JPH11253564A - Sponge for radiotherapy - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prevent a heavy corpuscular ray trouble from occurring by crosslinking between molecules of, collagen, or a mixture of collagen and gelatin is, and a sponge having an elastic force is formed. SOLUTION: For example, oxygen-soluble athero-collagen is prepared to be an acidic solution (approx. PH3) of a concentration of approx. 1%. The solution is poured into a plastic tray of four edges of approx. 10 cm, in a manner to become approx. 15 cm high, and neutralized in an ammonia saturated gas. Then, a freeze-drying is performed, and a collagen sponge with a thickness of approx. 15 mm, is obtained. The collagen sponge is dipped in an ethanol solution of approx. 1% for approx. 3 hours, and after being crosslinked, the collagen sponge is dried with air. Then, the collagen sponge is dipped in water, and is pinched between plastic plates under the water-contained state, and is compressed to a height of 5 mm, and freeze-dried as is, and a compression- molded sponge is obtained. The compressed sponge is placed in water and swollen, and returned to the original thickness which is approx. 15 mm. Thus, this sponge which is used to prevent a heavy corpuscular ray trouble from occurring, is obtained.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a radiotherapy sponge used for preventing heavy ion beam damage caused during radiotherapy.

[0002]

2. Description of the Related Art Conventionally, removal of a malignant tumor or the like has involved removing the tumor directly by laparotomy. This method imposes a heavy burden on the patient, takes a long time to recover after the operation, and further increases the burden when reoperation is performed. Therefore, it is desired that the treatment can be performed without laparotomy. As one of the methods, irradiation with radiation to destroy malignant tumor cells has been performed.

[0003] Radiotherapy is a method of irradiating and treating a malignant tumor site. This method can treat only a target site without impairing the physical function of the patient.
Moreover, since there is no need for laparotomy, the burden on the patient during and after the operation is not only light, but also the recovery is quick. Radiation used in radiation therapy includes X-rays, gamma rays, heavy ion beams, fast neutron beams, and proton beams, all of which are intended to pass through the skin and act on the target site. .

[0004] Due to the high transmittance of radiation, there is a problem in that it passes through a target site and affects a site behind the target site or damages tissue up to the target site. However, among those treatments, it is said that particle beams, for example, heavy particle beams, use very fast charged particles, so that damage to other tissues is small, but organs still When they are in close contact, it is difficult to perform treatment. Therefore, it is conceivable to insert a spacer between these organs to separate the organs from each other. However, in this radiotherapy, irradiation cannot be performed on the laparotomy-stitched skin, and its use is greatly limited.

[0005]

Therefore, the present inventor has proposed:
As a result of various investigations to solve the above problems, it was found that a small spacer was inserted into the abdominal cavity under an endoscope and placed between predetermined organs to irradiate only the target organ. As a result of further investigation, it was found that by using collagen or a mixture of collagen and gelatin as a spacer, the spacer was eventually absorbed, so that reoperation for removing the spacer was unnecessary. An object of the present invention is to provide a radiotherapy consisting of collagen or a mixture of collagen and gelatin used to prevent heavy ion beam damage caused during radiotherapy. Is to provide a sponge.

[0006]

The gist of the present invention is to provide a radiation treatment sponge which is insolubilized by introducing an intermolecular crosslink into collagen or a mixture of collagen and gelatin, wherein the sponge is released from a load applied thereto. A sponge for radiation therapy, characterized in that it has a force to return to its original state. That is, the sponge for radiotherapy of the present invention has an intermolecular cross-linked collagen or a mixture of collagen and gelatin, whereby the sponge has a sufficient elastic force, and has a sufficient elastic force to restore when compressed. Have.

