JP7309175B2 - Calcified lesion model, manufacturing method thereof, and test method for medical device - Google Patents

Description

TECHNICAL FIELD The present invention relates to a calcified lesion model having a calcified lesion that simulates a calcified lesion, a method for producing the same, and a method for testing a medical device using the calcified model.

Percutaneous coronary intervention (PCI) using balloons and stents, which are medical devices, is performed as one of the treatment methods for calcified stenotic lesions in which the inside of a coronary artery vessel is calcified and narrowed. PCI is a therapeutic method in which a catheter is passed through a blood vessel in the wrist or base of the leg, and a stent or balloon housed therein is expanded at the stenosis to restore blood flow that has been reduced due to stenosis. Since this PCI is a minimally invasive therapeutic method that does not involve open chest surgery, it is often applied to the treatment of the elderly and acute myocardial infarction. Here, when performing treatment with a stent, the stent may not expand sufficiently due to the high rigidity of the calcified portion that constitutes the constriction. If the expansion of the stent is insufficient in this way, it is still difficult to ensure blood flow, and if the stent is forced to expand, it may damage the normal vascular wall. Therefore, in such a case, it is useful to perform pre-dilatation by using a balloon to destroy the calcified portion, etc., and then place the stent. As balloons for treatment of calcified stenoses, non-compliant balloons that do not change in expanded diameter even when a predetermined expansion pressure or more is applied (see Patent Document 1, etc.) and balloons that have the effect of eliminating calcification on the balloon surface. There are drug-coated balloons coated with a drug (see Patent Document 1) and cutting balloons in which a blade attached to the surface of the balloon destroys the calcified portion (see Patent Document 2).

The range of vascular lumen where calcified stenotic lesions occur and the thickness of the calcified part differ from patient to patient. Is required. Currently, there is no established method for selecting or developing a therapeutic device such as a balloon that destroys calcified parts, and in the medical field, multiple therapeutic devices are used to exploratoryly select an appropriate therapeutic device. There is a problem that this leads to an increase in medical expenses and operation time.

By the way, Patent Document 3 discloses an arterial calcification model blood vessel for the purpose of development of surgical instruments and medical research. This arterial calcification model blood vessel was prepared by adding calcium phosphate to an aqueous solvent such as physiological saline, adjusting the pH, recrystallizing the blood vessel, sonicating it, injecting it into the lumen of the animal-derived blood vessel, and cooling it. obtained by depositing

Japanese Patent Application Publication No. 2013-502984 Japanese translation of PCT publication No. 2008-504059 JP 2015-136354 A

In the arterial calcification model blood vessel of Patent Document 3, a calcified lesion is simulated by depositing calcium phosphate, which is a component of an actual calcified lesion, in an animal-derived blood vessel, but an animal-derived blood vessel is prepared. However, mass production has certain limits and cannot be easily manufactured. In addition, although Patent Document 3 discloses the use of an arterial calcification model blood vessel for the purpose of evaluating the sealing performance of a surgical instrument for blood vessel sealing, regarding medical equipment, the hardness of the calcified part and its adjustment are disclosed. Not mentioned. Therefore, in the arterial calcification model blood vessel, a treatment device such as a balloon that destroys the calcified portion cannot be used to evaluate the destruction effect according to the mechanical properties such as the hardness of the calcified portion.

The present invention has been devised with a focus on the above problems, and its purpose is to accurately evaluate the destructive effect and other mechanical properties of therapeutic devices such as balloons that destroy calcified parts. It is an object of the present invention to provide a useful and easily manufactured calcified lesion model, a method for manufacturing the same, and a method for testing medical equipment using the same.

In order to achieve the above object, the present invention mainly employs a calcified lesion model that models a calcified lesion, which includes a calcified lesion containing polyurethane resin and gypsum.

In addition, the method for producing a calcified lesion model according to the present invention mainly comprises mixing powdery gypsum with a liquid polyurethane resin in a predetermined ratio, heating the mixed liquid, leaving it for a predetermined time, and performing the mixing. A method is adopted in which a calcified lesion that simulates the mechanical properties of the calcified lesion is produced by hardening the liquid.

Furthermore, in the method for testing a medical device using a calcified lesion model according to the present invention, a mechanical property test of the medical device is performed outside the human body by mainly bringing a predetermined medical device into contact with the calcified lesion model. , is adopted.

