Light-shielding hard capsule containing magnesium oxide

Abstract

The problem to be solved is to provide a light-shielding hard capsule shell film and a hard capsule shell for pharmaceutical preparations and the like, and a preparation method thereof. Solution: A hard capsule shell film is prepared from a film-forming composition comprising magnesium oxide, which has been safely used as a pharmaceutical product, as an opacifying agent rather than titanium oxide which is considered to have a health problem. A light-shielding hard capsule shell is formed from the film. Due to the fact that the hard capsule shell can reduce transmission of light rays and ultraviolet rays, the stability and quality of any active ingredient filled in the shell can be kept for a long time.

Description

Technical Field

[0001] The present invention relates to a light-shielding hard capsule shell film and a hard capsule shell formed by the light-shielding hard capsule shell film for pharmaceutical preparations, etc. The present invention also relates to a composition for forming the hard capsule shell, the composition containing a light-shielding agent, and a method for preparing the light-shielding hard capsule shell.

[0002] In addition, the present invention relates to a light-shielding hard capsule shell film and a hard capsule shell formed by the light-shielding hard capsule shell film, wherein the hard capsule shell film is prepared from a film-forming composition containing magnesium oxide as a light-shielding agent, and the hard capsule shell film and the hard capsule shell can reduce the transmission of light and ultraviolet rays, so that the hard capsule shell can maintain the stability and quality of any active ingredient filled in the shell for a long time. Background Art

[0003] Various preparations (including medicines and health foods) are given various colors. Some of the purposes of this coloring include: making the preparation highly recognizable; making the preparation have a beautiful appearance; and providing light-shielding properties to maintain quality. In particular, in the case where the preparation contains ingredients that are susceptible to light, it is common practice to add a white light-shielding agent to the film forming the hard capsule shell, so that a white light-shielding hard capsule shell can be produced. In addition, if necessary, in order to give the light-shielding film the desired color, various colorants can be added, such as various dyes, which can be edible colorants (such as blue No. 1, yellow No. 5, red No. 3, etc.), or various colorants, such as pigments (such as ferric oxide, aluminum lake, etc.), which can also be edible colorants.

[0004] Various sunscreens are known for imparting sunscreen properties to target materials. Among these sunscreens, titanium oxide (TiO2, also known as titanium dioxide) is one of the most commonly used sunscreens. Titanium oxide is a white pigment characterized by its excellent whiteness, opacity and coloring ability as well as its extremely high chemical stability. Therefore, titanium oxide has long been used in the pharmaceutical and cosmetic fields.

[0005] Some pharmaceuticals and cosmetics contain ingredients whose stability is destroyed by titanium oxide, or whose decomposition is accelerated by free radicals generated from titanium oxide by ultraviolet rays. Quality maintenance of such products has been a problem. In addition, light irradiation may cause film peeling of preparations coated with a film containing titanium oxide and / or the film may turn into powder over time, making it difficult to maintain the coating state of the preparation. As a result, the appearance and handling of these preparations may be impaired. Another concern is that light, oxygen and / or moisture may cause decomposition of ingredients contained in the preparations.

[0006] Subsequently, in the production of opaque or translucent gelatin hard capsules, natural calcium powder (mainly composed of calcium carbonate) having an average particle size of 3 μm or less was studied as an opacifying agent that is safer and has higher nutritional value than titanium oxide (Patent Document 1). However, according to the Food Safety Commission of the Cabinet Office, in 2020, the French Food, Environmental and Occupational Health Safety Agency (ANSES) published a written opinion on the identification of nanoparticles (also known as nanomaterials) in food and the assessment of consumer health risks. Calcium carbonate, as a food additive containing nanoparticles, is the subject of the assessment. Therefore, there are safety issues with the use of calcium carbonate in capsules. (See website: https: / / www.fsc.go.jp / fsciis / foodSafetyMaterial / show / syu05400370475 )

[0007] Regarding the carcinogenicity of titanium oxide, the International Agency for Research on Cancer (IARC) changed the carcinogenicity classification of titanium oxide from Group 3 (not classifiable as to its carcinogenicity to humans) to Group 2B (possibly carcinogenic to humans) in June 2006 because it considered that the results of animal experiments conducted by inhalation and intratracheal injection of pigment-grade and ultrafine TiO2 were sufficient to prove that TiO2 was carcinogenic to animals (Baan R, Staif K, Grosse Y, Secretan B, Ghissassi F, Cogliano V., on behalf of the WHO International Agency for Research on Cancer Monograph Working Group (2006): Carcinogenicity of carbon black, titanium dioxide, and talc; in The Lancet Oncology 2006 Vol. 7, Issue 4, Pages 295-296 https: / / doi.org / 10.1016 / S1470-2045(06)70651-9 )

[0008] Consideration of the above problems has led to the study of light-shielding film compositions that do not contain titanium oxide, such as compositions containing a film base of one or more substances selected from water-soluble calcium salts and a water-soluble cellulose-based polymer (Patent Document 2). However, the water-soluble calcium salt described in Patent Document 2 must be used in an amount of 1.0% or less in food in accordance with the use standards specified in "Standards and criteria for food and food additives, etc., 2. Additives". Therefore, there is a problem of limited white coloring density.

[0009] On the other hand, as an example of using magnesium oxide as a light-shielding material, Patent Document 3 discloses a coated solid hypnotic preparation obtained by coating a solid preparation (containing diphenhydramine or its acid addition salt as a medicinal ingredient having sleep and sedative effects) with a film (containing a light-shielding material and a water-soluble polymer material). In Patent Document 3, a hard capsule is mentioned as a solid preparation, and magnesium oxide is mentioned as one of the light-shielding materials. However, this preparation does not impart light-shielding properties to the capsule shell itself. Since it is obtained by coating a capsule containing a drug in a capsule shell with a film containing a light-shielding material and a water-soluble polymer material, there is a disadvantage of a complicated manufacturing process. Patent document 4 discloses a hard capsule shell, the inner layer of which is a gelatin film, and the outer layer contains 1 to 20% magnesium oxide and a polymer suitable for impregnation, such as HPMC, gelatin or PVP. However, the layer containing magnesium oxide is to prevent the gelatin capsule shell from adhering to the oral mucosa, and therefore should be located at the outermost layer of the capsule shell. Prior art literature

[0010] Patent Literature [Patent Document 1] JPH07-124462A [Patent Document 2] WO2004 / 054619 [Patent Document 3] JP2003-300872A [Patent Document 4] CN108992417B Summary of the invention Problems to be solved by the present invention

[0011] Although various alternative technologies that can replace the above titanium oxide have been studied so far, titanium oxide powder has been widely used as a sunscreen in various industrial fields including the food industry and the pharmaceutical industry. This is because the extremely fine particles and unparalleled opacity of titanium oxide provide sufficient sunscreening ability even in small amounts.

