JP2944393B2 - Contact medium for probe of ultrasonic diagnostic equipment - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a contact medium for a probe of an ultrasonic diagnostic apparatus.

[0002]

2. Description of the Related Art In recent years, in the treatment of internal organ diseases, in order to reduce the physical burden on a patient and improve the prognosis, a number of methods have been tried to carry out the treatment without performing a large-scale surgical operation. I have. Even if laparotomy is performed, it is extremely meaningful to know the state of the lesion in detail before the operation and to know the internal state without incising the organ surface during the operation. Will bring information. In order to achieve the object, ultrasonic diagnostics have been remarkably developed and spread in recent years, and the accuracy of preoperative diagnostics using the diagnostics has greatly contributed to the improvement of recent surgical results. In particular, the diagnostic ability has been dramatically improved by combining ultrasonic diagnostic method and fine needle aspiration cytology for thyroid disease.

However, when a probe of the ultrasonic diagnostic apparatus is directly applied to the surface of a body or an organ to observe the internal state, the characteristics of the ultrasonic diagnostic apparatus may cause
It is very difficult to get a clear image in the area within cm. Also, the actual body and organ surfaces are not flat, but each have characteristic curves and irregularities,
It is impossible for a non-variable probe having a certain shape to adhere to a target site. That is, when air is interposed between the living body and the probe, the ultrasonic wave propagation rate is significantly reduced, and an accurate image cannot be formed on the diagnostic apparatus.

In order to solve the above-mentioned problem, it is effective to interpose an appropriate spacer (contact medium) between the probe and the living body. It is preferable that the contact medium is formed into a sheet and sandwiched between the probe and the body surface or the like at the time of diagnosis, or formed into an appropriate shape and used directly or with a jig. Such a contact medium is required to have appropriate flexibility, mechanical strength, and good acoustic characteristics (low ultrasonic attenuation, etc.). A polymer gel is disclosed. However, the gels disclosed herein have problems such as insufficient mechanical strength and large attenuation of sound waves, and various efforts have been made thereafter to improve these problems. For example, a polyvinyl alcohol polymer gel (JP-A-62-298342, JP-B-2-4621)
1), highly water-absorbing resin (Japanese Patent Application Laid-Open No. 4-53544), and various organic and inorganic polymers (Japanese Patent Publication No. 2-2152) are known.

[0005]

However, the polymer gels as described above still have various problems. That is, in the case of using a synthetic polymer, there is a possibility that a part of the gel or the gel itself may be mixed and placed in a living body at the time of puncture or during surgery, and there is a concern about toxicity derived from the gel itself and residual monomers, There was a problem on safety. In addition, natural polymers and polyvinyl alcohol gels, which are considered to be highly safe, also have insufficient acoustic characteristics (for example, a high attenuation rate). To improve such acoustic characteristics, it is necessary to increase the water content. On the other hand, when the water content is increased, there is a disadvantage that the mechanical strength is reduced. In addition, polyvinyl alcohol gel is easily separated from water when pressure is applied, and is not suitable as a probe contact medium used by pressing against the surface of a body or organ. In addition, it is inferior in sterility (it is completely dissolved by heating at 121 ° C. in an autoclave which is a simple sterilization method, and the original form cannot be kept), so that it has not been put to practical use. Under such circumstances, there has been a demand for a safe probe contact medium that can be used during puncture and surgery.

[0006]

The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, have found that a gel containing curdlan, a natural polysaccharide as a main component, is used as a contact medium for a probe. As a result, the inventors have found that these problems can be all solved, and have completed the present invention. That is, the gel prepared by heating curdlan has extremely high safety, and has the property of being gradually degraded in vivo over a long period of time even if it is left in the body.
(10) 869-875, 1990). In addition, sterilization by autoclave or radiation, which is the most widely used sterilizer, is possible, and is extremely excellent as a contact medium of a probe for an ultrasonic diagnostic apparatus, particularly, a probe used during puncture and operation. Hereinafter, the configuration of the present invention will be described in detail.

