WO2019208668A1 - 軟カプセル皮膜組成物 - Google Patents
軟カプセル皮膜組成物 Download PDFInfo
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- WO2019208668A1 WO2019208668A1 PCT/JP2019/017529 JP2019017529W WO2019208668A1 WO 2019208668 A1 WO2019208668 A1 WO 2019208668A1 JP 2019017529 W JP2019017529 W JP 2019017529W WO 2019208668 A1 WO2019208668 A1 WO 2019208668A1
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- starch
- soft capsule
- gellan gum
- acid
- film composition
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4816—Wall or shell material
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
Definitions
- the present invention relates to a soft capsule film composition, and a soft capsule film and a soft capsule using the same.
- a rotary die filling method which is one of the methods for producing soft capsules, is a sheet-like method by spreading a coating composition solution on a cooled rotating drum on both sides of a capsule filling machine. Then, the coating sheet is fed between rotating cylindrical molds (die rolls), and the contents are press-fitted by a piston of a pump interlocking therewith, and a capsule is formed by cutting both molds. At this time, the film sheet is heated to an appropriate temperature by the segment, and is bonded by pressure and heat sealing to form a soft capsule.
- the properties required for the coating composition used for molding by this method are mechanical strength that can withstand continuous processes from molding to filling of the coating sheet and sol-gel thermoreversibility for heat sealing, or adhesion by pressure bonding. It is sex. Conventionally, gelatin having these characteristics at a high level has been used as a soft capsule film composition.
- starches are used in producing a soft capsule film. So far, natural starch and various processed starches have been used, and as natural starch, potato starch, tapioca starch, sago starch, sweet potato starch, mung bean starch, wheat starch, corn starch, rice starch, waxy corn starch, Waxy potato starch, waxy wheat starch, glutinous rice starch and the like are mentioned.
- the processed starch the above-mentioned natural starch is acetylated, hydroxypropylated, octenyl succinic acid oxidized, phosphorylated, crosslinked, acid treated, wet heat treated, ultrasonic treated Etc. (especially, Patent Documents 13 to 14).
- Gellan gum is attracting attention as a polysaccharide having a gel forming action other than carrageenan derived from seaweed.
- Gellan gum includes native gellan gum (also referred to as “native gellan gum”, “high acyl gellan gum”, or “HA gellan gum”) and deacylated gellan gum (also referred to as “deacyl gellan gum” or “LA gellan gum”). There is. However, the following problems remain in the soft capsule film composition using gellan gum and the production of the soft capsule.
- the rotary die type filling machine is designed to be suitable for filling and forming soft capsules consisting of gelatin coating with a lot of stickiness on the back side of the coating, which is the opposite of coating sheets using native gellan gum. This can be a serious problem when the soft capsule used is manufactured by utilizing an existing rotary die type filling machine without significantly modifying the equipment.
- carrageenan and native gellan gum are used in combination as a gelling agent, physical properties of the film are difficult, and it is pointed out that the elasticity and adhesion after encapsulation are inferior compared to the case of using carrageenan alone.
- the reason why the film sheet made of native gellan gum and starch exhibits such properties can be considered as follows. That is, since the gelation temperature of the film sheet using native gellan gum is considerably higher than that of gelatin or the like, when the film sheet is formed on the rotary drum of a rotary die filling machine, A place where gelation has advanced due to rapid air cooling below and a place slightly delayed are generated, and the gelation state of the sheet is uneven and insufficient, resulting in a sticky gel. On the other hand, on the inner surface (back surface) of the film in contact with the rotating drum, there is less air cooling than the surface and there is also heating from the drum, the gel slowly gels uniformly and forms a firm and less sticky sheet surface It is thought that it will come to do.
- the film strength does not reach a mechanical strength that can withstand continuous production, and breaks during the capsule filling process.
- the adhesive strength at the time of pressure bonding is low, and there may be a disadvantage that good adhesiveness cannot be obtained.
- Gellan gum is a gelling agent having a higher viscosity than gelatin and other vegetable polysaccharide gelling agents. In the production of a soft capsule coating composition using gellan gum, this is mixed with starch. When preparing a coating composition by heating and dissolving, the viscosity becomes very high, the operability at the time of capsule production (homogeneous mixing operability for uniformly mixing the compositions with each other) becomes very poor and the desired concentration is difficult to obtain. Can be mentioned. Particularly in the production of soft capsules, it is necessary to increase the solid content concentration from the viewpoint of the film strength. However, if the concentration is increased, the viscosity of the composition solution increases, so that the operability deteriorates, and further on an industrial scale. However, there are problems such as the need for major changes in machinery and equipment.
- Blocking is a phenomenon often seen in conventional capsule films made mainly from gelatin, and there is a strong demand for a solution to this problem.
- the present invention has been made in view of the above-mentioned problems, and is a soft capsule film composition using gellan gum derived from a non-animal raw material, including the use of existing soft capsule filling and manufacturing equipment such as a rotary die filling machine.
- the stickiness of the coating sheet surface is reduced, the mechanical strength of the coating sheet is increased to prevent breakage and the like, and soft capsules with good adhesion are stably produced by pressure bonding.
- the purpose is a soft capsule film composition using gellan gum derived from a non-animal raw material, including the use of existing soft capsule filling and manufacturing equipment such as a rotary die filling machine.
- the present inventors have obtained (A) native gellan gum, (B) one or more hydrophilic polysaccharides, (C) starch or modified starch, (D) If a composition containing a plasticizer and (E) water is used, the carrageenan is not required at all, the strength of the coating sheet is high, and the biting of the coating base into the joint portion is suppressed and good adhesiveness is achieved. It was found that the capsule film shown was obtained. Furthermore, it has been found that if the composition is used, excellent film performances such as blocking resistance, elasticity, transparency, and rapid disintegration can be obtained after encapsulation. The present invention has been completed based on these findings.
- the present invention relates to the following. (1) Contains (A) native gellan gum, (B) one or more hydrophilic polysaccharides, (C) starch or modified starch, (D) plasticizer, and (E) water, (A) native A soft capsule film composition characterized by not containing gelling agents other than gellan gum and (B) one or more hydrophilic polysaccharides as essential components.
- (C) Starch or modified starch is natural starch, oxidized starch, hydroxypropylated starch, acetylated starch, acetylated, hydroxypropylated, octenyl succinylated, phosphorylated, crosslinked, acid treated, in the presence of salt
- the soft capsule coating composition according to (1) which is one or more selected from starch that has been subjected to wet heat treatment, or a starch dispersion that has been subjected to ultrasonic treatment in a starch paste solution.
- (C) Starch or modified starch is sago starch, sweet potato starch, mung bean starch, wheat starch, corn starch, rice starch, waxy corn starch, waxy potato starch, waxy wheat starch, or glutinous rice starch, or from these The soft capsule film composition according to (1) or (2), wherein the composition is one or more selected from the obtained processed starch.
- (C) Starch or modified starch is selected from waxy potato starch, oxidized starch, starch that has been heat-moisture treated in the presence of salt, or starch dispersion that has been subjected to ultrasonic treatment of starch paste.
