JP6605169B1 - HMBCa powder composition - Google Patents
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- 239000000843 powder Substances 0.000 title claims abstract description 54
- 239000000203 mixture Substances 0.000 title claims abstract description 16
- 239000013078 crystal Substances 0.000 claims abstract description 18
- 239000002994 raw material Substances 0.000 claims abstract description 16
- 239000002775 capsule Substances 0.000 claims abstract description 7
- 238000011049 filling Methods 0.000 claims description 5
- 239000007902 hard capsule Substances 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
- 239000013589 supplement Substances 0.000 abstract description 4
- 238000002360 preparation method Methods 0.000 abstract description 3
- NTCLNUAUXFHGFO-UHFFFAOYSA-N 3-hydroxy-3-methylbutanoic acid;hydrate Chemical compound O.CC(C)(O)CC(O)=O NTCLNUAUXFHGFO-UHFFFAOYSA-N 0.000 abstract description 2
- 230000000052 comparative effect Effects 0.000 description 19
- 238000000034 method Methods 0.000 description 16
- SWXVUIWOUIDPGS-UHFFFAOYSA-N diacetone alcohol Chemical compound CC(=O)CC(C)(C)O SWXVUIWOUIDPGS-UHFFFAOYSA-N 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- 238000001694 spray drying Methods 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000005708 Sodium hypochlorite Substances 0.000 description 4
- 238000010298 pulverizing process Methods 0.000 description 4
- 238000007873 sieving Methods 0.000 description 4
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 4
- 238000000605 extraction Methods 0.000 description 3
- 235000013402 health food Nutrition 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000011575 calcium Substances 0.000 description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
- 239000000920 calcium hydroxide Substances 0.000 description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000000691 measurement method Methods 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000008934 Muscle Proteins Human genes 0.000 description 1
- 108010074084 Muscle Proteins Proteins 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- WLJUMPWVUPNXMF-UHFFFAOYSA-L calcium;3-hydroxy-3-methylbutanoate Chemical compound [Ca+2].CC(C)(O)CC([O-])=O.CC(C)(O)CC([O-])=O WLJUMPWVUPNXMF-UHFFFAOYSA-L 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002614 leucines Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- General Preparation And Processing Of Foods (AREA)
Abstract
【課題】流動性を向上させたＨＭＢＣａ粉末状組成物を提供する。また、タブレット錠剤やカプセル錠剤などの製剤やサプリメントなどの原料として好適なＨＭＢＣａ粉末組成物を提供する。【解決手段】本発明の実施形態に係るＨＭＢＣａ粉末状組成物は、ＨＭＢＣａ（３−ヒドロキシ−３−メチル酪酸カルシウム）水和物を主成分とし、結晶が球状であり、安息角が３５°以下であり、見かけ密度が０．５ｇ／ｍｌ以上である。好ましくは、安息角が３０°以下であって、見かけ密度が０．５４ｇ／ｍｌ以上である。【選択図】図２An HMBCa powder composition having improved fluidity is provided. In addition, an HMBCa powder composition suitable as a raw material for preparations such as tablet tablets and capsule tablets and supplements is provided. An HMBCa powder composition according to an embodiment of the present invention includes HMBCa (3-hydroxy-3-methylbutyrate) hydrate as a main component, a crystal is spherical, and an angle of repose is 35 ° or less. The apparent density is 0.5 g / ml or more. Preferably, the angle of repose is 30 ° or less and the apparent density is 0.54 g / ml or more. [Selection] Figure 2
Description
本発明は、ＨＭＢＣａ水和物を主成分とするＨＭＢＣａ粉末組成物に関する。 The present invention relates to an HMBCa powder composition mainly composed of HMBCa hydrate.
ＨＭＢ（ビス−３−ヒドロキシ−３−メチルブチレートモノハイドレート）は、必須アミノ酸の一種であるロイシンの代謝物質である。ＨＭＢは、一般的に、筋たんぱく質の合成を活性化すると共に、分解を抑制する効果があることが確認されている。そのため、ＨＭＢは、健康食品向けの原料とされ、特に粉末状のＨＭＢＣａ水和物は、タブレット錠剤やカプセル錠剤などの製剤やサプリメントなどの原料とされている。 HMB (bis-3-hydroxy-3-methylbutyrate monohydrate) is a metabolite of leucine, which is a kind of essential amino acid. It has been confirmed that HMB generally has an effect of activating muscle protein synthesis and suppressing degradation. Therefore, HMB is used as a raw material for health foods, and in particular, powdered HMBCa hydrate is used as a raw material for preparations and supplements such as tablet tablets and capsule tablets.
