WO2020065753A1 - Drug administration body, drug administration system, and drug administration method - Google Patents

Drug administration body, drug administration system, and drug administration method Download PDF

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Publication number
WO2020065753A1
WO2020065753A1 PCT/JP2018/035630 JP2018035630W WO2020065753A1 WO 2020065753 A1 WO2020065753 A1 WO 2020065753A1 JP 2018035630 W JP2018035630 W JP 2018035630W WO 2020065753 A1 WO2020065753 A1 WO 2020065753A1
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Prior art keywords
drug administration
drug
derivative
porous body
precursor
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PCT/JP2018/035630
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French (fr)
Japanese (ja)
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秀雄 伊藤
小川　哲朗
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オリンパス株式会社
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Priority to PCT/JP2018/035630 priority Critical patent/WO2020065753A1/en
Publication of WO2020065753A1 publication Critical patent/WO2020065753A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form

Definitions

  • the present invention relates to a drug administration body, a drug administration system, and a drug administration method.
  • Patent Literature 1 describes a ceramic porous body having a sustained drug release property.
  • This ceramic porous body is a spherical porous body having many fine pores, and can be impregnated with a drug or the like through the small pores. By filling the porous ceramic body impregnated with the drug into the bone defect portion, the drug can be gradually released and bone regeneration can be promoted.
  • Patent Document 1 describes that a porous ceramic body can be used for a drug for oral administration.
  • the ceramic porous body can release the drug slowly, it flows through the gastrointestinal tract, so it is difficult for the drug to act at a specific location in the gastrointestinal tract.
  • an object of the present invention is to provide a drug administration body, a drug administration system, and a drug administration method capable of staying at a desired place in the body to release a drug slowly.
  • the first aspect of the present invention has a plurality of small pores, a porous body in which a drug is retained, and a precursor that exhibits adhesiveness by contacting a derivative, and at least a part of the outer surface of the porous body. And a precursor layer disposed on the substrate.
  • a second aspect of the present invention provides a drug having a plurality of small pores, a porous body in which a drug is held, a precursor that exhibits adhesiveness by contacting the derivative, and a derivative solution containing the derivative. It is an administration system.
  • a third aspect of the present invention has a plurality of small pores, a porous body in which a drug is retained, and a precursor that exhibits adhesiveness by contacting a derivative, and at least a part of the outer surface of the porous body.
  • Precursor with a precursor layer disposed in the body is placed at the indwelling position in the body, the derivative is supplied to the disposed drug-administered body, and the precursor and the derivative are brought into contact with each other, and the precursor exhibiting adhesiveness Is a drug administration method in which the drug administration body is placed at the placement position.
  • FIG. 1 is a perspective view schematically showing a drug administration body 1 of the present embodiment.
  • the drug administration body 1 includes a porous body 10 that holds a drug to be administered, and a precursor layer 20 that covers the surface of the porous body 10.
  • the porous body 10 has an outer shape such as a polyhedron, a sphere, a column, and a cone, and has a large number of small holes 10a on the surface and inside.
  • bioceramic refers to a medical material used for diagnosis and treatment that is used by reacting with a living body. Examples of bioceramics include bioglass, hydroxyapatite, carbonate apatite, fluorapatite, calcium hydrogen phosphate, tricalcium phosphate, dicalcium phosphate, tetracalcium phosphate, octacalcium phosphate, calcium phosphate glass, gypsum, etc.
  • the bioceramic may be used alone or as a composite of a plurality of types of bioceramics.
  • the porous body 10 can be formed of a material other than bioceramic. For example, collagen sponge, silica gel, calcium carbonate and the like can be exemplified.
  • the outer shape and the specific shape of the outer surface of the porous body 1 can be appropriately determined in consideration of the usage mode and the like.
  • the porous body 10 carries the drug 11 to be administered.
  • the drug 11 is not particularly limited as long as it can enter the inside of the small hole 10a formed in the porous body 10, and can be appropriately selected based on a target disease or the like.
  • it may be a therapeutic drug such as an antitumor drug or a supplementary drug such as a nutritional supplement.
  • the method for supporting the drug 11 on the porous body 10 is not particularly limited.
  • the drug 11 can be supported on the porous body 10 by adjusting the drug 11 to an aqueous solution, dispersion, emulsion, or the like, and immersing the porous body 10 in these liquids.
  • the drug When the drug is impregnated under pressure, the drug can be retained in a deeper portion inside the porous body, and the total dose can be increased or the release time can be lengthened.
  • the precursor layer 20 is formed of a material that exhibits viscosity when it comes into contact with a derivative described later.
  • the precursor layer 20 of the present embodiment is formed of alginic acid and covers the entire outer surface of the porous body 10.
  • the derivative in the present embodiment is a calcium ion. Alginic acid gels upon contact with calcium ions and exhibits viscosity.
  • the flow at the time of using the drug administration body of the present embodiment configured as described above will be described.
  • a description will be given using a case where the drug administration body 1 carrying the antitumor drug as the drug 11 is placed in a tumor formed on the stomach wall.
  • the following description includes the drug administration method according to the present embodiment.
  • the user inserts the endoscope through the patient's mouth and introduces the distal end of the endoscope to the vicinity of the tumor in the stomach.
  • the user observes the tumor with an endoscope and determines the placement position of the drug administration object 1.
  • the user mounts the drug administration body 1 on the tip of the catheter. Subsequently, the catheter is passed through the channel of the endoscope, and the distal end of the catheter is protruded from the endoscope.
  • the user operates the endoscope 51 and the catheter 52 to cause the distal end of the catheter 52 to approach the tumor Tm as shown in FIG.
  • the user releases the drug administration body 1 from the catheter 52.
  • the released drug administration body 1 is placed on the tumor Tm or in the indwelling position near the tumor Tm as shown in FIG. 3 (step A).
  • the method of releasing the drug administration object 1 from the catheter 52 is not particularly limited. For example, a method of pushing out with a stylet inserted from the proximal end side of the catheter 52, a method of pushing out by feeding a fluid from the proximal end side of the catheter 52, and the like can be exemplified.
  • a derivative is supplied to the drug administration body 1 via an endoscope (step B).
  • a syringe (not shown) is connected to the catheter 52 after the drug administration body 1 is released, and the liquid L containing the derivative is sprayed from the catheter 52 to the drug administration body 1 as shown in FIG.
  • the liquid containing the derivative may be supplied from a water supply channel (not shown) of the endoscope 51.
  • the placed drug administration body 1 maintains close contact with the tumor Tm due to the viscosity of alginic acid, which is the gelled precursor layer 20. Since alginic acid has a network structure, water and the like contained in digestive juices and food and beverages pass through alginic acid and reach the porous body 10 and the inside thereof. As a result, the drug 11 held in the porous body 10 is gradually dissolved and released from the porous body 10. The released drug 11 reaches the tumor Tm through a network of alginic acid located between the porous body 10 and the tumor Tm, and exerts a drug effect.
  • the porous body 10 holding the drug is securely adhered to the target tissue at the indwelling position by the precursor layer 20 which has exhibited viscosity by contact with the derivative.
  • the drug 11 can be kept at the indwelling position without being swallowed by food or drink, digestive juices, or the like, and can continue to act on the target site such as the tumor Tm.
  • the porous body 10 can freely set the size and density (porosity) of the small holes 10a by appropriately setting the particle diameter of the material, the firing conditions, and the like. Therefore, the drug release time, concentration, and the like can be optimized according to the target tissue, disease, and the like, and the effect of the drug can be enhanced.
  • the precursor layer 20 does not exhibit viscosity unless it comes into contact with the derivative, there is no problem that the precursor layer 20 is clogged in the loaded catheter 52 and cannot be released. Therefore, delivery by the catheter can be performed smoothly, and after release, it can be surely kept at the indwelling position. Further, since administration via the catheter 52 can be performed, the drug administration body 1 can be delivered to the indwelling position by a continuous operation after determining the optimal indwelling position by observing the target site with the endoscope 51.
  • the precursor layer may cover only a part of the outer surface of the porous body. Also in this case, by contacting the gelled precursor layer with the tissue, the drug administration target can be adhered to the target tissue.
