Bioabsorbable particles

Abstract

To provide bioabsorbable particles for an injectable liquid to be filled in an injector equipped with an injection needle and a syringe, the bioabsorbable particles being capable of preventing the injectable liquid from a local site when using the injector, which can inject the injectable liquid, and being produced easily and efficiently, when administering the injectable solution to the local site using the injector equipped with the injection needle and the syringe.SOLUTION: Provided are bioabsorbable particles for an injectable liquid to be filled in an injector equipped with an injection needle and a syringe. The bioabsorbable particles have D50 of 10 μm or more and 140 μm or less, D95 of 300 μm or less, and an average circularity of 0.5 or more and less than 0.8.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present disclosure relates to bioabsorbable particles. [Background technology]

[0002] A method is known in which a drug suspension in which a drug is suspended in saline or the like, or a cell suspension in which cells for transplantation are suspended in saline or the like, is administered to a local site using an injector equipped with a needle and a syringe (Non-Patent Document 1). It is also known that bioabsorbable particles such as gelatin particles are used as an adjuvant in the above method (Patent Document 1). Patent Document 2 discloses gelatin particles (bioresorbable particles) that are solid spherical and have a circularity of 0.8 or more. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Patent Publication No. 2021-19719 [Patent Document 2] Japanese Patent Application Laid-Open No. 2014-58466 [Non-patent literature]

[0004] [Non-Patent Document 1] Laurila JP et al., “Human embryonic stem cell-derived mesenchymal stromal cell transplantation in a rat hind limb injury model”, Cytotherapy, 11, 726-737, 2009 Summary of the Invention [Problem to be solved by the invention]

[0005] Conventionally, when a drug suspension in which a drug is suspended in saline or the like, or a cell suspension in which cells for transplantation are suspended in saline or the like, is administered as an injection to a local site using a syringe, leakage of the injection from the local site has sometimes occurred due to backflow of the injection. In particular, when a suspension containing saline is administered to a local site using a syringe, backflow tends to occur easily, and therefore leakage of the injection from the local site has tended to occur easily.

[0006] Therefore, an object of the present disclosure is to provide bioabsorbable particles for an injection solution to be filled into a syringe equipped with an injection needle and a syringe, which can be easily and efficiently manufactured and can suppress leakage of the injection solution from the local site when an injection solution capable of injecting the injection solution is administered to the local site using a syringe equipped with an injection needle and a syringe. [Means for solving the problem]

[0007] The bioabsorbable particles according to one aspect of the present disclosure include: Bioabsorbable particles for an injection solution to be filled into a syringe having an injection needle and a syringe, The D50 of the bioabsorbable particles is 10 μm or more and 140 μm or less, The bioabsorbable particles have a D95 of 300 μm or less, The average circularity of the bioabsorbable particles is 0.5 or more and less than 0.8. [Effects of the Invention]

[0008] According to the present disclosure, when an injection liquid is administered to a local site using a syringe equipped with an injection needle and a syringe, leakage of the injection liquid from the local site can be suppressed when a syringe capable of injecting the injection liquid is used, and bioabsorbable particles for an injection liquid to be filled into a syringe equipped with an injection needle and a syringe can be provided which can be manufactured simply and efficiently. DETAILED DESCRIPTION OF THE INVENTION

[0009] [Description of the embodiments of the present disclosure] First, embodiments of the present disclosure will be listed and described. [1] The bioabsorbable particles according to one embodiment of the present disclosure include: Bioabsorbable particles for an injection solution to be filled into a syringe having an injection needle and a syringe, The D50 of the bioabsorbable particles is 10 μm or more and 140 μm or less, The bioabsorbable particles have a D95 of 300 μm or less, The average circularity of the bioabsorbable particles is 0.5 or more and less than 0.8.

[0010] The bioabsorbable particles of the present disclosure can be easily and efficiently manufactured, and when an injection solution containing the bioabsorbable particles is administered to a local site using a syringe equipped with an injection needle and a syringe, leakage of the injection solution from the local site can be suppressed when a syringe capable of injecting the injection solution is used.

[0011] [2] The injection needle is a 21G injection needle, a 22G injection needle, a 23G injection needle, a 24G injection needle, a 25G injection needle, or a 26G injection needle; The D50 of the bioabsorbable particles is 10 μm or more and 140 μm or less, The D95 of the bioabsorbable particles is 20 μm or more and 290 μm or less, The bioabsorbable particles preferably have a D10 of 55 μm or less. By using such bioabsorbable particles in an injection solution, leakage of the injection solution from a local site can be further suppressed when the injection solution is administered to a local site in an injector equipped with a 21G, 22G, 23G, 24G, 25G, or 26G injection needle and a syringe.

[0012] [3] The injection needle is either a 27G injection needle, a 28G injection needle, or a 29G injection needle; The D50 of the bioabsorbable particles is 10 μm or more and 60 μm or less, The D95 of the bioabsorbable particles is 20 μm or more and 120 μm or less, The bioabsorbable particles preferably have a D10 of 30 μm or less. By using such bioabsorbable particles in an injection solution, leakage of the injection solution from a local site can be further suppressed when the injection solution is administered to a local site using a syringe equipped with a 27G, 28G, or 29G injection needle and a syringe.

[0013] [4] The injection needle is either a 30G injection needle, a 31G injection needle, or a 32G injection needle, The D50 of the bioabsorbable particles is 10 μm or more and 55 μm or less, The D95 of the bioabsorbable particles is 20 μm or more and 80 μm or less, The bioabsorbable particles preferably have a D10 of 20 μm or less. By using such bioabsorbable particles in an injection solution, leakage of the injection solution from a local site can be further suppressed when the injection solution is administered to a local site in an injector equipped with a 30G injection needle, a 31G injection needle, or a 32G injection needle and a syringe.

[0014] [5] In a first liquid containing the bioabsorbable particles in water at a ratio of 5 w / v%, It is preferable that the retention rate of the first liquid is 60% or more when the first liquid is stirred at 300 rpm for 1 minute and then allowed to stand for 1 minute. By using such bioabsorbable particles in an injection solution, leakage of the injection solution from a local site can be further suppressed when the injection solution filled in an injector equipped with an injection needle and a syringe is administered to the local site.

