Detailed Description
The viscoelastic composition of the present invention contains a thickening substance (thickening substance) and water.
The viscoelastic composition of the present invention is prepared by combining one or more thickening substances having an effect of increasing viscosity when dispersed in water. Examples of such a thickening substance include: alcohols such as methanol, ethanol, 2-propanol, 1, 4-butanediol, 1, 3-butanediol, propylene glycol, glycerol catechin (glycerol catechin), glucose, fructose, galactose, sucrose, lactose, maltose, trehalose, xylitol, sorbitol, mannitol, glucosamine, and galactosamine; <xnotran> (Aureobasidium) , , , , , , , (Cassia gum), (Ghatti gum), (Curdlan), (Carrageenan), (Karaya Gum), , , , (Psyllium Seed Gum), (Artemisia sphaerocephala seed gum), , , , (Tara gum), , (Tragacanth gum), , (Funoran), , , (Macrophomopsis Gum), (Rhamsan Gum), , , , , , , , , , , , , , , , , , , , , , , , , , (Fucoidan), (Diutan gum), (Glucomannan), , (keratan sulfate), </xnotran> Polysaccharides such as heparin, chondroitin sulfate, dermatan sulfate (Dermatan sulfate), scleroglucan, schizophyllan (schizophyllan), okra extract, aloe arborescens extract (Krantz aloe extracts), sesbania gum, agarose, agar gum (Agar), amylose (Amylose), amylopectin (Amylopectin), pregelatinized starch, inulin, levan, caminan, agar (Agar), hydrophobized hydroxypropyl methylcellulose, sodium starch glycolate, dextran, dextrin, croscarmellose sodium, glucuronoxylan (Glucuronoxylan), arabinoxylan (Arabinoxylan), and the like; gelatin (Gelatin), hydrolyzed Gelatin, collagen, and other proteins; polyamino acids such as polyglutamic acid, polylysine and polyaspartic acid; hydrophilic polymers such as carboxyvinyl polymers, polyacrylic acid and salts thereof, partially neutralized polyacrylic acid, polyvinyl alcohol/polyethylene glycol graft copolymers, polyethylene glycol, polypropylene glycol, and polybutylene glycol; and metal salts such as calcium chloride, aluminum hydroxide, magnesium chloride, and copper sulfate.
The water used in the viscoelastic composition of the present invention is not particularly limited, but soft water, pure water, deionized water, distilled water, and the like, or physiological aqueous solutions such as physiological saline, ringer's solution, ringer's acetate, and the like are preferable.
The viscoelastic composition of the present invention may contain additives such as a preservative (preservative), a preservative (antiseptic agent), and the like.
The problem of the present invention is to provide a viscoelastic composition that is excellent in handling properties and can ensure a good visual field, and ideally to provide a viscoelastic composition that can assist a simple hemostatic treatment, and as a result, it is considered that: among these problems, the main reason why the view of the endoscope is obstructed is due to: 1) Liquid such as blood, intestinal juice and bile, food residue, and semisolid matter such as excrement are accumulated in the tube cavity; 2) The transparency of a mixture of a liquid such as blood, intestinal juice, bile, food waste, excrement, or the like, and water; 3) The semi-solid substances such as blood, intestinal juice, bile, etc., food residue, excrement, etc. flow and spread by the water. In order to ensure a good visual field, a transparent composition having viscoelasticity different from that of a liquid such as blood, intestinal fluid, bile, or a semisolid such as an excretion is injected into a lumen, and these substances are physically pushed away and removed to secure a space. The problem of excellent operability is that the viscoelastic composition can be passed through the jaw opening of an endoscope without excessive resistance. The problem of being able to assist a simple hemostatic treatment is that a bleeding site can be confirmed in the presence of the viscoelastic composition, and a hemostatic treatment using a high-frequency current can be assisted.