- the content mass ratio [(A) :( B)] of (A) native gellan gum and (B) one or more hydrophilic polysaccharides is 1: 1 to 1: 0.01
- the soft capsule coating composition of the present invention is a combination of native gellan gum, one or more hydrophilic polysaccharides, and a specific starch or modified starch, which does not contain carrageenan and has a drying time at room temperature. Shortening, stickiness of the coating sheet surface is suppressed, the coating sheet strength that can withstand continuous production in the factory production of rotary die filling machines and the like is given, and the production of a good soft capsule coating with high adhesiveness is enabled.
- FIG. 1 is a schematic view showing a rotary die type capsule filling machine.
- the soft capsule film composition of the present invention is used for a film of a soft capsule used in pharmaceuticals, quasi drugs, foods, health foods, cosmetics, etc., and at least native gellan gum and one or two kinds
- the above hydrophilic polysaccharide, starch or processed starch, a plasticizer, and water are included. That is, the minimum necessary components for the soft capsule film composition of the present invention are (A) native gellan gum, (B) one or more hydrophilic polysaccharides, (C) starch or processed starch.
- the mass ratio of native gellan gum to one or more hydrophilic polysaccharides is 1: 1 to 1: 0.01.
- Gellan gum (also called “gellan gum”) is a heteropolysaccharide produced outside the cell by a microorganism called Pseudomonas elodea, 1-3 linked glucose, 1-4 linked glucuronic acid, 1- Four sugars, 4-linked glucose and 1-4-bonded rhamnose, are linearly bound as repeating units.
- Pseudomonas elodea 1-3 linked glucose, 1-4 linked glucuronic acid, 1-
- sugars, 4-linked glucose and 1-4-bonded rhamnose are linearly bound as repeating units.
- those in which an acyl group is not bonded to the aforementioned saccharides constituting the polysaccharide are generally referred to as deacylated gellan gum and generally have a property of forming a hard and brittle gel.
- a repeating unit in which an acetyl group and a glyceryl group are bonded to 1-3 bonded glucose is generally called native gellan gum and has a property of forming a soft and stretchable gel.
- native gellan gum examples include “Kelcogel CG-HA”, “Kelcogel LT100”, “Kelcogel HM”, “Kelcogel HT”, and examples of the deacylated gellan gum include “Kelcogel” and “Kelcogel F”. Etc. (both manufactured by CP Kelco).
- Gellan gum has a high heat resistance and forms a strong gel as compared with a gelling agent derived from seaweed such as carrageenan and agar.
- gelling agent in the present specification means a chemical substance that causes gelation of a liquid sol. Further, “gelation” means a phenomenon in which a liquid sol is solidified in a jelly form. For example, there are gelling agents that gel by cooling such as agar and gelatin, and gelling agents that gel by the presence of specific ions such as alginate.
- native gellan gum does not require acetyl groups and glyceryl groups to be bonded to glucose in all repeating units, and all gellan gums in which acylated groups are present in the entire gellan gum It is included in native gellan gum as used in the present invention.
- gellan gum with a “degree of acylation: 0” is “deacylated gellan gum”, and all other gellan gums (with a degree of acylation not 0) are “native gellan gum”.
- native gellan gum means gellan gum with a degree of acylation that is not zero.
- “degree of acylation” was determined by 1 HNMR measurement using a Bruker Avance DRX-400 (Bruker), a peak derived from the methyl group of rhamnose appearing around 1.3 ppm, and a hydroxyl group at the 6-position of ⁇ -glucose appearing around 2.1 ppm.
- the hydrophilic polysaccharide means a polysaccharide having water solubility excluding native gellan gum. That is, the hydrophilic polysaccharide in the present invention refers to a polysaccharide that dissolves in water (regardless of temperature).
- hydrophilic polysaccharides examples include pectin (low methoxy pectin (LM pectin), high methoxy pectin (HM pectin)), locust bean gum, glucomannan, xanthan gum, carrageenan, farsellan, deacylated gellan gum, chondroitin and its Sulfates, alginic acid and alginates, alginic acid derivatives such as alginic acid propylene glycol ester, gum polymer such as gum arabic, guar gum, tamarind gum, carboxymethylcellulose, hydroxypropyl starch, pregelatinized starch, pullulan, hydroxyalkylcellulose, polyvinyl Examples include pyrrolidone, polyvinyl alcohol, and agar.
- Low methoxy pectin means a pectin having an esterification degree (DE) of less than 50%
- high methoxy pectin means a pectin having an esterification degree (DE) of 50% or more.
- the degree of esterification means the ratio of methyl esterification in the total galacturonic acid, and the value obtained by dividing the number of methyl esterified galacturonic acids by the total number of galacturonic acids and multiplying by 100 (%) You can ask.
- the content mass ratio of native gellan gum to one or more hydrophilic polysaccharides is preferably 1: 1 to 1: 0.01, and preferably 1: 0.8 to 1: 0.03. It is more preferable that the ratio is 1: 0.6 to 1: 0.05.
- the content of the hydrophilic polysaccharide is preferably 0.1% by mass or more and more preferably 0.5% by mass or more in the total amount of the solid components from the viewpoint of gelation ability. Further, from the viewpoint of the viscosity of the coating liquid, the total amount of the solid components is preferably 10% by mass or less, more preferably 5% by mass or less, and still more preferably 3% by mass or less.
- the “solid component” is a product obtained by removing water from the coating composition.
- starch means raw ⁇ -1,4-glucan obtained from seeds, roots, rhizomes, etc. of higher plants as storage polysaccharide.
- starch and “starch” used in this specification have the same meaning.
- processed starch means that starch, water, chemicals (various salts, adipic acid, sodium hypochlorite, vinyl acetate, phosphoric acid compound, etc.) are added to starch as necessary, heat treatment, ultrasonic
- the starch obtained by performing a process or other processes is meant.
- modified starch include waxy corn starch (waxy corn starch) mentioned below.
- the starch or modified starch used in the present invention is not particularly limited.
- starch or processed starch used in the present invention natural starch, oxidized starch, hydroxypropylated starch, acetylated starch, acetylated, hydroxypropylated, octenyl succinic acid oxidation, phosphorylation, crosslinking, acid treatment, in the presence of salt
- examples include one or two or more selected from starch that has been subjected to wet heat treatment, or starch dispersion that has been subjected to ultrasonic treatment in starch paste liquid.
- Waxy corn starch that has been heat-moisture treated in the presence of salt is starch obtained by heating waxy corn starch in a wet state in the presence of salt.
- Such starches are known, and are produced, for example, from waxy corn starch by the method described in Japanese Patent No. 4608051 or a method analogous thereto.
- the viscosity of the starch paste solution of waxy corn starch that has been heat-treated in the presence of salt is preferably 100 to 3000 mPa ⁇ s.
- the viscosity is 100 mPa ⁇ s or more, the “body feeling” of the starch is obtained, and the coating sheet becomes flexible, tends to be stretched, and tends to have good adhesion.
- Waxy corn starch subjected to wet heat treatment is preferably unprocessed, that is, not subjected to processing such as acid treatment, pregelatinization, etherification or acetylation.
