Seamless Capsule

Abstract

To provide novel seamless capsules with less "unevenness" and "eyes," which are common drawbacks of seamless capsules.SOLUTION: The present invention is, for example, a seamless capsule produced by using capsule contents and a capsule film composition as materials. The seamless capsule contains phospholipids in the capsule contents. The phospholipid is lecithin containing 85% by weight or more of phosphatidylcholine. According to the present invention, for example, uneven thickness and eyes in the seamless capsule can be reduced.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present invention belongs to the technical field of capsule preparations useful in medicines, quasi-drugs, functional foods, luxury items, etc. Among such capsule preparations, the present invention relates to so-called seamless capsules. [Background technology]

[0002] Seamless capsules are a type of soft capsule, and are produced by utilizing the property that liquid droplets become round due to their surface tension, so they are nearly spherical, and unlike soft capsules, they have no seams. Features of seamless capsules include the ability to select a wide range of particle sizes, such as the ability to produce microcapsules with a diameter of 0.5 mm, the ability to select a wide range of capsule thickness and hardness, the ability to produce capsules that dissolve quickly because the thickness of the capsule can be made thin, the ability to produce heat-resistant capsules, and the ability to use a capsule base other than gelatin because heat sealing of the capsule is not required. Due to these features, seamless capsules are widely used in the pharmaceutical and food industries.

[0003] As described above, seamless capsules have various advantages, but they have disadvantages called "uneven thickness" and "eyes" that are not seen in ordinary soft capsules. Seamless capsules are usually produced by simultaneously discharging the oily capsule content liquid from the inner nozzle of a double nozzle and the capsule shell liquid such as gelatin from the outer nozzle into the cooling oil liquid at a constant speed, cutting the two layers of liquid at regular intervals and forming droplets due to interfacial tension, and then gelling the outer shell to form capsules. In this way, seamless capsules are produced by dropping the two-layer solution using a double nozzle and pouring the oily capsule content liquid into the capsule. At this time, depending on the properties of the content liquid such as viscosity and specific gravity, the content liquid may not necessarily be contained in the center of the capsule. This causes a phenomenon in which the shell is thin and the strength of that part is weakened. This phenomenon in which the thickness of the shell is uneven is called "uneven thickness" and is considered a defect of seamless capsules because it causes partial weakness.

[0004] Seamless capsules are manufactured by pushing out the combined shell liquid and content liquid through a double nozzle while cutting them into the desired size evenly, adjusting the gravity, the pulse and vibration applied to the nozzle, and the flow rate of the cooling oil. At the moment they are cut into a certain size, surface tension comes into play, and they take on the most stable shape, i.e., a sphere. At this time, because they are pushed out through a concentric nozzle, air bubbles and oil droplets from the content inevitably remain in the shell. These are called "eyes," and like the uneven thickness mentioned above, eyes are considered a drawback of seamless capsules because they reduce the capsule strength.

[0005] In order to reduce the above-mentioned defects of seamless capsules, such as "uneven thickness" and "eyes," components such as interfacial tension adjusters and gelation accelerators have been incorporated into the shell composition or capsule contents. Meanwhile, Patent Document 1 discloses a seamless capsule that does not contain an interfacial tension adjuster or gelation accelerator in either the shell composition or the capsule contents, and claims that a seamless capsule with less uneven thickness and eyes can be obtained even without the inclusion of an interfacial tension adjuster or gelation accelerator. Patent Document 2 discloses a seamless capsule with a single-layered membrane that encapsulates an oil agent (capsule contents) containing phospholipids. However, the invention of Patent Document 2 is based on the finding that when manufacturing seamless capsules with a single-layered membrane that encapsulate an oil agent containing phospholipids, a small amount of phospholipids gets mixed into the cooling oil from the double nozzle and the capsules are destroyed by the phospholipids, and in order to solve this problem, an emulsifier with an HLB of 3 or less is further blended into the capsule contents. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] International Publication No. 2009 / 004999 [Patent Document 2] JP 2015-199698 A Summary of the Invention [Problem to be solved by the invention]

[0007] The main object of the present invention is to provide a new seamless capsule with less "uneven wall thickness" and "eyes", which are general defects of seamless capsules. Another object of the present invention is to provide a method for producing such seamless capsules and a method for reducing the uneven wall thickness and eyes in seamless capsules. [Means for solving the problem]

[0008] As a result of extensive research, the present inventors discovered that the above-mentioned problems could be solved by incorporating lecithin containing at least 85% by weight or more of phosphatidylcholine into the capsule contents, and thus completed the present invention.