The viscoelastic composition of the invention has a hardness of 550N/m2 Below, it is preferably 400N/m2 The viscosity (25 ℃) is 200 to 2000 mPas, preferably 500 to 1500 mPas, and the loss tangent is preferably 0.6 or less.
By setting the hardness to the above range, the operability at the time of injection through the channel of the endoscope is good. In addition, by setting the viscosity and the loss tangent to the above ranges, improvement is made from the viewpoint of securing the field of view. The viscoelastic composition may be transparent from the viewpoint of ensuring a visual field.
The viscoelastic composition of the present invention preferably has an electrical conductivity of 250. Mu.S/cm or less, more preferably 200. Mu.S/cm or less.
By setting the electrical conductivity to the above range, a viscoelastic composition which suppresses electric leakage, and is particularly suitable for treatment such as electrosection and electrocoagulation can be obtained.
When the viscoelastic composition of the present invention is obtained by mixing the above-described thickening substance with water, specifically, it can be obtained as follows: combining two or more of the viscosity-increasing substances; alternatively, a thickening agent is dissolved in water or the like, and heat treatment is performed to impart elasticity to the solution; and so on. The viscoelastic composition of the present invention preferably has substantially no bubbles because it blocks the field of view when bubbles are present therein.
The method for ensuring the visual field of the endoscope comprises the following steps: the viscoelastic composition of the present invention is fed from the hand portion of an endoscope through a channel to the distal end portion of the endoscope.
Fig. 1 is a diagram showing a photograph of a hand portion of a medical endoscope as a representative example of an endoscope. The hand edge portion is provided with: a dial (dial) 11 for performing angle operation; an endoscope connector section 12 for transmitting light from the light source device and transmitting image information to the processor for the electronic endoscope; and a forceps opening 15 through which a treatment tool (a treatment tool) such as a forceps is inserted and fed to the distal end portion 1. A channel communicating from the forceps opening to the distal end portion, a water supply pipe for water washing of the lens at the distal end portion, an optical system, and the like are provided in the endoscope flexible tube 17. A forceps cover 16 is attached to a forceps opening 15 of the medical endoscope shown in fig. 1. One end of the tube 13 is connected to the forceps cover 16, and the other end of the tube is connected to the connector 14 for attaching a syringe or the like. The forceps cover 16 has a valve body, and one end of the tube 13 opens to a wall surface of the valve body in the forceps cover 16 on the forceps port 15 side, so that even when a treatment tool such as forceps is inserted, the liquid sent through the tube does not flow out by the valve body (see, for example, japanese patent application laid-open No. 2014-155677).
Examples
Reference example
An endoscope can be inserted into an alimentary canal such as rectum, and the inside of the alimentary canal can be observed by the endoscope. When bleeding occurs in the digestive tract 4, blood 3 accumulates in the digestive tract, and the bleeding site 2 cannot be observed (fig. 2A). At this time, an attempt was made to: tap water is filled into the syringe, and the syringe feeds water from the opening of the endoscope distal end portion 1 into the digestive tract through the tube 13, the forceps port 15, and the channel, thereby flushing away the accumulated blood water. However, the accumulated blood and the supplied water are mixed and suspended, and become turbid water 3 ″. When the turbid water 3 "is accumulated in the digestive tract, the endoscope cannot observe the bleeding part 2 because the visual field is blocked by the turbid water 3" and the operation cannot be continued (fig. 2B and 9).
As shown in fig. 3A and 3B, when a bleeding site 2 is formed in the digestive tract 4, the viscoelastic composition of the present invention is fed from the distal end of the endoscope to push away blood 3 (blood 3') accumulated in the digestive tract, thereby enabling observation of the bleeding site 2.
Examples and comparative examples
In the present example or comparative example, the relationship between the viscoelastic properties of the viscoelastic composition used in the endoscope and the securing of the visual field and the operability at the time of the operation of the endoscope was examined.
Hereinafter, a method of measuring a physical property value of the viscoelastic composition, and a method of evaluating the viscoelastic composition from the viewpoint of securing a visual field and the viewpoint of operability when the viscoelastic composition is used in an endoscope will be described.
