bone growth bag

Abstract

The bag (1) is used for bone growth and includes a first membrane (2a) and a second membrane (2b) made of biodegradable components. An opening (3) is provided between the overlapping and bonded first membrane (2a) and second membrane (2b). The biodegradation time of the first membrane (2a) is longer than that of the second membrane (2b). When the biodegradation times of the first membrane (2a) and the second membrane (2b) are different, the first membrane (2a) and the second membrane (2b) are visually or tactilely distinguishable from each other.

Description

Technical Field

[0001] This utility model relates to a bag used for bone growth and a method for manufacturing the same. Background Technology

[0002] Bone insufficiency during implant treatment (see [reference]) Figure 1 (A)(D)) Many. In this case, in addition to filling with replacement bone, bone growth (bone grafting) is also performed using non-absorbable or absorbable occlusal membranes. Absorbable occlusal membranes are used very frequently during tooth extraction because the alveolar bone around the tooth is resorbed.

[0003] Existing absorbent occlusive membranes (absorbent membranes) use a sheet-like material that fixes an absorbent component (poly-L-lactic acid / poly-D-lactic acid; see Non-Patent Literature 1-3), and are supplied by various companies. If the occlusive membrane is stable, bone growth is reduced; therefore, the occlusive membrane should be kept immobile to successfully accommodate bone growth. There are also recommendations to use occlusive membrane fixation pins to stabilize the occlusive membrane.

[0004] Currently, the surgical procedures for bone grafting in the gingival incision bone regeneration induction method (GBR method) are as follows.

[0005] (I) A substitute bone of bone growth material is placed in the treatment site in the oral cavity, and the mucosa is sutured to complete the procedure (hereinafter referred to as "Surgical Method I", using only substitute bone).

[0006] (II) A bone substitute material is placed in the treatment area inside the oral cavity, and an absorbable blocking membrane is placed on it. The mucosa is then sutured to complete the procedure (hereinafter referred to as "Surgical Method II", which uses both bone substitute and blocking membrane).

[0007] (III) After setting up the occluder membrane as in surgical procedure II, it is fixed with sutures to prevent the replacement bone and occluder membrane from moving, and the mucosal suture is performed to finish (hereinafter referred to as "surgical procedure III", which uses replacement bone, occluder membrane and sutures).

[0008] (IV) To address the issues in surgical procedure II, the sutures used in surgical procedure III are replaced by pins to fix the occlusive membrane, followed by mucosal suturing to complete the procedure (hereinafter referred to as "surgical procedure IV," using substitute bone, occlusive membrane, and pins). See also Figure 1 (B)

[0009] (V) To address the issues in surgical procedure II, a titanium frame or non-absorbable membrane is installed instead of the blocking membrane and fixed with pins to prevent the replacement bone from shifting. The procedure is then completed by mucosal suturing (hereinafter referred to as "surgical procedure V", which uses three types of replacement bone, titanium frame (or non-absorbable membrane), and pins).

[0010] Existing technical documents

[0011] Non-patent literature

[0012] Non-patent document 1: Masaharu Kobayashi et al., "Jaw correction surgery: におけるポリ-L-lactic acid / ポリ-D-lactic acid / ポリグリコール acid bioabsorption" "Clinical Evaluation of Retractable Bone Joint Materials", Journal of the Japanese Jaw Deformity Society, 2011, Volume 21, No. 4, p. 238-243 Non-patent literature 2: Hiroyuki Kana, "Maximum and Mandibular Movement Techniques" Nairoli-L-Lactic Acid / Naru-D-Lactic Acid / Naruto-Acid Bioabsorbable Bone Joint Materials Postoperative jawbone stability in patients with mandibular prognathism using this method”, Journal of the Japanese Society of Jaw Deformity, 2013, Volume 23, No. 1, p.8-14

[0013] Non-patent document 3: Takehihiko Kinoshita et al., "Use of Absorbable Biological Materials L-Lactic Acid and Homemade Bone Bone Sponge Bone Slices for Jaw Reconstruction Department", Head and Neck Cancer, 2000, Vol. 26, No. 3, p. 525-530

[0014] Non-patent document 4: Shuichi Sato, "Current status of regenerative therapy and circumferential treatment", Nihon University School of Dentistry, 2015, No. 89, p. 93-99 Utility Model Content

[0015] The problem to be solved by utility models

[0016] Bone regeneration requires three conditions: cells, growth factors, and a scaffold (see Non-Patent Literature 4). Regarding the scaffold, a substitute bone can be used; however, if only a substitute bone is placed as in surgical method I, the placed substitute bone will migrate from its placement site, and bone growth will be halved (reduced), thus preventing the expectation of bone regeneration. Therefore, by preventing the substitute bone from migrating, further bone regeneration can be expected. Therefore, absorbable blocking membranes are used as in surgical methods II-IV, or non-absorbable materials such as titanium frames or non-absorbable membranes are used as in surgical method V.

[0017] However, in surgical method II, the implanted bone often moves along with the blocking membrane, and the bone growth of the implanted bone is often halved. Furthermore, in surgical methods III to V, the intraoral procedures used to fix the implanted bone are difficult and complex, requiring a significant amount of surgical time. In other words, these surgical methods are not user-friendly. It should be noted that the currently sold absorbable blocking membrane is a sheet-like product.