[0007]

Next, the present invention will be described in detail. The collagen in the present invention may be any collagen, for example, acid-soluble collagen, neutral salt-soluble collagen, enzyme-solubilized collagen, alkali-solubilized collagen and succinylated collagen obtained by chemically modifying these collagens, acylated collagen, There are methylated collagen and the like. Gelatin is a parent gelatin having a molecular weight of about 100,000 obtained by thermally denaturing such collagen, or a gelatin having a molecular weight of 100,000 or less obtained by hydrolyzing it.

[0008] The collagen concentration in the preparation of the sponge of the present invention is desirably in the range of 0.5% to 10%, particularly 1% to 5%. Collagen concentration affects the elasticity and degradation rate of the sponge. That is, if the concentration is too high, compression cannot be performed, and the decomposition rate is too slow. Conversely, if the concentration is too low, restoration cannot be performed, and the decomposition rate is too fast. Also, the elasticity and the decomposing ability of the sponge can be adjusted by mixing the same concentration of gelatin as collagen. Although depending on the collagen concentration, the mixing ratio of gelatin is preferably 1/10 to 1/2 of that of collagen.

A sponge is prepared from the prepared collagen solution or a mixed solution of collagen and gelatin. At that time, if the thickness of the sponge is small, the sponge is out of the indwelling area when irradiating radiation, and there is a possibility of damaging surrounding tissues. Therefore, it is necessary to provide a certain thickness. Therefore, it is desirable that the thickness of the sponge is 10 mm or more. The means for producing the sponge is not particularly limited. For example, the sponge can be poured into a mold and then freeze-dried to obtain a sponge.

The obtained sponge is crosslinked so that it does not collapse even when it is put in water. The crosslinking method is not limited, and for example, ultraviolet crosslinking, glutaraldehyde (GA) crosslinking, hexamethylene diisocyanate (HMDIC) crosslinking, formalin crosslinking, epoxy crosslinking and the like can be used. Since the sponge of the present invention is used as a spacer, and it is desired that the sponge is reduced in size and introduced into the abdominal cavity and then expanded in the abdominal cavity as described later, it is necessary to have a restoring force even in a water-containing state. Become. The sponge of the present invention has a thickness of 10 mm
As described above, the restoring force is 40 g / cm in a hydrated state.
Desirably, the thickness is reduced to 5 mm or less when a load of ² is applied, and the force restores the original thickness when the load is removed.

Although the present sponge can be put into the place where it is to be kept, it is necessary to open the abdomen. Therefore, it is desirable that a sponge can be placed at a predetermined site by an operation under a laparoscope. For this purpose, the sponge is compressed and placed through a device such as a tracker through a small-diameter hole opened in the abdominal cavity. The sponge is compression-molded into a cylindrical shape according to the inner diameter of the tracker to be introduced into the body, and is freeze-dried to a shape that can be passed through the tracker. When the obtained sponge is to be kept in the body by an operation under a laparoscope, the sponge can be swollen with a physiological saline or the like in the tracker. In addition, after being placed, the sponge becomes hydrated and is restored to a desired shape, so that a function as a spacer can be exhibited at a target portion.

[0012]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but it should not be construed that the invention is limited thereto. Example 1 A 1% concentration of an acidic solution (p
H3). This solution was poured into a 10 cm square plastic tray so as to have a height of 15 mm, neutralized by standing in an ammonia saturated gas, and then freeze-dried to obtain a collagen sponge having a thickness of 15 mm. This sponge was placed in a methanol solution of HMDIC (1
%) For 3 hours to crosslink and air dry. This is immersed in water and sandwiched between two plastic plates in a water-containing state, and the height is 5 m.
m, and then freeze-dried to obtain a compression-molded sponge. The thickness of the compression sponge was 5 mm. It was confirmed that when the compressed sponge was put in water, it swelled and was restored to its original thickness (15 mm).

