Bone augmentation bag and manufacturing method therefor

Abstract

To provide a novel bag and a method for producing the same capable of realizing a user-friendly bone augmentation operation in implant treatment.SOLUTION: A bag 1 is used for bone augmentation, includes a first film 2a and a second film 2b each made of a biodegradable component, and has an opening between the first film 2a and the second film 2b superimposed and bonded with each other, wherein an in vivo degradation time of the first film 2a is equal to or longer than an in vivo degradation time of the second film 2b, and when the in vivo degradation times of the first film 2a and the second film 2b are different from each other, the first film 2a and the second film 2b are different from each other so as to be visually or tactilely identifiable.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a pouch used for bone augmentation and a method for producing the same. [Background technology]

[0002] There are many cases where there is a lack of bone when implant treatment is performed (see Figure 1 (A) (D)). In such cases, bone augmentation (bone grafting) is performed using a non-resorbable or resorbable barrier membrane in addition to filling with substitute bone. When a tooth is extracted, the alveolar bone surrounding the tooth is resorbed, so resorbable barrier membranes are used very frequently.

[0003] Existing absorbable barriers (absorbable membranes) are sheets of solidified absorbable components (poly-L-lactic acid / poly-D-lactic acid; see Non-Patent Documents 1-3) and are provided by various companies. Since an unstable barrier reduces the amount of bone augmentation, the barrier must be stabilized to prevent movement in order to achieve successful bone augmentation. Some groups recommend using barrier fixation pins to stabilize the barrier.

[0004] The following are currently available bone grafting procedures for guided bone regeneration (GBR) after gingival incision. (I) A procedure in which a bone substitute made of bone augmentation material is placed at the treatment site in the oral cavity and the procedure is completed by suturing the mucosa (hereinafter referred to as "Procedure I", in which only a bone substitute is used). (II) A procedure in which a bone substitute made of bone augmentation material is placed at the treatment site in the oral cavity, an absorbable barrier membrane is placed on top of it, and the procedure is completed by suturing the mucosa (hereinafter referred to as "Procedure II", which uses two types of material: a bone substitute and a barrier membrane). (III) A procedure in which, after placing a barrier membrane as in Procedure II, the placed bone substitute and barrier membrane are fixed with sutures to prevent movement, and the mucosa is sutured to complete the procedure (hereinafter referred to as "Procedure III," which uses three types of material: bone substitute, barrier membrane, and suture). (IV) To solve the problems of Procedure II, a blocking membrane is fixed with pins instead of the sutures used in Procedure III, and the procedure is completed by suturing the mucosa (hereinafter referred to as "Procedure IV," which uses three materials: a bone substitute, a blocking membrane, and pins. See Figure 1(B)). (V) To solve the problems with Procedure II, a titanium frame or non-absorbable membrane is placed in place of the barrier membrane to prevent the placed bone substitute from moving, and is fixed with pins. The procedure is then completed by suturing the mucosa (hereinafter referred to as "Procedure V," which uses three items: a bone substitute, a titanium frame (or a non-absorbable membrane), and pins). [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] Masaharu Kobayashi et al., "Clinical Evaluation of Bioabsorbable Poly-L-lactic Acid / Poly-D-lactic Acid / Polyglycolic Acid Bone Fixation Materials in Orthognathic Surgery," Journal of the Japanese Society for Jaw Deformities, Vol. 21, No. 4, 2011, pp. 238-243 [Non-patent document 2] Hiroyuki Kano et al., "Postoperative jaw stability in patients with mandibular prognathism using bioabsorbable poly-L-lactic acid / poly-D-lactic acid / polyglycolic acid bone bonding materials for maxillary and mandibular repositioning surgery," Journal of the Japanese Society for Jaw Deformities, Vol. 23, No. 1, 2013, pp. 8-14 [Non-patent document 3] Kinoshita, Takehiko et al., "Application of Implants to Jaw Reconstruction Using Absorbable Biomaterial Poly-L-Lactic Acid and Autologous Bone Marrow and Cancellous Bone Grafts," Head and Neck Tumor, 2000, Vol. 26, No. 3, pp. 525-530 [Non-patent document 4] Shuichi Sato, "Current Status of Periodontal Treatment Applying Regenerative Therapy," Nihon University School of Dentistry, 2015, No. 89, pp. 93-99 Summary of the Invention [Problem to be solved by the invention]

[0006] Bone regeneration requires three conditions: cells, growth factors, and a scaffold (Non-Patent Document 4). Here, a bone substitute can be used as a scaffold, but simply placing a bone substitute, as in Method I, will result in the bone substitute moving from the placement site, halving (reducing) the amount of bone augmentation, and therefore no bone regeneration effect can be expected. Therefore, by preventing the bone substitute from moving, even greater bone regeneration effects can be expected. For this reason, an absorbable barrier membrane is used, as in Methods II to IV above, or a non-absorbable material such as a titanium frame or a non-absorbable membrane is used, as in Method V.

[0007] However, in Procedure II, the placed bone substitute moves along with the barrier membrane, often reducing the amount of bone growth achieved by the placed bone substitute by half. Furthermore, in Procedures III to V, the intraoral manipulation required to fix the bone substitute is difficult and cumbersome, resulting in a significant amount of surgical time. In other words, these procedures are not user-friendly. Furthermore, the absorbable barrier membranes currently on the market are single-sheet products.

