Capsule filling method

Abstract

The invention relates to a capsule filling method which comprises the following steps: (1) adding auxiliary materials into medicine powder on the basis of the property of a main material of the medicine powder, and uniformly mixing to prepare a mixture; (2) the mixture is spread on a metering panel of a capsule filling device, the metering panel is driven to move along a preset path, meanwhile, a filling rod is controlled to reciprocate in the vertical direction, and the inner diameter d1 of a capsule shell, the diameter d2 of a metering hole and the diameter d3 of the filling rod meet the following relational expressions that d1 is larger than or equal to (d3 + 1.2) mm and smaller than or equal to (d3 + 2) mm, and d2 is larger than or equal to (d3 + 0.1) mm and smaller than or equal to (d3 + 0.3) mm; and (3) locking the capsule shell filled with the mixture with a matched capsule cap to form the sealed capsule. The filling rod and the metering hole which are smaller than the standard capsule shell in inner diameter are adopted, and specific auxiliary materials are added into the medicine powder, so that the capsule filling precision is improved, the risk of powder leakage is reduced, and the consistency and reliability of the filling process are ensured.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of capsule filling, in particular to a capsule filling method. BACKGROUND

[0002] In the modern pharmaceutical and health product industry, capsule dosage forms are widely used due to their convenience of use, good taste masking and other advantages. However, the problem of weight deviation commonly existing in the capsule filling production process seriously affects the quality stability, efficacy reliability and production efficiency of the product.

[0003] At present, capsule filling mainly relies on hard capsule filling machines, but due to the differences in physical properties such as flowability, density and adhesion of the materials, the phenomenon of uneven weight of single capsule is prone to occur in the actual production process. If the weight is insufficient, it will lead to the content of the active ingredient in the capsule being lower than the design standard, directly affecting the expected effect of the product; while if the weight is compensated by using high material feeding amount, although the active ingredient of each capsule can meet the standard, the cost of raw materials will be greatly increased, and the excess material not encapsulated will be wasted. In addition, excessive feeding will also exacerbate the problem of powder leakage, leading to an increase in the amount of powder adhering to the capsule shell, thereby affecting the locking precision of the capsule, and even causing defects such as misalignment and poor sealing, reducing the product pass rate.

[0004] On the other hand, some materials (such as some dry and rough powders or particles) are prone to adhere to the capsule module during the filling process, causing poor filling of the capsule shell, increasing the breakage rate of the capsule shell, and causing the overall weight to be lighter.

[0005] Therefore, there is an urgent need for an efficient, low-cost and stable and reliable solution that can ensure the accuracy of the capsule weight while reducing material waste, reducing the risk of powder leakage, and avoiding damage to the capsule shell. SUMMARY

[0006] The purpose of the present application is to provide a capsule filling method to improve the accuracy of the capsule weight, reduce material waste, reduce the risk of powder leakage, and avoid damage to the capsule shell.

[0007] To achieve the above purpose, the technical solution adopted by the present application is as follows:

[0008] The present application provides a capsule filling method based on a capsule filling device, wherein the capsule filling device comprises a rack, a metering disc movably arranged on the rack, and a filling rod. The metering disc is configured to move along a predetermined path and has at least one group of holes arranged in sequence along the predetermined path, wherein the holes comprise a plurality of metering holes penetrating through the metering disc. The filling rod has a plurality of rods arranged in sequence along the predetermined path and is configured to move in a vertical direction to insert or withdraw the metering hole located directly below. The capsule filling method comprises the following steps:

[0009] (1) based on the nature of the main material of the powder, adding excipients to the powder, mixing uniformly, and preparing a mixture;

[0010] Among them, the excipients are selected from one or more of silicon dioxide, stearic acid, hydrated silicon dioxide;

[0011] (2) spread the mixture on the metering disc, drive the metering disc to move along the preset path, and control the filling rod to reciprocate vertically,

[0012] Among them, except for the last filling rod, the filling rod sequentially compacts the mixture in the corresponding metering hole, and the last filling rod compacts the mixture in the corresponding metering hole into the capsule shell;

[0013] The inner diameter d1 of the capsule shell, the diameter d2 of the metering hole, and the diameter d3 of the filling rod satisfy the following relationship:

[0014] (d3+1.2)mm≤d1≤(d3+2)mm, and (d3+0.1)mm≤d2≤(d3+0.3)mm;

[0015] (3) lock the capsule shell filled with the mixture with a matching capsule cap to form a sealed capsule;

[0016] Among them, the height H of the sealed capsule and the thickness T of the metering disc satisfy the following relationship:

[0017] T=(H±0.5)mm, and further preferably T=(H±0.3)mm.

