WO2023058760A1

WO2023058760A1 - Storage device

Info

Publication number: WO2023058760A1
Application number: PCT/JP2022/037681
Authority: WO
Inventors: 慶一今井; 優芽芹川; 賢洋兒玉; 真一岡本
Original assignee: 凸版印刷株式会社
Priority date: 2021-10-07
Filing date: 2022-10-07
Publication date: 2023-04-13
Also published as: JP2023056312A

Abstract

A storage device that is to be used for placement of an object in a living body. The storage device comprises a needle-shaped body equipped with a needle-shaped part which is shaped so as to be capable of piercing a living body. The needle-shaped body is configured to hold an object inside the needle-shaped part. Materials of the needle-shaped body include a water-soluble material and a material hardly soluble in water.

Description

containment device

The present disclosure relates to a containment device used to place an object in vivo.

The use of technology for transplanting cell groups into the body is progressing. For example, attempts have been made to regenerate hair by culturing a group of cells that contribute to the formation of hair-producing organs of the hair follicle and intradermally transplanting this group of cells. For good hair regeneration, it is desirable that the transplanted cell population yields a follicular organ with a normal tissue structure and good hair-forming ability. Therefore, various researches and developments have been conducted on methods for producing cell groups capable of forming such hair follicle organs (see, for example, Patent Documents 1 to 3).

WO2017/073625 WO2012/108069 Japanese Unexamined Patent Application Publication No. 2008-29331

When placing the cell group in the body, the cell group is held with instruments such as tweezers and syringes, the surface of the tissue of the body is cut, and the instrument is inserted into the tissue. After placement of the cell population, the instrument is then withdrawn from the tissue. However, in such a cell group transplantation method, when the instrument is pulled out from the tissue, the cell group may sometimes come out of the tissue together with the instrument, which leads to a decrease in transplantation efficiency.

It should be noted that such problems are not limited to the transplantation of cell groups, but are common when placing an object in vivo from the surface of a tissue such as skin.

A storage device for solving the above problems is a storage device used for arranging an object in a living body, and is a needle-like body having a needle-like portion having a shape capable of piercing the living body, The needle-shaped body is configured to hold the object inside the needle-shaped portion, and the material of the needle-shaped body includes a water-soluble material and a poorly water-soluble material. .

The figure which shows the cross-section of the cell transplantation unit in 1st Embodiment. FIG. 4 is a diagram showing another example of the cross-sectional structure of the cell transplantation unit according to the first embodiment; FIG. 2 is a diagram showing a cross-sectional structure of a cell transplantation unit having a plurality of needle-like portions according to the first embodiment; FIG. 2 shows a procedure for placement of a transplant using the cell transplantation unit of the first embodiment; FIG. 2 shows a procedure for placement of a transplant using the cell transplantation unit of the first embodiment; FIG. 2 shows a procedure for placement of a transplant using the cell transplantation unit of the first embodiment; FIG. 4 is a diagram showing a manufacturing process of the cell transplantation unit of the first embodiment; FIG. 4 is a diagram showing a manufacturing process of the cell transplantation unit of the first embodiment; The figure which shows the cross-section of the cell transplantation unit of the 1st example in 2nd Embodiment. The figure which shows the cross-section of the cell transplantation unit of the 2nd example in 2nd Embodiment. The figure which shows the cross-section of the cell transplantation unit of the 3rd example in 2nd Embodiment. The figure which shows the cross-section of the accommodation device of 3rd Embodiment. The figure which shows the cross-section of the cell transplantation unit of 3rd Embodiment. The figure which shows the cross-section of the accommodation device of the modification of 3rd Embodiment. The figure which shows the cross-section of the accommodation device of the modification of 3rd Embodiment. The figure which shows the cross-section of the accommodation device of the modification of 3rd Embodiment. FIG. 11 shows a procedure for placement of a transplant using the cell transplantation unit of the third embodiment; FIG. 11 shows a procedure for placement of a transplant using the cell transplantation unit of the third embodiment; FIG. 11 shows a procedure for placement of a transplant using the cell transplantation unit of the third embodiment; FIG. 11 shows a procedure for placement of a transplant using the cell transplantation unit of the third embodiment; The figure which shows the cross-section of the accommodation device of the modification of 3rd Embodiment. The figure which shows the cross-section of the accommodation device of the modification of 3rd Embodiment. The figure which shows the cross-section of the accommodation device of the modification of 3rd Embodiment. The figure which shows the cross-section of the accommodation device of the modification of 3rd Embodiment. The figure which shows the cross-section of the accommodation device of the modification of 3rd Embodiment. The figure which shows the cross-section of the accommodation device of the modification of 3rd Embodiment. The figure which shows the cross-section of the accommodation device of the modification of 3rd Embodiment.

(First embodiment)
A first embodiment of a containing device, a cell transplantation unit, and a method for manufacturing the containing device will be described with reference to FIGS. 1 to 8. FIG. The cell transplantation unit of the present embodiment is used for placing an object such as a group of cells in vivo. The area in which the object is placed is within the tissue of the living body, for example, at least one of intradermal and subcutaneous, or an organ or the like. In the present embodiment, the term “living body” includes not only the body and tissues of living organisms, but also biological models, which are artificial products simulating the bodies and tissues of living organisms. That is, the cell transplantation unit of the present embodiment can be used not only for arranging an object on an organism, but also for arranging an object on a biological model.
In this specification, the statement "at least one of A and B" should be understood to mean "only A, or only B, or both A and B."

[Structure of Cell Transplantation Unit]
As shown in FIG. 1, the cell transplantation unit 10 has a needle-like portion 20 extending into a shape capable of being pierced into a living body. The needle-like portion 20 holds an implant 50, which is an example of an object, inside thereof. Needle-like part 20 is an example of a needle-like object. Furthermore, the cell transplantation unit 10 preferably includes a support plate portion 30 that supports the proximal end of the needlelike portion 20 . The support plate portion 30 is plate-shaped and has a first surface 31F and a second surface 31R opposite to the first surface 31F. And the needle-like part 20 is extended from the 1st surface 31F. The needle-like portion 20 or the structure including the needle-like portion 20 and the support plate portion 30 is an example of a containing device configured to be able to contain an object.

The needle-like portion 20 may have any shape as long as it can pierce the tissue in which the implant 50 is placed. From the viewpoint of increasing the ease with which the needle-like portion 20 can be stuck into the living body, it is preferable that the needle-like portion 20 has a shape that extends along one direction and that the tip of the needle-like portion 20 is sharp. The direction in which the needle-like portion 20 extends may be a direction orthogonal to the first surface 31F of the support plate portion 30, or may be a direction inclined with respect to the first surface 31F.

For example, the needle-like portion 20 may have a shape such as a conical shape or a pyramidal shape in which the cross-sectional area decreases from the proximal end to the distal end. Further, for example, the needle-like portion 20 has a shape obtained by cutting a cylinder obliquely to the direction in which it extends, or a shape in which a cone extends from the upper surface of the cylinder. , may have a shape in which the cross-sectional area decreases toward the tip. Alternatively, the needle-like portion 20 may have a blade-like structure at its tip.

However, as long as the needle-like portion 20 can pierce the tissue in which the implant 50 is placed, the distal end portion of the needle-like portion 20 may have a curved shape, or the needle-like portion 20 may have a circular shape. It may have a shape with a blunt tip, such as a columnar shape or a prismatic shape.
The length of the needle portion 20 is, for example, 200 μm or more and 2 mm or less, and the maximum value of the outer diameter of the needle portion 20 is, for example, 100 μm or more and 1 mm or less.

The needle-like portion 20 and the support plate portion 30 may be integrally formed from the same material, or may be formed separately and joined together. Further, the support plate portion 30 includes a first plate-like portion integrally formed with the needle-like portion 20 and continuing from the proximal end of the needle-like portion 20, and a second plate joined to the first plate-like portion. It may be a laminate comprising a shape portion.

In the cell transplantation unit 10A of FIG. 1, which is an example of the cell transplantation unit 10, the transplant 50 is embedded inside the needle-like portion 20. Alternatively, like the cell transplantation unit 10B of FIG. 2, which is another example of the cell transplantation unit 10, the needle-like portion 20 has a receiving hole 25 which is a hole recessed inward from the proximal end of the needle-like portion 20. and the implant 50 may be accommodated in the accommodation hole 25 .

The housing hole 25 opens at the proximal end of the needle-like portion 20 . The opening of the accommodation hole 25 is closed by the support plate portion 30 . The shape and size of the accommodation hole 25 are not particularly limited as long as the implant 50 can be accommodated therein. In the example shown in FIG. 2 , the accommodating hole 25 extends with a constant inner diameter from the opening located at the proximal end of the needle-like portion 20 and then decreases in diameter toward the bottom of the accommodating hole 25 . The sectional shape of the receiving hole 25 along the direction perpendicular to the extending direction of the needle-like portion 20 is circular, and the bottom of the receiving hole 25 is a curved surface. Alternatively, the side surface of the accommodation hole 25 may be an inclined surface, and the inner diameter of the accommodation hole 25 may gradually change from the opening. Also, the bottom surface of the accommodation hole 25 may be flat.

In addition to the implant 50, the accommodation hole 25 accommodates an auxiliary liquid 51, which is a fluid for maintaining the activity of cells in the accommodation hole 25 and assisting the engraftment of the cells after being placed in the living body. may The implant 50 is surrounded by an auxiliary liquid 51 within the receiving hole 25 . The auxiliary liquid 51 does not have to surround the entire periphery of the implant 50. For example, the implant 50 is arranged at the bottom of the receiving hole 25, and the auxiliary liquid 51 is not present in the region from the top of the implant 50 to the opening. may cover the implant 50 .

FIG. 3 shows a cell transplantation unit 10C, which is another example of the cell transplantation unit 10. FIG. As shown in FIG. 3 , the cell transplantation unit 10 may have multiple needle-like parts 20 . An implant 50 is held in each needle 20 . By connecting the support plate portions 30 of the needle-like portions 20 adjacent to each other, an assembly of the plurality of needle-like portions 20 is formed. That is, one common support plate portion 30 is arranged for a plurality of needle-like portions 20 .

When the cell transplantation unit 10 includes a plurality of needle-like portions 20, the needle-like portions 20 may be arranged regularly or may be arranged irregularly. For example, the plurality of needle-like portions 20 may be arranged in one row, or may be arranged in a plurality of rows so that each needle-like portion 20 is positioned at each lattice point of a square lattice or a triangular lattice. Moreover, in the arrangement of the plurality of needle-like portions 20, the intervals between the needle-like portions 20 adjacent to each other may be constant or may not be constant.
Since the cell transplantation unit 10 has a plurality of needle-like portions 20, a plurality of transplants 50 can be collectively placed in the living body.

[Configuration of implant]
Implant 50 includes a group of cells. A cell group contains a plurality of cells. For example, a population of cells includes one or more clusters of cells. A cell mass is an aggregate of multiple cells. A cell cluster may be an aggregate of a plurality of aggregated cells, or an aggregate of a plurality of cells bound by intercellular junctions. Alternatively, the cell population may consist of a plurality of dispersed cells. In addition, the cells that constitute the cell group may be undifferentiated cells or cells that have completed differentiation, and the cell group includes undifferentiated cells and differentiated cells. good too. The cell group is, for example, a cell cluster that is a spheroid, an primordium, a tissue, an organ, an organoid, a mini-sized organ, or the like.