[0008] The invention disclosed herein has been made in consideration of the above points, and aims to provide a novel bag body and a manufacturing method thereof that can realize user-friendly bone augmentation work. [Means for solving the problem]

[0009] The bag body of the present disclosure comprises: A bag used for bone augmentation, The film includes a first film and a second film made of biodegradable components, an opening is provided between the first film and the second film which are superimposed and adhered to each other; the biodegradation time of the first film is equal to or longer than the biodegradation time of the second film; When the first film and the second film have different biodegradation times, the first film and the second film are characterized by being visually or tactilely distinguishable from each other.

[0010] In addition, in the bag body of the present disclosure, The biodegradable component may include collagen.

[0011] In addition, in the bag body of the present disclosure, The biodegradable component may include lactic acid (L)-glycolic acid (G) copolymer.

[0012] In addition, in the bag body of the present disclosure, the L / G ratio of each of the first film and the second film is within a range of 45 / 55 to 88 / 12; The proportion of lactic acid in the L / G ratio of the first film may be equal to or greater than the proportion of lactic acid in the L / G ratio of the second film.

[0013] In addition, in the bag body of the present disclosure, The L / G ratio of the first film may be set to a value within the range of 55 / 45 to 88 / 12.

[0014] In addition, in the bag body of the present disclosure, The L / G ratio of the second film may be set to a value within the range of 45 / 55 to 55 / 45.

[0015] In addition, in the bag body of the present disclosure, The intrinsic viscosity of the lactic acid-glycolic acid copolymer may be set within a range of 0.6 dL / g to 1.4 dL / g.

[0016] In addition, the bag body of the present disclosure is A bone substitute can be accommodated.

[0017] The method for manufacturing a bag body of the present disclosure includes: 1. A method of manufacturing a bag of the present disclosure, comprising: The first film and the second film are formed by spreading the material containing the biodegradable component on a flat surface and then drying it.

[0018] The bag body of the present disclosure comprises: A bag used for bone augmentation, The film includes a first film and a second film made of biodegradable components, the edges of the first film and the second film are adhered together; the biodegradation time of the first film is equal to or longer than the biodegradation time of the second film; When the first film and the second film have different biodegradation times, the first film and the second film are characterized by being visually or tactilely distinguishable from each other. [Effects of the Invention]

[0019] According to the present disclosure, a novel bag body and a manufacturing method thereof can be provided that can realize user-friendly bone augmentation procedures. [Brief explanation of the drawings]

[0020] [Figure 1] 1A and 1B show examples of a state in which alveolar bone is missing before implant treatment (A), a conventional absorbable barrier membrane (B), a bag according to an embodiment of the present disclosure (C), an implant and artificial tooth (D), and a bag and implant according to an embodiment of the present disclosure (E) (F). [Figure 2] 1A and 1B are diagrams illustrating examples of the shape of a bag according to an embodiment of the present disclosure. [Figure 3] FIG. 10 is a top view showing the opening of the bag according to an embodiment of the present disclosure. [Figure 4] 10A and 10B are diagrams illustrating examples of other bag body shapes according to embodiments of the present disclosure and examples of cases in which an opening is provided by an operator. DETAILED DESCRIPTION OF THE INVENTION

[0021] Hereinafter, exemplary embodiments of the present disclosure will be described with reference to the drawings, but the invention according to the present disclosure is not limited thereto.

[0022] [Bag body 1] FIG. 1(C) shows a pouch 1 according to an exemplary embodiment of the present disclosure. This pouch 1 includes a first film 2a and a second film 2b made of biodegradable components and used for bone augmentation (bone grafting). The biodegradation time of the first film 2a is equal to or longer than the biodegradation time of the second film 2b. That is, the degradation time of the outer first film 2a is the same as or slower (longer) than that of the second film 2b, preferably 4 to 9 months, and more preferably 4 to 6 months. On the other hand, the degradation time of the inner second film 2b is the same as or faster (shorter) than that of the first film 2a, preferably 3 to 6 months, and more preferably 1 to 1.5 months.

[0023] The bag 1 is expected to be absorbed submucosally in approximately 3 to 9 months. Furthermore, in bone augmentation procedures using the bag 1, the bone substitute can be retained within the bag 1. This prevents the bone substitute from moving, which, unlike the above-mentioned methods I and II, reduces the amount of bone growth achieved by the bone substitute. Furthermore, in procedures using the bag 1, after the gum incision, the bag 1 containing the bone substitute is simply placed at the treatment site (the missing part of the alveolar bone) and the mucosa is sutured. Unlike methods III to V, there is no need for an intraoral procedure to fix the bone substitute to the alveolar bone, and there is little risk of damaging the alveolar bone, making this method user-friendly (including the surgeon and patient). Furthermore, the procedure is completed more quickly and at a lower cost than methods III to V.