- Waxy potato starch is preferably starch obtained by treating waxy potato starch with an acid.
- the viscosity of starch paste (starch content: 30% by mass, liquid temperature: 80 ° C.) is a comprehensive point of view (in terms of film strength, gelation) From the viewpoint of strength, it is preferably 6 mPa ⁇ s or more, and more preferably 10 to 20 mPa ⁇ s.
- Waxy potato starch may be added in place of waxy corn starch that has been heat-treated in the presence of salt, or waxy corn starch and / or sonicated waxy corn that has been heat-treated in the presence of salt. You may add together with starch.
- the content of waxy corn starch and waxy potato starch that has been heat-moisture treated in the presence of salt is preferably 1% by mass or more, more preferably 5% by mass or more, in the total amount of solid components, as the total amount thereof. 10 mass% or more is still more preferable. Further, in terms of the strength of the coating sheet, the content is preferably 50% by mass or less, more preferably 40% by mass or less, and still more preferably 30% by mass or less in the total amount of the solid components.
- the starch dispersion obtained by subjecting the starch paste solution to ultrasonic treatment is a known substance, and is produced, for example, from starch by a method described in Japanese Patent No. 4288381 or a method analogous thereto.
- the starch paste solution is prepared by a conventional method, for example, by heating the starch in water to gelatinize the starch.
- the starch content in the starch paste solution is not particularly limited, but is preferably 1% by mass or more, more preferably 5% by mass or more, and still more preferably 10% by mass or more.
- Starch types include, for example, potato starch, tapioca starch, sago starch, sweet potato starch, mung bean starch, wheat starch, corn starch (corn starch), rice starch, waxy corn starch, waxy potato starch, waxy wheat starch or glutinous rice starch Or the processed starch obtained from these is mentioned. These starches and processed starches can be used singly or in combination of two or more.
- starch or modified starch used in the present invention, potato starch, tapioca starch, sago starch, sweet potato starch, mung bean starch, wheat starch, corn starch, rice starch, waxy corn starch, waxy potato starch, waxy wheat
- starch or processed starch waxy potato starch, oxidized starch, starch that has been heat-moisture treated in the presence of salt, or starch paste solution is subjected to ultrasonic treatment. 1 type or 2 types or more chosen from the starch dispersion formed.
- the starch used for the preparation of the starch paste is preferably unprocessed, that is, not subjected to processing such as acid treatment, pregelatinization, etherification or acetylation.
- the viscosity of the starch paste liquid when subjected to ultrasonic treatment (B-type viscometer, starch content 5 mass%, liquid temperature 95 ° C.) varies depending on the type of starch, but is 400 to 800 mPa ⁇ s. 400 to 600 mPa ⁇ s is preferable.
- the conditions for ultrasonic treatment can be set as appropriate.
- the viscosity (B-type viscometer, starch content 20 mass%, liquid temperature 80 ° C.) of the starch dispersion after ultrasonic treatment is preferably 350 mPa ⁇ s or less, although it varies depending on the type of starch, 10 to 350 mPa ⁇ s. s is more preferable.
- the starch dispersion obtained by subjecting the starch paste solution to ultrasonic treatment may be in the form of a liquid, but is preferably a dried product obtained by drying the starch dispersion.
- the drying method include spray drying, freeze drying, evaporation to dryness, and the like.
- a commercially available product can be used as the starch dispersion obtained by subjecting the starch paste solution to ultrasonic treatment.
- the content of the starch dispersion obtained by subjecting the starch paste solution to ultrasonic treatment is preferably 10% by mass or more, and 20% by mass in the total amount of solid components from the viewpoint of adhesiveness.
- dry mass hereinafter the same
- the above is more preferable, and 30% by mass or more is still more preferable.
- 60 mass% or less is preferable in the total amount of a solid component from the point of film sheet intensity
- the soft capsule film composition of the present invention includes, in addition to starch dispersion formed by ultrasonic treatment of waxy corn starch, waxy potato starch and starch paste solution that have been heat-moisture treated in the presence of salt, Other starches can be contained as required.
- the content of starches other than the starch dispersion obtained by ultrasonic treatment of waxy corn starch and starch paste solution that have been heat-treated in the presence of salt are the film sheet strength, adhesive strength, and elasticity after drying. From the above point, in the total amount of the solid components, 50% by mass or less is preferable, 40% by mass or less is more preferable, 30% by mass or less is further preferable, and 10% by mass or less is even more preferable.
- the lower limit is 0% by mass.
- starch examples include potato starch, tapioca starch, sago starch, sweet potato starch, mung bean starch, wheat starch, corn starch, rice starch, waxy corn starch, waxy potato starch, waxy wheat starch, and sticky rice starch. Etc. These can be used alone or in combination of two or more.
- the soft capsule film composition of the present invention contains only (A) native gellan gum and (B) one or more hydrophilic polysaccharides as gelling agents, and may not contain other gelling agents. .
- the plasticizer is not particularly limited, and examples thereof include sugar alcohols such as glycerin, sorbitol, erythritol, propylene glycol, and polyethylene glycol. These may be used alone or as a mixture. Of these, glycerin and sorbitol are preferable.
- the content of the plasticizer in the soft capsule film composition of the present invention is preferably 20 parts by mass or more and more preferably 30 parts by mass or more in the total amount of solid components from the viewpoint of flexibility. Moreover, from an adhesive point, 60 mass parts or less are preferable with respect to 100 mass parts of total amounts of a solid component, and 50 mass parts or less are more preferable.
- Water is preferably 80 parts by mass or more, and more preferably 100 parts by mass or more with respect to 100 parts by mass of the total amount of solid components.
- the water to be used is preferably purified water (for example, purified water obtained by passing tap water through an ion exchange resin).
- the prescription of the soft capsule film composition of the present invention which is characterized by not containing a gelling agent other than one or two or more hydrophilic polysaccharides as an essential component, is exemplified below.
- the soft capsule film composition of the present invention further includes various additives used in the soft capsule film composition, for example, natural dyes, synthetic dyes, various sweeteners, preservatives, and water activity lowering agents, if necessary.
- various additives used in the soft capsule film composition for example, natural dyes, synthetic dyes, various sweeteners, preservatives, and water activity lowering agents, if necessary.
- a pH adjusting agent and the like can be contained.
- a soft capsule can be obtained by forming such a soft capsule film composition into a predetermined shape and drying it.
- the soft capsule can be produced, for example, by a conventionally used method for producing a soft capsule, for example, a punching method using a rotary die type soft capsule filling machine, or a flat plate method.
- a rotary die type soft capsule filling machine is a method of punching two coated sheets formed by spreading a soft capsule coating solution on a rotating drum into a capsule shape with a pair of rotating molds (die rolls). Molding and filling of the capsule contents are performed simultaneously.
- the solution of the soft capsule coating composition of the present invention can be obtained by heating the rotary drum to 30 to 80 ° C. in the step of forming the coating sheet by spreading on a rotary drum such as a rotary die type filling machine. Mechanical strength and adhesive force for pressure bonding are added to the sheet, and a soft capsule having sufficient strength can be formed. Sealing the contents with a mold when filling the capsule is performed by heating the two coating sheets with segments and then heat-sealing, pressing, or a combination thereof. From the viewpoint of protection from heating in the case of the above, it is desirable that the segment temperature is low. In the present invention, as shown in an example of a later rotary die capsule filling machine, filling and sealing are possible even at room temperature, and it can be sufficiently adapted to such a case.