[0009] The present invention can include, for example, the following. [1] A seamless capsule manufactured using a capsule content and a capsule shell composition as materials, the capsule content containing a phospholipid, the phospholipid being lecithin containing 85% or more by weight of phosphatidylcholine. [2] The seamless capsule described in [1] above, wherein the phospholipid is soybean lecithin or egg yolk lecithin. [3] The seamless capsule according to [1] or [2] above, wherein the capsule shell composition contains gelatin or bovine gelatin as a base. [4] The seamless capsule according to any one of [1] to [3] above, wherein the capsule contents contain an omega-3 fatty acid or an ethyl ester thereof. [5] The seamless capsule described in [4] above, wherein the omega-3 fatty acid is eicosapentaenoic acid and / or docosahexaenoic acid. [6] A pharmaceutical preparation comprising the seamless capsule according to any one of [1] to [5] above.

[0010] [7] A method for producing a seamless capsule made from a capsule content and a capsule shell composition, comprising a step of blending a phospholipid with the capsule content, the phospholipid being lecithin containing 85% or more by weight of phosphatidylcholine. [8] The method for producing a seamless capsule according to the above [7], wherein the phospholipid is soybean lecithin or egg yolk lecithin. [9] The method for producing a seamless capsule according to the above [7] or [8], wherein the capsule shell composition contains gelatin or bovine gelatin as a base.

[10] The method for producing a seamless capsule according to any one of the above [7] to [9], wherein the capsule contents contain an omega-3 fatty acid or an ethyl ester thereof.

[11] The method for producing a seamless capsule described in

[10] above, wherein the omega-3 fatty acid is eicosapentaenoic acid and / or docosahexaenoic acid.

[0011]

[12] A method for reducing eyes or thickness irregularities occurring in the shell of a seamless capsule, comprising a step of blending a phospholipid with the capsule contents during a process for producing a seamless capsule using a capsule contents and a capsule shell composition as materials, wherein the phospholipid is lecithin containing 85% or more by weight of phosphatidylcholine.

[13] The method according to

[12] above, wherein the phospholipid is soybean lecithin or egg yolk lecithin.

[14] The method according to

[12] or

[13] above, wherein the capsule shell composition contains gelatin or bovine gelatin as a base.

[15] The method according to any one of

[12] to

[14] above, wherein the capsule contents contain omega-3 fatty acids or ethyl esters thereof.

[16] The method according to

[15] above, wherein the omega-3 fatty acid is eicosapentaenoic acid and / or docosahexaenoic acid. Effect of the Invention

[0012] According to the present invention, for example, uneven thickness and eyes in seamless capsules can be reduced. [Brief description of the drawings]

[0013] [Figure 1] Photo of seamless capsule (grayscale). [Diagram 2] 1 is a photograph (grayscale) of a seamless capsule according to Example 1 (using bovine gelatin). [Diagram 3] Photograph (grayscale) of a seamless capsule according to Example 2 (using pork gelatin). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] 1 Seamless capsule according to the present invention The seamless capsule according to the present invention (hereinafter referred to as "seamless capsule of the present invention") is a seamless capsule manufactured using a capsule content and a capsule shell composition as materials, and is characterized in that the capsule content contains a phospholipid, and the phospholipid is a lecithin containing 85% by weight or more of phosphatidylcholine. The lecithin preferably contains 90% by weight or more of phosphatidylcholine. The lecithin more preferably contains 94% by weight or more to 95% by weight or more of phosphatidylcholine. The lecithin may contain almost 100% by weight of phosphatidylcholine. Here, lecithin containing 85% by weight or more of phosphatidylcholine means that the content of phosphatidylcholine in the lecithin is 85% by weight or more.