(1) Viscosity and loss tangent
The measurement was carried out using viscosity/viscoelasticity HAAKE RS-6000 (Thermo Fisher Scientific Co., ltd.). The viscoelastic composition was placed on a sample stage, and the measurement was carried out using a P35 Ti L parallel plate (measurement conditions: temperature 25 ℃, gap 1.000mm, stress 1000mPa, frequency 0.5000 Hz), and the value 30 minutes after the start of the measurement was measured.
(2) Hardness of
The measurement was carried out using a deep meter Model RE2-33005C (Kyoho, co., ltd.). A stainless steel petri dish (45 mm outer diameter, 41mm inner diameter, 18mm outer dimension, 15mm inner dimension) was filled with the viscoelastic composition, aligned with the height of the petri dish and the sample surface was leveled. Measurements were carried out using a Plugger (Kyowa Kagaku Co., ltd., shape: circular plate, type: P-56, abstract: φ 20 × t 8) (measurement conditions: storage pitch 0.02sec, measurement distortion rate 66.67%, measurement speed 10mm/sec, return distance 5.00mm, sample thickness 15.00mm, contact surface diameter 20.00mm, contact area 0.000 mm)2 )。
(3) Electrical conductivity of
The measurement was carried out using a conductivity meter CM-41X (DKK, toyo K.) and a CT-57101C cell for low conductivity (measurement conditions: temperature 25 ℃ C.).
(4) Method for evaluating visual field assurance
A Dean-Stark tube was injected with 3mL of 1% Evans blue solution (pigment solution), and a catheter (catheter tube) equipped with a wire was inserted. In this state, the visual field is blocked by the dye solution, and the wire at the tip of the tube is not observed (fig. 4A and 5A). 10mL of a viscous composition having different loss tangent, hardness and viscosity was injected into the dye solution through a catheter (inner diameter: 2.5 to 3mm, length: 1000 mm), and the quality of visual field assurance was visually judged. When a certain viscous composition a was injected, a physical space was secured, and it was also difficult to mix the composition with the dye solution, and therefore, the viscous composition a was judged to exhibit the desired viscoelastic properties and was judged as "acceptable" as a viscoelastic composition (fig. 4B). On the other hand, when a certain viscous composition B different from the viscous composition a was injected, the physical space was not ensured clearly, and mixing with the dye solution was observed, and therefore, it was judged that the viscous composition B did not exhibit the desired viscoelastic properties, and it was judged as "failed" as the viscoelastic composition (fig. 5B).
The results obtained in this evaluation of visual field assurance correspond to, for example, differences in provision of visual fields as shown in fig. 9 and 10. That is, when the endoscope is inserted into a bleeding site and tap water is poured into the bleeding site, the visual field obtained from the camera is poor due to turbid water as shown in fig. 9. When the endoscope is inserted into the bleeding site and a viscoelastic composition exhibiting desired viscoelastic properties is injected, the bleeding site 2 can be clearly grasped in the visual field obtained from the camera, as shown in fig. 10.
(5) Method for evaluating operability
Since the viscoelastic composition for securing the visual field is injected into the digestive tract through the jaw opening (inner diameter of 2.8 to 3.8 mm) of the endoscope, it is desirable that the viscoelastic composition can be smoothly injected without excessive resistance. The passage of the viscoelastic composition was subjectively determined by filling a 50mL syringe (j.m.s, ltd.) with the viscoelastic composition having different loss tangent, hardness and viscosity, and attaching a catheter (inner diameter 3mm, length 1.000 mm) that simulates the inner diameter of a jaw opening of an endoscope to the tip of the syringe. A viscoelastic composition that can pass through smoothly or is within a practically allowable range despite some resistance is judged to be "suitable". On the other hand, a viscoelastic composition that has too much resistance to be practical or too much resistance to pass is judged to be "unsuitable".