  • the drug administration body may be grasped with forceps or the like, and the surface in contact with the tissue may be temporarily separated from the tissue.
  • the derivative does not easily come into contact with the precursor layer between the porous body and the tissue, but by spraying the liquid containing the derivative in the above-described state, the outer surface of the drug administration body is dispersed. The liquid containing the derivative can be sprayed evenly.
  • FIG. 6 shows the configuration of the drug administration system according to the present embodiment.
  • the drug administration system 101 includes a plurality of porous bodies 110, a precursor solution 120, and a derivative solution 130.
  • the porous body 110 is formed of the same material as the porous body 10 of the first embodiment.
  • the structure is the same as that of the porous body 10, and has a large number of small holes 10a (not shown), and the drug 11 (not shown) is held in a similar manner. Since it is assumed that a plurality of porous bodies 110 are to be placed at the target site, the dimensions are smaller than the porous bodies 10 of the first embodiment.
  • the porous body 110 of the present embodiment is spherical, the shape can be appropriately set.
  • an aqueous solution, dispersion, emulsion, or the like of a substance serving as a material of the precursor layer 20 can be used as the precursor solution 120.
  • the derivative contained in the derivative solution 130 is selected according to the components of the precursor solution 120.
  • an appropriate structure such as an aqueous solution, a dispersion, or an emulsion can be selected according to the physical properties of the derivative.
  • the liquid L described in the first embodiment is also included in the derivative solution 130.
  • the drug administration system 101 of the present embodiment is suitable for a case where the area of a lesion or the like of a drug administration target is large.
  • FIG. 7 shows the tumor Tm2 to be administered with the drug.
  • Tm2 has a larger area in plan view than the tumor Tm of the first embodiment. Therefore, when using the drug administration body 1 of the first embodiment, it is difficult to determine where to place the drug administration body 1 to optimize the medicinal effect.
  • the user packs a necessary amount of the porous body 110 into the distal end portion of the catheter 52 in consideration of the size of the tumor Tm2 and the like. Subsequently, the catheter 52 is introduced near the tumor Tm2 in the same procedure as in the first embodiment, and the porous body 110 is pushed out from the tip of the catheter. As shown in FIG. 8, the user spreads a plurality of porous bodies 110 on the tumor Tm2 to cover the tumor Tm2.
  • the user connects a syringe or the like to the catheter 52, and sprays the precursor solution 120 onto the porous body 110 from the tip of the catheter 52. Further, the syringe or the like connected to the catheter 52 is replaced, and the derivative solution 130 is sprayed onto the porous body 110 and the precursor solution 120 from the tip of the catheter 52. The precursor contained in the precursor solution 120 contacts the derivative contained in the derivative solution 130 and gels. As a result, as shown in FIG. 9, the plurality of porous bodies 110 are favorably retained on the tumor Tm2 by the action of the gelled precursor solution 120A, and release the drug.
  • the porous body 110 holding the drug can be securely adhered to the indwelling position, and the drug can continue to act on the target site.
  • the number and arrangement of the porous bodies 110 can be flexibly adapted to administration target tissues having various shapes and sizes. Furthermore, since the precursor is prepared separately from the porous body 110 as the precursor solution 120, the arrangement range of the porous body and the arrangement range of the precursor can be set independently and optimally. Therefore, it is easy to optimize the detention state.
  • the precursor need not be a solution, and may be, for example, a film.
  • FIG. 10 schematically shows the drug administration body 201 of the present embodiment.
  • the drug administration body 201 includes the porous body 10 holding a drug, an adhesive layer 220 disposed around the porous body 10, and a coating 230 covering the adhesive layer 220.
  • the adhesive layer 220 has adhesiveness to a tissue.
  • the material of the adhesive layer 220 include a material obtained by gelling the above-described precursor, a bioadhesive, and the like.
  • the coating 230 covers the adhesive layer 220 to prevent the adhesive layer 220 from sticking to another object before being placed. Since the coating 230 is dissolved and removed as described below, it can be selected from various substances that can be dissolved by a predetermined method in consideration of biocompatibility and the like. Specific examples include an MPC polymer into which a phospholipid polar group has been introduced, and polyvinyl alcohol.
  • the flow at the time of using the drug administration body 201 is substantially the same as in the first embodiment.
  • the drug administration body 201 is mounted on a catheter, and the drug administration body 201 is arranged on a target tissue via an endoscope.
  • the dissolving agent is sprayed on the drug administration body 201 after disposing the drug administration body 201, the coating layer 230 is melted and the covered adhesive layer 220 is exposed.
  • the exposed adhesive layer 220 exhibits adhesiveness to the tissue, and the porous body 10 suitably adheres to the target tissue.
  • the method of dissolving the coating 230 can be set as appropriate. Typically, this is performed by spraying a substance that dissolves the coating 230.
  • the coating 230 is made of an MPC polymer, the coating 230 can be dissolved by irradiation with ultraviolet light.
  • the porous body holding the drug can be reliably adhered to the indwelling position, and the drug can continue to act on the target site.
  • parameters such as the composition of the drug, the microstructure, composition, and surface characteristics of the drug administration body, the response characteristics to the surrounding environment such as the local residence time of the drug, the slow release diffusion rate, the ambient temperature, and the pH can be adjusted. It is also possible to control.
  • the adhesive layer 220 is previously bonded to the porous body including the drug and can be fixed by removing the coating 230, it can be fixed as it is at the place where the drug administration body 201 is arranged, There is an advantage that the accuracy of the placement position is high. Some examples of placements that can take advantage of this advantage are described below.
  • the tumor Tm3 shown in FIG. 11 has a region Tm3a requiring treatment and a region Tm3b existing around the region Tm3a and already undergoing repair. Since it is necessary to observe the surface of the region Tm3b with an endoscope or the like, it is not preferable that the drug administration body is fixed on the region Tm3b.
  • the drug administration body of the present embodiment can be suitably used.
  • a plurality of drug administration bodies 201A in which the size of the drug administration body 201 is reduced are prepared, and as shown in FIG. 12, the drug administration bodies 201A are arranged only on the region Tm3a.
  • the inflated balloon 300 is pressed against the drug administration object 201A to temporarily fix the drug administration object 201A.
  • each drug administration body 201A is placed on the region Tm3a by the adhesive layer 220 exposed by dissolving the coating 230. It is fixed precisely only to.
  • the treatment for the region Tm3a and the observation of the region Tm3b can be preferably compatible.
  • FIG. 15 shows an example of the endoscope 310 and the balloon catheter 320.
  • the endoscope 310 includes an observation unit 311 having an objective optical system, an imaging mechanism, and the like, and an illumination unit 312 having a light guide, an LED, and the like at its distal end.
  • the balloon catheter 320 provided with the balloon 300 protrudes from a channel 313 provided in the endoscope 310.
  • the dissolving agent may be sprayed from the second channel 314 for air / water supply or may be sprayed from the channel 313. When the balloon catheter 320 has a water supply lumen, the dissolving agent may be sprayed from the water supply lumen of the balloon catheter 320.
  • the drug administration body 201A from which the coating 230 has been removed is unlikely to adhere to the balloon 300.
  • the dissolving agent from entering between the balloon 300 and the drug administration object 201A.
  • the dissolution of the coating 230 in contact with the balloon 300 can be suppressed, and the drug administration target 201A can be first adhered to the tissue.
  • the drug administration body 201A having a small size can be suitably placed in a bag-shaped lesion such as a diverticulum that occurs in the digestive tract.
  • a bag-shaped lesion such as a diverticulum that occurs in the digestive tract.
  • the use of an appropriate number of the drug administration bodies 201A allows the diverticulum to be located in the affected area L regardless of the size of the internal space of the bag-shaped lesion L as shown in FIG.
  • the plurality of drug administration bodies 201A are formed in a spherical shape or a substantially spherical shape, a gap always occurs between the plurality of drug administration bodies 201A filled in the affected part L.
  • the drug-administered body 201A is fixed in the affected area L and maintains a state of evenly contacting the inner surface of the affected area L. Therefore, the drug administration body 201A enables long-term administration of the drug to the affected area L.