[0024] (First film 2a, second film 2b) The first film 2a and the second film 2b constitute the main body of the bag 1 and are components that house and hold the bone substitute. Biodegradable components that can be used to make the first film 2a and the second film 2b include bovine collagen, atelocollagen, tendon collagen, porcine collagen, and placenta membrane, which have traditionally been used as absorbable membranes. The biodegradable components that make up the first film 2a and the second film 2b preferably contain lactic acid (L)-glycolic acid (G) copolymer (hereinafter also referred to as PLGA). PLGA is characterized by its biodegradability. When implanted in the body, it is hydrolyzed to lactic acid and glycolic acid, which are then metabolized in the body and harmlessly eliminated as water and carbon dioxide. PLGA decomposes more quickly than polylactic acid (PLA) and other materials. When the first film 2a and the second film 2b have different bioabsorption performances, it is preferable to place the first film 2a, which has a longer biodegradation time, closer to the mucosal surface (mucosal side), and the second film 2b, which has a shorter biodegradation time, closer to the alveolar bone (bone side) (see Figure 1(C)). Because bone regeneration begins from the bone side, the need to fixate the bone substitute contained in the bag 1 is greater on the mucosal side than on the bone side, and it is desirable to maintain the mucosal side portion of the bag 1 (first film 2a) for a long time.

[0025] As demonstrated in the examples (experimental examples), the degradation rate of PLGA in vivo can vary significantly depending on the L / G ratio (the ratio of lactic acid (L) to glycolic acid (G)). While PLGA with an L / G ratio of 50 / 50 is considered to have the highest degradation rate, PLGA generally degrades faster when the glycolic acid (G) content in the PLGA is high (i.e., when the L content is low). This is thought to be because polyglycolic acid (PGA) is more sensitive to water than polylactic acid (PLA), resulting in faster degradation. Therefore, assuming that the L / G ratios of the first film 2a and the second film 2b are within the range of 45 / 55 to 88 / 12, the proportion of lactic acid in the L / G ratio of the first film 2a placed on the mucosa side (the value of L in the L:G ratio, where L + G in PLGA is 100) is preferably equal to or greater than the proportion of lactic acid in the L / G ratio of the second film 2b placed on the bone side.

[0026] When a difference in bioabsorption performance is to be achieved between the first film 2a and the second film 2b, the L / G ratio of the first film 2a is preferably 55 / 45 to 88 / 12. Specifically, the L / G ratio of the first film 2a can be within the ranges of 55 / 45 to 72 / 28, 55 / 45 to 75 / 25, 55 / 45 to 82 / 18, 55 / 45 to 85 / 15, 72 / 28 to 88 / 12, 78 / 22 to 88 / 12, 75 / 25 to 88 / 12, 82 / 18 to 88 / 12, 85 / 15, or up to 88 / 12. On the other hand, when a difference in bioabsorption performance is to be achieved between the first film 2a and the second film 2b, the L / G ratio of the second film 2b is preferably within the range of 45 / 55 to 55 / 45. Specifically, the L / G ratio of the second film 2b can be set to a value within the range of 45 / 55 to 50 / 50 or 50 / 50 to 55 / 45.

[0027] Furthermore, when there is no difference in bioabsorption performance between the first film 2a and the second film 2b, the L / G ratio of each of the first film 2a and the second film 2b can be set within a range of 45 / 55 to 88 / 12. Therefore, the L / G ratio of the first film 2a may be set within a range of 45 / 55 to 55 / 45 or 50 / 50 to 88 / 12, and the L / G ratio of the second film 2b may be set within a range of 55 / 45 to 88 / 12. As described above, the L / G ratio of each of the first film 2a and the second film 2b may be set to 45 / 55, 50 / 50, 55 / 45, 72 / 28, 78 / 22, 75 / 25, 82 / 18, 85 / 15, or 88 / 12, and the design can be modified appropriately depending on the intended use of the bag 1.

[0028] The L / G ratio of PLGA has a significant effect on the degradability (in vivo degradation time, bioabsorption performance), mechanical properties, and biocompatibility of the bag 1, and is also considered to be an important factor in expanding its range of application. <761> ) in accordance with 1 It can be measured by H-NMR spectroscopy.

[0029] In addition, the intrinsic viscosity (IV) value of PLGA is preferably 0.6 dL / g or more and 1.4 dL / g or less, taking into consideration the necessary strength of the bag body 1 and an appropriate hardness in the oral cavity. The IV value can be measured, for example, using an Ubbelohde viscometer according to the United States Pharmacopoeia (USP <911> ) can be measured in accordance with

[0030] It is preferable that the bag 1 be foldable and easily shaped. Furthermore, the size (volume) and shape of the bag 1 and the dimensions (thickness, length, etc.) of the first film 2a and the second film 2b are not particularly limited, and the bag 1 may be formed into a rectangular shape (FIG. 2), a disk, a trapezoid, a triangle, etc. The bag 1 may be trimmed to fit the actual teeth and dentition when the bone substitute is placed therein or during treatment. To allow for this, for example, if the bag 1 is rectangular, the length of one side of the bag 1 may be set to 13 mm to 17 mm.

[0031] If the first film 2a and the second film 2b have the same biodegradation time, there is no need to distinguish between the first film 2a and the second film 2b, and it makes no difference which side of the bag body 1 is placed on the treatment site (bone side or mucous membrane side).

