Method for stably producing seamless capsules

Abstract

To provide a method for producing seamless capsules by a dropping process, the method making it possible to stably produce seamless capsules less apt to suffer film breakage.SOLUTION: The present invention provides a method for producing seamless capsules using a capsule production device, and the use thereof. The capsule production device comprises: concentric multiple nozzles comprising, concentrically from the inner side, a filling nozzle, a film nozzle and optionally one or more intermediate nozzles present between the filling nozzle and the film nozzle; and a formation pipe in which capsule droplets ejected from an ejection port of the concentric multiple nozzles are coagulated in a flowing coagulating liquid. The method comprises forming, in the formation pipe, two kinds of capsule particles, i.e., main-capsule particles and sub-capsule particles. The main-capsule particles have a larger particle diameter than the sub-capsule particles. When a formation ratio of the main-capsule particles is taken as 1, then a formation ratio of the sub-capsule particles exceeds 0.5.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a novel and stable manufacturing method for seamless capsules.

Background Art

[0002] Seamless capsules are usually formed by dropping droplets, called the dropping method, into a coagulating liquid. For example, in the case of a seamless capsule 4 composed of three layers of a content 1, an intermediate layer 3, and a film 2 shown in FIG. 1, it is manufactured using the manufacturing apparatus schematically shown in FIG. 2. In FIG. 2, a concentric multi-nozzle A has a content nozzle 11, an intermediate layer nozzle 12, and a film nozzle 13 formed concentrically, and a content liquid 14, an intermediate layer liquid 15, and a film liquid 16 are discharged from the lower end (discharge port) of the concentric multi-nozzle A to where a coagulating liquid 18 is flowing downward in a forming tube 19, separated into droplets in a forming part B, and finally a seamless capsule 17 is formed after coagulation.

[0003] In Japanese Patent Application Laid-Open No. 2022-26425 (Patent Document 1), in the production of seamless capsules produced as described above, by blending lecithin containing 85% by weight or more of phosphatidylcholine in the capsule content (content 1), a method is disclosed for preventing defects called "biased meat" and "eyes" from occurring in the film (film 2). Here, according to Patent Document 1, both "biased meat" and "eyes" are considered to cause a decrease in the strength of the film.

[0004] However, simply blending lecithin containing 85% by weight or more of phosphatidylcholine in the content 1 as in Patent Document 1 has not easily enabled the stable production of seamless capsules with a film that is difficult to crack.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Summary of the Invention

[0006] Therefore, the present invention has been found in view of the above, and an object of the present invention is to provide a method capable of stably producing a seamless capsule with a film that is difficult to crack when producing the seamless capsule by the dropping method. [Means for Solving the Problems]

[0007] The present invention pays attention to the fact that when producing a seamless capsule by the dropping method, a seamless capsule with a small particle size is formed beside a seamless capsule with a large particle size, and actively forms two types (a large particle size and a small particle size) to obtain a target seamless capsule (usually, a large seamless capsule) stably. That is, the present invention provides the following aspects:

[0008] [1] Using a capsule manufacturing apparatus including a concentric multi-nozzle having a concentric arrangement of an inner content nozzle, a film nozzle, and one or more intermediate nozzles that may exist between the content nozzle and the film nozzle as needed from the inside, and a forming tube for solidifying the capsule droplets discharged from the discharge port of the concentric multi-nozzle in a flowing coagulating liquid, Two types of capsule particles, namely main capsule particles and sub-capsule particles, are formed in the forming tube, The particle size of the main capsule particles is larger than that of the sub-capsule particles, When the generation ratio of the main capsule particles is set to 1, the generation ratio of the sub-capsule particles is more than 0.5, A method for manufacturing a seamless capsule. [2] The method for manufacturing a seamless capsule according to [1], wherein the main capsule particles are formed in a pair with the sub-capsule particles. [3] The average flow velocity of the coagulating liquid in the forming tube of the capsule particles, the particle size of the main capsule particles, and the number of generated main capsule particles have the following relationship: 0.7 ≦ V / (R × N) ≦ 2.1 (Formula 1) (In Formula 1, V is the average flow velocity of the coagulating liquid, R is the particle size of the main capsule particles, and N is the number of generated main capsule particles.) The method for producing seamless capsules according to [1] or [2], which satisfies . [4] Further, after separating the main capsule particles from the sub-capsule particles, drying the method for producing seamless capsules according to [1] or [2]. [5] In a method for producing seamless capsules using a capsule manufacturing apparatus including a concentric multi-nozzle having a content nozzle, a film nozzle, and one or more intermediate nozzles that may be present between the content nozzle and the film nozzle, concentrically arranged from the inside, and a forming tube in which capsule droplets discharged from the discharge port of the concentric multi-nozzle solidify in a flowing coagulating liquid, Solidifying the droplets discharged from the concentric multi-nozzle in the forming tube to form two types of capsule particles, main capsule particles and sub-capsule particles, wherein the particle size of the main capsule particles is larger than the particle size of the sub-capsule particles, when the generation ratio of the main capsule particles is 1, the generation ratio of the sub-capsule particles is more than 0.5, A method for preventing cracking of the film of seamless capsules. [6] The method for preventing cracking of the film of seamless capsules according to [5], wherein the main capsule particles are formed in pairs with the sub-capsule particles. [7] The average flow velocity of the coagulating liquid in the forming tube of the capsule particles, the particle size of the main capsule particles, and the number of generated main capsule particles have the following relationship: 0.7 ≦ V / (R×N) ≦ 2.1 (Formula 1) (In Formula 1, V is the average flow velocity of the coagulating liquid, R is the particle size of the main capsule particles, and N is the number of generated main capsule particles.) The method for preventing cracking of the film of seamless capsules according to [5] or [6], which satisfies . [8] Further, after separating the main capsule particles from the sub-capsule particles, drying the method for preventing cracking of the film of seamless capsules according to [5] or [6]. [9] A method for manufacturing capsule particles using a capsule manufacturing apparatus comprising a concentric multi-nozzle that concentrically includes an inner content nozzle, a film nozzle, and one or more intermediate nozzles that may exist between the content nozzle and the film nozzle as needed, and a forming tube that solidifies the capsule droplets discharged from the discharge port of the concentric multi-nozzle in a coagulating liquid that flows. Solidify the droplets discharged from the concentric multi-nozzle in the forming tube to form two types of capsule particles, namely main capsule particles and sub-capsule particles. The particle size of the main capsule particles is larger than that of the sub-capsule particles. When the generation ratio of the main capsule particles is set to 1, the generation ratio of the sub-capsule particles is more than 0.5. A method for simultaneously manufacturing two types of seamless capsules.