- the shape of the soft capsule is not particularly limited as long as it is suitable for oral administration.
- a special type such as an oval (football) type, an oblong (ellipse) type, a round (spherical) type, a tube type, etc. Can be mentioned.
- the soft capsules produced using the soft capsule film composition of the present invention can be used for various uses such as pharmaceuticals, quasi drugs, cosmetics, foods, etc.
- the composition of the capsule content is appropriately determined according to the use. It is determined.
- the content may be in the form of a solution, a suspension, a paste, a powder, a granule or the like. Below, what can be contained in a capsule is illustrated. Each of these components can be contained in any part of the capsule.
- waxes and waxes shellac wax, beeswax, carnauba wax, whale wax, lanolin, liquid lanolin, reduced lanolin, hard lanolin, cyclic lanolin, lanolin wax, candelilla wax, molasses, montan wax, shellac wax, rice wax, etc.
- the hardened oil it is possible to contain a hardened vegetable oil obtained by hydrogenating vegetable fats, hardened beef fat, hardened tallow oil, and the like.
- mineral oil liquid paraffin, petrolatum, paraffin, ozokelide, ceresin, microcrystalline wax and the like can be contained.
- fatty acids lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, conjugated linoleic acid, linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, 12-hydroxystearic acid, undecylenic acid, tall oil , Natural fatty acids such as lanolin fatty acid, isononanoic acid, caproic acid, 2-ethylbutanoic acid, isopentanoic acid, 2-methylpentanoic acid, 2-ethylhexanoic acid, isopentanoic acid and the like, and fats and oils containing these fatty acids as fatty acid composition Etc. can be contained.
- vitamin A group retinol, retinal (vitamin A1), dehydroretinal (vitamin A2), carotene, lycopene (provitamin A), vitamin B group: fursultiamine, thiamine hydrochloride, thiamine sulfate (vitamin B1 ), Riboflavin (vitamin B2), pyridoxine (vitamin B6), cyanocobalamin, methylcobalamin (vitamin B12), folic acid, nicotinic acids, pantothenic acids, biotins, choline, inositols, vitamin C group: ascorbic acid or its derivatives, Vitamin D group: Ergocalciferol (vitamin D2), cholecalciferol (vitamin D3), dihydrotaxosterol, vitamin E group: vitamin E or its derivatives, ubiquinones, vitamin K group: phytonadione (vitamin) K1), menaquinone (vitamin K2), menate
- pepper tincture red pepper oil, nonyl acid vanillamide, cantalis tincture, ginger tincture, ginger oil, mint oil, l-menthol, camphor, benzyl nicotinate, and the like can be contained.
- benzophenone derivatives (2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid sodium, dihydroxydimethoxy Benzophenone, dihydroxydimethoxybenzophenone-sodium sulfonate, 2,4-dihydroxybenzophenone, tetrahydroxybenzophenone, etc.
- paraaminobenzoic acid derivatives paraaminobenzoic acid, ethyl paraaminobenzoate, glyceryl paraaminobenzoate, amyl paradimethylaminobenzoate, para Octyl dimethylaminobenzoate
- methoxycinnamate derivatives ethyl paramethoxycinnamate, isopropyl paramethoxycinnamate, paramethoxycinnamon
- whitening agents paraaminobenzoic acid derivatives, salicylic acid derivatives, anthranilic acid derivatives, coumarin derivatives, amino acid compounds, benzotriazole derivatives, tetrazole derivatives, imidazoline derivatives, pyrimidine derivatives, dioxane derivatives, camphor derivatives, furan derivatives, pyrone derivatives, nucleic acids Derivatives, allantoin derivatives, nicotinic acid derivatives, vitamin C or derivatives thereof (vitamin C phosphate magnesium salt, vitamin C glucoside, etc.), vitamin E or derivatives thereof, kojic acid or derivatives thereof, oxybenzone, benzophenone, arbutin, guaiazulene, shikonin , Baicalin, baicalein, berberine, placenta extract, ellagic acid, lucinol and the like.
- tyrosinase activity inhibitors include vitamin C or derivatives thereof (vitamin C phosphate magnesium salt, vitamin C glucoside, etc.), hydroquinone or derivatives thereof (hydroquinone benzyl ether, etc.), kojic acid or derivatives thereof, vitamin E or derivatives thereof, N -Acetyltyrosine or its derivatives, glutathione, hydrogen peroxide, zinc peroxide, placenta extract, ellagic acid, arbutin, lucinol, silk extract, plant extract (camomile, mulberry, gardenia, touki, firewood, clara, mugwort, honeysuckle, Yellowfin, Butterflies, Pinewood, Barley, Oyster, Hops, Hawthorn, Eucalyptus, Achillea millefolium, Artea, Keihi, Mankeishi, Hamamelis, Karagowa or Yamaguwa, Life-surviving grass, bellflower, Toshishi, Ze
- phenylmercury hexachlorophene As a melanin reduction or decomposition substance, phenylmercury hexachlorophene, mercuric oxide, mercuric chloride, hydrogen peroxide solution, zinc peroxide, hydroquinone or a derivative thereof can be contained.
- hydroquinone As a turnover promoting action and cell activator, hydroquinone, lactic acid bacteria extract, placenta extract, ganoderma extract, vitamin A, vitamin E, allantoin, spleen extract, thymus extract, yeast extract, fermented milk extract, plant extract (aloe, ougone) , Cedar, gentian, burdock, shikon, carrot, hammelis, hop, yokuinin, mandarin duck, sea bream, cypress, pearl millet, achacha, hypericum, cucumber, red ginger, mannen wax, parsley) and the like.
- succinic acid As astringents, succinic acid, allantoin, zinc chloride, zinc sulfate, zinc oxide, calamine, zinc paraphenol sulfonate, potassium aluminum sulfate, resorcin, ferric chloride, tannic acid (including catechin compounds), etc. can be included is there.
- SOD active oxygen scavenger
- catalase catalase
- glutathione peroxidase glutathione peroxidase
- Anti-inflammatory agents include ictamol, indomethacin, kaolin, salicylic acid, sodium salicylate, methyl salicylate, acetylsalicylic acid, diphenhydramine hydrochloride, d-camphor, dl-camphor, hydrocortisone, guaiazulene, camazulene, chlorpheniramine maleate, glycyrrhizic acid or its salts , Glycyrrhetinic acid or a salt thereof, licorice extract, coconut extract, age extract, propolis and the like.
