Indwelling medications and indwelling medication delivery devices

Abstract

The present invention provides a novel indwelling drug that enables stable administration of a predetermined amount of drug to a target site within the body over a predetermined period of time. [Solution] The solid drug 10 consists of a base material 30 made of biodegradable material containing a drug 32, and comprises a membrane holding portion 20 that is held in a penetrating state against the biological tissue membrane 14 of the administration site, and a tip reaching portion 22 that is located on the tip side of the membrane holding portion 20 and is exposed to the administration site 12, wherein the base material 30 contains the drug 32 in the tip reaching portion 22, and the drug 32 is released slowly to the administration site 12.

Description

Technical Field

[0001] The present invention relates to an indwelling agent for realizing the administration of a drug little by little over a predetermined period to a specific part of a living body, and related technologies thereof.

Background Art

[0002] Drugs are used for the purpose of treating, alleviating, preventing, etc. diseases in animals including humans. A drug is a substance that causes physiological and psychological changes when ingested by the human body or the like, and there are various types. And various drugs are generally adjusted so as to efficiently obtain the intended efficacy while suppressing side effects by administering a predetermined amount to a target target site (organ or tissue) at a predetermined time.

[0003] However, depending on the type of drug and the target site for administration, etc., it may be difficult to accurately administer a predetermined amount at a predetermined time.

[0004] For example, in the treatment of ear diseases such as sudden deafness, it has been proposed to administer drugs such as corticosteroids and dexamethasone orally or to the cochlea which is one of the inner ear organs. However, it is considered difficult for the drug to reach the cochlea by an easy drug administration method such as oral administration, transdermal administration, or sublingual administration.

[0005] Therefore, Patent Document 1 (Japanese Patent No. 5551685) describes injection administration (intratympanic injection) of directly administering a drug to the cochlea by puncturing through the round window exposed in the tympanic cavity located behind the eardrum, and absorption administration of the drug by applying a drug solution to the membrane surface of the round window, etc.

[0006] However, the inventors' investigations revealed that the former method, injection administration, carries the risk of side effects such as hearing abnormalities due to damage to cochlear hair cells, as it disrupts the cochlear fluid, which has sensory functions that govern hearing and balance. Furthermore, the amount of drug that can be injected at one time is limited, making it difficult to administer the drug multiple times over a predetermined period. In addition, the latter method, transmembrane absorption administration, not only is it difficult to obtain sufficient and accurate drug delivery efficiency into the cochlea, but it also carries the same risk of eardrum damage as injection administration, making it difficult to administer the drug multiple times over a predetermined period. [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] Patent No. 5551685 [Overview of the Initiative] [Problems that the invention aims to solve]

[0008] The problem to be solved by this invention is to provide a novel drug and drug administration device that can efficiently and stably administer a predetermined amount of a drug to a target site in the body over a predetermined period of time, while reducing the burden on practitioners such as doctors and patients. [Means for solving the problem]

[0009] The present invention, which was made to solve these problems, is described below in several aspects. The components used in each of the aspects described below can be used in any combination as much as possible. Furthermore, it should be understood that the aspects or technical features of the present invention are not limited to those described below, but are recognized based on the inventive concept described in the entire specification and drawings, or as can be grasped by those skilled in the art from such descriptions.

[0010] A first aspect of the present invention relates to an indwelling drug, and is as follows: It consists of a solid drug containing a drug in a base material made of biodegradable material. A membrane-holding portion is held in a penetrating state with respect to the biological tissue membrane that constitutes the outer boundary layer of the site where the drug is intended to be administered, A tip portion located on the tip side of the membrane holding portion and exposed to the administration target site. It is equipped with, An indwelling drug characterized in that the drug is contained in the base material at the tip portion, and the drug is released gradually to the administration site.

[0011] In this embodiment, the implanted drug is retained in the body with the membrane-holding portion attached to the biological tissue membrane and the tip exposed to the administration site. Over a predetermined period until the membrane-holding portion decomposes in the body, the drug is gradually released from the tip into the administration site.

[0012] Therefore, it becomes possible to precisely set the duration and amount of drug administration to the target site by release. In particular, it can easily accommodate the requirement to administer very small amounts of drug over a predetermined long period. Furthermore, because the drug is held in a position by the biological tissue membrane, it remains precisely at the administration site and is administered, preventing the drug from dispersing to other sites compared to injection administration, and preventing drug migration due to detachment from the body compared to transdermal patch administration. Moreover, since there is generally no need for further drug placement procedures until the drug held by the biological tissue membrane decomposes, the burden on patients and doctors during the prescribed medication period is reduced, and the risks associated with procedures can be avoided.

[0013] A second aspect of the present invention is an indwelling drug according to the first aspect, The aforementioned tip portion has a tapered shape at its tip, The film-holding portion has an outer surface shape with a smaller axial inclination than the tip portion.

[0014] In this embodiment of the indwelling drug, the tapered shape reduces resistance when inserting the abutment into the biological tissue membrane. Therefore, the procedure of inserting such an indwelling drug into the biological tissue membrane from the tip side becomes easier.

[0015] A third aspect of the present invention is an indwelling drug according to the first or second aspect, The proximal end of the membrane-holding portion is provided with a proximal protrusion that extends outward from the biological tissue membrane.

[0016] In this embodiment of the indwelling drug, the presence of a basal protrusion reduces the risk of detachment due to, for example, slipping out from the biological tissue membrane towards the target site, and makes it easier to confirm the indwelling status of the drug by observing the protrusion of the basal protrusion with an endoscope or the like.

[0017] A fourth aspect of the present invention is an indwelling drug according to any of the first to third aspects described above, A locking portion is provided on the outer surface that engages with the aforementioned biological tissue membrane.

[0018] In this embodiment of the implanted drug, the locking action of the locking portion on the biological tissue membrane stabilizes the retention state by the biological tissue membrane, thereby preventing, for example, the detachment of the implanted drug from the biological tissue membrane or changes in the amount of protrusion from the biological tissue membrane toward the target site.

[0019] A fifth aspect of the present invention is an indwelling drug according to the fourth aspect, The locking portion is provided in the form of a projection that protrudes from the outer surface.

[0020] In this embodiment of the implanted drug, it becomes possible to more effectively obtain the effect of holding and positioning the implanted drug by locking, for example, by hooking the locking portion onto the biological tissue membrane.

[0021] A sixth aspect of the present invention is an indwelling drug according to the fifth aspect, The locking portion, which has a protruding shape, is designed to be deformable.

[0022] In the indwelling agent of this aspect, for example, when delivering to the target site, the protruding height of the locking portion is reduced to make it compact and facilitate delivery by preventing snagging during the process, while in the indwelling state, the protruding height of the locking portion can be increased to improve the holding force on the biological tissue membrane.