[0018] In the traditional hard capsule filling process, accessories matched with the capsule model are usually used (such as 0# capsule shell matched with 0# filling rod, 0# capsule shell mold and 0# metering disc), but this standard configuration has obvious defects when processing materials with poor columnar properties: the material in the metering disc cannot completely fall into the capsule shell, resulting in material waste and filling amount deviation, and also causing the occurrence of locking wrong edge.

[0019] The present application solves the problem of loading precision by pretreating the material and optimizing the accessories used for filling (such as filling rod and metering disc), and avoids damage to the capsule shell. Specifically, the present application uses a filling rod and a metering hole with a smaller inner diameter than the standard capsule shell. This size optimization design ensures that the powder can fall more accurately from the metering disc into the capsule shell, significantly reducing the amount of powder scattered outside the capsule shell. In addition, the thickness of the metering disc is appropriately extended to maintain the filling precision while ensuring the loading amount. On the other hand, by adding specific excipients to the powder, the columnar performance of the powder is significantly improved, effectively preventing the powder from leaking due to the elongation of the column, greatly improving the accuracy of the powder falling, and ensuring the consistency and reliability of the filling process.

[0020] The capsule filling device according to the present application can be of any conventional type, for example a fully automatic capsule filling machine, and will not be described in detail.

[0021] In some embodiments, the diameter d2 of the metering hole and the diameter d3 of the filling rod satisfy the following relationship:

[0022] (d3+1.2)mm≤d1≤(d3+1.8)mm, and (d3+0.1)mm≤d2≤(d3+0.2)mm. In some embodiments, the capsule shell is selected from any one of a plurality of sizes, the sizes being 000#, 00#, 0#, 1#, 2#, 3#, 4# and 5# in order of decreasing volume, and the size of the filling rod and the size of the metering disc are each one size smaller than the size of the capsule shell being filled.

[0023] In some specific embodiments, when the size of the capsule shell is 000#, the diameter of the filling rod is 7.07±0.05mm, the diameter of the metering hole is 7.17-7.27mm, and the thickness of the metering disc is 26.1±0.3mm.

[0024] In some specific embodiments, when the size of the capsule shell is 00#, the diameter of the filling rod is 6.22±0.05mm, the diameter of the metering hole is 6.32-6.42mm, and the thickness of the metering disc is 23.3±0.3mm.

[0025] In some specific embodiments, when the size of the capsule shell is 0#, the diameter of the filling rod is 5.57±0.05mm, the diameter of the metering hole is 5.67-5.77mm, and the thickness of the metering disc is 21.7±0.3mm.

[0026] In some specific embodiments, when the size of the capsule shell is 1#, the diameter of the filling rod is 5.12±0.05mm, the diameter of the metering hole is 5.22-5.32mm, and the thickness of the metering disc is 19.4±0.3mm.

[0027] In some specific embodiments, when the size of the capsule shell is 2#, the diameter of the filling rod is 4.70±0.05mm, the diameter of the metering hole is 4.80-4.90mm, and the thickness of the metering disc is 18.0±0.3mm.

[0028] In some specific embodiments, when the size of the capsule shell is 3#, the diameter of the filling rod is 4.20±0.05mm, the diameter of the metering hole is 4.30-4.40mm, and the thickness of the metering disc is 15.9±0.3mm.

[0029] In some specific embodiments, when the capsule shell is of size 4#, the diameter of the filling rod is 3.79±0.05mm, the diameter of the metering hole is 3.89-3.99mm, and the thickness of the metering disc is 14.3±0.3mm.

[0030] In some specific embodiments, when the capsule shell is of size 5#, the diameter of the filling rod is 3.40±0.05mm, the diameter of the metering hole is 3.50-3.60mm, and the thickness of the metering disc is 11.1±0.3mm.

[0031] In some embodiments, the auxiliary material accounts for 0.5%-5% by mass in the mixture, such as 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, or 5%.