- Antibacterial, bactericidal and antiseptics include acrinol, sulfur, calcium gluconate, chlorhexidine gluconate, sulfamine, mercurochrome, lactoferrin or hydrolysates thereof, alkyldiaminoethylglycine chloride solution, triclosan, sodium hypochlorite, chloramine T, salashi Powder, iodine compound, iodoform, sorbic acid or salt thereof, propionic acid or salt thereof, salicylic acid, dehydroacetic acid, parahydroxybenzoic acid esters, undecylenic acid, thiamine lauryl sulfate, thiamine lauryl nitrate, phenol, cresol, p- Chlorophenol, p-chloro-m-xylenol, p-chloro-m-cresol, thymol, phenethyl alcohol, o-phenylphenol, Irgasan CH3565,
- glycerin As humectants, glycerin, propylene glycol, 1,3-butylene glycol, polyethylene glycol, glycerin tricaprycapric acid, glycolic acid ( ⁇ -hydroxy acid), hyaluronic acid or its salt, chondroitin sulfate or its salt, water-soluble chitin or its Derivatives or chitosan derivatives, pyrrolidone carboxylic acids or salts thereof, sodium lactate, urea, sorbitol, amino acids or derivatives thereof (valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, Cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid, hydroxylysine, arginine, ornithine, hist
- glycolic acid citric acid, malic acid, tartaric acid, lactic acid, ferulic acid, phytic acid and the like can be contained.
- selenium disulfide for hair, selenium disulfide, alkylisoquinolinium bromide, zinc pyrithione, biphenamine, thianthol, castari tincture, pepper tincture, pepper tincture, quinine hydrochloride, strong ammonia water, potassium bromate, sodium bromate, thioglycol It can contain an acid or the like.
- natural animal fragrances such as musk, civet, castorium, ambergris, anise essential oil, angelica essential oil, ylang ylang essential oil, iris essential oil, fennel essential oil, orange essential oil, cananga essential oil, caraway essential oil, cardamom essential oil, guayakwood essential oil, cumin Essential oil, black letter essential oil, cinnamon essential oil, cinnamon essential oil, geranium essential oil, copaiba balsam essential oil, coriandel essential oil, perilla essential oil, cedarwood essential oil, citronella essential oil, jasmine essential oil, gingergrass essential oil, cedar essential oil, spearmint essential oil, western peppermint essential oil, large Perfume essential oil, tuberose essential oil, clove essential oil, orange flower essential oil, winter green essential oil, trout balsam essential oil, buttery essential oil, rose essential oil, palmarosa essential oil, persimmon essential oil, hiba essential oil, sandalwood essential oil, petit gren essential oil, bay essential oil
- soft capsules are packaged, stored and distributed in packaging forms such as bottling packaging, PTP packaging, and pouches.
- Examples 1-2 and Comparative Examples 1-2 Production of soft capsules using a rotary die type soft capsule filling machine (1) In the presence of native gellan gum, low methoxy pectin, and salt in the amounts (parts by mass) shown in Table 1 Wet and heat-treated waxy corn starch, starch dispersion obtained by ultrasonic treatment of starch paste, waxy potato starch and glycerin are each stirred and dispersed in water and dissolved at 90 to 98 ° C with stirring. And degassed in vacuo. Sheets and soft capsules were produced from the coating solution using a rotary die type soft capsule filling machine. First, the coating liquid was spread on a rotating drum by a casting apparatus to prepare a coating sheet. At this stage, the following [a. Evaluation of film sheet strength], [b. Evaluation of elongation of film sheet] and [c. Evaluation of Stickiness of Film Sheet].
- the two coated sheets obtained are sent between a pair of rotating cylindrical molds via a lubricating roller and a deflector roll, respectively, and encapsulated to produce an oval (football) type soft capsule. Molded. At this stage, [d. Evaluation of adhesion of film sheet immediately after capsule formation] and [e. Evaluation of manufacturability with a capsule filling machine].
- Comparative Example 1 containing no low methoxy pectin, although the strength of the coating sheet was strong, there was much stickiness and it was unsuitable for production in a capsule filling machine. Further, in Comparative Example 2 which does not contain a starch dispersion obtained by subjecting the starch paste solution to ultrasonic treatment, the adhesion was weak although it was less sticky, and it was also unsuitable for production in a capsule filling machine. On the other hand, in Example 1 and Example 2 which concern on this invention, the physical property of the membrane
- Examples 3-7, Comparative Examples 3-4 Production of soft capsules with a rotary die type soft capsule filling machine
- Ultrasonicated waxy corn starch, waxy potato starch, and glycerin were each stirred and dispersed in water, dissolved at 90 to 98 ° C. with stirring, and vacuum degassed.
- Sheets and soft capsules were produced from the coating solution using a rotary die type soft capsule filling machine.
- the coating liquid was spread on a rotating drum by a casting apparatus to prepare a coating sheet. At this stage, the following [a. Evaluation of film sheet strength], [b. Evaluation of elongation of film sheet] and [c. Evaluation of Stickiness of Film Sheet].
- the two coated sheets obtained are sent between a pair of rotating cylindrical molds via a lubricating roller and a deflector roll, respectively, and encapsulated to produce an oval (football) type soft capsule. Molded. At this stage, [d. Evaluation of adhesion of film sheet immediately after capsule formation] and [e. Evaluation of manufacturability with a capsule filling machine].
- the soft capsules produced using the soft capsule film composition according to the present invention can be used for various uses such as pharmaceuticals, quasi drugs, cosmetics and foods.