ＨＭＢは、典型的にはジアセトンアルコールと次亜塩素酸ソーダによる酸化反応によって生成される。反応収率が比較的低いＨＭＢは、その後、抽出・精製などの工程を経て純度が高められる。粉末状のＨＭＢＣａ水和物は、ＨＭＢの溶液に水酸化カルシウム等のカルシウム塩を添加してＨＭＢＣａを生成し、棚式乾燥、粉砕、篩等を行って粉末状とする。製剤やサプリメントを製造する場合、例えば打錠機で打錠してタブレット錠剤とする。或いは充填機でハードカプセルに充填されてカプセル錠剤とする。一般的に、打錠或いは充填するには粉末原料に流動性が要求されるが、これまでの粉末状のＨＭＢＣａ水和物はその流動性が十分ではなかった。そのため、錠剤の質量にばらつきがでたり仕上がりが悪くなったりすることがあった。特に流動性が求められる直接打錠の場合は、実際には打錠が不可能である。 HMB is typically produced by an oxidation reaction with diacetone alcohol and sodium hypochlorite. The purity of the HMB having a relatively low reaction yield is then increased through steps such as extraction and purification. The powdered HMBCa hydrate is formed into powder by adding a calcium salt such as calcium hydroxide to the HMB solution to produce HMBCa, and performing shelf drying, pulverization, sieving, and the like. When manufacturing a formulation or a supplement, for example, it is compressed into tablets by a tableting machine. Alternatively, the capsules are filled into hard capsules with a filling machine. Generally, fluidity is required for the powder raw material for tableting or filling, but the powdery HMBCa hydrate so far has not been sufficiently fluid. For this reason, the tablet mass may vary or the finish may be poor. In particular, in the case of direct tableting that requires fluidity, tableting is actually impossible.
対策の一つとして、流動性を高めるための副原料を混合することも検討されているが、不経済である。それ故、流動性を向上させた粉末状のＨＭＢＣａ水和物の出現が望まれてきたが、未だ実現されていなかった。 As one of the countermeasures, mixing of auxiliary materials for improving fluidity has been studied, but it is uneconomical. Therefore, the appearance of powdered HMBCa hydrate with improved fluidity has been desired, but has not been realized yet.
本発明は、このような事情に基づいてなされたものであり、その目的は、流動性を向上させたＨＭＢＣａ粉末組成物を提供することにある。 This invention is made | formed based on such a situation, The objective is to provide the HMBCa powder composition which improved fluidity | liquidity.
さらに本発明の他の目的は、タブレット錠剤やカプセル錠剤などの製剤やサプリメントなどの原料として好適なＨＭＢＣａ粉末組成物を提供することにある。 Still another object of the present invention is to provide a HMBCa powder composition suitable as a raw material for preparations and supplements such as tablet tablets and capsule tablets.
本発明のＨＭＢＣａ粉末組成物は、ＨＭＢＣａ（３−ヒドロキシ−３−メチル酪酸カルシウム）水和物を主成分とし、結晶が球状であり、安息角が３５°以下であり、見かけ密度が０．５ｇ／ｍｌ以上である。好ましくは、安息角が３０°以下であって、見かけ密度が０．５４ｇ／ｍｌ以上である。 The HMBCa powder composition of the present invention is mainly composed of HMBCa (3-hydroxy-3-methylbutyrate) hydrate, the crystals are spherical, the angle of repose is 35 ° or less, and the apparent density is 0.5 g. / Ml or more. Preferably, the angle of repose is 30 ° or less and the apparent density is 0.54 g / ml or more.
以下、本発明の好ましい実施形態に従うＨＭＢＣａ粉末組成物について、添付図面を参照しながら詳しく説明する。但し、以下に説明する実施形態によって本発明の技術的範囲は何ら限定解釈されることはない。 Hereinafter, the HMBCa powder composition according to a preferred embodiment of the present invention will be described in detail with reference to the accompanying drawings. However, the technical scope of the present invention is not construed as being limited by the embodiments described below.