[0015] The seamless capsule of the present invention contains a capsule content and a capsule shell composition. The seamless capsule of the present invention usually has a structure in which the surfaces of oil droplets consisting of the capsule content are covered with a single layer of the capsule shell composition.

[0016] 1.1 Capsule Contents The capsule contents according to the present invention may contain, in addition to the above phospholipids, for example, physiologically active ingredients, foods, flavorings, etc. (hereinafter, these are referred to as "main ingredients") depending on the purpose. When the main ingredient is an oily ingredient, the capsule contents may consist of only the above phospholipids and the main ingredient. When the main ingredient is not an oily ingredient, the capsule contents may further contain an oily ingredient that is medicamentally or food-production-acceptable. In either case, the capsule contents may further contain an appropriate amount of an additive that is medicamentally or food-production-acceptable.

[0017] The term "oily component" as used herein refers to a hydrophobic substance that is essentially incompatible with water and that is liquefied at room temperature or when heated. In the present invention, there is no particular limitation as long as the substance is of this type.

[0018] In the present invention, examples of the main component of an oily physiologically active ingredient (hereinafter also referred to as "oily active ingredient") include ω3-fatty acids and their esters (e.g., C1-6 alkyl esters; preferably ethyl esters). Examples of such "ω3-fatty acids" include, for example, C 18 - 22 Examples of omega-3 fatty acids include octadecatrienoic acid, octadecatetraenoic acid, eicosatetraenoic acid, eicosapentaenoic acid, heneicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid.

[0019] Specific examples of ω3-fatty acid ethyl esters include octadecatrienoic acid ethyl ester, octadecatetraenoic acid ethyl ester, eicosatetraenoic acid ethyl ester, eicosapentaenoic acid (EPA) ethyl ester, heneicosapentaenoic acid ethyl ester, docosapentaenoic acid ethyl ester, docosahexaenoic acid (DHA) ethyl ester, and mixtures of two or more thereof (e.g., useful for treating hyperlipidemia (e.g., hypercholesterolemia, hyper LDL cholesterolemia, hypo HDL cholesterolemia, hypertriglyceridemia (TG)), and preventing cardiovascular events, European Pharmacopoeia name OMEGA-3-ACID ETHYL ESTERS 90). The above-mentioned oily active ingredients having a main component having physiological activity (eg, ω3-fatty acids) can be used alone or in combination of two or more kinds.

[0020] When an oily active ingredient is encapsulated in a seamless capsule, the oily active ingredient is encapsulated in the seamless capsule as it is, or as a mixture of the oily active ingredient and an additive acceptable for pharmaceutical or food manufacturing. Examples of such additives include those described below, and among them, a stabilizer (preferably α-tocopherol) is preferable. When a stabilizer is contained, the content of the stabilizer in the mixture of the oily active ingredient and the additive acceptable for pharmaceutical or food manufacturing is suitably within the range of 0.3 to 0.5% by weight.

[0021] The mixture of the oily active ingredient and the medicamentously or food-production-acceptable additive can be provided for the production of the seamless capsule of the present invention in the form of, for example, a solution, an emulsion, a suspension, or other liquid agent. When the oily active ingredient itself is liquid, it can be provided for the production of the seamless capsule of the present invention as it is.

