JPH07124154A - Contact medium for probe of ultrasonic diagnostic device - Google Patents

Abstract

PURPOSE:To improve the heating resistance of a curdlan gel and enable sterilization by heating in the autoclave of a sterilizing device by using the gel essentially consisting of the curdlan which is natural polysaccharides as a contact medium for a probe after subjecting the gel to a high-pressure treatment. CONSTITUTION:This contact medium for the probe which is excellent in safety, acoustic characteristics and sterilization characteristic when a part of the gel or the gel itself is incorporated and indwelt in a living body during pricking or operation consists of the gel essentially consisting of the curdlan which is one kind of the polysaccharides produced by microorganisms and of which the constituting sugar is D glucose and having a moisture content of >=80%. The contact medium is obtd. by gelatinizing the curdlan by heating, then subjecting the gel to the high-pressure treatment. The sterilization and gel intensification are attained by further reheating the gel. The curdlan concn. of this contact medium is adequately 1 to 10% and the contact medium satisfies the conditions under which the sound velocity of ultrasonic propagation is 1480 to 1550m/s and the attenuation rate is <=0.3dB/MHz.cm. In addition, the contact medium is treated under the high-pressure treatment condition of >=100kg/cm<2>.

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 the operation and to know the internal state of the organ without cutting the surface of the organ during the operation. 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 is sandwiched between the probe and the body surface or the like at the time of diagnosis, or formed into an appropriate shape and can be used by being attached to the probe directly or by a jig. 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 diligent research to solve the above-mentioned problems, and as a result, have conducted a high-pressure treatment on a gel containing curdlan, which is a natural polysaccharide, as a main component to bring it into contact with a probe. We have found that all these problems can be solved by using it as a medium, and completed the present invention. Gels prepared from curdlan are extremely safe and have the property of gradually degrading in vivo over a long period of time even if they are left in the body (Pharmaceutical Journal 110 (10) 869-87).
5, 1990). However, the gel obtained from highly purified curdlan is still not sufficiently satisfactory in terms of heat resistance, such as cracking when autoclaved at 121 ° C. for 20 minutes. However, the present inventors have found that by subjecting the gelation to a high pressure treatment,
They found that the heating resistance of curdlan gel could be improved and solved this problem. That is, the high-pressure treated curdlan gel can be heat sterilized by a simple sterilizer autoclave, and 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., the 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 ion or magnesium ion to the alkaline aqueous solution to form a cross-linked structure with the dissociated hydroxyl group and the cation.

The probe contact medium of the present invention is a gel containing curdlan as a main component and having a water content of 80% or more, and is obtained by subjecting gelation by heating to high-pressure treatment. Depending on the case, it is possible to further sterilize and improve the gel strength by further reheating. Next, an example of the manufacturing method will be introduced. First, the above-mentioned curdlan aqueous dispersion is prepared. For curdlan concentration,
1 to 10%, preferably 2 to 5%. After degassing this dispersion under vacuum, gently inject it into a flat plate or molding mold,
Fully degas under vacuum again. This is heated in a heat sterilizer or a water bath at a temperature of 60 ° C. or higher, preferably 80 ° C. or higher, preferably for 10 minutes or longer to perform gelation. After cooling, the gel should be 100 kg / cm ² or more, preferably 1000 kg / cm ²
High-pressure treatment is performed as above, and then 60 ° C. or higher, preferably 80
A stronger gel can be obtained by heating at a temperature of ℃ or more, preferably for 10 minutes or more, or by sterilization by irradiation with radiation. The heating temperature at this time is the first time or more, and the strength of the gel can be increased by performing the heating for a longer time.

Recently, a method of increasing the gel strength by subjecting an aqueous dispersion of curdlan to high pressure treatment and then heat treatment has been disclosed (Japanese Patent Laid-Open No. 4-158752), but the mechanism is still clear. Absent. Contact media used for puncture / intraoperative must be sterile when used. Therefore, for sterilization of the contact medium, it is desirable that the sterilization operation can be easily performed in a hospital and that the most popular heat sterilizer (autoclave) can be used. Curdlan powder used at the food level contains a large amount of impurities derived from culture media and microorganisms, and the powder is slightly brownish. As a raw material of the contact medium used for puncture and intraoperative use, it is naturally desirable to use a highly purified raw material containing no such impurities. However, when the curdlan powder thus purified is used to prepare a heated gel, the gel becomes cracked as the temperature rises (mostly 100 ° C. or higher). Although crystallization of curdlan molecules due to heating is expected as a cause of the above-mentioned cracks, a method of adding another substance is generally used to suppress such crystallization. In the case of curdlan, since it is insoluble in water, it is difficult to prepare a completely homogeneous mixed solution at the molecular level. Therefore, it has been very difficult to avoid cracking of the purified curdlan gel.