実施形態に従うＨＭＢＣａ粉末組成物は、ＨＭＢカルシウム（ＨＭＢＣａ；３−ヒドロキシ−３−メチル酪酸カルシウム）の水和物を主成分とする粉末である。以下、ＨＭＢＣａ水和物を主成分とする粉末を「ＨＭＢＣａ粉末」と称することがある。また、図１には、ＨＭＢＣａ水和物の化学式の一表記例を示している。ＨＭＢＣａ水和物は、例えば一水和物（ｎ＝１）である。なお、「主成分とする」とは、ＨＭＢＣａの含有量が、乾燥物で、例えば９０質量％以上、好ましくは、９８％質量以上である The HMBCa powder composition according to the embodiment is a powder based on a hydrate of HMB calcium (HMBCa; calcium 3-hydroxy-3-methylbutyrate). Hereinafter, the powder mainly composed of HMBCa hydrate may be referred to as “HMBCa powder”. FIG. 1 shows an example of a chemical formula of HMBCa hydrate. HMBCa hydrate is, for example, monohydrate (n = 1). The “main component” means that the content of HMBCa is a dried product, for example, 90% by mass or more, preferably 98% by mass or more.
ＨＭＢＣａ粉末の結晶系は、これまでのＨＭＢＣａ粉末の結晶系が針状であるのに対し、本実施形態では球状を呈している。結晶が球状であるか或いは針状であるかは、後述する実施例の結果からも明らかなように、顕微鏡写真等で確認することができる。球状結晶の平均粒子径は、好ましくは１００μｍ以下である。 The crystal system of the HMBCa powder has a spherical shape in the present embodiment, whereas the crystal system of the conventional HMBCa powder is needle-shaped. Whether the crystal is spherical or acicular can be confirmed by a micrograph or the like, as is apparent from the results of Examples described later. The average particle size of the spherical crystals is preferably 100 μm or less.
ＨＭＢＣａ粉末の安息角は、３５°以下、好ましくは３０°以下であり、且つ、ＨＭＢＣａ粉末の見かけ密度は、０．５ｇ／ｍｌ以上、好ましくは０．５４ｇ／ｍｌ以上である。安息角は、重力場において粉末が堆積して自由面を形成するときの、粉末層表面と水平面とのなす角である。測定方法の一例として、ＪＩＳ Ｒ ９３０１−２−２に準じ、ロート等を用いて一定面積の水平面上にＨＭＢＣａ粉末を上方から自由落下させて円錐状の堆積層を形成させ、その円錐表面と水平面とのなす角を測定する注入法を用いる。また、見かけ密度は、粉末の単位容積当たりの質量であり、「かさ比重」と同義である。測定方法の一例として、ＪＩＳ Ｋ ３３６２に準じ、ロート等を用いて容器内にＨＭＢＣａ粉末を上方から自由落下させ、容器内のＨＭＢＣａ粉末のかさ体積と質量を測定し、演算により見かけ密度を算出する。 The angle of repose of the HMBCa powder is 35 ° or less, preferably 30 ° or less, and the apparent density of the HMBCa powder is 0.5 g / ml or more, preferably 0.54 g / ml or more. The angle of repose is an angle formed by the powder layer surface and a horizontal plane when powder is deposited in a gravitational field to form a free surface. As an example of the measurement method, according to JIS R 9301-2-2, a HMBCa powder is freely dropped from above on a horizontal surface of a certain area using a funnel or the like to form a conical deposited layer. The injection method is used to measure the angle between The apparent density is the mass per unit volume of the powder and is synonymous with “bulk specific gravity”. As an example of the measuring method, in accordance with JIS K 3362, the HMBCa powder is freely dropped from above into the container using a funnel, the bulk volume and mass of the HMBCa powder in the container are measured, and the apparent density is calculated by calculation. .