[0012] Therefore, although the health food industry does not want to add substances that may be harmful to the human body (such as titanium oxide) in capsules, it is difficult to find a suitable substitute for titanium oxide as a sunscreen. Therefore, it is necessary to develop a sunscreen to replace titanium oxide.

[0013] Another requirement that needs to be met is that any titanium oxide substitute should provide acceptable mechanical properties for the hard capsule shell. For example, it is desired that the capsule is sufficiently stable when stored under different relative humidity conditions. Mechanical properties include, for example, the fracture and elastic behavior of the capsule (e.g., obtained by a tube test), the top strength (e.g., obtained by a capsule top compression test), and the (pre) locking force strength (e.g., obtained by a (pre) locking force measurement test, i.e., the force required when the capsule body and the capsule cap are temporarily connected). They may be important parameters, which should be within an acceptable range. Alternatively, in order to evaluate the mechanical behavior, several mechanical properties of the film formed by the gel composition can be measured, such as: elongation (e.g., measured by a film tensile test), fracture deformation (e.g., measured by a film tensile test), impact resistance (e.g., measured by a fracture impact energy test), puncture time of a dissolving liquid (e.g., measured by a puncture time measurement test), or puncture resistance (e.g., measured by a puncture test). It is necessary to find a balance between the sufficient light-shielding properties of the capsule and the appropriate mechanical properties.

[0014] For example, when titanium oxide or its substitute particles are added to an aqueous film-forming polymer solution to produce a capsule shell, the particles make the capsule shell membrane brittle because the film thickness is only about 100 μm. There is a risk that the capsule shell will break during the filling operation. That is, as the particle size of the particles increases or the amount of particles added increases, the elongation of the film decreases significantly and the capsule shell will easily break. In order to avoid the risk of deteriorating the mechanical properties of the hard capsule shell, the particle size and amount of opacifier to be added need to be optimized. Problem Solution

[0015] In order to develop a long-awaited sunscreen in the health food industry that can replace titanium oxide, the inventors of the present invention solved the above technical problems and studied the possibility of adding magnesium oxide as a sunscreen to a film-forming polymer. It was found that magnesium oxide can achieve an aesthetic appearance and sunscreen performance comparable to titanium oxide. It was also found that by combining with other coloring materials, free coloring can be performed while sunscreening. By combining various edible tar pigments with natural pigments such as safflower pigment, caramel pigment and gardenia, light-shielding capsules with high safety and beautiful colors can be provided, especially for the health food market.

[0016] Furthermore, it was found that by using magnesium oxide in particulate form as an opacifier, a hard capsule shell having the above-mentioned basic mechanical properties can be provided without excessively reducing the elongation of the film. Preferably, magnesium oxide having an optimized particle size and an optimized amount can be used.

[0017] The present invention has been accomplished based on the above findings, and includes the following aspects. [1] A hard capsule shell, wherein the shell is formed by a hard capsule shell membrane, the hard capsule shell membrane comprising a film-forming polymer and magnesium oxide, wherein the hard capsule shell membrane does not contain titanium oxide, a white colorant; and wherein the hard capsule shell has only one layer, which is the hard capsule shell membrane, or The hard capsule shell has more than one layer and at least one layer different from the outermost layer is the hard capsule shell membrane. [2] The hard capsule shell according to [1], wherein the hard capsule shell membrane does not contain calcium carbonate which is a white colorant. [3] The hard capsule shell according to [1] or [2], wherein the hard capsule shell membrane does not contain a white colorant other than magnesium oxide. [4] The hard capsule shell according to any one of [1] to [3], wherein the particle size of the magnesium oxide is 50 μm or less. [5] The hard capsule shell according to any one of [1] to [4], wherein the particle size distribution D10 value of the magnesium oxide is 0.1 um to 2.0 um. [6] The hard capsule shell according to any one of [1] to [5], wherein the particle size distribution D90 value of the magnesium oxide is 4 um to 45 um. [7] The hard capsule shell according to any one of [1] to [6], wherein the amount of the film-forming polymer is at least 75% by weight, wherein the weight % is based on the dry weight of the hard capsule shell membrane. [8] The hard capsule shell according to any one of [1] to [7], wherein the magnesium oxide is heavy magnesium oxide. [9] The hard capsule shell according to any one of [1] to [8], wherein the amount of magnesium oxide is 0.25 wt% to 20 wt%, wherein the wt% is based on the dry weight of the film-forming polymer.

[10] The hard capsule shell according to any one of [1] to [9], wherein the amount of magnesium oxide is 2 wt% to 10 wt%, wherein the wt% is based on the dry weight of the film-forming polymer.

[11] The hard capsule shell according to any one of [1] to

[10] , wherein the amount of magnesium oxide is 5 wt% to 8 wt%, wherein the wt% is based on the dry weight of the film-forming polymer.

[12] A hard capsule shell according to any one of [1] to

[11] , wherein the film-forming polymer is selected from the group consisting of gelatin, polyglutamic acid, cellulose derivatives, pullulan, starch, dextrin, agar, chitosan, acid-treated crushed yeast, polyvinyl alcohol (PVA), PVA-methyl methacrylate copolymer, and polyvinyl pyrrolidone (PVP).

[13] The hard capsule shell according to any one of [1] to

[12] , further comprising a plasticizer.

[14] The hard capsule shell according to

[13] , wherein the plasticizer is selected from the group consisting of xylitol, fructose, sorbitan fatty acid esters, triethyl citrate, glycerol, sorbitol, mannitol, trehalose, vegetable oils, medium chain fatty acid triglycerides, triacetin, phthalates, phytosterols, propylene glycol, polysorbate and polyethylene glycol.

[15] The hard capsule shell according to

[13] or

[14] , wherein the amount of the plasticizer is 0.01 wt % to 10 wt %, wherein the wt % is based on the dry weight of the film-forming polymer.

[16] The hard capsule shell according to

[14] , wherein the plasticizer is sorbitan fatty acid ester.

[17] The hard capsule shell according to

[16] , wherein the plasticizer is sorbitan monolaurate.

[18] The hard capsule shell according to any one of [1] to

[17] , which is colored by adding a colorant, wherein the colorant has a color other than white.

[19] A method for preparing a hard capsule shell according to claim [1], wherein the hard capsule shell film comprising a film-forming polymer and magnesium oxide is prepared by dip molding. Unless otherwise specified, the unit "um" has the same meaning as the unit "μm", i.e. "micrometer".

[0018] The hard capsule shell of the present invention is intended for use in the pharmaceutical and food fields. Therefore, the materials used to produce the hard capsule shell are limited to those materials that can be safely used in the pharmaceutical and food fields.