[10] The method for simultaneously manufacturing two types of seamless capsules according to [9], wherein the main capsule particles are formed in a pair with the sub-capsule particles.

[11] The average flow velocity of the coagulating liquid in the forming tube of the capsule particles, the particle size of the main capsule particles, and the number of generated main capsule particles have the following relationship: 0.7 ≦ V / (R × N) ≦ 2.1 (Formula 1) (In Formula 1, V is the average flow velocity of the coagulating liquid, R is the particle size of the main capsule particles, and N is the number of generated main capsule particles.) The method for simultaneously manufacturing two types of seamless capsules according to [9] or

[10] , which satisfies the above condition.

[12] Further, after separating the main capsule particles and the sub-capsule particles, each is dried. The method for simultaneously manufacturing two types of seamless capsules according to [9] or

[10] .

Advantages of the Invention

[0009] According to the present invention, seamless capsules with a film that is difficult to crack can be stably manufactured.

Brief Description of the Drawings

[0010]

Figure 1

Figure 2

Figure 3

Embodiments for Carrying Out the Invention

[0011] The inventors of the present invention focused on the fact that when manufacturing a seamless capsule by the dropping method, two types of capsule particles (namely, main capsule particles and sub-capsule particles) are formed. These two types of capsule particles are different in size from each other. In the basic idea of the inventors, one of the capsule particles (specifically, the main capsule particles) is the capsule particle for the purpose of manufacturing, and the other capsule particle (specifically, the sub-capsule particles) is generated secondarily and is not the capsule particle for the purpose of manufacturing.

[0012] The generation of sub-capsule particles is usually considered as a factor that reduces the yield of main capsule particles. However, as a result of intensive studies by the inventors of the present invention, it has been found that by actively manufacturing sub-capsule particles, conversely, main capsule particles can be stably manufactured. Here, "stable" refers to the stability of the quality of the product (seamless capsule) in which cracks in the film are less likely to occur and the variation in particle size is reduced.

[0013] Hereinafter, embodiments of the present invention will be described in detail. In the method for manufacturing seamless capsules according to the present invention, the dropping method is adopted to manufacture both main capsule particles and sub-capsule particles. In such a manufacturing method, when a discharge liquid (jet) is discharged from the tip of a nozzle, with the tip of the nozzle present on the liquid surface or in the liquid of the coagulating liquid, the initial discharge liquid first falls into the coagulating liquid in a cylindrical shape. However, due to the action of surface tension, it becomes a spherical droplet for capsule formation, which ideally becomes the target seamless capsule. However, when the cylindrical discharge liquid becomes a spherical droplet, for example, a state may occur where a plurality of particles are temporarily connected before the droplet particles are formed. Just before it finally becomes a spherical droplet, small particles may be formed from the portion extending and connecting between adjacent particles, which is considered to become sub-capsule particles with a small particle size.

[0014] Sub-capsule particles are basically particles that are not the manufacturing target. However, as described above, by actively manufacturing sub-capsule particles as well, the properties of the main capsule particles can be stably maintained. That is, if both the main capsule particles and the sub-capsule particles are manufactured, the main capsule particles are less likely to crack, and moreover, the variation in the particle size of the main capsule particles can be reduced (abnormal capsule particles do not occur).

[0015] The capsule particles that are the manufacturing target are the main capsule particles in the above description. However, in the present invention, since sub-capsule particles are actively manufactured, if the quality such as the particle size of the sub-capsule particles is not a problem in commerce, they can be used as a product. Therefore, it is also possible to make both the main capsule particles and the sub-capsule particles the manufacturing target. Of course, the main capsule particles have the particle form of seamless capsules including a film and contents. However, the sub-capsule particles often also have the particle form of seamless capsules.