このようなＨＭＢＣａ粉末を製造する方法の一例を説明する。まず原料となるＨＭＢＣａ水和物を準備する。ＨＭＢＣａ水和物は、公知の方法で製造することができる。すなわち、ジアセトンアルコールと次亜塩素酸ソーダを原料にして生成したＨＭＢに水酸化カルシウム等のカルシウム塩を添加してＨＭＢＣａを生成し、棚式乾燥による乾燥工程、粉砕工程、及び篩工程を得て生成された粉末状のＨＭＢＣａ水和物である。勿論、他の方法で製造されたものであってもよい。或いは、市販されている粉末状のＨＭＢＣａ水和物を用いてもよい。これらはいずれも結晶系が針状であることを確認している。 An example of a method for producing such HMBCa powder will be described. First, HMBCa hydrate as a raw material is prepared. HMBCa hydrate can be produced by a known method. That is, HMBCa is produced by adding calcium salt such as calcium hydroxide to HMB produced using diacetone alcohol and sodium hypochlorite as raw materials, and a drying process, a pulverizing process, and a sieving process by shelf drying are obtained. It is a powdery HMBCa hydrate produced in this way. Of course, it may be manufactured by other methods. Alternatively, commercially available powdered HMBCa hydrate may be used. These confirm that the crystal system is needle-shaped.
次に原料となるＨＭＢＣａ水和物を水、好ましくは温水に溶解させ、例えばフィルタ―プレスなどの濾過装置、もしくは、カートリッジフィルターで濾過して不溶解残渣等を除去する。濾材は、例えば濾過精度が０．５μｍ〜５μｍ相当のものを用いる。次に濾液をスプレードライ噴霧乾燥により乾燥させることによって、実施形態に従うＨＭＢＣａ粉末を得る。上述した公知の製造方法における反応工程で生成されるＨＭＢＣａ含有溶液は、スプレードライ噴霧乾燥を行うことができないことから棚式乾燥されるがこのように棚式乾燥で製造された針状物のＨＭＢＣａ水和物を温水に溶解させて、溶液を調製することによってスプレードライ噴霧乾燥を実現可能とした。そして後述する実施例の結果から明らかなように、スプレードライ噴霧乾燥により得られたＨＭＢＣａ粉末は、結晶が球状であり、安息角が３５°以下、見かけ密度が０．５ｇ／ｍｌ以上である。さらにＨＭＢＣａ１００質量部中のＨＭＢ含有量は、８５質量％以上であり、ＨＭＢＣａ１００質量部中のＣａ含有量は１４質量％以上である。 Next, HMBCa hydrate as a raw material is dissolved in water, preferably warm water, and filtered through a filter device such as a filter press or a cartridge filter to remove insoluble residues and the like. As the filter medium, for example, one having a filtration accuracy of 0.5 μm to 5 μm is used. The filtrate is then dried by spray drying spray drying to obtain HMBCa powder according to the embodiment. The HMBCa-containing solution produced in the reaction step in the above-mentioned known production method is shelf-dried because it cannot be spray-dried and spray-dried. Thus, the needle-like HMBCa produced by shelf-type drying is used. Spray drying spray drying was made feasible by dissolving the hydrate in warm water to prepare a solution. As is clear from the results of Examples described later, the HMBCa powder obtained by spray-drying spray-drying has spherical crystals, an angle of repose of 35 ° or less, and an apparent density of 0.5 g / ml or more. Furthermore, the HMB content in 100 parts by mass of HMBCa is 85% by mass or more, and the Ca content in 100 parts by mass of HMBCa is 14% by mass or more.
得られたＨＭＢＣａ粉末は、好ましい一例として、健康食品の原料に用いる。その中にタブレット錠剤やカプセル錠剤などの錠剤にしたものがある。タブレット錠剤は、例えばＨＭＢＣａ粉末に賦形剤，結合剤，崩壊剤などの添加剤を、または、他の機能性成分を添加して打錠機で打錠することによって成形する。打錠方法は、そのまま打錠する直接打錠法と、顆粒にしてから打錠する顆粒打錠法があるが、いずれであってもよい。一方、カプセル錠剤は、例えば充填機でハードカプセル内にＨＭＢＣａ粉末を充填することによって製造する。勿論、健康食品は、錠剤に限定されることはなく、粉末状のままであってもよく、或いは液体に溶かして健康飲料水等としてもよい。 The obtained HMBCa powder is used as a raw material for health food as a preferred example. Some of them are tablets such as tablet tablets and capsule tablets. Tablet tablets are formed by, for example, adding additives such as excipients, binders, and disintegrants to HMBCa powder, or adding other functional ingredients, and then compressing with a tableting machine. The tableting method includes a direct tableting method in which tableting is performed as it is, and a granule tableting method in which tableting is performed after granulating, but either method may be used. On the other hand, a capsule tablet is manufactured by filling HMBCa powder in a hard capsule with a filling machine, for example. Of course, the health food is not limited to tablets, and may remain in powder form, or may be dissolved in a liquid to form health drinking water or the like.