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Abstract
Description
また、軟カプセル皮膜を製造する際には多種多様な澱粉類が使用されている。これまでに、天然澱粉や種々の加工澱粉が用いられており、天然澱粉としては、馬鈴薯澱粉、タピオカ澱粉、サゴ澱粉、甘藷澱粉、緑豆澱粉、小麦澱粉、とうもろこし澱粉、米澱粉,ワキシーコーン澱粉、ワキシーポテト澱粉、ワキシー小麦澱粉、もち米澱粉等が挙げられ、加工澱粉としては、上記の天然澱粉をアセチル化、ヒドロキシプロピル化、オクテニルコハク酸化、リン酸化、架橋、酸処理、湿熱処理、超音波処理等を施した澱粉が挙げられる(特に特許文献13~14)。
しかしながら、ジェランガムを用いた軟カプセル皮膜組成物及びその軟カプセル剤製造においては、以下の課題が残されている。
(1)(A)ネイティブジェランガム、(B)一種若しくは二種以上の親水性多糖類、(C)澱粉又は加工澱粉、(D)可塑剤、及び(E)水を含有し、(A)ネイティブジェランガム及び(B)一種若しくは二種以上の親水性多糖類以外のゲル化剤を必須成分としないことを特徴とする軟カプセル皮膜組成物。
(2)(C)澱粉又は加工澱粉が、天然澱粉、酸化澱粉、ヒドロキシプロピル化澱粉、アセチル化澱粉、アセチル化、ヒドロキシプロピル化、オクテニルコハク酸化、リン酸化、架橋、酸処理、塩の存在下で湿熱処理がされてなる澱粉、又は澱粉糊液に超音波処理がされてなる澱粉分散物から選ばれる一種又は二種以上であることを特徴とする、(1)の軟カプセル皮膜組成物。
(3)(C)澱粉又は加工澱粉が、サゴ澱粉、甘藷澱粉、緑豆澱粉、小麦澱粉、とうもろこし澱粉、米澱粉,ワキシーコーン澱粉、ワキシーポテト澱粉、ワキシー小麦澱粉、もしくはもち米澱粉、又はこれらから得られる加工澱粉、から選ばれる一種又は二種以上であることを特徴とする、(1)又は(2)の軟カプセル皮膜組成物。
(4)(C)澱粉又は加工澱粉が、ワキシーポテト澱粉、酸化澱粉、塩の存在下で湿熱処理がされてなる澱粉、又は澱粉糊液に超音波処理がされてなる澱粉分散物から選ばれる一種又は二種以上であることを特徴とする、(1)~(3)のいずれかの軟カプセル皮膜組成物。
(5)(A)ネイティブジェランガムと(B)一種若しくは二種以上の親水性多糖類の含有質量比[(A):(B)]が1:1~1:0.01である(1)~(4)のいずれかの軟カプセル皮膜組成物。
(6)澱粉糊液に超音波処理がされてなる澱粉分散物が、ワキシーコーン澱粉に由来する澱粉分散物である(1)~(5)のいずれかの軟カプセル皮膜組成物。
(7)澱粉糊液に超音波処理がされてなる澱粉分散物に用いられるワキシーコーン澱粉が未加工の天然澱粉である(6)の軟カプセル皮膜組成物。
(8)(C)澱粉又は加工澱粉が、塩の存在下で湿熱処理がされてなるワキシーコーン澱粉である(1)~(5)のいずれかの軟カプセル皮膜組成物。
(9)(1)~(8)のいずれかの軟カプセル皮膜組成物を用いて得られる軟カプセル皮膜。
(10)(1)~(8)のいずれかの軟カプセル皮膜組成物を用いて得られる軟カプセル。
なお、本明細書でいう「ゲル化剤」とは、液状ゾルのゲル化を起こさせる化学物質を意味する。また、「ゲル化」とは、液状ゾルがゼリー状に固化する現象を意味する。例えば寒天、ゼラチン等のように冷却によりゲル化するゲル化剤や、アルギン酸塩等のように特定のイオンの存在によってゲル化するゲル化剤などがある。
本明細書でいうネイティブジェランガムとは、すべての反復ユニットのグルコースにアセチル基とグリセリル基とが結合している必要はなく、ジェランガム全体の中にアシル化された基が存在しているジェランガムはすべて本発明でいうネイティブジェランガムに包含される。換言すると、「アシル化度:0」のジェランガムが「脱アシル化ジェランガム」、それ以外の(アシル化度が0ではない)ジェランガムはすべて「ネイティブジェランガム」である。本明細書でいうネイティブジェランガムとは、アシル化度が0ではないジェランガムを意味する。ここで、「アシル化度」は1HNMR測定により、Bruker Avance DRX-400(Bruker)を用い1.3ppm付近に現れるラムノースのメチル基由来のピークと2.1ppm付近に現れるβグルコースの6位のヒドロキシル基に結合したアセチル基のピークの信号強度比により測定できる。(安藤暢毅、「ネイティブジェランのゲル化機構に関する基礎研究」東京海洋大、2009年9月)
本発明において使用するジェランガムとしてネイティブジェランガムを採用した理由は以下の通りである。
(1)脱アシル化ジェランガムを軟カプセルの製造に顕著に使用すると、ゲルが硬いため、品質の低下につながる。
(2)ネイティブジェランガムはゲルが柔軟性を有し、軟カプセルの製造に好適である。
低メトキシペクチン(LMペクチン)は、エステル化度(DE)が50%未満のペクチンを意味し、高メトキシペクチンは、エステル化度(DE)が50%以上のペクチンを意味する。なお、エステル化度とは、総ガラクツロン酸中、メチルエステル化されているものの割合を意味し、メチルエステル化されたガラクツロン酸数を総ガラクツロン酸数で割って100を乗じた値(%)として求めることができる。
なお、本発明において、「固形成分」とは、皮膜組成物の中から、水を除いた物のことである。
本発明において、加工澱粉とは、澱粉に必要に応じて水、化学薬品(種々の塩類、アジピン酸、次亜塩素酸ナトリウム、酢酸ビニル、リン酸化合物、等)を加え、加熱処理、超音波処理、若しくはその他の処理を行って得られる澱粉を意味する。加工澱粉として、例えば、以下で言及するワキシーコーン澱粉(ワキシーコーンスターチ)が挙げられる。
塩の存在下で湿熱処理がされてなるワキシーコーン澱粉は、ワキシーコーン澱粉を、塩の存在下、湿潤状態で加熱を行った澱粉である。湿熱処理後、乾燥、必要に応じて粉砕することにより製造することができる。
このような澱粉は公知であり、例えば、ワキシーコーン澱粉から特許第4608051号公報に記載の方法又はこれに準じた方法により製造される。
なお、澱粉糊液の調製に用いられる澱粉は、未加工、すなわち、酸処理、アルファ化、エーテル化、アセチル化等の加工を行っていないものが好ましい。
超音波処理により、澱粉糊液の粘度は低下し、澱粉分散物が得られる。超音波処理後の澱粉分散物の粘度(B型粘度計、澱粉の含有量20質量%、液温80℃)は、澱粉の種類によって相違するものの、350mPa・s以下が好ましく、10~350mPa・sがより好ましい。
本発明において、澱粉糊液に超音波処理がされてなる澱粉分散物は市販品を使用することもできる。
塩の存在下で湿熱処理がされてなるワキシーコーン澱粉及び澱粉糊液に超音波処理がされてなる澱粉分散物以外の澱粉類の含有量は、皮膜シート強度、接着力及び乾燥後の弾力性の点から、固形成分の合計量中、50質量%以下が好ましく、40質量%以下がより好ましく、30質量%以下が更に好ましく、10質量%以下が更により好ましい。下限値は0質量%である。
そのような澱粉の種類としては、例えば、馬鈴薯澱粉、タピオカ澱粉、サゴ澱粉、甘藷澱粉、緑豆澱粉、小麦澱粉、とうもろこし澱粉、米澱粉,ワキシーコーン澱粉、ワキシーポテト澱粉、ワキシー小麦澱粉、もち米澱粉等が挙げられる。これらは一種又は二種以上を組み合わせて用いることができる。