[0032] If the first film 2a and the second film 2b have different biodegradation times (if there is a difference in bioabsorption performance), they are made different from each other so that they can be visually or tactilely distinguished by the user of the bag 1 (for example, an implant treatment surgeon). In this way, an surgeon who uses the bag 1 in a procedure can easily grasp the positions of the first film 2a and the second film 2b in the bag 1 (i.e., the front and back of the bag 1), and can place the desired side of the bag 1 (the first film 2a or the second film 2b, or a desired position thereof) on the treatment site (for example, the bone side).

[0033] Examples of embodiments in which the first film 2a and the second film 2b are "visually distinguishable" include marking one of the first film 2a and the second film 2b, and different markings on both the first film 2a and the second film 2b. Here, "marking" refers to the application of letters, numbers, symbols, lines, patterns, and the like. These marks are not particularly limited. For example, providing a blank space for the surgeon to make their own marks is also included in the "visually distinguishable" embodiment. The marking method is also not particularly limited, and examples include handwriting, engraving, stamping, labeling, and heat treatment. Furthermore, as described in the examples below, the first film 2a and the second film 2b may be "visually distinguishable" using colorants, dyes, and the like.

[0034] Examples of how the first film 2a and the second film 2b can be "tactilely distinguishable" are not particularly limited, and the first film 2a and / or the second film 2b may be embossed to create irregularities (which may be Braille, patterns, etc.), or may be subjected to surface treatments such as heat treatment, foaming treatment, etc., so that each film feels different to the touch.

[0035] Furthermore, as an example of an embodiment in which the first film 2a and the second film 2b are "visually or tactilely distinguishable," the first film 2a and the second film 2b may be processed into different shapes (appearances). For example, holes or slits to prevent leakage of the bone substitute contained therein may be provided in the first film 2a and / or the second film 2b, or they may simply be creased. The first film 2a and the second film 2b may also be distinguished from each other by their thickness. In this case, for example, if both films are made of the same material, a thicker film will decompose more slowly than a thinner film, and therefore the thicker film will be placed on the mucosal side (in the example of FIG. 1(C) , the first film 2a is a thick film and the second film 2b is a thin film).

[0036] The above-mentioned differences in appearance, shape, etc. do not need to be provided on the entire surface of the first film 2a and / or second film 2b; as long as the surgeon can distinguish between the first film 2a and the second film 2b, the differences can be provided in any desired location on the bag body 1 (first film 2a and / or second film 2b).

[0037] The breaking strength of the first film 2a and the second film 2b can be 4N to 14N, and a reference value for strength for molding is preferably 6N or more, taking into account peelability, etc. This breaking strength is the maximum pressure at which a film (15mm x 60mm x 0.05mm) set in a tensile tester (A&D Force Tester MCT-1150) is pulled at a rate of 300mm / min and breaks or stretches to its full extent.

[0038] (Opening 3) The bag 1 has an opening 3 between the first film 2a and the second film 2b, which are overlapped and have their edges glued together. That is, in the bag 1, the first film 2a and the second film 2b are overlapped and glued (sealed), but the first film 2a and the second film 2b are not glued together in a portion of the bag 1, and the opening 3 is provided. For example, when the bag 1 is a rectangular sheet, one of the four sides may be open (FIG. 2), or two sides may be open. A bone substitute can be inserted into the bag 1 through the opening 3 and accommodated therein. The width of the opening 3 may be the same as the length of one side of the bag 1 (the first film 2a and the second film 2b) as shown in FIG. 3(A), or may be smaller as shown in FIG. 3(B). The side of the bag 1 where the opening 3 is provided may be tapered toward the outside of the bag 1 as shown in FIG. 3(C). Compared to the form shown in Figure 3(A), this tapered bag 1 can be brought into the oral cavity through the spaces between the teeth before and after the missing tooth without prior trimming, and can be easily slid between the alveolar bone and gums at that site. In other words, this improves workability during the procedure. The width of the opening 3 can be adjusted as needed as long as it allows the bone substitute to be inserted. After the bone substitute is placed inside, the opening 3 may be sealed (including by heat sealing or folding). Note that it is preferable to heat seal the opening 3 during the procedure to prevent leakage of the bone substitute.

[0039] The bone substitute contained in the bag 1 and used for bone augmentation is not particularly limited, and may be autologous bone, allogeneic bone, artificial bone, etc. Bone substitutes from various companies are also available and are commercially available materials.

[0040] [Manufacturing method of bag body 1] The method for producing the pouch 1 is not limited, but a so-called solution casting method can be used. For example, a prepared PLGA solution is evenly spread (casting) on ​​a smooth surface (a substrate such as glass or a silicon wafer). This is then dried to form a first film 2a and a second film 2b. The first film 2a and the second film 2b are then superimposed and sealed (in the example shown in FIG. 2(A) , sealing is performed on three sides other than the opening 3). In this manner, the pouch 1 can be produced. Furthermore, the pouch 1 of the present disclosure is not limited to a pouch formed by superimposing two films. When the pouch 1 is produced using only one type of film (2a or 2b) (each side of the pouch 1 has the same biodegradation time), sealing may be performed on two sides. For example, when preparing a 40 mm x 50 mm film to manufacture a 40 mm x 25 mm bag body 1, the long sides (50 mm) may be folded in half and only the 25 mm portions of the two opposing sides (the vertical direction in Fig. 2(B)) may be sealed, or the 40 mm and 25 mm portions of the two adjacent sides (the vertical and horizontal directions in Fig. 2(C)) may be sealed. In this way, by providing a folding step in the manufacturing process for bag body 1 in which first film 2a and second film 2b are formed from the same type of film, the number of sealing operations can be reduced.