[0016] The sub-capsule particles do not necessarily have to be of one type. The sub-capsule particles may be smaller than the particle size of the main capsule particles, and two or more types of sub-capsule particles smaller than the particle size of the main capsule particles may be obtained. However, when producing the main capsule particles more stably, it is preferable that the variation in the particle size of the sub-capsule particles is reduced to a certain extent. If the particle size of the main capsule particles is 1, the particle size of the sub-capsule particles is 0.9 or less, preferably 0.5 or less. Also, the lower limit of the particle size of the sub-capsule particles is not particularly limited. For example, the particle size of the sub-capsule particles may be larger than 0.03. It is less likely to produce sub-capsule particles with a particle size larger than that of the main capsule particles, which may make it unclear which are the main capsule particles.

[0017] The generation ratio of the sub-capsule particles is more than 0.5 when the generation ratio of the main capsule particles is set to 1. When the generation ratio of the sub-capsule particles is 0.5 or less, it becomes difficult to stabilize the quality of the main capsule particles. When the generation ratio of the main capsule particles is 1, the generation ratio of the sub-capsule particles is preferably 0.6 or more. Also, the upper limit of the generation ratio of the sub-capsule particles may be, for example, 1.2 or less. The above generation ratio is calculated from the number of generated main capsule particles and sub-capsule particles. As a method for measuring each generation number, in the examples described later, the number of main capsule particles and sub-capsule particles passing through a predetermined observation position in the formation tube per unit time is used, but it may also be the number of recovered main capsule particles and sub-capsule particles flowing out downstream of the formation tube per unit time.

[0018] The main capsule particles and the sub-capsule particles are usually formed in pairs. The sub-capsule particles often exist around the main capsule particles, for example, as described in FIG. 3. To represent this state, the sub-capsule particles may also be called "satellites".

[0019] In this manufacturing method, in order to actively form sub-capsule particles and stably manufacture the main capsule particles, it is preferable that there is a relationship shown in the following formula (1) between the average velocity (V) of the coagulating liquid in the forming tube through which the discharge liquid that becomes capsule particles passes during manufacturing, the particle size (R) of the main capsule particles, and the number of generated main capsule particles (N): 0.7 ≦ V / (R×N) ≦ 2.1 (Formula 1) When this relational expression is satisfied, the main capsule particles are more likely to be stably manufactured. The lower limit of the above formula (1) is preferably 0.75, more preferably 0.8, still more preferably 0.85. The upper limit is preferably 2.05, more preferably 2.0, still more preferably 1.95, and even more preferably 1.9. The unit of the average velocity (V) of the coagulating liquid is mm / second, the unit of the particle size of R is mm, and the unit of the number of generated N is particles / second.

[0020] "V / (R×N)" in the above formula (1) represents the ratio of the moving distance of the coagulating liquid to the total particle size of the main capsule particles passing through the forming tube per unit time. Therefore, the smaller "V / (R×N)" is, the smaller the interval between adjacent main capsule particles, and the smaller the particle size of the sub-capsule particles is likely to be, so in some cases, it becomes difficult to form sub-capsule particles. On the other hand, the larger "V / (R×N)" is, the larger the interval between adjacent main capsule particles, and the larger the particle size of the sub-capsule particles is likely to be.

[0021] <Capsule particles (also referred to as "seamless capsules".)> Capsule particles usually have a film (or outermost layer) and a content (the content or inner layer encapsulated within this film). In other words, capsule particles have a content and a film covering this content. Also, in the present invention, an intermediate layer may be provided between the film and the content. The intermediate layer is provided to protect the content and the film from each other and to prevent deterioration of the performance of the content. Note that when referring to "capsule particles" in this specification, it means both "main capsule particles" and "sub-capsule particles".

[0022] <Content> In the capsule particles, the state of the content is not particularly limited. The content may be, for example, liquid at room temperature, solid, or semi-solid. Examples of components that can be incorporated into such content include fatty acids (e.g., caprylic acid, capric acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid, linoleic acid, etc.), fatty acid esters [e.g., triglycerides (such as medium-chain fatty acid triglycerides (MCT, etc.), glycerin esters (fats); non-glycerin-based fatty acid esters such as isopropyl myristate, etc.)], vegetable oils (e.g., olive oil, sunflower oil, corn oil, peanut oil, grape seed oil, wheat germ oil, rapeseed oil, jojoba oil, safflower oil), hardened oils, mineral oils, silicone oils, sucrose fatty acid esters, liquid paraffin, squalane, fragrances (e.g., esters, alcohols, aldehydes, ketones, phenols, ethers, lactones, hydrocarbons, nitrogen-containing compounds, sulfur-containing compounds, acids, etc.), functional components (e.g., vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, folic acid, niacin, pantothenic acid, biotin, caffeine, iron, copper, zinc, manganese, selenium, chromium, molybdenum, polyglutamic acid, Ampelopsis grossedentata polyphenol, blueberry extract, blackcurrant extract, bilberry extract, Salacia extract, carrot powder, Gokahi, licorice, peony, cinnamon, Aster tataricus, Schizonepeta tenuifolia, Lactobacillus, Bifidobacterium, yeast), etc.

[0023] Functional components mean components that are expected to exert physiological effects on the living body when present in the living body. Functional components are not limited to the above, and any component can be used according to the physiological effects on the living body.