[0019] Magnesium oxide occurs naturally in the colorless crystalline mineral periclase. By heating magnesium hydroxide or magnesium carbonate, magnesium oxide can be made into a lumpy white powder (light) or a relatively dense white powder (heavy). Heating these magnesium salts under mild conditions (400°C to 900°C for several hours) produces what is known as light magnesium oxide. Heating the salts under more severe conditions (e.g. 1200°C for 12 hours) produces what is known as heavy magnesium oxide. By continued heating at high temperatures, light magnesium oxide is converted to heavy magnesium oxide. The magnesium oxide used in the present invention is preferably produced at a calcination temperature of at least 700° C., preferably at least 800° C., more preferably at least 900° C., even more preferably at least 925° C. Specific embodiments of the calcination temperature are 950° C. and 1300° C.

[0020] The magnesium oxide used in the present invention is widely used as an antacid and a laxative in the medical field. In the food field, it is also used as a magnesium fortifier, a supplement, a dietary supplement, etc. However, so far, it has never been used as an opacifier for a hard capsule shell, that is, it has not been used as an opacifier for a hard capsule shell membrane used to form a hard capsule shell.

[0021] The magnesium oxide in the hard capsule shell film serves as a sunscreen and / or a whitening agent, and the hard capsule shell film comprises the film-forming polymer and the magnesium oxide. The magnesium oxide as a sunscreen for hard capsule shell membrane preferably has a particle size of 50 um or less, or 45 um or less, or 40 um or less, or 35 um or less, or 30 um or less, or 25 um or less, or 20 um or less, or 15 um or less. If it exceeds 50 um, the membrane strength decreases.

[0022] The particle size distribution can also be characterized by the D10 and / or D90 values; the D10 / D90 value is the particle size at which 10% / 90% of the particles are smaller than the D10 / D90 value. In this case, the % refers to the cumulative volume. The D50 and D100 values ​​are defined as: the D50 or D100 value is the particle size at which 50% or 100% of the particles are smaller than the D50 or D100 value, respectively. In one embodiment, the D10 value of the particle size distribution of magnesium oxide is 2.0 um or less, preferably 1.5 um or less, more preferably 1.0 um or less. In one embodiment, the D10 value of the particle size distribution of magnesium oxide is 0.1 um or more. In one embodiment, magnesium oxide has a particle size distribution with a D10 value of 0.1 to 2.0 um, preferably 0.1 to 1.5 um, more preferably 0.1 to 1 um.

[0023] Preferably, the magnesium oxide has a particle size distribution with a D90 value of 45 um or less, preferably 40 um or less, more preferably 35 um or less, even more preferably 30 um or less, especially 25 um or less, more especially 20 um or less, even more especially 15 um or less, especially 10 um or less, more especially 9 um or less. In another embodiment, the magnesium oxide has a particle size distribution with a D90 value of 20 μm or less, preferably 15 μm or less, more preferably 10 μm or less, even more preferably 7.5 μm or less, especially 5 μm or less, more especially 2 μm or less, even more especially 1.5 μm or less, especially 1.25 μm or less. Preferably, the magnesium oxide has a particle size distribution with a D90 value of 4 um or more. In another preferred embodiment, the D90 value of the particle size distribution of magnesium oxide is 0.3 um or greater. Preferably, the magnesium oxide has a particle size distribution with a D90 value of 4um to 45um, preferably 4um to 40um, more preferably 4um to 35um, even more preferably 4um to 30um, especially 4um to 25um, more especially 4um to 20um, even more especially 4um to 15um, especially 4um to 10um, more especially 4um to 9um. In another preferred embodiment, the magnesium oxide has a particle size distribution with a D90 value of 0.3 um to 20 um, preferably 0.3 um to 15 um, more preferably 0.3 um to 10 um, even more preferably 0.3 um to 7.5 um, especially 0.3 um to 5 um, more especially 0.3 um to 2 um, even more especially 0.3 um to 1.5 um, especially 0.3 um to 1.25 um.

[0024] Any given range of D10 values ​​may be combined with any given range of D90 values. In one embodiment, the magnesium oxide has a particle size distribution with a D10 value of 0.1 um to 2.0 um; and a D90 value of 4 um to 45 um. In another embodiment, the magnesium oxide has a particle size distribution with a D10 value of 0.1 um to 2.0 um, and a D90 value of 0.3 um to 20 um. Preferably, the magnesium oxide has a particle size distribution with a D10 value of 0.1 um to 1.5 um, and a D90 value of 5.0 um to 8.0 um. In another preferred embodiment, the magnesium oxide has a particle size distribution with a D10 value of 0.1 um to 1.0 um and a D90 value of 0.3 um to 7.5 um.

[0025] The particle size distribution is measured as follows: A dispersion containing 40 wt% magnesium oxide was prepared in water and stirred at 6600 rpm for 15 minutes using an Ultra Turrax high-speed stirrer. Diluted to about 1×10 -4 g MgO / L. The particle size distribution was measured with a Shimadzu particle size distribution analyzer SALD-2000J at a wavelength of 680 nm. Both light magnesium oxide and heavy magnesium oxide can be used as a sunscreen, but heavy magnesium oxide is preferred.

[0026] Typical grades of magnesium oxide are shown in Table 1. [Table 1]

[0027] In preparing a film-forming polymer solution containing magnesium oxide, it is best to disperse the magnesium oxide as concentratedly as possible in water in order to achieve maximum flexibility. Therefore, 20% and 40% dispersions of MS-0 and MS-2 were prepared, and their viscosity changes were measured for 8 days. The dispersion was prepared as follows: A mixture of magnesium oxide product and water was dispersed at 10000 rpm using a homogenizer for 10 minutes, and the mixture was stirred with a spatula to prepare a dispersion. The viscosity of the dispersion was measured with a Brookfield DV2T digital viscometer at the time of preparation, after 1 day and after 8 days. Table 2 shows the results.

[0028] [Table 2] (*) As hard as plaster (**)Still stirable Once MS-0 is made into a 40% dispersion, the viscosity of the dispersion rises and hardens like plaster. Therefore, the 40% MS-0 dispersion must be added to the film-forming polymer solution immediately after preparation to reduce the MgO concentration and avoid solidification. Since MS-2 does not have this solidification phenomenon, a high concentration dispersion such as 40% can be stored and used to prepare the film-forming polymer solution when needed; thus MS-2 has greater flexibility.

[0029] The film-forming polymer used in the present invention includes those that can be used for medicine and food. For example, polyvinyl alcohol (PVA), PVA-methyl, methacrylic acid copolymer, polyvinyl pyrrolidone (PVP), protein (such as gelatin and polyglutamic acid as common raw materials for capsule membranes), polysaccharides (such as cellulose derivatives), pullulan, starch, dextrin, agar, chitosan, acid-treated broken yeast, etc. can be used. The film-forming polymer is not limited to the above, as long as it is a film-forming polymer. Preferred film-forming polymers are gelatin, cellulose derivatives or pullulan.