[0041] The PLGA solution is prepared by dissolving PLGA in a suitable organic solvent, such as chloroform or dichloromethane. This solvent is used to process the PLGA into a film. The PLGA concentration in the solution may vary depending on the desired film thickness and physical properties. In the casting method described above, the viscosity of the PLGA solution is preferably 15 mPa·s or less.

[0042] The prepared PLGA solution can be spread using a spin coater or manually with a pipette and spreader. Drying can be performed at room temperature or in a temperature-controlled environment for accelerated drying until the solvent evaporates. The time required for complete drying varies depending on the concentration of the solution and the environmental conditions.

[0043] When the bag 1 (or one of the first film 2a and the second film 2b) is made of a collagen membrane, the bag 1 can be manufactured by processing a commercially available material into the desired shape. The films may be sewn together with thread, or may be bonded using an adhesive or by heat treatment (heat sealing). Collagen membranes and PLGA membranes can be bonded by heat treatment, and different types of collagen membranes can also be bonded together by heat treatment.

[0044] [Use of bag 1] As described above, the bag 1 is used for bone augmentation (bone grafting). As an example, a bone augmentation method using the bag 1 can include the steps of incising the gums in the oral cavity, placing the bag 1 containing the bone substitute on the missing part of the alveolar bone (see FIG. 1(C)), and suturing the gums. The bone substitute contained in the bag 1 is immobile because it is contained in a bag-like shape. In this way, even when the bone substitute is placed, it can be ensured that it does not move from the placement location.

[0045] Another bone augmentation method using the bag 1 may include the steps of incising the gums in the oral cavity, placing the bag 1 containing a bone substitute on the missing part of the alveolar bone (as shown in FIG. 1(A)) so as to cover the implant when implanting the implant in the missing part of the alveolar bone (see FIG. 1(E) or (F)), and suturing the gums. Finally, an artificial tooth (crown) is attached, and the patient's treatment site becomes as shown in FIG. 1(D) (the bag 1 decomposes and disappears).

[0046] Here, the "implant" in the step of placing the bag 1 containing the bone substitute into the missing portion of the alveolar bone so as to cover the implant may be a bone level implant or a tissue level implant. Furthermore, it may be not only an implant (fixture) but also an implant and cover screw (a so-called two-piece type, see FIG. 1(E)), an implant and healing cap (see FIG. 1(F)), or an implant and healing abutment. The implant insertion procedure may be a one-stage procedure (see FIG. 1(F)) or a two-stage procedure (see FIG. 1(E)). The bag 1 can be widely applied to implant insertion procedures. For example, when a bone level implant or tissue level implant is inserted in a one-stage procedure, it can be combined with a healing abutment or healing cap. When a bone level implant or tissue level implant is inserted in a two-stage procedure, it can also be combined with a cover screw.

[0047] Another use of the bag 1 of the present disclosure is as a material to be filled into the tooth extraction socket (the cavity left after tooth extraction) during tooth extraction. That is, immediately after tooth extraction, the bag 1 placed in the tooth extraction socket inhibits alveolar bone resorption, and therefore filling the socket with the bag 1 is more effective at increasing bone mass when placing an implant in the future than not filling the socket with the bag 1. This inhibitory effect is significant when the bag 1 is made of multiple films, and it is used to store a bone substitute (simultaneous bone augmentation during tooth extraction). Even in this use, the shape of the bag 1 is not particularly limited, and it can be appropriately deformed (folded) to fit the tooth extraction socket. Furthermore, when the bag 1 is filled into the tooth extraction socket after tooth extraction, the amount (required amount) of bone substitute used in implant treatment for that patient can be reduced.

[0048] [Bag body 1'] According to the present disclosure, a bag 1' is provided that differs from the bag 1 described above in that it does not have an opening 3 (see FIG. 4(A)). That is, the edges of the first film 2a and the second film 2b are overlapped and bonded (sealed). The contents of the bag 1' (the overlapping and bonded first film 2a and / or second film 2b) are not limited, and may contain air (gas) or the like. The bag 1' has the same uses as the bag 1 and can be used for bone augmentation, implant treatment, etc. In these treatments, the surgeon can cut the bag 1' at the desired location (FIGS. 4(B) and (C)) and shape the bag 1' to a desired shape according to the case in order to accommodate a bone substitute in the bag 1' and / or to place the bag 1' at the treatment site.

[0049] The manufacturing method of bag 1' is the same as that of bag 1, but as described above, bag 1' does not have an opening 3 at the manufacturing stage, so bag 1' is sealed on all four sides (all edges) of bag 1'. As described above, this sealing method includes sewing with thread, heat sealing, etc., and may also include folding when first film 2a and second film 2b are formed from the same type of film.