  • the above-described administration to the bag-shaped lesion can be performed in substantially the same manner by using the drug administration system of the second embodiment.
  • the combination of the precursor and the derivative in the present invention is not limited to the above-mentioned alginic acid.
  • Other examples of the combination of the precursor and the derivative include pectin and calcium, chitosan and calcium, and the like.
  • -Chemical bonding may be involved in the bonding between the adhesive layer and the tissue.
  • the binding strength between the adhesive layer and the indwelling tissue may be improved by chemically modifying alginic acid so as to be able to bind to phospholipids on the cell surface constituting the tissue.
  • the mucus covering the tissue may be removed or coagulated to make the adhesive layer easily adhere to the tissue.
  • a protease having an effect of removing mucus may be contained in the coating of the third embodiment.
  • Pronase can be exemplified as a proteolytic enzyme.
  • Pronase can exert a sufficient effect in an environment of pH 7 to 10, and such an environment can be realized using, for example, sodium hydrogen carbonate (baking soda) and water.
  • control of coagulation proteins, coagulation enzymes, heat energy by an argon laser or an energy device, pH value of buffer solution, isoelectric point, ionic strength and the like can be used.
  • tissue to which the present invention is applied is not limited to the digestive tract described above.
  • Other examples include blood vessels (veins), lymph vessels, bile ducts, respiratory organs (such as nasal cavity and trachea), urinary organs (such as bladder and urethra), and genital organs (such as vagina).
  • the present invention can be applied to almost any site accessible by a soft or hard scope. Local administration to which the present invention is applied can be applied to the surface of bone, cartilage, connective tissue, or the like, or to a defect or lesion.
  • -A plurality of types of drug administration bodies and porous bodies according to the present invention may have different drug holding amounts and precursor layer thicknesses.
  • the therapeutic effect can be enhanced by the user selecting the most suitable drug administration substance or porous body according to the indwelling site, disease state, and the like.
  • the present invention can be applied to local administration of various drugs.

Abstract

A drug administration body comprises: a porous body which has a plurality of small holes and has a drug carried thereon; and a precursor layer which contains a precursor capable of exhibiting adhesiveness upon the contact with a derivative and is arranged on at least a part of the outer surface of the porous body.

Description

薬物投与体、薬物投与システム、および薬物投与方法Drug administration body, drug administration system, and drug administration method
　本発明は、薬物投与体、薬物投与システム、および薬物投与方法に関する。  The present invention relates to a drug administration body, a drug administration system, and a drug administration method.
　薬物の投与に関しては、副作用を抑えつつ薬効を最大限に得る観点から種々の提案がされている。
　特許文献１には、薬物徐放性を有するセラミックス多孔体が記載されている。このセラミックス多孔体は微細な小孔を多数有する球形の多孔体であり、小孔から内部に薬剤等を含浸させることができる。薬剤を含浸させたセラミックス多孔体を骨欠損部分に充填することで、薬剤を徐放させ、骨再生を促進することができる。 Regarding drug administration, various proposals have been made from the viewpoint of maximizing drug efficacy while suppressing side effects.
Patent Literature 1 describes a ceramic porous body having a sustained drug release property. This ceramic porous body is a spherical porous body having many fine pores, and can be impregnated with a drug or the like through the small pores. By filling the porous ceramic body impregnated with the drug into the bone defect portion, the drug can be gradually released and bone regeneration can be promoted.
日本国特開２００３－１２３８３号公報Japanese Patent Application Laid-Open No. 2003-12383
　特許文献１には、セラミックス多孔体を経口投与薬に使用できると記載されている。しかし、セラミックス多孔体は薬剤を徐放できるものの、消化管内を流れるために、消化管内の特定の場所で薬剤を作用させることは困難である。 Patent Document 1 describes that a porous ceramic body can be used for a drug for oral administration. However, although the ceramic porous body can release the drug slowly, it flows through the gastrointestinal tract, so it is difficult for the drug to act at a specific location in the gastrointestinal tract.
　上記事情を踏まえ、本発明は、体内の所望の場所に留まらせて薬物を徐放できる薬物投与体、薬物投与システム、および薬物投与方法を提供することを目的とする。 を Based on the above circumstances, an object of the present invention is to provide a drug administration body, a drug administration system, and a drug administration method capable of staying at a desired place in the body to release a drug slowly.
　本発明の第一の態様は、複数の小孔を有し、薬物が保持された多孔体と、誘導体と接触することにより粘着性を発揮する前駆体を含み、多孔体の外面の少なくとも一部に配置された前駆体層とを備える薬物投与体である。 The first aspect of the present invention has a plurality of small pores, a porous body in which a drug is retained, and a precursor that exhibits adhesiveness by contacting a derivative, and at least a part of the outer surface of the porous body. And a precursor layer disposed on the substrate.
　本発明の第二の態様は、複数の小孔を有し、薬物が保持された多孔体と、誘導体と接触することにより粘着性を発揮する前駆体と、誘導体を含む誘導体溶液とを備える薬物投与システムである。 A second aspect of the present invention provides a drug having a plurality of small pores, a porous body in which a drug is held, a precursor that exhibits adhesiveness by contacting the derivative, and a derivative solution containing the derivative. It is an administration system.
　本発明の第三の態様は、複数の小孔を有し、薬物が保持された多孔体と、誘導体と接触することにより粘着性を発揮する前駆体を含み、多孔体の外面の少なくとも一部に配置された前駆体層とを備える薬物投与体を体内の留置位置に配置し、配置された薬物投与体に誘導体を供給して前駆体と誘導体とを接触させ、粘着性を発揮した前駆体により薬物投与体を留置位置に留置する薬物投与方法である。 A third aspect of the present invention has a plurality of small pores, a porous body in which a drug is retained, and a precursor that exhibits adhesiveness by contacting a derivative, and at least a part of the outer surface of the porous body. Precursor with a precursor layer disposed in the body is placed at the indwelling position in the body, the derivative is supplied to the disposed drug-administered body, and the precursor and the derivative are brought into contact with each other, and the precursor exhibiting adhesiveness Is a drug administration method in which the drug administration body is placed at the placement position.
　本発明によれば、体内の所望の場所に留まらせて薬物を徐放できる薬物投与体を提供できる。 According to the present invention, it is possible to provide a drug administration body that can stay at a desired place in the body and release a drug slowly.
本発明の第一実施形態に係る薬物投与体の模式図である。It is a schematic diagram of a drug administration object concerning a first embodiment of the present invention. 同薬物投与体の留置動作の一過程を示す図である。It is a figure which shows one process of the indwelling operation | movement of the same drug administration body. 同薬物投与体の留置動作の一過程を示す図である。It is a figure which shows one process of the indwelling operation | movement of the same drug administration body. 同薬物投与体の留置動作の一過程を示す図である。It is a figure which shows one process of the indwelling operation | movement of the same drug administration body. 同薬物投与体の留置動作の一過程を示す図である。It is a figure which shows one process of the indwelling operation | movement of the same drug administration body. 本発明の第二実施形態に係る薬物投与システムを示す図である。It is a figure showing the drug administration system concerning a second embodiment of the present invention. 投与対象組織の一例を示す図である。It is a figure which shows an example of a tissue for administration. 同薬物投与システムの留置動作の一過程を示す図である。It is a figure showing one process of an indwelling operation of the drug administration system. 同薬物投与システムの留置動作の一過程を示す図である。It is a figure showing one process of an indwelling operation of the drug administration system. 本発明の第三実施形態に係る薬物投与体の模式図である。It is a schematic diagram of a drug administration object concerning a third embodiment of the present invention. 変形例における同薬物投与体の対象病変を示す図である。It is a figure showing the target lesion of the same drug administration object in a modification. 同薬物投与体の留置動作の一過程を示す図である。It is a figure which shows one process of the indwelling operation | movement of the same drug administration body. 同薬物投与体の留置動作の一過程を示す図である。It is a figure which shows one process of the indwelling operation | movement of the same drug administration body. 同薬物投与体の留置動作の一過程を示す図である。It is a figure which shows one process of the indwelling operation | movement of the same drug administration body. 変形例の留置に用いる内視鏡およびバルーンカテーテルの一例を示す図である。It is a figure showing an example of an endoscope and a balloon catheter used for indwelling of a modification. 同薬物投与体を袋状病変に留置した状態を示す図である。It is a figure showing the state where the same drug administration object was left in a bag-like lesion.