上述の実施形態に従うＨＭＢＣａ水和物を主成分とするＨＭＢＣａ粉末は、結晶系が球状を呈し、安息角が３５°以下（好ましくは３０°以下）であり、且つ、見かけ密度が０．５ｇ／ｍｌ以上（好ましくは０．５４ｇ／ｍｌ以上）であり、高い流動性を備えている。そして後述する実施例の結果からも明らかなように、直接打錠法で打錠することが可能である。すなわち、実施形態に従うＨＭＢＣａ粉末によれば、高い流動性が要求される直接打錠に対する打錠適性を有するまで流動性を向上させたＨＭＢＣａ粉末を提供することができる。 The HMBCa powder mainly composed of HMBCa hydrate according to the above-described embodiment has a spherical crystal system, an angle of repose of 35 ° or less (preferably 30 ° or less), and an apparent density of 0.5 g / It is ml or more (preferably 0.54 g / ml or more) and has high fluidity. As is apparent from the results of the examples described later, it is possible to perform tableting by the direct tableting method. That is, according to the HMBCa powder according to the embodiment, it is possible to provide an HMBCa powder having improved fluidity until it has tableting suitability for direct tableting that requires high fluidity.
（実施例１〜６）
続いて、実施形態に従うＨＭＢＣａ粉末の結晶系、安息角、及び見かけ密度を確認するために行った実施例について説明する。実施例１〜６は、既述したように、粉末状のＨＭＢＣａ水和物を原料に用い、温水に溶解、濾過、及びスプレードライ噴霧乾燥することによって得たＨＭＢＣａ粉末の実施例であり、結晶系、安息角、及び見かけ密度を確認した。原料としたＨＭＢＣａ水和物は、公知の製造方法であるジアセトンアルコールと次亜塩素酸ソーダによる酸化反応工程、抽出・精製などの精製工程、棚式乾燥による乾燥工程、粉砕工程、及び篩工程を得て製造されたものである。なお、実施例１〜３と実施例４〜６は、それぞれ同じ製造元のＨＭＢＣａ水和物を原料に用いた。各実施例１〜６の結晶系、安息角、及び見かけ密度の結果を図２に示す。
(Examples 1-6)
Then, the Example performed in order to confirm the crystal system, angle of repose, and apparent density of the HMBCa powder according to the embodiment will be described. Examples 1 to 6 are examples of HMBCa powder obtained by using powdered HMBCa hydrate as a raw material, dissolving in hot water, filtering, and spray-drying spray drying, as described above. The system, angle of repose, and apparent density were confirmed. HMBCa hydrate used as a raw material is an oxidation reaction process using diacetone alcohol and sodium hypochlorite, which is a known production method, a purification process such as extraction / purification, a drying process by shelf drying, a pulverizing process, and a sieving process Is manufactured. In Examples 1 to 3 and Examples 4 to 6, the same manufacturer's HMBCa hydrate was used as a raw material. The crystal system, angle of repose, and apparent density results of Examples 1 to 6 are shown in FIG.
さらに、実施例１の顕微鏡の写真を図３に示し、実施例２の顕微鏡写真を図４に示し、実施例３の顕微鏡写真を図５に示す。 Furthermore, the microscope picture of Example 1 is shown in FIG. 3, the microscope picture of Example 2 is shown in FIG. 4, and the microscope picture of Example 3 is shown in FIG.
