JPH06296611A - Contact medium for probe of ultrasonic diagnostic device - Google Patents

Abstract

PURPOSE:To provide the contact medium for the probe of an ultrasonic diagnostic device having excellent ultrasonic characteristics and mechanical strength and having safety by using a gel consisting essentially of curdlar as the contact medium for the probe and specifying the concn. of this curdlan and the sound velocity and attenuation rate of ultrasonic propagation respectively specific values. CONSTITUTION:The contact medium for the probe of the ultrasonic diagnostic device is formed out of a gel consisting essintially of the curdlan. The concn. of the curdlan is specified to 1 to 10%, the sound velocity of the ultrasonic propagation to 1480 to 1550m/s and the attenuation rate to 0.3db/NHz.cm. The contact medium for the probe contains one or >= 2 kinds selected from the group consisting of sodium salts or potassium salts of inorg. acids or org. acids, sodium chloride, sugar and urea. Further, the contact medium for the probe contains high-molecular materials, such as alginic acid, carrageenin, agar, glucomannnan, starch, hyaluloronic acid, sclerglucan, schizophyllar, etc.

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, many methods have been tried in order to reduce the physical burden on the patient and to improve the prognosis, without the need for major surgery. There is. Even if a laparotomy is performed, it is extremely meaningful to know the state of the lesion before surgery and to know the internal state without making an incision on the surface of the organ during the surgery. It will bring information. In order to achieve this purpose, ultrasonic diagnosis has been remarkably developed and spread in recent years, and the accuracy of preoperative diagnosis using it has greatly contributed to the improvement of recent surgical results. Especially, by combining ultrasonic diagnosis and fine needle aspiration cytology with thyroid disease, the diagnostic ability has been dramatically improved.

However, when the probe of the ultrasonic diagnostic apparatus is directly applied to the body surface or the surface of the organ to observe the internal state, due to the characteristics of the ultrasonic diagnostic apparatus, the subsurface number
It is very difficult to get a clear image in the area within cm. In addition, the actual surface of the body / organ is not in a flat state, but each has its own characteristic curves and irregularities,
It is impossible to adhere to a target site with an immutable probe that maintains a certain shape. That is, if air is present between the living body and the probe, the ultrasonic wave transmissivity is significantly reduced, and an accurate image cannot be formed on the diagnostic device.

In order to solve the above problems, it is effective to interpose an appropriate spacer (contact medium) between the probe and the living body. The contact medium is preferably in the form of a sheet, which can be sandwiched between the probe and the body surface or the like at the time of diagnosis, or can be molded into an appropriate shape and used by being directly or jig-fitted to the probe. Such a contact medium is required to have appropriate flexibility, mechanical strength, and good acoustic characteristics (low ultrasonic attenuation rate, etc.). For example, Japanese Patent Laid-Open No. 55-63636 discloses Polymer gels are disclosed. However, the gels disclosed here have problems such as insufficient mechanical strength and large attenuation of sound waves, and various efforts have been made since then to improve them. For example, polyvinyl alcohol type polymer gel (Japanese Patent Laid-Open No. 62-298342, Japanese Patent Publication No. 2-4621).
1), super absorbent polymer (JP-A-4-53544) and various organic and inorganic polymers (Japanese Patent Publication No. 2152) are known.

[0005]

However, the polymer gel as described above still has various problems. That is, when using a synthetic polymer, there is a possibility that part of the gel or the gel itself may be mixed and left in the body during puncture or during surgery, and there is concern about the toxicity derived from the gel itself and residual monomers. There was a safety issue. Also, natural polymers and polyvinyl alcohol gels, which are considered to have high safety, have insufficient acoustic characteristics (for example, high attenuation rate), and it is necessary to increase the water content in order to improve such acoustic characteristics. On the other hand, there is a drawback that the mechanical strength is lowered when the water content is increased. Further, polyvinyl alcohol gel easily releases water when pressure is applied, and is not suitable as a contact medium for a probe that is pressed against the surface of a body or an organ for use. In addition, it has poor sterility (it cannot be put into practical use because it cannot be retained in its original form because it is completely dissolved by heating at 121 ° C. in an autoclave, which is a simple sterilization method). Under such circumstances, there has been a demand for a safe contact medium for a probe that can be used during puncture and surgery.