[0022] When the main component is not an oily component, the oily component contained in the capsule contents can be, for example, fats and oils, waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, essential oils, and silicone oils.Specifically, fats and oils can be, for example, soybean oil, rice bran oil, jojoba oil, avocado oil, almond oil, olive oil, cacao butter, sesame oil, persic oil, castor oil, coconut oil, mink oil, beef tallow, lard, and other natural fats and oils, or hydrogenated oils obtained by hydrogenating these natural fats and oils, and synthetic triglycerides such as myristic acid glyceride and 2-ethylhexanoic acid glyceride.Waxes can be, for example, carnauba wax, whale wax, beeswax, and lanolin.Hydrocarbons can be, for example, liquid paraffin, petrolatum, paraffin microcrystalline wax, ceresin, squalane, and pristane. Examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, lanolic acid, isostearic acid, etc. Examples of higher alcohols include lauryl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, lanolin alcohol, cholesterol, 2-hexyldecanol, etc. Examples of esters include cetyl octanoate, myristyl lactate, cetyl lactate, isopropyl myristate, myristyl myristate, isopropyl palmitate, isopropyl adipate, butyl stearate, decyl oleate, etc. Examples of essential oils include peppermint oil, jasmine oil, camphor oil, cypress oil, spruce oil, lychee oil, turpentine oil, cinnamon oil, bergamot oil, mandarin oil, calamus oil, pine oil, lavender oil, bay oil, clove oil, Japanese cedar oil, rose oil, eucalyptus oil, lemon oil, peppermint oil, rose oil, sage oil, menthol, cineole, eugenol, citral, citronellal, borneol, linalool, gellarol, camphor, thymol, spilanthol, pinene, limonene, terpene-based compounds, etc. Examples of silicone oils include, but are not limited to, dimethylpolysiloxane, etc. The above oily components can be used alone or in combination of two or more.

[0023] The additives that may be contained in the capsule contents are not particularly limited as long as they can be used in seamless capsules. For example, colorants (e.g., food colorants such as Yellow Color No. 5, Red Color No. 2, and Blue Color No. 2; β-carotene; food lake color; ferric oxide, yellow ferric oxide), monosaccharides (e.g., pentoses such as arabinose, xylose, ribose, and 2-deoxyribose; hexoses such as glucose, fructose, galactose, mannose, sorbose, rhamnose, and fucose), disaccharides (e.g., maltose, cellobiose, α,α-trehalose, lactose, and sucrose), celluloses (e.g., crystalline cellulose (including microcrystalline cellulose)), inorganic substances (e.g., anhydrous calcium phosphate, , precipitated calcium carbonate, calcium silicate), diluents or solubilizing agents (e.g., medium-chain triglyceride (MCT) oil, olive oil, soybean oil, corn oil, water, ethanol, or mixtures thereof), pH adjusters (e.g., citrates, phosphates, carbonates, tartrates, fumarates, acetates, amino acid salts), stabilizers (e.g., α-tocopherol, tetrasodium edetate, nicotinamide, cyclodextrins), acidulants (e.g., ascorbic acid, citric acid, tartaric acid, malic acid), flavorings (e.g., menthol, peppermint oil, lemon oil, vanillin, blueberry flavor), and flow agents (e.g., light anhydrous silicic acid, hydrated silicon dioxide, talc). The above additives can be used alone or in combination of two or more.

[0024] The capsule contents according to the present invention contain a phospholipid, which is a lecithin containing 85% or more by weight of phosphatidylcholine. Preferably, the phospholipid is a lecithin containing 90% or more by weight of phosphatidylcholine. More preferably, the phospholipid is a lecithin containing 94% or more to 95% or more by weight of phosphatidylcholine.

[0025] Phosphatidylcholine is a compound well known to those skilled in the art and is a compound represented by the following general formula (I): 1 and R 2 are the same or different, C 12-22represents a hydrocarbon group. Phosphatidylcholine is usually 1 and R 2 The phosphatidylcholines are provided as mixtures of different types and combinations of phosphatidylcholines.

[0026] [ka]

[0027] The phosphatidylcholine according to the present invention is 1 and R 2 Both may be hydrogenated, but R 1 , R 2 Preferably, at least one of R is an unsaturated hydrocarbon group. 1 and R 2 Specific examples of the unsaturated hydrocarbon groups include palmitoyl (16:1), oleyl (18:1), linoleyl (18:2), linolenyl (18:3), and saturated hydrocarbon groups such as palmityl (16:0), stearyl (18:0), etc. In the present invention, the unsaturated phosphatidylcholine preferably has a content of 30% or more of unsaturated hydrocarbon groups having 18 carbon atoms, such as oleyl, linoleyl, and linolenyl, more preferably 40% or more, and particularly preferably 50% or more.