A group of cells has the ability to affect tissue formation in the body by being placed in the body. One example of such cell populations are cell aggregates containing cells with stemness. The cell group contributes to hair growth or growth, for example, by being placed intradermally or subcutaneously. Specifically, the cell group has the ability to function as a hair follicle organ, the ability to differentiate into the hair follicle organ, the ability to induce or promote the formation of the hair follicle organ, or the ability to induce or promote the formation of hair in the hair follicle organ. have the ability to The cell group may also contain cells that contribute to the control of coat color, such as pigment cells or stem cells that differentiate into pigment cells. In addition, the cell group may contain vascular cells.

A specific example of a cell group is an organ primordium. The organ primordium contains mesenchymal and epithelial cells. Examples of organ primordium include cell groups such as hair follicle primordium that differentiates into hair follicle organ, liver primordium, kidney primordium, pancreatic primordium, nervous system primordium cells, and vascular system primordium cells. is.

For example, the hair follicle primordium contains a cell mass composed of mesenchymal cells and a cell mass composed of epithelial cells, and these two types of cell masses are in contact with each other. In the hair follicle organ, dermal papilla cells contained in the mesenchymal cell mass induce differentiation of hair follicle epithelial stem cells contained in the epithelial cell mass, and hair matrix cells are formed in the hair bulb formed by this. Hair is formed by repeated division of . A hair follicle primordium is a group of cells that differentiate into such hair follicle organs.

For the hair follicle primordium, for example, mesenchymal cells derived from mesenchymal tissue such as dermal papilla, and epithelial cells derived from epithelial tissue located in the bulge region, hair bulb base, etc. It is formed by forming cell clusters by culturing and bringing these cell clusters into contact. However, the method for producing the hair follicle primordia is not limited to the above examples. In addition, the origin of the mesenchymal cells and epithelial cells used for the production of the hair follicle primordium is not limited, and these cells may be cells derived from the hair follicle organ. Cells derived from different organs may be used, or cells derived from pluripotent stem cells may be used.

In addition to mesenchymal cell masses and epithelial cell masses, the cell masses may also contain cell masses that contribute to engraftment and functional improvement. Examples of such cell clusters are cell clusters involved in hair color, cell clusters containing vascular cells, and cell clusters that release growth factors.

In addition to the cell group, the implant 50 may contain a member that assists the transplantation and engraftment of the cell group, and a gel-like body that protects the cell group. An example of a member that assists transplantation or engraftment of cell groups is gel beads that slowly release growth factors.

The auxiliary liquid 51 may be a component that does not easily inhibit the survival of cells, and is preferably a component that has a small effect on the living body when injected into the living body. The auxiliary liquid 51 surrounds the implant 50 and suppresses contact and friction between the implant 50 and the inner surface of the receiving hole 25 , thereby helping to maintain the activity of the implant 50 . Alternatively, the implant 50 contains a component close to the body fluid of the living body to wrap the implant 50 or provide nutrition to the implant 50, thereby assisting the maintenance of the activity of the implant 50 and engraftment. good too.

The auxiliary liquid 51 is, for example, a physiological saline solution, a substance that protects the skin such as vaseline or lotion, or a mixture thereof. In addition, the auxiliary liquid 51 may contain nutritional components and components such as oxygen necessary for cell survival. Also, the auxiliary liquid 51 may be a medium for culturing cells. The auxiliary liquid 51 can be a low viscosity fluid or a high viscosity fluid. The auxiliary liquid 51 may be a sol or gel.

[Materials for Cell Transplantation Unit]
Materials for each part of the cell transplantation unit 10 will be described in detail.
The needle-like portion 20 contains a water-soluble material and an oily material, and loses its shape due to dissolution, melting, or decomposition of these materials in vivo. In other words, the needle-like portion 20 dissolves in vivo. In the needle-like portion 20, the water-soluble material and the oily material are uniformly mixed. In other words, the material of needle 20 is a mixture of water-soluble material and oily material.

The water-soluble material preferably has biocompatibility. A specific example of a water-soluble material is a water-soluble polymer. Water-soluble polymers used as main components of water-soluble materials are, for example, hydroxypropylcellulose, pullulan, pectin, sodium chondroitin sulfate, dextran, collagen, atelocollagen, hyaluronic acid, and sodium hyaluronate. Needles 20 may contain more than one type of water-soluble material.

The oily material is water-insoluble. Specific examples of oily materials are vegetable oils, animal oils, mineral oils, and oils synthesized using these as raw materials. The oily material should be a material that is unlikely to harm the living body, that is, a material that is unlikely to cause damage such as severe inflammation when in contact with the living body, and that does not have serious toxicity to tissues such as organs. is preferred.

Oily materials are, for example, olive oil, rapeseed oil, palm oil, squalane, vaseline, paraffin, and hard fat. Needle 20 may contain more than one type of oily material.

The oily material is preferably solid or semi-solid such as cream at room temperature. The melting point of the oily material is, for example, preferably 15° C. or higher and 70° C. or lower, and more preferably 30° C. or higher and 40° C. or lower. If the melting point of the oil-based material is within the above range, the oil-based material is prevented from becoming liquid at room temperature, and thus the needle-like portion 20 can be easily maintained in a desired shape before use. On the other hand, since the temperature in the living body makes the oily material more likely to be liquefied, it is possible to prevent the needle-like portion 20 from remaining in the living body for a long period of time.

The ratio of the oily material to the total mass of the needle-like portion 20 is preferably 1% by mass or more and 60% by mass or less. Moreover, the ratio of the water-soluble material to the total mass of the needle-like portion 20 is preferably 40% by mass or more and 99% by mass or less. If the ratio of the oil-based material is 60% by mass or less and the ratio of the water-soluble material is 40% by mass or more, the strength of the needle-like portion 20 can be appropriately obtained. In addition, it becomes easier to mix the water-soluble material and the oily material, and it becomes easier to form the needle-like portion 20 into a desired shape. Further, when the ratio of the oily material is 1% by mass or more and the ratio of the water-soluble material is 99% by mass or less, rapid dissolution of the needle-like portion 20 upon contact between the living body and the needle-like portion 20 can be suppressed. .

The needle-like portion 20 may further contain an additive having a component that contributes to shaping of the needle-like portion 20 or maintenance of cell activity and engraftment. For example, the needle-like portion 20 may contain a surfactant or an emulsifier as an additive for facilitating the formation of the needle-like portion 20 . Specifically, when the oil-based material is a material with a high melting point, such as vaseline, the addition of a surfactant makes it easier to mix the water-soluble material and the oil-based material. As the surfactant, for example, sucrose fatty acid ester is preferably used. A ratio of the surfactant to the total mass of the needle-like portion 20 is preferably 0.1% by mass or more and 5% by mass or less.

For example, when palm oil is used as the oily material, the content of palm oil in the needle-like portion 20 is preferably 1% by mass or more and 30% by mass or less. Further, when petrolatum is used as the oily material, the needle-like portion 20 contains petrolatum and sucrose fatty acid ester, and the content of petroleum jelly in the needle-like portion 20 is 5% by mass or more and 40% by mass or less, and sucrose It is preferable that the content of the fatty acid ester is 0.5% by mass or more and 2% by mass or less. Such a configuration makes it easier to form the needle-like portion 20 into a desired shape.

Materials that the needle-like portion 20 may contain in addition to the materials described above include, for example, hydroxypropylmethylcellulose, dextrin, starch, cellulose, chitosan, pectic acid, galactan, chondroitin sulfate, carboxymethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, and polyvinyl alcohol. , polyacrylic acid-based polymer, polyacrylamide, polyethylene oxide, alginate, chondroitin sulfate, poly 2-ethyl-2-2 oxazoline, poly 2-methyl-2-oxazoline, carboxyvinyl polymer, galactan, leozan, xanthan gum, casein , polyvinylpyrrolidone, glucomannan, polymalic acid, and curdlan.
In addition, it is preferable that the needle-like portion 20 is transparent because the state of the implant 50 in the needle-like portion 20 can be easily confirmed from the outside.

The material of the support plate portion 30 may be the same as that of the needle-like portion 20 or may be different from that of the needle-like portion 20 . Further, the support plate portion 30 may or may not have the property of dissolving in water. For example, the support plate portion 30 may contain only the water-soluble material or both the water-soluble material and the oil-based material, out of the water-soluble material and the oil-based material. Alternatively, the support plate portion 30 may be made of a material different from both the water-soluble material and the oil-based material.

As the material of the support plate portion 30, for example, the above various materials exemplified as the material of the needle portion 20 are used. Moreover, a resin sheet made of a biocompatible resin may be used as the support plate portion 30 .

It should be noted that in the present embodiment, the needle-like portion 20 dissolves in water. An object such as the needle-like portion 20 or the support plate portion 30 dissolves in water means that when the object is immersed in stirring water at 25° C. for 5 minutes, the weight of the object in the water is reduced. , means that 0.05% or more is eluted.

[Method of placement of implant]
A method of placing the implant 50 in vivo using the cell transplantation unit 10, that is, a method of implanting the implant 50 will be described with reference to FIGS. 4 to 6. FIG. The method of placing the implant 50 is, in other words, the method of using the cell transplantation unit 10 .

As shown in FIG. 4, first, the needle-like portion 20 of the cell transplantation unit 10 is pressed against the target tissue Sk in which the implant 50 is to be placed, thereby piercing the target tissue Sk with the needle-like portion 20 . The target tissue Sk is, for example, skin. At this time, an applicator may be used that assists the needle-like portion 20 to enter the target tissue Sk by adjusting the force applied to the needle-like portion 20 and the direction of the needle-like portion 20 . In addition, in a state in which the needle-like portion 20 is stuck in the target tissue Sk, the support plate portion 30 is arranged on the surface of the target tissue Sk without entering the inside of the target tissue Sk.

As shown in FIG. 5, when the needle-like portion 20 enters the target tissue Sk, the needle-like portion 20 comes into contact with moisture in the tissue, and the needle-like portion 20 reaches a temperature close to the body temperature of the living body. Due to being warmed, the needle-like portion 20 melts.

When the support plate portion 30 has the property of dissolving in water, the support plate portion 30 also dissolves due to the contact between the support plate portion 30 and the moisture on the surface of the target tissue Sk. If the support plate portion 30 does not have the property of dissolving in water, the support plate portion 30 is peeled off from the surface of the target tissue Sk. The peeling of the support plate portion 30 may be performed before the needle-like portion 20 is completely melted, or may be performed after the needle-like portion 20 is completely melted. If the support plate portion 30 is in a form that dissolves, the support plate portion 30 does not need to be peeled off, and the labor required for using the cell transplantation unit 10 is reduced.

As shown in FIG. 6 , when the needle-like portion 20 melts and deforms, the needle-like portion 20 collapses and disappears, exposing the implant 50 held inside the needle-like portion 20 to expose the target tissue Sk. kept inside. Moreover, when the auxiliary liquid 51 is contained together with the implant 50 , the auxiliary liquid 51 also permeates the tissue around the implant 50 . Components of the needle-like portion 20 are diffused and absorbed in the living body. This completes the placement of the implant 50 in vivo.

As described above, according to the placement method of the implant 50 of the present embodiment, the implant 50 is inserted into the living body while being held by the needle-like portion 20, and the needle-like portion 20 disappears into the living body. placed. Therefore, since an instrument such as tweezers is not pulled out of the living body when the implant 50 is placed in the living body, the implant 50 is prevented from coming out of the living body together with the instrument. Therefore, the placement efficiency of the implant 50 is enhanced, and the placement depth of the implant 50 within the tissue of the living body can be easily controlled to a desired depth.