[0024] As for the fragrance, there is no particular limitation as long as the content can be fragranced, and either natural fragrance or synthetic fragrance may be used. The fragrance may be used alone or in combination of two or more kinds. The natural fragrance is not particularly limited. For example, rose, jasmine, bitter orange neroli, chamomile, ylang-ylang, geranium, eucalyptus, tea tree, petitgrain, satsuma mandarin, orange, lemon, lime, bergamot, pepper, juniper, vanilla, sandalwood, pine, hinoki, cinnamon, frankincense, myrrh, vetiver, spikenard, orris root, lavender, lemongrass, basil, rosemary, mints (such as spearmint, menthol, peppermint, etc.) and berries (such as blueberry, cranberry, lingonberry, huckleberry, raspberry, blackberry, loganberry, salmonberry, boysenberry, strawberry, bilberry, elderberry, and kuwaberry, etc.) and other oils can be mentioned. The synthetic fragrance is not particularly limited as long as it has been conventionally used for the purpose of imparting aroma and flavor.

[0025] When the content is solid or semi-solid at room temperature, the content can contain a lipid (specifically, an oil or fat) having an ascending melting point of 24°C to 55°C. The "ascending melting point" is defined as "the temperature at which the sample softens sufficiently and floats in an open capillary tube" and is measured in accordance with ISO6321:2002.

[0026] Fats and oils are glycerin esters of fatty acids and may be any of monoglycerides, diglycerides, and triglycerides. The fatty acids in the fats and oils preferably have a carbon number within the range of 10 to 20. Such fatty acids include, for example, lauric acid (carbon number 12), myristic acid (carbon number 14), palmitic acid (carbon number 16), stearic acid (carbon number 18), oleic acid (carbon number 18: number of unsaturated double bonds 1), linoleic acid (carbon number 18: number of unsaturated double bonds 2), linolenic acid (carbon number 18: number of unsaturated double bonds 3), arachidic acid (carbon number 20), eicosenoic acid (carbon number 20: number of unsaturated double bonds 1), and are at least one selected from the group consisting of the above, but are not limited to the above, and any fatty acid can be used.

[0027] When the content is solid or semi-solid at room temperature, the content can contain fats and oils with a melting point rise of 60°C or higher. For the convenience of explanation, the fats and oils with a melting point rise of 60°C or higher are also referred to as the second fats and oils, and the fats and oils with a melting point rise of 24 to 55°C are sometimes referred to as the first fats and oils. The melting point rise of the second fats and oils is usually 190°C or lower, preferably 150°C or lower, more preferably 100°C or lower, and even more preferably 80°C or lower.

[0028] The second oil or fat is, like the first oil or fat, a fatty acid glycerin ester, but may be at least one selected from the group consisting of glycerin fatty acid esters other than the oils or fats used for the first oil or fat, polyglycerin fatty acid esters, and beeswax. The polyglycerin fatty acid ester is an esterified product of a polyglycerin formed by condensation of a fatty acid and a plurality of glycerins, and the number of glycerin skeletons constituting the polyglycerin, the number of fatty acids, and the types of fatty acids are not particularly limited as long as the melting point of the second oil or fat is 60°C or higher. The fatty acid contained in the fatty acid ester or polyglycerin fatty acid ester preferably has 10 to 30 carbon atoms. Such fatty acids include, for example, lauric acid (12 carbon atoms), myristic acid (14 carbon atoms), palmitic acid (16 carbon atoms), palmitoleic acid (16 carbon atoms: number of unsaturated double bonds 1), stearic acid (18 carbon atoms), oleic acid (18 carbon atoms: number of unsaturated double bonds 1), linoleic acid (18 carbon atoms: number of unsaturated double bonds 2), linolenic acid (18 carbon atoms: number of unsaturated double bonds 3), arachidic acid (20 carbon atoms), eicosenoic acid (20 carbon atoms: number of unsaturated double bonds 1), behenic acid (22 carbon atoms), and lignoceric acid (24 carbon atoms), and are at least one selected from the group consisting of these, but are not limited to the above, and any fatty acid can be used.

[0029] Excipients, stabilizers, surfactants, adjuvants, foaming agents, etc. may be appropriately blended in the contents of the capsule particles of the present invention. The amounts of these blending agents are not particularly limited as long as the effects of the present invention are not inhibited.

[0030] <Film> The capsule particles of the present invention are coated with a film on the outside of the contents. The film contains a water-soluble natural polymer. The water-soluble natural polymer is selected from, for example, gelatin, casein, zein, pectin or its derivatives, alginic acid or its salts, agar, gellan gum, carrageenan, fausellaran, chitosan, curdlan, starch, modified starch, pullulan, mannan, and mixtures thereof. Of course, the water-soluble natural polymer is not limited to these. These water-soluble natural polymers are preferably in the range of 50% to 90% by weight based on the total solid content weight of the film composition of the seamless capsule. When using alginate, gellan gum, pectin, or carrageenan, an alkali metal salt, alkaline earth metal salt, ammonium salt, etc. may be added as appropriate.

[0031] In order to impart flexibility to the film of the capsule particles of the present invention in a dry state, a plasticizer may be further contained. Examples of the plasticizer include glycerin, sorbitol, etc. The blending amount of the plasticizer is 1 to 50% by weight, preferably 5 to 40% by weight, more preferably 15 to 35% by weight based on the total weight of the film after drying. If the blending amount of the plasticizer is less than 1% by weight, the film cannot withstand vacuum drying, or it cannot maintain sufficient flexibility in a dry state and cracks occur. If it exceeds 50% by weight, the film softens and adhesion or melting occurs at high temperatures.