[0028] As the phospholipid according to the present invention, naturally occurring lecithin such as soybean lecithin, egg yolk lecithin, rice lecithin, etc., which is highly purified to contain 85% by weight or more of phosphatidylcholine, is used. Among them, soybean lecithin highly purified to contain 85% by weight or more of phosphatidylcholine is preferably used. The phospholipid or lecithin according to the present invention may be contained in the capsule contents in an amount ranging from 0.01 to 0.5% by weight, preferably 0.02 to 0.1% by weight, depending on the type, the type and amount of other components such as the main component, the desired particle size, etc.

[0029] 1.2 Capsule shell composition The capsule shell composition according to the present invention is mainly composed of a film-forming base capable of gelling at low temperature to form a film on the surface of the capsule contents, and a plasticizer capable of adjusting the hardness and strength of the film. Here, "mainly composed" means that other components may be included as long as they do not impair the effects of the present invention, and specifically means that the capsule shell composition contains, for example, 50% by weight or more of the film-forming base and the plasticizer, preferably 80% by weight or more, and more preferably 90% by weight or more of the film-forming base and the plasticizer. The capsule shell composition may be composed of only the film-forming base and the plasticizer.

[0030] The film-forming base according to the present invention is not particularly limited as long as it can be used as a film-forming base for seamless capsules and is a hydrophilic polymer that is medicamentally or food-production-acceptable. Examples of the hydrophilic polymer include natural hydrophilic polymers such as gelatin, casein, zein, pectin and derivatives thereof, alginic acid or its salts (e.g., sodium salt, potassium salt), agar, tragacanth gum, guar gum, locust bean gum, gum arabic, xanthan gum, gellan gum, glucomannan, carrageenan, tamarind, mannan, hemilose, starch, chitosan, collagen protein, furcellaran, pectin, pullulan, and starch; semi-synthetic hydrophilic polymers such as carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, cellulose acetate phthalate, alginic acid propylene glycol ester, oxidized starch, esterified starch, etherified starch, and cationic starch; and synthetic hydrophilic polymers such as sodium polyacrylate, polyethyleneimine, polyvinyl alcohol, polyethylene oxide, and polyvinylpyrrolidone. Among these, gelatin is preferred, and bovine or porcine gelatin is more preferred.

[0031] In some cases, in order to promote the gelation of the film-forming base, an appropriate amount of alkali metal salts which generate potassium ions, sodium ions, etc.; alkaline earth metal salts which generate calcium ions, magnesium ions, etc.; or ammonium salts which generate ammonium ions can be blended.

[0032] The above film-forming bases can be used alone or in combination of two or more. The film-forming base may be contained in the capsule shell composition in an amount ranging from 1 to 90% by weight, for example, depending on the type, the type and amount of other components such as the main component, the desired particle size, etc., preferably in the range of 20 to 90% by weight, and more preferably in the range of 50 to 85% by weight.

[0033] Examples of the plasticizer according to the present invention include water-soluble polyhydric alcohols such as sorbitol, mannitol, glycerin, propylene glycol, polyethylene glycol, glucose, fructose, galactose, arabinose, mannose, rhamnose, maltose, raffinose, sucrose, erythritol, maltitol, trehalose, lactose, and xylose. Among these, sorbitol and glycerin are preferred.

[0034] The above plasticizers can be used alone or in combination of two or more kinds. The plasticizer may be contained in the capsule shell composition in an amount ranging from 10 to 40% by weight, preferably 10 to 25% by weight, and more preferably 10 to 20% by weight, although this may vary depending on the type, the type and amount of other components such as the main component, the desired particle size, etc.

[0035] The capsule shell composition of the present invention may contain, if desired, suitable amounts of coloring agents, acidulants, and flavoring agents. Examples of the coloring agents include food coloring agents such as Yellow Color No. 5, Red Color No. 2, and Blue Color No. 2; β-carotene; food lake color; red ferric oxide and yellow ferric oxide. Examples of the acidulants include ascorbic acid, citric acid, tartaric acid, and malic acid. Examples of the flavoring agents include menthol, peppermint oil, lemon oil, vanillin, and blueberry flavor.

