 Water 84.571

[0073] Using the obtained dispersion 3, an ink was prepared in the same manner as in Example 1, except that the formulation for ink formation was as follows. Ingredient amount (parts) Dispersion 2 (solid content 10%) 62.5 Propylene glycol 25.0 water 12.5 The obtained ink had an average dispersed particle size of 346 nm, a viscosity of 7.7 mPa·s, and a pH of 9.2. Furthermore, the obtained ink exhibited a uniform black appearance. The ink was then evaluated in the same manner as in Example 1. The results are shown in Table 1.

[0074] [Example 9] In Example 5, the ink was prepared in the same manner as described below, except that the composition during ink formation was as follows. Ingredient amount (parts) Dispersion 2 (solid content 10%) 62.5 Propylene glycol 20.0 Ethanol 5.0 Polyvinylpyrrolidone 2.0 (Viscosity average molecular weight; 25,000) water 10.5 The obtained ink had an average dispersed particle size of 307 nm, a viscosity of 7.6 mPa·s, and a pH of 8.0. Furthermore, the obtained ink exhibited a uniform black appearance. The ink was then evaluated in the same manner as in Example 1. The results are shown in Table 1.

[0075] [Comparative Example 1] • Preparation of dispersion The following ingredients were mixed and stirred at room temperature for 1 hour using a propeller agitator. Ingredient amount (parts) Bengara 10.0 Polyvinylpyrrolidone 8.5 (Viscosity average molecular weight: 40,000) Sodium carbonate 0.1 Wednesday 81.4

[0076] Next, 150g of 0.7mm diameter glass beads were added to the resulting mixture in a paint shaker pot and shaken for 3 hours. The coarse particles contained in this dispersion were removed, and the dispersion was adjusted so that more than 90% of the total particles had a diameter of 500 nm or less and a solid content concentration of 10% by weight, resulting in "Dispersion 3".

[0077] • Ink Next, the following mixture was stirred in a propeller agitator at room temperature for 30 minutes to obtain the ink. Ingredient amount (parts) Dispersion liquid 3 (solid content 10%) 50.0 Propylene glycol 10.0 Water 30.0 The obtained ink had an average dispersed particle size of 452 nm, a viscosity of 5.5 mPa·s, and a pH of 8.2. Furthermore, the obtained ink exhibited a uniform black appearance. The ink was then tested and evaluated in the same manner as in Example 1. The results are shown in Table 1.

[0078] [Comparative Example 2] In Comparative Example 1, an ink was prepared in the same manner as in the previous example, except that black iron oxide was used instead of red iron oxide. The resulting ink had an average dispersed particle size of 1130 nm, a viscosity of 5.4 mPa·s, and a pH of 9.1. The ink also exhibited a uniform black appearance. Furthermore, the ink was tested and evaluated in the same manner as in Example 1. The results are shown in Table 1.

[0079] [Comparative Example 3] In Comparative Example 1, an ink was prepared in the same manner as in the previous example, except that red iron oxide was used as a water-soluble black dye. The resulting ink had a viscosity of 4.2 mPa·s and a pH of 7.1. The ink also exhibited a uniform black appearance. Furthermore, the ink was tested and evaluated in the same manner as in Example 1. The results are shown in Table 1.

[0080] Table 1 [Table 1]

[0081] [Performance evaluation test: Writing on the human skin] Next, in order to confirm the performance in more detail, the ink obtained in Example 5 and the ink obtained by classifying the ink obtained in Example 5 using a centrifuge to remove coarse particles (referred to as "Example 7") were filled into a pen as described below, and performance evaluation tests were conducted when writing on the human body using the methods (A) and (B) below. The ink obtained in Example 5 was filled into a cotton-filled marker pen with a fiber bundle core (12 mm in diameter) consisting of polyurethane resin-bonded PET resin fiber bundles with a roughly hemispherical tip, and designated as "Pen a". Next, the ink obtained in Example 5 was filled into a marker pen similar to Pen a, except that the diameter of the fiber bundle core was 9 mm, and designated as "Pen b". Similarly, a pen similar to Pen a, except that the ink obtained in Example 7 was filled instead of the ink obtained in Example 5, was designated as "Pen c", and a pen similar to Pen b, except that the ink obtained in Example 7 was filled instead of the ink obtained in Example 5, was designated as "Pen d".

[0082] (Test method) (A) Intraoral written examination Using the pens a-d described above, we performed writing on the following locations in the oral cavity of adult males using the following method, and evaluated the performance of each pen. (1) Gums: Draw a curve about 5 cm long from near the two front teeth of the upper jaw to the base of the gums. (2) Buccal mucosa: Draw three straight lines about 3 cm long on the inside of the right cheek. (3) Tongue: Draw three straight lines about 3 cm long on the center of the upper surface of the tongue. After writing, the writing area was checked. Furthermore, five minutes after writing, the erasability was checked by passing a water-moistened gauze over the writing area three times.