[0007]

DETAILED DESCRIPTION OF THE STRUCTURE The probe contact medium is a high water content gel containing curdlan as a main component. For curdlan, see Journal of the Japan Food Industry Association, Vol. 38, No. 8, 736-742 (199
1) and other microorganisms (Alcaligenes faeca
Many strains of lis var.myxogenes or Agrobacterium
Rizobium) is a kind of polysaccharide that is composed only of D-glucose, and 99% or more of the glucosidic bonds are β-1,3 bonds. Curdlan is insoluble in water but soluble in alkaline aqueous solutions such as sodium hydroxide.
As a method for preparing a uniform aqueous dispersion of curdlan, water is added to curdlan powder and vigorously stirred with a high-speed homogenizer or a cutter mixer, or stirred with warm water of about 55 ° C using a hand or a propeller stirrer. A method of cooling after adding a curd run is known. When this aqueous dispersion is heated, a gel is formed. Gels obtained by heating are roughly classified into two types depending on the processing temperature. That is, a thermo-irreversible gel obtained by heating at 80 ° C. or higher, and a thermo-reversible gel obtained by heating at about 60 ° C. and then cooling, and are called a high-set gel and a low-set gel, respectively. It is also possible to prepare a gel by dissolving curdlan in an alkaline aqueous solution without heating and neutralizing it with carbon dioxide or the like while standing, or by removing sodium hydroxide using a dialysis membrane. it can. Alternatively, a gel can be formed by adding a cation such as calcium or magnesium ion to an alkaline aqueous solution to form a crosslinked structure by the dissociated hydroxyl group and the cation.

The method for producing the probe contact medium of the present invention may be any method as long as a gel containing curdlan as a main component and having a water content of 80% or more and containing no bubbles can be obtained, and the production method is particularly limited. Not something. For example, a few preparation methods are introduced. First, the above-mentioned aqueous dispersion of curdlan is prepared. Curd concentration is 1 ~
10 wt%, preferably 2 to 5 wt%. Although gels can be prepared at less than 1%, the gels prepared are extremely low in strength, and the gel collapses with a slight application of force, causing inconvenience in handling. For this reason, it is desirable to prepare substantially 2% or more. Similarly, gels can be prepared at a concentration of 10% or more, but when the curdlan is dispersed, the viscosity becomes extremely high, and the subsequent degassing operation becomes difficult. Moreover, the elastic modulus of the prepared gel becomes too high, and the adhesion to the body surface is impaired, which makes the gel unsuitable for ultrasonic diagnosis. Those prepared at 5% or less are suitable for actual diagnosis. The prepared dispersion is sufficiently degassed under vacuum and gently poured into a flat plate or a mold. This is heated in a pressure sterilizer or a hot water bath at a temperature of 60 ° C. or more, preferably 80 ° C. or more, preferably for 10 minutes or more to perform gelation. After cooling, a stronger gel can be obtained by reheating or sterilizing by irradiation. The heating temperature at this time is 1
The longer the time is, the more the gel strength can be increased.

As a method for preparing a neutralized gel, curdlan powder in an amount of 1 to 10% by weight is dissolved in an alkaline aqueous solution, for example, an aqueous solution of sodium hydroxide of 5 mM or more, preferably 10 to 500 mM, and degassed under vacuum. Thereafter, an equimolar aqueous solution of hydrochloric acid is injected intravenously and left for neutralization. At this time, whether or not the inside is neutralized can be easily determined from the appearance by gelling and becoming cloudy with the neutralization. The neutralized curdlan gel obtained as described above is treated at 60 ° C. or higher, preferably 8 ° C.
By heating at a temperature of 0 ° C. or more, it is possible to further firmly gel. The above gel preparation methods may be used alone or in combination.

The contact medium for a probe of the present invention includes, in addition to curdlan, which is a main component of the gel, other polymer substances (for example, alginic acid, carrageenan, agar, glucomannan,
Starch, hyaluronic acid, scleroglucan, schizophyllan, lentinan, paramylon, callose, laminaran, cellulose, methylcellulose, ethylcellulose, nitrocellulose, polyvinyl alcohol) and various salts (eg, phosphoric acid, acetic acid, lactic acid, citric acid, boric acid) Compound of one or more of the following sodium salts or potassium salts, sodium chloride), various sugars (eg, glucose, sucrose, maltose, galactose, mannose, lactose, etc.), urea, glycerin, and silicone. By doing so, a gel having better properties is obtained.

The gel prepared in this way has a moderate flexibility and is extremely easy to mold, and is very advantageous when a probe having a certain shape is connected to a contact medium. . The gels thus prepared all showed good acoustic properties. That is, the sound velocity is 1497-1504 m / s, which is close to that of water, and the attenuation is 0.06-0.16 dB / MHz.
Cm and exhibited the lowest decay rate among gels known so far. The measured mechanical strength of the gel breaking strength ^{5.37 x 10 2 ~ 4.22 x 10} 3 g / c
It showed m ² and Young's modulus of 1.96 × 10 ⁶ to 6.71 × 10 ⁶ dyn / cm ^2, and it was clear that it had sufficient strength to be used as a probe contact medium.