[0018] The present invention is proposed in consideration of the above aspects, with the aim of providing a new bag body and its manufacturing method that enables user-friendly bone growth operations.

[0019] Methods for solving problems

[0020] The disclosed pouch is used for bone growth, characterized in that,

[0021] It includes a first membrane and a second membrane made of biodegradable components.

[0022] An opening is provided between the overlapping and bonded first film and the second film.

[0023] The in vivo degradation time of the first membrane is longer than the in vivo degradation time of the second membrane.

[0024] When the degradation times of the first membrane and the second membrane in vivo are different, the first membrane and the second membrane are visually or tactilely identifiable as being different from each other.

[0025] Alternatively, it could be within the bag structure disclosed herein.

[0026] The biodegradable component includes collagen.

[0027] Alternatively, it could be within the bag structure disclosed herein.

[0028] The biodegradable component comprises a lactic acid (L)-glycolic acid (G) copolymer.

[0029] Alternatively, it could be within the bag structure disclosed herein.

[0030] The L / G ratio of the first membrane and the second membrane are each in the range of 45 / 55 to 88 / 12.

[0031] The proportion of lactic acid in the L / G ratio of the first membrane is greater than the proportion of lactic acid in the L / G ratio of the second membrane.

[0032] Furthermore, in the bag body disclosed herein,

[0033] The L / G ratio of the first membrane can be set to a value in the range of 55 / 45 to 88 / 12.

[0034] Furthermore, in the bag body disclosed herein,

[0035] The L / G ratio of the second membrane can be set to a value in the range of 45 / 55 to 55 / 45.

[0036] Furthermore, in the bag body disclosed herein,

[0037] The intrinsic viscosity of the lactic acid-glycolic acid copolymer can be set to a range of 0.6 dL / g to 1.4 dL / g.

[0038] In addition, the bag disclosed herein can contain substitute bone.

[0039] The method for manufacturing the bag body disclosed herein is characterized by,

[0040] The first film and the second film are formed by spreading the material containing the biodegradable component on a plane and then drying it.

[0041] The disclosed pouch is used for bone growth, characterized in that,

[0042] It includes a first membrane and a second membrane made of biodegradable components.

[0043] The edges of the first membrane and the second membrane are bonded together.

[0044] The in vivo degradation time of the first membrane is longer than the in vivo degradation time of the second membrane.

[0045] When the degradation times of the first membrane and the second membrane in vivo are different, the first membrane and the second membrane are visually or tactilely identifiable as being different from each other.

[0046] Utility Model Effect

[0047] According to this disclosure, a new bag body and its manufacturing method are provided that enable user-friendly bone growth operations. Attached Figure Description

[0048] Figure 1 The figures show examples of alveolar bone defects before implant treatment (A), existing resorbable blocking membrane (B), pocket of the present disclosure (C), implant and artificial tooth (D), pocket and implant of the present disclosure (E) (F).

[0049] Figure 2 This is a diagram illustrating an example of the shape of a bag according to an embodiment of the present disclosure.

[0050] Figure 3 This is a top view showing the opening of the bag body according to an embodiment of the present disclosure.

[0051] Figure 4 The diagram illustrates examples of other bag shapes according to embodiments of the present disclosure, as well as examples of cases where the opening is set by the surgeon. Detailed Implementation

[0052] Hereinafter, embodiments of the present disclosure will be described with reference to the accompanying drawings, but the utility model of the present disclosure is not limited thereto.

[0053] [Bag 1]

[0054] Figure 1(C) shows a bag 1 according to an embodiment of this disclosure. This bag 1 is used for bone growth (bone grafting) and includes a first membrane 2a and a second membrane 2b made of a biodegradable component. The biodegradation time of the first membrane 2a is longer than that of the second membrane 2b. That is, the degradation time of the outer first membrane 2a is the same as or slower (longer) than that of the second membrane 2b, preferably 4 to 9 months, more preferably 4 to 6 months. On the other hand, the degradation time of the inner second membrane 2b is the same as or earlier (shorter) than that of the first membrane 2a, preferably 3 to 6 months, more preferably 1 to 1.5 months.

[0055] The pocket 1 is expected to be absorbed submucosally within 3 to 9 months. Furthermore, in bone reconstruction surgeries using the pocket 1, the replacement bone can be retained within the pocket 1. Therefore, unlike surgical methods I and II described above, it prevents the replacement bone from shifting or its growth being halved. In addition, surgeries using the pocket 1 only require placing the pocket 1 containing the replacement bone at the surgical site (the area of ​​alveolar bone loss) after gingival incision and mucosal suturing. Unlike surgical methods III to V, it eliminates the need for intraoral fixation of the replacement bone to the alveolar bone, reducing the risk of alveolar bone damage and making it more user-friendly (including surgeons and patients). Moreover, compared to surgical methods III to V, the surgery is completed faster and is less expensive.