[0030] Examples of cellulose derivatives include non-enteric cellulose derivatives and enteric cellulose derivatives. Non-enteric cellulose derivatives include water-soluble cellulose ethers, preferably water-soluble cellulose ethers in which a portion of the hydrogen atoms of the cellulose hydroxyl group are substituted by an alkyl group (e.g., a C1-4 alkyl group), a hydroxyalkyl group (e.g., a C1-4 hydroxyalkyl group), or a combination thereof; examples include hydroxy-lower alkyl celluloses, such as methyl cellulose, hydroxypropyl cellulose (HPC), and hydroxy-lower alkyl alkyl celluloses, such as hydroxyethyl methyl cellulose, hydroxyethyl ethyl cellulose, and hydroxypropyl methyl cellulose (HPMC); among them, hydroxypropyl methyl cellulose (hydroxypropyl methyl cellulose, HPMC) is preferred. Examples of HPMCs that may be appropriately used are: HPMC 2910 containing 7.0 to 12.0% hydroxypropoxyl groups and 28.0 to 30.0% methoxyl groups; HPMC 2906 containing 4.0 to 7.5% hydroxypropoxyl groups and 27.0 to 30.0% methoxyl groups; HPMC 2208 containing 4.0 to 12.0% hydroxypropoxyl groups and 19.0 to 24.0% methoxyl groups; HPMC 1828 containing about 23.0 to 32.0% hydroxypropoxyl groups and about 16.5 to 20.0% methoxyl groups, and mixtures thereof.

[0031] In the present invention, the methoxy and hydroxypropoxy contents of HPMC are expressed in accordance with the United States Pharmacopoeia. For example, HPMC 2910, HPMC 2906 and HPMC 2208 are listed in USP43-NF38. Various HPMC grades can be used alone or in combination. Preferred HPMCs are HPMC 2906, HPMC 2910 and mixtures thereof. Enteric cellulose derivatives include enteric polymers such as hydroxypropylmethylcellulose acetate succinate (HPMCAS), polyacrylic acid copolymers, carboxymethylethylcellulose, hydroxypropylmethylcellulose phthalate (HPMCP), and cellulose acetate phthalate (CAP).

[0032] In a preferred embodiment, the cellulose derivative is selected from the group consisting of hydroxypropyl methylcellulose (hypromellose), hydroxypropyl methylcellulose acetate succinate (HPMCAS), carboxymethyl ethyl cellulose, hydroxypropyl methylcellulose phthalate (HPMCP) and cellulose acetate phthalate (CAP), wherein hydroxypropyl methylcellulose is more preferred, embodiments of which are also described herein.

[0033] The gelatin may include alkali-treated gelatin extracted from cattle bones or pig bones or acid-treated gelatin extracted from cattle hides, pig hides or fish scales. A mixture of the alkali-treated gelatin and the acid-treated gelatin may also be used.

[0034] The amount of film-forming polymer in the film is preferably at least 75 wt%, or at least 77.5 wt%, or at least 80 wt%, or at least 82.5 wt%, or at least 85 wt%, or at least 87.5 wt%, or at least 90 wt%, or at least 92.5 wt%, or at least 95 wt%, or at least 97.5 wt%, wherein the wt% are based on the dry weight of the film. The amount of film-forming polymer is preferably from 83.3 to 99.75 wt. %, preferably from 90.9 to 98.0 wt. %, more preferably from 92.6 to 95.2 wt. %, wherein the wt. % are based on the dry weight of the film.

[0035] The amount of magnesium oxide added is 0.25 to 20% by weight, preferably 2 to 10% by weight, and more preferably 5 to 8% by weight of the film-forming polymer weight (dry weight). If it exceeds 20% by weight, the film becomes brittle and easily cracks, and if it is less than 0.25% by weight, it will not turn white, or the color will be too light to achieve the light-shielding effect. In one embodiment of the invention, the hard capsule shell membrane and thus the hard capsule shell consists, apart from water in the form of residual moisture, only of film-forming polymers and magnesium oxide. If the hard capsule shell film and thus the hard capsule shell, apart from water in the form of residual moisture, consists only of film-forming polymer and magnesium oxide, possible ranges for the weight of film-forming polymer and magnesium oxide, based on the dry film or dry capsule shell, respectively, are: 83.33 to 99.75% by weight of a film-forming polymer and 0.25 to 16.67% by weight of magnesium oxide, Best 90.91 to 98.04 wt. % of a film-forming polymer and 1.96 to 9.09% by weight of magnesium oxide, More preferred 92.59 to 95.24% by weight of a film-forming polymer and 4.76 to 7.41 wt. % magnesium oxide. Adding magnesium oxide tends to reduce the elongation of the film, making it more susceptible to impact. Adding plasticizers can increase the elongation of the film.

[0036] Some examples of the above plasticizers include xylitol, fructose, sorbitan fatty acid esters, triethyl citrate, glycerol, sorbitol (sorbitol / sorbitol solution), mannitol, trehalose, vegetable oils (sesame oil, castor oil), medium chain fatty acid triglycerides, triacetin, phthalates (dioctyl phthalate), phytosterols, propylene glycol, polysorbate, polyoxyethylene (polyethylene glycol), etc. Preferred plasticizers are sorbitan fatty acid esters, and more preferred are sorbitan monolaurate (CAS 1338-39-2, sorbitan monolaurate).

[0037] Based on the weight (dry weight) of the film-forming polymer, the amount of plasticizer used is 0.01 to 10% by weight, preferably 0.05 to 5% by weight, more preferably 0.05 to 2.5% by weight, and even more preferably 0.3 to 1.5% by weight. If it is less than 0.01% by weight, or greater than 10% by weight, the plasticizing effect may be impaired. In one embodiment of the invention, the hard capsule shell membrane and thus the hard capsule shell consists only of film-forming polymer, magnesium oxide and plasticizer, apart from water in the form of residual moisture. If the hard capsule shell film and thus the hard capsule shell consists, apart from water in the form of residual moisture, only of film-forming polymer, magnesium oxide and plasticizer, the film-forming polymer, magnesium oxide and plasticizer may range, based on the weight of dry film or dry capsule shell, respectively: Film-forming polymer 76.92 to 99.74% by weight, magnesium oxide 0.25 to 15.38% by weight, plasticizer 0.01 to 7.69 wt. %; Preferably, the film-forming polymer is 86.96 to 97.94% by weight, magnesium oxide is 1.96 to 8.70% by weight, and the plasticizer is 0.05 to 4.35% by weight; More preferably Film-forming polymer 91.32 to 94.97% by weight, magnesium oxide 4.75 to 7.31% by weight, plasticizer 0.28~1.37wt%.

[0038] The hard capsule shell film of the present invention may contain gelling agents, gelling aids, pH regulators, sweeteners, acidulants, preservatives, flavors, binders, thickeners, colorants other than magnesium oxide, etc., depending on the type of film-forming polymer used and the purpose of use.