[0012]

EXAMPLES The present invention will be described more specifically with reference to the following examples. Example 1 Curdlan powder (Takeda Pharmaceutical Company Limited) 3 parts by weight 97
Add parts by weight of water, and add a high-speed homogenizer (Nippon Seiki;
The mixture was stirred for 10 minutes with a power homogenizer (PM-1). The above-mentioned curdlan aqueous dispersion was sufficiently degassed under vacuum, poured into a mold, and gelled by heating at 100 ° C. for 10 minutes.
After cooling and removing from the mold, heating was performed at 121 ° C. for 20 minutes in a high-pressure heat sterilizer (manufactured by Tommy Seiko; autoclave, SS-245), and complete gelation and sterilization were simultaneously possible by this operation. The obtained probe contact medium is 1 vertical.
It was 00 mm x width 50 mm x thickness 15 mm. As a result of measuring the acoustic characteristics of the probe contact medium prepared as described above, a value of a sound velocity of 1499 m / s and an attenuation of 0.12 dB / MHz · cm were obtained. In addition, a rheometer (Fudo Industry Co., Ltd .: NRM-2010)
When the physical properties were measured by J-CW), the breaking strength was 1.80 x 10 ³ g.
/ cm ² and Young's modulus 3.84 × 10 ⁶ dyn / cm ² . next,
The above contact medium is used as an ultrasonic diagnostic device (Aloka Co., Ltd .; SSD-
2000), the image was diagnosed by placing it between the probe and the skin. As a result, a clearer image (FIG. 1) was obtained as compared to the case where the contact medium was not interposed.

Comparative Example 1 (according to Japanese Patent Publication No. 62-298342) A 10% aqueous solution of polyvinyl alcohol having an average degree of polymerization of 1000 and a saponification degree of 87% was poured into a flat plate having a thickness of 15 mm.
The frozen body obtained by cooling to 30 ° C. was thawed. This freeze-thaw operation is repeated eight times to obtain a water content of 90%.
Gel was obtained. The gel was measured for sound velocity and attenuation according to Example 1. As a result, the sound velocity was 1500 m / s, which was equivalent to that of Example 1. However, the attenuation was about 10 times as high as 1.0 dB / MHz · cm, which was insufficient as a contact medium for a probe of an ultrasonic diagnostic apparatus. . FIG. 2 shows an ultrasonic diagnostic image using this contact medium.

Comparative Example 2 (as described in Japanese Patent Publication No. 1-288243) A 3% aqueous solution of polyvinyl alcohol having an average degree of polymerization of 1500 and a saponification value of 95% was heated and dissolved at 80 ° C., and then placed in a vacuum heating and stirring apparatus to degas. After cooling to 50 ° C.,
After cooling to 0 ° C. and freezing, it was warmed to room temperature and thawed.
This freeze-thaw was repeated 9 times to obtain a gel having a water content of 97%. When this gel was heat-sterilized at 121 ° C. for 20 minutes in the same manner as in Example 1, the gel was dissolved, and the original shape could not be maintained. On the other hand, in the curdlan gel shown in Example 1, no deformation due to heating at 121 ° C. for 20 minutes was observed at all, and no change was observed in the acoustic characteristics.

Comparative Example 3 (according to the description of Japanese Patent Publication No. 22152/1000) An aqueous solution containing 150 g of acrylamide monomer and 8 g of N, N-methylenebisacrylamide was prepared in 1000 ml, and 100 ml of a 5% aqueous solution of dimethylaminopropionitrile was added to this solution. Add 100 ml of 1% potassium persulfate and mix well, taking care not to contain air bubbles. Immediately pour the mixture into a 10 cm long, 15 cm wide, 10 cm deep container.
The reaction was performed at 10 ° C. for 10 hours. Unreacted acrylamide monomer remained in the gel prepared as described above, and when this was used for ultrasonic diagnosis, its toxicity was concerned.

Comparative Example 4 (according to the description in JP-A-55-63636) A copolymerization ratio of ethylene oxide and propylene oxide was 80/20 in 100 parts by weight of water at room temperature, and
The ratio of H to tolylene diisocyanate -NCO is 2/4
8 parts by weight of hydrophilic polyurethane was added and dispersed quickly and uniformly. Immediately, the mixture was poured into a polypropylene container and left as it was for 30 minutes to obtain a polyurethane-containing hydrogel. In the gel prepared as described above, unreacted ethylene oxide remained. In recent years, there is a concern that ethylene oxide used for gas sterilization may exhibit toxicity due to its residual, and thus the prepared gel was considered to be inappropriate as a contact medium for a probe of an ultrasonic diagnostic apparatus.