　本発明の第一実施形態について、図１から図５を参照して説明する。
　図１は、本実施形態の薬物投与体１を模式的に示す斜視図である。薬物投与体１は、投与対象の薬物を保持する多孔体１０と、多孔体１０の表面を覆う前駆体層２０とを備えている。 A first embodiment of the present invention will be described with reference to FIGS.
FIG. 1 is a perspective view schematically showing a drug administration body 1 of the present embodiment. The drug administration body 1 includes a porous body 10 that holds a drug to be administered, and a precursor layer 20 that covers the surface of the porous body 10.
　多孔体１０は、多面体状、球状、柱状、錐体状等の外形を有し、表面および内部に多数の小孔１０ａを有する。
　多孔体１０を形成する材料としては、バイオセラミックが好適である。本明細書において、「バイオセラミック」とは、診断や治療に用いられる医療材料のうち、生体と反応させて用いられる材料を意味する。バイオセラミックとしては、バイオガラス、水酸アパタイト、炭酸アパタイト、フッ素アパタイト、リン酸水素カルシウム、リン酸三カルシウム、第二リン酸カルシウム、リン酸四カルシウム、リン酸八カルシウム、リン酸カルシウム系ガラス、石膏などを例示できる。バイオセラミックは、単体で使用されてもよいし、複数種類のバイオセラミックの複合体として使用されてもよい。
　多孔体１０は、バイオセラミック以外の材料でも形成できる。例えば、コラーゲンスポンジ、シリカゲル、炭酸カルシウムなどを例示できる。
　多孔体１の外形および外面の具体的形状は、使用態様等を考慮して適宜決定することができるが、少なくとも一部に平面を有する形状であると、留置が容易である。 The porous body 10 has an outer shape such as a polyhedron, a sphere, a column, and a cone, and has a large number of small holes 10a on the surface and inside.
As a material for forming the porous body 10, bioceramic is preferable. As used herein, “bioceramic” refers to a medical material used for diagnosis and treatment that is used by reacting with a living body. Examples of bioceramics include bioglass, hydroxyapatite, carbonate apatite, fluorapatite, calcium hydrogen phosphate, tricalcium phosphate, dicalcium phosphate, tetracalcium phosphate, octacalcium phosphate, calcium phosphate glass, gypsum, etc. it can. The bioceramic may be used alone or as a composite of a plurality of types of bioceramics.
The porous body 10 can be formed of a material other than bioceramic. For example, collagen sponge, silica gel, calcium carbonate and the like can be exemplified.
The outer shape and the specific shape of the outer surface of the porous body 1 can be appropriately determined in consideration of the usage mode and the like.
　多孔体１０には、投与対象の薬物１１が担持されている。薬物１１は、多孔体１０に形成された小孔１０ａの内部に進入できるものであれば特に制限はなく、対象疾患等に基づいて適宜選択できる。例えば、抗腫瘍薬等の治療的薬物であってもよいし、栄養剤等の補給的薬物であってもよい。薬物１１を多孔体１０に担持させる方法に特に制限はない。例えば、薬物１１を水溶液、分散液、エマルジョン等の状態に調整し、これら液体に多孔体１０を浸漬することにより、多孔体１０に薬物１１を担持させることができる。加圧下で薬物の含浸を行うと、多孔体内部のより深い部位に薬物を保持させることができ、総投与量を増加させたり、放出時間を長くしたりできる。 薬 物 The porous body 10 carries the drug 11 to be administered. The drug 11 is not particularly limited as long as it can enter the inside of the small hole 10a formed in the porous body 10, and can be appropriately selected based on a target disease or the like. For example, it may be a therapeutic drug such as an antitumor drug or a supplementary drug such as a nutritional supplement. The method for supporting the drug 11 on the porous body 10 is not particularly limited. For example, the drug 11 can be supported on the porous body 10 by adjusting the drug 11 to an aqueous solution, dispersion, emulsion, or the like, and immersing the porous body 10 in these liquids. When the drug is impregnated under pressure, the drug can be retained in a deeper portion inside the porous body, and the total dose can be increased or the release time can be lengthened.
　前駆体層２０は、後述する誘導体と接触することで粘性を発揮する材料で形成されている。本実施形態の前駆体層２０は、アルギン酸で形成され、多孔体１０の外面全体を覆っている。本実施形態における誘導体は、カルシウムイオンである。アルギン酸は、カルシウムイオンと接触することによりゲル化し、粘性を発揮する。 (4) The precursor layer 20 is formed of a material that exhibits viscosity when it comes into contact with a derivative described later. The precursor layer 20 of the present embodiment is formed of alginic acid and covers the entire outer surface of the porous body 10. The derivative in the present embodiment is a calcium ion. Alginic acid gels upon contact with calcium ions and exhibits viscosity.
　上記のように構成された本実施形態の薬物投与体の使用時の流れについて説明する。以下では、抗腫瘍薬を薬物１１として担持した薬物投与体１を、胃壁に形成された腫瘍に留置するケースを使って説明する。
　以下の説明は、本実施形態に係る薬物投与方法を含む。 The flow at the time of using the drug administration body of the present embodiment configured as described above will be described. In the following, a description will be given using a case where the drug administration body 1 carrying the antitumor drug as the drug 11 is placed in a tumor formed on the stomach wall.
The following description includes the drug administration method according to the present embodiment.
　留置前の準備として、使用者は、患者の口から内視鏡を挿入し、内視鏡の先端部を、胃内の腫瘍付近まで導入する。使用者は、内視鏡で腫瘍を観察し、薬物投与体１の留置位置を決定する。 As a preparation prior to placement, the user inserts the endoscope through the patient's mouth and introduces the distal end of the endoscope to the vicinity of the tumor in the stomach. The user observes the tumor with an endoscope and determines the placement position of the drug administration object 1.
　次に、使用者は、薬物投与体１をカテーテルの先端に装てんする。続いて、このカテーテルを内視鏡のチャンネルに通し、カテーテルの先端部を内視鏡から突出させる。 Next, the user mounts the drug administration body 1 on the tip of the catheter. Subsequently, the catheter is passed through the channel of the endoscope, and the distal end of the catheter is protruded from the endoscope.
　使用者は、内視鏡５１およびカテーテル５２を操作して、図２に示すように、カテーテル５２の先端部を腫瘍Ｔｍに接近させる。カテーテル５２の先端部が望んだ位置となったら、使用者は、カテーテル５２から薬物投与体１を放出する。放出された薬物投与体１は、図３に示すように、腫瘍Ｔｍ上あるいは腫瘍Ｔｍ付近の留置位置に置かれる（ステップＡ）。
　カテーテル５２から薬物投与体１を放出する方法は、特に制限されない。例えば、カテーテル５２の基端側から挿入したスタイレットで押し出す方法や、カテーテル５２の基端側から流体を送り込むことにより押し出す方法等を例示できる。 The user operates the endoscope 51 and the catheter 52 to cause the distal end of the catheter 52 to approach the tumor Tm as shown in FIG. When the distal end of the catheter 52 reaches a desired position, the user releases the drug administration body 1 from the catheter 52. The released drug administration body 1 is placed on the tumor Tm or in the indwelling position near the tumor Tm as shown in FIG. 3 (step A).
The method of releasing the drug administration object 1 from the catheter 52 is not particularly limited. For example, a method of pushing out with a stylet inserted from the proximal end side of the catheter 52, a method of pushing out by feeding a fluid from the proximal end side of the catheter 52, and the like can be exemplified.