[0015] [6] The bulk density of the bioabsorbable particles is 0.3 g / cm 3 More than 0.7g / cm 3 This makes it difficult for the bioabsorbable particles to aggregate and allows them to remain in the injection solution for a certain period of time or longer, thereby achieving a stable effect of suppressing leakage.

[0016] [7] The bioabsorbable particles are preferably made of at least one material selected from the group consisting of gelatin, alginic acid, and calcium alginate, which can suppress leakage and be absorbed by the body with little toxicity, thereby achieving a leakage suppression effect more safely.

[0017] [8] The gelatin is preferably a gelatin hydrolysate, which can more safely suppress leakage.

[0018] [Details of the embodiments of the present disclosure] An embodiment of the present disclosure (hereinafter referred to as "this embodiment") will be described below. However, this embodiment is not limited to this. In this specification, an expression in the form "A to B" means the upper and lower limits of a range (i.e., A or more and B or less), and when no unit is specified for A and a unit is specified only for B, the unit of A and the unit of B are the same.

[0019] [Embodiment 1: Bioabsorbable particles] The bioabsorbable particles according to this embodiment are Bioabsorbable particles for an injection solution to be filled into a syringe having an injection needle and a syringe, The D50 of the bioabsorbable particles is 10 μm or more and 140 μm or less, The bioabsorbable particles have a D95 of 300 μm or less, The average circularity of the bioabsorbable particles is 0.5 or more and less than 0.8.

[0020] The bioabsorbable particles of the present disclosure can suppress leakage of an injection solution from a local site when the injection solution is administered to the local site using a syringe capable of injecting the injection solution, and can be produced simply and efficiently. The reasons for this are presumed to be as follows.

[0021] (a) The D50 of the bioabsorbable particles is 10 μm or more and 140 μm or less, and the D95 of the bioabsorbable particles is 300 μm or less. This makes it difficult for the bioabsorbable particles to clog the injection needle due to the relationship between the diameter of the injection needle and the particle size distribution of the bioabsorbable particles. Furthermore, when the injection needle is removed after injection, the particles dispersed in the injection solution quickly move to the puncture site, thereby preventing leakage of the injection solution from the local site when the injection solution is administered to the local site.

[0022] (b) As described in (a) above, the D50 of the bioabsorbable particles is 10 μm or more and 140 μm or less, and the D95 of the bioabsorbable particles is 300 μm or less. When bioabsorbable particles having the above D50 and D95 ​​are used as described in (a) above, the bioabsorbable particles are less likely to clog injection needles, and when an injection solution is administered to a localized site, leakage of the injection solution from the localized site can be suppressed. However, in the production of bioabsorbable particles, it has been common to impart a high degree of circularity close to a perfect sphere in order to provide high shape retention against swelling caused by absorption of an impregnating solution such as physiological saline. Therefore, to obtain such bioabsorbable particles, complicated processes using granulation methods such as W / O dispersion methods have been required.

[0023] However, the average circularity of the bioabsorbable particles of this embodiment is 0.5 or more and less than 0.8. The production of such bioabsorbable particles does not require the above-mentioned granulation method, and therefore such bioabsorbable particles can be produced simply and efficiently.

[0024] In addition, when administering an injection to a local site, in order to prevent leakage of the injection from the local site, it is important to set the "particle size distribution" of the bioabsorbable particles within a desired range, and even if the "average circularity" of the bioabsorbable particles is 0.5 or more and less than 0.8, this does not impair the effect of preventing leakage of the injection from the local site. The reason for this is presumably because particle size distribution is important for the effect of preventing leakage, and particle shapes with an average circularity of 0.5 or more and less than 0.8 do not significantly impair the accuracy of particle size distribution measurement.

[0025] In other words, when an injection liquid is administered to a local site using a syringe equipped with an injection needle and a syringe, the bioabsorbable particles of the present disclosure can suppress leakage of the injection liquid from the local site when a syringe capable of injecting the injection liquid is used, and can be manufactured simply and efficiently.

[0026] ≪Syringe≫ The syringe according to this embodiment (hereinafter, sometimes simply referred to as "syringe") includes an injection needle and a syringe. The syringe according to the present disclosure may further include a catheter or the like that connects the injection needle and the syringe.

[0027] <syringe needle> The injection needle of this embodiment may be any conventionally known injection needle of this type, for example, preferably one selected from the group consisting of 21G injection needles, 22G injection needles, 23G injection needles, 24G injection needles, 25G injection needles, 26G injection needles, 27G injection needles, 28G injection needles, 29G injection needles, 30G injection needles, 31G injection needles, and 32G injection needles.

[0028] The 21G, 22G, 23G, 24G, 25G, and 26G injection needles are preferably used for transplantation of suspended cells, local administration of cell therapy drugs, local administration of viral preparations, etc. The 27G, 28G, and 29G injection needles are preferably used for local administration of antibody drugs, etc. The 30G, 31G, and 32G injection needles are preferably used for ophthalmic treatments such as intravitreal injections. However, these descriptions do not limit the uses of each injection needle.

[0029] The outer diameter of the 21G syringe needle is 0.81 mm (tolerance: ±0.02 mm), and the inner diameter of the 21G syringe needle is 0.51 mm (tolerance: ±0.03 mm).

[0030] The outer diameter of the 22G injection needle is 0.72 mm (tolerance: ±0.02 mm), and the inner diameter of the 22G injection needle is 0.41 mm (tolerance: ±0.03 mm).

[0031] The outer diameter of the 23G injection needle is 0.64 mm (tolerance: ±0.02 mm), and the inner diameter of the 23G injection needle is 0.35 mm (tolerance: ±0.03 mm).

[0032] The outer diameter of the 24G injection needle is 0.56 mm (tolerance: ±0.02 mm), and the inner diameter of the 24G injection needle is 0.30 mm (tolerance: ±0.03 mm).

[0033] The outer diameter of the 25G injection needle is 0.51 mm (tolerance: ±0.02 mm), and the inner diameter of the 25G injection needle is 0.25 mm (tolerance: ±0.03 mm).

[0034] The outer diameter of the 26G injection needle is 0.46 mm (tolerance: ±0.02 mm), and the inner diameter of the 26G injection needle is 0.26 mm (tolerance: ±0.03 mm).