[0056] (Membrane 1 2a, Membrane 2 2b)

[0057] The first membrane 2a and the second membrane 2b constitute the main body of the bag 1 and are the constituent elements for containing and retaining the replacement bone. Examples of biodegradable components used as materials for the first membrane 2a and the second membrane 2b include bovine collagen, terminal collagen, tendon collagen, porcine collagen, and placental membrane, which have been conventionally used as absorbable membranes. Preferably, the biodegradable component forming the first membrane 2a and the second membrane 2b includes a lactic acid (L)-glycolic acid (G) copolymer (hereinafter also referred to as PLGA). PLGA is biodegradable and, when implanted, decomposes into lactic acid and glycolic acid through hydrolysis, which are then harmlessly eliminated from the body as water and carbon dioxide. PLGA degrades faster than polylactic acid (PLA) and the like. It should be noted that, given the difference in bioabsorption performance between the first membrane 2a and the second membrane 2b, it is preferable to place the first membrane 2a, which has a longer biodegradation time, on the side closer to the mucosa (mucosal side), and the second membrane 2b, which has a shorter biodegradation time, on the side closer to the alveolar bone (bone side) (see...). Figure 1 (C)). Bone regeneration begins from the bone side, therefore the need to fix the substitute bone contained in the bag 1 on the mucosal side is higher than that on the bone side, and it is desirable that the mucosal side portion (first membrane 2a) of the bag 1 survives for a longer period of time.

[0058] As shown in the examples (experimental examples), the degradation rate of PLGA in vivo varies significantly depending on the L / G ratio (the ratio of lactic acid (L) to glycolic acid (G). L:G). PLGA with an L / G ratio of 50 / 50 exhibits the highest degradation rate, but if the proportion of glycolic acid (G) in the PLGA is high (in other words, if the proportion of L is low), it generally degrades more rapidly. This is because polyglycolic acid (PGA) is more sensitive to water and degrades more rapidly than polylactic acid (PLA). Therefore, assuming that the L / G ratios of the first membrane 2a and the second membrane 2b are each within the range of 45 / 55 to 88 / 12, it is preferable that the proportion of lactic acid in the L / G ratio of the first membrane 2a located on the mucosal side (the value of L in L:G expressed as L+G=100 in PLGA) is higher than the proportion of lactic acid in the L / G ratio of the second membrane 2b located on the bone side.

[0059] When there is a difference in the bioabsorption performance between the first membrane 2a and the second membrane 2b, the L / G ratio of the first membrane 2a is preferably 55 / 45 to 88 / 12. Specifically, the L / G ratio of the first membrane 2a can also be set within the range 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 ~88 / 12. On the other hand, when there is a difference in the bioabsorption performance between the first membrane 2a and the second membrane 2b, the L / G ratio of the second membrane 2b is preferably within the range of 45 / 55 to 55 / 45. Specifically, the L / G ratio of the second membrane 2b can also be set to a value within the range of 45 / 55 to 50 / 50 or 50 / 50 to 55 / 45.

[0060] Furthermore, when there is no difference in bioabsorption performance between the first membrane 2a and the second membrane 2b, the L / G ratio of each membrane can be set to a range of 45 / 55 to 88 / 12. Therefore, the L / G ratio of the first membrane 2a can be set in the range of 45 / 55 to 55 / 45, 50 / 50 to 88 / 12, or the L / G ratio of the second membrane 2b can be set in the range of 55 / 45 to 88 / 12. As described above, the L / G ratio of each membrane can be set to 45 / 55, 50 / 50, 55 / 45, 72 / 28, 78 / 22, 75 / 25, 82 / 18, 85 / 15, or 88 / 12, and can be appropriately designed and modified according to the intended use of the bag 1.

[0061] It should be noted that the L / G ratio of PLGA has a significant impact on the biodegradability (biodegradation time, bioabsorption performance), mechanical properties, and biocompatibility of bag 1, and is considered an important factor in expanding its application range. The L / G ratio can be determined by 1H-NMR spectroscopy based on the United States Pharmacopeia (USP<761>).

[0062] Furthermore, the intrinsic viscosity (IV) value of PLGA is preferably between 0.6 dL / g and 1.4 dL / g, taking into account the necessary strength of the bag body 1 and the appropriate hardness within the oral cavity. The IV value can be determined, for example, using an Uberloud viscometer based on the United States Pharmacopeia (USP<911>).

[0063] The bag body 1 is preferably foldable and easily shaped. Furthermore, the size (volume) and shape of the bag body 1, as well as the dimensions (thickness, length, etc.) of the first membrane 2a and the second membrane 2b, are not particularly limited and can be formed into a rectangle. Figure 2 ( ), disc, trapezoid, triangular, etc. The bag body 1 can also be modified according to the actual teeth and tooth rows during bone replacement and surgery. Considering the margin of error, for example, when the bag body 1 is rectangular, the length of one side of the bag body 1 can be set to 13mm to 17mm.

[0064] When the degradation time of the first membrane 2a and the second membrane 2b in vivo is the same, there is no need to distinguish between the first membrane 2a and the second membrane 2b, even if a certain side of the bag 1 is set at the surgical site (bone side, mucosal side).

[0065] In cases where the degradation times of the first membrane 2a and the second membrane 2b in vivo differ (where there is no difference in bioabsorption performance), they are distinguished visually or tactilely by the user of the bag 1 (e.g., a surgeon performing implant treatment). This allows the surgeon using the bag 1 to easily grasp the positions of the first membrane 2a and the second membrane 2b within the bag 1 (i.e., the front and back of the bag 1) and position the desired side of the bag 1 (the first membrane 2a or the second membrane 2b, or its desired position) at the surgical site (e.g., the bone side).