In addition, since the implant 50 is inserted into the living body while being held inside the needle-like portion 20, it is possible to protect the implant 50 from impact during insertion. Compared to the case where the implant is inserted into the living body, it becomes easier to grasp the implantation site of the implant 50 when viewed from the outside.

Here, when the needle-like portion 20 is formed only from a water-soluble material, dissolution of the needle-like portion 20 progresses rapidly from the time the needle-like portion 20 comes into contact with the surface of the living body. Such dissolution of the needle-like portion 20 progresses from the tip portion of the needle-like portion 20 that first comes into contact with the living body. Therefore, before the distal end of the needle-like portion 20 reaches a desired depth, the shape of the distal end may be lost, making it difficult for the needle-like portion 20 to enter the tissue. Further, when the base of the needle-like portion 20 dissolves, the force that presses the cell transplantation unit 10 is less likely to be transmitted to the needle-like portion 20, which also makes it difficult for the needle-like portion 20 to enter the tissue. obtain. As a result, the needle-like portion 20 may not penetrate to the desired depth, and placement of the implant 50 into the living body may be hindered.

On the other hand, in the present embodiment, since the needle-like portion 20 contains an oil-based material in addition to the water-soluble material, the needle-like portion 20 is more dense than the case where the needle-like portion 20 is made of only the water-soluble material. The collapse of the shape progresses gently. For example, when the ratio of the oil-based material in the needle-like portion 20 is about 50% by mass, the time required for the needle-like portion 20 to completely lose its shape is 1.2 times to 10 times of Therefore, at the initial stage when the needle-like part 20 enters the living body, the shape of the needle-like part 20 is easily maintained, so that the needle-like part 20 can be easily stabbed to a desired depth. Therefore, it becomes easier to place the implant 50 at the desired depth. In addition, the speed at which the needle-like portion 20 dissolves can be adjusted by the types of the water-soluble material and the oil-based material, and the ratio of the oil-based material.

Further, when the liquefaction of the support plate portion 30 is completed after the needle portion 20 is melted, or when the support plate portion 30 is peeled off after the needle portion 20 is melted, the needle portion 20 is melted. On the way, the surface of the target tissue Sk where the needle-like portion 20 is stuck is covered with the support plate portion 30 . Therefore, the needle-like portion 20 and the implant 50 are prevented from slipping out of the target tissue Sk even when receiving an external impact.

On the other hand, when the liquefaction of the support plate portion 30 is completed before the needle portion 20 melts, or when the support plate portion 30 is peeled off before the needle portion 20 melts, the needle portion 20 is stuck. Makes it easier to see the position. Therefore, additional processing such as protection of the position where the needle-like portion 20 is stuck and application of medicine to this position can be easily performed.

When the support plate portion 30 has the property of dissolving in water, the speed at which the support plate portion 30 dissolves can be adjusted by the material of the support plate portion 30 . For example, the support plate portion 30 contains the same types of water-soluble material and oily material as the needle-like portion 20, and the ratio of the oily material in the support plate portion 30 and the ratio of the oily material in the needle-like portion 20 are different from each other, the melting speed of the support plate portion 30 and the melting speed of the needle-like portion 20 can be made different.

In addition, when the cell transplantation unit 10 includes a plurality of needle-like portions 20, the proportion of the oily material in each needle-like portion 20 may not be constant. That is, the first needle-like portion 20 and the second needle-like portion 20 are included in the plurality of needle-like portions 20, and the ratio of the oily material in the first needle-like portion 20 and the second needle-like portion 20 may differ from each other. According to such a configuration, the first needle-like portion 20 and the second needle-like portion 20 can have different times required for the shape to disappear. Furthermore, the oily material contained in the first needle-like portion 20 and the oily material contained in the second needle-like portion 20 may be different from each other. Moreover, the cell transplantation unit 10 may have a needle-like portion that does not contain an oily material.

[Method for producing cell transplantation unit]
A method for manufacturing the cell transplantation unit 10 will be described with reference to FIGS. 7 and 8. FIG.
As shown in FIG. 7, the needle-shaped portion 20 is formed by filling an intaglio 80 having recesses 81 corresponding to the desired shape of the needle-shaped portion 20 with a needle-shaped portion forming liquid, which is a liquid containing the material of the needle-shaped portion 20 . and formed by solidifying the filling. The implant 50 is placed inside the needle 20 from a tray such as a culture vessel after solidification of the filler.

The needle-shaped portion forming liquid is produced by, for example, dissolving a water-soluble material in a solvent such as water, and then mixing the solution with an oily material. The material may be heated when generating the needle-shaped portion forming liquid. Solidification of the filling may be performed by drying, or ultraviolet rays or heat may be used.

When forming the accommodation hole 25 , by controlling the filling and solidification of the needle-shaped portion forming liquid so that air bubbles gather in the central portion of the filling that becomes the needle-shaped portion 20 , a void is formed inside the needle-shaped portion 20 . is formed. Accordingly, the accommodating hole 25, which is the gap, can be formed. Alternatively, a pin-shaped structure having a shape corresponding to the receiving hole 25 may be inserted into the central portion of the filling and removed after the filling is solidified. As a result, a gap, which is the receiving hole 25, can be formed in the portion where the pin-shaped structure was positioned.

As shown in FIG. 8, the support plate portion 30 is arranged on the surface positioned at the proximal end of the needle portion 20, and the needle portion 20 and the support plate portion 30 are joined. The support plate portion 30 is formed, for example, by sandwiching the material of the support plate portion 30 between two plate-like members and solidifying the material.

The support plate portion 30 may be joined with an adhesive, or may be joined by heat welding or welding using ultrasonic vibration. Moreover, the needle-like portion 20 may be softened by heat or the like when the support plate portion 30 is joined.
By releasing the needle-like portion 20 from the intaglio 80, the cell transplantation unit 10 is obtained. The release may be performed before the support plate portion 30 is joined.

As long as the cell transplantation unit 10 holding the implant 50 inside the needle-like portion 20 can be formed, the manufacturing method of the cell transplantation unit 10 may be different from the manufacturing method described above. For example, a concave portion corresponding to the support plate portion 30 may be provided in the intaglio 80, and the support plate portion 30 may be formed by filling the concave portion with the material of the support plate portion 30 and solidifying the material.

As described above, according to the first embodiment, the following effects can be obtained.
(1) The implant 50 is inserted into the living body while being held by the needle-like portion 20, and is arranged in the living body by the needle-like portion 20 melting. Therefore, since the implant 50 is prevented from coming out of the living body, the placement efficiency of the implant 50 is enhanced, and the placement depth of the implant 50 in the tissue of the living body can be controlled to a desired depth. (2) Since needle-like portion 20 contains a water-soluble material and an oily material, rapid dissolution of needle-like portion 20 is suppressed. Therefore, at the initial stage when the needle-like part 20 enters the living body, the shape of the needle-like part 20 is easily maintained, so that the needle-like part 20 can be easily stabbed to a desired depth. Therefore, it becomes easier to place the implant 50 at the desired depth.

(3) The water-soluble material contains a water-soluble polymer, and the oily material contains at least one of vegetable oil, animal oil, mineral oil, and oil synthesized using these as raw materials. According to such a configuration, the needle-like portion 20 that is gently dissolved in the living body is preferably realized.

(4) When the ratio of the oily material in the needle-like portion 20 is 60% by mass or less, the strength of the needle-like portion 20 can be appropriately obtained. Further, it becomes easy to mix the water-soluble material and the oil-based material to form the needle-like portion 20 into a desired shape.

(5) Since the water-soluble material and the oily material are uniformly mixed in the needle-like portion 20, rapid dissolution of the needle-like portion 20 can be suppressed in the entire needle-like portion 20.
(6) If the material of the needle-like portion 20 contains a surfactant, the water-soluble material and the oil-soluble material can easily be mixed even when the melting point of the oil-soluble material is high.

(7) Since the support plate portion 30 contains a water-soluble material and an oily material, the support plate portion 30 melts when the support plate portion 30 comes into contact with the surface of the living body. This eliminates the need to peel off the support plate portion 30 , thereby reducing the labor required for using the cell transplantation unit 10 . In addition, the melting speed of the support plate portion 30 can be adjusted by containing the oily material.

(8) If the ratio of the oil-based material in the support plate portion 30 is different from the ratio of the oil-based material in the needle-like portion 20, the dissolving speed of the support plate portion 30 can be made different from the dissolving speed of the needle-like portion 20. can.

(9) If the cell transplantation unit 10 has a plurality of needle-like portions 20 and the ratio of the oily material in the first needle-like portion 20 is different from the ratio of the oily material in the second needle-like portion 20, The melting speed of the first needle-like portion 20 can be made different from the melting speed of the second needle-like portion 20 .

(Second embodiment)
A second embodiment of the containing device, the cell transplantation unit, and the manufacturing method of the containing device will be described with reference to FIGS. 9 to 11. FIG. In the second embodiment, the configuration of the needle-like portion is different from that in the first embodiment. The configuration of the implant and the placement of the implant in the second embodiment are the same as in the first embodiment. In the following, the differences between the second embodiment and the first embodiment will be mainly described, and the same reference numerals will be given to the same configurations as in the first embodiment, and the description thereof will be omitted.

The concentration of the oily material is uneven in the needle-like portion 20 of the cell transplantation unit 11 of the second embodiment. Specifically, the needle-like portion 20 has a water-soluble portion 21 and an oily portion 22 . Needle-like part 20 is an example of a needle-like object. The water-soluble part 21 contains a water-soluble material, and the oily part 22 contains an oily material. Materials exemplified in the first embodiment are used as the water-soluble material and the oily material. The configuration of the support plate portion 30 is the same as that of the first embodiment. Also, placement of the transplant 50 in vivo using the cell transplantation unit 11 of the second embodiment is performed in the same procedure as in the first embodiment.

A cell transplantation unit 11A of the first example shown in FIG. In other words, the oily part 22 covers the surface of the water-soluble part 21 . The water-soluble portion 21 has a shape capable of piercing a living body, like the needle-like portion 20 of the first embodiment. The implant 50 is held in the water-soluble portion 21 . The transplant 50 may be housed in the housing hole formed in the water-soluble portion 21, as in the cell transplantation unit 10B of the first embodiment.

According to the cell transplantation unit 11A of the first example, when the needle-shaped part 20 is pierced into the living body, the water-soluble part 21 becomes difficult to come into contact with water until the oily part 22 dissolves. Therefore, the start of dissolution of the water-soluble portion 21 can be delayed compared to the case where the entire needle-like portion 20 is the water-soluble portion 21 . Therefore, in the initial period after the needle-like portion 20 has entered the living body, the needle-like portion 20 can easily stick to the living body to a desired depth because the shape of the needle-like portion 20 can easily be maintained. Therefore, it becomes easier to place the implant 50 at the desired depth.

Note that the oily part 22 may cover only part of the surface of the water-soluble part 21 . For example, even if the oily part 22 covers only the tip of the water-soluble part 21, the shape of the tip of the needle-like part 20 is easily maintained, so that the needle-like part 20 can be easily stuck to a desired depth. .

In the cell transplantation unit 11A of the first example, for example, after forming the oily portion 22 by applying the material of the oily portion 22 to the inner surface of the concave portion corresponding to the shape of the needle-like portion 20 in the intaglio, the water-soluble portion 21 is formed. It can be formed by filling the material to form the water-soluble portion 21 . Alternatively, after the water-soluble portion 21 is formed using an intaglio, the oily portion 22 may be formed by coating the surface of the water-soluble portion 21 with the material for the oily portion 22 .