Example 2 A contact medium for a probe was prepared by using an isotonic aqueous solution of sodium chloride instead of water in the above example and further adjusting the curdlan concentration to 2 to 5%. By adding the salt in this manner, it became possible to prevent the deterioration of the gel during storage as compared with the case of water. In addition, no decrease in acoustic characteristics due to the addition of the salt was observed at all (Table 1), and a clear diagnostic image was obtained by using the probe contact medium.

[Table 1] Influence of salt on acoustic properties of curdlan gel ━━━━━━━━━━━━━━━━━━━━━━━━━ Preparation liquid curdlan sound speed attenuation concentration m / s dB / MHz ・ cm ───────────────────────── Water 2% 1497 0.06 3% 1499 0.12 4% 1501 0.14 5% 1504 0.16 ───────────────────────── Saline 2% 1508 0.07 3% 1512 0.08 4% 1513 0.13 5% 1519 0.16 ━━━━━ ━━━━━━━━━━━━━━━━━━━━

EXAMPLE 3 9 parts by weight of 2.7 parts by weight of curdlan and 0.3 parts by weight of alginic acid
Add 7 parts by weight of water, and use a high-speed homogenizer.
Spin and stir for 5 minutes. After degassing this under vacuum, it was poured into a mold and gelled by heating at 100 ° C. for 10 minutes. After cooling and removing from the mold, it was immersed in a 10% calcium chloride solution to gel the alginic acid. Twenty-four hours later, the gel is taken out and washed with water.
The mixture was heated at 21 ° C. for 20 minutes to perform complete gelation and sterilization at the same time. Ultrasonic diagnosis was performed using the obtained probe contact medium, and a clearer image was obtained than when no contact medium was used.

Example 4 To 7 parts by weight of curdlan, 3 parts by weight of the additives shown in the following table were added, and 90 parts by weight of water were added thereto.
The mixture was stirred at 000 rpm for 10 minutes. After degassing this under vacuum, it was intravenously injected into a flat plate and gelled by heating at 100 ° C. for 10 minutes. Table 2 shows the results of visual observation of the prepared gel and the results of ultrasonic image diagnosis.

[Table 2] Additive effect of additive ━━━━━━━━━━━━━━━━━━━━━━━━━━━ Additive Visual observation result Ultrasonic image ━━━ ━━━━━━━━━━━━━━━━━━━━━━━━ ゜ 良好 良好 良好 良好 ゜ ゜ Polyvinyl alcohol Slightly wet on the surface 良好 Good Karachinan Good Methyl cellulose Slightly wet on the surface ス ルYellow, good good ━━━━━━━━━━━━━━━━━━━━━━━━━━━

Example 5 3 parts by weight of a curdlan powder was dissolved in 97 parts by weight of a 150 mM sodium hydroxide solution and deaerated under vacuum.
Gently pour the same amount of 150 mM hydrochloric acid aqueous solution from above.
Neutralization was carried out by allowing to stand for a time. After neutralization, the gel was taken out and washed in physiological saline to obtain a contact medium for a probe. Ultrasonic diagnosis using this probe contact medium has revealed that a clear image can be obtained.

Example 6 To 6 parts by weight of curdlan, 94 parts by weight of physiological saline was added, stirred for 10 minutes with a high-speed homogenizer, degassed under vacuum, and then gelled by heating at 100 ° C. for 10 minutes. went. After cooling and removal from the mold, it was placed in a container filled with physiological saline and sterilized by gamma irradiation. The physical properties of the obtained probe contact medium are as follows: breaking strength 5.23 x 10 ³ g /
cm ² and Young's modulus 7.23 × 10 ⁶ dyn / cm ² . Ultrasonic diagnosis was performed using this probe contact medium, and as a result, a clearer image was obtained as compared with the case where no probe was used.

Example 7 97 parts by weight of a urea solution having the concentration shown in the following table were added to 3 parts by weight of curdlan powder, and the mixture was stirred with a high-speed homogenizer for 10 minutes. After sufficiently degassing the curdlan dispersion under vacuum,
It was poured into a mold and gelled by heating at 100 ° C. for 10 minutes. After cooling and removing from the mold, heating was performed at 121 ° C. for 20 minutes in a high-pressure heat sterilizer, and by this operation, complete gelation and sterilization were simultaneously possible. Table 3 shows the gel breaking strength and Young's modulus at this time. When the above-mentioned contact medium was placed between the probe of the ultrasonic diagnostic apparatus and the skin to perform an image diagnosis, a clearer image was obtained as compared to the case where no gel was interposed.