[0066] Examples of visually recognizable patterns for the first membrane 2a and the second membrane 2b include marking one of the first membrane 2a and the second membrane 2b, or marking the two membranes 2b differently. Here, marking refers to markings such as text, numbers, symbols, lines, patterns, etc., and these markings are not particularly limited. For example, providing blank spaces for surgeons to mark their own markings is also included in the category of "visually recognizable patterns." The methods of marking are also not particularly limited, and examples include handwriting, engraving, lamination, labeling, and heat treatment. Furthermore, as shown in the embodiments described later, colorants, dyes, etc., can also be used to make the first membrane 2a and the second membrane 2b "visually different."

[0067] There are no particular limitations on the examples of the "tactilely recognizable" patterns of the first membrane 2a and the second membrane 2b. The first membrane 2a and / or the second membrane 2b may also be subjected to embossing (which may be Braille, patterns, etc.), heat treatment, foaming, etc., so that the skin feel of each membrane is different.

[0068] Furthermore, as an example of a pattern in which the first membrane 2a and the second membrane 2b are "visually or tactilely identifiable," the first membrane 2a and the second membrane 2b can be processed into different shapes (appearances). For example, holes or slits that prevent the contained substitute bone from being exposed can be provided on the first membrane 2a and / or the second membrane 2b, or only folds can be provided. Additionally, the first membrane 2a and the second membrane 2b can be distinguished based on their thickness. In this case, for example, if formed from the same material, the thicker membrane degrades more slowly than the thinner membrane; therefore, the thicker membrane is placed on the mucosal side (in...). Figure 1 In example (C), the first membrane 2a is set as a thick membrane and the second membrane 2b is set as a thin membrane.

[0069] The differences in appearance, shape, etc., do not need to be set on the entire surface of the first membrane 2a and / or the second membrane 2b. The surgeon only needs to be able to distinguish between the first membrane 2a and the second membrane 2b. The differences can be set at the desired locations on the bag body 1 (the first membrane 2a and / or the second membrane 2b).

[0070] It should be noted that the tensile strength of the first membrane 2a and the second membrane 2b can be set to 4N to 14N. From the perspective of peelability, etc., as a strength reference value for molding, it is preferably 6N or more. This tensile strength is the maximum value of the pressure when the membrane (15mm×60mm×0.05mm) placed on a tensile testing machine (A&D ForceTester MCT-1150) breaks or elongates at a speed of 300mm / min.

[0071] (Opening 3)

[0072] The bag body 1 has an opening 3 between the first film 2a and the second film 2b, which are bonded at their overlapping edges. That is, in the bag body 1, the first film 2a and the second film 2b are bonded together (sealed), while in a portion of the bag body 1, the first film 2a and the second film 2b are not bonded, and an opening 3 is provided. For example, if the bag body 1 is a rectangular sheet, it can have an opening in one of four directions. Figure 2 It can also have openings in two directions. It allows a substitute bone to be inserted into the bag body 1 through opening 3 and contained therein. For example... Figure 3 As shown in (A), the width of the opening 3 can be the same as the length of one side of the bag body 1 (the first membrane 2a and the second membrane 2b), or it can be as shown in (A). Figure 3 (B) is smaller than it. Additionally, as shown in [the diagram]... Figure 3 As shown in (C), the side portion of the bag body 1 with the opening 3 can also be a tapered shape (conical shape) that tapers towards the outer side of the bag body 1. As long as the bag body 1 has such a tapered shape, even with... Figure 3 Compared to the method without pre-treatment, method (A) allows the bag 1 to be brought into the oral cavity through the spaces between the front and back teeth at the site of tooth loss, making it easy to slide into the alveolar bone and gingiva at that location. In other words, the operability during surgery is improved. The width of the opening 3 is sufficient to insert the substitute bone, and can be appropriately adjusted. The opening 3 can also be closed (including heat sealing and folding) after the substitute bone is received. It should be noted that heat sealing of the opening 3 during surgery is preferred to prevent leakage of the substitute bone.

[0073] The substitute bone housed in the bag 1 and used for bone growth is not particularly limited and can be autologous bone, allogeneic bone, artificial bone, etc. Substitute bones from various companies are also readily available materials.

[0074] [Manufacturing method of bag 1]

[0075] The manufacturing method of the bag body 1 is not limited, and a so-called casting method (solution casting method) can be used. That is, for example, the prepared PLGA solution is uniformly spread (casting, casting) on ​​a smooth surface (a substrate such as glass or silicon wafer). Then, the first film 2a and the second film 2b are formed by drying them. Then, the first film 2a and the second film 2b are overlapped and sealed (in... Figure 2 In the example shown in (A), the bag body 1 is sealed in three directions in the non-opening portion 3. This allows the bag body 1 to be manufactured. Furthermore, the bag body 1 of this disclosure is not limited to a structure formed by overlapping two films; when the bag body 1 is manufactured using only one film (2a or 2b) (where the biodegradation time of the bag body 1 is the same on either side), it can also be sealed in two directions. For example, when preparing a 40mm × 50mm film to manufacture a 40mm × 25mm bag body 1, the long side (50mm) portion can be folded in half, and only the 25mm portions of the two opposite sides (in the...) are sealed. Figure 2 (B) is in the longitudinal direction) seal, or seal the 40mm portion and 25mm portion of the two adjacent sides (in Figure 2 (C) is sealed in both the longitudinal and transverse directions. In this way, in the manufacturing process of the bag body 1 formed by the same film forming the first film 2a and the second film 2b, by setting a folding step, the number of sealing operations can be reduced.