[0035] The outer diameter of the 27G injection needle is 0.41 mm (tolerance: ±0.02 mm), and the inner diameter of the 27G injection needle is 0.22 mm (tolerance: ±0.03 mm).

[0036] The outer diameter of the 28G injection needle is 0.36 mm (tolerance: ±0.02 mm), and the inner diameter of the 28G injection needle is 0.17 mm (tolerance: ±0.03 mm).

[0037] The outer diameter of the 29G injection needle is 0.33 mm (tolerance: ±0.02 mm), and the inner diameter of the 29G injection needle is 0.15 mm (tolerance: ±0.03 mm).

[0038] The outer diameter of the 30G injection needle is 0.31 mm (tolerance: ±0.02 mm), and the inner diameter of the 30G injection needle is 0.12 mm (tolerance: ±0.03 mm).

[0039] The outer diameter of the 31G injection needle is 0.27 mm (tolerance: ±0.02 mm), and the inner diameter of the 31G injection needle is 0.10 mm (tolerance: ±0.03 mm).

[0040] The outer diameter of the 32G injection needle is 0.23 mm (tolerance: ±0.02 mm), and the inner diameter of the 32G injection needle is 0.08 mm (tolerance: ±0.03 mm).

[0041] <Syringe> The syringe of this embodiment may be any conventionally known syringe of this type, and may include, for example, a barrel, a luer lock, a finger grip, a plunger rod, a piston, a tip cap, and the like.

[0042] <Bioabsorbable particles> In this specification, the term "bioabsorbable particles" refers to particles that, after being administered into a living body, are decomposed and absorbed within a certain period of time without exhibiting toxicity.

[0043] The bioabsorbable particles have a D50 of 10 μm or more and a D95 of 300 μm or less. This makes it difficult for the bioabsorbable particles to clog the injection needle due to the relationship between the needle diameter and the particle size distribution of the bioabsorbable particles. Furthermore, when the injection needle is removed after injection, the particles dispersed in the injection solution quickly move to the puncture site, thereby preventing leakage of the injection solution from the local site when the injection solution is administered to the local site.

[0044] Here, the D50 of the bioabsorbable particles is determined by measuring the cumulative distribution of the bioabsorbable particles using a laser diffraction / scattering particle size distribution analyzer (Microtrac T3200II, Microtrac Bell Co., Ltd.) (measurement time: 10 seconds) and reading the value of the cumulative 50% diameter.

[0045] Here, D95 is determined by measuring the cumulative distribution of the bioabsorbable particles using a laser diffraction / scattering particle size distribution analyzer (Microtrac T3200II, Microtrac Bell Co., Ltd.) (measurement time: 10 seconds) and reading the cumulative 95% diameter.

[0046] When the bioabsorbable particles are bioabsorbable particles for injection to be filled into a syringe equipped with a 21G needle, a 22G needle, a 23G needle, a 24G needle, a 25G needle, or a 26G needle and a syringe, it is preferable that the D50 of the bioabsorbable particles is 10 μm or more and 140 μm or less, the D95 of the bioabsorbable particles is 20 μm or more and 290 μm or less, and the D10 of the bioabsorbable particles is 55 μm or less. This prevents injection needles having the inner diameter of a 21G injection needle, a 22G injection needle, a 23G injection needle, a 24G injection needle, a 25G injection needle, or a 26G injection needle from being blocked by the bioabsorbable particles, and when the injection needle is removed after injection, the particles dispersed in the injection solution tend to move quickly to the puncture site. Therefore, when an injection solution filled in a syringe equipped with a 21G injection needle, a 22G injection needle, a 23G injection needle, a 24G injection needle, a 25G injection needle, or a 26G injection needle and a syringe is administered to a local site, leakage of the injection solution from the local site can be further suppressed.

[0047] Here, the D10 of the bioabsorbable particles is determined by measuring the cumulative distribution of the bioabsorbable particles using a laser diffraction / scattering particle size distribution analyzer (Microtrac T3200II, Microtrac Bell Co., Ltd.) (measurement time: 10 seconds) and reading the cumulative 10% diameter value.

[0048] Furthermore, when the bioabsorbable particles are for injection filled into a syringe equipped with a 21G, 22G, 23G, 24G, 25G, or 26G needle and a syringe, the lower limit of the D50 is preferably 20 μm or more, more preferably 25 μm or more. Furthermore, when the bioabsorbable particles are for injection filled into a syringe equipped with a 21G, 22G, 23G, 24G, 25G, or 26G needle and a syringe, the upper limit of the D50 is preferably 130 μm or less, more preferably 120 μm or less. Furthermore, when the bioabsorbable particles are bioabsorbable particles for injection to be filled into a syringe equipped with a 21G injection needle, a 22G injection needle, a 23G injection needle, a 24G injection needle, a 25G injection needle, or a 26G injection needle and a syringe, the D50 is preferably 20 μm or more and 130 μm or less, and more preferably 25 μm or more and 120 μm or less.

[0049] Furthermore, when the bioabsorbable particles are for injection filled into a syringe equipped with a 21G, 22G, 23G, 24G, 25G, or 26G needle and a syringe, the lower limit of the D95 is preferably 30 μm or more, more preferably 40 μm or more. Furthermore, when the bioabsorbable particles are for injection filled into a syringe equipped with a 21G, 22G, 23G, 24G, 25G, or 26G needle and a syringe, the upper limit of the D95 is preferably 280 μm or less, more preferably 270 μm or less. Furthermore, when the bioabsorbable particles are bioabsorbable particles for injection to be filled into a syringe equipped with a 21G injection needle, a 22G injection needle, a 23G injection needle, a 24G injection needle, a 25G injection needle, or a 26G injection needle and a syringe, the D95 is preferably 30 μm or more and 280 μm or less, and more preferably 40 μm or more and 270 μm or less.