[0039] Colorants are generally classified as dyes or pigments, dyes being defined as colorants soluble in the application medium, i.e. they are soluble in the film-forming polymer solution of the hard capsule shell membrane, and pigments being defined as colorants insoluble in the application medium, i.e. they are insoluble in the film-forming polymer solution of the hard capsule shell membrane. Any colorant included in the hard capsule shell membrane preferably has a color other than white, so in one embodiment the hard capsule shell membrane does not contain the white colorant titanium oxide; In one embodiment, the hard capsule shell membrane is free of titanium oxide; In one embodiment, the hard capsule shell film does not contain the white colorant calcium carbonate; In one embodiment, the hard capsule shell membrane does not contain calcium carbonate; In one embodiment, the hard capsule shell film contains no white colorant titanium oxide and no white colorant calcium carbonate; In one embodiment, the hard capsule shell membrane contains no titanium oxide and no calcium carbonate; In one embodiment, the hard capsule shell film does not contain a white colorant (also referred to as a white colorant) other than magnesium oxide. In the case of colorants, the hard capsule shell film may contain one or more colorants other than magnesium oxide, preferably any such colorant has a color other than white; the colorant or a mixture of such colorants can be used to color the hard capsule shell film, for example, black, gray or a color. Color refers to all colors other than black, white and gray.

[0040] In the case where a colorant is used in a pharmaceutical preparation or a health food preparation, the colorant may be used as long as the colorant is permitted for use in the pharmaceutical and food fields. As examples of the colorant, tar lakes, colorants and natural colorants, caramel, cochineal pigment, lac pigment, riboflavin, sodium iron chlorophyllin, sodium copper chlorophyllin, copper chlorophyllin, ferric oxide, black iron oxide, etc. may be mentioned. In order to impart pearl luster, pearl pigments made of an appropriate amount of fine powder such as fish scale foil, pearl layer of shellfish or mica, silicon dioxide, etc. may be used. In a preferred embodiment, magnesium oxide is the only component in the hard capsule shell film that provides white color. In a preferred embodiment, the hard capsule shell membrane contains no other components that provide a white color.

[0041] In one embodiment of the invention, the hard capsule shell membrane and thus the hard capsule shell consists, apart from water in the form of residual moisture, only of a film-forming polymer and magnesium oxide and optionally a plasticizer and optionally a colorant other than a white colorant. If the hard capsule shell film and the hard capsule shell consist, apart from water in the form of residual moisture, only of a film-forming polymer and magnesium oxide and optionally a plasticizer and optionally a colorant other than a white colorant, the hard capsule shell film and thus the hard capsule shell preferably contains, based on the weight of the dry film or dry capsule shell, respectively: at least 75% by weight of a film-forming polymer, At least 1% by weight of magnesium oxide Optionally at least 0.1 wt. % plasticizer; Optionally at least 0.5% by weight of a colorant other than a white colorant; Wherein the amount of film-forming polymer, magnesium oxide, optional plasticizer and optional colorant other than white colorant adds up to 100 wt %; wherein film-forming polymer, magnesium oxide, plasticizer and white colorant are as defined herein, also including all embodiments thereof.

[0042] Some examples of the gelling agent used in the film-forming composition of the present invention include carrageenan, gellan gum, agar, pectin, gelatin, xanthan gum, locust bean gum, curdlan, sodium alginate, glucomannan, tamarind seed gum and methylcellulose. However, they are not limited to those described above. The amount of gelling agent may be up to 10% by weight, preferably up to 5% by weight, wherein the % by weight is based on the amount of film-forming polymer (dry weight).

[0043] Examples of gelling aids used in the film-forming composition of the present invention include sodium salts, potassium salts, calcium salts, etc. suitable for the gelling agent used. These can be used alone or in combination in appropriate amounts. The amount of gelling aid can be up to 10% by weight, preferably up to 5% by weight, wherein the weight % is based on the amount of film-forming polymer (dry weight).

[0044] Thickeners include alginic acid, furcellaran, tara gum, karaya gum, succinan, xanthan gum, gum arabic, karaya gum, guar gum, tamarind seed gum, tara gum, tragacanth gum, CMC-Ca, CMC-Na, glucosamine, pullulan, sodium polyacrylate, curdlan, and modified starch. Thickeners or binders can increase gel strength and supplement the strength of the film or shell.

[0045] Another subject of the invention is a hard capsule shell, wherein the shell is formed by a hard capsule shell membrane as defined herein, including all embodiments thereof. Another subject of the present invention is a method for producing a hard capsule shell, wherein the hard capsule shell is produced by dip-molding, wherein the shell of the hard capsule shell is formed by a hard capsule shell membrane, the hard capsule shell membrane being as defined herein, including all embodiments thereof.

[0046] The hard capsule shell according to the present invention can be prepared by any known dip molding method for preparing hard capsule shells. As an example, the case of a gelatin capsule will be described.

[0047] First, 20 to 40 parts by weight of gelatin are uniformly dissolved in hot water to prepare a light yellow transparent impregnation liquid derived from gelatin colorant. A magnesium oxide dispersion and an optional plasticizer aqueous solution are added to the impregnation liquid. After adjusting the viscosity of the liquid, a stainless steel molding needle is immersed in the liquid and then pulled out of the liquid. The impregnation liquid adhering to the pulled molding needle is immediately cooled and gelled to ensure a film thickness suitable for the capsule. After drying, the unnecessary parts are cut off, and a pair of capsule caps are assembled with the capsule body to manufacture the capsule. Some examples of drying conditions include high temperature drying in an oven at a temperature of 60°C for 15 minutes, high temperature drying in an oven at a temperature of 60°C for 30 minutes, and natural drying at room temperature.

[0048] The hard capsule shell may comprise one or more polymer film layers, preferably one or more film-forming polymer film layers. For ease of reading, such polymer film layers are referred to herein as layers. For the definition of layers in the sense of the present invention, and in the case of more than one layer, each layer is made in its own process step, which is separate from the process step for making the other layers. Typical process steps for producing the layers may be dip molding, banding or coating, such as spraying. In the case where the hard capsule shell has only one layer, this layer is the hard capsule shell membrane as described herein; this means that the hard capsule shell has no further layers; this means, for example, that it is not edged or coated, but only has said one layer. Preferably, in the case where the hard capsule shell has only one layer, this layer is said hard capsule shell membrane, which layer is formed by dip molding. In case the hard capsule shell has more than one layer, at least one layer different from the outermost layer, preferably the innermost layer, is a hard capsule shell membrane as described herein, preferably formed by dip molding. In the case where the hard capsule shell has more than one layer, then preferably the hard capsule shell has 2, 3, 4 or 5 layers. In the case of more than one layer, the composition of each layer may be the same or different, preferably the composition of each layer in contact with each other is different. In a specific embodiment, the composition of all layers is different from each other. Preferably, where there is more than one layer, at least the innermost layer is formed by dip moulding.