[0032] The film of the capsule particles of the present invention may, if necessary, contain various additives commonly used in this field, such as fragrances, sweeteners, colorants, preservatives such as parabens, etc. in addition to the above composition. When using such additives, the total content of all additives is, for example, 0.01% to 10% by weight, preferably 0.1% to 5% by weight based on the total solid content weight of the composition that forms the film of the capsule.

[0033] The thickness of the film (film thickness) is not particularly limited because it can be arbitrarily selected according to the purpose of use of the capsule particles. For example, the film thickness may be 10 to 600 μm, may be 30 to 400 μm, or may be 40 to 250 μm.

[0034] <Intermediate layer> The intermediate layer is provided as needed. The intermediate layer is formed by making the contents into multiple layers or making the film layer into multiple layers. For example, in the case of liquids with different viscosities for the contents, a low-viscosity one can be used for the inner layer and a high-viscosity one can be used for the second layer (the second layer from the inner layer) to make it into multiple layers. Or when using multiple contents with different melting points of fats and oils, the melting point of the inner layer can be made the lowest and the melting point of the second layer can be made higher than that of the inner layer to make it into multiple layers. Also, for the film, similarly, for example, a film with low oxygen permeability can be used as the outermost layer, and a film of a normal water-soluble natural polymer can be formed as the second layer from the outside inside it.

[0035] <Method for producing capsule particles> The method for producing the capsule particles of the present invention can be carried out using a production apparatus as shown in FIG. 2. FIG. 2 is a diagram schematically showing the production apparatus used in the method for producing the capsule particles of the present invention, and the figure used in the description of Patent Document 1 is used. This production apparatus includes a concentric multi-layer nozzle A and a cooling pipe 19 for flowing down a coagulating liquid.

[0036] FIG. 2 will be described. FIG. 2 shows an apparatus for producing three-layer capsule particles. The content liquid 14 is discharged from the tip (discharge port) of the inner nozzle 11, and the film liquid 16 is discharged from the tip (discharge port) of the outer nozzle 13. In FIG. 2, the case where the intermediate layer is one layer is shown, so the intermediate layer liquid 14 is discharged from the tip (discharge port) of the intermediate nozzle 12 arranged between the nozzle 11 and the nozzle 13. Each nozzle is formed in a concentric circle with the central axis of the inner nozzle 11 as a reference. Although FIG. 2 shows the intermediate layer nozzle 12 for forming the intermediate layer, the case where there is no intermediate layer nozzle or where there are multiple intermediate layer nozzles is also included in the present invention.

[0037] The arrow existing in Fig. 2 indicates the flowing direction of the solidifying liquid 18 within the forming tube 19. The solidifying liquid 18 flows downward inside the forming tube 19. The droplets (the droplets forming the capsule particles) ejected from the concentric multiple nozzles are ejected into the solidifying liquid 18 within the forming tube 19, initially forming a long and continuous rod-shaped ejected liquid B, which becomes spherical due to surface tension and solidifies simultaneously while descending within the forming tube 19, thereby forming the capsule particles 17.

[0038] In the present invention, as shown in Fig. 3, these capsule particles are formed in pairs of two types, namely main capsule particles 20 and sub-capsule particles 21 as much as possible. Fig. 3 is a diagram schematically showing that the main capsule particles 20 and the sub-capsule particles 21 form pairs in the solidifying liquid 18 flowing in the arrow direction at the lower part of the forming tube 19. In Fig. 2, only the main capsule particles 17 are described for the capsule particles, but it is adjusted such that sub-capsule particles also exist in the vicinity of the capsule particles. Incidentally, in Fig. 3, the sub-capsule particles 21 are shown as existing in pairs with the main capsule particles 20, but a state where zero or a plurality of sub-capsule particles exist with respect to one main capsule particle 20 may be partially formed in the flowing direction of the solidifying liquid 18. However, when stably manufacturing the main capsule particles, as shown in Fig. 3, it is preferable that the main capsule particles 20 are formed in pairs with one sub-capsule particle 21.

[0039] In the present invention, as already described, it is necessary that the particle size of the main capsule particles is larger than that of the sub-capsule particles, and when the generation ratio of the main capsule particles is set to 1, the generation ratio of the sub-capsule particles exceeds 0.5.

[0040] The particle size (diameter of the sphere) of the main capsule particles is considered based on the target particle size and is not particularly limited. For example, it preferably has a diameter of 0.3 to 10 mm, more preferably 1 to 8 mm. If the diameter of the main capsule particles is less than 0.3 mm, it is difficult to manufacture by the dropping method used in the present invention. Although there is no particular problem with the particle size of the main capsule particles exceeding 10 mm, when the main capsule particles are orally ingested, it tends to be difficult to swallow.

[0041] There is no problem as long as the particle size of the sub-capsule particles is smaller than that of the main capsule particles. However, when the particle size of the sub-capsule particles is larger than that of the main capsule particles, it becomes difficult to determine which are the main capsule particles, making control difficult, which is not desirable.