[0006]

The inventors of the present invention have conducted extensive studies to solve the above-mentioned problems, and as a result, have found that a gel containing curdlan, which is a natural polysaccharide, as a main component is used as a contact medium for a probe. As a result, they have found that all of these problems can be solved, and completed the present invention. That is, the gel prepared by heating curdlan has extremely high safety and has the property of gradually degrading in vivo over a long period of time even if it is left in the body (Pharmaceutical Journal 110
(10) 869-875, 1990). Moreover, it is possible to sterilize by using the most commonly used sterilizer autoclave or radiation, and it is extremely excellent as a contact medium for a probe for an ultrasonic diagnostic apparatus, particularly for a probe used during puncture or surgery. Hereinafter, the configuration of the present invention will be described in detail.

[0007]

[Detailed Description of Configuration] The contact medium for the present probe is a highly hydrous gel containing curdlan as a main component. For curdlan, Vol.38, No.8,736-742 (199
1) etc., microorganisms (Alcaligenes faeca
Many strains of lis var.myxogenes or Agrobacterium
Rizobium) is a type of polysaccharide that is composed of only D-glucose, and 99% or more of its glucoside bonds are β-1,3 bonds. Curdlan is insoluble in water but soluble in alkaline aqueous solutions such as sodium hydroxide.
To prepare a uniform aqueous dispersion of curdlan, add water to curdlan powder and stir vigorously with a high-speed homogenizer or a cutter mixer, or stir hot water at about 55 ° C using a hand or a propeller stirrer. While adding curdlan, a method of cooling is known. A gel is formed when this aqueous dispersion is heated. Gels obtained by heating are roughly classified into two types depending on the treatment 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, which are respectively called a high set gel and a low set gel. It is also possible to prepare a gel by dissolving curdlan in an alkaline aqueous solution without heating and neutralizing it with carbon dioxide gas while still 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 with the dissociated hydroxyl group and the cation.

The method for producing the contact medium for a probe 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 no bubbles is obtained, and the production method is not particularly limited. Not something. For example, to introduce a few preparation methods, first, the above-mentioned curdlan aqueous dispersion is prepared. The curdlan concentration is 1 to
10 wt% and preferably 2 to 5 wt%. Although the gel can be prepared with 1% or less, the strength of the prepared gel is remarkably low, and the gel disintegrates even if a slight force is applied, which causes inconvenience in handling. Therefore, it is desirable that the amount is substantially adjusted to 2% or more. Similarly, a gel can be prepared even at a concentration of 10% or more, but the viscosity becomes extremely high when the curdlan is dispersed, and the subsequent deaeration operation becomes difficult. In addition, the elastic modulus of the prepared gel becomes too high, and the adhesion to the body surface is impaired, making it unsuitable for ultrasonic diagnosis. Those prepared at 5% or less are suitable for actual diagnosis. The prepared dispersion is thoroughly degassed under vacuum and gently poured into a flat plate or a molding mold. This is heated in an autoclave or a hot water bath at a temperature of 60 ° C. or higher, preferably 80 ° C. or higher, preferably 10 minutes or longer to perform gelation. After cooling, a stronger gel is obtained by heating again or sterilizing by irradiation. The heating temperature at this time is 1
The strength of the gel can be increased by performing the treatment more than the first time and for a longer time.