[0023] The seventh aspect of the present invention is the indwelling agent according to the sixth aspect, the locking portion is elastically deformable, the protruding height can be deformed to be smaller by an external pressing force, and the protruding height can be restored when such an external pressing force is removed.

[0024] In the indwelling agent of this aspect, since the protruding height of the locking portion can be changed by the action and release of an external pressing force, it becomes possible to easily control the protruding height of the locking portion. In addition, by making the locking portion elastically deformable, it is possible to reduce the risk of damage such as the locking portion being snagged during the handling of the indwelling agent.

[0025] The eighth aspect of the present invention is the indwelling agent according to any one of the first to seventh aspects, in the tip reaching portion, the drug content in the base material is made larger than that on the base end side where the membrane holding portion is provided.

[0026] In the indwelling agent of this aspect, in the tip reaching portion exposed to the administration target site such as treatment by drug administration, while ensuring the amount of the drug to be gradually released, by suppressing the amount of the drug gradually released to the biological tissue membrane and the internal tissue outside the membrane, it is also possible to reduce risks such as side effects and improve the administration efficiency to the target site.

[0027] The ninth aspect of the present invention is the indwelling agent according to any one of the first to eighth aspects, the biological tissue membrane is a perfect circular window membrane, and the membrane holding portion is held in a penetrating state to the perfect circular window membrane, The drug is released gradually from the tip of the device to the cochlea, which is the target site for administration.

[0028] According to this embodiment of the implanted medication, it becomes possible to efficiently administer medication to the cochlea for a predetermined period, which was previously difficult, while avoiding excessive burden on the patient and the practitioner.

[0029] A tenth aspect of the present invention relates to an indwelling drug delivery device, and is as follows: An indwelling drug administration device that delivers an indwelling drug according to any of the first to ninth of the above-mentioned indwelling drugs to the biological tissue membrane of the administration target site and holds it in a penetrating state within the biological tissue membrane, A delivery tube having a lumen for drug delivery that penetrates in the longitudinal direction and is inserted into the body from outside, A protruding rod is inserted into the drug delivery lumen of the delivery tube, and the indwelling drug is pushed out from the distal end opening of the drug delivery lumen. A protrusion control means controls the amount of movement of the protruding rod within the drug delivery lumen, thereby controlling the protrusion of the indwelling drug from the distal end opening of the drug delivery lumen. An indwelling drug delivery device characterized by containing the following.

[0030] The indwelling drug delivery device of this embodiment not only enables the precise delivery of solid indwelling drugs to target sites on biological tissue membranes within the body, but also includes a protrusion control means for controlling the protrusion of the indwelling drug from the delivery tube, thereby facilitating the process of administering the indwelling drug by penetrating it into the biological tissue membrane. Specifically, for example, it becomes easier to precisely adjust the insertion speed and insertion depth when inserting the indwelling drug into the biological tissue membrane.

[0031] An eleventh aspect of the present invention is an indwelling drug delivery device according to the tenth aspect, The protrusion control means is a continuous feeding mechanism that continuously controls the amount of movement of the protruding rod toward the distal end within the drug dispensing lumen.

[0032] According to the indwelling drug delivery device of this embodiment, the amount of drug inserted into the biological tissue membrane, and consequently the speed and amount of protrusion of the tip of the drug into the target site for administration, can be precisely set by continuously adjusting them. The continuous feeding mechanism in this embodiment can be realized by a continuous movement mechanism, and for example, a continuous feeding mechanism such as the screw feeding mechanism described later in the embodiment may be employed.

[0033] A twelfth aspect of the present invention is an indwelling drug delivery device according to the tenth aspect, The protrusion control means is a stepped feeding mechanism that controls the amount of movement of the protruding rod toward the distal end within the drug dispensing lumen in a stepwise manner.

[0034] The indwelling drug delivery device of this embodiment makes it possible to precisely set, in stages, the amount of drug inserted into the biological tissue membrane, and consequently, the speed and amount of protrusion of the tip of the drug into the target site for administration. The stepwise feeding mechanism in this embodiment can be realized by an intermittent movement mechanism, and for example, a stepwise feeding mechanism such as the lead-feeding mechanism of a mechanical pencil, as described later in the embodiment, can be employed.

[0035] A thirteenth aspect of the present invention is an indwelling drug delivery device according to any of the tenth to twelfth aspects, The protrusion control means includes a moving end defining means that defines the moving end of the protruding rod in the direction of protrusion toward the distal end side of the drug dispensing lumen.

[0036] According to the indwelling drug delivery device of this embodiment, the indwelling drug is prevented from being inserted excessively inward into the biological tissue membrane, thereby preventing the risk of the indwelling drug falling out, for example, through the biological tissue membrane into the interior of an organ, and ensuring a more stable retention force of the indwelling drug by the biological tissue membrane.

[0037] A fourteenth aspect of the present invention is an indwelling drug delivery device according to any of the tenth to thirteenth aspects, The distal end of the delivery tube is provided with a contact surface that is in contact with the surface of the biological tissue membrane in an overlapping state.

[0038] According to the indwelling drug delivery device of this embodiment, by abutting the contact surface of the delivery tube against the surface of the biological tissue membrane, it becomes possible to accurately position the distal end of the delivery tube relative to the surface of the biological tissue membrane in the axial direction of the tube. As a result, the amount of protrusion of the indwelling drug, which is delivered in a penetrating state into the biological tissue membrane by protruding from the distal end opening of the delivery tube toward the biological tissue membrane, and consequently the puncture depth into the biological tissue membrane, can be set with greater precision.

[0039] A fifteenth aspect of the present invention is an indwelling drug delivery device according to any of the tenth to fourteenth aspects, The distal end of the delivery tube is provided with a sharp tip that penetrates the biological tissue membrane.

[0040] According to the drug delivery device of this embodiment, when delivering the drug to the target position on the biological tissue membrane through the drug delivery lumen, the sharp tip penetrates the biological tissue membrane, thereby positioning the distal end of the territorial tube through which the drug delivery lumen opens relative to the biological tissue membrane, making it possible to accurately set the delivery position of the drug. It is also possible to use a sharp tip that penetrates the biological tissue membrane, thereby creating a pre-puncture hole in the biological tissue membrane for drug delivery and improving the workability of drug delivery by allowing the drug to penetrate the biological tissue membrane.

[0041] A sixteenth aspect of the present invention relates to an indwelling drug, and is as follows: An indwelling drug delivered to the biological tissue membrane of the administration site by an indwelling drug delivery device according to any of the above embodiments 10 to 15, The locking portion that engages with the biological tissue membrane is formed in the shape of a projection that protrudes from the outer surface, The locking portion is made deformable so that the protruding height of the locking portion when it is held in the biological tissue membrane is greater than the protruding height of the locking portion when it is inserted into the drug delivery lumen of the delivery tube.