[0032] In some embodiments, the properties of the medicinal powder include the type of main material, the particle size, and whether the medicinal powder contains a cereal plant extract. Generally, for ordinary medicinal powder (e.g., the main material of the medicinal powder is a nicotinamide nucleotide), silica can be added. However, when the particle size of the medicinal powder is too fine (more than 80 mesh) or the medicinal powder contains a cereal plant extract, the addition of silica does not significantly improve the columnar property of the medicinal powder, and hydrated silica needs to be added.

[0033] In some embodiments, when the main material of the medicinal powder is a nicotinamide nucleotide, the auxiliary material is silica.

[0034] When the main material of the medicinal powder is a flavonoid compound, the auxiliary material is silica and stearic acid.

[0035] When the main material of the medicinal powder is a nicotinic acid vitamin, or the medicinal powder contains a cereal plant extract and the cereal plant extract accounts for 20% or more of the total mass of the medicinal powder, the auxiliary material is hydrated silica. In the present application, the "cereal plant extract" refers to a natural product extracted from cereals (such as wheat, corn, oat, and rice), such as wheat germ extract.

[0036] In some specific embodiments, when the main material of the medicinal powder is a nicotinamide nucleotide, the auxiliary material accounts for 0.5%-1% by mass in the mixture. The nicotinamide nucleotide is selected from one or more of nicotinamide riboside, nicotinamide mononucleotide, nicotinamide adenine dinucleotide, and nicotinamide adenine dinucleotide phosphate. As an example, the mixture includes, based on the total mass of the mixture being 100%:

[0037] nicotinamide mononucleotide 45%-54%,

[0038] vitamin B complex 35%-40%,

[0039] Dextrin 10%~15%,

[0040] Silica 0.5%~1%.

[0041] In some specific embodiments, when the main material of the medicine powder is flavonoids, the mass ratio of the auxiliary material in the mixture is 2%~3.5%, and the mass ratio of the silica and the stearic acid is 1:(3~5). The flavonoids are selected from one or more of flavones, flavonols (such as quercetin, etc.), flavanones, flavan-3-ols, and anthocyanidins. As an example, the mixture includes, based on the total mass of the mixture being 100%:

[0042] Quercetin 65%~70%,

[0043] Citrus flavonoids 5%~15%,

[0044] Vitamin C 4%~8%,

[0045] Dextrin 10%~15%,

[0046] Silica 0.5%~1%,

[0047] Stearic acid 1.5%~2.5%.

[0048] In some specific embodiments, when the main material of the medicine powder is a nicotinic acid vitamin, or the medicine powder contains a cereal plant extract and the cereal plant extract accounts for 20% or more of the total mass of the medicine powder, the mass ratio of the auxiliary material in the mixture is 2.5%~3.5%. The nicotinic acid vitamin is selected from one or more of hydrochloric acid, nicotinamide, and nicotinamide riboside. As an example, the mixture includes, based on the total mass of the mixture being 100%:

[0049] Nicotinamide riboside 45%~55%,

[0050] Ergothioneine 3%~8%,

[0051] Wheat germ extract 15%~25%,

[0052] Pyrroloquinoline quinone 1%~5%,

[0053] Microcrystalline cellulose 14%~18%,

[0054] Hydrated silica 2.5%~3.5%.

[0055] In some embodiments, the hydrated silica is obtained by mixing silica with water, shaking, sealing, and standing overnight.

[0056] Further, the silica and water are mixed in a mass ratio of 1:(0.5-1.5).

[0057] Thanks to the above technical solution, the present application has the following advantages compared with the prior art:

[0058] The present application ensures that the medicine powder can fall more accurately from the metering disc into the capsule shell by using a filling rod and a metering hole smaller than the inner diameter of the standard capsule shell, thereby significantly reducing the amount of powder scattered outside the capsule shell; the filling accuracy is maintained while ensuring the loading amount by appropriately extending the thickness of the metering disc. The present application also significantly improves the columnar performance of the medicine powder by adding a specific excipient to the medicine powder, effectively prevents the powder leakage phenomenon caused by the elongation of the medicine powder column, significantly improves the accuracy of the falling of the medicine powder, and ensures the consistency and reliability of the filling process.