[0050] Furthermore, when the bioabsorbable particles are for injection filled into a syringe equipped with a 21G, 22G, 23G, 24G, 25G, or 26G needle and a syringe, the lower limit of D10 is preferably 5 μm or more, more preferably 10 μm or more. Furthermore, when the bioabsorbable particles are for injection filled into a syringe equipped with a 21G, 22G, 23G, 24G, 25G, or 26G needle and a syringe, the upper limit of D10 is preferably 50 μm or less, more preferably 45 μm or less. Furthermore, when the bioabsorbable particles are bioabsorbable particles for injection to be filled into a syringe equipped with a 21G injection needle, a 22G injection needle, a 23G injection needle, a 24G injection needle, a 25G injection needle, or a 26G injection needle and a syringe, the D10 is preferably 5 μm or more and 50 μm or less, and more preferably 10 μm or more and 45 μm or less.

[0051] When the bioabsorbable particles are bioabsorbable particles for an injection solution filled in a syringe equipped with a 27G, 28G, or 29G injection needle and a syringe, it is preferable that the D50 of the bioabsorbable particles is 10 μm or more and 60 μm or less, the D95 of the bioabsorbable particles is 20 μm or more and 120 μm or less, and the D10 of the bioabsorbable particles is 30 μm or less. This prevents an injection needle having an inner diameter of a 27G, 28G, or 29G injection needle from being clogged by the bioabsorbable particles, and when the injection needle is removed after injection, the particles dispersed in the injection solution are likely to move quickly to the puncture site. Therefore, when an injection solution filled in a syringe equipped with a 27G, 28G, or 29G injection needle and a syringe is administered to a local site, leakage of the injection solution from the local site can be further suppressed.

[0052] Furthermore, when the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 27G, 28G, or 29G needle and a syringe, the lower limit of the D50 is preferably 20 μm or more, and more preferably 25 μm or more. When the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 27G, 28G, or 29G needle and a syringe, the upper limit of the D50 is preferably 50 μm or less, and more preferably 45 μm or less. When the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 27G, 28G, or 29G needle and a syringe, the D50 is preferably 20 μm or more and 50 μm or less, and more preferably 25 μm or more and 45 μm or less.

[0053] Furthermore, when the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 27G, 28G, or 29G needle and a syringe, the lower limit of the D95 is preferably 30 μm or more, and more preferably 40 μm or more. When the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 27G, 28G, or 29G needle and a syringe, the upper limit of the D95 is preferably 110 μm or less, and more preferably 100 μm or less. When the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 27G, 28G, or 29G needle and a syringe, the D95 is preferably 30 μm or more and 110 μm or less, and more preferably 40 μm or more and 100 μm or less.

[0054] Furthermore, when the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 27G, 28G, or 29G needle and a syringe, the lower limit of D10 is preferably 5 μm or more, and more preferably 10 μm or more. When the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 27G, 28G, or 29G needle and a syringe, the upper limit of D10 is preferably 28 μm or less, and more preferably 26 μm or less. When the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 27G, 28G, or 29G needle and a syringe, the D10 is preferably 5 μm or more and 28 μm or less, and more preferably 10 μm or more and 26 μm or less.

[0055] When the bioabsorbable particles are bioabsorbable particles for an injection solution filled in a syringe equipped with a 30G, 31G, or 32G injection needle and a syringe, it is preferable that the D50 of the bioabsorbable particles is 10 μm or more and 55 μm or less, the D95 of the bioabsorbable particles is 20 μm or more and 80 μm or less, and the D10 of the bioabsorbable particles is 20 μm or less. This prevents an injection needle having an inner diameter of a 30G, 31G, or 32G injection needle from being clogged by the bioabsorbable particles, and when the injection needle is removed after injection, the particles dispersed in the injection solution are likely to move quickly to the puncture site. Therefore, when an injection solution filled in a syringe equipped with a 30G, 31G, or 32G injection needle and a syringe is administered to a local site, leakage of the injection solution from the local site can be further suppressed.

[0056] Furthermore, when the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 30G, 31G, or 32G needle and a syringe, the lower limit of the D50 is preferably 20 μm or more, and more preferably 25 μm or more. When the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 30G, 31G, or 32G needle and a syringe, the upper limit of the D50 is preferably 50 μm or less, and more preferably 45 μm or less. When the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 30G, 31G, or 32G needle and a syringe, the D50 is preferably 20 μm or more and 50 μm or less, and more preferably 25 μm or more and 45 μm or less.

[0057] Furthermore, when the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 30G, 31G, or 32G needle and a syringe, the lower limit of the D95 is preferably 30 μm or more, and more preferably 40 μm or more. When the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 30G, 31G, or 32G needle and a syringe, the upper limit of the D95 is preferably 70 μm or less, and more preferably 60 μm or less. When the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 30G, 31G, or 32G needle and a syringe, the D95 is preferably 30 μm or more and 70 μm or less, and more preferably 40 μm or more and 60 μm or less.

[0058] Furthermore, when the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 30G, 31G, or 32G needle and a syringe, the lower limit of D10 is preferably 5 μm or more, and more preferably 8 μm or more. When the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 30G, 31G, or 32G needle and a syringe, the upper limit of D10 is preferably 18 μm or less, and more preferably 16 μm or less. When the bioabsorbable particles are for use in an injection solution to be filled into a syringe equipped with a 30G, 31G, or 32G needle and a syringe, the D10 is preferably 5 μm or more and 18 μm or less, and more preferably 8 μm or more and 16 μm or less.

[0059] <Average circularity> The average circularity of the bioabsorbable particles is 0.5 or more and less than 0.8. Here, "circularity" refers to the ratio of the particle area (S) projected two-dimensionally to the particle perimeter (L), expressed as 4πS / L. 2 This can be obtained by the formula: As a result, the production of such bioabsorbable particles does not require complicated steps using granulation methods such as W / O dispersion methods, and therefore such bioabsorbable particles can be produced simply and efficiently. Furthermore, the lower limit of the average circularity of the bioabsorbable particles is preferably 0.55 or more, and more preferably 0.59 or more. Furthermore, the upper limit of the average circularity of the bioabsorbable particles is preferably 0.78 or less, and more preferably 0.75 or less. Furthermore, the average circularity of the bioabsorbable particles is preferably 0.55 or more and 0.78 or less, and more preferably 0.59 or more and 0.75 or less.

[0060] The average circularity is determined by the following method. First, a scanning electron microscope (Hitachi High-Technologies Corporation) is used to project any bioabsorbable particle to obtain a projected image. Next, the particle area (S) and perimeter (L) are obtained for the projected image using the image analysis software "Image J." Then, 4πS / L2 The circularity of any bioabsorbable particle can be obtained by the following formula: The average circularity can be determined by calculating the average of the circularities of any five bioabsorbable particles.