A cell transplantation unit 11B of the second example shown in FIG. The portion other than the oily portion 22 is the water-soluble portion 21 , and the tip portion of the needle-like portion 20 is included in the water-soluble portion 21 . The oily portion 22 may be in contact with the support plate portion 30 or may be surrounded by the water-soluble portion 21 at the base of the needle-like portion 20 . FIG. 10 shows a configuration in which the oily portion 22 is surrounded by the water-soluble portion 21 and the support plate portion 30. The entire base of is the oily part 22 , and the oily part 22 may be exposed on the surface of the needle-like part 20 .

The implant 50 may be held by the water-soluble portion 21 or may be held by the oily portion 22 . In addition, similarly to the cell transplantation unit 10B of the first embodiment, the implant 50 is accommodated in the accommodation hole formed in the water-soluble portion 21 and the oily portion 22 or the accommodation hole formed in the oily portion 22. may

According to the cell transplantation unit 11B of the second example, compared to the case where the needle-like portion 20 is entirely water-soluble portion 21, when the needle-like portion 20 is pierced into the living body, the base of the needle-like portion 20 is It takes longer to dissolve. Therefore, it is suppressed that the base portion of the needle-like portion 20 rapidly dissolves and the force that presses the cell transplantation unit 11 is less likely to be transmitted to the needle-like portion 20 . Therefore, the needle-like portion 20 can easily stick to a desired depth.

Also, if the base of the needle-like portion 20 rapidly dissolves, the implant 50 may receive pressure from the liquid that is the dissolved base. By including the oily part 22 in the base of the needle-like part 20, such sudden pressure on the implant 50 is also suppressed. Furthermore, since the shape of the base portion of the needle-like portion 20 is easily maintained, the position where the needle-like portion 20 is stuck can be easily visually recognized due to liquefaction or peeling of the support plate portion 30 .

In the cell transplantation unit 11B of the second example, for example, after filling the material of the water-soluble portion 21 into the concave portion corresponding to the shape of the needle-like portion 20 in the intaglio to form the water-soluble portion 21, the material of the oily portion 22 is formed. to form the oily part 22 .

FIG. 11 shows a cell transplantation unit 11C of the third example. When sufficient strength of the oily part 22 can be obtained, the cell transplantation unit 11C may include the oily part 22 at the distal end of the needle-like part 20, as shown in FIG. The portion other than the oily portion 22 is the water-soluble portion 21 , and the base portion of the needle-like portion 20 is included in the water-soluble portion 21 .

The implant 50 may be held by the water-soluble portion 21 or may be held by the oily portion 22 . In addition, similarly to the cell transplantation unit 10B of the first embodiment, the implant 50 is accommodated in the accommodation hole formed in the water-soluble portion 21 or the accommodation hole formed in the water-soluble portion 21 and the oily portion 22. may be

According to the cell transplantation unit 11C of the third example, compared to the case where the entire needle-like portion 20 is the water-soluble portion 21, when the needle-like portion 20 is pierced into the living body, the tip portion of the needle-like portion 20 It becomes easy to keep the shape of Therefore, the needle-like portion 20 can easily be inserted to the desired depth, and the implant 50 can be easily arranged at the desired depth.

In the cell transplantation unit 11C of the third example, for example, after forming the oily portion 22 by filling the concave portion corresponding to the shape of the needle-like portion 20 in the intaglio to form the oily portion 22, the material for the water-soluble portion 21 is added. It can be formed by filling to form the water-soluble portion 21 .

[Modification]
In the cell transplantation unit 11 of the second embodiment, if the needle-like portion 20 has the water-soluble portion 21 and the oily portion 22, the position of the oily portion 22 is the same as in the first to third examples described above. can be different. For example, the oily part 22 may be located in the central part of the needle-like part 20 , or the needle-like part 20 may have a plurality of oily parts 22 separated from each other within the needle-like part 20 .

In addition, as shown in the first to third examples, there may be a boundary surface between the water-soluble portion 21 and the oil-based portion 22, or the boundary surface between the water-soluble portion 21 and the oil-based portion 22 may be It may not be present, and the concentration of the oily material may gradually change between the water-soluble portion 21 and the oily portion 22 .

The water-soluble part 21 may not contain an oily material, or may contain an oily material mixed with a water-soluble material. Moreover, the oily part 22 may not contain a water-soluble material, or may contain a water-soluble material in a state of being mixed with the oily material. However, the mass ratio of the oily material in the oily portion 22 is greater than the mass ratio of the oily material in the water-soluble portion 21 . That is, the concentration of the oily material is higher in the oily part 22 than in the water-soluble part 21 . Moreover, each of the water-soluble portion 21 and the oil-based portion 22 may contain various materials such as the additives exemplified in the first embodiment, in addition to the water-soluble material and the oil-based material. As in the first embodiment, the ratio of the oil-based material to the entire needle-like portion 20 is preferably 1% by mass or more and 60% by mass or less, and the ratio of the water-soluble material to the entire needle-like portion 20 is 40% by mass. % or more and 99 mass % or less.

Also, the cell transplantation unit 11 may include a plurality of needle-like parts 20, as in the first embodiment. In this case, the arrangement of the oily portions 22 may or may not be the same among the plurality of needle-like portions 20 . For example, the plurality of needle-like portions 20 include the first needle-like portion 20 and the second needle-like portion 20, and the position of the oily portion 22 in the first needle-like portion 20 and the second needle-like portion The position of the oily part 22 in 20 may be different. Furthermore, the ratio and type of the oily material contained in the first needle-like portion 20 and the oily material contained in the second needle-like portion 20 may be different from each other. Moreover, the cell transplantation unit 11 may include the needle-like portion 20 of the first embodiment and the needle-like portion 20 of the second embodiment, or may include a needle-like portion that does not contain an oily material. .

As described above, according to the second embodiment, in addition to the effects (1) to (4) and (7) to (9) of the first embodiment, the following effects can be obtained.
(11) Since the concentration of the oily material in the needle-like portion 20 is uneven within the needle-like portion 20, the dissolving speed of the needle-like portion 20 can be partially slowed down.

(12) The needle-like portion 20 having the water-soluble portion 21 and the oil-based portion 22 suitably realizes the needle-like portion 20 having partially different concentrations of the oil-based material.
(13) If the oily part 22 is located on the surface layer of the needle-shaped part 20, the start of dissolution of the water-soluble part 21 can be delayed. It becomes easy to keep the shape that is easy to stab. Therefore, the needle-like portion 20 can easily be inserted to the desired depth, and the implant 50 can be easily arranged at the desired depth.

(14) If the oily part 22 is positioned at the base of the needle-shaped part 20 , the base of the needle-shaped part 20 dissolves rapidly, and the force that presses the cell transplantation unit 11 is less likely to be transmitted to the needle-shaped part 20 . Also, pressure on the implant 50 from the dissolved base fluid is reduced. In addition, since the shape of the base of the needle-like portion 20 is easily maintained, the position where the needle-like portion 20 is stuck can be easily recognized visually by the liquefaction or peeling of the support plate portion 30 .

(15) If the oily part 22 is positioned at the distal end of the needle-shaped part 20, the shape of the distal end of the needle-shaped part 20 is easily maintained at the initial stage when the needle-shaped part 20 enters the living body. Therefore, the needle-like portion 20 can easily be inserted to the desired depth, and the implant 50 can be easily arranged at the desired depth.

(Third embodiment)
A third embodiment of a containing device, a cell transplantation unit, and a method for manufacturing the containing device will be described with reference to FIGS. 12 to 27. FIG. The third embodiment differs from the first and second embodiments in the configuration of the needle-like portion. The configuration of the implant and the target of placement of the implant in the third embodiment are the same as in the first embodiment. The following description will focus on the differences between the third embodiment and the first and second embodiments, and the same reference numerals will be assigned to the same configurations as in the first and second embodiments. omitted.

[Accommodating device]
As FIG. 12 shows, the containment device 15 comprises needles 20 extending along one direction. The needle-like portion 20 has an accommodation hole 25 that is a hole for partitioning the interior of the needle-like portion 20 into a space for accommodating an implant. The receiving hole 25 opens at the proximal end of the needle-like portion 20 . Furthermore, the containment device 15 comprises a water-impermeable portion 28 that covers the inner surface of the containment hole 25 . In the third embodiment, the needle-shaped body is composed of the needle-shaped portion 20 and the non-water-soluble portion 28 .

The non-water-soluble portion 28 has a film shape along the inner surface of the accommodation hole 25 . A region defined inside the non-water-soluble portion 28 is a storage portion 26 in which the implant is stored. That is, the water-impervious portion 28 surrounds the area within the receiving cavity 25 where the implant is to be placed. The housing portion 26 has a shape substantially similar to that of the housing hole 25 and opens at the proximal end of the needle-like portion 20 . In addition to the implant, the material to be stored in the storage unit 26 may also include a substance for protecting the implant.

The shape of the needle-like part 20 is not particularly limited as long as the tip of the needle-like part 20 has a shape that can pierce the tissue in which the implant is placed. From the viewpoint of increasing the ease with which the needle-like portion 20 sticks into the living body, the tip of the needle-like portion 20 is preferably sharp. For example, the needle-like portion 20 may have a shape such as a conical shape or a pyramidal shape in which the width decreases from the proximal end to the distal end. Alternatively, the needle-like portion 20 may have a shape obtained by cutting a cylinder obliquely to the direction in which it extends, or a shape in which a cone extends from the upper surface of the cylinder. It may have a shape with a narrower width.

The thinner needle portion 20 can reduce the scar formed when the needle portion 20 is pierced into the living body, while the thicker needle portion 20 increases the degree of freedom regarding the size of the accommodation hole 25. Increased, ie greater flexibility in the size and amount of implants that can be accommodated. From the viewpoint of suppressing the enlargement of the scar while suppressing the limitation on the implant that can be accommodated, in the cross section in the width direction at the position where the width of the needle-like part 20 is the largest, the outer shape of the needle-like part 20 When a virtual inscribed circle is used as a reference circle, the radius of the reference circle is preferably 50 μm or more and 2000 μm or less, more preferably 400 μm or more and 800 μm or less. The width direction is a direction perpendicular to the direction in which the needle-like portion 20 extends, and the width of the needle-like portion 20 is the length of the needle-like portion 20 in the width direction.

The shape and size of the accommodation hole 25 are not particularly limited as long as the accommodation section 26 capable of accommodating the implant can be defined. The shape and size of the accommodation hole 25 may be selected according to the size and amount of the implant within a range that does not excessively reduce the strength of the needle-like portion 20 . In the example shown in FIG. 12 , each of accommodation hole 25 and accommodation portion 26 extends from an opening located at the proximal end of needle-like portion 20 with a constant diameter, and then toward the bottom of accommodation hole 25 and accommodation portion 26 . shrink. The bottoms of the accommodation hole 25 and the accommodation portion 26 are the ends opposite to the opening, in other words, the ends of the accommodation hole 25 and the accommodation portion 26 near the tip of the needle-like portion 20 . The cross-sectional shape of each of the accommodation hole 25 and the accommodation portion 26 along the width direction of the needle-like portion 20 is circular, and the bottom of each of the accommodation hole 25 and the accommodation portion 26 is a curved surface. That is, it can be said that each of the accommodation hole 25 and the accommodation portion 26 has a cylindrical shape with a curved bottom.

For example, when the transplant is a cell mass such as a hair follicle primordium, in order to smoothly insert the transplant into the housing portion 26 from the opening 27 of the housing portion 26 at the proximal end of the needle-like portion 20, , the diameter of the opening 27 is preferably 30 μm or more and 1800 μm or less, more preferably 300 μm or more and 700 μm or less.