[0059] The present application has high filling accuracy, low material loss, and low capsule breakage rate. BRIEF DESCRIPTION OF DRAWINGS

[0060] Figure 1 For the phenomenon of locking the wrong edge of the capsule during the preparation process of the comparative example 1;

[0061] Figure 2 For the damage phenomenon of the capsule shell during the preparation process of the comparative example 3;

[0062] Figure 3 For the damage phenomenon of the capsule locking during the preparation process of the comparative example 3. DETAILED DESCRIPTION

[0063] The present application will be further described below in conjunction with the examples. However, the present application is not limited to the following examples. The implementation conditions used in the examples can be further adjusted according to different requirements of specific use, and the implementation conditions not mentioned are the conventional conditions in the industry. The technical features involved in each embodiment of the present application can be combined with each other as long as there is no conflict between them.

[0064] Unless otherwise specified, the reagents involved in the following text are commercially available or can be prepared according to the prior art method, and the instruments used are conventional instruments in the art. Among them, the capsule filling device is a full-automatic capsule filling machine of Tianjin Hanlin Space, model: NJP-400A.

[0065] Unless otherwise specified, the capsule filling process involved in the following text can refer to the prior art.

[0066] Example 1: The present example provides a capsule filling method, using 0# capsule shell (shell weight 100 mg per), material filling 405 mg per, which includes the following steps:

[0067] (1) The materials were weighed according to the formulation in Table 1 below, and all the materials were stirred at a speed of 20 rpm for 25 min, and uniformly mixed for standby use;

[0068] Table 1

[0069]

[0070] (2) The mixture in step (1) was spread on a metering disc, and the metering disc was driven to move along a preset path, while a plurality of filling rods were controlled to reciprocate in the vertical direction. Except for the last filling rod, the filling rods sequentially pressed the mixture in the corresponding metering holes, and the last filling rod pressed the mixture in the corresponding metering hole into the capsule shell.

[0071] In the formula, the filling rod is a 1# filling rod (with a diameter of 5.57 mm), and the metering disc is a 1# metering disc (with a diameter of 5.67 mm and a thickness of 21.7 mm).

[0072] (3) The capsule shell filled with the mixture was locked with a matching capsule cap to form a sealed capsule.

[0073] Ten sealed capsules prepared in this embodiment were randomly selected to detect the filling amount deviation and material loss rate of the capsules, and the results are shown in Table 2 below.

[0074] Table 2

[0075]

[0076]

[0077] In the formula, the filling amount deviation = (single-shell weight - average weight of 10 shells) / average weight of 10 shells x 100%; and the material loss rate = (loss amount ÷ net amount) x 100%, wherein the loss amount refers to the difference between the actual amount of material consumed in the production process and the theoretical value, and the net amount refers to the total amount of material directly used for capsule filling.

[0078] Embodiment 2: This embodiment provides a capsule filling method, which uses a 0# capsule shell (with a shell weight of 100 mg per capsule) and fills 405 mg per capsule of material, and includes the following steps:

[0079] (1) The materials were weighed according to the formulation in Table 3 below, and all the materials were stirred at a speed of 20 rpm for 25 min, and uniformly mixed for standby use;

[0080] Table 3

[0081]

[0082] (2) spreading the mixture of step (1) on the metering disc, driving the metering disc to move along a preset path, and controlling a plurality of filling rods to reciprocate in the vertical direction, wherein the filling rods except the last one press the mixture in the corresponding metering hole in turn, and the last filling rod presses the mixture in the corresponding metering hole into the capsule shell;

[0083] The filling rod is a 1# filling rod (with a diameter of 5.57 mm), and the metering disc is a 1# metering disc (with a metering hole diameter of 5.67 mm and a thickness of 21.7 mm).

[0084] (3) locking the capsule shell filled with the mixture with a matching capsule cap to form a sealed capsule.

[0085] Ten sealed capsules prepared in this embodiment were randomly selected to detect the filling deviation and material loss rate of the capsules, and the results are shown in Table 4.