[0061] <Retention rate> A first liquid containing 5 w / v% bioabsorbable particles in water preferably exhibits a retention rate of 60% or more when the first liquid is stirred at 300 rpm for 1 minute and then allowed to stand for 1 minute. Here, retention rate refers to the concentration of particles remaining in the liquid after standing for a certain period of time immediately after stirring, assuming that the particle concentration remaining in the liquid immediately after stirring is 100%. This allows the bioabsorbable particles to be delivered from the syringe to the local site along with the injection solution, and the particles quickly move to the puncture site after injection. This further prevents leakage of the injection solution from the local site when the injection solution filled in an injector equipped with a needle and syringe is administered to the local site. The lower limit of the retention rate is preferably 70% or more, more preferably 80% or more. The upper limit of the retention rate is preferably as close to 100% as possible. From a manufacturing standpoint, the upper limit of the retention rate can be 99% or less, 98% or less, or 97% or less. Furthermore, from the viewpoint of measurement error of "Absorbance 1" described later and "Absorbance 2" described later, the retention rate may occasionally exceed 100%, so the upper limit of the retention rate can be set to 101% or less.

[0062] The retention rate is determined by the following method. First, a first liquid containing 5 w / v% bioabsorbable particles is prepared. Next, the first liquid is stirred at 300 rpm for 1 minute, and immediately thereafter, 3.0 mL of the first liquid is poured into a plastic cell. The absorbance (wavelength: 600 nm) of the first liquid immediately after pouring is measured to obtain "absorbance 1." Next, the first liquid is allowed to stand in the plastic cell for 1 minute immediately after the measurement. The absorbance (wavelength: 600 nm) of the first liquid is measured immediately after the standing to obtain "absorbance 2." The retention rate can then be determined by substituting the values ​​into the formula: "(Retention rate when a first liquid containing 5 w / v% bioabsorbable particles in water is stirred at 300 rpm for 1 minute and then allowed to stand for 1 minute) = 100 × (absorbance 2) / (absorbance 1)."

[0063] <Bulk density> The bulk density of the bioabsorbable particles is 0.3 g / cm 3 More than 0.7g / cm 3 This makes it possible to prevent aggregation of the bioabsorbable particles and to suppress a decrease in the retention rate over time immediately after stirring. The lower limit of the bulk density is 0.4 g / cm. 3 It is preferable that the concentration is 0.45 g / cm or more. 3 The upper limit of the bulk density is preferably 0.68 g / cm. 3 Preferably, it is 0.65 g / cm or less. 3 It is more preferable that the bulk density is 0.4 g / cm or less. 3 More than 0.68g / cm 3 Preferably, it is 0.45 g / cm or less. 3 More than 0.65g / cm 3 More preferably, it is:

[0064] The bulk density is calculated by placing particles in a 100 mL measuring cylinder, measuring the weight, and multiplying the weight (g) by the volume (cm 3 ) can be calculated by dividing by

[0065] The bioabsorbable particles are preferably made of at least one selected from the group consisting of gelatin, alginic acid, and calcium alginate, which makes the bioabsorbable particles particularly safe and allows them to be decomposed in the body without exhibiting toxicity and to be easily absorbed safely.

[0066] <Gelatin> As used herein, "gelatin" refers to a polypeptide in which the triple helix structure of collagen has been unwound by heat denaturation, acid denaturation, or the like, as well as chemically modified forms and pharmaceutically acceptable salts thereof. Specifically, gelatin can be obtained by subjecting collagen derived from at least one species selected from the group consisting of Groups 1 to 6 below to conventionally known processes such as degreasing, decalcification, acid or alkali treatment, and hot water extraction. Gelatin may be a polypeptide obtained by fermentation using a microorganism, a recombinant polypeptide obtained by chemical synthesis or genetic engineering, or a synthetic polypeptide. Furthermore, "collagen" refers to a protein derived from the extracellular matrix of vertebrate skin, etc., classified into Groups 1 to 6 below. Collagen has a right-handed helical structure consisting of three peptide chains, and the amino acid residues that make up these peptide chains have a primary structure in which glycine residues are repeated every three residues (a so-called collagen-like sequence). Group 1: A group consisting of cow hides, skin, bones, cartilage, and tendons Group 2: Pig hide, skin, bone, cartilage and tendon Group 3: sheep hide, skin, bone, cartilage and tendons Group 4: Chicken skin, skin, bones, cartilage and tendons Group 5: Ostrich hide, skin, bone, cartilage and tendons Group 6: A group consisting of fish bones, skin and scales.

[0067] Here, the "chemically modified" polypeptide (gelatin) refers to a polypeptide in which the amino group, carboxyl group, hydroxyl group, or thiol group in the amino acid residues constituting gelatin has been chemically modified. Chemically modified gelatin can change its solubility in water, isoelectric point, etc. Specifically, hydroxyproline in gelatin The hydroxyl groups of the residues can be chemically modified, such as O-acetylation. The α-carboxyl groups of glycine residues in gelatin can be chemically modified, such as esterification, amidation, etc. The α-amino groups of proline residues in gelatin can be chemically modified, such as polypeptidylation, succinylation, maleylation, acetylation, deamination, benzoylation, alkylsulfonylation, arylsulfonylation, dinitrophenylation, trinitrophenylation, carbamylation, phenylcarbamylation, thiolation, etc.

[0068] Specific means and treatment conditions for chemically modifying gelatin can be those of conventionally known chemical modification methods. Regarding the chemical modification of the hydroxy group of a hydroxyproline residue, for example, O-acetylation can be carried out by reacting acetic anhydride in an aqueous or non-aqueous solvent. Regarding the chemical modification of the α-carboxyl group of a glycine residue, for example, esterification can be carried out by suspending the gelatin in methanol and then bubbling dry hydrogen chloride gas through it. Regarding the chemical modification of the α-carboxyl group of a glycine residue, amidation can be carried out by reacting a carbodiimide or the like.