[0076] Here, the PLGA solution is prepared by dissolving PLGA in a suitable organic solvent. Examples of organic solvents include chloroform and dichloromethane. This solvent is used to process PLGA into a film. The PLGA concentration of the solution can also be adjusted appropriately according to the desired film thickness and physical properties, depending on the type of film. Furthermore, in the above-described casting method, it is preferable that the viscosity of the PLGA solution is 15 mPa·s or less.

[0077] To allow the prepared PLGA solution to diffuse, it can be done manually using a spin coater or a pipette / coating machine. Drying can be carried out at room temperature before the solvent evaporates or, to accelerate the process, in a temperature-controlled environment. The time required for complete drying varies depending on the solution concentration and environmental conditions.

[0078] When a bag body 1 (or one of the first membrane 2a and the second membrane 2b) is formed from a collagen membrane, commercially available materials can be processed into the desired shape to manufacture the bag body 1. The membranes can be sewn together with thread, or bonded using adhesives or by heat treatment (heat sealing). It should be noted that collagen membranes can be bonded to PLGA membranes by heat treatment, and different types of collagen membranes can also be bonded to each other by heat treatment.

[0079] [Purpose of bag 1]

[0080] As previously mentioned, the pocket 1 is used for bone growth (bone grafting). As an example, a bone growth method using the pocket 1 may include the steps of cutting the gum line in the oral cavity and placing the pocket 1, which contains the substitute bone, into the missing portion of the alveolar bone (see [link to original text]). Figure 1 (C) and the process of suturing the gums. The substitute bone contained in the bag 1 enters the bag shape and is therefore in a stationary state. In this way, even if a substitute bone is installed, it can be ensured that the substitute bone does not move from the installation site.

[0081] Alternatively, another bone growth method using the bag 1 may also include the procedure of cutting the gingiva inside the mouth and embedding the implant ( Figure 1 The procedure of placing a bag containing replacement bone in the alveolar bone missing part in a manner that covers the implant (see State A) for details. Figure 1(E) or (F) and the procedure of suturing the gums. Finally, the artificial tooth (crown) is installed, and the patient's surgical site becomes... Figure 1 The state of (D) (bag 1 decomposes and disappears).

[0082] Here, the "implant" in the process of placing a bag 1 containing substitute bone in the missing portion of alveolar bone in a manner that covers the implant can be a bone-level implant or a tissue-level implant. In addition, it can also be not only an implant (implant), but also an implant and a cap screw (so-called two-piece type). See Figure 1 (E)), implants and healing caps (see Figure 1 (F)), implant and healing abutment. Implant placement can be a one-time procedure. Figure 1 (F) can also be a two-step embedding method ( Figure 1 (E)) In any implant surgery, the bag body 1 is widely used. As a specific example, in the case of implanting a bone-level or tissue-level implant in a single procedure, the healing abutment and healing cap can also be used together, and in the case of implanting a bone-level or tissue-level implant in two procedures, the cap screw can also be used together.

[0083] As another application of the pocket 1 disclosed herein, it can also be used as a material to fill the extraction socket (the depression after tooth extraction) during tooth extraction. That is, immediately after tooth extraction, since the pocket 1, which is disposed in the extraction socket, inhibits alveolar bone resorption, the addition of the pocket 1 during future implant placement is beneficial for bone growth compared to the case where the pocket 1 is not filled. In the pocket 1 containing multiple membranes, this inhibitory effect is significant, and it accommodates and uses substitute bone (bone growth occurs simultaneously with tooth extraction). For this application, the shape of the pocket 1 is not particularly limited and can be appropriately deformed (folded) according to the extraction socket. Furthermore, when the pocket 1 is filled into the extraction socket after tooth extraction, the amount of substitute bone used (the necessary amount) in implant treatment for the patient can be reduced.

[0084] [Pocket 1']

[0085] According to this disclosure, a bag body 1' is provided that differs from the bag body 1 described above in that it does not have an opening 3 (see [link]). Figure 4 (A)). That is, the edges of the first membrane 2a and the second membrane 2b are overlapped and bonded (sealed). The contents of the bag 1' (the overlapped and bonded first membrane 2a and / or second membrane 2b) are not limited; it may contain air (gas) or not. The purpose of the bag 1' is the same as that of the bag 1, and it can be used for bone growth, implant treatment, etc., but in these surgeries, the surgeon cuts the bag 1' at the desired location (A). Figure 4(B)(C)) The bag 1' is shaped to correspond to the desired condition so as to accommodate the substitute bone in the bag 1' and / or to place the bag 1' at the surgical site.

[0086] The manufacturing method of bag body 1' is the same as that of bag body 1. As mentioned above, since bag body 1' does not have an opening 3 during the manufacturing stage, it is sealed around its entire perimeter (all edges). As mentioned above, this sealing method includes sewing with thread, heat sealing, etc., and may also include folding if the first film 2a and the second film 2b are formed from the same film.