　次に、薬物投与体１に内視鏡経由で誘導体を供給する（ステップＢ）。薬物投与体１を放出した後のカテーテル５２にシリンジ（不図示）を接続し、図４に示すように、カテーテル５２から誘導体を含む液体Ｌを薬物投与体１に散布する。誘導体と接触した前駆体層２０は、ゲル化して粘性を発揮し、図５に示すように薬物投与対象の腫瘍Ｔｍに対して確実に接着する（ステップＣ）。
　誘導体を含む液体は、内視鏡５１の送水チャンネル（不図示）から供給されてもよい。
　以上で、薬物投与体１の留置が完了する。 Next, a derivative is supplied to the drug administration body 1 via an endoscope (step B). A syringe (not shown) is connected to the catheter 52 after the drug administration body 1 is released, and the liquid L containing the derivative is sprayed from the catheter 52 to the drug administration body 1 as shown in FIG. The precursor layer 20 that has come into contact with the derivative gels and exhibits viscosity, and adheres reliably to the tumor Tm to be administered with the drug as shown in FIG. 5 (step C).
The liquid containing the derivative may be supplied from a water supply channel (not shown) of the endoscope 51.
Thus, the placement of the drug administration body 1 is completed.
　留置された薬物投与体１は、ゲル化した前駆体層２０であるアルギン酸の粘性により、腫瘍Ｔｍへの密着状態を維持する。アルギン酸は網目状構造を有するため、消化液や飲食物に含まれる水分等はアルギン酸を透過して多孔体１０およびその内部に到達する。その結果、多孔体１０に保持された薬物１１は、徐々に溶解して多孔体１０から放出される。放出された薬物１１は、多孔体１０と腫瘍Ｔｍとの間に位置するアルギン酸の網目を通って腫瘍Ｔｍに到達し、薬効を発揮する。 (4) The placed drug administration body 1 maintains close contact with the tumor Tm due to the viscosity of alginic acid, which is the gelled precursor layer 20. Since alginic acid has a network structure, water and the like contained in digestive juices and food and beverages pass through alginic acid and reach the porous body 10 and the inside thereof. As a result, the drug 11 held in the porous body 10 is gradually dissolved and released from the porous body 10. The released drug 11 reaches the tumor Tm through a network of alginic acid located between the porous body 10 and the tumor Tm, and exerts a drug effect.
　本実施形態の薬物投与体１によれば、薬物が保持された多孔体１０が、誘導体と接触して粘性を発揮した前駆体層２０により、留置した位置において対象組織に確実に粘着する。その結果、飲食物や消化液等によって流されずに留置位置にとどまり続け、薬物１１を腫瘍Ｔｍ等の標的部位に作用させ続けることができる。 According to the drug administration body 1 of the present embodiment, the porous body 10 holding the drug is securely adhered to the target tissue at the indwelling position by the precursor layer 20 which has exhibited viscosity by contact with the derivative. As a result, the drug 11 can be kept at the indwelling position without being swallowed by food or drink, digestive juices, or the like, and can continue to act on the target site such as the tumor Tm.
　多孔体１０は、材料の粒子径や焼成条件等を適宜設定することにより、小孔１０ａの寸法や密度（気孔率）を自在に設定することができる。したがって、薬物の放出時間や濃度等を、対象組織や疾患等に応じて最適化し、薬物の効果を高めることができる。 寸 法 The porous body 10 can freely set the size and density (porosity) of the small holes 10a by appropriately setting the particle diameter of the material, the firing conditions, and the like. Therefore, the drug release time, concentration, and the like can be optimized according to the target tissue, disease, and the like, and the effect of the drug can be enhanced.
　前駆体層２０は、誘導体と接触しない限り粘性を発揮しないため、装てんしたカテーテル５２内に詰まって放出できなくなる等の不具合は発生しない。したがって、カテーテルによるデリバリーを円滑に行うことができ、放出後は留置位置に確実にとどまらせることができる。
　さらに、カテーテル５２経由の投与ができるため、内視鏡５１で対象部位を観察して最適な留置位置を決定した後、連続した操作で留置位置に薬物投与体１を送達することができる。 Since the precursor layer 20 does not exhibit viscosity unless it comes into contact with the derivative, there is no problem that the precursor layer 20 is clogged in the loaded catheter 52 and cannot be released. Therefore, delivery by the catheter can be performed smoothly, and after release, it can be surely kept at the indwelling position.
Further, since administration via the catheter 52 can be performed, the drug administration body 1 can be delivered to the indwelling position by a continuous operation after determining the optimal indwelling position by observing the target site with the endoscope 51.
　本実施形態については、種々の変更が行われてよい。以下にいくつか変更を例示するが、これらはすべてではなく、それ以外の変更も可能である。これらの変更が２以上適宜組み合わされてもよい。 種 々 Various changes may be made to the present embodiment. Some modifications are illustrated below, but not all, and other modifications are also possible. Two or more of these changes may be appropriately combined.
・多孔体の外面の一部のみを前駆体層が覆っていてもよい。この場合も、ゲル化した前駆体層を組織と接触させることにより、薬物投与体を対象組織に粘着させることができる。
・誘導体を含む液体を散布する際に、薬物投与体を鉗子等で把持し、組織と接触している面をいったん組織から離間させてもよい。組織に置かれた薬物投与体において、多孔体と組織との間にある前駆体層には誘導体が接触しにくいが、上述の状態で誘導体を含む液体を散布することにより、薬物投与体の外面にまんべんなく誘導体を含む液体を散布することができる。 -The precursor layer may cover only a part of the outer surface of the porous body. Also in this case, by contacting the gelled precursor layer with the tissue, the drug administration target can be adhered to the target tissue.
When spraying the liquid containing the derivative, the drug administration body may be grasped with forceps or the like, and the surface in contact with the tissue may be temporarily separated from the tissue. In the drug administration body placed on the tissue, the derivative does not easily come into contact with the precursor layer between the porous body and the tissue, but by spraying the liquid containing the derivative in the above-described state, the outer surface of the drug administration body is dispersed. The liquid containing the derivative can be sprayed evenly.
　本発明の第二実施形態について、図６から図９を参照して説明する。
　以降の説明において、すでに説明したものと共通する構成については、同一の符号を付して重複する説明を省略する。 A second embodiment of the present invention will be described with reference to FIGS.
In the following description, the same components as those already described are denoted by the same reference numerals, and redundant description will be omitted.
　本実施形態に係る薬物投与システムの構成を図６に示す。
　薬物投与システム１０１は、複数の多孔体１１０と、前駆体溶液１２０と、誘導体溶液１３０とを備えている。 FIG. 6 shows the configuration of the drug administration system according to the present embodiment.
The drug administration system 101 includes a plurality of porous bodies 110, a precursor solution 120, and a derivative solution 130.
　多孔体１１０は、第一実施形態の多孔体１０と同様の材質で形成されている。構造も多孔体１０と同様で多数の小孔１０ａ（不図示）を有し、同様の態様で薬物１１（不図示）が保持されている。多孔体１１０は、複数個を目的部位に留置することが想定されているため、第一実施形態の多孔体１０よりも寸法が小さい。本実施形態の多孔体１１０は球状であるが、形状は適宜設定できる。 The porous body 110 is formed of the same material as the porous body 10 of the first embodiment. The structure is the same as that of the porous body 10, and has a large number of small holes 10a (not shown), and the drug 11 (not shown) is held in a similar manner. Since it is assumed that a plurality of porous bodies 110 are to be placed at the target site, the dimensions are smaller than the porous bodies 10 of the first embodiment. Although the porous body 110 of the present embodiment is spherical, the shape can be appropriately set.
　前駆体溶液１２０としては、前駆体層２０の材料となる物質の水溶液、分散液、エマルジョンなどを使える。
　誘導体溶液１３０に含まれる誘導体は、前駆体溶液１２０の成分に応じて選択される。誘導体溶液１３０についても、誘導体の物性等に応じて、水溶液、分散液、エマルジョン等の適宜の構成を選択できる。第一実施形態で説明した液体Ｌも、誘導体溶液１３０に含まれる。 As the precursor solution 120, an aqueous solution, dispersion, emulsion, or the like of a substance serving as a material of the precursor layer 20 can be used.
The derivative contained in the derivative solution 130 is selected according to the components of the precursor solution 120. Regarding the derivative solution 130, an appropriate structure such as an aqueous solution, a dispersion, or an emulsion can be selected according to the physical properties of the derivative. The liquid L described in the first embodiment is also included in the derivative solution 130.