[0069] Furthermore, the "derivatives" of the above polypeptides (gelatins) may include gelatin derivatives in which functional groups have been introduced into gelatin, copolymers of gelatin with lactic acid, glycolic acid, etc., copolymers of gelatin with polyethylene glycol, propylene glycol, etc. Examples of gelatin derivatives include derivatives in which functional groups such as guanidyl groups, thiol groups, amino groups, carboxyl groups, sulfate groups, phosphate groups, alkyl groups, acyl groups, phenyl groups, and benzyl groups have been introduced into gelatin.

[0070] The term "pharmaceutically acceptable salt" of the polypeptide (gelatin) refers to a salt that is pharmaceutically acceptable and has the desired activity (e.g., gelling ability) of the original polypeptide (gelatin). Examples of pharmaceutically acceptable salts include inorganic acid salts such as hydrochloride, sulfate, phosphate, and hydrobromide; organic acid salts such as acetate, methanesulfonate, benzenesulfonate, p-toluenesulfonate, succinate, oxalate, fumarate, and maleate; inorganic base salts such as sodium salt, potassium salt, and calcium salt; and organic base salts such as triethylammonium salt. Specific peptides in gelatin can be converted into pharmaceutically acceptable salts using standard methods.

[0071] The gelatin is preferably a gelatin hydrolysate. Here, "gelatin hydrolysate" refers to a peptide aggregate (hydrolysate) obtained by hydrolyzing both or either of gelatin and collagen. In other words, "gelatin hydrolysate" refers to something equivalent to a peptide aggregate generally referred to as collagen peptide or collagen hydrolysate. Among these, the "gelatin hydrolysate" constituting the bioabsorbable particles according to this embodiment has the D50, D95, and average circularity described above. Furthermore, since gelatin hydrolysate refers to a peptide aggregate as described above, it has the same characteristics as collagen and gelatin, such as a primary structure in which glycine is repeated every three residues in the amino acid sequence constituting the peptide chain. Gelatin is a polypeptide derived from collagen, which is found in many organisms, and therefore has excellent biocompatibility. Therefore, gelatin hydrolysates obtained by hydrolyzing the above collagen and gelatin also have excellent biocompatibility and are suitable as a component of injection solutions filled in syringes equipped with injection needles and syringes.

[0072] Here, whether gelatin is a gelatin hydrolysate can be determined by dissolving gelatin in water at 50°C or higher at a concentration of 2 w / v% or higher to obtain a gelatin solution, and then confirming that the gelatin solution does not gel when the temperature of the gelatin solution is lowered to 25°C or lower.

[0073] [Embodiment 2: Method for producing bioabsorbable particles] The following describes a method for producing the bioabsorbable particles of embodiment 1. Note that the following production method is an example, and the bioabsorbable particles of embodiment 1 may be produced by other methods.

[0074] The bioabsorbable particles according to this embodiment can be obtained by a conventionally known manufacturing method, such as, for example, when the bioabsorbable particles are gelatin, a method of finely pulverizing the gelatin using various grinders, or a method of dissolving gelatin in a solvent to obtain a gelatin solution, and then using a spray dryer or the like to obtain a fine dried gelatin product from the gelatin solution. [Example]

[0075] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

[0076] [Example 1] <Production of bioabsorbable particles> [Samples 1-11, 101-103] Bioabsorbable particles of Samples 1 to 11 and Samples 101 to 103 were produced using the following production method.

[0077] <Sample 1> First, gelatin powder (manufactured by Nitta Gelatin Co., Ltd., product name: MRK2) was prepared. Next, the gelatin powder was classified using a 32 μm sieve, and the particles that passed through this sieve were collected to obtain bioabsorbable particles of Sample 1. Note that the entry "None" in the "Presence or Absence of Hydrolysis" column in Table 1 means that the "gelatin powder" used in producing the bioabsorbable particles of Sample 1 was gelatin other than gelatin hydrolysate. The same applies to Samples 2 to 8 and 101 to 103.

[0078] <Sample 2> First, gelatin powder (manufactured by Nitta Gelatin Co., Ltd., product name: MRK2) was prepared. Next, the gelatin powder was classified using a 32 μm sieve and a 90 μm sieve, and particles that passed through the 90 μm sieve but not the 32 μm sieve were collected to obtain bioabsorbable particles of Sample 2.

[0079] <Sample 3> First, gelatin powder (manufactured by Nitta Gelatin Co., Ltd., product name: MRK2) was prepared. Next, the gelatin powder was classified using a 20 μm sieve, and the particles that passed through this sieve were collected to obtain bioabsorbable particles of Sample 3.

[0080] <Sample 4> First, gelatin powder (manufactured by Nitta Gelatin Co., Ltd., product name: MRK2) was prepared. Next, the gelatin powder was classified using a 106 μm sieve and an 180 μm sieve, and particles that passed through the 180 μm sieve but not the 106 μm sieve were collected. 3.5 g of these particles were mixed with 6.5 g of the bioabsorbable particles of Sample 1 to obtain the bioabsorbable particles of Sample 4.

[0081] <Sample 5> First, gelatin powder (manufactured by Nitta Gelatin Co., Ltd., product name: MRK2) was prepared. Next, the gelatin powder was classified using a 180 μm sieve and a 300 μm sieve, and particles that passed through the 300 μm sieve but not the 180 μm sieve were collected. 0.5 g of these particles were mixed with 9.5 g of the bioabsorbable particles of Sample 1 to obtain the bioabsorbable particles of Sample 5.

[0082] <Sample 6> First, gelatin powder (manufactured by Nitta Gelatin Co., Ltd., product name: B-Matrix Gelatin LS-250) was prepared. Next, the gelatin powder was classified using a 125 μm sieve and a 32 μm sieve, and particles that passed through the 125 μm sieve but not the 32 μm sieve were collected to obtain bioabsorbable particles of Sample 6.

[0083] <Sample 7> First, gelatin powder (manufactured by Nitta Gelatin Co., Ltd., product name: MRK2) was prepared. Next, the gelatin powder was classified using a 75 μm sieve, and the particles that passed through this sieve were collected to obtain bioabsorbable particles of Sample 7.

[0084] <Sample 8> First, gelatin powder (manufactured by Nitta Gelatin Co., Ltd., product name: MRK2) was prepared. Next, the gelatin powder was classified using a 38 μm sieve, and the particles that passed through this sieve were collected to obtain bioabsorbable particles of Sample 8.