As a method for preparing the neutralized gel, 1 to 10 wt% of curdlan powder is dissolved in an alkaline aqueous solution, for example, an aqueous solution of 5 mM or more of sodium hydroxide, preferably a solution of 10 to 500 mM, and degassed under vacuum. After that, an equimolar hydrochloric acid aqueous solution is intravenously injected and left to neutralize. At this time, whether or not the inside has been neutralized can be easily judged from the appearance by the appearance of gelation and white turbidity accompanying neutralization. The neutralized curdlan gel obtained as above is treated at 60 ° C. or higher, preferably 8
By heating at a temperature of 0 ° C. or higher, gelation can be further strengthened. The gel preparation methods described above may be used alone or in combination.

In the contact medium for a probe of the present invention, in addition to the curdlan which is the main component of the gel, other polymeric substances (eg, alginic acid, carrageenan, agar, glucomannan,
Starch, hyaluronic acid, scleroglucan, schizophyllan, lentinan, paramylon, callose, laminaran, cellulose, methyl cellulose, ethyl cellulose, nitrocellulose, polyvinyl alcohol) and various salts (eg phosphoric acid, acetic acid, lactic acid, citric acid, boric acid) Each sodium salt or potassium salt, sodium chloride), various sugars (for example, glucose, sucrose, maltose, galactose, mannose, lactose, etc.), urea, glycerin, silicone, and one or more substances are mixed. By doing so, a gel having more excellent properties can be obtained.

The gel thus prepared has appropriate flexibility and is extremely easy to mold, and is extremely advantageous in connection with the connection between the probe having a certain shape and the contact medium. . The gels thus prepared all showed good acoustic properties. That is, the speed of sound is 1497 to 1504 m / s, which is close to that of water, and the attenuation is 0.06 to 0.16 dB / MHz.
-Cm, which showed the lowest attenuation of any gel known to date. Further, the mechanical strength of the gel was measured, and the breaking strength was 5.37 x 10 ² to 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 also clear that it has sufficient strength to be used as a contact medium for a probe.

[0012]

The present invention will be described in more detail with reference to the following examples. Example 1 3 parts by weight of curdlan powder (Takeda Pharmaceutical Co., Ltd.) to 97 parts
Add parts by weight of water and add a high speed homogenizer (Nippon Seiki;
The mixture was stirred with a power homogenizer, PM-1) for 10 minutes. The above curdlan aqueous dispersion was thoroughly degassed under vacuum, poured into a mold, and gelled by heating at 100 ° C. for 10 minutes.
After cooling and taking out from the mold, heating was performed at 121 ° C. for 20 minutes with a high-pressure heat sterilizer (Tomy Seiko; autoclave, SS-245), and by this operation, complete gelation and sterilization were possible at the same time. The obtained contact medium for the probe has a length of 1
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, values of a sound velocity of 1499 m / s and an attenuation of 0.12 dB / MHz · cm were obtained. Rheometer (Fudo Kogyo Co., Ltd .: NRM-2010)
J-CW) measured the physical properties, the breaking strength 1.80 x 10 ³ g
/ cm ² , Young's modulus was 3.84 x 10 ⁶ dyn / cm ² . next,
The contact medium is an ultrasonic diagnostic device (Aloka Co., Ltd .; SSD-
2000), the image was placed between the probe and the skin, and a clear image (Fig. 1) was obtained as compared with the case where no contact medium was interposed.

Comparative Example 1 (as described in JP-B-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 8 times to obtain a water content of 90%.
A gel of The speed of sound and the attenuation of this gel were measured in accordance with Example 1. As a result, the sound velocity was 1500 m / s, which was the same as in Example 1, but the attenuation was 1.0 dB / MHz · cm, which was about 10 times higher, and was insufficient as the contact medium for the probe of the ultrasonic diagnostic apparatus. . An ultrasonic diagnostic image using this contact medium is shown in FIG.