[0036] 1.3 Other The particle size of the seamless capsule of the present invention can be appropriately adjusted by the manufacturing method, etc., but is usually within the range of 0.5 mm to 10 mm. The seamless capsule of the present invention after manufacturing can be used as it is without drying and moisture remains in the capsule depending on the application, or it can be used after drying by normal pressure or vacuum drying method.

[0037] The particle size of the seamless capsule of the present invention can be measured using, for example, an optical microscope (measuring microscope, digital microscope, etc.), an image analyzer (image measuring machine, projector, etc.), or a measuring tool (vernier caliper, scale, etc.). The seamless capsule of the present invention has no seams and is uniform in size and shell thickness. The shell thickness is usually about 100 μm to about 500 μm. It can be appropriately adjusted depending on the production method, etc.

[0038] The thickness deviation and eyes of the seamless capsule of the present invention are both reduced, for example, to the following extent. Regarding thickness deviation, when observed under a microscope immediately after encapsulation, the minimum / maximum thickness ratio of the coating before drying is 0.6 or more, more preferably 0.8 or more, and even more preferably 0.9 or more. The thickness can be measured by a general image analysis method. If the minimum / maximum thickness ratio of the coating is less than 0.6, the thickness deviation is large, and the coating may crack during drying and storage after drying, causing the capsule contents to leak.

[0039] Regarding eyes, they are absent, or even if they are present, they are extremely small. If eyes are present, when observed under a microscope immediately after encapsulation and before drying, the eyes diameter is 1 / 2 or less, more preferably 1 / 4 or less, and even more preferably 1 / 8 or less of the average thickness of the film before drying ((maximum + minimum) / 2). If the eyes diameter exceeds 1 / 2 of the average thickness of the film ((maximum + minimum) / 2), the film may crack during drying and storage after drying, causing the capsule contents to leak out.

[0040] Here, eyes refer to spherical, air-bubble-like defects occurring in the shell, and the air bubbles may contain capsule contents. Eyes are usually spherical with little distortion, but may be distorted. The "eye diameter" of non-spherical eyes refers to the diameter in the maximum direction. A plurality of eyes may occur in a seamless capsule, and each diameter is within the above range. Measurement of thickness and eye diameter can be performed by a general image analysis method, as with thickness deviation.

[0041] The seamless capsule of the present invention can be used in the fields of medicines, quasi-drugs, functional foods, luxury items, etc. The seamless capsule of the present invention, which contains a medicinal physiologically active ingredient in the capsule content, can be provided as a pharmaceutical preparation. In addition, the seamless capsule of the present invention, which contains a physiologically active ingredient having a biological regulation function as a food in the capsule content, can be provided as a functional food such as a food for specified health uses (special purpose food) or a functional food. The form of the provided pharmaceutical preparation or functional food is not particularly limited. For example, it can be provided in a bottle or container, a plastic bag or a plastic bag, or in the form of a PTP. It is preferable that the form is one that can withstand transportation and transport. If necessary, secondary packaging or tertiary packaging can be applied. In addition, light shielding can be applied depending on the ingredients in the capsule content.

[0042] 2. Manufacturing method according to the present invention The manufacturing method according to the present invention (hereinafter referred to as "the manufacturing method of the present invention") is a method for manufacturing a seamless capsule manufactured using a capsule content and a capsule shell composition as materials, and is characterized in that it includes a step of blending a phospholipid with the capsule content, and that 85% by weight or more of the phospholipid is phosphatidylcholine. The seamless capsule of the present invention can be manufactured by the manufacturing method of the present invention.

[0043] In the present invention, the terms capsule content, capsule shell composition, phospholipid, phosphatidylcholine, etc. are defined as above. The present invention is particularly preferred for producing seamless capsules containing omega-3 fatty acids (e.g., eicosapentaenoic acid and / or docosahexaenoic acid) or their ethyl esters as the capsule content.