In current medical practice, the selection of treatment methods and treatment devices for calcified stenotic lesions is determined by each doctor's experience, and there are no appropriate guidelines. Therefore, by using the calcified lesion model according to the present invention, it is possible to quantitatively perform mechanical comparative evaluation of various treatment devices in nonclinical conditions, and a guideline for evaluating the mechanical performance of treatment devices. can contribute to the creation of Therefore, in the medical field, it is expected that appropriate treatment according to the state of calcified lesions will be possible, leading to a reduction in medical costs and an increase in healthy life expectancy, as well as the early development of higher performance treatment devices. .

In addition, according to the present invention, therapeutic devices for calcified stenotic lesions having different shapes and thicknesses of stenotic parts can be evaluated in vitro. As a result, it is possible to suggest an appropriate device that matches the shape and thickness of the stenosis based on engineering data, and the patient can receive treatment with greater peace of mind. In addition, it prevents the use of high-risk treatment devices for mild lesions. In addition, test conditions for calcified stenotic lesions can be established using an artificially produced calcified stenotic model, and the performance of treatment devices can be evaluated according to standards unified by third-party institutions. As a result, only devices that are effective for treatment can be clinically reflected.

Furthermore, according to the present invention, artificial models simulating various calcified lesions and having different mechanical properties and shapes can be produced by a simple method using readily available materials.

The calcified lesion model according to the present embodiment includes a cylindrical calcified lesion containing components of polyurethane resin and gypsum, and a non-calcified lesion surface layer provided in the lumen of the calcified lesion. It is composed of a simulated lesion surface layer. Note that the surface layer of the lesion can be omitted if necessary.

The calcified lesion model is produced by the following procedure.

First, liquid polyurethane resin and powdery gypsum are mixed in a vacuum deaerator while being stirred and vacuum deaerated.

Here, as the polyurethane resin, a main agent made of polyol and a curing agent made of polyisocyanate are prepared. Gypsum is used for the purpose of weakening the bonding strength of polyurethane. The blending ratio of the main agent, hardening agent and gypsum is appropriately selected according to the desired hardness of the calcified lesion. Examples of the compounding ratio include 2:3:6, 2:3:7, and 2:3:8 for main agent:hardener:gypsum. Also, by changing the vacuum defoaming time here, it is possible to adjust the hardness of the obtained calcified lesion, and the longer the time, the higher the hardness of the obtained calcified lesion.

Next, the mixture of polyurethane resin and gypsum powder obtained above is poured into a silicone mold and heated in an oven for a predetermined time. The heating temperature and heating time here can be exemplified by 70 degrees and 20 minutes. Here, by changing the heating temperature and heating time in the oven, the hardness of the resulting calcified lesion can be adjusted, and the longer the time, the greater the hardness of the resulting calcified lesion. . The mold is formed so as to obtain a cylindrical calcified lesion that is open at both ends in the extending direction.

After that, the mixture heated in the oven is taken out from the oven together with the mold, and left at normal temperature for a predetermined time. As the leaving time here, 48 hours can be exemplified, but by changing the leaving time, the hardness of the obtained calcified lesion can be adjusted. The hardness of the part increases.

Then, the cylindrical calcified lesion obtained by hardening the mixture is removed from the mold.

Finally, silicone is applied to the lumen of the obtained calcified lesion to form a simulated surface layer of the lesion that is not calcified. The silicone used here is made by blending a main agent, a curing agent, and a silicone oil at a ratio of 3:3:1, for example. This compounding ratio corresponds to an elastic modulus that approximates the actual lesion surface layer when the silicone is cured, and a single material provides a lesion surface layer with a hardness equivalent to the actual uncured lesion surface layer. It will be.

As a calcified lesion model, in addition to models simulating circumferential lesions in which calcified lesions are formed on the entire circumference, a partial circumferential direction (for example, 180 Various shapes can also be produced, including those with calcified lesions in the range of degree).

Hereinafter, the present invention will be described in detail with reference to one example, but the present invention is not limited to the example.

Assuming a calcified stenotic lesion that occurs in a coronary artery, three types of calcified lesion models with different outer diameters having thicknesses of the lesion (stenosis) of 400, 450, and 500 μm were prepared by the following procedure. In these models, the inner diameter of the calcified lesion is 1.6 mm and the length is 5 mm, and the thickness of the lesion surface layer existing in the lumen is 50 μm.

(1) Preparation of calcified lesion A polyurethane resin main agent and curing agent were mixed with gypsum powder in a vacuum deaerator. The compounding ratio of the main agent, hardening agent, and gypsum was 2:3:8. Specifically, it is as follows.