　薬物投与システム１０１の使用時の流れについて説明する。
　本実施形態の薬物投与システム１０１は、薬物投与対象の病変等の面積が大きい場合等に適している。 The flow at the time of using the drug administration system 101 will be described.
The drug administration system 101 of the present embodiment is suitable for a case where the area of a lesion or the like of a drug administration target is large.
　図７に、薬物投与対象の腫瘍Ｔｍ２を示す。Ｔｍ２は、第一実施形態の腫瘍Ｔｍよりも平面視における面積が大きい。したがって、第一実施形態の薬物投与体１を使う場合、どこに留置すると薬効を最適化できるかの見極めが難しい。 FIG. 7 shows the tumor Tm2 to be administered with the drug. Tm2 has a larger area in plan view than the tumor Tm of the first embodiment. Therefore, when using the drug administration body 1 of the first embodiment, it is difficult to determine where to place the drug administration body 1 to optimize the medicinal effect.
　使用者は、腫瘍Ｔｍ２の大きさ等を考慮して、必要量の多孔体１１０をカテーテル５２の先端部に詰める。続けて、第一実施形態と同様の手順でカテーテル５２を腫瘍Ｔｍ２の付近に導入し、カテーテルの先端から多孔体１１０を押し出す。使用者は、図８に示すように、腫瘍Ｔｍ２上に複数の多孔体１１０を敷き詰めて腫瘍Ｔｍ２を覆う。 The user packs a necessary amount of the porous body 110 into the distal end portion of the catheter 52 in consideration of the size of the tumor Tm2 and the like. Subsequently, the catheter 52 is introduced near the tumor Tm2 in the same procedure as in the first embodiment, and the porous body 110 is pushed out from the tip of the catheter. As shown in FIG. 8, the user spreads a plurality of porous bodies 110 on the tumor Tm2 to cover the tumor Tm2.
　続いて使用者は、カテーテル５２にシリンジ等を接続し、カテーテル５２の先端から前駆体溶液１２０を多孔体１１０上に散布する。さらに、カテーテル５２に接続したシリンジ等を交換して、カテーテル５２の先端から誘導体溶液１３０を多孔体１１０および前駆体溶液１２０上に散布する。前駆体溶液１２０に含まれる前駆体は、誘導体溶液１３０に含まれる誘導体と接触してゲル化する。その結果、複数の多孔体１１０は、図９に示すように、ゲル化した前駆体溶液１２０Ａの働きで腫瘍Ｔｍ２上に良好にとどまり、薬物を放出する。 Next, the user connects a syringe or the like to the catheter 52, and sprays the precursor solution 120 onto the porous body 110 from the tip of the catheter 52. Further, the syringe or the like connected to the catheter 52 is replaced, and the derivative solution 130 is sprayed onto the porous body 110 and the precursor solution 120 from the tip of the catheter 52. The precursor contained in the precursor solution 120 contacts the derivative contained in the derivative solution 130 and gels. As a result, as shown in FIG. 9, the plurality of porous bodies 110 are favorably retained on the tumor Tm2 by the action of the gelled precursor solution 120A, and release the drug.
　本実施形態の薬物投与システム１０１においても、第一実施形態と同様に、薬物を保持した多孔体１１０を確実に留置位置に粘着させ、薬物を標的部位に作用させ続けることができる。 薬 物 Also in the drug administration system 101 of the present embodiment, similarly to the first embodiment, the porous body 110 holding the drug can be securely adhered to the indwelling position, and the drug can continue to act on the target site.
　また、寸法の小さな複数の多孔体１１０を備えるため、様々な形状や大きさの投与対象組織に対し、多孔体１１０の数や配置を適宜設定することで柔軟に対応することができる。
　さらに、前駆体が、前駆体溶液１２０として多孔体１１０と別に準備されているため、多孔体の配置範囲と、前駆体の配置範囲とをそれぞれ独立して最適な状態に設定できる。したがって、留置状態を最適化しやすい。 In addition, since a plurality of porous bodies 110 having small dimensions are provided, the number and arrangement of the porous bodies 110 can be flexibly adapted to administration target tissues having various shapes and sizes.
Furthermore, since the precursor is prepared separately from the porous body 110 as the precursor solution 120, the arrangement range of the porous body and the arrangement range of the precursor can be set independently and optimally. Therefore, it is easy to optimize the detention state.
　本実施形態において、前駆体は溶液でなくてもよく、例えばフィルム状であってもよい。 In the present embodiment, the precursor need not be a solution, and may be, for example, a film.
　本発明の第三実施形態について、図１０から図１６を参照して説明する。
　図１０に、本実施形態の薬物投与体２０１を模式的に示す。薬物投与体２０１は、薬物が保持された多孔体１０と、多孔体１０の周囲に配置された粘着層２２０と、粘着層２２０を覆う被膜２３０とを備えている。 A third embodiment of the present invention will be described with reference to FIGS.
FIG. 10 schematically shows the drug administration body 201 of the present embodiment. The drug administration body 201 includes the porous body 10 holding a drug, an adhesive layer 220 disposed around the porous body 10, and a coating 230 covering the adhesive layer 220.
　粘着層２２０は、組織に対する粘着性を有する。粘着層２２０の材料としては、上述した前駆体がゲル化したものや、生体接着剤等を例示できる。
　被膜２３０は、粘着層２２０を覆うことにより、粘着層２２０が留置前に他の物体に粘着することを抑止する。被膜２３０は、後述するように溶解除去されるため、所定の方法で溶解可能な各種物質から、生体適合性等を考慮して選択できる。具体的には、リン脂質極性基が導入されたＭＰＣポリマーや、ポリビニルアルコールなどを例示できる。 The adhesive layer 220 has adhesiveness to a tissue. Examples of the material of the adhesive layer 220 include a material obtained by gelling the above-described precursor, a bioadhesive, and the like.
The coating 230 covers the adhesive layer 220 to prevent the adhesive layer 220 from sticking to another object before being placed. Since the coating 230 is dissolved and removed as described below, it can be selected from various substances that can be dissolved by a predetermined method in consideration of biocompatibility and the like. Specific examples include an MPC polymer into which a phospholipid polar group has been introduced, and polyvinyl alcohol.
　薬物投与体２０１の使用時の流れは、概ね第一実施形態と同様であり、カテーテルに薬物投与体２０１を装てんし、内視鏡経由で対象組織に薬物投与体２０１を配置する。
　薬物投与体２０１の配置後、薬物投与体２０１に溶解剤を散布すると、被膜２３０が溶けて覆われていた粘着層２２０が露出する。露出した粘着層２２０は、組織への粘着性を発揮し、多孔体１０が好適に対象組織に粘着する。
　被膜２３０の溶解方法は適宜設定できる。典型的には、被膜２３０を溶解する物質を散布することにより行うが、被膜２３０がＭＰＣポリマーからなる場合は、紫外線を照射することによっても溶解させることができる。 The flow at the time of using the drug administration body 201 is substantially the same as in the first embodiment. The drug administration body 201 is mounted on a catheter, and the drug administration body 201 is arranged on a target tissue via an endoscope.
When the dissolving agent is sprayed on the drug administration body 201 after disposing the drug administration body 201, the coating layer 230 is melted and the covered adhesive layer 220 is exposed. The exposed adhesive layer 220 exhibits adhesiveness to the tissue, and the porous body 10 suitably adheres to the target tissue.
The method of dissolving the coating 230 can be set as appropriate. Typically, this is performed by spraying a substance that dissolves the coating 230. However, when the coating 230 is made of an MPC polymer, the coating 230 can be dissolved by irradiation with ultraviolet light.
　本実施形態においても、既に説明した各実施形態と同様に、薬物を保持した多孔体を確実に留置位置に粘着させ、薬物を標的部位に作用させ続けることができる。
　さらに、薬物の組成、薬物投与体の微細構造、組成、表面特性等のパラメーターを調整することにより、薬物の局所滞留時間、徐放拡散速度、周囲の温度、ｐＨなど周囲環境に対する応答特性などを制御することも可能となる。 Also in the present embodiment, as in each of the embodiments described above, the porous body holding the drug can be reliably adhered to the indwelling position, and the drug can continue to act on the target site.