[0085] <Sample 9> First, an alginic acid powder (manufactured by Kimica, product name: Kimica Acid) was prepared. Next, the alginic acid powder was classified using a 90 μm sieve, and the particles that passed through the sieve were collected to obtain bioabsorbable particles of Sample 9.

[0086] <Sample 10> First, calcium alginate powder (manufactured by Kimica Co., Ltd., product name: Kimica Algin) was prepared. Next, the calcium alginate powder was classified using a 90 μm sieve, and the particles that passed through the sieve were collected to obtain bioabsorbable particles of Sample 10.

[0087] <Sample 11> First, gelatin powder (manufactured by Nitta Gelatin Co., Ltd., product name: B-Matrix Gelatin HG) was prepared. Next, the gelatin powder was classified using a 32 μm sieve and a 90 μm sieve, and particles that passed through the 90 μm sieve but not the 32 μm sieve were collected. These particles were heated at 150°C under vacuum for 48 hours to obtain bioabsorbable particles of Sample 11. The entry "Yes" in the "Presence or Absence of Hydrolysis" column in Table 1 indicates that the "gelatin powder" used in producing the bioabsorbable particles of Sample 11 was a "gelatin hydrolysate."

[0088] <Sample 101> First, gelatin powder (manufactured by Nitta Gelatin Co., Ltd., product name: MRK2) was prepared. Next, the gelatin powder was dissolved in distilled water to obtain a 5 w / v% aqueous solution. This was then spray-dried using a spray dryer (manufactured by Okawara Manufacturing Co., Ltd.) to obtain a dry powder. The resulting powder was then classified using a 20 μm sieve, and the particles that passed through the sieve were collected to obtain bioabsorbable particles of Sample 101.

[0089] <Sample 102> First, gelatin powder (manufactured by Nitta Gelatin Co., Ltd., product name: MRK2) was prepared. Next, the gelatin powder was classified using a 106 μm sieve and a 212 μm sieve, and particles that passed through the 212 μm sieve but not the 106 μm sieve were collected to obtain bioabsorbable particles of Sample 102.

[0090] <Sample 103> First, gelatin powder (manufactured by Nitta Gelatin Co., Ltd., product name: MRK2) was prepared. Next, the gelatin powder was classified using a 180 μm sieve, and particles that did not pass through the sieve were collected. Next, 2.0 g of these particles were mixed with 8.0 g of the bioabsorbable particles of Sample 1 to obtain the bioabsorbable particles of Sample 103.

[0091] <Characteristic evaluation of bioabsorbable particles> The properties of the bioabsorbable particles, Samples 1 to 11 and Samples 101 to 103, prepared as described above, were evaluated as follows. Note that the bioabsorbable particles, Samples 1 to 11, correspond to Examples, and the bioabsorbable particles, Samples 101 to 103, correspond to Comparative Examples.

[0092] <Measurement of D10, D50, and D95 ​​of bioabsorbable particles> The D10, D50, and D95 ​​of the bioabsorbable particles of Samples 1 to 11 and Samples 101 to 103 were determined by the method described in Embodiment 1. The results obtained are shown in Table 1 under the headings "D10 [μm]," "D50 [μm]," and "D95 [μm]," respectively.

[0093] [Table 1]

[0094] <Measurement of the average circularity of bioabsorbable particles> The average circularity of the bioabsorbable particles of Samples 1 to 11 and Samples 101 to 103 was determined by the method described in Embodiment 1. The results obtained are shown in the "Average circularity" section of Table 1.

[0095] <Measurement of retention rate of bioabsorbable particles> For the bioabsorbable particles of Samples 1 to 11 and Samples 101 to 103, the retention rate was determined by the method described in Embodiment 1 when "a first liquid containing the bioabsorbable particles in water at a ratio of 5 w / v % was stirred at 300 rpm for 1 minute and then allowed to stand for 1 minute" using the first liquid. The results obtained are shown in the "Retention Rate [%]" section of Table 1.

[0096] <Measurement of bulk density of bioabsorbable particles> The "bulk density" of the bioabsorbable particles of Samples 1 to 11 and Samples 101 to 103 was determined by the method described in Embodiment 1. The results obtained are shown in Table 1 as "bulk density [g / cm 3]" section.

[0097] <Leakage rate measurement test> A suspension of bioabsorbable particles of Sample 1 prepared as described above was prepared in PBS (phosphate-buffered saline) at a concentration of 1% (w / v). The suspension was then stirred at 300 rpm for 1 minute and immediately thereafter dispensed into a 1 mL syringe equipped with a 21G needle. The suspension was then allowed to stand in the 1 mL syringe for 10 seconds. Immediately after the suspension, 0.2 g of the suspension was injected via the 21G needle into a punctured site (localized site) of a chicken thigh that had been incubated at 37°C. The punctured site (localized site) was then covered with a 1 cm square piece of filter paper (approximately 0.03 g) immediately after the 23G needle was removed from the chicken thigh, allowing the leaked fluid to be absorbed by the filter paper. The weight of the leaked fluid was measured by measuring the weight [g] of the filter paper that had absorbed the leaked fluid. Next, the weight of the leaked liquid was substituted into the formula "leakage rate [%] = 100 × (weight of leaked liquid [g] / 0.2 [g])" to calculate the leakage rate of the bioabsorbable particles of Sample 1. The leakage rates of the bioabsorbable particles of Sample 1 were determined in the same manner for each of the 26G syringe needle, 27G syringe needle, 29G syringe needle, 30G syringe needle, and 32G syringe needle.

[0098] The same leakage rate measurement test was also conducted for the bioabsorbable particles of Samples 2 to 11 and Samples 101 to 103 prepared as described above. The same leakage rate measurement test was also conducted for Sample 1001 (PBS), prepared as a negative control. Here, the smaller the leakage rate value, the better the bioabsorbable particles' effectiveness in suppressing leakage of an injection solution from a localized site when the injection solution is administered to the localized site using an injector equipped with an injection needle and syringe. The leakage rate when a "21G injection needle" was used is listed in the "21G" section of Table 1. The leakage rate when a "26G injection needle" was used is listed in the "26G" section of Table 1. The leakage rate when a "27G injection needle" was used is listed in the "27G" section of Table 1. The leakage rate when a "29G injection needle" was used is listed in the "29G" section of Table 1. The leakage rate when a "30G injection needle" was used is shown in the "30G" section of Table 1. The leakage rate when a "32G injection needle" was used is shown in the "32G" section of Table 1. If the bioabsorbable particles clogged the injection needle and all of the 0.2 g of the suspension could not be injected into the puncture site (local area), this was recorded as "injection impossible." The "-" in the "Leakage Rate [%]" section of Table 1 indicates that there is no relevant data.