（比較例１〜９）
一方、比較例１〜９として、実施例のように温水に溶解、濾過、及びスプレードライ噴霧乾燥を行っていないＨＭＢＣａ粉末の、結晶系、安息角、及び見かけ密度を確認した。これらは、公知の製造方法であるジアセトンアルコールと次亜塩素酸ソーダによる酸化反応工程、抽出・精製などの精製工程、棚式乾燥による乾燥工程、粉砕工程、及び篩工程を得て製造されたものである。比較例１と比較例７は市販品であり、比較例２〜４、比較例５〜６、比較例８、及び比較例９は製造元が夫々異なるが、いずれも実施例で原料とした粉末状のＨＭＢＣａ水和物に相当する。各比較例１〜９の結晶系、安息角、及び見かけ密度の結果を図２に併せて示す。なお、結晶系は、顕微鏡写真により確認した。安息角及び見かけ密度は、既述の測定法により測定した。
(Comparative Examples 1-9)
On the other hand, as Comparative Examples 1 to 9, the crystal system, the angle of repose, and the apparent density of the HMBCa powder that was not dissolved in hot water, filtered, and spray-dried and spray-dried as in Examples were confirmed. These were produced by obtaining a known manufacturing method, such as an oxidation reaction step with diacetone alcohol and sodium hypochlorite, a purification step such as extraction / purification, a drying step by shelf drying, a pulverizing step, and a sieving step. Is. Comparative Example 1 and Comparative Example 7 are commercially available products, and Comparative Examples 2 to 4, Comparative Examples 5 to 6, Comparative Example 8, and Comparative Example 9 are different from each other in the manufacturer, but all are powdered as raw materials in the examples. It corresponds to HMBCa hydrate. The results of the crystal system, angle of repose, and apparent density of each of Comparative Examples 1 to 9 are also shown in FIG. The crystal system was confirmed by a micrograph. The angle of repose and the apparent density were measured by the measurement methods described above.
さらに、比較例１の顕微鏡の写真を図６に示し、比較例２の顕微鏡写真を図７に示し、比較例７の顕微鏡写真を図８に示す。 Furthermore, the microscope picture of the comparative example 1 is shown in FIG. 6, the microscope picture of the comparative example 2 is shown in FIG. 7, and the microscope picture of the comparative example 7 is shown in FIG.
図２〜図５の結果から明らかなように、実施例１〜６は、いずれも結晶構造が球状であることを確認した。併せて、実施例１〜６は、平均粒子径が１００μｍ以下であることを確認した。さらに、安息角が３５°以下、見かけ密度が０．５ｇ／ｍｌ以上であることを確認した。一方、比較例１〜９（市販品含む）は、いずれも結晶構造が針状であった。さらに、安息角が４５°以上、見かけ密度が０．４１ｇ／ｍｌ以下であった。 As is clear from the results of FIGS. 2 to 5, Examples 1 to 6 each confirmed that the crystal structure was spherical. In addition, Examples 1 to 6 confirmed that the average particle diameter was 100 μm or less. Furthermore, it was confirmed that the angle of repose was 35 ° or less and the apparent density was 0.5 g / ml or more. On the other hand, Comparative Examples 1 to 9 (including commercial products) all had needle-like crystal structures. Furthermore, the angle of repose was 45 ° or more and the apparent density was 0.41 g / ml or less.
（打錠試験）
さらに、実施例１〜６のＨＭＢＣａ粉末と、比較例１〜９のＨＭＢＣａ粉末を原料にして直接打錠を実施したときの打錠適性を確認した。実施例１〜６のＨＭＢＣａ粉末は、いずれも打錠障害は発生せず、直接打錠法での打錠が可能であった。これに対し、比較例１〜９のＨＭＢＣａ粉末は、打錠障害が発生し、直接打錠法での打錠が不可能であった。すなわち、直接打錠法を採用することはできず、顆粒にしてから打錠する顆粒打錠法での打錠となる。
(Tablet test)
Furthermore, tableting aptitude was confirmed when direct tableting was carried out using the HMBCa powders of Examples 1 to 6 and the HMBCa powders of Comparative Examples 1 to 9 as raw materials. The HMBCa powders of Examples 1 to 6 did not cause any tableting trouble and could be tableted by the direct tableting method. On the other hand, the HMBCa powders of Comparative Examples 1 to 9 had tableting troubles and could not be tableted by the direct tableting method. That is, the direct tableting method cannot be adopted, and the tableting is performed by the granule tableting method in which the tablets are granulated and then tableted.
以上、本発明を具体的な実施形態に則して詳細に説明したが、形式や細部についての種々の置換、変形、変更等が、特許請求の範囲の記載により規定されるような本発明の精神及び範囲から逸脱することなく行われることが可能であることは、当該技術分野における通常の知識を有する者には明らかである。
Although the present invention has been described in detail according to the specific embodiments, various substitutions, modifications, changes, etc., in form and detail are defined by the description of the claims. It will be apparent to those skilled in the art that this can be done without departing from the spirit and scope.
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