[0049] In one embodiment, the hard capsule shell has two layers, the inner layer is the hard capsule shell membrane, and preferably the hard capsule shell membrane is prepared by dip molding. In one embodiment, the hard capsule shell has two layers, the inner layer is the hard capsule shell membrane, and the outer layer is a coating or a edging; preferably, the hard capsule shell membrane is prepared by dip molding. In one embodiment, the hard capsule shell has two layers, the inner layer is the hard capsule shell membrane, and the outer layer is prepared by dip molding. Preferably, the hard capsule shell membrane is prepared by dip molding. In one embodiment, the hard capsule shell has two layers, the inner layer is the hard capsule shell membrane, and the outer layer is not a binding or coating. Preferably, the hard capsule shell membrane is prepared by dip molding. In one embodiment, the hard capsule shell has two layers, the inner layer is the hard capsule shell membrane, and the outer layer is not prepared by dip molding. Preferably, the hard capsule shell membrane is prepared by dip molding. In any of the above embodiments where the hard capsule shell has two layers, the outer layer may comprise magnesium oxide; preferably, the outer layer may comprise magnesium oxide as a whitening agent.

[0050] In any of the above embodiments where the hard capsule shell has two layers, the outer layer may be free of magnesium oxide as a whitening agent. In any of the above embodiments where the hard capsule shell has two layers, the outer layer may be free of magnesium oxide. In one embodiment, if the hard capsule shell comprises two or more layers, at least one layer different from the outermost layer, preferably at least the innermost layer, is the hard capsule shell membrane, and at least one of the other layers may contain magnesium oxide, preferably as a whitening agent. In one embodiment, if the hard capsule shell comprises two or more layers, at least one layer different from the outermost layer, preferably at least the innermost layer, is the hard capsule shell membrane, and at least one of the other layers, preferably the outermost layer, may not contain magnesium oxide as a whitening agent. In one embodiment, if the hard capsule shell comprises two or more layers, at least one of the layers different from the outermost layer, preferably at least the innermost layer, is the hard capsule shell membrane, and at least one of the other layers, preferably the outermost layer, may not contain magnesium oxide. Effects of the Invention

[0051] According to the present invention, by using magnesium oxide, which is harmless to health and is generally used in the fields of medicine and food, the material filled in the hard capsule can be shielded from light without using titanium oxide, which may cause carcinogenicity. Since magnesium oxide has a light shielding property comparable to titanium oxide, it can be applied not only to normal whitening of capsules but also to the preparation of light-unstable medicines and foods.

[0052] Furthermore, the light-shielding hard capsule shell of the present invention can maintain stable light-shielding properties for a long period of time without reducing solubility even if it contains magnesium oxide. In addition, when used in combination with color colorants such as dyes or pigments, opaque and colored films can be obtained.

[0053] Therefore, especially for the health food market, by combining with natural colorants such as gardenia, safe and beautiful colored light-shielding capsule shells can be provided.

[0054] A further embodiment of the present invention is: (A) A hard capsule shell film comprising a film-forming polymer and magnesium oxide, wherein the hard capsule shell film does not contain titanium dioxide, a white colorant. (B) The hard capsule shell film according to embodiment (A), wherein the hard capsule shell film does not contain calcium carbonate, a white colorant. (C) The hard capsule shell film according to embodiment (A) or (B), wherein the hard capsule shell film does not contain a white colorant other than magnesium oxide. (D) The hard capsule shell film according to any one of embodiments (A) to (C), wherein the particle size of magnesium oxide is 50 um or less. (E) The hard capsule shell film according to any one of embodiments (A) to (D), wherein the particle size distribution D10 value of the magnesium oxide is 0.1 um to 2.0 um. (F) The hard capsule shell film according to any one of embodiments (A) to (E), wherein the particle size distribution D90 value of the magnesium oxide is 4 um to 45 um. (G) The hard capsule shell film according to any one of embodiments (A) to [F], wherein the amount of the film-forming polymer is at least 75 wt %, wherein the wt % is based on the dry weight of the hard capsule shell film. (H) The hard capsule shell film according to any one of embodiments (A) to (G), wherein the magnesium oxide is heavy magnesium oxide. (I) The hard capsule shell film according to any one of embodiments (A) to (H), wherein the amount of the magnesium oxide is 0.25 wt % to 20 wt %, wherein the wt % is based on the dry weight of the film-forming polymer. (J) The hard capsule shell film according to any one of embodiments (A) to (I), wherein the amount of the magnesium oxide is 2 wt % to 10 wt %, wherein the wt % is based on the dry weight of the film-forming polymer. (K) The hard capsule shell film according to any one of embodiments (A) to (J), wherein the amount of the magnesium oxide is 5 wt % to 8 wt %, wherein the wt % is based on the dry weight of the film-forming polymer. (L) A hard capsule shell film according to any one of embodiments (A) to (K), wherein the film-forming polymer is selected from the group consisting of gelatin, polyglutamic acid, cellulose derivatives, pullulan, starch, dextrin, agar, chitosan, acid-treated broken yeast, polyvinyl alcohol (PVA), PVA-methyl methacrylate copolymer, and polyvinyl pyrrolidone (PVP). (M) The hard capsule shell film according to any one of embodiments (A) to (L), further comprising a plasticizer. (N) The hard capsule shell film according to embodiment (M), wherein the plasticizer is selected from the group consisting of sorbitan fatty acid esters, triethyl citrate, glycerol, sorbitol, mannitol, trehalose, vegetable oils, medium chain fatty acid triglycerides, triacetin, phthalates, plant sterols, propylene glycol, polysorbate and polyethylene glycol. (O) The hard capsule shell film according to embodiment (M) or (N), wherein the amount of the plasticizer is 0.01 wt % to 10 wt %, wherein the wt % is based on the dry weight of the film-forming polymer. (P) The hard capsule shell film according to embodiment (N), wherein the plasticizer is sorbitan fatty acid ester. (Q) The hard capsule shell film according to embodiment (P), wherein the plasticizer is sorbitan monolaurate. (R) The hard capsule shell film according to any one of embodiments (A) to (Q), which is colored by adding a colorant, wherein the colorant has a color other than white. (S) A hard capsule shell, wherein the shell is formed of the hard capsule shell membrane according to any one of embodiments (A) to (R). (T) A method for preparing a hard capsule shell according to embodiment (S), wherein the hard capsule shell membrane is prepared by dip molding. BRIEF DESCRIPTION OF THE DRAWINGS

[0055]

Figure 1

Figure 2

Figure 3

Figure 4

[0056] (A) Analysis of magnesium oxide particle size Using IKA's T50 ULTRA TURRAX, at a maximum speed of 6600 rpm for 15 minutes, magnesium oxide and sorbitol monolaurate were dispersed in ion exchange water to obtain a dispersion containing 40 wt % of magnesium oxide, 2.7 wt % of SML and 57.3 wt % of ion exchange water. Magnesium oxide used was "MgO, food grade" (MS-0) from TOMITA Pharmaceutical CO., Ltd. The calcination temperature of MS-0 was 600°C. The dispersion prepared above was added dropwise into ion exchange water in the required amount. The particle size distribution was measured using a Shimadzu SALD-2000J laser reflection particle size distribution measuring instrument at a wavelength of 680 nm. The obtained D10, D50 and D90 were 0.801, 2.577 and 5.739 respectively.