[0042] In the indwelling drug according to this embodiment, when administered using the indwelling drug administration device described above, the drug can be delivered through a small-diameter drug delivery lumen, and when placed in the administration site, the locking portion, whose protruding height has been greatly restored, can advantageously obtain retention force from the biological tissue membrane. [Effects of the Invention]

[0043] According to the present invention, it becomes easy to efficiently and stably administer a predetermined amount of a drug to a target site in the body over a predetermined period of time, while avoiding excessive burden on the patient or practitioner. [Brief explanation of the drawing]

[0044] [Figure 1] Overall diagram showing an indwelling drug as one embodiment of the present invention. [Figure 2] Figure 1 illustrates the different aspects of the indwelling drug, including the tip, base, and shaft, as shown in (a), (b), and (c). Overall schematic diagram of the indwelling drug. [Figure 3] Figure 1 illustrates one aspect of the locking mechanism used in the indwelling drug, and shows an overall schematic diagram of the indwelling drug. [Figure 4] Overall diagram showing one embodiment of an indwelling drug delivery device. [Figure 5]Enlarged longitudinal section illustrating an example of the tip structure of the indwelling drug delivery device shown in Figure 4. [Figure 6] Figure 4 shows an enlarged longitudinal section illustrating an example of a different structure of the tip of the indwelling drug delivery device. [Figure 7] Schematic diagram of key components showing an example of a protrusion control means used in the indwelling drug delivery device shown in Figure 4. [Figure 8] Schematic diagram of key components showing an example of another ejection control means used in the indwelling drug delivery device shown in Figure 4. [Figure 9] An enlarged perspective view illustrating the tip surface of the delivery tube in the indwelling drug delivery device shown in Figure 4. [Figure 10] Figure 4 shows an enlarged perspective view illustrating another example of the tip surface of the delivery tube used in the indwelling drug delivery device. [Figure 11] Figure 4 shows an enlarged perspective view illustrating yet another example of the tip surface of the delivery tube used in the indwelling drug delivery device. [Modes for carrying out the invention]

[0045] Embodiments of the present invention will be described below with reference to the drawings.

[0046] First, Figure 1 shows a schematic diagram of the indwelling drug 10, which is the first embodiment of the present invention, as a lateral view of its external appearance.

[0047] In this embodiment, the indwelling drug 10 is shown as an example in which the drug is directly administered into the cochlea 12 through a circular window-shaped biological tissue membrane 14, which serves as the external boundary layer of the cochlea 12, with the cochlea 12 as the target site for drug administration. However, the administration site of the drug targeted by the present invention is not limited, and indwelling drugs can be administered to various tissues and organs present in the body of animals, including humans, with the administration site being one of these.

[0048] The indwelling drug 10 in this embodiment is a solid drug that can be handled as a drug with a consistent external shape until administration. In this embodiment, the drug has an overall elongated, bullet-shaped form and has an axial portion 16 that extends linearly along the central axis with a substantially constant circular cross-sectional shape from the base end to the tip end. Furthermore, a tapered tip portion 18 is integrally formed at the tip of the axial portion 16, which is cone-shaped and gradually tapers, protruding along the central axis.

[0049] The specific dimensions of these axial portion 16 and tip portion 18 are not limited, but the overall length L of the implanted drug 10, including the axial portion 16 and tip portion 18, is at least greater than the thickness Lb of the biological tissue membrane 14. Preferably, the length of the axial portion 16 is greater than the thickness of the biological tissue membrane 14.

[0050] This allows the proximal end of the implanted drug 10 to be held in a penetrating state across substantially the entire thickness of the biological tissue membrane 14, while the tip end of the implanted drug 10 is exposed to the internal region of the cochlea 12. In this embodiment, the intermediate portion in the longitudinal direction of the axial portion 16 constitutes a membrane holding portion 20 that is held by the biological tissue membrane 14.

[0051] Furthermore, the protrusion length from the biological tissue membrane 14 at the tip of the implanted drug 10 should be set appropriately considering the efficacy of the drug and the dosage, but it is preferable that at least the tip portion 18 is exposed to the internal region of the cochlea 12 over substantially its entire length. In this embodiment, the tip portion 21 of the shaft portion 16 and the tip portion 18 constitute a tip reaching portion 22 that protrudes from the biological tissue membrane 14 and is exposed to the inside of the cochlea 12.

[0052] In other words, in this embodiment, the axial portion 16 of the implanted drug 10 penetrates the biological tissue membrane 14 from front to back in the middle portion in the longitudinal direction, and the proximal projection 24 located on the proximal end side of the axial portion 16 protrudes outward from the biological tissue membrane 14 to the cochlea 12 for a predetermined length: Lc, while the tip side of the axial portion 16 protrudes inward from the biological tissue membrane 14 to the inside of the cochlea 12 for a predetermined length.

[0053] In this configuration, the entire tip portion 22 of the implanted drug 10 can be more reliably and stably exposed within the internal region of the cochlea 12. Furthermore, since the axial portion 16 of the implanted drug 10 protrudes from both the front and back surfaces of the biological tissue membrane 14, even if the insertion position relative to the biological tissue membrane 14 shifts or changes slightly in the longitudinal direction, the holding force of the biological tissue membrane 14 on the axial portion 16 of the implanted drug 10 can be stably exerted, more effectively preventing detachment.

[0054] Furthermore, in the drug-administered state, the axial inclination angle α of the outer surface of the membrane-holding portion 20 that penetrates the biological tissue membrane 14 is smaller than the axial inclination angle β of the tip portion 18 (α < β), and in this embodiment, α < β is maintained throughout the entire length of the shaft-like portion 16. Note that, as shown by β in Figure 1, the axial inclination angle is defined as a positive (+) inclination angle in the tapering direction with respect to the central axis and a negative (-) inclination angle in the widening direction. Therefore, even if, for example, the outer surface of the membrane-holding portion 20 is a reverse tapered surface with a widening shape, the requirement of α < β is satisfied.

[0055] In this context, the indwelling drug 10 is formed from a base material 30 made entirely of biodegradable material, and is a solid (not limited to hard, but including soft) sustained-release drug containing (including supporting) the drug 32 to be administered by this base material 30.

[0056] The biodegradable base material 30 can be any material that decomposes over time and is absorbed or excreted by the human body, effectively disappearing. For example, it may be a metallic material or a polymer material. Preferably, a biodegradable polymer that is decomposed in vivo by enzymes, acids, water, etc., can be used. Specifically, natural polymers such as gelatin, collagen, albumin, globulin, starch, cyclodextrin, and polysaccharides, as well as synthetic polymers such as polypeptides, poly-α-amino acids, and polylactic acid, can be used.