[0050] In the bag 1 and manufacturing method for the bag 1 according to the present disclosure having the above-described configuration, the bag 1 is used for bone augmentation, includes a first film 2a and a second film 2b made of biodegradable components, and has an opening 3 between the first film 2a and the second film 2b that are superimposed and bonded together, the biodegradation time of the first film 2a is equal to or longer than the biodegradation time of the second film 2b, and if the biodegradation times of the first film 2a and the second film 2b are different, the first film 2a and the second film 2b are visually or tactilely distinguishable from each other. Furthermore, the bag 1 may contain a bone substitute.

[0051] The bag 1 according to the present disclosure and the bag 1 obtained by the manufacturing method according to the present disclosure are bag-shaped and can accommodate and retain a bone substitute through at least one opening 3. Therefore, during bone augmentation, the bone substitute can be fixed simply by placing the bag 1 over the missing portion of the alveolar bone, achieving a user-friendly bone augmentation procedure that does not require the complicated procedures of Procedures III to V. Furthermore, the bag 1, which is composed of a first film 2a and a second film 2b made of biodegradable components, is a novel fixation method that differs from the single absorbable barrier membrane used in Procedures II to IV and the titanium frame or non-absorbable membrane used in Procedure V. Furthermore, the bag 1 can also use first films 2a and second films 2b with different biodegradation times (bioabsorption performance), allowing for design tailored to the treatment site (mucosal side, bone side).

[0052] In addition, in the bag 1 and the method for manufacturing the bag 1 according to the present disclosure, the biodegradable component may include collagen. In this way, materials that have traditionally been recognized as safe for the human body can also be used in the user-friendly bone augmentation procedure according to the present disclosure.

[0053] Furthermore, in the bag 1 and the manufacturing method for the bag 1 according to the present disclosure, the biodegradable component may include lactic acid (L)-glycolic acid (G) copolymer. Using PLGA as the first film 2a and the second film 2b is preferable because it decomposes faster than, for example, polylactic acid alone. It is also possible to use bovine collagen, atelocollagen, tendon collagen, porcine collagen, placenta membrane, lactic acid, or glycolic acid as the biodegradable component. The first film 2a and the second film 2b may be formed from a combination of biodegradable components, with one film being made from one of these materials and the other being made from PLGA.

[0054] In the bag 1 and manufacturing method for the bag 1 according to the present disclosure, the L / G ratio of each of the first film 2a and the second film 2b may be within a range of 45 / 55 to 88 / 12, and the proportion of lactic acid in the L / G ratio of the first film 2a may be equal to or greater than the proportion of lactic acid in the L / G ratio of the second film 2b. The L / G ratio of the first film 2a may be within a range of 55 / 45 to 88 / 12, and the L / G ratio of the second film 2b may be within a range of 45 / 55 to 55 / 45. In this way, the biodegradation time (bioabsorption performance) of each film can be adjusted.

[0055] In the bag 1 and the method for manufacturing the bag 1 according to the present disclosure, the intrinsic viscosity of the lactic acid-glycolic acid copolymer may be in the range of 0.6 dL / g to 1.4 dL / g. It is preferable that the intrinsic viscosity of the PLGA is in this range in terms of the required strength and hardness of the bag 1.

[0056] In the bag 1 and the method for manufacturing the bag 1 according to the present disclosure, the first film 2a and the second film 2b may be formed by spreading a material containing a biodegradable component on a flat surface and then drying it, thereby easily manufacturing the bag 1.

[0057] In the bag 1' and its manufacturing method according to the present disclosure, the bag 1' is used for bone augmentation and includes a first film 2a and a second film 2b made of biodegradable components, the edges of the first film 2a and the second film 2b are bonded, the biodegradation time of the first film 2a is equal to or longer than the biodegradation time of the second film 2b, and if the biodegradation times of the first film 2a and the second film 2b are different, the first film 2a and the second film 2b are visually or tactilely distinguishable from each other. In this way, because the edges (all four sides) of the bag 1' are sealed, the surgeon can process the bag 1' into a desired shape according to the procedure.

[0058] The bags 1, 1' and the method for manufacturing the bag 1 according to the present disclosure are not limited to the above-described embodiments and combinations, and various modifications can be made.

[0059] For example, the bags 1, 1' may include other bioabsorbable films in addition to the first film 2a and the second film 2b, and the materials of the other bioabsorbable films may be the same as or different from those of the first film 2a and the second film 2b. For example, it is also possible to provide multiple types of absorbent films on one surface of the bag 1.

[0060] Furthermore, the shape of the bags 1, 1' is not limited to a sheet shape, and may be formed into various shapes such as a cylindrical shape, a cone shape, a sphere shape, a rectangular parallelepiped shape, a tooth shape, etc. depending on the tooth alignment and the missing part of the alveolar bone. Each surface of the bags 1, 1' may have a laminated structure.