A container was prepared by mixing the main agent and gypsum at a ratio of 2:3 (A cup), and a container was prepared by mixing the hardener and gypsum at a ratio of 3:5 (B cup).
Silicone molds for A cup, B cup, and calcified lesion models were set in a vacuum deaerator (vacuum casting machine manufactured by MCP). The silicone mold used here was preformed with silicone using an aluminum mold so as to obtain a calcified lesion having the shape described above.

Then, the mixture of polyurethane resin and gypsum was stirred in a vacuum deaerator, and vacuum deaeration was performed for 23 minutes.

The silicone mold filled with the mixture of polyurethane and gypsum powder was taken out from the vacuum deaerator and cooled in a refrigerator for 30 minutes.
After that, the silicone mold was taken out from the refrigerator and heated in an oven at 70°C for 20 minutes.
Then, the silicone mold was taken out from the oven and left at room temperature for 48 hours.
After that, the cured portion of the mixture was removed from the silicone mold to obtain a calcified lesion.

(2) Preparation of lesion surface layer A lesion surface layer having a thickness of 50 μm by blending a silicone main agent, a curing agent and silicone oil, and applying the silicone containing the compound to the lumen of the prepared calcified lesion model. and obtained a calcified lesion model in which the lesion surface layer was integrated with the calcified lesion. Here, the compounding ratio of the main agent of silicone, curing agent and silicone oil was 3:3:1.

The present inventors conducted an experiment to verify the practicality of the calcified lesion model obtained as described above.

According to the research of the present inventors, the clinical threshold for destruction of calcified lesions based on the performance of existing non-compliant balloons is that of circumferential lesions in which calcified lesions occur all around the lumen of the blood vessel. It was found that calcified lesions with a thickness of about 400 μm can be destroyed in some cases, but there is a tendency that calcified lesions with a thickness of about 500 μm cannot be destroyed.

Therefore, an existing non-compliant balloon was inserted into the lumen of the three types of calcified lesion models obtained in the above example, where the thickness of the calcified lesion was 400, 450, and 500 μm, and the calcified lesion was We investigated whether or not it is possible to destroy the Here, NC image manufactured by Boston Scientific was used as a non-compliant balloon. The recommended inflation pressure for this non-compliant balloon is 12.0 atm, and the maximum inflation pressure is 20.0 atm.

As a result of the above experiment, at an expansion pressure of less than 20.0 atm, a calcified lesion model with a thickness of 400 μm could be destroyed, while a calcified lesion model with a thickness other than 400 μm could not be destroyed. , the calcified lesion model was demonstrated to be a model with a hardness close to that of an actual calcified lesion.

In another experiment using a cutting balloon, it became possible to quantitatively grasp the expansion pressure required for destruction of the calcified lesion model corresponding to the thickness of the calcified lesion.

Claims (7)

A calcified lesion model that models a calcified lesion,
A calcified lesion model comprising a calcified lesion made of polyurethane resin and gypsum. 2. The calcification according to claim 1, wherein said calcified lesion has a tubular shape, and a silicone lesion surface layer simulating a non-calcified lesion surface layer is provided in the lumen of said calcified lesion. Metabolism model. A method for producing a calcified lesion model in which a calcified lesion is modeled,
A main agent and a curing agent are prepared as a liquid polyurethane resin, and the main agent, the curing agent, and powdered gypsum are mixed in a predetermined ratio, the mixed liquid is heated, and then left for a predetermined time to harden the mixed liquid. A method for producing a calcified lesion model, characterized in that a calcified lesion having a hardness close to that of an actual calcified lesion is produced by applying a calcified lesion. By forming a lumen portion in the calcified lesion and applying silicone to the lumen portion, the lesion surface layer portion having an elastic modulus similar to the actual non-calcified lesion surface layer is defined as the calcified lesion portion. 4. The method for producing a calcified lesion model according to claim 3, wherein the calcified lesion model is integrated. A mixture of the main agent and the gypsum at a predetermined mixing ratio and a mixture of the hardening agent and the gypsum at a predetermined mixing ratio are prepared, and after vacuum defoaming while stirring, the heating is performed. 5. The method for producing a calcified lesion model according to claim 3 or 4, characterized in that: Hardening of the calcified lesion can be achieved by changing the blending ratio of the main agent and curing agent of the polyurethane resin and the gypsum, the vacuum degassing time of the mixed liquid, the heating temperature and time, and/or the standing time. 6. The method for producing a calcified lesion model according to claim 5, wherein the thickness is adjusted. A method for testing a medical device using the calcified lesion model according to claim 1 or 2,
A method for testing a medical device, comprising the step of bringing a predetermined medical device into contact with the calcified lesion model to perform a mechanical property test of the medical device outside the human body.