[0057] On the other hand, the drug 32 contained in such a base material 30 is not limited to any particular drug and can be selected depending on the therapeutic purpose. Furthermore, in Figure 1, the drug 32 is conceptually shown as a relatively large black circle to facilitate understanding, and this illustration does not exclusively represent the drug 32's containment structure in the base material 30. In other words, the method of containing the drug 32 in the base material 30 is not limited; it is sufficient for the drug 32 to be chemically bonded to the base material 30 or physically mixed and dispersed so that it is gradually released from the base material 30 over a predetermined period of time.

[0058] For example, in addition to a homogeneous structure in which the drug is dispersed and compounded substantially uniformly within the polymer matrix constituting the base material, it may also be a heterogeneous structure in which the drug layer and polymer layer are separated, or in which multiple membranes or parts with different types and concentrations of drug are combined. Specifically, the implanted drug 10 of the homogeneous structure can be formed by curing a mixture of monomers or prepolymers and the drug through reactions such as polymerization, polycondensation, and curing, or by mixing a polymer and the drug and applying energy such as radiation, light, pressure, or heat to the mixture.

[0059] In this structured manner, the implanted drug 10 is held in place by penetrating the biological tissue membrane 14 as described above, and as the base material 30 biodegrades and disappears, the drug 32 is gradually released into the cochlea 12, which is the target site in the body.

[0060] In particular, in this embodiment, when the implanted drug 10 is administered, the drug content (density) in the base material 30 of the tip portion 18 located inside the cochlea 12 is greater than that of the basal side, such as the basal side projection 24. Preferably, as shown modeled in Figure 1, the drug content in the base material 30 is greater than that of the membrane holding portion 20 and the basal side projection 24 in substantially the entire tip portion 22 that is exposed inside the cochlea 12, which is the target site for drug administration. This allows the drug 32 to be efficiently administered inside the cochlea 12, which is the target site for drug administration, thereby improving the bioavailability of the drug and reducing the impact on the body outside the target site, such as the biological tissue membrane 14.

[0061] Furthermore, it is possible to schedule the sustained release of the drug 10 over time. For example, it is possible to keep the drug release rate constant or change it over time by partially adjusting the dispersion state or concentration of the drug 32 in the base material 30. For example, by creating a non-uniform structure in which the concentration or density of the drug 32 in the base material 30 gradually changes from the surface to the interior of the base material 30, the amount of drug 32 released over time can be controlled. It is also possible to employ a layered drug structure consisting of multiple layers with different types and concentrations of drug 32, and different materials and thicknesses of the base material 30, thereby enabling more sophisticated scheduling of the drug 32 release over time.

[0062] A layered drug structure can be formed, for example, by sequentially layering layers of the base material 30 and / or drug 32 in different states using coatings or the like, or by forming a drug-containing region in an appropriate location inside the base material 30 and encapsulating the drug 32 in the form of a fine powder or liquid into the drug-containing region. Furthermore, as illustrated in Figure 1, a form in which the drug 32 is contained in a specific part of the base material 30 can also be formed, for example, by molding a base material 30 containing the drug 32 and a base material 30 without the drug 32, either separately or sequentially, as in two-color molding, and then integrating them.

[0063] Furthermore, the implanted drug 10 may contain various additives in addition to the base material 30 and the drug 10 for purposes such as adjusting the drug release rate and other properties, improving moldability, and adjusting hardness. Specifically, hydrophilic or hydrophobic modifiers (monomers), hardening agents, blast-forming agents, and fillers may be used as appropriate.

[0064] With this type of implanted drug 10, the drug 32 is retained by the biological tissue membrane 14 for a period until it is substantially eliminated by biodegradation, and is then directly and slowly released into the cochlea 12 from the tip 22. Therefore, the drug 32 can be administered accurately and stably to the target organ in the body (cochlea 12), and it is also possible to administer it in small amounts over a relatively long period of time.

[0065] In particular, even in cases where only very small amounts of drug can be administered over a long period of time to avoid excessive impact on nerves such as hearing, which would place a significant burden on the patient, such as in the cochlea 12, a single procedure to deliver the implanted drug 10 to the biological tissue membrane 14 makes it possible to administer small amounts of drug 32 over a long period of time, thereby significantly reducing risks and burdens for both the patient and the practitioner.

[0066] Furthermore, the implanted drug 10 blocks the perforations in the biological tissue membrane 14 from the time of administration until it disappears, thus mitigating or avoiding the biological problems caused by the presence of such perforations. In addition, since the entire implanted drug 10, including the axial portion 16 that penetrates the biological tissue membrane 14, gradually disappears over time, the biological tissue membrane 14 regenerates as the implanted drug 10 disappears, thus mitigating or avoiding the risk of damage to the biological tissue membrane 14 associated with the disappearance of the implanted drug 10.

[0067] In Figure 1, the implanted drug 10 is shown as a single bullet-shaped device, but the specific shape is not limited. For example, in addition to the circular shape shown in the example, elliptical or polygonal shapes can also be used as cross-sectional shapes, and flat, corrugated, or block shapes can be used as appropriate depending on the organ to which the drug is to be administered and the required dosage. It is also possible to increase the exposure area into the cochlea 12 by making the surface uneven, thereby increasing the sustained release rate of the drug 32. Furthermore, multiple implanted drugs 10 may be administered by penetrating the biological tissue membrane 14 of the organ to be administered.

[0068] Furthermore, in the above embodiment, a cone-shaped tip 18 was used to improve the workability of the procedure of penetrating the biological tissue membrane 14 when administering medication to the cochlea 12. However, such a tip 18 is not essential, and the shape of the tip and proximal end of the implanted drug 10 is not limited.

[0069] For example, as shown in Figure 2(A) for the implanted drug 10a, a low, V-shaped tip 36 may be used instead of the cone-shaped tip 18. Alternatively, as shown in Figure 2(B) for the implanted drug 10b, a proximal outer peripheral projection 38 that protrudes onto the outer peripheral surface at the proximal end of the shaft 16 may be integrally formed. By providing such a proximal outer peripheral projection 38, the contact of the proximal outer peripheral projection 38 with the outer surface of the biological tissue membrane 14 allows for more precise control of the insertion depth of the implanted drug 10b into the biological tissue membrane 14, and also prevents the implanted drug 10b from falling out of the organ of the cochlea 12.

[0070] Furthermore, as illustrated in Figure 2(C) for the implanted drug 10c, at least a portion of the outer circumferential surface of the membrane holding portion 20 that penetrates the biological tissue membrane 14 in the axial portion 16 may be provided with an inverted inclined surface 40 that slopes inward from the tip to the proximal end. For example, the inverted inclined surface 40 shown in Figure (C) has an inverted tapered shape on the outer circumferential surface of the axial portion 16, gradually decreasing in diameter from the tip to the proximal end. By providing such an inverted inclined surface 40, it becomes possible to apply the component force of the contact pressure exerted from the biological tissue membrane 14 on the outer circumferential surface of the implanted drug 10c (membrane holding portion 20) in a direction that prevents the implanted drug 10c from coming out of the biological tissue membrane 14 toward the outside of the organ (cochlea 12).