Comparative Example 2 (as described in JP-B-1-288243) A 3% aqueous solution of polyvinyl alcohol having an average degree of polymerization of 1500 and a saponification number of 95% was heated and dissolved at 80 ° C., and then placed in a vacuum heating and stirring apparatus for degassing. And then allowed to cool to 50 ° C, then -3
After cooling to 0 ° C. and freezing, the mixture was warmed to room temperature and thawed.
This freeze-thawing was repeated 9 times to obtain a gel having a water content of 97%. When this gel was sterilized by heating 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 retained. 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, and no change in acoustic characteristics was observed.

Comparative Example 3 (according to the description in Japanese Patent Publication No. 2-21252) 1000 ml of an aqueous solution containing 150 g of acrylamide monomer and 8 g of N, N-methylenebisacrylamide was prepared, and 100 ml of 5% dimethylaminopropionitrile aqueous solution was added to this solution. Add 100 ml of 1% potassium persulfate and mix well, being careful not to contain air bubbles, and immediately pour into a container 10 cm in length, 15 cm in width, 10 cm in depth and 40
The reaction was carried out at 0 ° C for 10 hours. Unreacted acrylamide monomer remained in the gel prepared as described above, and its toxicity was feared when this was used for ultrasonic diagnosis.

Comparative Example 4 (as described in JP-A-55-63636) 100 parts by weight of water at room temperature has a copolymerization ratio of ethylene oxide and propylene oxide of 80/20 and -O.
The ratio of H to tolylene diisocyanate -NCO is 2/4.
Then, 8 parts by weight of the hydrophilic polyurethane was rapidly added and uniformly dispersed, and then immediately poured into a polypropylene container and allowed to stand for 30 minutes to obtain a polyurethane hydrogel. Unreacted ethylene oxide remained in the gel prepared as described above. In recent years, it has been feared that ethylene oxide, which is also used for gas sterilization, may develop toxicity due to its residue, and the prepared gel was considered to be unsuitable 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 sodium chloride aqueous solution instead of the water in the above example and further adjusting the curdlan concentration to 2 to 5%. By adding salt in this way, it became possible to prevent the deterioration of the gel during storage as compared with the case of water. Further, no deterioration in acoustic characteristics due to the addition of salt was observed (Table 1), and a clear diagnostic image was obtained by using the contact medium for a probe.

[Table 1] Effect of salt on acoustic characteristics of curdlan gel ━━━━━━━━━━━━━━━━━━━━━━━━━ Preparation liquid curdlan Sound velocity attenuation Concentration m / s dB / MHz ・ cm ───────────────────────── Water 2% 1497 0.06 3% 1499 0.12 4% 1501 0.14 5% 1504 0.16 ───────────────────────── Physiological saline 2% 1508 0.07 3% 1512 0.08 4% 1513 0.13 5% 1519 0.16 ━━━━━ ━━━━━━━━━━━━━━━━━━━━

Example 3 2.7 parts by weight of curdlan and 9 parts by weight of 0.3 parts by weight of alginic acid
Add 7 parts by weight of water and use a high speed homogenizer to
Spin for 5 minutes. This was degassed under vacuum, then poured into a mold and heated at 100 ° C. for 10 minutes to cause gelation. After cooling and removing from the mold, the gel was dipped in a 10% calcium chloride solution to gel alginic acid. Take out the gel after 24 hours, wash it with water, and use a high-pressure heat sterilizer to
Complete gelation and sterilization were performed simultaneously by heating at 21 ° C. for 20 minutes. When ultrasonic diagnosis was performed using the obtained contact medium for a probe, a clear and clear image was obtained as compared with the case where the contact medium was not used.