[0083] (B) Written test on the skin surface Using the pens a-d described above, we performed writing on the skin surface of the inner forearms of adult women using the following methods, and evaluated the performance of each pen. (1) With the writing tip dry, write a straight line about 5 cm long and a number. (2) With the writing tip wet, write a straight line about 5 cm long and a number. After writing as described above, the writing area was examined. Furthermore, on the right arm, five minutes after writing, the writing area was exposed to running tap water for one minute to check for color fading or bleeding. On the left arm, five minutes after writing, the area was rubbed three times with a water-dampened gauze to check for erasability.

[0084] (Test results) (A) Results of the written examination inside the mouth The writing sections are shown in Figures 1 to 12. The following favorable results were obtained regardless of the pen used or the writing location. • Writing performance and ink flow: There were no issues with ink flow or clogging on any part of the pen, and writing was smooth and effortless. • Adhesion: The ink adhered well even to areas covered with mucous membranes or saliva, remaining on the writing surface without flowing. • Color development: The written area was clearly visible. • Water resistance and drying properties: The ink did not smudge or fade even when exposed to saliva, and the written area remained clearly visible. • Erasability: The ink disappeared without bleeding or spreading, leaving no traces or pigment stains.

[0085] (B) Results of the written test on the skin surface The different writing areas are shown in Figures 13 and 14. In Figure 13, the line with the number "107-12" written to the right was written with pen a, the line with "107-9" was written with pen b, the line with "109-12" was written with pen c, and the line with "109-9" was written with pen d. The numbers in Figure 13 were written using the corresponding pens. In Figure 14, the lines written to the left of the numbers are lines written on wet skin. In both writing tests using pens, the following favorable results were obtained for both (1) and (2). • Writing performance and ink flow: When writing straight lines or numbers, there were no issues with ink flow failure or clogging, and writing was smooth and effortless. • Fixation: Even when wet, the ink fixed and remained on the writing surface without flowing. • Color development: The written area was clearly visible. • Water resistance and drying properties: The ink did not smudge or fade even when exposed to running water, and the written area remained clearly visible. • Erasability: The ink disappeared without bleeding or spreading, leaving no traces or pigment stains.

[0086] [Performance evaluation test: Written test on rats] (Test method) Furthermore, after irradiating the above-mentioned pen a with gamma rays under the following conditions in accordance with JIS / ISO standards (JIS T 0806-1 / ISO 11137-1 and JIS T 0806-2 / ISO 11137-2), writing was performed using the pen a on the following locations of experimental rats (male SD rats, body weight 292g-346g, "manufactured by Nippon SLC Co., Ltd.") in the following manner, and the writing performance was confirmed and the writing area was observed over time. • Gamma ray irradiation treatment: Radioactive nuclide: Co60 Irradiation facility: Located within the Tokai Center of Japan Irradiation Service Co., Ltd. Irradiation container: Tote box (78 x 50 x 150 cm) Irradiation device: (Model) JS10000HD, IR-199, (Manufacturer) MDS Nordion Target absorbed dose: 50 kGy (Actual measured value: 54.0 kGy ~ 67.6 kGy) Irradiation time: 26,000 seconds • Places where writing is done: Abdominal skin, skull, thigh muscles, tongue, buccal mucosa ·Writing method: For the abdominal skin, the abdominal hair was shaved under general anesthesia, and an oval approximately 1 cm wide and 2 cm long was drawn on the outer skin. To confirm the position of the drawing, a dotted tattoo was made around the drawing area using a blue pigment dispersion (Mikuni Shikaku Co., Ltd., "SA Blue 5636"). For the skull and thigh muscles, incisions were made in each area under general anesthesia, and ovals approximately 1 cm wide and 2 cm long were drawn in each area using a marker pen, similar to the abdominal skin. Dotted tattoos were also made in the thigh muscles, and the areas were sutured. For the tongue and buccal mucosa, the openings were made under general anesthesia, and circles and dotted tattoos approximately 5 mm in diameter were applied. As a comparative example, writing was performed using a surgical pen (Mizuho Co., Ltd., "Tajima-style Mark Pen (Skin Pen)" (hereinafter referred to as "Pen e")) filled with a 0.2% aqueous solution of methylrosalinine chloride (Honzo Pharmaceutical Co., Ltd., "Honzo") as ink, and the color development was compared. • Observation over time: The rats that had written were kept at 25°C for 14 days, and the condition of the writing area was checked on the 7th and 14th days as follows: For the abdominal skin, the condition of the outer layer was checked on the 7th day, and since the ink had disappeared, the outer layer was excised under general anesthesia, and the degree of deposition in the endothelium was checked. For the skull and thigh muscles, each area was incised again under general anesthesia, visually inspected, and then sutured. For the tongue and buccal mucosa, the mouth was opened under general anesthesia and visually inspected.