[0071] Furthermore, the proximal outer peripheral projection 38 shown in Figure 2(B) and the reverse inclined surface 40 shown in Figure 2(C) above may be formed only partially in the circumferential direction. In particular, the reverse inclined surface 40 shown in (C) does not need to be provided along the entire length of the axial portion 16; it is sufficient that at least a part of it is located on the outer peripheral surface of the membrane holding portion 20 so that it receives the contact pressure in the tightening direction applied from the inner peripheral surface of the through-hole formed in the biological tissue membrane 14.

[0072] Furthermore, as illustrated in Figure 3, it is also possible to employ a locking portion in the axial portion 16 that engages with the biological tissue membrane 14.

[0073] In the indwelling drug 10d shown in Figure 3, a locking portion 42 in the shape of a spike or pin protruding from the outer surface of the shaft portion 16 is employed. The tip of this locking portion 42 is thinner than the base, and the part that comes into contact with the biological tissue membrane 14 when the drug is administered is made sharp, making it easier to catch on the biological tissue membrane 14.

[0074] In particular, the locking portion 42a, located at the tip of the axial portion 16 and positioned on the inner surface side of the biological tissue membrane 14 (right side in Figure 3) when the drug is administered, is curved or bent so that its protruding tip faces the proximal end. This reduces resistance from the locking portion 42a and minimizes damage to the biological tissue membrane 14 when the indwelling drug 10d is penetrated from the tip side into the biological tissue membrane 14. Furthermore, it is designed to easily catch on the biological tissue membrane 14 from the inner side, and provides greater resistance to slipping out to the outer surface side of the biological tissue membrane 14 (left side in Figure 3), thus exhibiting a greater positioning and holding function.

[0075] On the other hand, the locking portion 42b, located on the proximal end side of the axial portion 16 and positioned on the outer surface side (left side in Figure 3) of the biological tissue membrane 14 in the drug administration state, is curved or bent so that its protruding tip is directed toward the tip side. This makes it easier to catch on the outer surface side of the biological tissue membrane 14 and also functions as the proximal end outer peripheral projection 38 exemplified in Figure 2(B). Furthermore, this locking portion 42b provides greater resistance to protrusion toward the inner surface side (right side in Figure 3) of the biological tissue membrane 14, thereby enabling a positioning and holding function.

[0076] Furthermore, in Figure 3, a locking portion 42c, consisting of a relatively small projection that protrudes onto the outer surface of the membrane holding portion 20, is provided in the axial middle portion of the shaft-shaped portion 16. Similar to the locking portion 42a described above, it is desirable that this locking portion 42c protrudes at an angle toward the proximal end side (left side in Figure 3) of the implanted drug 10d in order to reduce resistance and damage to the biological tissue membrane 14 when administering the drug by penetrating it from the tip side to the biological tissue membrane 14.

[0077] Furthermore, it is desirable that each of the aforementioned locking portions 42, particularly locking portion 42a, be elastically deformable. For example, it is desirable that the locking portion 42 initially protrudes with a sufficient protrusion height toward the outer circumference, and that, due to the action of pressing force toward the inner circumference, the protruding tip approaches or comes into contact with the outer surface of the shaft portion 16, reducing the protrusion height, and that it can be elastically restored so that the protrusion height increases when the pressing force is released or reduced. This makes it easier to secure a large locking force toward the biological tissue membrane 14 while suppressing resistance and damage to the biological tissue membrane 14 when administering the indwelling drug 10d by penetrating it from the tip side into the biological tissue membrane 14.

[0078] However, the manner in which shape change is permitted in the locking portion 42 is not limited to elasticity. Specifically, by giving the locking portion 42 shape memory properties, for example, the locking portion, which has a small protrusion height in the low-temperature state before drug administration, may change to a shape that protrudes significantly outward when it is heated by body temperature after drug administration. Alternatively, the shape may change by expanding due to cochlear fluid (body fluid), etc., so that the protrusion height under implantation conditions is increased. For example, it is possible to achieve a change in shape (protrusion height) by using a biodegradable material that expands due to water absorption, such as gelatin or collagen. Furthermore, by combining multiple properties that enable shape change in the locking portion 42, such as elastic properties, shape memory properties, and expansion properties due to water absorption, it is possible to achieve a change in shape that is advantageous for securing retention force to the biological tissue membrane 14.

[0079] Furthermore, the locking portion 42 only needs to exhibit a locking action that prevents the implanted drug 10d from moving in the longitudinal direction (axial direction) relative to the biological tissue membrane 14, thereby improving the positioning force or holding force, and its specific shape, structure, position, and number are not limited. For example, only one of the locking portion 42a and the locking portion 42b may be used, or only the locking portion 42c may be used and provided in large numbers along substantially the entire length of the axial portion 16. Also, the locking portion does not need to have a pointed or claw-shaped tip that catches on the biological tissue membrane 14, as illustrated, but may be a columnar or hemispherical projection. In addition, the outer surface of the membrane holding portion 20 may be made rough, and a locking portion consisting of an uneven surface structure that engages with the biological tissue membrane 14 through uneven engagement or frictional engagement may be used, or an engaging portion that exhibits a locking action by an anchoring action in which the biological tissue membrane 14 enters through a recess that opens on the outer surface of the membrane holding portion 20 can be used. Furthermore, these various types of locking mechanisms may be used in combination as appropriate.

[0080] Furthermore, the locking portion 42 is also provided integrally with the implanted drug 10 and is made of a biodegradable material. However, it is possible to adjust the material of the portion where the locking portion 42 is formed so that it degrades more slowly than other parts, thereby ensuring that even as the release of drug 32 due to the biodegradation of the implanted drug 10 progresses, the locking portion 42 continues to maintain its ability to lock the implanted drug 10 to the biological tissue membrane 14.

[0081] Incidentally, the method of administering the indwelling drug 10, which has the structure described above, to the biological tissue membrane 14 inside the body in a penetrating manner is not limited, and various methods can be adopted depending on the location and type of organ or other body part to be administered the drug. An example of an indwelling drug administration device, which is a drug administration device that can be used when administering such a drug, is shown in Figure 4.

[0082] The indwelling drug administration device 50 shown in Figure 4 is equipped with a long delivery tube 52. This delivery tube 52 is made of metal, hard resin, or flexible resin that can be bent and deformed. The proximal end, located on the left side in the figure, is grasped by the operator, and the tip end, located on the right side in the figure, is inserted into the patient's body. Its length and flexibility are set so that the tip end can reach the target site for administration of the indwelling drug 10.