However, the above pressure treatment (100 kg
/ cm ² or more, preferably 1000 to 10,000 kg / cm ² ) makes it possible to solve the problem of cracking due to heating. The pressure treatment method is 100 kg / c
Any method may be used as long as a high pressure of m ² or more can be obtained, but in recent years, an apparatus capable of performing a high pressure treatment at an arbitrary temperature is commercially available from Mitsubishi Heavy Industries. The pressurizing process is carried out by heating the curdlan dispersion at a temperature at which cracking does not occur first, preferably at 60 to 100 ° C., as compared with pressurizing the curdlan dispersion liquid and then heat-gelling it as described in JP-A-4-158755. It is preferable to perform pressure treatment after gelling, and high resistance to cracking due to heating is obtained. Since the temperature at the time of pressure treatment is already gelled, it is not necessary to carry out below the gelation temperature, and it can be set to any temperature.

The concentration of curdlan may be any concentration as long as a uniform dispersion can be obtained, but it is 1 to 10%.
It is preferably 2 to 5%. When it is 1% or less, the strength of the prepared gel is insufficient, and when it is 10% or more, the viscosity of the dispersion becomes high, and it becomes difficult to obtain a uniform gel containing no bubbles. When the gel is used as a contact medium, it must have a high water content in order to provide excellent acoustic characteristics, and the curdlan concentration is preferably 5% or less. Even at a concentration of 2 to 5%, the strength of the gel is sufficient, and the gel will not be destroyed even if it is pressed against the body surface and undergoes deformation.

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. Also by doing so, a gel showing more excellent properties can be obtained.

The gel thus prepared has appropriate flexibility and is extremely easy to mold, and is extremely advantageous in consideration of connection between a probe having a certain shape and a contact medium. . The gels thus prepared all showed good acoustic properties. That is, the speed of sound is close to that of water 1490 to 1543 m / s, and the attenuation is 0.05 to 0.2.
It was 3 dB / MHz · cm, and showed the lowest attenuation rate among the gels known so far. In addition, the mechanical strength of the gel was measured, and it was found that the fracture strength was 5.91x10 ² to 4.64x10 ³ g / c.
m ² , Young's modulus 2.16x10 ⁶ to 7.38x10 ⁶ dyn / cm ² ,
It was also clear that it had sufficient strength to be used as a contact medium for probes.

[0014]

The present invention will be described in more detail with reference to the following examples. Example 1 96.5 parts by weight of curdlan (Takeda Pharmaceutical Co., Ltd.)
By weight of water was added, and the mixture was stirred with a high speed homogenizer 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, it is filled in a heat-sealed pack and heated at 21 ° C and 3000 kg / c by a high-pressure processing device.
A treatment of m ² for 10 minutes was performed. Then, 1 with a heat sterilizer
By performing heating at 21 ° C. for 20 minutes, complete gelation and sterilization were possible at the same time by this operation. As a result of measuring the acoustic characteristics of the gel prepared as described above, a sound velocity of 150
Values of 2 m / s and 0.14 dB / MHz · cm attenuation were obtained. Also,
When the physical properties were measured with a rheometer (NRM-2010J-CW manufactured by Fudo Kogyo Co., Ltd.), the breaking strength was 2.97x10 ³ g / cm ² , and the Young's modulus was 5.19x10 ⁶ dyn / cm ² . Next, 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.

Comparative Example 1 A curdlan gel was obtained by the same procedure as in Example 1 except for the high pressure treatment. The gel was cracked by heating at 121 ° C. for 20 minutes and was unsuitable as a contact medium for a probe of an ultrasonic diagnostic apparatus. On the other hand, the high-pressure treated gel of Example 1 had no cracking even after repeated treatment at 121 ° C. for 20 minutes, and the heat resistance was clearly improved.

Comparative Example 2 (as described in JP-A-4-158755) Based on Example 1, a 3.5% curdlan dispersion was prepared and deaerated. This dispersion was filled in a heat-sealed pack, which was then heated at 21 ° C. and 3000 kg / cm ² , 10 kg.
A treatment for 1 minute was performed. Then, this treated dispersion liquid was intravenously injected into a mold, heated at 100 ° C. for 10 minutes for gelation, cooled, and then removed from the mold. Then 121 ℃, 20
When sterilized by heating for a minute, many cracks were formed, which was 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% 1495 0.07 3% 1498 0.09 4% 1508 0.13 5% 1507 0.16 ───────────────────────── Physiological saline 2% 1510 0.08 3% 1515 0.09 4% 1519 0.14 5% 1522 0.17 ━━━━━ ━━━━━━━━━━━━━━━━━━━━

Example 3 7 parts by weight of curdlan and 0.3 parts by weight of alginic acid were mixed with 92.7 parts by weight of water, and the mixture was stirred with a high-speed homogenizer at 13000 rpm 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. After 24 hours, take out the gel, wash it with water, fill it in a heat-seal pack, and use a high-pressure processor at 21 ° C for 10 minutes to 5000 kg / c.
m ² was processed. Then, heat sterilizer at 121 ℃, 2
After heating for 0 minutes, complete gelation and sterilization were performed at the same time. 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.

[0020]

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

Claims (3)

[Claims] 1. A contact medium for a probe of an ultrasonic diagnostic apparatus, which is obtained by high-pressure treatment 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 contact medium for an ultrasonic diagnostic apparatus probe according to claim 1, wherein the high-pressure treatment condition is 100 kg / cm ² or more.