[0042] In the present invention, as already described, in order to stably produce capsule particles, it is desirable that the average velocity (V) of the coagulating liquid in the forming tube, the particle size (R) of the main capsule particles, and the number of generated main capsule particles (N) satisfy the following formula (1). 0.7 ≦ V / (R × N) ≦ 2.1 (Formula 1) When within this range, the main capsule particles can be stably produced. Secondly, although it is secondary, since the sub-capsule particles are actively produced, the sub-capsule particles can also be produced, and the sub-capsule particles are also generated stably and steadily. Therefore, it is also possible to produce sub-capsule particles (particle sizes smaller than the main capsule particles).

[0043] After separating the obtained capsule particles into main capsule particles and sub-capsule particles, the target capsule particles (seamless capsules) can be produced by drying the target particles.

[0044] In the production of the capsule particles of the present invention, a capsule film preparation liquid and a capsule content liquid are prepared in advance. Then, each of the capsule film preparation liquid and the capsule content liquid is discharged from a multi-layer nozzle to form a composite jet.

[0045] The capsule film preparation liquid contains a natural polymer and a solvent. The natural polymer is a component that coagulates the capsule film preparation liquid and is water-soluble. This natural polymer quotes the description of the above-mentioned water-soluble natural polymer.

[0046] The solvent is a liquid that disperses the components in the capsule film preparation liquid. Such a solvent is, for example, at least one selected from the group consisting of water and ethanol. Examples of water include tap water, ion-exchanged water, distilled water, ultrapure water, or mixtures thereof.

[0047] The capsule film preparation liquid may further contain a plasticizer. The plasticizer is a component that imparts flexibility to the coagulum of the capsule film preparation liquid. In particular, in a dry capsule that is a dried product of a wet capsule (wet capsule particles), the plasticizer can maintain sufficient flexibility for the film and make it less likely to crack. Examples of the plasticizer include polyhydric alcohols such as glycerin and sorbitol. The plasticizer is not limited to the above, and any component can be applied.

[0048] The capsule film preparation liquid may further contain additives such as dyes, flavor components, preservatives, or fragrances, if necessary.

[0049] In the method for producing capsule particles, the coagulation liquid is typically 20°C or lower, preferably 1 - 18°C. Also, the temperature of each liquid extruded from each nozzle is not particularly limited, but is typically 15 - 70°C, preferably 20 - 65°C.

[0050] As the coagulation liquid, for example, medium-chain fatty acid triglycerides (MCT), vegetable oils (such as coconut oil, sunflower oil, safflower oil, sesame oil, rapeseed oil, grape seed oil, and mixtures thereof), liquid paraffin, and mixtures thereof can be used.

[0051] In the above production method, although not shown in the figure, vibration means may be used to apply appropriate vibration to the composite jet flow (B in Figure 2) to improve the breakage of the composite jet.

[0052] The capsule particles of the present invention can be washed with water, heat-sterilized, or heat-sterilized as necessary depending on the usage conditions.

Example

[0053] The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto. In the examples, "parts" and "%" are based on weight unless otherwise specified.

[0054] In the examples and comparative examples, the following components were used. · Medium-chain fatty acid triglyceride (density: 0.960 g / cm 3 (10 °C)) · Gelatin: Gelatin CP-771 manufactured by Gelice Co., Ltd. · Agar: Agar T-1 manufactured by Ina Food Industry Co., Ltd.

[0055] Examples 1 to 5 and Comparative Examples 1 to 2 Content liquid: A capsule content liquid was prepared using only medium-chain fatty acid triglyceride (MCT). Capsule film preparation liquid: 80 parts of gelatin, 20 parts of sorbitol, and 400 parts of ion-exchanged water were mixed until uniform, and then this mixture was heated and dissolved at 60 °C to prepare a capsule film preparation liquid. The viscosity of the capsule film preparation liquid was 50 mPa·s (60 °C).

[0056] Next, in a seamless capsule manufacturing apparatus (manufactured by Morishita Jintan Co., Ltd.) as illustrated in Fig. 2, using a concentric double nozzle, the capsule content liquid was discharged from the innermost nozzle and the capsule film preparation liquid was discharged from the outermost nozzle simultaneously into a coagulating liquid at 10 °C so that the solid content of the capsule film preparation liquid was 30 parts with respect to 70 parts of the capsule content liquid, thereby forming a two-layer wet capsule.

[0057] During capsule manufacturing, it was confirmed that main capsule particles and sub-capsule particles were continuously manufactured in pairs in the forming tube. At this time, the number of main capsule particles and sub-capsule particles passing through the observation position for 10 seconds in a video taken near the center of the length of the forming tube was measured to calculate the number of occurrences of main capsule particles and sub-capsule particles (unit: particles / second). Also, the average flow rate of the coagulating liquid was calculated by measuring the weight of the coagulating liquid flowing out of the forming tube for 10 seconds and introducing this coagulating liquid weight into the following formula 2. Average flow velocity = Weight of solidified liquid / (Density of solidified liquid × Flow path cross-sectional area of forming tube) / 10 seconds ··· (Equation 2)

[0058] According to the following evaluation method, the pharmaceutical property I (cracking) and pharmaceutical property II (particle size variation) of the main capsule particles were evaluated, and the presence or absence of abnormally shaped sub-capsule particles, the generation rate of abnormally shaped sub-capsule particles, and the particle size variation of the sub-capsule particles were evaluated as described below, and the evaluation results are shown in Table 1. Table 1 shows the particle size (mm) of the main capsule particles, the ratio of the average solidification liquid velocity to the product of the particle size of the main capsule particles and the number of generated main capsule particles (V / (R × N)), the particle size (mm) of the sub-capsule particles, the ratio of the particle size of the sub-capsule particles to the particle size of the main capsule particles, and the generation rate of the sub-capsule particles when the generation rate of the main capsule particles is set to 1.