[0083] The delivery tube 52 is provided with a drug delivery lumen 54 that extends through it in the longitudinal direction, and the indwelling drug 10 is delivered by protruding from the distal opening 56 of this drug delivery lumen 54. Specifically, a projection rod 58 is inserted into the drug delivery lumen 54 from the proximal end so as to be movable in the longitudinal direction. This projection rod 58 may be made of, for example, a wire made of metal or resin or a flexible wire, and is made longer than the delivery tube 52 so that the portion protruding from the delivery tube 52 toward the proximal end can be operated to insert and remove it from the drug delivery lumen 54.

[0084] Furthermore, the drug delivery lumen 54 of the delivery tube 52 is made to have an inner diameter slightly larger than the outer diameter of the indwelling drug 10, as shown in Figure 5, for example. This makes it possible to insert the indwelling drug 10 from the proximal end opening of the drug delivery lumen 54 and then push it through the drug delivery lumen 54 toward the distal end using the ejection rod 58. This allows the drug delivery lumen 52 to be inserted into the body under observation using a microscope or endoscope as needed, with its distal end positioned at the drug delivery site, and the indwelling drug 10 to be delivered to the target site through the drug delivery lumen 54. Subsequently, by pushing the indwelling drug 10 out with the ejection rod 58, the drug delivery lumen 10 can be pushed out from the distal opening 56 of the delivery tube 52 and pushed into the target site of the biological tissue membrane 14 opposite the opening, thereby being placed in the penetrating state described above and administered. A low-friction layer, such as a fluororesin, may be provided on the inner surface of the drug delivery lumen 54 for purposes such as facilitating the delivery of the indwelling drug 10 through the drug delivery lumen 54 or facilitating the movement of the protruding rod 58 to the drug delivery lumen 54.

[0085] The delivery tube 52 only needs to have a drug delivery lumen 54 through which the protruding rod 58 is inserted, and additional lumens may be provided. For example, by providing a drug delivery lumen 54 in the tube of an endoscope and using it as the delivery tube 52, the operator can administer the indwelling drug 10 while viewing the image from the endoscope. Also, when using forceps or the like, the drug delivery lumen 54 may be used as a working channel for the forceps or the like, or a separate working channel may be provided in addition to the drug delivery lumen 54. Furthermore, it is also possible to provide lumens for cleaning or suction parallel to the drug delivery lumen 54. In addition, various known configurations such as radiopaque markers may be appropriately adopted depending on the expected usage situation.

[0086] Furthermore, the drug delivery lumen 54 of the delivery tube 52 only needs to allow the protruding rod 58 to pass through, and it is not essential that the indwelling drug 10 passes through it. For example, as shown in Figure 6, the inner diameter of the drug delivery lumen 54 may be made smaller than the outer diameter of the indwelling drug 10, and the opening at the distal end may be made larger in diameter to form a fitting and holding portion 60 into which the indwelling drug 10 can be fitted. In this embodiment, with the indwelling drug 10 fitted and held in the fitting and holding portion 60, the delivery tube 52 can be inserted into the body from the distal end to reach the target site, and then the indwelling drug 10 can be pushed out by the protruding rod 58 inserted through the drug delivery lumen 54 and inserted into the biological tissue membrane 14. Furthermore, in order to improve the holding force of the indwelling drug 10 to the fitting and holding part 60, a locking structure with irregularities may be provided on the inner and outer surfaces of the fitting between the indwelling drug 10 and the fitting and holding part 60, or an adhesive may be applied between the fitting surfaces.

[0087] Furthermore, the indwelling drug administration device 50 of this embodiment includes a protrusion control means 62 at the protruding end of the delivery tube 52 that controls the amount of movement of the protruding rod 58 within the drug administration lumen 54, thereby controlling the protrusion of the indwelling drug 10 from the distal opening 56 of the drug administration lumen 54.

[0088] Such protrusion control means 62 may be composed of a continuous feed mechanism 62a that continuously controls the amount of movement of the protruding rod 58 within the drug delivery lumen 54 using a screw feed mechanism, as shown in Figure 7, for example. Specifically, the continuous feed mechanism 62a consists of a fixed sleeve 66 having a female threaded portion 64 on its inner circumferential surface and a rotating sleeve 70 having a male threaded portion 68 on its outer circumferential surface, which are screwed together and connected to each other, and the relative position of the delivery tube 52 and the protruding rod 58 is controlled by the screw feed action.

[0089] In other words, the fixed sleeve 66 is secured to the proximal end of the delivery tube 52 by a connecting ring 72. On the other hand, the rotating sleeve 70 is removably fixed to the ejection rod 58 by a connecting chuck 76. When the connecting chuck 76 is released, the ejection rod 58 is free, allowing it to be quickly inserted into and removed from the drug delivery lumen 54 of the delivery tube 52.

[0090] Furthermore, the connecting chuck 76, while fixed by chucking the protruding rod 58, connects the protruding rod 58 to the rotating sleeve 70 in a way that prevents movement in the central axis direction (rod length direction), while allowing relative rotation around the rod's central axis.

[0091] In this continuous feeding mechanism 62a, with the ejection rod 58 fixed by the connecting chuck 76, when the operator rotates the rotating sleeve 70 relative to the fixed sleeve 66, the screw feed operation at the threaded portion between the female thread 64 and the male thread 68 allows the ejection rod 58, fixed to the rotating sleeve 70, to move continuously relative to the delivery pipe 52 fixed to the fixed sleeve 66 in the insertion and removal direction. Furthermore, during this relative movement caused by the screw feed operation, the connecting chuck 76 is allowed to rotate freely relative to the rotating sleeve 70, thereby avoiding rotation of the ejection rod 58 relative to the delivery pipe 52.

[0092] By using such a continuous feeding mechanism 62a, it becomes possible to precisely adjust and set the amount of protrusion of the implanted drug 10 by the protrusion rod 58, and consequently the insertion depth into the biological tissue membrane 14, as well as the amount of protrusion of the implanted drug 10 into the organ from the inner surface of the biological tissue membrane 14.

[0093] Figure 8 illustrates a stepped feed mechanism 62b as another example of the ejection control means 62, which controls the amount of movement of the ejection rod 58 within the drug delivery lumen 54 in stages by intermittent feeding operation. This stepped feed mechanism 62b has a structure similar to the lead feeding mechanism of a mechanical pencil, and intermittently feeds the ejection rod 58 axially by a predetermined amount within the delivery tube 52.

[0094] Specifically, the stepped feeding mechanism 62b includes a bottomed sleeve-shaped guide housing 80, and the proximal end of the delivery pipe 52 is fixed to the bottom wall of the guide housing 80 by a connecting ring 82. In addition, a projection rod 58 is inserted through the guide housing 80 in the axial direction, and the projection rod 58 is inserted with a predetermined frictional resistance against a return-stopping sleeve 84 mounted in the center of the bottom wall of the guide housing 80.