The depth of each of the receiving hole 25 and the receiving portion 26 may be selected according to the target depth of placement of the implant. However, from the viewpoint of suppressing the transplanted material from coming out of the opening 27 after being housed, the depth of the housing part 26 is preferably 50 μm or more, which facilitates the insertion of the transplanted material into the vicinity of the bottom of the housing part 26. In view of this, it is preferable that the depth of the accommodating portion 26 is 3000 μm or less. Note that the length of the needle-like portion 20 is not particularly limited as long as it is longer than the accommodation hole 25 .

The needle-like portion 20 is made of a material that dissolves in water. A main component of the needle-like portion 20 is a water-soluble polymer. The needle-like portion 20 is made of a material such that the needle-like portion 20 has a strength that allows it to pierce the tissue in which the implant is placed, and that the needle-like portion 20 dissolves in the tissue after it pierces the tissue. The material is selected from materials capable of forming the needle-like portion 20 in

However, if the dissolution of the needle-like portion 20 in the tissue takes too long, the implant may come out of the housing portion 26 due to the movement of the living body or the like before the dissolution of the needle-like portion 20 is completed. It can happen. From the viewpoint of suppressing detachment of the implant, it is preferable that dissolution of the needle-like portion 20 in the tissue in which the implant is placed be completed within 48 hours.

Examples of water-soluble polymers contained in the material of the needle-like portion 20 include carboxymethylcellulose, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, ethylcellulose, hydroxyethylcellulose, polyvinyl alcohol, polyacrylic acid-based polymer, polyacrylamide, polyethylene oxide, pullulan, alginate, starch, pectin, chitosan, chitosan succinamide, oligochitosan, chondroitin sulfate, poly 2-ethyl-2-2 oxazoline, poly 2-methyl-2-oxazoline, carboxyvinyl polymer, dextran, dextrin, Cellulose, chitin, galactan, collagen, atelocollagen, gelatin, leozan, xanthan gum, casein, polyvinylpyrrolidone, hyaluronic acid, glucomannan, polymalic acid, curdlan, and the like. The needle-like portion 20 may be made of a single material among these materials, or may be made of a mixture of a plurality of materials. The main component of the needle-like portion 20 is the material with the highest content ratio in the needle-like portion 20 .

The water-insoluble portion 28 is sparingly soluble in water and deforms in vivo so as to lose its shape. For example, the water-insoluble portion 28 deforms by melting, dissolving, or decomposing in vivo. The water-insoluble portion 28 may have a thickness capable of suppressing permeation of moisture. For example, the thickness of the water-insoluble portion 28 is 20 μm or more.

The main component of the water-insoluble portion 28 is a material that is sparingly soluble in water and undergoes changes such as melting, dissolution, and decomposition in vivo. Preferably, the material of the water-insoluble portion 28 is biocompatible. The material of the water-insoluble portion 28 is, for example, fat or higher alcohol. Examples of fats and oils are saturated fatty acids, olive oil, oleic acid, rapeseed oil, palm oil, cacao butter, petrolatum, liquid lanolin, beeswax, liquid paraffin and the like. Examples of higher alcohols are stearyl alcohol, 1-hexadecanol and the like. As the material of the water-insoluble portion 28, each material mentioned as the oily material in the first embodiment can also be used. An oily material is an example of a material that is sparingly soluble in water. The main component of the water-insoluble portion 28 is the material with the highest content ratio in the water-insoluble portion 28 . In addition, "poorly soluble in water" means that when 1 g of a powdered material is put into 1000 ml of pure water and vigorously shaken for 30 seconds every 5 minutes in an environment of 20 ± 5 ° C, the entire amount will be dissolved within 30 minutes. It means insoluble.

For rapid disintegration of the water-insoluble portion 28 in vivo, the water-insoluble portion 28 preferably has the property of melting at a temperature near body temperature. For example, the melting point of the main component of the water-insoluble portion 28 is preferably 10° C. or higher and 37° C. or lower. If the water-insoluble portion 28 melts in the living body due to the temperature in the living body, it is preferable that the containing device 15 be stored in a cold storage before being inserted into the living body.

Before the needle-shaped part 20 is inserted into the living body, the non-water-soluble part 28 may be solid or semi-solid such as cream as long as it maintains its film-like shape. If the non-water-soluble portion 28 is solid, the non-water-soluble portion 28 contacts the inner surface of the receiving hole 25 due to contact between the implant and the non-water-soluble portion 28 when the implant is stored in the receiving portion 26 . It is possible to suppress peeling from the

The material of the water-insoluble portion 28 may contain an additive in order to facilitate the coating of the inner surface of the accommodation hole 25 and improve the wettability of the inner surface. Examples of additives include polymeric materials such as hydroxypropyl cellulose, ethyl cellulose, zein and shellac, and surfactants such as sucrose fatty acid esters, magnesium stearate and lecithin.

The non-water-soluble portion 28 may have a single-layer structure, or may have a multi-layer structure consisting of a plurality of layers formed from mutually different materials. Moreover, a layer for improving the ease of coating may be provided between the water-insoluble portion 28 and the inner surface of the accommodation hole 25 as a layer serving as a base for the water-insoluble portion 28 .

By providing the non-water-soluble portion 28 , the contents including the implant are prevented from coming into contact with the inner surface of the receiving hole 25 . Therefore, when the content contains water, the dissolution of the needle-like portion 20 from the inside is suppressed before the needle-like portion 20 is pierced into the living body.

[Cell transplantation unit]
A form in which the containing device 15 is used for cell transplantation will be described with reference to FIG. 13 . The housing device 15 in which the implant is housed is the cell transplantation unit.

As shown in FIG. 13, the cell transplantation unit 16 comprises a containment device 15 and an implant 50 . The implant 50 is housed in the housing 26 . In addition, the containing portion 26 contains the auxiliary liquid 51 together with the implant 50 , and surrounds the implant 50 with the auxiliary liquid 51 . Implant 50 and auxiliary fluid 51 are the contents of containment device 15 . A non-water-soluble portion 28 surrounds the stored material.

The auxiliary liquid 51 is a fluid that assists in maintaining the activity of the cell group in the housing part 26 and the engraftment of the cell group after being placed in the living body. For example, the auxiliary liquid 51 surrounds the implant 50 to reduce contact between the implant 50 and the inner surface of the container 26, thereby helping to maintain the activity of the cell population. Alternatively, the auxiliary liquid 51 may contain components close to body fluids of the living body to wrap the implant 50 or provide nutrition to the implant 50, thereby assisting the maintenance of cell group activity and engraftment. good.

The auxiliary liquid 51 contains an aqueous material as a main component. The main component of the auxiliary liquid 51 is the material with the highest content ratio in the auxiliary liquid 51 . Specific examples of the auxiliary liquid 51 are pure water, physiological saline, and the like.
Also, the auxiliary liquid 51 may contain an additive that reduces the vapor pressure of water. If the auxiliary liquid 51 contains such an additive, the needle-shaped portion 20 may dissolve when the auxiliary liquid 51 adheres to the surface of the needle-shaped portion 20 or the like when the auxiliary liquid 51 is stored in the storage portion 26 . suppressed. Examples of additives that reduce the vapor pressure of water are gelatin, agar, sodium alginate, pullulan, gellan gum, hydroxypropylcellulose, collagen, and the like.

The auxiliary liquid 51 may be composed of a single material, or may be a mixture of multiple materials. Also, the auxiliary liquid 51 may be a low-viscosity fluid or a high-viscosity fluid.

It should be noted that the auxiliary liquid 51 does not have to surround the entire circumference of the implant 50 . For example, the implant 50 may be placed at the bottom of the container 26 and the supplemental fluid 51 may cover the implant 50 in the area above the implant 50 to the opening 27 .

[Modified example of housing device and cell transplantation unit]
As FIG. 14 shows, the containment device 15 may comprise a base portion 23 integrally formed with the needle portion 20 . The substrate portion 23 has a plate shape extending from the base end portion of the needle-like portion 20 in a direction perpendicular to the extending direction of the needle-like portion 20 . In other words, the substrate portion 23 supports the proximal end portion of the needle portion 20 .

Specifically, the substrate portion 23 has a first surface 23F and a second surface 23R opposite to the first surface 23F, and the needle-like portion 20 extends from the first surface 23F. The accommodation hole 25 and the accommodation portion 26 are open to the second surface 23R.

The substrate portion 23 is made of the same material as the needle-like portion 20 . The non-water-soluble portion 28 extends continuously from the inner side surface of the accommodation hole 25 to the second surface 23R and covers at least a portion of the second surface 23R.

Since the substrate portion 23 is provided, it is easy to hold the containing device 15 by holding the substrate portion 23 with another tool or the like. Therefore, it becomes easier to move the containing device 15 or to pierce the living body with the containing device 15 .

In addition, since the substrate portion 23 is provided, the substrate portion 23 prevents the stored material from adhering to the surface of the needle-shaped portion 20 when the stored material is put into the storage portion 26 from the opening 27 . So it can be suppressed. Therefore, dissolution of the needle-like portion 20 is suppressed before the needle-like portion 20 is pierced into the living body. In addition, the non-water-soluble portion 28 also covers the second surface 23</b>R of the substrate portion 23 continuously from the inner surface of the accommodation hole 25 . That is, since the substrate portion 23 is covered with the non-water-soluble portion 28 in the vicinity of the opening 27, it is possible to suppress the adhesion of the stored object to the substrate portion 23 when the stored object is put into the storage portion 26 through the opening 27. be done. Therefore, the melting of the substrate portion 23 is also suppressed.

In particular, when a water-based fluid such as the auxiliary liquid 51 is contained in the content, droplets from the content tend to scatter around and adhere to the storage device 15 when the content is stored. Therefore, as described above, it is highly beneficial to suppress the dissolution of the needle-shaped portion 20 and the substrate portion 23 by the substrate portion 23 and the water-insoluble portion 28 on the substrate portion 23 .

If the substrate portion 23 is too large, the force applied to the containing device 15 when the needle-like portion 20 is inserted into the living body is likely to escape to the substrate portion 23. Therefore, the substrate portion assigned to one needle-like portion 20 The area of the first surface 23F of 23 is preferably 625 mm ² or less. Alternatively, the substrate portion 23 may be reduced in size by cutting or the like after the contents are accommodated, or the substrate portion 23 and the needle may be separated from the substrate portion 23 so that the needle-like portion 20 can be separated from the substrate portion 23 when the living body is punctured. The boundary with the shaped portion 20 may be processed.

The containment device 15 may comprise a seal 40, as shown in FIGS. The sealing portion 40 closes the opening portion 27 in a state in which the storage portion 26 accommodates an object. The sealing portion 40 extends along the surface located at the proximal end of the needle-like portion 20 or along the second surface 23R of the substrate portion 23 . The sealing portion 40 is made of a material that does not dissolve in water.

The sealing portion 40 before closing the opening 27 may be managed separately from the needle-like portion 20 and the substrate portion 23, or may be connected to the end portion of the substrate portion 23 or the like.
For example, the sealing portion 40 is a resin sheet having an adhesive surface. may be placed above. Alternatively, the sealing portion 40 may be formed by applying an oily sealing material so as to cover the opening 27 . The sealing material is, for example, an oily cream such as vaseline. The seal 40 is preferably capable of adhering to the surface of the tissue in which the implant 50 is placed.

By providing the sealing portion 40, the contents can be prevented from leaking out of the storage portion 26 due to vibrations during transportation of the storage device 15, impact when the storage device 15 pierces the living body, or the like. can be done.