Example 2 An enzyme-solubilized atelocollagen was added to an acidic solution (p
H3). 1/5 of this is 60 ° C
For 30 minutes to form a gelatin solution, and mixed at a collagen: gelatin = 4: 1 ratio to obtain a collagen / gelatin mixed solution. This solution was poured into a 10 cm square plastic tray so as to have a height of 15 mm, and neutralized by standing in an ammonia-saturated gas, followed by freeze-drying to obtain a 15 mm thick collagen / gelatin sponge.
This sponge was immersed in a methanol solution of HMDIC (1%) for 3 hours to crosslink, and air-dried. This is 50mm × 3
It was cut into a flat surface of 0 mm (height: 15 mm), immersed in water, swollen, packed in a 10 ml disposable syringe (made by Terumo) in a compressed state, freeze-dried as it was, and compression-molded into a cylindrical shape. Got a sponge. The thickness of the compression sponge was 5 mm. When this compressed sponge was taken out of the syringe outer cylinder and put in water, it was confirmed that the sponge swelled and was restored to a flat plate shape having the original thickness (15 mm).

Example 3 A collagen / gelatin sponge was prepared in the same manner as in Example 2. This sponge was placed in a methanol solution of HMDIC (1
%) For 3 hours to crosslink and air dry. This is immersed in water and sandwiched between two plastic plates in a water-containing state, and the height is 5 m.
m, and then freeze-dried to obtain a compression-molded sponge. The thickness of the compression sponge was 5 mm. When this compressed sponge was placed in the rabbit abdominal cavity,
It was confirmed that even when swelled in the abdominal cavity, it was restored to its original thickness (15 mm), and that it had sufficient elasticity as a spacer during irradiation.

Example 4 A collagen / gelatin sponge was prepared in the same manner as in Example 2. This sponge was placed in a methanol solution of HMDIC (1
%) For 3 hours to crosslink and air dry. This was immersed in water to obtain a water-containing state, and when a load was applied at 40 g / cm ² , the reduction in thickness was 3 mm, and when the load was removed, the original thickness was restored.

Example 5 A collagen / gelatin sponge was prepared in the same manner as in Example 2. At this time, the mixing ratio of collagen and gelatin was set to collagen: gelatin = 2: 1. When this sponge was irradiated with a heavy particle beam, it was confirmed that the sponge maintained its shape before irradiation without being decomposed in both the dry state and the water-containing state, and had sufficient strength as a spacer during irradiation. did.

[0017]

As described above, the present invention relates to a radiotherapy sponge which is placed between organs during radiotherapy to prevent radiation damage at locations other than the target site, and the sponge has a restoring property. Since it can be introduced into the abdominal cavity by a tracker or the like, radiation therapy can be performed without performing laparotomy, and the sponge is made of collagen having an intermolecular cross-link or a mixture of collagen and gelatin. Although it is insoluble in water when introduced into the abdominal cavity, it has effects such as being absorbed into the body over time.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Akiko Tanaka 2-2-6 Okubo, Shinjuku-ku, Tokyo 10th floor of the 3rd Matsuda Building Inside the Koken Research Institute Co., Ltd.

Claims (6)

[Claims] 1. A radiotherapy sponge insolubilized by introducing an intermolecular crosslink into collagen or a mixture of collagen and gelatin, and having a force to return to its original state when the load applied to the sponge is released. A sponge for radiation therapy, characterized by the following. 2. A force that reduces the thickness by a maximum of 5 mm when a load of 40 g / cm ² is applied at a thickness of 10 mm or more in a hydrated state and restores the original thickness when the load is removed. The sponge for radiotherapy according to claim 1, characterized by having: 3. The sponge for radiotherapy according to claim 1, wherein an intermolecular cross-link is introduced after neutralizing collagen or a mixture of collagen and gelatin. 4. The sponge for radiotherapy according to claim 1, wherein the sponge is compressed after the introduction of intermolecular crosslinks, reduced in volume, and then dried. 5. Atelocollagen is used as collagen.
The sponge for radiotherapy according to claim 1, characterized in that it contains 0% or more. 6. The sponge for radiation therapy according to claim 1, wherein freeze-drying is performed when drying.