[0087] (Test results) The writing areas are shown in Figures 15 to 20. In Figure 15, the lower of the two ellipses represents the writing area with pen a, and the upper one represents the writing area with pen e. The dots around each are tattoos used for position confirmation with a blue pigment dispersion. In Figure 16, the lower ellipse represents the writing area with pen a, and the upper ellipse represents the writing area with pen e. In Figure 17, the left side of the figure shows the thigh muscle written with pen a, and the right side shows the thigh muscle written with pen e. In Figure 18, writing was done with pen a and pen e in the same locations as in Figure 15, but both have disappeared as shown below. Writing with pen a yielded the following good results in all locations. • Writing performance and ink flow: There were no issues with ink flow failure or clogging, and I was able to write smoothly without any slipping. • Fixation: Even when wet with blood or other substances, the ink fixed and remained on the writing surface without flowing. • Color development: The written area was clearly visible. It was confirmed to be as visible as or better than Pen e. (Figures 15, 16, 17) • Water resistance and drying properties: It did not smudge or fade even when exposed to blood or bodily fluids, and the written area remained clearly visible. • Erasure (checked over time): For the abdominal skin, the disappearance of the outer layer ink was confirmed after 7 days (Figure 18), and the endothelium directly beneath the written outer layer was examined, but no discoloration was observed (Figure 19). For the thigh muscles, almost all of the ink had disappeared after 14 days (Figure 20). Discrimination was not possible for the tongue and buccal mucosa. For the skull, some ink remained after 14 days.

[0088] [Performance Evaluation Test: Comparison of Physical Properties Before and After Gamma Ray Irradiation, and Time-Long-Term Evaluation Test] Next, the ink was prepared again in the same manner as in Examples 5 and 6, and the average dispersed particle size, viscosity, and pH of the obtained inks were measured for Example 5-2 and Example 6-2, respectively. Subsequently, each ink was placed in a plastic container and subjected to gamma irradiation using the same equipment and conditions as the writing test on rats. Viscosity, mean dispersion particle size, and pH were then measured again. Furthermore, to confirm whether or not there was any change in physical properties during long-term storage, the ink before and after gamma ray treatment was stored in constant temperature rooms at 25°C and 50°C, respectively, as part of a time-series evaluation test. The average dispersed particle size, viscosity, and pH were measured after 30, 60, and 90 days. The results are shown in Table 2. In Table 2, "rate of change" refers to the decrease from the physical property value before storage (after 0 days) under each condition before and after irradiation, with the value set at 100%, and an increase indicated as -%.

[0089] Table 2 [Table 2]

[0090] [Time-based written examination] The ink obtained in Example 5 was subjected to a writing test over time using the following method. First, the ink obtained in Example 5 was filled into marker pens similar to those used in the writing performance test in (b) above to create pens. Multiple pens were made and divided equally into six groups: A, B, C, D, E, and F. The pens from groups A, B, and C were placed in a constant temperature room at 25°C, and the pens from groups D, E, and F were placed in a constant temperature room at 50°C, with each group set in the following orientation. Groups A and D: Upward (Pen tip pointing upwards, pen placed perpendicular to the horizontal plane) Groups B and E: Downward (pen tip pointing towards the ground, pen placed perpendicular to the horizontal plane) Groups C and F: Sideways (pen placed horizontally) After 30, 60, and 90 days of standing, lines were manually drawn on plain paper using each pen, with a writing distance of 60 cm. Of the groups A through F, half were drawn in straight lines, and the other half were drawn in curves. For straight lines, the writing speed was 15 cm per 10 seconds, and for curves, the writing speed was 60 cm per 10 seconds. The written lines were visually inspected for smudging and fading. Lines with severe smudging or fading that significantly reduced visibility to the point of being impractical were marked with ×, lines with some smudging or fading but not to the point of being impractical were marked with △, and lines with almost no smudging or fading and clearly visible were marked with ○.

[0091] In the same manner as in Example 5, time-lapse writing tests were also performed for Examples 8 and 9. However, for Example 9, the test was not performed after 90 days of standing. The results for each are shown in Table 3.

[0092] [Table 3]

[0093] From the above examples and comparative examples, as well as the results of the effectiveness verification tests, it can be seen that the ink of the present invention, which uses a carbon material as a colorant and contains a predetermined water-soluble polymer, has excellent properties as a surgical ink.