[Manufacturing method of storage device and cell transplantation unit]
The needle-like portion 20 is formed by filling a solution containing the material of the needle-like portion 20 into a mold having recesses corresponding to the desired shape of the needle-like portion 20, solidifying the filling by drying, and then releasing the mold. manufactured.

By controlling the filling and drying of the solution so that air bubbles gather in the central portion of the filling that will become the needle-like portion 20 , a void is formed inside the needle-like portion 20 . Accordingly, the accommodating hole 25, which is the gap, can be formed. Alternatively, a pin-shaped structure having a shape corresponding to the receiving hole 25 may be inserted into the central portion of the filling and removed after the filling is solidified. As a result, a gap, which is the receiving hole 25, can be formed in the portion where the pin-shaped structure was positioned.

In addition, in the case where the containing device 15 includes the substrate portion 23 , the substrate portion 23 is also formed at the same time as the needle portion 20 .
The water-insoluble portion 28 is formed by applying the material of the water-insoluble portion 28 into the receiving hole 25 . When forming the water-insoluble portion 28 , the shape of the accommodating portion 26 may be adjusted by inserting a pin-shaped structure corresponding to the desired shape of the accommodating portion 26 into the accommodating hole 25 .

The storage of the contents in the storage section 26 may be performed by a method according to the properties of the contents. As an example, a case where a transplant 50 containing a group of cells and an auxiliary liquid 51 are accommodated in the accommodation portion 26 will be described.

First, the storage portion 26 is filled with the auxiliary liquid 51 . For example, the auxiliary liquid 51 may be injected into the container 26 using a nozzle, or after the auxiliary liquid 51 is dropped toward the opening 27, the container 26 may be evacuated or a centrifuge may be used. The storage part 26 may be filled with the auxiliary liquid 51 by using it.

Then, the implant 50 is put into the housing portion 26 . For example, if the implant 50 is dropped toward the opening 27, the implant 50 will sink into the housing 26 due to gravity. At this time, in order to facilitate accommodation of the implant 50 in the container 26, a centrifuge may be used, or a rod-shaped or pipe-shaped instrument may be used to push the implant 50 to move the implant 50 to the bottom of the container 26. You can move it towards

Although the implant 50 does not necessarily need to be submerged near the bottom of the container 26 , the closer the implant 50 is placed to the bottom of the container 26 , the less likely the implant 50 will leak out of the container 26 . preferable. If the needle-like portion 20 and the non-water-soluble portion 28 are transparent, the placement of the implant 50 can proceed while confirming the position of the implant 50 in the storage portion 26 .
In the case where the containing device 15 has the sealing portion 40 , the opening portion 27 is covered with the sealing portion 40 after the object is contained in the containing portion 26 .

[Method of placement of implant]
A method of placing an implant using containment device 15 will now be described with reference to FIGS. 17-20. That is, the method of placing the transplant is a method of transplanting cells using the cell transplantation unit 16 .

As shown in FIG. 17, first, the needle-like portion 20 of the cell transplantation unit 16 is pressed against the target tissue Sk where the implant 50 is to be placed, thereby piercing the target tissue Sk with the needle-like portion 20 . The target tissue Sk is, for example, skin. At this time, an applicator may be used that assists the needle-like portion 20 to enter the target tissue Sk by adjusting the force applied to the needle-like portion 20 and the direction of the needle-like portion 20 . If the housing device 15 has the substrate portion 23, it is easy to hold the cell transplantation unit 16 on the applicator. Note that in a state in which the needle-like portion 20 is stuck in the target tissue Sk, the substrate portion 23 does not enter the target tissue Sk and is arranged on the surface of the target tissue Sk.

As shown in FIG. 18, when the needle-like portion 20 enters the target tissue Sk, the needle-like portion 20 is dissolved by the contact between the needle-like portion 20 and the moisture in the tissue. In addition, the water-insoluble portion 28 also collapses as it is placed inside the target tissue Sk. For example, when the non-water-soluble portion 28 melts at a temperature near body temperature, the non-water-soluble portion 28 is warmed to a temperature near body temperature as the needle-like portion 20 enters the target tissue Sk. Melt. As a result, the water-insoluble portion 28 is deformed, and the implant 50 surrounded by the water-insoluble portion 28 is exposed from the water-insoluble portion 28 .

Either the deformation of the needle-like portion 20 or the deformation of the water-insoluble portion 28 may occur first. The speed at which the needle-shaped portion 20 collapses and the speed at which the water-insoluble portion 28 collapses can be adjusted by the materials of the needle-shaped portion 20 and the water-insoluble portion 28 . For example, when the needle-like portion 20 collapses before the non-water-soluble portion 28, the wound formed by the needle-like portion 20 piercing the target tissue Sk, in other words, the cut portion in the tissue is needle-like. As the portion 20 dissolves, it closes. At this time, the water-insoluble portion 28 is deformed and exists around the implant 50, and the water-insoluble portion 28 having a larger surface area than the implant 50 is likely to be caught inside the tissue. Therefore, since the implant 50 is caught in the water-insoluble portion 28, the implant 50 is prevented from being pushed out to the tissue surface when the wound is closed.

As shown in FIG. 19, as the deformation of the needle-like portion 20 and the water-insoluble portion 28 progresses, the containing device 15 collapses and disappears, and the contained implant 50 is retained within the target tissue Sk. The components of the needle-like portion 20 and the water-insoluble portion 28 are diffused and absorbed into the living body. This completes the placement of the implant 50 in vivo. It should be noted that in the case where the housing device 15 includes the substrate portion 23, the substrate portion 23 is dissolved by coming into contact with water on the surface of the target tissue Sk.

By using the housing device 15 of the present embodiment, the implant 50 is prevented from being pulled out of the living body when the implant 50 is placed in the body, thereby preventing the implant 50 from coming out of the body together with the instrument. Therefore, the efficiency of implant 50 placement is also enhanced. In addition, since the implant 50 is inserted into the living body while being housed in the needle-like portion 20, the implant 50 can be protected from impact during insertion.

As shown in FIG. 20 , when the containment device 15 is provided with a sealing portion 40 , the sealing portion 40 forms a needle-like shape on the surface of the target tissue Sk after disappearance of the needle-like portion 20 and the water-insoluble portion 28 . The part 20 covers the wound Ct formed by stabbing the target tissue Sk. This can also prevent the implant 50 from coming out of the wound Ct.

[Modified Example of Accommodating Hole and Accommodating Portion]
As shown in FIG. 21, the shape of the accommodation hole 25 and the shape of the accommodation portion 26 may not be similar. In the example shown in FIG. 21, the bottom of the accommodation hole 25 is curved, whereas the bottom of the accommodation portion 26 is flat. The receiving hole 25 has, for example, a cylindrical shape with a curved bottom, and the receiving portion 26 has, for example, a cylindrical shape with a flat bottom surface.

As described in the manufacturing method of the housing device 15, any manufacturing method for forming the water-insoluble portion 28 by inserting a pin-shaped structure corresponding to the desired shape of the housing portion 26 into the housing hole 25 can be used. The shape of the hole 25 and the shape of the housing portion 26 can be different.

The accommodation hole 25 having a cylindrical shape with a curved bottom can be preferably formed by a manufacturing method of forming the accommodation hole 25 using air bubbles. On the other hand, the housing portion 26 having a cylindrical shape with a flat bottom surface can be preferably formed by the manufacturing method using the pin-shaped structure.

Also, the thickness of the water-insoluble portion 28 may not be constant. For example, in the example shown in FIG. 21 , the non-water-soluble portion 28 on the side surface of the accommodation hole 25 is thicker than the water-insoluble portion 28 on the bottom surface of the accommodation hole 25 . As shown in FIG. 22, even when the accommodation hole 25 and the accommodation portion 26 have substantially similar shapes, the thickness of the non-water-soluble portion 28 may not be constant.

If the non-water-soluble portion 28 is thicker on the bottom surface than on the side surface of the receiving hole 25, the tip of a tool such as a nozzle or a pipette may be inserted into the receiving portion 26 when the container 26 contains a material. Even if the tip of the instrument contacts the bottom of the housing portion 26 and the non-water-soluble portion 28 is scraped off when it is inserted into the housing portion 26, the inner surface of the housing hole 25 is less likely to be exposed.

In addition, by varying the thickness of the water-insoluble portion 28 on the side surface of the receiving hole 25, it is possible to change the diameter of the receiving portion 26, thereby preventing the implant from being caught in the receiving portion 26. It is also possible to control the depth to which it is clipped. Similarly, by adjusting the thickness of the water-impermeable portion 28 on the bottom surface of the receiving hole 25, the depth to which the implant is anchored within the receiving hole 25 can be controlled. The ability to control the depth at which a contained implant is anchored allows for more precise control over the depth at which the implant is placed within the tissue of the body.
In addition, as shown in FIGS. 21 and 22 , the non-water-soluble portion 28 may not cover the second surface 23R of the substrate portion 23 and may cover only the inner surface of the receiving hole 25 .

As shown in FIG. 23, the side surface of the accommodation hole 25 and the side surface of the accommodation portion 26 may be inclined with respect to the direction in which the needle-like portion 20 extends. In the example shown in FIG. 23, the side surfaces of each of the accommodation hole 25 and the accommodation portion 26 are inclined such that the diameter of each of the accommodation hole 25 and the accommodation portion 26 gradually decreases from the opening 27 toward the bottom. there is For example, each of the accommodation hole 25 and the accommodation portion 26 has a conical concave shape.

If the side surface of the accommodation hole 25 is inclined so that the diameter of the accommodation hole 25 decreases toward the bottom, it is easy to apply the material of the non-water-soluble portion 28 to the inner surface of the accommodation hole 25 from the opening of the accommodation hole 25 . In addition, since the diameter of the accommodating portion 26 is maximized at the opening portion 27, it is easy to accommodate the contents.

Furthermore, in the example shown in FIG. 23 , the thickness of the needle-like portion 20 , that is, the thickness from the inner surface of the accommodation hole 25 to the surface of the needle-like portion 20 increases toward the base end portion of the needle-like portion 20 . It's becoming With such a configuration, the strength of the base end portion of the needle-like portion 20 is increased, so that the needle-like portion 20 is less likely to break. In particular, when the accommodating portion 26 has a shape that maximizes the diameter at the opening 27, it is easy to accommodate the content, but the strength near the proximal end portion of the needle-like portion 20 is weakened. Cheap. On the other hand, if the thickness of the needle-like portion 20 increases toward the base end portion, it is possible to suppress a decrease in strength near the base end portion of the needle-like portion 20 due to the shape of the housing portion 26 .

On the other hand, from the viewpoint of increasing the ease with which the needle-like portion 20 sticks into the living body, it is preferable that the tip portion of the needle-like portion 20 is difficult to deform when the needle-like portion 20 is stuck into the living body. It is preferable that the strength of the tip portion of is high. From this point of view, it is preferable that the accommodation hole 25 does not extend to the tip of the needle-like portion 20 . For example, it is preferable that the accommodation hole 25 is not arranged in a region of 1/10, preferably 1/3 of the total length of the needle-like portion 20 from the tip of the needle-like portion 20 .

As shown in FIG. 24 , the diameter of the accommodation hole 25 may be maximum at the central portion of the accommodation hole 25 in the depth direction. It may be maximum in the central part of the direction. With such a form, it is easy to secure a wide space for accommodating the implant.