[0044] The present invention can be carried out in the same manner as the conventional method (e.g., the liquid dropping method) for producing seamless capsules, except that the present invention includes a step of blending the capsule contents with the above-mentioned phospholipid. Specifically, when the present invention seamless capsule having a single-layered shell is produced by the liquid dropping method, the method can be carried out by a method including a step of simultaneously extruding the liquid capsule contents containing the main component (e.g., an oily active component such as ω3-fatty acid) and the phospholipid (e.g., refined soybean lecithin: Phospholipon (registered trademark) 90G, Phospholipon (registered trademark) 85G, etc.) consisting of 85% by weight or more of phosphatidylcholine from the first nozzle, and the liquid capsule shell composition containing the shell-forming base and the plasticizer from the second nozzle into the carrier liquid.

[0045] The "carrier liquid" is not particularly limited as long as it is one that can be used in the production of seamless capsules by the submerged dropping method, and examples thereof include oil-based base materials such as medium-chain triglyceride (MCT) oil, olive oil, soybean oil, and corn oil. The capsule contents are controlled at a temperature in the range of, for example, 0 to 40° C. during production. The capsule shell composition is controlled at a temperature in the range of, for example, 50 to 80° C. during production. The carrier liquid is controlled at a temperature in the range of, for example, 1 to 15° C. during production.

[0046] When the liquid capsule contents are extruded (injected) from the first inner nozzle of a concentric double nozzle, and the liquid capsule shell composition is extruded (injected) from the second outer nozzle simultaneously at a constant speed into a carrier liquid flowing down at a steady speed, a two-layered jet is formed by the interfacial tension acting between the carrier liquid and the capsule shell composition. The jet then becomes spherical droplets. To increase the uniformity of the size of the resulting seamless capsules, vibration may be applied to this jet stream. Next, in order to form a film on the surface of the droplets, the droplets in the carrier liquid are cooled, and a film is formed on the surface of the droplets. Then, if necessary, a deoiling process and a drying process are performed to produce the seamless capsule of the present invention.

[0047] 3. Method of the Present Invention The method according to the present invention (hereinafter referred to as "the method of the present invention") is a method for reducing eyes or uneven thickness of the shell of a seamless capsule, which includes a step of blending a phospholipid with the capsule contents in the process of producing a seamless capsule using a capsule contents and a capsule shell composition as materials, and is characterized in that 85% by weight or more of the phospholipid is phosphatidylcholine.

[0048] In the method of the present invention, the terms capsule content, capsule shell composition, phospholipid, phosphatidylcholine, etc. are defined as above. The method of the present invention is particularly preferable in reducing eyes occurring in the shell or uneven thickness of the shell when producing seamless capsules containing omega-3 fatty acids (e.g., eicosapentaenoic acid and / or docosahexaenoic acid) or their ethyl esters as the capsule content. EXAMPLES

[0049] The present invention will be described below with reference to test examples and examples, but the present invention is not limited to these examples in any way.

[0050] [Test Example 1] Screening test The formulation properties (eyes and weave) of seamless capsules prepared with several interfacial tension modifiers were evaluated. Each seamless capsule was manufactured as follows. A medium chain triglyceride (MCT; Coconard MT, Kao Corporation) was used as an oil component, to which 0.5% by weight of an interfacial tension modifier was added, mixed and dissolved to prepare the capsule contents. Separately, the capsule shell composition shown in Table 1 was prepared. Using the capsule contents and capsule shell composition thus prepared, single-layer seamless capsules with a particle size of 4 mm were produced by the usual method of submerged dropping method using an SPX-LABO seamless capsule filling machine (Freund Corporation). Lecithin CL (manufactured by J-Oil Mills) contains approximately 18% by weight of phosphatidylcholine.

[0051] The temperature of the capsule contents near the nozzle was controlled at 15 to 30°C, the temperature of the capsule shell composition was controlled at 50 to 70°C, MCT oil was used as the carrier liquid, and its temperature was controlled at 5 to 10°C. Capsulation was performed at a rate of 25 to 35 capsules per second. The obtained seamless capsules were cooled in a refrigerator and dried in a dryer. Micrographs of the produced seamless capsules are shown in Figure 1. The evaluation results of their formulation properties are shown in the lower part of Table 1. In Table 1, "○" indicates that the content liquid interface was uniform and the seamless capsule was well formed as a result of observation under a microscope, and "×" indicates that the content liquid interface was not sufficiently uniform and the seamless capsule was poorly formed.