[0061] Furthermore, in the bag 1, the position of the opening 3 is not limited to between the first film 2a and the second film 2b; the first film 2a and the second film 2b may be overlapped and their edges bonded together (closing the bag 1 in all four directions) to form the opening 3 in the first film 2a or the second film 2b. The opening 3 may make the first film 2a and the second film 2b visually or tactilely different. The number of openings 3 is also not limited to one. Multiple openings 3 may be provided between the overlapping and bonded first film 2a and second film 2b or within each of them. [Example]

[0062] The present disclosure will be described in more detail below using examples (experimental examples). Specifically, bags 1 as shown in Fig. 3(A) were manufactured using the following materials, and the degradability (i.e., biodegradation time and bioabsorption performance) of each bag 1 (example) was examined. Note that the first film 2a and the second film 2b were made with the same composition, and therefore will be simply referred to as film or membrane in the following description.

[0063] (1) Experimental reagents PLGA solution: PLGA: Ashland DLG 8513 E Lot No. 0002633992 Ashland DLG 8509 A Lot No. 0002480336 Ashland DLG 8507 A Lot No. 0002591847 Ashland DLG 7507 A Lot No. 0002510702 Mitsui Chemicals PLGA 5-50 Dichloromethane (solvent): Fujifilm Wako Pure Chemical Industries, Ltd. Lot No. DLR5072 Additives Tween 80: Kanto Chemical Co., Ltd., Lot No. 104K1486 Food Yellow No. 5: Lot No. R10401M1 manufactured by Osaka Food Color Co., Ltd. (used as a colorant for type identification in Example 5) Riboflavin: Tokyo Chemical Industry Co., Ltd., Lot No. CJCTO-YT (used as a colorant for type identification in Example 6) Elution solution: Polyvinyl alcohol EG-05P: Nippon Synthetic Chemical Industry Co., Ltd. Lot No. 68N69 Tween 80: Kanto Chemical Co., Ltd., Lot No. 104K1486 Lactic acid: Kanto Chemical Co., Ltd. Lot No. 010B2087 Distilled water: Kyoei Pharmaceutical Co., Ltd. Lot No. 18D671, Lot No. 18D685 Washing water: Distilled water: Kyoei Pharmaceutical Co., Ltd. Lot No. 18D671, Lot No. 18D685

[0064] (2) Experimental equipment Micrometer: Mitutoyo M110-25 Sealer: Fuji Impulse POLYSEALER P-200 Tabletop tension and compression testing machine: A&D Force Tester MCT-1150

[0065] (3) Experimental method ·Bag creation: Specified amounts of PLGA and Tween 80 were weighed and dissolved in dichloromethane in a sealed container and left overnight. Each solution volume was 25 mL (32 g). The PLGA solution concentration was 2.5% w / w (0.8 g / 32 g), and the additive content was 0.5% w / w (0.16 g / 32 g, 20% PLGA). The resulting solution was cast into a stainless steel tray. The dimensions of the tray were 105 x 135 mm for a 0.05 mm film thickness and 130 x 195 mm for a 0.03 mm film thickness. After leaving the tray overnight (air-drying), the film was peeled off, visually inspected, and the film thickness was measured. For each example, a bag 1 (25 mm x 40 mm) and a test piece (15 mm x 60 mm) were prepared from the peeled film. The test piece was used to measure the breaking strength (tensile speed: 300 mm / min).

[0066] Decomposition period confirmation (elution test): One pouch 1 was precisely weighed into a 125 mL glass container, and 100 mL of dissolution solution (2% PVA aqueous solution: 20% Tween 80 aqueous solution: 0.9% lactic acid aqueous solution / water = 40:1:40 / 200) heated to 37 ± 0.5 °C was added. Each container was then capped with a 2 mm-thick septum, secured, and immersed in a water bath at 37 ± 0.5 °C. During the dissolution test, the water bath temperature was increased from 37 °C to 61 °C at a rate of 0.5 °C / hour. After the start of the temperature increase, the container was removed 3 hours (38.5 °C), 28 hours (51.0 °C), and 48 hours (61.0 °C), and the solution was filtered. The removed film was washed with water and dried. The weight was measured to confirm the weight retention rate. In Examples 1 to 4, the above method was repeated four times, and each sampling time (3, 28, and 48 hours later) was assumed to be 1 to 12 months after placement in the living body, and confirmation was performed at nine time points (1, 3, 4, 6, 7, 8, 9, 10, and 12 months). However, in Examples 5 and 6, the above method was repeated twice, and each sampling was assumed to be 1 to 6 months after placement in the living body, and confirmation was performed at six time points (1, 2, 3, 4, 5, and 6 months).

[0067] (4) Disassembly confirmation test results [Example 1: DLG 8513 E film (0.05 mm) (L / G ratio: nominal value 85 / 15, specification 82.0 / 18.0 to 88.0 / 12.0, inspection value 84.5 / 15.5 (USP <761> In accordance with 1 H-NMR spectroscopy), IV: 1.30 dL / g, breaking strength: 13.62 N)] The weight retention rate decreased at the third month and remained almost constant thereafter. The appearance of the material became rounded, and by the ninth month, it had become transparent and brittle when it dried.

[0068] [Example 2: DLG 8509 A film (0.05 mm) (L / G ratio: nominal value 85 / 15, specification 82.0 / 18.0 to 88.0 / 12.0, inspection value 84.5 / 15.5 (USP <761> In accordance with 1 H-NMR spectroscopy), IV: 0.99 dL / g, breaking strength: 12.72 N)] The weight retention rate dropped in the third month and remained roughly the same thereafter. At six and eight months, the absorbed moisture was difficult to dry and exceeded that of the previous month. At six months, changes in appearance began to be seen before and after drying, and the material became brittle and prone to cracking when dry.