As shown in FIG. 25, each of the accommodation hole 25 and the accommodation portion 26 may have a funnel shape. That is, the diameter of each of the accommodation hole 25 and the accommodation portion 26 becomes constant after gradually decreasing from the end where the opening 27 is located. In the example shown in FIG. 25, the diameter of each of the accommodation hole 25 and the accommodation portion 26 becomes constant and then decreases toward the bottom.

With such a configuration, as shown in FIG. 26 , when an injection device 60 such as a nozzle or a pipette is used to put a contained object into the container 26 , the injection device 60 is placed near the opening 27 in the container 26 . By injecting the content with the tip pointed, scattering of the content can be suppressed and the content can be smoothly accommodated in the accommodation section 26 .

Further, the surface roughness of the inner surface of the accommodation hole 25 and the accommodation portion 26 may be made larger than the surface roughness of the surface of the needle-like portion 20 . If the surface roughness of the inner surface of the accommodation hole 25 is greater than the surface roughness of the surface of the needle-shaped portion 20, compared with the case where the surface roughness of the inner surface of the accommodation hole 25 is equal to the surface of the needle-shaped portion 20. As a result, the non-water-soluble portion 28 is less likely to peel off from the inner surface of the accommodation hole 25 . Further, when the material of the non-water-soluble portion 28 is applied to the inner surface of the accommodation hole 25 , the material tends to adhere to the inner surface of the accommodation hole 25 . Therefore, the degree of freedom in selecting the material for the water-insoluble portion 28 and setting the coating conditions is increased.

Further, if the surface roughness of the inner surface of the accommodating portion 26 is greater than the surface roughness of the surface of the needle-shaped portion 20, the surface roughness of the inner surface of the accommodating portion 26 is equivalent to the surface of the needle-shaped portion 20. , the implant is more likely to get caught on the inner surface of the housing part 26 . Therefore, the housed implant is prevented from coming out of the housing part 26 .

The surface roughness of the inner surface of the accommodation hole 25 and the accommodation portion 26 can be adjusted, for example, by the surface roughness of the pin-shaped structure used in manufacturing and the coating method of the water-insoluble portion 28 .
As shown in FIG. 27 , the water-insoluble portion 28 may be fluid and filled in the accommodation hole 25 . In this case, the area defined by the accommodation hole 25 is the accommodation portion 26 , and the implant 50 is entirely surrounded by the water-insoluble portion 28 in the accommodation portion 26 and is in contact with the water-insoluble portion 28 . The water-insoluble portion 28 may be filled into the accommodation hole 25 before the implant 50 is accommodated, or may be put into the accommodation hole 25 simultaneously with the implant 50 .

Even in this form, the inner surface of the accommodation hole 25 is covered with the non-water-soluble portion 28, so contact between the implant 50 and the inner surface of the accommodation hole 25 can be suppressed. Therefore, when the implant 50 contains moisture, the dissolution of the needle-like portion 20 from the inside is suppressed before the needle-like portion 20 is pierced into the living body. In vivo, deformation of the non-water-soluble portion 28 is a change in the area occupied by the non-water-soluble portion 28 so that the state in which the non-water-soluble portion 28 surrounds the implant 50 is broken.

[Other Modifications]
The containment device 15 may comprise a plurality of needles 20 each containing an implant 50 . Thereby, a plurality of implants 50 can be collectively placed in the living body. A plurality of needle-like portions 20 may be connected by one substrate portion 23, for example.

The accommodation hole 25 and the accommodation portion 26 may be opened on the side surface of the needle-like portion 20 . When the receiving portion 26 is open on the side surface of the needle-like portion 20, the degree of freedom regarding adjustment of the opening area and the placement depth of the implant 50 can be improved. On the other hand, if the accommodating part 26 is open at the proximal end of the needle-like part 20, the implant 50 can be easily accommodated, and the strength of the needle-like part 20 can be easily ensured. In particular, when the containment device 15 has a plurality of needle-like portions 20 , if the containment portion 26 is open at the proximal end of the needle-like portion 20 , the implant 50 can be efficiently contained in each needle-like portion 20 . can do.

Note that when the non-water-soluble portion 28 is regarded as a part of the member that constitutes the needle-shaped portion 20, the non-water-soluble portion 28 is an example of the oily portion 22 of the second embodiment, and the needle-shaped portion other than the non-water-soluble portion 28 is used. The portion 20 can also be regarded as an example of the water-soluble portion 21 of the second embodiment.

As described above, according to the third embodiment, the following effects can be obtained.
(21) The implant 50 is accommodated in the needle-like portion 20, and the needle-like portion 20 piercing the living body dissolves in the living body, and the non-water-soluble portion 28 deforms in the living body to expose the implant 50. The implant 50 is thereby placed in the living body. Therefore, since the device is not pulled out from the living body when the implant 50 is placed in the living body, it is possible to prevent the implant 50 from coming out of the living body together with the device. This also increases the efficiency of implant 50 placement.

(22) Since the inner surface of the accommodation hole 25 is covered with the water-insoluble portion 28 and the implant 50 is surrounded by the water-insoluble portion 28, the contents of the accommodation portion 26 including the implant 50 are Contact with the inner surface is suppressed. Therefore, even when the content contains water, it is possible to prevent needle-like portion 20 from dissolving from the inside before stabbing needle-like portion 20 into the living body.

(23) The non-water-soluble portion 28 has a film-like shape that covers the inner surface of the accommodation hole 25 , and the inside of the water-insoluble portion 28 defines a storage portion 26 that is a region that stores the implant 50 . According to such a configuration, a fluid for protecting the implant 50 or the like can be accommodated together with the implant 50, or an object that is a fluid can be accommodated.

(24) If the water-insoluble portion 28 is filled in the accommodation hole 25, the implant 50 desired to be protected by the water-insoluble fluid is placed in the water-insoluble portion 28 functioning as the fluid. It can be contained in an enclosed state.

(25) If the accommodating hole 25 and the accommodating portion 26 are open at the proximal end of the needle portion 20, the implant 50 can be easily accommodated, and the strength of the needle portion 20 can be easily ensured. . Alternatively, the implant 50 can be placed in the housing portion 26 immediately before the needle-like portion 20 is pierced into the living body.

(26) If the containing device 15 is provided with a sealing portion 40 configured to be able to block the openings of the containing hole 25 and the containing portion 26, the contents contained in the containing portion 26 will not leak from the openings. is suppressed. In addition, even after the implant 50 is placed in the living body, the sealing part 40 closes the wound formed by the entry of the needle-like part 20, so that the implant 50 is prevented from being detached from the living body.

(27) If the containing device 15 is provided with the substrate portion 23 that supports the base end portion of the needle-like portion 20, other instruments or the like may be used when the containing device 15 is transported or when the needle-like portion 20 pierces the living body. It is easy to hold the containment device 15 with the Moreover, when accommodating the content in the needle-like portion 20 , the content is prevented from adhering to the surface of the needle-like portion 20 . Therefore, even when the content contains water, dissolution of the needle-like portion 20 before the needle-like portion 20 is pierced into the living body can be suppressed.

(28) If the non-water-soluble portion 28 extends continuously from the inner surface of the accommodation hole 25 to the second surface 23R of the substrate portion 23, when the needle-like portion 20 accommodates the content, , the contents are prevented from adhering to the substrate portion 23 . Therefore, even if the content contains water, it is possible to prevent the substrate portion 23 from dissolving before the needle-like portion 20 is pierced into the living body.

(29) If the water-insoluble portion 28 has the property of being melted in the living body due to the temperature in the living body, the deformation of the water-insoluble portion 28 in the living body proceeds favorably. Therefore, the implant 50 is accurately placed in the living body.

(30) The implant 50 containing the cell group contains water. Therefore, the beneficial effect of arranging the water-insoluble portion 28 is highly obtained. In addition, even when fluid containing an aqueous material is accommodated in the accommodation portion 26 together with the implant 50, the effect of arranging the water-insoluble portion 28 is highly beneficial.

(Modifications of the first to third embodiments)
In each of the above embodiments, the object to be housed in the housing device is not limited to the implant 50, and may be a member such as a medicine or an IC chip. The object may be liquid, solid, gel, or a mixture thereof. The containing device containing the object is the containing unit, and the cell transplantation unit is an example of the containing unit.

(Example)
[Test Examples 1 to 12]
A test example of the needle-shaped portion was produced for the above-described containing device, and a test was conducted to evaluate the moldability and melting speed of the needle-shaped portion. In addition, the acicular part of the test example corresponds to the acicular part of the first embodiment.

(Test example 1)
On a magnetic stirrer heated to 40 ° C., add palm oil to an aqueous pullulan solution in a thermally conductive container and mix for 10 minutes using a stirrer bar to form a needle-shaped part. A liquid needle-like portion forming liquid was prepared. Pullulan is a water-soluble material and palm oil is an oily material. The ratio of palm oil to the total mass of pullulan and palm oil contained in the needle-forming liquid was 50% by mass. The palm oil was used after being heated in a heating device such as a clean oven and dissolved in a liquid state.

An intaglio plate having quadrangular pyramid-shaped recesses was prepared, and the recesses were filled with the needle-shaped portion forming liquid. The opening surface of the recess has a square shape with one side of 800 μm, and the depth of the recess is 1.8 mm. Furthermore, the portion corresponding to the support plate portion was formed by spreading the needle-shaped portion forming liquid over the concave portion as well. Then, the intaglio plate filled with the needle-shaped portion forming liquid was dried in an environment of 25° C. temperature and 30% humidity for 72 hours while being ventilated. As a result, the needle-like portion, which is the filling material for the recess, and the support plate portion were formed.

Subsequently, the needle-like portion of Test Example 1 was obtained by holding the support plate portion and releasing the needle-like portion from the intaglio.
(Test example 2)
Needles of Test Example 2 were obtained using the same materials and processes as those of Test Example 1, except that the proportion of palm oil in the needle-like portion-forming liquid was changed. The proportion of palm oil in the needle-shaped portion-forming liquid in Test Example 2 was 10% by mass.

(Test example 3)
Needles of Test Example 3 were obtained using the same materials and processes as in Test Example 1, except that the proportion of palm oil in the needle-shaped portion-forming liquid was changed. The proportion of palm oil in the needle-shaped portion-forming liquid in Test Example 3 was 1% by mass.

(Test example 4)
Needles of Test Example 4 were obtained using the same materials and processes as in Test Example 1, except that a sucrose fatty acid ester, which is a surfactant, was added as an additive to the needle-like portion-forming liquid. The ratio of the sucrose fatty acid ester in the needle-shaped portion-forming liquid in Test Example 4 was 1% by mass.

(Test Example 5)
Needles of Test Example 5 were obtained using the same materials and processes as in Test Example 1, except that a surfactant, sucrose fatty acid ester, was added as an additive to the needle-like portion-forming solution. The ratio of the sucrose fatty acid ester in the needle-shaped portion-forming liquid in Test Example 5 was 0.1% by mass.

(Test example 6)
Test Example 6 was performed using the same materials and processes as in Test Example 1, except that petrolatum was used as the oily material, and sucrose fatty acid ester, which is a surfactant, was added as an additive to the needle-shaped portion-forming liquid. needles were obtained. In the needle-shaped portion-forming liquid of Test Example 6, the percentage of petroleum jelly was 67% by mass, and the percentage of sucrose fatty acid ester was 1% by mass.

(Test Example 7)
A needle-like portion of Test Example 7 was obtained using the same material and process as in Test Example 6, except that the proportion of petroleum jelly in the needle-like portion-forming liquid was changed. The proportion of petroleum jelly in the needle-shaped portion-forming liquid in Test Example 7 was 50% by mass.