Test example 1 relationship among loss tangent, hardness, and viscosity of viscoelastic composition
Viscoelastic compositions having different loss tangents, hardnesses, and viscosities were prepared, visual field assurance and operability were evaluated for each viscoelastic composition, and each physical property value and correlation were evaluated. The loss tangent of each of the viscoelastic compositions judged as "acceptable" in terms of visual field assurance was about 0.6 or less, and when the loss tangent exceeds this value, the compositions were all "unacceptable" (fig. 6). The hardness of the viscoelastic composition whose handling was judged to be "adequate" was about 550N/m2 The viscosity was about 2000 mPas or less, and when it exceeded this value, the film was "unsuitable" (FIG. 7). The loss tangent and hardness of the viscoelastic composition satisfying both "pass" for visual field assurance and "fit" for handling were the same values as described above (fig. 8). From these experimental examples, it is preferable that the viscoelastic composition excellent in visual field securing and handling property in endoscopic treatment has a loss tangent of 0.6 or less and a hardness of 550N/m2 The viscosity is set to 200 to 2000 mPas.
Test example 2 Electrical conductivity of viscoelastic composition
Among hemostasis by an endoscope, there are three methods: a method based on thermal coagulation using a high-frequency current, a method using a clip (clip), and a method using a drug. In the thermal coagulation method, a high-frequency current is passed through a bleeding part, and coagulation hemostasis is performed on tissue by heat generated intensively at the bleeding part. In this case, generally, when a solution or a substance having high conductivity exists around the bleeding site, a high-frequency current leaks, and sufficient thermal coagulation cannot be performed.
Based on this finding, the treatment and evaluation were performed in the following steps.
A small cylinder (diameter of about 1.5 cm) was pressed against the liver surface of a rat, the cylinder was filled with physiological saline, distilled water, or a viscoelastic composition prepared so as to have different conductivities, the tip of a single pole (Edge coating blade electrode E1450X) was gently pressed against the liver surface, and the liver surface was electrified for 2 seconds in a coagulation mode (SurgiStat II, covidien Japan, setting coagulation output to 20). Sufficient thermal coagulation was observed in the gas phase (fig. 11) and in tap water with low conductivity (fig. 12), but poor thermal coagulation was observed in physiological saline with high conductivity (fig. 13). In addition, although sufficient thermal setting was observed in the viscoelastic composition (fig. 14 and 15) having an electrical conductivity of 12.8mS/m (128 μ S/cm) or less, and thermal setting was observed to such an extent that no practical problem was observed in the viscoelastic composition (fig. 16) having an electrical conductivity of 25mS/m (250 μ S/cm) or less, for example, 22.4mS/m (224 μ S/cm) or less, thermal setting was found to be poor in the viscoelastic composition having a large electrical conductivity, for example, 60.8mS/m (608 μ S/cm) (fig. 17). From these experimental examples, it is found that the electric conductivity of the viscoelastic composition excellent in the field of view securing and handling property in endoscopic therapy is preferably 25mS/m or less, more preferably 20mS/m or less, in view of thermal coagulation hemostasis using a high-frequency current. The results are also shown in table 1 below.
[ Table 1]
TABLE 1 Electrical conductivity (thermal setting) of viscoelastic compositions
* E: excellent (sufficient thermal setting was observed)
G: good (observe heat setting)
NG: not good (insufficient heat coagulation)
Shown in table 2 below: the viscoelastic composition was evaluated as "suitable" in the operability in the endoscopic treatment, and also achieved thermal coagulation using a high-frequency current, and the respective viscoelastic compositions were also indicated as being acceptable or not for securing the visual field.
[ Table 2]
Description of the reference numerals:
1. endoscope front end portion
2. Bleeding site
3. 3' blood
3' turbid water
11. Dial scale
12. Connector part of mirror body
13. Pipe
14. Connector with a locking member
15. Clamp mouth
16. Pliers cover
17. An endoscope flexible tube.