[0095] Furthermore, a hollow operating rod 86, which is externally fitted onto a protruding rod 58, is assembled to the base end opening of the guide housing 80. The operating rod 86 has an insertion cylinder portion 88 that is fitted into the guide housing 80, and an outer flange-shaped operating portion 90 is provided on the base end side of the insertion cylinder portion 88 that protrudes to the outside from the guide housing 80. The operating portion 90 is positioned opposite the base end face of the guide housing 80, and the operating rod 86 is elastically positioned in a state where it protrudes from the guide housing 80 toward the base end by the biasing force of a compression coil spring 92 disposed between the opposing surfaces of the guide housing 80 and the operating rod 86.

[0096] Furthermore, a chuck sleeve 94 is fixed to the tip of the operating rod 86, which is inserted into the guide housing 80, and the chuck sleeve 94 extends into the guide housing 80. The chuck sleeve 94 has an opening / closing chuck portion 96 at its tip, which consists of multiple elastic pieces divided in the circumferential direction, and is formed with an initial shape in which each divided elastic piece is stable in a state where it is spread outwards toward the outer circumference.

[0097] Furthermore, a chuck ring 98, fixed within the guide housing 80, is positioned on the outer circumference of the opening / closing chuck portion 96. The chuck sleeve 94 is elastically pulled toward its base end within the guide housing 80 by the biasing force of the compression coil spring 92, causing the outer tapered surface 100 of the opening / closing chuck portion 96 to be pressed against the leading edge of the chuck ring 98. The reaction force of this pressing against the chuck ring 98 then pushes each elastic piece constituting the opening / closing chuck portion 96 toward its inner circumference, chucking and fixing it to the outer surface of the inserted projection rod 58.

[0098] In this stepped feeding mechanism 62b, the opening / closing chuck section 96 is opened and released by pressing and holding the operating rod 86 against the biasing force of the compression coil spring 92. In this released state of the opening / closing chuck section 96, the protruding rod 58 can be easily moved in the insertion / removal direction relative to the drug delivery lumen 54 of the delivery tube 52.

[0099] Furthermore, when the pressure on the operating rod 86 is released, the ejection rod 58 is chucked by the opening / closing chuck 96 and fixed in position relative to the delivery pipe 52 in the insertion / removal direction. In this state, when the operating rod 86 is pressed once, the ejection rod 58 moves axially forward relative to the delivery pipe 52 by a predetermined unit amount corresponding to the amount the opening / closing chuck 96 moves forward. This unit amount of movement is set as the distance traveled until the fixing of the ejection rod 58 by the opening / closing chuck 96 is released, and since inertial movement is prevented by the return stopper sleeve 84, it is carried out with high precision. In short, by repeatedly pressing the operating rod 86, the ejection rod 58 can be moved axially forward by a unit amount relative to the delivery pipe 52 with high precision.

[0100] Therefore, by using such a stepwise feeding mechanism 62b, it becomes possible to precisely adjust and set the amount of protrusion of the implanted drug 10 by the protrusion rod 58, and consequently the insertion depth into the biological tissue membrane 14, as well as the amount of protrusion of the implanted drug 10 into the organ from the inner surface of the biological tissue membrane 14.

[0101] Furthermore, the ejection control means 62 having a stepped feeding mechanism 62b as illustrated in Figure 8 includes a moving end defining means that defines the moving end of the ejection rod 58 in the direction of protrusion toward the distal end in the drug delivery lumen 54. Specifically, this moving end defining means is composed of a defining ring 102 fixed by crimping or the like to a predetermined portion of the ejection rod 58 that protrudes toward the base end from the operating rod 86 of the stepped feeding mechanism 62b. That is, when the ejection rod 58 is inserted into the delivery tube 52 and moved toward the tip, the defining ring 102 comes into contact with the base end surface of the operating rod 86, thereby restricting the movement of the ejection rod 58 toward the tip. Such a defining ring 102 can also be similarly adopted in the indwelling drug delivery device 50 equipped with a continuous feeding mechanism 62a shown in Figure 7, and can also be adopted in configurations without a continuous feeding mechanism 62a or a stepped feeding mechanism 62b.

[0102] Furthermore, the specific embodiment of the ejection control means 62 is not limited to the continuous feed mechanism 62a or the stepped feed mechanism 62b described above. For example, a rack and pinion mechanism may be employed, and the ejection control may be performed by rotating a rack rotatably supported by a gripping member, thereby feeding the pinion chucked to the ejection rod 58.

[0103] Incidentally, in the indwelling drug administration device 50 with the structure described above, the distal end of the delivery tube 52 is positioned close to the site where the indwelling drug 10 is to be administered, and the indwelling drug 10 is extended from the distal opening 56 of the delivery tube 52 and inserted into the opposing biological tissue membrane 14 to administer the drug. When administering the drug in this manner, it is desirable to accurately position the distal opening 56 of the delivery tube 52 relative to the biological tissue membrane 14, thereby enabling accurate setting of the drug administration position and penetration state of the indwelling drug 10 in the biological tissue membrane 14.

[0104] Therefore, at the distal end of the delivery tube 52 in the indwelling drug administration device 50, a structure such as those illustrated in Figures 9 to 11 can be suitably adopted.

[0105] Specifically, in the embodiment shown in Figure 9, the distal end of the delivery pipe 52, which has a distal opening 56, is formed with a cutting edge-shaped end surface 106 that is inclined and spreads diagonally with respect to the central axis of the pipe.

[0106] The delivery tube 52, equipped with such a blade-shaped end face 106, can be inserted into the body during drug administration by cutting into the biological tissue membrane 14, thereby cutting or coring the biological tissue membrane 14 to form a pre-hole. Therefore, during drug administration, by simultaneously or before the indwelling drug 10 is pushed out from the distal opening 56 of the delivery tube 52, the blade-shaped end face 106 can be pierced into the biological tissue membrane 14, making it possible to easily insert the indwelling drug 10 into the biological tissue membrane 14 and suppressing excessive stress or load on the biological tissue membrane 14 and the indwelling drug 10.

[0107] Furthermore, in another embodiment shown in Figure 10, the distal end of the delivery pipe 52, which has a distal opening 56, is formed with a flat end surface 104 that serves as an annular contact surface extending substantially perpendicular to the central axis of the pipe.

[0108] When the delivery tube 52, which has such a flat end face 104, comes into contact with the surface of the biological tissue membrane 14 during insertion into the body for drug administration, it is easy to define the tip position without penetrating the biological tissue membrane 14 while overlapping with the surface. Therefore, when the indwelling drug 10 is pushed out from the distal opening 56 of the delivery tube 52 with the protrusion rod 58 under these conditions, the amount of protrusion of the indwelling drug 10 can be accurately determined and set as the amount of penetration of the indwelling drug into the biological tissue membrane 14.