[0057] Figure 1 It can be seen that the particle sizes are less than 50μm, less than 45μm, less than 40μm, less than 35μm, and less than 30μm. (B) Analysis of film elongation A 40 wt% aqueous dispersion of magnesium oxide (MS-0) at room temperature was added to an aqueous solution of hydroxypropyl methylcellulose (HPMC2906) at room temperature to prepare three solutions having a 20 wt% hydroxypropyl methylcellulose concentration (solid content) and a weight ratio of magnesium oxide to hydroxypropyl methylcellulose of 0.5, 7.5, and 15 wt% magnesium oxide. Hydroxypropyl methylcellulose HPMC 2906 manufactured by Shin-Etsu Chemical Industry Co., Ltd. was used in the test. After the dispersion was fully stirred and defoamed, a film was made using a CAMAG applicator as follows: a 20×20×0.3 cm glass plate was preheated to 70°C, and the film was pulled to a thickness of 100 um when dry using an applicator, and immediately placed in a 60°C oven to dry for 15 minutes. The film was cut into strips measuring 1 cm in length and 10 cm in width, and stored in a humidity control box at a relative humidity of 2.5% RH for 7 days to adjust the moisture content. Afterwards, the film was pulled at a speed of 5 mm / min using a 68TM-5 universal testing machine manufactured by INSTRON, and the film elongation % was measured until the film was cut (Table 3). It was found that the elongation of the film decreased with increasing magnesium oxide content.

[0058] [Table 3-1] MS-0

[0059] The elongation of the film was measured in the same manner as above using MS-2 as magnesium oxide. [Table 3-2] MS-2

[0060] The film containing MS-2 had a higher film elongation than MS-0, which indicated that MS-2 brought about better elongation.

[0061] In the following examples (C) to (D) and (F), the same hypromellose as in (B) was used. In the following examples (C) to (E), MS-0 and MS-2 were used as magnesium oxide. In (F), MS-0 was used.

[0062] (C) The role of plasticizers Using dispersions containing 0.5, 7.5 and 15 wt % of magnesium oxide relative to hypromellose, 5 films containing sorbitan monolaurate (SML; CAS 1338-39-2) were prepared, and the weight ratios thereof to hypromellose were shown in Table 2, and the dispersions were prepared using a 40 wt % aqueous dispersion of magnesium oxide (MS-0). After drying and adjusting the water content in the same manner as in (B), the film elongation was measured using the same universal testing machine (Table 4).

[0063] [Table 4-1] MS-0 The results were compared with those in Table 3, and it was confirmed that the addition of SML made the film softer and the elongation also increased. This indicates that SML acts as a plasticizer. It was confirmed that the addition of a plasticizer improved the decrease in the plasticity of the film caused by magnesium oxide. In experience, the higher the elongation of the film, the less likely the capsule is to break due to impact.

[0064] The elongation of the film was measured in the same manner as above using MS-2 as magnesium oxide.

[0065] [Table 4-2] MS-2 Even if MS-2 is used instead of magnesium oxide (MS-0), sorbitan monolaurate (SML) can still act as a plasticizer, and the elongation of MS-2&SML is higher than that of MS-0&SML.

[0066] (D) Light-shielding effect of magnesium oxide In the same manner as (B), 5 wt%, 10 wt%, 15 wt% and 20 wt% of magnesium oxide (MS-0) were added to the hypromellose solution relative to the weight of the hypromellose to prepare sample films. Films without magnesium oxide were also prepared. The films were prepared using a UV-1900i ( Figure 2A , 2B and Table 5) measured the transmittance at wavelengths from 190 nm to 1100 nm. Similarly, 0.25 wt%, 0.5 wt%, 1 wt%, 2 wt%, 7.5 wt%, 15 wt% of magnesium oxide relative to the weight of hypromellose was suspended in the hypromellose solution, and a sample film was prepared in the same manner as (B). The light transmittance of the film was also measured ( Figure 3 , Table 5).

[0067] [Table 5-1] MS-0 200nm 400nm 600nm 800nm 1100nm MgO 0% 11.5 82.1 87.7 89.7 92.9 MgO 0.25% 9.9 76.1 83.1 85.9 88.2 MgO 0.5% 8.7 66.3 75.6 80.5 85.2 MgO 1% 5.2 43.5 55.3 63.3 72.5 MgO 2% 2.2 23.9 35.9 46.3 59 MgO 5% 0.1 2.9 6.4 10.9 19.6 MgO 7.5% 0 1.3 3.0 5.8 12.3 MgO 10% 0 0.6 1.4 2.7 6.3 MgO 13% 0 0.6 1.0 1.8 4.4 MgO 15% 0 0.5 0.8 1.3 3.0 MgO 20% 0 0.3 0.5 0.7 1.7 It was found that even when only 0.25 wt% of magnesium oxide was dispersed in hydroxypropylmethylcellulose, light was shielded compared to the case where no magnesium oxide was added.

[0068] The light transmittance was measured in the same manner as above using MS-2 as magnesium oxide.

[0069] [Table 5-2] MS-2 200nm 400nm 600nm 800nm 1100nm MgO 0% 11.5 82.1 87.7 89.7 92.9 MgO 0.25% 3.7 57.5 74.5 82.0 87.0 MgO 0.5% 2.1 43.3 65.0 76.1 84.5 MgO 1% 0.7 20.0 42.7 59.6 74.0 MgO 2% 0.1 6.2 21.7 40.0 60.5 MgO 5% 0 0.9 2.7 9.1 26.5 MgO 7.5% 0 0.6 1.1 3.8 16.2 MgO 10% 0 0.5 0.8 1.5 7.5 MgO 13% 0 0.5 0.7 0.9 4.1 MgO 15% 0 0.5 0.6 0.8 2.8 MgO 20% 0 0.4 0.6 0.6 1.3 At least at visible light wavelengths of 400 / 600 / 800, the transmittance of MS-2 is lower than that of MS-0, indicating that MS-2 has better light-shielding performance.