[0087] In the bag 1 and its manufacturing method of the present disclosure, which include the above-described components, the bag 1 is used for bone growth and includes a first membrane 2a and a second membrane 2b made of a biodegradable component. An opening 3 is provided between the overlapping and bonded first membrane 2a and second membrane 2b. The biodegradation time of the first membrane 2a is greater than or equal to the biodegradation time of the second membrane 2b. When the biodegradation times of the first membrane 2a and the second membrane 2b are different, the first membrane 2a and the second membrane 2b are visually or tactilely distinguishable from each other. Furthermore, the bag 1 can also contain substitute bone.

[0088] The bag 1 disclosed herein, and the bag 1 obtained by the manufacturing method of this disclosure, are bag-shaped structures capable of receiving and holding substitute bone through at least one opening 3. Therefore, in bone reconstruction surgery, the received substitute bone can be fixed simply by placing the bag 1 on the missing portion of the alveolar bone, enabling user-friendly bone growth procedures such as surgical methods III to V that do not require complex operations. Furthermore, the bag 1, composed of a first membrane 2a and a second membrane 2b made of biodegradable materials, is a novel fixation mechanism different from the absorbable blocking membrane used in surgical methods II to IV and the titanium frame and non-absorbable membrane used in surgical method V. In addition, the bag 1 can also use the first membrane 2a and the second membrane 2b with different biodegradation times (bioabsorption properties), enabling designs corresponding to the surgical site (mucosal side, bone side).

[0089] Furthermore, in the bag body 1 and its manufacturing method disclosed herein, the biodegradable component may also include collagen. Thus, materials previously considered safe for human use can also be used in the user-friendly bone growth procedures of this disclosure.

[0090] Furthermore, in the bag body 1 and the method for manufacturing the bag body 1 disclosed herein, the biodegradable component may also include a lactic acid (L)-glycolic acid (G) copolymer. In this way, if PLGA is used as the first membrane 2a and the second membrane 2b, it degrades faster, for example, compared to the case where polylactic acid is used in the monomer, and is therefore preferred. It should be noted that bovine collagen, terminal collagen, tendon collagen, porcine collagen, placental membrane, lactic acid, or glycolic acid may also be used as the biodegradable component. As a combination of biodegradable components forming the first membrane 2a and the second membrane 2b, one membrane may be formed from these materials, while the other membrane is formed from PLGA.

[0091] Furthermore, in the bag body 1 and its manufacturing method disclosed herein, the L / G ratio of each of the first membrane 2a and the second membrane 2b may be in the range of 45 / 55 to 88 / 12, and the proportion of lactic acid in the L / G ratio of the first membrane 2a may be greater than the proportion of lactic acid in the L / G ratio of the second membrane 2b. Alternatively, the L / G ratio of the first membrane 2a may be in the range of 55 / 45 to 88 / 12, and the L / G ratio of the second membrane 2b may be in the range of 45 / 55 to 55 / 45. In this way, the biodegradation time (bioabsorption performance) of each membrane can be adjusted.

[0092] Furthermore, in the bag body 1 and the manufacturing method of the bag body 1 disclosed herein, the intrinsic viscosity of the lactic acid-glycolic acid copolymer can also be in the range of 0.6 dL / g to 1.4 dL / g. From the perspective of the necessary strength and hardness of the bag body 1, the intrinsic viscosity of PLGA is preferably within this range.

[0093] Alternatively, in the bag body 1 and the method for manufacturing the bag body 1 disclosed herein, the first film 2a and the second film 2b can be formed by spreading a material containing biodegradable components on a flat surface and then drying it. In this way, the bag body 1 can be easily manufactured.

[0094] In the disclosed bag 1' and its manufacturing method, the bag 1' is used for bone growth and includes a first membrane 2a and a second membrane 2b made of a biodegradable component. The edges of the first membrane 2a and the second membrane 2b are bonded together. The biodegradation time of the first membrane 2a is greater than that of the second membrane 2b. When the biodegradation times of the first membrane 2a and the second membrane 2b are different, the first membrane 2a and the second membrane 2b are visually or tactilely distinguishable from each other. In this way, since the edges (around the perimeter) of the bag 1' are sealed, the surgeon can process the bag 1' into a desired shape according to the surgery.

[0095] It should be noted that the manufacturing method of bag 1, 1' and bag 1 disclosed herein is not limited to the above-described methods and combinations, and various modifications can be implemented.

[0096] For example, the bags 1 and 1' may also contain other biological absorbent membranes in addition to the first membrane 2a and the second membrane 2b, and the materials of the other biological absorbent membranes may be the same as or different from the first membrane 2a and the second membrane 2b. For example, multiple absorbent membranes may be provided on one surface of the bag 1.

[0097] Furthermore, the shapes of the bags 1 and 1' can be not only sheet-like, but can also be shaped into various forms such as cylindrical, conical, spherical, cuboid, or tooth-shaped, depending on the tooth arrangement and the defects in the alveolar bone. The surfaces of the bags 1 and 1' can also have a layered structure.

[0098] Furthermore, in the bag body 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 can overlap and their edges can be bonded together (closing the bag body 1 in four directions), forming the opening 3 in either the first film 2a or the second film 2b. The opening 3 can also be used to make the first film 2a and the second film 2b visually or tactilely different. The number of openings 3 is not limited to one. Multiple openings 3 can be provided between or on each of the overlapping and bonded first film 2a and second film 2b.