[0052] [Table 1]

[0053] As shown in Table 1, there was concern that problems might occur in the formulation of seamless capsules if glycerol fatty acid esters were used as interfacial tension modifiers.

[0054] [Example] Seamless capsules of the present invention with a particle size of 4 mm were produced by the liquid dropping method (SPX-LABO seamless capsule filling machine, manufactured by Freund Corporation) according to the recipe shown in Table 2 below. The soybean lecithin used was refined soybean lecithin manufactured by Lipoid (Phospholipon (registered trademark) 90G; phosphatidylcholine content of 94% by weight or more). The concentration of lecithin in the capsule contents was 0.05% by weight.

[0055] The temperature of the capsule contents near the nozzle was controlled at 15 to 30°C, the temperature of the capsule shell composition was controlled at 50 to 70°C, MCT oil was used as the carrier liquid, and its temperature was controlled at 5 to 10°C. Capsulation was performed at a rate of 25 to 35 capsules per second. The obtained seamless capsule of the present invention was cooled in a refrigerator and dried in a dryer.

[0056] [Table 2]

[0057] Micrographs of the obtained seamless capsules of the present invention are shown in Figures 2 and 3. No particular unevenness in thickness or eyes were observed in any of the seamless capsules of the present invention. [Industrial Applicability]

[0058] The seamless capsule of the present invention is useful, for example, in the fields of medicines, quasi-drugs, functional foods, luxury items, and the like.

Claims

1. A seamless capsule manufactured from a capsule content containing an oily component as a main component and a capsule shell composition containing gelatin or bovine-derived gelatin as a base, wherein the capsule content contains a phospholipid, and the phospholipid is a lecithin containing 85% or more by weight of phosphatidylcholine.

2. 2. The seamless capsule according to claim 1, wherein the phospholipid is soybean lecithin or egg yolk lecithin.

3. The seamless capsule according to claim 1 or 2, wherein the oil component contains an omega-3 fatty acid or an ethyl ester thereof.

4. The seamless capsule according to claim 3, wherein the omega-3 fatty acid is eicosapentaenoic acid and / or docosahexaenoic acid.

5. A pharmaceutical formulation comprising the seamless capsule according to any one of claims 1 to 4.

6. A method for producing seamless capsules made from capsule contents containing an oily component as a main component and a capsule shell composition containing gelatin or bovine-derived gelatin as a base, comprising the steps of blending a phospholipid with the capsule contents and blending gelatin or bovine-derived gelatin with the capsule shell composition, wherein the phospholipid is lecithin containing 85% or more by weight of phosphatidylcholine.

7. 7. The method for producing a seamless capsule according to claim 6, wherein the phospholipid is soybean lecithin or egg yolk lecithin.

8. The method for producing a seamless capsule according to claim 6 or 7, wherein the oil component contains an omega-3 fatty acid or an ethyl ester thereof.

9. The method for producing a seamless capsule according to claim 8, wherein the omega-3 fatty acid is eicosapentaenoic acid and / or docosahexaenoic acid.

10. A method for reducing eyes or thickness irregularities occurring in the shell of a seamless capsule, comprising the steps of blending a phospholipid into the capsule contents and blending gelatin or bovine-derived gelatin into the capsule shell composition during the process of manufacturing a seamless capsule made from a capsule content containing an oily component as a main component and a capsule shell composition containing gelatin or bovine-derived gelatin as a base, wherein the phospholipid is a lecithin containing 85% or more by weight of phosphatidylcholine.

11. The method of claim 10, wherein the phospholipid is soybean lecithin or egg yolk lecithin.

12. The method according to claim 10 or 11, wherein the oil component comprises an omega-3 fatty acid or an ethyl ester thereof.

13. The method of claim 12, wherein the omega-3 fatty acid is eicosapentaenoic acid and / or docosahexaenoic acid.

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