(Test Example 8)
A needle-shaped portion of Test Example 8 was obtained using the same material and process as in Test Example 6, except that the proportion of petroleum jelly in the needle-shaped portion-forming liquid was changed. The ratio of petroleum jelly in the needle-shaped portion-forming liquid in Test Example 8 was 33% by mass.

(Test Example 9)
A needle-shaped portion of Test Example 9 was obtained using the same material and process as in Test Example 6, except that the proportion of petrolatum in the needle-shaped portion-forming liquid was changed. The proportion of petroleum jelly in the needle-shaped portion-forming liquid in Test Example 9 was 10% by mass.

(Test Example 10)
Needles of Test Example 10 were obtained using the same materials and processes as in Test Example 6, except that the proportions of petrolatum and sucrose fatty acid ester in the needle-like portion-forming liquid were changed. In the needle-shaped portion-forming liquid of Test Example 10, the percentage of petroleum jelly was 50% by mass, and the percentage of sucrose fatty acid ester was 5% by mass.

(Test Example 11)
Needles of Test Example 11 were obtained using the same materials and processes as in Test Example 6, except that the proportions of petrolatum and sucrose fatty acid ester in the needle-like portion-forming liquid were changed. In the needle-shaped portion-forming liquid of Test Example 11, the percentage of petrolatum was 30% by mass, and the percentage of sucrose fatty acid ester was 5% by mass.

(Test Example 12)
Needles of Test Example 12 were obtained using the same materials and processes as in Test Example 6, except that the proportions of petrolatum and sucrose fatty acid ester in the needle-like portion-forming liquid were changed. In the needle-shaped portion-forming liquid of Test Example 12, the percentage of petroleum jelly was 10% by mass, and the percentage of sucrose fatty acid ester was 5% by mass.

(Moldability evaluation)
<Releasability>
For each test example, mold release was performed so as to separate the needle-like portion from the intaglio plate, and ease of mold release was evaluated on a three-grade scale. In the evaluation, when it was difficult to peel the needle-like portion from the intaglio, and a sample in which the needle-like portion was split into a plurality of parts was generated, one score was given. 2 points when more than 10% of the samples were partially chipped, and 90% or more of the samples had no chipped needles if the needles could be peeled off from the intaglio. The case where it was obtained was set as 3 points.

<Followability>
For each test example, the shape of the needle-like portion was observed, and the followability of the shape of the needle-like portion to the shape of the concave portion was evaluated in three stages. In the evaluation, 1 point was obtained when the needle-shaped part-forming liquid did not enter the concave part, and a sample in which the needle-shaped part was not formed was formed. A score of 2 was given when it occurred at a rate exceeding 3, and a score of 3 was given when a needle-like portion having a shape matching the shape of the concave portion was obtained for 90% or more of the samples. In addition, the needle-shaped portion different from the shape of the recess includes a needle-shaped portion that is smaller or larger than the recess, and a needle-shaped portion that has unevenness on the surface due to the inclusion of air bubbles or the like and does not have a surface along the recess. part is included.

<Stability>
For each test example, the shape of the needle-like portion was observed, and the stability of the shape in a plurality of samples was evaluated on a three-grade scale. In the evaluation, in a plurality of samples, 1 point when the ratio of needle-like portions formed in the desired shape is less than 50%, and in a plurality of samples, the ratio of needle-like portions formed in the desired shape is 50. % or more and less than 85% was given 2 points, and a case where the ratio of needle-like portions formed in a desired shape in a plurality of samples was 85% or more was given 3 points. The desired shape of the needle-like portion is a needle-like portion that has no chipping and matches the shape of the recess.

(Evaluation of shape disappearance rate)
The needle-shaped portion of each test example was immersed in water, and the time required for the needle-shaped portion to lose its shape, that is, until the needle-shaped portion was completely dissolved, was measured. In the evaluation, 1 point was given when the measurement result was 3 minutes or more and less than 4 minutes, and 2 points were given when the measurement result was 4 minutes or more. In Test Examples 4, 5, 6, 10, 11, and 12, the desired shape of the needle-like portion was not obtained, or the needle-like portion was brittle and the needle-like portion was soaked in water while maintaining its shape. Due to the difficulty of conducting the immersion test, the shape disappearance rate was not measured.

As a reference example, a needle-like portion was produced by the same process as in Test Example 1 using an aqueous pullulan solution as a needle-like portion-forming liquid. The needle-shaped portion of the reference example does not contain an oily material or additives, and is formed only from a water-soluble material. When the needle-shaped portion of the reference example was soaked in water and the time required for the needle-like portion to lose its shape was measured, the measurement result was about 1 minute.

(Evaluation results)
Table 1 shows the type of oily material, the proportion of oily material, the proportion of additive, evaluation results of formability evaluation and shape disappearance rate evaluation, and overall evaluation for each test example. Comprehensive evaluation is the sum of the points of each evaluation.

As shown in Table 1, the easiness of forming the needle-like portion varies depending on the ratio of the oily material and whether or not the surfactant is added and the amount of surfactant added. As a whole, there is a tendency that the smaller the ratio of the oily material, the higher the formability of the needle-shaped portion. When the oily material was palm oil, the contribution of the sucrose fatty acid ester to the improvement of moldability could not be confirmed. On the other hand, when the oily material is petrolatum, the addition of the sucrose fatty acid ester facilitates the mixing of the petrolatum with the needle-like portion-forming liquid, and the addition ratio of the sucrose fatty acid ester of about 1% by mass is favorable. It was confirmed that there is a tendency that good moldability is easily obtained.

Further, regarding the disappearance rate of the shape, in all test examples in which measurement was performed, the time required for the disappearance of the shape was longer than that of the needle-shaped portion of the reference example made of only the water-soluble material. It was confirmed that the melting speed of the part slowed down.
A total evaluation of 8 points or more is preferable because it can be said that the acicular portion has well-balanced characteristics related to each evaluation.

[Example 1]
The accommodation device and cell transplantation unit of the third embodiment will be described using specific examples.

(Production method)
A mold having quadrangular pyramid-shaped concave portions was prepared, and an aqueous pullulan solution was dropped into the concave portions as a solution for forming the needle-like portions. Then, the mold filled with the pullulan aqueous solution was dried in an environment of temperature 25° C. and humidity 30% for 72 hours while being ventilated. As drying progresses, cavities grow inside the filling of the recesses due to the balance between the wettability of the mold and the surface tension of the aqueous pullulan solution. After the drying was completed, the filling was released from the mold to obtain a needle-like portion having the above-mentioned hollow accommodation hole. The face located at the proximal end of the needle-like portion has a square shape with a side of 500 μm, and the length of the needle-like portion is 1.8 mm.

Subsequently, a film-like water-insoluble portion was formed by applying fatty acid glyceride inside the accommodation hole. As a result, storage portions partitioned by water-insoluble portions were formed, and the storage device of Example 1 was obtained. The diameter of the opening of the container was measured using a microscope. As a result, the diameter of the opening was 300 μm.

(Functional test)
Colored water was injected into the storage portion of the storage device of Example 1, and the progress was observed. The appearance of the needle-like portion did not change even after 10 minutes, and dissolution of the needle-like portion was not confirmed. In addition, when the agarose gel kept at 37° C. was pierced with the needle-like part and the progress was observed, the needle-like part dissolved rapidly, and a cage-like structure consisting of the deformed water-insoluble part was formed inside the agarose gel. was confirmed. Furthermore, it was confirmed that the deformation of the non-water-soluble portion proceeded and became liquid 30 minutes after the needle-like portion was pricked.

(Containment test)
4×10 ³ cells of human dermal papilla cells were seeded in each well of a round-bottomed 96-well plate and cultured for 3 days. This resulted in the formation of cell clumps in each well. The diameter of the formed cell mass was about 300 µm.

A phosphate buffer solution was injected as an auxiliary liquid into the housing portion of the housing device of Example 1 using a tube. Furthermore, using a micropipette, the cell mass was dropped into the opening of the container. When the containing device was left with the opening facing upward, the cell clusters sank into the containing part due to gravity. Since cell masses larger than the diameter of the opening do not enter the storage unit by the action of gravity alone, the storage device was subjected to centrifugation using a desktop centrifuge to sink the cell masses into the storage unit. . The centrifugation speed is 5000 rpm, and the treatment time is 60 seconds.

Cell clusters were placed in 10 storage devices by the above method, and each storage device was observed from the outside with a microscope. Since the acicular part and the water-insoluble part of Example 1 are transparent, the position of the cell mass can be confirmed from the outside. As a result of observation, it was confirmed that in 90% or more of the containing devices, the cell mass was contained near the bottom of the containing portion.

After that, the storage device containing the cell mass was immersed in a liquid medium kept at 37°C to liquefy the needle-shaped part and the water-insoluble part, and the cell mass was recovered. In order to confirm whether the cell aggregates were damaged due to accommodation in the needle-like portion, the sizes of the cell aggregates before and after accommodation in the needle-like portion were compared. The size comparison was carried out by comparing the areas of the cell clusters projected onto a predetermined surface by observation using an epi-illumination microscope. As a result, 80% or more of the cell aggregate area was maintained for all cell aggregates. Therefore, it can be concluded that the cell aggregates were not damaged due to accommodation in the needle-like portion.

Claims

A containment device for use in placing an object in vivo, comprising:
A needle-like body having a needle-like portion having a shape capable of piercing a living body, the needle-like body configured to hold the object inside the needle-like portion,
The material of the needle-shaped body includes a water-soluble material and a material that is sparingly soluble in water.
The needle-like portion includes a water-soluble polymer, which is the water-soluble material, and has an accommodation hole for partitioning a region configured to accommodate the object inside the needle-like portion,
The needle-shaped body is a water-insoluble portion surrounding a region in which the object is arranged in the accommodation hole, and is configured to deform in the living body so as to expose the object. having a department,
The containing device according to claim 1, wherein the water-insoluble portion includes a material that is sparingly soluble in the water.
3. The containment device of claim 2, wherein the non-aqueous portion is configured to melt in-vivo due to in-vivo temperature.
The housing device according to claim 2 or 3, wherein the non-water-soluble portion has a film-like shape that covers the inner surface of the housing hole.
The accommodation hole is open to the proximal end of the needle-like portion,
The housing device according to any one of claims 2 to 4, further comprising a sealing portion configured to be able to close the opening of the housing hole.
The containment device includes a base portion that supports a proximal end portion of the needle-like portion,
The substrate portion has a first surface and a second surface opposite to the first surface,
The needle-like portion extends from the first surface,
The accommodation hole opens to the second surface,
The storage device according to any one of claims 2 to 5, wherein the non-water-soluble portion extends continuously from the inner side surface of the storage hole to the second surface.
The storage device according to any one of claims 2 to 6, wherein the water-insoluble portion contains at least one of fat and higher alcohol.
5. The containment device of claim 4, wherein the area configured to contain the object contains a fluid comprising an aqueous material together with the object.
the needle-shaped portion includes the water-soluble material and the oily material that is a material that is poorly soluble in water;
The water-soluble material comprises a water-soluble polymer,
The storage device according to claim 1, wherein the oily material includes at least one of vegetable oil, animal oil, mineral oil, and oil synthesized using these as raw materials.
The containing device according to claim 9, wherein the ratio of the oily material in the needle-like portion is 60% by mass or less.
The containing device according to claim 9, wherein the needle-like portion has a water-soluble portion containing the water-soluble material and an oily portion containing the oily material.
The containing device according to claim 11, wherein the oily portion is located on the surface layer of the needle-like portion.