[0070] (E) Light-shielding effect of magnesium oxide in gelatin film A 30 wt % gelatin aqueous solution at 50° C. was prepared using pig skin gelatin (acid-treated gelatin, type A / gelatin) produced by Lucero and bovine bone gelatin (alkali-treated gelatin, type B / gelatin) produced by Nitta Gelatin. As gelatin, six types of gelatin were used, with the weight ratios of type A / type B of the above two gelatins being 100 / 0, 80 / 20, 60 / 40, 50 / 50, 40 / 60 and 0 / 100% respectively. Magnesium oxide (MS-0) dispersion was added to each gelatin solution in an amount of 10% by weight based on the weight of gelatin, and the mixture was stirred thoroughly to defoam. The dispersion was formed into a film having a thickness of 100 μm after drying using a film forming machine ( Figure 4B ). The light transmittance of the film was measured using the same method as in (D). Figure 4A , Table 6)

[0071] [Table 6-1] MS-0 200nm 400nm 600nm 800nm 1100nm A / B=100 / 0% 0 1.8 5.0 10.8 22.4 A / B=80 / 20% 0 1.7 5.0 11.3 23.7 A / B=60 / 40% 0 1.7 4.9 11.0 23.1 A / B=50 / 50% 0 1.6 4.8 10.8 22.7 A / B=40 / 60% 0 1.7 4.7 10.6 22.1 A / B=0 / 100% 0 2.1 6.5 13.9 26.8

[0072] The light transmittance was measured in the same manner as above using MS-2 as magnesium oxide.

[0073] [Table 6-2] MS-2 200nm 400nm 600nm 800nm 1100nm A / B=100 / 0% 0 0.7 1.5 4.9 17.1 A / B=80 / 20% 0 0.7 2.0 7.7 24.4 A / B=60 / 40% 0 0.7 1.9 7.4 24.5 A / B=50 / 50% 0 0.8 2.6 9.6 27.6 A / B=40 / 60% 0 0.8 2.8 9.9 27.9 A / B=0 / 100% 0 0.9 3.7 12.4 31.7 At least at visible light wavelengths of 400 / 600 / 800, the transmittance of MS-2 is lower than that of MS-0, indicating that MS-2 has better light-shielding performance.

[0074] (F) Dissolution test Using 40% by weight of magnesium oxide aqueous dispersion, a dispersion containing 20% ​​by weight of hypromellose, 7.5% by weight of magnesium oxide and 0.5% by weight of SML relative to the weight of hypromellose was prepared. Using a hard capsule manufacturing machine (manufactured by CAPSUGEL), a No. 1 hypromellose capsule was manufactured by immersing a capsule metal mold heated to 80°C in the dispersion to gel the hypromellose. The capsule was filled with 280mg of acetaminophen powder, and a dissolution test was performed using an NTR-6300A dissolution tester manufactured by Toyama Sangyo at 37°C of USP pH1.2 solution, a settler, and a paddle speed of 50rpm. As a reference, a No. 1 hypromellose capsule without magnesium oxide was produced under the same production conditions as above. The average dissolution rates of the six capsules are as follows (Table 7).

[0075] [Table 7] It has been demonstrated that no reduction in dissolution was observed in hypromellose capsules containing magnesium oxide. [Industrial Applicability]

[0076] According to the present invention, magnesium oxide can be used as a sunscreen to replace titanium oxide, which is considered to have health problems, to give capsule shells sunscreen properties. Magnesium oxide has been safely used as a medicine. The sunscreen capsules obtained by the present invention maintain solubility and maintain stable sunscreen properties for a long time. In addition, when used with a dye, it can produce an opaque colored film. Therefore, magnesium oxide is very useful and safe for manufacturing capsules for filling drugs, veterinary drugs, pesticides, cosmetics, health foods, etc.

Claims

1. A hard capsule shell, wherein the shell is formed by a hard capsule shell membrane, the hard capsule shell membrane comprising a film-forming polymer and magnesium oxide, wherein the hard capsule shell membrane does not contain titanium oxide, a white colorant; and wherein the hard capsule shell has only one layer, which is the hard capsule shell membrane, or The hard capsule shell has more than one layer and at least one layer different from the outermost layer is the hard capsule shell membrane.

2. The hard capsule shell according to claim 1, wherein the hard capsule shell membrane does not contain white colorant calcium carbonate.

3. The hard capsule shell according to claim 1 or 2, wherein the hard capsule shell membrane does not contain a white colorant other than magnesium oxide.

4. The hard capsule shell according to any one of claims 1 to 3, wherein the particle size of the magnesium oxide is 50 um or less.

5. The hard capsule shell according to any one of claims 1 to 4, wherein the particle size distribution D10 value of the magnesium oxide is 0.1 um to 2.0 um.

6. The hard capsule shell according to any one of claims 1 to 5, wherein the particle size distribution D90 value of the magnesium oxide is 4 um to 45 um.

7. The hard capsule shell according to any one of claims 1 to 6, wherein the amount of the film-forming polymer is at least 75% by weight, wherein the weight % is based on the dry weight of the hard capsule shell membrane.

8. The hard capsule shell according to any one of claims 1 to 7, wherein the magnesium oxide is heavy magnesium oxide.

9. A hard capsule shell according to any one of claims 1 to 8, wherein the amount of magnesium oxide is from 0.25 wt% to 20 wt%, wherein the wt% is based on the dry weight of the film-forming polymer.

10. A hard capsule shell according to any one of claims 1 to 9, wherein the amount of magnesium oxide is from 2 wt% to 10 wt%, wherein the wt% is based on the dry weight of the film-forming polymer.

11. A hard capsule shell according to any one of claims 1 to 10, wherein the amount of magnesium oxide is 5 to 8 wt%, wherein the wt% is based on the dry weight of the film-forming polymer.

12. The hard capsule shell according to any one of claims 1 to 11, wherein the film-forming polymer is selected from the group consisting of gelatin, polyglutamic acid, cellulose derivatives, pullulan, starch, dextrin, agar, chitosan, acid-treated broken yeast, polyvinyl alcohol (PVA), PVA-methyl methacrylate copolymer, polyvinyl pyrrolidone (PVP).

13. The hard capsule shell according to any one of claims 1 to 12, further comprising a plasticizer.

14. The hard capsule shell according to claim 13, wherein the plasticizer is selected from the group consisting of xylitol, fructose, sorbitan fatty acid esters, triethyl citrate, glycerol, sorbitol, mannitol, trehalose, vegetable oils, medium chain fatty acid triglycerides, triacetin, phthalates, phytosterols, propylene glycol, polysorbate and polyethylene glycol.

15. The hard capsule shell according to claim 13 or 14, wherein the amount of the plasticizer is from 0.01 wt% to 10 wt%, wherein the wt% is based on the dry weight of the film-forming polymer.

16. The hard capsule shell according to claim 14, wherein the plasticizer is sorbitan fatty acid ester.

17. The hard capsule shell according to claim 16, wherein the plasticizer is sorbitan monolaurate.

18. The hard capsule shell according to any one of claims 1 to 17, which is colored by adding a colorant, wherein the colorant has a color other than white.

19. A method for preparing a hard capsule shell according to claim 1, wherein the hard capsule shell film comprising a film-forming polymer and magnesium oxide is prepared by dip molding.

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