本発明の軟カプセル皮膜組成物における可塑剤の含有量は、柔軟性の点から、固形成分の合計量中、20質量部以上が好ましく、30質量部以上がより好ましい。また、付着性の点から、固形成分の合計量100質量部に対して、60質量部以下が好ましく、50質量部以下がより好ましい。
(A)ネイティブジェランガム、(B)一種若しくは二種以上の親水性多糖類、(C)澱粉又は加工澱粉、(D)可塑剤、及び(E)水を含有し、(A)ネイティブジェランガム及び(B)一種若しくは二種以上の親水性多糖類以外のゲル化剤を必須成分としないことを特徴とする、本発明の軟カプセル皮膜組成物の処方を以下に例示する。
処方例1
(A)ネイティブジェランガム
(B)低メトキシペクチン
(C)ワキシーポテト澱粉
(C)澱粉糊液に超音波処理がされてなる澱粉分散物
(D)グリセリン
(E)精製水
処方例2
(A)ネイティブジェランガム
(B)低メトキシペクチン
(C)ワキシーポテト澱粉
(C)塩の存在下で湿熱処理がされてなるワキシーコーン澱粉
(D)グリセリン
(E)精製水
処方例3
(A)ネイティブジェランガム
(B)低メトキシペクチン
(C)ワキシーポテト澱粉
(C)酸化澱粉
(D)グリセリン
(E)精製水
処方例4
(A)ネイティブジェランガム
(B)低メトキシペクチン
(C)塩の存在下で湿熱処理がされてなるワキシーコーン澱粉
(C)澱粉糊液に超音波処理がされてなる澱粉分散物
(D)グリセリン
(E)精製水
処方例5
(A)ネイティブジェランガム
(B)ローカストビーンガム
(C)ワキシーポテト澱粉
(C)澱粉糊液に超音波処理がされてなる澱粉分散物
(D)グリセリン
(E)精製水
処方例6
(A)ネイティブジェランガム
(B)ローカストビーンガム
(C)ワキシーポテト澱粉
(C)塩の存在下で湿熱処理がされてなるワキシーコーン澱粉
(D)グリセリン
(E)精製水
処方例7
(A)ネイティブジェランガム
(B)ローカストビーンガム
(C)ワキシーポテト澱粉
(C)酸化澱粉
(D)グリセリン
(E)精製水
処方例8
(A)ネイティブジェランガム
(B)ローカストビーンガム
(C)塩の存在下で湿熱処理がされてなるワキシーコーン澱粉
(C)澱粉糊液に超音波処理がされてなる澱粉分散物
(D)グリセリン
(E)精製水
処方例9
(A)ネイティブジェランガム
(B)キサンタンガム
(C)ワキシーポテト澱粉
(C)澱粉糊液に超音波処理がされてなる澱粉分散物
(D)グリセリン
(E)精製水
処方例10
(A)ネイティブジェランガム
(B)キサンタンガム
(C)ワキシーポテト澱粉
(C)塩の存在下で湿熱処理がされてなるワキシーコーン澱粉
(D)グリセリン
(E)精製水
処方例11
(A)ネイティブジェランガム
(B)キサンタンガム
(C)ワキシーポテト澱粉
(C)酸化澱粉
(D)グリセリン
(E)精製水
処方例12
(A)ネイティブジェランガム
(B)キサンタンガム
(C)塩の存在下で湿熱処理がされてなるワキシーコーン澱粉
(C)澱粉糊液に超音波処理がされてなる澱粉分散物
(D)グリセリン
(E)精製水
処方例13
(A)ネイティブジェランガム
(B)低メトキシペクチン
(B)ローカストビーンガム
(C)ワキシーポテト澱粉
(C)澱粉糊液に超音波処理がされてなる澱粉分散物
(D)グリセリン
(E)精製水
処方例14
(A)ネイティブジェランガム
(B)低メトキシペクチン
(B)ローカストビーンガム
(C)ワキシーポテト澱粉
(C)塩の存在下で湿熱処理がされてなるワキシーコーン澱粉
(D)グリセリン
(E)精製水
処方例15
(A)ネイティブジェランガム
(B)低メトキシペクチン
(B)ローカストビーンガム
(C)ワキシーポテト澱粉
(C)酸化澱粉
(D)グリセリン
(E)精製水
処方例16
(A)ネイティブジェランガム
(B)低メトキシペクチン
(B)ローカストビーンガム
(C)塩の存在下で湿熱処理がされてなるワキシーコーン澱粉
(C)澱粉糊液に超音波処理がされてなる澱粉分散物
(D)グリセリン
(E)精製水
処方例17
(A)ネイティブジェランガム
(B)低メトキシペクチン
(B)キサンタンガム
(B)ローカストビーンガム
(C)ワキシーポテト澱粉
(C)澱粉糊液に超音波処理がされてなる澱粉分散物
(D)グリセリン
(E)精製水
処方例18
(A)ネイティブジェランガム
(B)低メトキシペクチン
(B)キサンタンガム
(B)ローカストビーンガム
(C)ワキシーポテト澱粉
(C)塩の存在下で湿熱処理がされてなるワキシーコーン澱粉
(D)グリセリン
(E)精製水
処方例19
(A)ネイティブジェランガム
(B)低メトキシペクチン
(B)キサンタンガム
(B)ローカストビーンガム
(C)ワキシーポテト澱粉
(C)酸化澱粉
(D)グリセリン
(E)精製水
処方例20
(A)ネイティブジェランガム
(B)低メトキシペクチン
(B)キサンタンガム
(B)ローカストビーンガム
(C)塩の存在下で湿熱処理がされてなるワキシーコーン澱粉
(C)澱粉糊液に超音波処理がされてなる澱粉分散物
(D)グリセリン
(E)精製水
処方例21
(A)ネイティブジェランガム
(B)低メトキシペクチン
(C)ワキシーポテト澱粉
(C)澱粉糊液に超音波処理がされてなる澱粉分散物
(C)塩の存在下で湿熱処理がされてなるワキシーコーン澱粉
(D)グリセリン
(E)精製水
処方例22
(A)ネイティブジェランガム
(B)低メトキシペクチン
(C)ワキシーポテト澱粉
(C)澱粉糊液に超音波処理がされてなる澱粉分散物
(C)酸化澱粉
(D)グリセリン
(E)精製水
処方例23
(A)ネイティブジェランガム
(B)低メトキシペクチン
(C)ワキシーポテト澱粉
(C)塩の存在下で湿熱処理がされてなるワキシーコーン澱粉
(C)酸化澱粉
(D)グリセリン
(E)精製水
処方例24
(A)ネイティブジェランガム
(B)低メトキシペクチン
(C)澱粉糊液に超音波処理がされてなる澱粉分散物
(C)塩の存在下で湿熱処理がされてなるワキシーコーン澱粉
(C)酸化澱粉
(D)グリセリン
(E)精製水
以下に、カプセルに含有し得るものを例示する。これら各成分は、カプセル剤中のいかなる部分にも含有しうる。
ネイティブジェランガム:ケルコゲルHM(登録商標)(CP Kelco社製)
低メトキシペクチン:NEW GELIN(登録商標) LP-4(三菱商事フードテック社製)
塩の存在下で湿熱処理がされてなるワキシーコーン澱粉:ソフトスターチSF-930(三和澱粉工業社製)
澱粉糊液に超音波処理がされてなる澱粉分散物:エフスマッシュ(登録商標)(フタムラ化学社製)(ワキシーコーン澱粉に由来)
ワキシーポテト澱粉:エリアンGEL 100(松谷化学工業社製)
グリセリン:食品添加物グレード(阪本薬品工業社製)
水:精製水
(1)表1に示した量(質量部)のネイティブジェランガム、低メトキシペクチン、塩の存在下で湿熱処理がされてなるワキシーコーン澱粉、澱粉糊液に超音波処理がされてなる澱粉分散物、ワキシーポテト澱粉、グリセリンをそれぞれ水に攪拌・分散させた後、90~98℃で攪拌しながら溶解させ、真空脱泡した。この皮膜液から、ロータリーダイ式軟カプセル充填機を用いてシート及び軟カプセルを製造した。