[Table 3] Effect of urea addition 尿素 Urea concentration Breaking strength Young's modulus (mM) (× 10 ³ g / cm ² ) (× 10 ⁶ dyn / cm ² ) ━━━━━━━━━━━━━━━━━━━━━━━━━10 1.70 4.44 50 2.49 4 .97 100 2.98 4.20 500 1.50 1.99

Example 8 To 3.5 parts by weight of curdlan powder, 96.5 parts by weight of an aqueous solution of glucose and sucrose shown in the table below was added, and the mixture was stirred with a high-speed homogenizer for 10 minutes. The above curdlan dispersion was sufficiently degassed under vacuum, poured into a mold, and gelled by heating at 100 ° C. for 10 minutes. After cooling and removing from the mold, heating was performed at 121 ° C. for 20 minutes in a high-pressure heat sterilizer, and by this operation, complete gelation and sterilization were simultaneously possible. Table 4 shows the breaking strength and Young's modulus of the gel at this time.
Shown in When the above-mentioned contact medium was placed between the probe of the ultrasonic diagnostic apparatus and the skin to perform an image diagnosis, a clearer image was obtained as compared to the case where no gel was interposed.

[Table 4] Effect of adding urea ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Aqueous sugar solution Breaking strength Young's modulus (concentration: mM ) (× 10 ³ g / cm ² ) (× 10 ⁶ dyn / cm ² ) ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ glucose ( 75) 3.41 7.10 Glucose (150) 3.12 6.51 Sucrose (75) 2.24 5.48 Sucrose (150) 2.68 5.52 ━━━━━━━━━━━━━━━━━━━

Example 9 To 3.5 parts by weight of curdlan powder was added 96.5 parts by weight of an aqueous solution of 150 mM sodium lactate, and 10 parts by weight of a high-speed homogenizer.
Stirred for minutes. The above curdlan dispersion was sufficiently degassed under vacuum, poured into a mold, and gelled by heating at 100 ° C. for 10 minutes. After cooling and removing from the mold, heating was performed at 121 ° C. for 20 minutes in a high-pressure heat sterilizer, and by this operation, complete gelation and sterilization were simultaneously possible. When the above-mentioned contact medium was placed between the probe of the ultrasonic diagnostic apparatus and the skin to perform an image diagnosis, a clearer image was obtained as compared to the case where no gel was interposed.

[0029]

The contact medium for the probe of the ultrasonic diagnostic apparatus according to the present invention is made of a gel having a high water content and has extremely excellent ultrasonic characteristics and mechanical strength. In addition, since natural polysaccharides are used as raw materials, the safety is high, and in addition, large quantities can be supplied at low cost. Further, an ordinary autoclave can be used and sterilization is easy. Further, the probe contact medium of the present invention can be directly fixed to the probe of the ultrasonic diagnostic apparatus using appropriate connecting parts, and the usability thereof is considered to be much improved as compared with the conventional art. Can be

[Brief description of the drawings]

FIG. 1 is a photograph of an ultrasonic diagnostic image. The left side is an ultrasonic diagnostic image of a human neck when the probe contact medium prepared in Example 1 is used, and the right side is an image without the use thereof. is there.

FIG. 2 is a photograph of an ultrasonic diagnostic image, the right side is an ultrasonic diagnostic image of a human neck when the probe contact medium prepared in Example 1 is used, and the left side is a probe prepared in Comparative Example 1. It is an image at the time of using the contact medium for use.

Continuation of the front page (56) References JP-A-4-158752 (JP, A) JP-A-3-10680 (JP, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) A61B 8 / 00-8/15 JICST file (JOIS)

Claims (4)

(57) [Claims] 1. A probe contact medium for an ultrasonic diagnostic apparatus, comprising a gel containing curdlan as a main component. 2. The method according to claim 1, wherein the curd run concentration is 1 to 10%, the sound speed of ultrasonic wave propagation is 1480 m / s to 1550 m / s, and the attenuation rate is 0.3 dB / MHz.
The contact medium for a probe of the ultrasonic diagnostic apparatus according to claim 1, which is not more than cm. 3. The composition according to claim 1, wherein the composition contains one or more members selected from the group consisting of sodium or potassium salts of inorganic or organic acids, sodium chloride, sugar, and urea. A contact medium for a probe of the ultrasonic diagnostic apparatus according to the above. 4. A compound selected from the group consisting of alginic acid, carrageenan, agar, glucomannan, starch, hyaluronic acid, scleroglucan, schizophyllan, lentinan, paramylon, callose, laminaran, cellulose, methylcellulose, ethylcellulose, nitrocellulose, and polyvinyl alcohol. 3. The method according to claim 1, further comprising at least one or more kinds of polymer substances.
A contact medium for a probe of the ultrasonic diagnostic apparatus according to the above.