[0069] [Example 3: DLG 8507 A film (0.05 mm) (L / G ratio: nominal value 85 / 15, specification 82.0 / 18.0 to 88.0 / 12.0, inspection value 84.6 / 15.4 (USP <761> In accordance with 1 H-NMR spectroscopy), IV: 0.64 dL / g, breaking strength: 8.36 N)] The weight retention rate dropped significantly at the third month and then gradually decreased. The appearance was transparent after drying at the fourth month, brittle after drying at the sixth month, and brittle even before drying at the seventh month.

[0070] [Example 4: DLG 7507 A film (0.05 mm) (L / G ratio: nominal value 75 / 25, specification 72.0 / 28.0 to 78.0 / 22.0, inspection value 74.9 / 25.1 (USP <761> In accordance with 1 H-NMR spectroscopy), IV: 0.68 dL / g, breaking strength: 8.38 N)] The weight retention rate dropped significantly at 3 months and then gradually decreased. The appearance was transparent after drying at 4 months, brittle after drying at 4 months, and brittle even before drying at 7 months.

[0071] [Example 5: PLGA 5-50 colored film (0.05 mm) (L / G ratio: nominal value 50 / 50, specification 45.0 / 55.0 to 55.0 / 45.0, test value 50.5 / 49.5) 1 H-NMR spectroscopy), IV: 0.50 dL / g, breaking strength: 4.78 N)] The weight retention rate decreased between the second and third months and remained roughly the same between the third and fifth months. It began to decrease again between the fifth and sixth months. The film appeared to be curling up until the second month, becoming transparent as it dried, but retaining its shape. By the third month, it had become brittle as it dried. Furthermore, no noticeable difference in the physical properties was observed when a dye was added to the film.

[0072] [Example 6: DLG 7507 A colored film (0.03 mm) (breaking strength: 7.22 N)] The weight retention rate dropped significantly in the second month and then gradually decreased. Its appearance showed that it began to curl from the second month onwards, and became transparent when it dried, but it still maintained its shape. By the sixth month, it had become quite brittle. Since no significant differences were observed in either weight retention rate or appearance compared to the 0.05 mm thick film (Example 4), it was found that a bag body 1 could be produced without any problems in strength as long as the film thickness was within the range of 0.03 to 0.05 mm.

[0073] (5) Summary Regarding the maintenance period, no significant changes (differences) were observed in weight, and the following trends were found in relation to the L / G ratio based on appearance and brittleness. If the L / G ratio is 85 / 15, it will become brittle in more than 6 months. If the L / G ratio is 75 / 25, it will become brittle in more than four months. If the L / G ratio is 50 / 50, it will become brittle in less than four months. From the above findings, it can be seen that different degradability (in vivo degradation time, bioabsorption performance) can be achieved by varying the L / G ratio of the first film 2a and the second film 2b that make up the bag body 1. Furthermore, it is suggested that if the L / G ratio of the first film 2a is within the range of 55 / 45 to 88 / 12 and the L / G ratio of the second film 2b is 45 / 55 to 55 / 45, the respective in vivo degradation times will be approximately 4 to 9 months and 1 to 4 months.

Claims

1. A bag used for bone augmentation, The film includes a first film and a second film made of biodegradable components, an opening is provided between the first film and the second film that are superimposed and adhered to each other; the biodegradation time of the first film is equal to or longer than the biodegradation time of the second film; When the first film and the second film have different biodegradation times, the first film and the second film are visually or tactilely distinguishable from each other.

2. The pouch of claim 1 , wherein the biodegradable component comprises collagen.

3. 2. The bag of claim 1, wherein the biodegradable component comprises a lactic acid (L)-glycolic acid (G) copolymer.

4. the L / G ratio of each of the first film and the second film is within a range of 45 / 55 to 88 / 12; The bag according to claim 3 , wherein the proportion of lactic acid in the L / G ratio of the first film is equal to or greater than the proportion of lactic acid in the L / G ratio of the second film.

5. 5. The bag according to claim 3, wherein the L / G ratio of the first film is within a range of 55 / 45 to 88 / 12.

6. The bag according to any one of claims 3 to 5, wherein the L / G ratio of the second film is within a range of 45 / 55 to 55 / 45.

7. 7. The bag according to claim 3, wherein the intrinsic viscosity of the lactic acid-glycolic acid copolymer is in the range of 0.6 dL / g to 1.4 dL / g.

8. The pouch according to any one of claims 1 to 7, containing a bone substitute.

9. A method for manufacturing the bag of claim 1, comprising: A method for manufacturing a bag, wherein the first film and the second film are formed by spreading a material containing the biodegradable component on a flat surface and then drying it.

10. A bag used for bone augmentation, The film includes a first film and a second film made of biodegradable components, the edges of the first film and the second film are adhered together; the biodegradation time of the first film is equal to or longer than the biodegradation time of the second film; When the first film and the second film have different biodegradation times, the first film and the second film are visually or tactilely distinguishable from each other.

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