先ず、皮膜液をキャスティング装置により、回転ドラム上に展延して皮膜シートを調製した。この段階で、下記〔a.皮膜シート強度の評価〕、〔b.皮膜シートの伸びの評価〕及び〔c.皮膜シートのべたつきの評価〕を行った。
結果を表1に示す。
専門パネル5名の感覚により、以下に示す評価基準に従って、皮膜シートの強さを評価した。
5:とても強い
4:強い
3:やや弱い
2:弱い
1:とても弱い。
専門パネル5名の感覚により、皮膜シートの強度の評価時に同時に、以下に示す評価基準に従って、皮膜シートの伸びを評価した。
5:とても伸びて、弾力性がある
4:伸びて、弾力性がある
3:伸びはあるが、弾力性がやや弱い
2:ほとんど伸びがなく、弾力性が弱い
1:伸びがなく、弾力性がない
専門パネル5名の感覚により、皮膜シートの強度の評価時に同時に、以下に示す評価基準に従って、皮膜シートの伸びを評価した。
5:べたつきがない
4:べたつきが少ない
3:べたつきがややある
2:べたつきが多い
1:べたつきが非常に多い
専門パネル5名で乾燥前のカプセルを指で押しつぶして、以下に示す評価基準に従って、カプセル成形直後の皮膜シートの接着性を評価した。
5:強く押しても内容液が全く漏れ出さないし、24時間静置してもすべてのカプセルに浸出が発生しない
4:強く押しても内容液は漏れ出さないが、24時間静置すると一部のカプセルに浸出が発生する
3:強く押すとごく少量の内容液が漏れてしまう
2:弱く押しても少量の内容液が漏れてしまう
1:弱く押しても内容液が漏れてしまう
上記a~dの評価を元に、以下に示す評価基準に従って、カプセル充填機での製造性を評価した。
○:従来の設備を使用し、カプセル充填機での製造が可能である。
△:カプセル充填機での製造は可能であるが、従来の設備からの変更が必要である。
×:皮膜シートの物性から、カプセル充填機での製造は不可能である。
一方、本発明に係る実施例1及び実施例2では、皮膜シートの物性が良好であり、いずれもカプセル充填機での製造が容易であった。
(1)表2に示した量(質量部)のネイティブジェランガム、低メトキシペクチン、ローカストビーンガム、キサンタンガム、超音波処理ワキシーコーンスターチ、ワキシーポテトスターチ、グリセリンをそれぞれ水に攪拌・分散させた後、90~98℃で攪拌しながら溶解させ、真空脱泡した。この皮膜液から、ロータリーダイ式軟カプセル充填機を用いてシート及び軟カプセルを製造した。
先ず、皮膜液をキャスティング装置により、回転ドラム上に展延して皮膜シートを調製した。この段階で、下記〔a.皮膜シート強度の評価〕、〔b.皮膜シートの伸びの評価〕及び〔c.皮膜シートのべたつきの評価〕を行った。
結果を表2に示す。
表2における評価の基準は、前記「実施例1~2、比較例1~2:ロータリーダイ式軟カプセル充填機による軟カプセルの製造」の表1における評価基準と同一である。
本発明に係る軟カプセル皮膜組成物を用いて製造された軟カプセルは、医薬品、医薬部外品、化粧品、食品等種々の用途に利用することができる。
11 タンク
12 キャスティング装置
13 回転ドラム
14 潤滑ローラー
15 デフレクトロール
16 金型
16A 金型の凹部
17 セグメント
18 ポンプ
18A ピストン
A 皮膜シート
B 内容物
C カプセル
Claims (10)
- (A)ネイティブジェランガム、(B)一種若しくは二種以上の親水性多糖類、(C)澱粉又は加工澱粉、(D)可塑剤、及び(E)水を含有し、(A)ネイティブジェランガム及び(B)一種若しくは二種以上の親水性多糖類以外のゲル化剤を必須成分としないことを特徴とする軟カプセル皮膜組成物。
- (C)澱粉又は加工澱粉が、天然澱粉、酸化澱粉、ヒドロキシプロピル化澱粉、アセチル化澱粉、アセチル化、ヒドロキシプロピル化、オクテニルコハク酸化、リン酸化、架橋、酸処理、塩の存在下で湿熱処理がされてなる澱粉、又は澱粉糊液に超音波処理がされてなる澱粉分散物から選ばれる一種又は二種以上であることを特徴とする、請求項1記載の軟カプセル皮膜組成物。
- (C)澱粉又は加工澱粉が、サゴ澱粉、甘藷澱粉、緑豆澱粉、小麦澱粉、とうもろこし澱粉、米澱粉,ワキシーコーン澱粉、ワキシーポテト澱粉、ワキシー小麦澱粉、もしくはもち米澱粉、又はこれらから得られる加工澱粉、から選ばれる一種又は二種以上であることを特徴とする、請求項1又は2記載の軟カプセル皮膜組成物。
- (C)澱粉又は加工澱粉が、ワキシーポテト澱粉、酸化澱粉、塩の存在下で湿熱処理がされてなる澱粉、又は澱粉糊液に超音波処理がされてなる澱粉分散物から選ばれる一種又は二種以上であることを特徴とする、請求項1~3のいずれか1項記載の軟カプセル皮膜組成物。
- (A)ネイティブジェランガムと(B)一種若しくは二種以上の親水性多糖類の含有質量比[(A):(B)]が1:1~1:0.01である請求項1~4のいずれか1項記載の軟カプセル皮膜組成物。
- 澱粉糊液に超音波処理がされてなる澱粉分散物が、ワキシーコーン澱粉に由来する澱粉分散物である請求項1~5のいずれか1項記載の軟カプセル皮膜組成物。
- 澱粉糊液に超音波処理がされてなる澱粉分散物に用いられるワキシーコーン澱粉が未加工の天然澱粉である請求項6に記載の軟カプセル皮膜組成物。
- (C)澱粉又は加工澱粉が、塩の存在下で湿熱処理がされてなるワキシーコーン澱粉である請求項1~5のいずれか1項記載の軟カプセル皮膜組成物。
- 請求項1~8のいずれか1項記載の軟カプセル皮膜組成物を用いて得られる軟カプセル皮膜。
- 請求項1~8のいずれか1項記載の軟カプセル皮膜組成物を用いて得られる軟カプセル。
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CN113398088B (zh) * | 2021-06-28 | 2023-10-03 | 仙乐健康科技股份有限公司 | 软胶囊囊壳及软胶囊 |
AU2021416461B2 (en) * | 2021-06-28 | 2023-11-09 | Sirio Pharma Co., Ltd. | Soft capsule shells and soft capsules |
JP7443521B2 (ja) | 2021-06-28 | 2024-03-05 | 仙楽健康科技股▲フン▼有限公司 | ソフトカプセルのカプセルシェルおよびソフトカプセル |
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US20210196641A1 (en) | 2021-07-01 |
EP3785707A4 (en) | 2022-03-02 |
SG11202010239UA (en) | 2020-11-27 |
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JP7388718B2 (ja) | 2023-11-29 |
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