Example 4 To 7 parts by weight of curdlan, 3 parts by weight of the additives shown in the table below were added, and 90 parts by weight of water was added thereto, and the mixture was mixed with a high-speed homogenizer at 10 parts by weight.
The mixture was stirred at 000 rpm for 10 minutes. This was degassed under vacuum, then intravenously injected onto a flat plate and heated at 100 ° C. for 10 minutes for gelation. 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 ━━━ ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ ━━━━━━━ Yellow, good Good ━━━━━━━━━━━━━━━━━━━━━━━━━━━

Example 5 3 parts by weight of curdlan powder was dissolved in 97 parts by weight of 150 mM sodium hydroxide solution and deaerated under vacuum,
Pour an equal volume of 150 mM hydrochloric acid solution gently from above 48
It was left to stand for a period of time for neutralization. After neutralization, the gel was taken out and washed in physiological saline to obtain a probe contact medium. Ultrasonic diagnosis using this contact medium for a probe 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, deaerated under vacuum, and then heated at 100 ° C. for 10 minutes to cause gelation. went. After cooling and removing from the mold, it was placed in a container filled with physiological saline and sterilized by γ-ray irradiation. The physical properties of the obtained contact medium for a probe have a breaking strength of 5.23 x 10 ³ g /
It was cm ² , and Young's modulus was 7.23 x 10 ⁶ dyn / cm ² . As a result of ultrasonic diagnosis using this contact medium for a probe, a clear and clear image was obtained as compared with the case where this was not used.

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

[Table 3] Effect of Urea Addition ━━━━━━━━━━━━━━━━━━━━━━━━━ 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 was added 96.5 parts by weight of the glucose / sucrose aqueous solution shown in the table below, and the mixture was stirred with a high-speed homogenizer for 10 minutes. The curdlan dispersion was thoroughly degassed under vacuum, poured into a mold, and gelled by heating at 100 ° C. for 10 minutes. After cooling and taking out from the mold, heating was performed at 121 ° C. for 20 minutes in a high-pressure heat sterilizer, and this operation enabled complete gelation and sterilization at the same time. The breaking strength and Young's modulus of the gel at this time are shown in Table 4.
Shown in. When the above contact medium was placed between the probe of the ultrasonic diagnostic apparatus and the skin for image diagnosis, a clear and clear image was obtained as compared with the case where no gel was interposed.

[Table 4] Effect of Urea Addition ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Sugar aqueous 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, 96.5 parts by weight of a 150 mM sodium lactate aqueous solution was added, and the mixture was mixed with a high-speed homogenizer to obtain 10 parts.
Stir for minutes. The curdlan dispersion was thoroughly degassed under vacuum, poured into a mold, and gelled by heating at 100 ° C. for 10 minutes. After cooling and taking out from the mold, heating was performed at 121 ° C. for 20 minutes in a high-pressure heat sterilizer, and this operation enabled complete gelation and sterilization at the same time. When the above contact medium was placed between the probe of the ultrasonic diagnostic apparatus and the skin for image diagnosis, a clear and clear image was obtained as compared with the case where no gel was interposed.

[0029]

The contact medium for the probe of the ultrasonic diagnostic apparatus of the present invention is composed of a gel having a high water content and has extremely excellent ultrasonic characteristics and mechanical strength. Moreover, since the natural polysaccharide is used as a raw material, it is highly safe, and in addition, it can be inexpensively supplied in large quantities. In addition, 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 by using an appropriate connecting component, and its usability is considered to be much improved as compared with the conventional one. To be

[Brief description of 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 contact medium for a probe prepared in Example 1 is used, and the right side is an image when it is not used. is there.

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

Claims (4)

[Claims] 1. A contact medium for a probe of an ultrasonic diagnostic apparatus, which is made of a gel containing curdlan as a main component. 2. The curdlan concentration is 1 to 10%, the sound velocity 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 has a size of cm or less. 3. The method according to claim 1, which contains one or more 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 described ultrasonic diagnostic apparatus. 4. Selected from the group consisting of alginic acid, carrageenan, agar, glucomannan, starch, hyaluronic acid, scleroglucan, sizofiran, lentinan, paramylon, callose, laminaran, cellulose, methylcellulose, ethylcellulose, nitrocellulose, and polyvinyl alcohol. 3. At least one kind of polymer substance to be contained is contained.
A contact medium for a probe of the described ultrasonic diagnostic apparatus.