[0059] <Evaluation method> [Pharmaceutical property I (cracking)] 100 main capsule particles passing through the observation position were observed in the video taken near the center of the length of the forming tube, and the ratio of the number of cracked main capsule particles among these 100 particles was calculated as a percentage out of 100.

[0060] [Pharmaceutical property II (particle size variation)] 20 main capsule particles were randomly collected. Then, the particle size of each main capsule particle was measured with vernier calipers, and the average particle size, standard deviation, and coefficient of variation were calculated from the measured values. And the percentage of the coefficient of variation was taken as the evaluation result in "Pharmaceutical property II".

[0061] [Generation rate of abnormally shaped sub-capsule particles] 100 sub-capsule particles were randomly collected. Then, the appearance of each sub-capsule particle was visually confirmed, and the number of capsules with a shape other than spherical (abnormal shapes such as water droplet shape) was counted. After that, the percentage value obtained by dividing the number of abnormal-shaped particles by 100 was calculated.

[0062] [Particle size variation of sub-capsule particles] Twenty sub-capsule particles were randomly collected. Then, the particle size of each sub-capsule particle was measured with a vernier caliper, and the average particle size, standard deviation, and coefficient of variation were calculated from the measured values. And the percentage of the coefficient of variation was used as the evaluation result in "Formulation Property II".

[0063]

Table 1

[0064] Examples 6 to 9 and Comparative Examples 3 to 4 Content liquid: The capsule content liquid was prepared with only MCT. Capsule film preparation liquid: 68 parts of agar, 32 parts of sodium alginate, and 6000 parts of ion-exchanged water were mixed until uniform, and then this mixture was heated and dissolved in an autoclave at a temperature of 105°C to prepare a capsule film preparation liquid. The viscosity of the capsule film preparation liquid was 70 mPa·s (80°C).

[0065] Next, in a seamless capsule manufacturing apparatus (manufactured by Morishita Jintan Co., Ltd.) as illustrated in Figure 2, using a concentric double nozzle, the capsule content liquid was discharged from the innermost nozzle and the capsule film preparation liquid was discharged from the outermost nozzle simultaneously into a coagulating liquid at 10°C so that the solid content of the capsule film preparation liquid was 1.63 parts with respect to 100 parts of the capsule content liquid, thereby forming a two-layer wet capsule.

[0066] During capsule manufacturing, it was confirmed that the main capsule particles and the sub-capsule particles were continuously manufactured in pairs in the forming tube. At this time, the number of generated main capsule particles and sub-capsule particles and the average flow rate of the coagulating liquid were calculated in the same manner as in Example 1.

[0067] According to the above evaluation method, the formulation property I (cracking) and formulation property II (variation in particle size) of the main capsule particles were evaluated, and the presence or absence of abnormally shaped sub-capsule particles, the generation rate of abnormally shaped sub-capsule particles, and the variation in the particle size of the sub-capsule particles were evaluated, and the evaluation results are shown in Table 2. The same items as in Table 1 are also described in Table 2.

[0068]

Table 2

[0069] Examples 1 to 5 and Comparative Examples 1 to 2 are examples where the particle size of the main capsule particles is 4 mm. In all examples, sub-capsule particles with a particle size smaller than that of the main capsule particles are generated. However, in Comparative Examples 1 to 2, when the generation ratio of the sub-capsule particles is set to 1, the generation ratio of the sub-capsule particles is less than 0.5. In Comparative Examples 1 to 2, there are many cracks and variations in the main capsule particles, and the capsule particles cannot be stably manufactured. In Examples 1 to 5, there are few cracks in the main capsule particles and little variation in the particle size. Also, in all of the examples, the generation of sub-capsules with irregular shapes is very small, and there is little variation in the particle size of the sub-capsule particles. Incidentally, in Comparative Example 2, the cracking (%) of the main capsule particles is comparable to that of the examples, but the variation in the particle size of the main capsule particles is high, and the generation of irregular-shaped sub-capsule particles is also large.

[0070] Examples 6 to 9 and Comparative Examples 3 to 4 are examples where the particle size of the main capsule particles is 1.5 mm. In all examples, sub-capsule particles with a particle size smaller than that of the main capsule particles are generated. However, in Comparative Examples 3 to 4, when the generation ratio of the sub-capsule particles is set to 1, the generation ratio of the sub-capsule particles is less than 0.5. In Comparative Examples 3 to 4, there are many cracks and variations in the main capsule particles, and the main capsule particles cannot be stably manufactured. In Examples 1 to 5, there are few cracks in the main capsule particles and little variation in the particle size. Also, in all of the examples, the generation of sub-capsules with irregular shapes is very small, and there is little variation in the particle size of the sub-capsule particles. Incidentally, in Comparative Example 4, the cracking (%) of the main capsule particles is comparable to that of the examples, but the variation in the particle size of the main capsule particles is high, and the generation of irregular-shaped sub-capsule particles is also large.