[0109] Furthermore, in another embodiment shown in Figure 11, the distal end of the delivery tube 52, which has a distal opening 56, is provided with a flat end surface 104 similar to that in Figure 10, and a plurality of small needle-shaped projections 108 are formed that protrude toward the tip from the flat end surface 104.

[0110] The delivery tube 52, equipped with such small needle-like projections 108, has the small needle-like projections 108 piercing the biological tissue membrane 14 from its surface during drug delivery. As a result, the contact position of the flat end surface 104 superimposed on the surface of the biological tissue membrane 14 is stably positioned on the biological tissue membrane 14, making it possible to perform subsequent operations such as extruding the indwelling drug 10 more stably.

[0111] Furthermore, in delivery tubes 52 employing these various distal end shapes 104, 106, and 108, the manner in which the indwelling drug 10 is held in the distal opening 56 when the indwelling drug 10 is administered to the biological tissue membrane 14 is not limited. For example, as illustrated in Figures 4 to 6, the tip of the indwelling drug 10 may be held so that it protrudes a predetermined amount from the distal opening 56 toward the tip, or the indwelling drug 10 may be held in the administration lumen 54 so that it hardly protrudes from the distal opening 56.

[0112] Furthermore, the specific shape of the distal end of the delivery tube 52 is not limited to the various distal end shapes 104, 106, and 108 exemplified. For example, it is also possible to use a combination of the flat end surface 104 shown in Figure 9 and the blade-shaped end surface 106 shown in Figure 10, each covering half of the circumference. This allows for cutting the biological tissue membrane 14 with the blade-shaped end surface protruding from one half of the circumference, while preventing excessive insertion into the biological tissue membrane 14 and controlling the amount of protrusion of the indwelling drug 10 through the contact action of the flat end surface on the other half of the circumference.

[0113] Although embodiments of the present invention have been described above, the present invention is not limited by the specific descriptions above. [Explanation of Symbols]

[0114] 10a-d Indwelling medications 12 Cochlea 14. Biological tissue membrane 16 Shaft-shaped part 18. Details 20 Membrane holding part 21 Tip part (shaft part) 22 Tip reaching part 24 Proximal protrusion 30 Base material 32 Drugs 36. Yamagata tip 38 Proximal outer peripheral protrusion 40 Reverse slope 42a-c Locking part 50 Indwelling drug administration devices 52 Delivery pipe 54 Lumens for medication administration 56 Distal opening 58 Protruding rod 60 Fitting and holding part 62 Protrusion control means 62a Continuous feed mechanism 62b Stepped feed mechanism 64 Female thread section 66 Fixed Sleeve 68 Male threaded section 70 spin sleeves 72 connecting rings 76 Linked Chucks 80 Guide Housing 82 Connecting rings 84 Retractable Sleeve 86 Operating Rod 88 Insertion tube section 90 Operation section 92 Compression coil spring 94 Zippered Sleeve 96 Opening and closing chuck section 98 Chuck Rings 100 Outer circumference tapered surface 102 Standard Ring 104 Flat end face 106 Cutting edge end face 108 Small needles

Claims

1. It consists of a solid drug containing a drug in a base material made of biodegradable material. A membrane-holding portion is held in a penetrating state with respect to the biological tissue membrane that constitutes the outer boundary layer of the site where the drug is intended to be administered, A tip portion located on the tip side of the membrane holding portion and exposed to the administration target site. It is equipped with, An indwelling drug characterized in that the drug is contained in the base material at the tip portion, and the drug is released gradually to the administration site.

2. The aforementioned tip portion has a tapered shape at its tip, The film-holding portion has an outer surface shape with a smaller axial inclination than the tip portion. The indwelling drug according to claim 1.

3. The proximal end of the membrane-holding portion is provided with a proximal protrusion that extends outward from the biological tissue membrane. The indwelling drug according to claim 1 or 2.

4. A locking portion is provided on the outer surface that engages with the aforementioned biological tissue membrane. The indwelling drug according to claim 1 or 2.

5. The indwelling drug according to claim 4, wherein the locking portion has a protruding shape that extends outward on the outer surface.

6. The indwelling drug according to claim 5, wherein the locking portion, which is shaped like a protrusion, is deformable.

7. The indwelling drug according to claim 6, wherein the locking portion is elastically deformable, and the protruding height can be reduced by an external pressing force, and the protruding height can be restored when such external pressing force is removed.

8. In the tip-reaching portion, the amount of the drug in the base material is greater than in the base end portion where the film-holding portion is provided. The indwelling drug according to claim 1 or 2.

9. The biological tissue membrane is a round window membrane, and the membrane holding portion is held in a state of penetrating the round window membrane. The drug is slowly released from the tip of the device to the cochlea, which is the target site for administration. The indwelling drug according to claim 1 or 2.

10. An indwelling drug delivery device that delivers the indwelling drug described in claim 1 or 2 to the biological tissue membrane of the administration site and holds it in a penetrating state with respect to the biological tissue membrane, A delivery tube having a lumen for drug delivery that penetrates in the longitudinal direction and is inserted into the body from outside, A protruding rod is inserted into the drug delivery lumen of the delivery tube, and the indwelling drug is pushed out from the distal end opening of the drug delivery lumen. A protrusion control means controls the amount of movement of the protruding rod within the drug delivery lumen, thereby controlling the protrusion of the indwelling drug from the distal end opening of the drug delivery lumen. An indwelling drug delivery device characterized by containing the following.

11. The ejection control means is a continuous feeding mechanism that continuously controls the amount of movement of the ejection rod toward the distal end within the drug dispensing lumen. The indwelling drug delivery device according to claim 10.

12. The ejection control means is a stepwise feeding mechanism that controls the amount of movement of the ejection rod toward the distal end within the drug dispensing lumen in a stepwise manner. The indwelling drug delivery device according to claim 10.

13. The protrusion control means includes a moving end defining means that defines the moving end of the protruding rod in the direction of protrusion toward the distal end side of the drug dispensing lumen. The indwelling drug delivery device according to claim 10.

14. The distal end of the delivery tube is provided with a contact surface that is in an overlapping state with the surface of the biological tissue membrane. The indwelling drug delivery device according to claim 10.

15. The distal end of the delivery tube is provided with a sharp tip that penetrates the biological tissue membrane. The indwelling drug delivery device according to claim 10.

16. An indwelling drug delivered to the biological tissue membrane of the administration site by the indwelling drug delivery device according to claim 10, The locking portion that engages with the biological tissue membrane is formed in the shape of a projection that protrudes from the outer surface, An indwelling drug in which the locking portion is deformable, and the protruding height of the locking portion when held to the biological tissue membrane is greater than the protruding height of the locking portion when the delivery tube is inserted into the drug delivery lumen.

Images