[0099] In addition, a thick injection needle tends to make it difficult to prevent leakage when the injection needle is withdrawn from the puncture site (local site) because the hole made by the injection needle is larger than that made by a thin injection needle. Therefore, it is thought that bioabsorbable particles that show excellent leakage prevention effects with a thick injection needle will also show excellent leakage prevention effects with a thin injection needle.

[0100] Furthermore, since a thin injection needle has a smaller inner diameter than a thick injection needle, it tends to be difficult for bioabsorbable particles to pass through it, and therefore bioabsorbable particles that pass through a thin injection needle can also pass through a thick injection needle.

[0101] Therefore, for example, bioabsorbable particles that exhibit excellent leakage suppression effects with a 21G injection needle and can pass through a 26G injection needle (i.e., can be injected with a 26G injection needle) are also thought to exhibit excellent leakage suppression effects and be injectable with 22G injection needles, 23G injection needles, 24G injection needles, and 25G injection needles.

[0102] Here, in a leakage rate measurement test using a 21G syringe needle, a leakage rate of 10% or less means that the bioabsorbable particles have an excellent leakage suppression effect. Furthermore, in a leakage rate measurement test using a 26G syringe needle, a leakage rate of 5% or less means that the bioabsorbable particles have an excellent leakage suppression effect. Furthermore, in a leakage rate measurement test using a 27G syringe needle, a leakage rate of 5% or less means that the bioabsorbable particles have an excellent leakage suppression effect. Furthermore, in a leakage rate measurement test using a 29G syringe needle, a leakage rate of 5% or less means that the bioabsorbable particles have an excellent leakage suppression effect. Furthermore, in a leakage rate measurement test using a 30G syringe needle, a leakage rate of 5% or less means that the bioabsorbable particles have an excellent leakage suppression effect. Furthermore, in a leakage rate measurement test using a 32G syringe needle, a leakage rate of 1.5% or less means that the bioabsorbable particles have an excellent leakage suppression effect.

[0103] <Result> Samples 1 to 11 correspond to Examples. Samples 101 to 103 correspond to Comparative Examples. The results in Table 1 show that when an injection solution is administered to a localized area using a syringe equipped with a needle and syringe, the bioabsorbable particles of Samples 1 to 11, which correspond to Examples, have a superior effect of suppressing leakage of the injection solution from the localized area compared to the bioabsorbable particles of Samples 101 to 103, which correspond to Comparative Examples, when the injection solution is administered to the localized area using a syringe equipped with a needle and syringe.

[0104] From the above, it was found that the bioabsorbable particles of Samples 1 to 11 according to the examples can suppress leakage of an injection solution from a local site when an injection solution is administered to the local site using a syringe equipped with an injection needle and a syringe capable of injecting the injection solution. Furthermore, the bioabsorbable particles of Samples 1 to 11 according to the examples can be produced simply and efficiently because their production does not require complicated steps using granulation methods such as a W / O dispersion method.

[0105] Although the embodiments and examples of the present disclosure have been described above, it is originally intended that the configurations of the above-described embodiments and examples may be appropriately combined or modified in various ways.

[0106] The embodiments and examples disclosed herein are illustrative in all respects and should not be considered limiting. The scope of the present invention is defined by the claims, not by the embodiments and examples described above, and is intended to include meanings equivalent to the claims and all modifications within the scope of the claims.

Claims

1. A powder of bioabsorbable particles for suppressing leakage of an injection solution filled in a syringe equipped with an injection needle and a syringe, The D50 of the powder of the bioabsorbable particles is 10 μm or more and 140 μm or less, The D95 of the powder of the bioabsorbable particles is 300 μm or less, The average circularity of the powder of the bioabsorbable particles is 0.5 or more and less than 0.8, The powder of bioabsorbable particles is composed of at least one selected from the group consisting of gelatin, alginic acid, and calcium alginate.

2. the injection needle is any one of a 21G injection needle, a 22G injection needle, a 23G injection needle, a 24G injection needle, a 25G injection needle, and a 26G injection needle; The D50 of the powder of the bioabsorbable particles is 10 μm or more and 140 μm or less, The D95 of the powder of the bioabsorbable particles is 20 μm or more and 290 μm or less, The powder of bioabsorbable particles according to claim 1 , wherein the powder of bioabsorbable particles has a D10 of 55 μm or less.

3. the injection needle is either a 27G injection needle, a 28G injection needle, or a 29G injection needle; The D50 of the powder of the bioabsorbable particles is 10 μm or more and 60 μm or less, The D95 of the powder of the bioabsorbable particles is 20 μm or more and 120 μm or less, The powder of bioabsorbable particles according to claim 1 , wherein the powder of bioabsorbable particles has a D10 of 30 μm or less.

4. the injection needle is either a 30G injection needle, a 31G injection needle, or a 32G injection needle; The D50 of the powder of the bioabsorbable particles is 10 μm or more and 55 μm or less, The D95 of the powder of the bioabsorbable particles is 20 μm or more and 80 μm or less, The powder of bioabsorbable particles according to claim 1 , wherein the powder of bioabsorbable particles has a D10 of 20 μm or less.

5. In a first liquid containing the bioabsorbable particle powder in a proportion of 5 w / v % in water, A powder of bioabsorbable particles described in any one of claims 1 to 4, wherein the retention rate when the first liquid is stirred at 300 rpm for 1 minute and then allowed to stand for 1 minute is 60% or more.

6. The bulk density of the powder of the bioabsorbable particles is 0.3 g / cm ３ 0.7g / cm or more ３ The powder of bioabsorbable particles according to any one of claims 1 to 5, wherein:

7. The powder of bioabsorbable particles according to any one of claims 1 to 6, wherein the gelatin is a gelatin hydrolysate.

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