[0086] Table 4

[0087]

[0088]

[0089] Example 3: This embodiment provides a capsule filling method, which uses a 0# capsule shell (with a shell weight of 100 mg per capsule) and fills 405 mg per capsule of material, which includes the following steps:

[0090] (1) weighing the materials according to the following Table 5, and stirring the hydrated silicon dioxide and wheat germ extract at a speed of 20 rpm for 10 min, then adding the remaining other materials and stirring at a speed of 20 rpm for 15 min, and mixing uniformly for standby;

[0091] Table 5

[0092]

[0093] (2) spreading the mixture of step (1) on the metering disc, driving the metering disc to move along a preset path, and controlling a plurality of filling rods to reciprocate in the vertical direction, wherein the filling rods except the last one press the mixture in the corresponding metering hole in turn, and the last filling rod presses the mixture in the corresponding metering hole into the capsule shell;

[0094] The filling rod is a 1# filling rod (with a diameter of 5.57 mm), and the metering disc is a 1# metering disc (with a metering hole diameter of 5.67 mm and a thickness of 21.7 mm).

[0095] (3) locking the capsule shell filled with the mixture with a matching capsule cap to form a sealed capsule.

[0096] Ten capsules prepared in this example were randomly selected to test the weight deviation and material loss rate of the capsules, and the results are shown in Table 6 below.

[0097] Table 6

[0098]

[0099] Comparative Example 1: This comparative example provides a capsule filling method that is substantially the same as Example 1, except that the filling rod is a 0# filling rod (5.57 mm in diameter), and the metering disc is a 0# metering disc (5.67 mm in diameter and 17.1 mm in thickness).

[0100] Ten capsules prepared in this comparative example were randomly selected to test the weight deviation and material loss rate of the capsules, and the results are shown in Table 7 below.

[0101] Table 7

[0102]

[0103]

[0104] Even if a specific auxiliary material is added to the material, if the filling rod and the metering hole are not suitable, the material loss rate and the weight deviation will be large, and the misalignment of the capsule shell after locking will also occur (as shown in Figure 1

[0105] Comparative Example 2: This comparative example provides a capsule filling method that is substantially the same as Example 2, except that the auxiliary material added is different. The formula of the mixture in this comparative example is shown in Table 8 below.

[0106] Table 8

[0107]

[0108] Ten capsules prepared in this comparative example were randomly selected to test the weight deviation and material loss rate of the capsules, and the results are shown in Table 9 below.

[0109] Table 9

[0110]

[0111]

[0112] Even if a filling rod and a metering hole with a smaller inner diameter than the standard capsule shell are used, the overall weight will be light due to the strong escaping property of the main material, and the filling is still unqualified.

[0113] ​Comparative Example 3: This comparative example provides a capsule filling method which is substantially the same as Example 3, except that the blend formulation is different. The blend formulation of this comparative example is shown in Table 10 below.

[0114] Table 10

[0115]

[0116] Ten of the sealed capsules produced in this comparative example were randomly selected and tested for fill weight deviation and material loss rate. The results are shown in Table 11 below.

[0117] Table 11

[0118]

[0119]

[0120] Because the material was relatively dry and harsh, it tended to stick to the capsule module, causing the capsule shell to not enter the module smoothly (see Figure 2 ), resulting in damage to the capsule shell (see Figure 3 ), and an overall light fill weight.

[0121] The foregoing detailed description of the application has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the application to the precise form disclosed, and obviously many modifications and variations are possible in light of these teachings. The described embodiments were chosen and described in order to best explain the principles of the application and its best mode of practice.

Claims

1. A capsule filling method, based on a capsule filling device, the capsule filling device comprising a frame and a metering disc and a filling rod movably disposed on the frame, the metering disc being configured to move along a preset path and having at least one set of channels thereon, the channels including a plurality of metering holes arranged sequentially along the preset path and penetrating the metering disc; the filling rod having a plurality of channels arranged sequentially along the preset path and configured to move in a vertical direction to insert into or withdraw from the metering holes located directly below it, characterized in that, The capsule filling method includes the following steps: (1) Based on the properties of the powder, add excipients to the powder, mix evenly, and prepare a mixture; The excipients are selected from one or more of silica, stearic acid, and hydrated silica. (2) Spread the mixture onto the metering disc, drive the metering disc to move along a preset path, and simultaneously control the filling rod to reciprocate in the vertical direction. Among them, except for the last filling rod, the filling rods sequentially press the mixture into the corresponding metering holes, and the last filling rod presses the mixture in its corresponding metering hole into the capsule shell; The inner diameter d1 of the capsule shell, the diameter d2 of the metering orifice, and the diameter d3 of the filling rod satisfy the following relationship: (d3+1.2)mm≤d1≤(d3+2)mm, and (d3+0.1)mm≤d2≤(d3+0.3)mm; (3) Lock the capsule shell filled with the mixture to a matching capsule cap to form a sealed capsule; The height H of the sealed capsule and the thickness T of the measuring disc satisfy the following relationship: T = (H ± 0.5) mm.