[0099]

Example

[0100] The present disclosure is illustrated in more detail below using examples (experimental examples). Specifically, the following materials are used to manufacture... Figure 3 The bag 1 shown in (A) is used to verify the decomposability (i.e., in vivo degradation time and in vivo absorption performance) of each bag 1 (example). It should be noted that since the first membrane 2a and the second membrane 2b are made of the same composition, they are simply referred to as films or membranes in the following description.

[0101] (1) Experimental reagents

[0102] ·PLGA solution:

[0103] PLGA:

[0104] Ashland Corporation DLG8513ELotNo. 0002633992

[0105] Ashland Corporation DLG8509ALotNo. 0002480336

[0106] Ashland Corporation DLG8507ALotNo. 0002591847

[0107] Ashland Corporation DLG7507ALotNo. 0002510702

[0108] Mitsui Chemicals PLGA5-50

[0109] Dichloromethane (solvent): Manufactured by Fujifilm and Kojun Pharmaceutical Co., Ltd. Lot No. DLR5072

[0110] ·additive

[0111] Tween 80: Manufactured by Kanto Chemical Co., Ltd. Lot No. 104K1486

[0112] Edible Yellow No. 5: Lot No. R10401M1 manufactured by Osaka Food Coloring Co., Ltd. (used as a coloring agent for species identification in Example 5)

[0113] Riboflavin: Manufactured by Tokyo Chemical Industry Co., Ltd., Lot No. CJCTO-YT (used as a colorant for species identification in Example 6)

[0114] ·Dissolution solution:

[0115] Polyvinyl alcohol EG-05P: Manufactured by Nippon Synthetic Chemicals Co., Ltd. Lot No. 68N69

[0116] Tween 80: Manufactured by Kanto Chemical Co., Ltd. Lot No. 104K1486

[0117] Lactic acid: Manufactured by Kanto Chemical Co., Ltd. Lot No. 010B2087

[0118] Distilled water: Kyoei Pharmaceutical Co., Ltd., Lot No. 18D671, Lot No. 18D685

[0119] • Cleaning water:

[0120] Distilled water: Kyoei Pharmaceutical Co., Ltd., Lot No. 18D671, Lot No. 18D685

[0121] (2) Experimental setup

[0122] Thermometer: Mitutoyo M110-25 (Mitutoyo Corporation)

[0123] Sealant: Fuji Pulse Manufacturing POLYSEALERP-200

[0124] Benchtop Tensile and Compression Testing Machine: A&D ForceTester MCT-1150

[0125] (3) Experimental methods

[0126] • Bag construction:

[0127] Weigh the specified amounts of PLGA and Tween 80, dissolve them in dichloromethane in a sealed container, and let stand overnight. Note that each solution volume is set to 25 mL (32 g), the PLGA solution concentration is 2.5% w / w (0.8 g / 32 g), and the dosage is 0.5% w / w (0.16 g / 32 g, 20% relative to PLGA). The resulting solution is then cast into a stainless steel container. For the stainless steel container dimensions, a 105 × 135 mm container is used for a film thickness of 0.05 mm, and a 130 × 195 mm container is used for a film thickness of 0.03 mm. After standing (naturally drying) for at least one night, the film is peeled off, its condition is visually confirmed, and the film thickness is measured.

[0128] For each embodiment, a bag body 1 (25mm × 40mm) and a test piece (15mm × 60mm) were made from the peeled film. The tensile strength (tensile speed: 300mm / min) was determined using the test piece.

[0129] • Confirmation during decomposition (dissolution test):

[0130] Accurately weigh one bag into a 125 mL glass container, add 100 mL of dissolution solution heated to 37 ± 0.5 °C (2% PVA aqueous solution: 20% Tween 80 aqueous solution: 0.9% lactic acid aqueous solution / water = 40:1:40 / 200), cover with a lid fitted with a 2 mm thick diaphragm, fix all containers and place them in a water bath at 37 ± 0.5 °C. In the dissolution test, the water bath temperature is increased from 37 °C to 61 °C at a rate of 0.5 °C / hour. After 3 hours (38.5 °C), 28 hours (51.0 °C), and 48 hours (61.0 °C) of heating, the containers are removed and the solution is filtered. The removed membrane is washed with water and dried. The weight is measured and the weight retention rate is confirmed.

[0131] In Examples 1 to 4, the above method was repeated four times, with each sampling time (after 3, 28, and 48 hours) assumed to be 1 to 12 months after placement in the organism, and confirmation was performed at 9 time points (1, 3, 4, 6, 7, 8, 9, 10, and 12 months).

[0132] It should be noted that in Examples 5 and 6, the above method was repeated twice, with the sampling time for each instance being assumed to be 1 to 6 months after placement in the organism, and confirmation was performed at 6 time points (1, 2, 3, 4, 5, and 6 months).

[0133] (4) Decompose and confirm the test results

[0134] [Example 1: DLG8513E membrane (0.05 mm) (L / G ratio: nominal 85 / 15, specification 82.0 / 18.0~88.0 / 12.0, test value 84.5 / 15.5 (determined by 1H-NMR spectroscopy according to USP<761>), IV: 1.30 dL / g, tensile strength: 13.62 N)]

[0135] Weight retention decreased in the third month and then stabilized. The product was initially round, becoming transparent and brittle upon drying in the ninth month.