[0094] In addition, the results of performance evaluation tests using human epidermis and rats for the ink obtained in Example 5, as well as the condition of the writing area shown in Figures 1 to 20, demonstrate that the ink of the present invention is an excellent surgical ink that can write well even on living organisms wet with liquids such as blood, saliva, and water, and that the writing area is clearly visible. Furthermore, performance evaluation tests using rats confirmed that the ink exhibits excellent performance as a surgical ink even after gamma ray irradiation, and that it has good erasability on the skin epidermis where erasability is required for aesthetic reasons. It was also confirmed that it exhibits color development and writing performance comparable to methylrosalinine chloride, which has been widely used as a surgical ink in the past.

[0095] Furthermore, the comparison of physical properties before and after gamma ray irradiation shown in Table 2 demonstrates that the ink of the present invention maintains suitable physical properties as a surgical ink even after gamma ray irradiation treatment. Furthermore, the results of the time-dependent evaluation shown in Table 2 confirmed that, for the ink of Example 5-2, regardless of whether or not gamma irradiation treatment was performed, the average dispersed particle size, viscosity, and pH values ​​remained within the most preferred range after 90 days of storage at 25°C. It was also confirmed that the average dispersed particle size, viscosity, and pH values ​​remained within the preferred range after 90 days of storage at 50°C. For the ink of Example 6-2, it was confirmed that the average dispersed particle size, viscosity, and pH values ​​all remained within the most preferable range after 90 days of storage at both 25°C and 50°C, regardless of whether or not gamma irradiation treatment was performed. Therefore, it has been shown that the ink of the present invention can be suitably used as surgical ink even when filled into a pen and stored for a long period of time.

[0096] Furthermore, time-lapse writing tests on the inks obtained in Examples 5, 8, and 9 showed that the inks of the present invention maintain good writing performance in any orientation, even when filled into pens and stored for a long period of time at 25°C. In addition, the inks of Examples 8 and 9, which had higher viscosity than those of Example 5, were shown to maintain usable writing performance for a long period of time, even when stored upside down at 50°C, a position where writing performance tends to deteriorate.

[0097] Furthermore, the inks obtained in Examples 1, 2, 3, 4, 6, 8, and 9 showed evaluation results similar to those of Example 5, as shown in Table 1. The average dispersed particle size and viscosity values, which are considered to significantly affect the writing and fixing properties of the ink, were not significantly different from those of Example 5. Moreover, they contained activated carbon and polyvinylpyrrolidone, which are presumed to contribute significantly to the performance of the ink, and thus had a similar composition to Example 5. Therefore, it is naturally foreseeable that the inks obtained in Examples 1, 2, 3, 4, 8, and 9 would also yield similar good results to those obtained in Examples 5 and 5-2 in performance evaluation tests on human skin and rats, as well as in physical property measurements and time-dependent evaluation tests before and after gamma ray irradiation, making them suitable for surgical applications. Similarly, it is naturally foreseeable that the ink obtained in Example 6 would also yield similar good results to those obtained in Example 5 in performance evaluation tests on human skin and rats, making it suitable for surgical applications. [Industrial applicability]

[0098] The present invention provides an excellent ink that satisfies the required characteristics of surgical ink using only ingestible components, and can be suitably used for writing with surgical pens, as well as a writing method using this ink and a method for manufacturing surgical marker ink. Furthermore, it can be suitably used for writing, decorating, and printing on cosmetics, hygiene products, food, toys, infant care products, pharmaceuticals, etc., and the ink of the present invention can be used for a variety of purposes.

Claims

1. A surgical ink comprising at least a colorant, a dispersion medium, and a water-soluble polymer having a viscosity-average molecular weight of 1,000 to 220,000, wherein the colorant is a carbon material, and the ink solution contains 0.01 to 1.00% by weight of one or more of sodium carbonate and sodium hydroxide, the pH of the ink is 4.0 to 11.0, the content of the water-soluble polymer is 20 to 200 parts by weight per 100 parts by weight of the colorant, and the dispersion medium contains 50% by weight or more of water in the liquid constituting the ink.

2. The surgical ink according to claim 1, wherein the carbon material is activated carbon.

3. The surgical ink according to claim 1, comprising 5% to 30% by weight of a water-soluble organic solvent in the ink solution.

4. The surgical ink according to claim 3, wherein the water-soluble organic solvent comprises one or more of ethanol, isopropanol, polyethylene glycol, propylene glycol, and glycerin.

5. The surgical ink according to claim 1, characterized in that the average dispersed particle size of the carbon material is 50 nm to 1 μm.

6. The surgical ink according to claim 1, which is an ink for surgical pens.

7. A method for producing surgical ink according to any one of claims 1 to 6, characterized by adding 0.01 to 1.00% by weight of a basic substance relative to the total weight of the ink.

8. The manufacturing method according to claim 7, wherein the basic substance comprises one or more of sodium carbonate and sodium hydroxide.

9. The manufacturing method according to claim 8, wherein the basic substance is sodium hydroxide.

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