[0071] In the examples, by actively manufacturing the sub-capsule particles, the particle size of the main capsule particles is stabilized, the cracking is reduced, and the main capsule particles can be stably manufactured. Also, since the particle size of the sub-capsule particles is also stable, it is possible to manufacture the sub-capsule particles. The sub-capsule particles clearly form two layers of an inner content layer and an outer film layer.

[0072] <Addition of aspects of the present invention> [1] Using a capsule manufacturing apparatus comprising a concentric multi-nozzle having, from the inside, a content nozzle, a film nozzle, and one or more intermediate nozzles, if necessary, existing between the content nozzle and the film nozzle, arranged concentrically, and a forming tube in which capsule droplets discharged from the discharge port of the concentric multi-nozzle solidify in a flowing coagulating liquid, forming two types of capsule particles, main capsule particles and sub-capsule particles, in the forming tube, wherein the particle size of the main capsule particles is larger than the particle size of the sub-capsule particles, when the generation ratio of the main capsule particles is set to 1, the generation ratio of the sub-capsule particles is more than 0.5, A method for manufacturing seamless capsules. [2] The method for manufacturing seamless capsules according to [1], wherein the main capsule particles are formed in a pair with the sub-capsule particles. [3] The average flow velocity of the coagulating liquid in the forming tube of the capsule particles, the particle size of the main capsule particles, and the number of generated main capsule particles satisfy the following relationship: 0.7 ≦ V / (R×N) ≦ 2.1 (Equation 1) (In Equation 1, V is the average flow velocity of the coagulating liquid, R is the particle size of the main capsule particles, and N is the number of generated main capsule particles.) The method for manufacturing seamless capsules according to [1] or [2], which satisfies the above. [4] Further, after separating the main capsule particles from the sub-capsule particles, drying them, the method for manufacturing seamless capsules according to any one of [1] to [3]. [5] In a method of manufacturing seamless capsules using a capsule manufacturing device including a concentric multiple nozzle having, from the inside, a content nozzle, a film nozzle, and one or more intermediate nozzles, if any, existing between the content nozzle and the film nozzle, arranged concentrically, and a forming tube in which capsule droplets discharged from the discharge port of the concentric multiple nozzle solidify in a flowing coagulating liquid, Solidify the droplets discharged from the concentric multiple nozzle in the forming tube to form two types of capsule particles, i.e., main capsule particles and sub-capsule particles, wherein the particle size of the main capsule particles is larger than that of the sub-capsule particles, when the generation ratio of the main capsule particles is set to 1, the generation ratio of the sub-capsule particles is more than 0.5, A method for preventing cracking of the film of seamless capsules. [6] The method for preventing cracking of the film of seamless capsules according to [5], wherein the main capsule particles are formed in a pair with the sub-capsule particles. [7] The average flow velocity of the coagulating liquid in the forming tube of the capsule particles, the particle size of the main capsule particles, and the number of generated main capsule particles satisfy the following relationship: 0.7 ≦ V / (R×N) ≦ 2.1 (Formula 1) (In Formula 1, V is the average flow velocity of the coagulating liquid, R is the particle size of the main capsule particles, and N is the number of generated main capsule particles.) The method for preventing cracking of the film of seamless capsules according to [5] or [6], which satisfies the above. [8] Further, after separating the main capsule particles from the sub-capsule particles, drying them. The method for preventing cracking of the film of seamless capsules according to any one of [5] to [7]. [9] In a method of manufacturing capsule particles using a capsule manufacturing device including a concentric multiple nozzle having, from the inside, a content nozzle, a film nozzle, and one or more intermediate nozzles, if any, existing between the content nozzle and the film nozzle, arranged concentrically, and a forming tube in which capsule droplets discharged from the discharge port of the concentric multiple nozzle solidify in a flowing coagulating liquid, The droplets ejected from the concentric multi-nozzle are solidified in the forming tube to form two types of capsule particles, namely main capsule particles and sub-capsule particles. The particle size of the main capsule particles is larger than that of the sub-capsule particles. When the generation ratio of the main capsule particles is set to 1, the generation ratio of the sub-capsule particles is more than 0.5. A method for simultaneously manufacturing two types of seamless capsules.

[10] The method for simultaneously manufacturing two types of seamless capsules according to [9], wherein the main capsule particles are formed in pairs with the sub-capsule particles.

[11] The average flow velocity of the coagulating liquid in the forming tube of the capsule particles, the particle size of the main capsule particles, and the number of generated main capsule particles have the following relationship: 0.7 ≦ V / (R×N) ≦ 2.1 (Formula 1) (In Formula 1, V is the average flow velocity of the coagulating liquid, R is the particle size of the main capsule particles, and N is the number of generated main capsule particles.) The method for simultaneously manufacturing two types of seamless capsules according to [9] or

[10] , which satisfies the above condition.

[12] Further, after separating the main capsule particles and the sub-capsule particles, each is dried. The method for simultaneously manufacturing two types of seamless capsules according to any one of [9] to

[11] .

Explanation of Reference Numerals

[0073] 1... Content 2... Film 3... Intermediate layer 11... Content nozzle 12... Intermediate layer nozzle 13... Film nozzle 14... Content liquid 15... Intermediate layer liquid 16... Film liquid 17... Seamless capsule 18... Coagulating liquid 19... Forming tube 20... Main capsule particle 21... Sub-capsule particle A... Concentric multi-nozzle B... Forming part

Claims

【Claim 1】 The invention described in this specification.

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