[0136] [Example 2: DLG8509A membrane (0.05 mm) (L / G ratio: nominal 85 / 15, specification 82.0 / 18.0~88.0 / 12.0, test value 84.5 / 15.5 (determined by 1H-NMR spectroscopy according to USP<761>), IV: 0.99 dL / g, tensile strength: 12.72 N)]

[0137] Weight retention decreased in the third month and then stabilized. Moisture ingested at 6 and 8 months was difficult to dry, exceeding that of the previous month. Appearance began to change around the time of drying in the sixth month, becoming brittle and prone to cracking during drying.

[0138] [Example 3: DLG8507A membrane (0.05 mm) (L / G ratio: nominal 85 / 15, specification 82.0 / 18.0~88.0 / 12.0, test value 84.6 / 15.4 (determined by 1H-NMR spectroscopy according to USP<761>), IV: 0.64 dL / g, tensile strength: 8.36 N)]

[0139] Weight retention decreased significantly in the third month and then gradually decreased. The appearance became transparent after drying in the fourth month, brittle during drying in the sixth month, and brittle before drying in the seventh month.

[0140] [Example 4: DLG7507A membrane (0.05 mm) (L / G ratio: nominal 75 / 25, specification 72.0 / 28.0~78.0 / 22.0, test value 74.9 / 25.1 (determined by 1H-NMR spectroscopy according to USP<761>), IV: 0.68 dL / g, tensile strength: 8.38 N)]

[0141] Weight retention decreased significantly in the third month and then gradually decreased. The appearance became transparent after drying in the fourth month, became brittle during drying in the fourth month, and was already brittle before drying in the seventh month.

[0142] [Example 5: PLGA5-50 colored film (0.05mm) (L / G ratio: nominal value 50 / 50, specification 45.0 / 55.0~55.0 / 45.0, test value 50.5 / 49.5 (measured by 1H-NMR spectroscopy), IV: 0.50 dL / g, tensile strength: 4.78N)]

[0143] Weight retention decreased in the 2nd to 3rd month, remained relatively stable in the 3rd to 5th month, and decreased again in the 5th to 6th month. The appearance was round before the 2nd month, becoming transparent but retaining its shape during drying. It became brittle during drying in the 3rd month. It should be noted that even when pigments were mixed during film production, no noticeable difference in physical properties was observed.

[0144] [Example 6: DLG7507A colored film (0.03mm) (tensile strength: 7.22N)]

[0145] Weight retention rate decreased significantly in the second month and then gradually decreased. The appearance became round from the second month onwards, becoming transparent while retaining its shape during drying. It became very brittle in the sixth month. Compared to a film with a thickness of 0.05 mm (Example 4), no significant difference could be observed in weight retention rate or appearance. Therefore, it can be concluded that if the film thickness is in the range of 0.03 to 0.05 mm, there is no problem with strength, and bag body 1 can be manufactured.

[0146] (5) Summary

[0147] During the maintenance period, the weight did not show significant changes (differences). In terms of appearance and brittleness, the relationship with the L / G ratio showed the following tendencies.

[0148] If the L / G ratio is 85 / 15, it will become brittle after 6 months.

[0149] If the L / G ratio is 75 / 25, it will become brittle after 4 months.

[0150] If the L / G ratio is 50 / 50, it will become brittle in less than 4 months.

[0151] From the above insights, it can be seen that changing the L / G ratio of the first membrane 2a and the second membrane 2b constituting the bag 1 results in different biodegradability (biodegradation time and bioabsorption performance). Furthermore, when the L / G ratio of the first membrane 2a is in the range of 55 / 45 to 88 / 12, and the L / G ratio of the second membrane 2b is 45 / 55 to 55 / 45, the biodegradation time for each is approximately 4 to 9 months and 1 to 4 months, respectively.

Claims

1. A bone growth bag, used for bone growth, characterized in that, It includes a first membrane and a second membrane made of biodegradable components. An opening is provided between the overlapping and bonded first film and the second film. The in vivo degradation time of the first membrane is longer than the in vivo degradation time of the second membrane. When the degradation times of the first membrane and the second membrane in vivo are different, the first membrane and the second membrane are visually or tactilely identifiable as being different from each other.

2. The bag body according to claim 1, characterized in that, The biodegradable component includes collagen.

3. The bag body according to claim 1, characterized in that, The biodegradable component comprises a lactic acid (L)-glycolic acid (G) copolymer.

4. The bag body according to claim 3, characterized in that, The L / G ratio of the first membrane and the second membrane are each in the range of 45 / 55 to 88 / 12. The proportion of lactic acid in the L / G ratio of the first membrane is greater than the proportion of lactic acid in the L / G ratio of the second membrane.

5. The bag body according to claim 3 or 4, characterized in that, The L / G ratio of the first membrane is in the range of 55 / 45 to 88 / 12.

6. The bag body according to claim 3 or 4, characterized in that, The L / G ratio of the second membrane is in the range of 45 / 55 to 55 / 45.

7. The bag body according to claim 3 or 4, characterized in that, 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 bag body according to any one of claims 1 to 4, characterized in that, It contains substitute bones.

9. A bone growth bag, used for bone growth, characterized in that, It includes a first membrane and a second membrane made of biodegradable components. The edges of the first membrane and the second membrane are bonded together. The in vivo degradation time of the first membrane is longer than the in vivo degradation time of the second membrane. When the degradation times of the first membrane and the second membrane in vivo are different, the first membrane and the second membrane are visually or tactilely identifiable as being different from each other.

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