In addition, by adjusting parameters such as the composition of the drug, the microstructure, composition, and surface characteristics of the drug administration body, the response characteristics to the surrounding environment such as the local residence time of the drug, the slow release diffusion rate, the ambient temperature, and the pH can be adjusted. It is also possible to control.
　本実施形態の薬物投与体２０１は、薬物を備える多孔体に粘着層２２０が予め結合されており、被膜２３０を除去することで固定できるため、薬物投与体２０１を配置した場所でそのまま固定でき、留置位置の精度が高いという利点がある。
　この利点が生かせる留置例のいくつかについて、以下に説明する。 In the drug administration body 201 of the present embodiment, since the adhesive layer 220 is previously bonded to the porous body including the drug and can be fixed by removing the coating 230, it can be fixed as it is at the place where the drug administration body 201 is arranged, There is an advantage that the accuracy of the placement position is high.
Some examples of placements that can take advantage of this advantage are described below.
　図１１に示す腫瘍Ｔｍ３は、治療を要する領域Ｔｍ３ａと、領域Ｔｍ３ａの周囲に存在し、既に修復過程にある領域Ｔｍ３ｂとを有する。領域Ｔｍ３ｂは、内視鏡等を用いて表面を経過観察する必要があるため、領域Ｔｍ３ｂ上に薬物投与体が固定されることは好ましくない。 腫 瘍 The tumor Tm3 shown in FIG. 11 has a region Tm3a requiring treatment and a region Tm3b existing around the region Tm3a and already undergoing repair. Since it is necessary to observe the surface of the region Tm3b with an endoscope or the like, it is not preferable that the drug administration body is fixed on the region Tm3b.
　このような領域Ｔｍ３に対して治療を行う場合、本実施形態の薬物投与体を好適に使用できる。
　まず、薬物投与体２０１の寸法を小さくした薬物投与体２０１Ａを複数準備し、図１２に示すように、薬物投与体２０１Ａを領域Ｔｍ３ａ上にのみ配置する。次に、図１３に示すように、膨張したバルーン３００を薬物投与体２０１Ａに押し当てて、薬物投与体２０１Ａを一時的に固定する。この状態で、薬物投与体２０１Ａに溶解剤を散布して被膜２３０を溶解すると、図１４に示すように、各薬物投与体２０１Ａは、被膜２３０の溶解により露出した粘着層２２０により、領域Ｔｍ３ａ上のみに精度よく固定される。その結果、領域Ｔｍ３ａに対する治療と、領域Ｔｍ３ｂの観察とを好適に両立できる。 When performing a treatment for such an area Tm3, the drug administration body of the present embodiment can be suitably used.
First, a plurality of drug administration bodies 201A in which the size of the drug administration body 201 is reduced are prepared, and as shown in FIG. 12, the drug administration bodies 201A are arranged only on the region Tm3a. Next, as shown in FIG. 13, the inflated balloon 300 is pressed against the drug administration object 201A to temporarily fix the drug administration object 201A. In this state, when the dissolving agent is sprayed on the drug administration body 201A to dissolve the coating 230, as shown in FIG. 14, each drug administration body 201A is placed on the region Tm3a by the adhesive layer 220 exposed by dissolving the coating 230. It is fixed precisely only to. As a result, the treatment for the region Tm3a and the observation of the region Tm3b can be preferably compatible.
　上述した手技は、例えば、内視鏡と、内視鏡に挿入して使用するバルーンカテーテルとを使って行うことができる。図１５に、内視鏡３１０とバルーンカテーテル３２０の一例を示す。内視鏡３１０は、対物光学系や撮像機構等を有する観察部３１１と、ライトガイドやＬＥＤ等を有する照明部３１２とを先端部に備えている。バルーン３００を備えたバルーンカテーテル３２０は、内視鏡３１０に設けられたチャンネル３１３から突出している。溶解剤は、送気送水用の第二チャンネル３１４から散布してもよいし、チャンネル３１３から散布してもよい。バルーンカテーテル３２０が送水ルーメンを備える場合は、バルーンカテーテル３２０の送水ルーメンから溶解剤を散布してもよい。 手 The above-described procedure can be performed using, for example, an endoscope and a balloon catheter used by being inserted into the endoscope. FIG. 15 shows an example of the endoscope 310 and the balloon catheter 320. The endoscope 310 includes an observation unit 311 having an objective optical system, an imaging mechanism, and the like, and an illumination unit 312 having a light guide, an LED, and the like at its distal end. The balloon catheter 320 provided with the balloon 300 protrudes from a channel 313 provided in the endoscope 310. The dissolving agent may be sprayed from the second channel 314 for air / water supply or may be sprayed from the channel 313. When the balloon catheter 320 has a water supply lumen, the dissolving agent may be sprayed from the water supply lumen of the balloon catheter 320.
　この手技において、バルーン３００の材質が撥水性の良いシリコン系材料であると、被膜２３０が除去された薬物投与体２０１Ａがバルーン３００に付着しにくい。また、適度な力でバルーン３００を薬物投与体２０１Ａに押し当てることにより、溶解剤がバルーン３００と薬物投与体２０１Ａとの間に進入することを抑制できる。その結果、バルーン３００と接触した被膜２３０が溶解することを抑制し、薬物投与体２０１Ａをまず組織に粘着させることができる。
　上述した手段を単独または組み合わせることにより、薬物投与体２０１Ａがバルーン３００に付着することを防げる。 In this procedure, if the material of the balloon 300 is a silicon-based material having good water repellency, the drug administration body 201A from which the coating 230 has been removed is unlikely to adhere to the balloon 300. Further, by pressing the balloon 300 against the drug administration object 201A with an appropriate force, it is possible to prevent the dissolving agent from entering between the balloon 300 and the drug administration object 201A. As a result, the dissolution of the coating 230 in contact with the balloon 300 can be suppressed, and the drug administration target 201A can be first adhered to the tissue.
By using the above-mentioned means alone or in combination, it is possible to prevent the drug administration body 201A from adhering to the balloon 300.
　寸法の小さい薬物投与体２０１Ａは、消化管に生じる憩室等の袋状の病変にも好適に留置できる。憩室はその内部空間の大きさも様々に異なるが、薬物投与体２０１Ａを適切な数量用いることにより、図１６に示すように、袋状の病変Ｌの内部空間の大きさによらず、患部Ｌ内を薬物投与体２０１Ａで十分に埋めることができる。
　複数の薬物投与体２０１Ａを球形あるいは略球形に形成すると、患部Ｌ内に充填された複数の薬物投与体２０１Ａ間には、必ず隙間が生じる。したがって、患部Ｌ内に溶解剤を注入すると、溶解剤がこの隙間に流入して被膜２３０を溶解させる。その結果、薬物投与体２０１Ａは、患部Ｌ内に固定されて患部Ｌの内面とまんべんなく接触した状態を保持する。したがって、薬物投与体２０１Ａにより、患部Ｌに対する薬物の長期投与が可能である。
　上述した袋状病変への投与は、第二実施形態の薬物投与システムを使っても概ね同様に行える。 The drug administration body 201A having a small size can be suitably placed in a bag-shaped lesion such as a diverticulum that occurs in the digestive tract. Although the size of the internal space of the diverticulum varies, the use of an appropriate number of the drug administration bodies 201A allows the diverticulum to be located in the affected area L regardless of the size of the internal space of the bag-shaped lesion L as shown in FIG. Can be sufficiently filled with the drug administration body 201A.
When the plurality of drug administration bodies 201A are formed in a spherical shape or a substantially spherical shape, a gap always occurs between the plurality of drug administration bodies 201A filled in the affected part L. Therefore, when a dissolving agent is injected into the affected part L, the dissolving agent flows into the gap to dissolve the coating 230. As a result, the drug-administered body 201A is fixed in the affected area L and maintains a state of evenly contacting the inner surface of the affected area L. Therefore, the drug administration body 201A enables long-term administration of the drug to the affected area L.
The above-described administration to the bag-shaped lesion can be performed in substantially the same manner by using the drug administration system of the second embodiment.