2. The capsule filling method according to claim 1, characterized in that, The capsule shells are sized in descending order of capacity as 000#, 00#, 0#, 1#, 2#, 3#, 4#, and 5#, and the capsule shells are selected from any of these sizes. The specifications of the filling rod and the measuring disc are both one size smaller than the specifications of the capsule shell being filled.

3. The capsule filling method according to claim 2, characterized in that, When the capsule shell specification is 000#, the diameter of the filling rod is 7.07±0.05mm, the diameter of the metering hole is 7.17~7.27mm, and the thickness of the metering disc is 26.1±0.3mm; When the capsule shell is of specification 00#, the diameter of the filling rod is 6.22±0.05mm, the diameter of the metering hole is 6.32~6.42mm, and the thickness of the metering disc is 23.3±0.3mm; When the capsule shell is of specification 0#, the diameter of the filling rod is 5.57±0.05mm, the diameter of the metering hole is 5.67~5.77mm, and the thickness of the metering disc is 21.7±0.3mm; When the capsule shell is of specification #1, the diameter of the filling rod is 5.12±0.05mm, the diameter of the metering hole is 5.22~5.32mm, and the thickness of the metering disc is 19.4±0.3mm; When the capsule shell is of specification #2, the diameter of the filling rod is 4.70±0.05mm, the diameter of the metering hole is 4.80~4.90mm, and the thickness of the metering disc is 18.0±0.3mm; When the capsule shell is of specification #3, the diameter of the filling rod is 4.20±0.05mm, the diameter of the metering hole is 4.30~4.40mm, and the thickness of the metering disc is 15.9±0.3mm; When the capsule shell is of specification 4#, the diameter of the filling rod is 3.79±0.05mm, the diameter of the metering hole is 3.89~3.99mm, and the thickness of the metering disc is 14.3±0.3mm; When the capsule shell is of specification 5#, the diameter of the filling rod is 3.40±0.05mm, the diameter of the metering hole is 3.50~3.60mm, and the thickness of the metering disc is 11.1±0.3mm.

4. The capsule filling method according to claim 1, characterized in that, The auxiliary material accounts for 0.5% to 5% of the mass of the mixture.

5. The capsule filling method according to claim 1, characterized in that, When the main ingredient in the powder is nicotinamide nucleotides, the excipient is silicon dioxide; When the main ingredient in the powder is a flavonoid, the excipients are silicon dioxide and stearic acid; When the main ingredient in the powder is niacin vitamin, or when the powder contains cereal plant extracts and the cereal plant extracts account for 20% or more of the total mass of the powder, the auxiliary ingredient is hydrated silica.

6. The capsule filling method according to claim 5, characterized in that, When the main ingredient of the powder is nicotinamide nucleotide, the mass percentage of the excipients in the mixture is 0.5% to 1%. And / or, when the main material of the powder is a flavonoid compound, the mass percentage of the excipient in the mixture is 2% to 3.5%, and the mass ratio of the silica to the stearic acid is 1:(3 to 5); And / or, when the main ingredient of the powder is niacin vitamin, or when the powder contains cereal plant extract and the cereal plant extract accounts for 20% or more of the total mass of the powder, the mass percentage of the excipient in the mixture is 2.5% to 3.5%.

7. The capsule filling method according to claim 5, characterized in that, The nicotinamide nucleotides are selected from one or more of nicotinamide ribose, nicotinamide mononucleotide, nicotinamide adenine dinucleotide, and nicotinamide adenine dinucleotide phosphate; And / or, the flavonoids are selected from one or more of flavones, flavonols, flavanones, flavan-3-ols, and anthocyanins; And / or, the niacin-like vitamins are selected from one or more of hydrochloric acid, nicotinamide, and nicotinamide ribose.

8. The capsule filling method according to claim 1, characterized in that, The hydrated silica is obtained by mixing silica with water, shaking and agitating, sealing, and letting it stand overnight.

9. The capsule filling method according to claim 8, characterized in that, The silica and water are mixed at a mass ratio of 1:(0.5 to 1.5).

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