　以上、本発明の各実施形態について説明したが、本発明の技術範囲は上記実施形態に限定されるものではなく、本発明の趣旨を逸脱しない範囲において実施形態を超えて構成要素の組み合わせを変えたり、各構成要素に種々の変更を加えたり、削除したりすることが可能である。
　以下にいくつか変更を例示するが、これらはすべてではなく、それ以外の変更も可能である。これらの変更は２以上適宜組み合わされてもよく、第一実施形態で説明した変更と組み合わされてもよい。 As described above, each embodiment of the present invention has been described, but the technical scope of the present invention is not limited to the above embodiment, and the combination of components may be changed beyond the embodiment without departing from the spirit of the present invention. It is also possible to make various changes to or delete each component.
Some modifications are illustrated below, but not all, and other modifications are also possible. These changes may be appropriately combined with two or more, or may be combined with the change described in the first embodiment.
・本発明における前駆体と誘導体の組み合わせは、上述したアルギン酸に限られない。前駆体と誘導体の組み合わせの他の例として、ペクチンとカルシウム、キトサンとカルシウム等を例示できる。
・粘着層と組織との結合に、化学結合が関与してもよい。例えば、アルギン酸に化学修飾を施し、組織を構成する細胞表面のリン脂質と結合可能に構成することにより、粘着層と留置組織との結合力を向上させてもよい。 -The combination of the precursor and the derivative in the present invention is not limited to the above-mentioned alginic acid. Other examples of the combination of the precursor and the derivative include pectin and calcium, chitosan and calcium, and the like.
-Chemical bonding may be involved in the bonding between the adhesive layer and the tissue. For example, the binding strength between the adhesive layer and the indwelling tissue may be improved by chemically modifying alginic acid so as to be able to bind to phospholipids on the cell surface constituting the tissue.
・薬物投与体や多孔体を組織上に配置する前に、組織を覆う粘液を除去したり凝固したりして粘着層を組織に粘着しやすくしてもよい。胃においては、粘液を除去する効果のある蛋白分解酵素が第三実施形態の被膜に含有されてもよい。蛋白分解酵素としてはプロナーゼが例示できる。プロナーゼは、ｐＨ７～１０の環境下で十分な効果を発揮することができ、そのような環境は、例えば炭酸水素ナトリウム（重曹）と水とを用いて実現できる。粘膜や表面蛋白の凝固には、凝固蛋白、凝固酵素、アルゴンレーザーやエネルギーデバイスによる熱エネルギー、緩衝液のｐＨ値、等電点、イオン強度などの制御を利用できる。 -Before arranging the drug administration body or the porous body on the tissue, the mucus covering the tissue may be removed or coagulated to make the adhesive layer easily adhere to the tissue. In the stomach, a protease having an effect of removing mucus may be contained in the coating of the third embodiment. Pronase can be exemplified as a proteolytic enzyme. Pronase can exert a sufficient effect in an environment of pH 7 to 10, and such an environment can be realized using, for example, sodium hydrogen carbonate (baking soda) and water. For coagulation of mucous membranes and surface proteins, control of coagulation proteins, coagulation enzymes, heat energy by an argon laser or an energy device, pH value of buffer solution, isoelectric point, ionic strength and the like can be used.
・本発明の適用組織は、上述した消化管に限られない。他の例として、血管（静脈）、リンパ管、胆管、呼吸器（鼻腔、気管など）、泌尿器（膀胱、尿道など）、生殖器（膣など）を例示できる。本発明は、軟性あるいは硬性のスコープでアクセス可能な部位であれば概ねすべてに適用することができる。骨、軟骨、結合組織などの表面や欠損部、病変部にも、本発明を適用した局所投与が可能である。 -The tissue to which the present invention is applied is not limited to the digestive tract described above. Other examples include blood vessels (veins), lymph vessels, bile ducts, respiratory organs (such as nasal cavity and trachea), urinary organs (such as bladder and urethra), and genital organs (such as vagina). The present invention can be applied to almost any site accessible by a soft or hard scope. Local administration to which the present invention is applied can be applied to the surface of bone, cartilage, connective tissue, or the like, or to a defect or lesion.
・本発明に係る薬物投与体や多孔体は、薬物保持量や前駆体層の膜厚が異なる複数種類存在してもよい。この場合、使用者が留置部位や病態等に応じて最適な薬物投与体または多孔体を選択することにより、治療効果を高めることができる。 -A plurality of types of drug administration bodies and porous bodies according to the present invention may have different drug holding amounts and precursor layer thicknesses. In this case, the therapeutic effect can be enhanced by the user selecting the most suitable drug administration substance or porous body according to the indwelling site, disease state, and the like.
　本発明は、各種薬物の局所投与に適用することができる。 The present invention can be applied to local administration of various drugs.
　１、２０１、２０１Ａ　薬物投与体
　１０　多孔体
　１０ａ　小孔
　１１　薬物
　２０　前駆体層
　１０１　薬物投与システム
　１２０　前駆体溶液（前駆体）
　１３０　誘導体溶液
　２２０　粘着層
　２３０　被膜 1, 201, 201A Drug administration body 10 Porous body 10a Small pore 11 Drug 20 Precursor layer 101 Drug administration system 120 Precursor solution (precursor)
130 Derivative solution 220 Adhesive layer 230 Coating

Claims (6)

  1. 　複数の小孔を有し、薬物が保持された多孔体と、
    　誘導体と接触することにより粘着性を発揮する前駆体を含み、前記多孔体の外面の少なくとも一部に配置された前駆体層と、
    　を備える薬物投与体。     A porous body having a plurality of small holes and holding a drug,
    Including a precursor exhibiting tackiness by contacting the derivative, a precursor layer disposed on at least a part of the outer surface of the porous body,
    A drug administration body comprising:
  2. 　複数の小孔を有し、薬物が保持された多孔体と、
    　誘導体と接触することにより粘着性を発揮する前駆体と、
    　前記誘導体を含む誘導体溶液と、
    　を備える薬物投与システム。     A porous body having a plurality of small holes and holding a drug,
    A precursor that exhibits tackiness by contacting the derivative,
    A derivative solution containing the derivative,
    A drug administration system comprising:
  3. 　複数の小孔を有し、薬物が保持された多孔体と、
    　前記多孔体の外面の少なくとも一部に配置された粘着層と、
    　前記粘着層を覆うように配置され、溶解可能な被覆と、
    　を備える薬物投与体。     A porous body having a plurality of small holes and holding a drug,
    An adhesive layer disposed on at least a part of the outer surface of the porous body,
    A dissolvable coating arranged to cover the adhesive layer,
    A drug administration body comprising:
  4. 　前記多孔体の主材料がリン酸カルシウムである、
    　請求項１に記載の薬物投与体。     The main material of the porous body is calcium phosphate,
    The drug administration body according to claim 1.
  5. 　前記前駆体がアルギン酸であり、前記誘導体がカルシウムである、
    　請求項１に記載の薬物投与体。     Wherein the precursor is alginic acid and the derivative is calcium,
    The drug administration body according to claim 1.
  6. 　複数の小孔を有し、薬物が保持された多孔体と、誘導体と接触することにより粘着性を発揮する前駆体を含み、前記多孔体の外面の少なくとも一部に配置された前駆体層とを備える薬物投与体を体内の留置部位に配置し、
    　配置された前記薬物投与体に前記誘導体を供給して前記前駆体と前記誘導体とを接触させ、
    　粘着性を発揮した前記前駆体により前記薬物投与体を前記留置部位に留置する、
    　薬物投与方法。     Having a plurality of small holes, a porous body in which the drug is held, including a precursor exhibiting adhesiveness by contacting the derivative, a precursor layer disposed on at least a part of the outer surface of the porous body, Place the drug administration body with the indwelling site in the body,
    Supplying the derivative to the arranged drug administration body to contact the precursor and the derivative,
    The drug administration body is placed at the placement site by the precursor exhibiting adhesiveness,
    Drug administration method.
PCT/JP2018/035630 2018-09-26 2018-09-26 Drug administration body, drug administration system, and drug administration method WO2020065753A1 (en)

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