JPH05246840A - Particle containing agent having medicinal action and its production - Google Patents
Particle containing agent having medicinal action and its productionInfo
- Publication number
- JPH05246840A JPH05246840A JP8324492A JP8324492A JPH05246840A JP H05246840 A JPH05246840 A JP H05246840A JP 8324492 A JP8324492 A JP 8324492A JP 8324492 A JP8324492 A JP 8324492A JP H05246840 A JPH05246840 A JP H05246840A
- Authority
- JP
- Japan
- Prior art keywords
- water
- insoluble substance
- drug
- medicinal agent
- particles
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- Medicinal Preparation (AREA)
- Glanulating (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、薬効剤含有粒子および
その製造方法に関するものであり、更に詳しくは、水中
における薬効剤含有粒子からの水溶性薬効剤の溶出を抑
制することにより安定化された薬効剤含有粒子、および
その製造方法に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a medicinal agent-containing particle and a method for producing the same, more specifically, it is stabilized by suppressing elution of a water-soluble medicinal agent from the medicinal agent-containing particle in water. And a method for producing the same.
【０００２】[0002]
【従来の技術】水溶性薬効剤を歯磨き、液状洗剤、シャ
ンプー、化粧品等の液状、ペースト状等の含水製品に配
合する際に、薬効剤粉末（酵素、ビタミン等）をそのま
ま配合した場合には、水や他の配合物との反応により経
時的に分解、変性し、薬効が著しく減少、あるいは消失
することがある。したがって、このような性状を有する
薬効剤をそのまま配合した製品では、流通段階、保存時
において薬効が減少または消失し、使用時に十分な効力
の発現が期待できない。2. Description of the Related Art When a water-soluble drug is blended into a water-containing product such as toothpaste, liquid detergent such as liquid detergent, shampoo, or cosmetics, or a paste-like water-containing drug, when the drug powder (enzyme, vitamin, etc.) is blended as it is, , The substance may decompose or denature over time due to reaction with water or other compounds, and drug efficacy may be significantly reduced or eliminated. Therefore, in a product in which a medicinal agent having such a property is blended as it is, the medicinal effect is reduced or disappears at the distribution stage and at the time of storage, and it is not expected that sufficient efficacy will be exhibited at the time of use.
【０００３】このような用途に対しては、薬効剤を水不
溶性物質でカプセル化することにより、安定化する手法
が従来より知られている。しかし、従来のカプセル化技
術の多くは薬効剤の徐放性に関するものであるため、薬
効剤の被覆が不十分であり、カプセルからの溶出による
薬効剤の分解、変性が見られ、長期間安定性を保つこと
は困難である。また、一般に、カプセルからの薬効剤の
溶出を抑制するには水不溶性物質からなるコート層を厚
くする方法が考えられるが、この場合には多大な水不溶
性物質が必要となり、薬効剤の含有率が低くなるととも
にコストの点からも不利である。For such applications, a method for stabilizing a medicinal agent by encapsulating a medicinal agent with a water-insoluble substance has been conventionally known. However, since most conventional encapsulation technologies are related to sustained release of the drug, the drug coating is insufficient, and the drug is decomposed and denatured due to elution from the capsule, resulting in long-term stability. It is difficult to maintain sex. Further, generally, in order to suppress the elution of the medicinal agent from the capsule, a method of thickening the coating layer made of a water-insoluble substance is considered, but in this case a large amount of a water-insoluble substance is required, and the content rate of the medicinal agent is Is low and it is also disadvantageous in terms of cost.
【０００４】このような、水溶性薬効剤を長期間安定化
させるカプセルの製造方法としては、特公昭５０−２５
０１１号公報において、歯磨き用薬効剤のカプセル化手
法が開示されている。しかしながら、この製造方法では
核（薬効剤）を加熱・溶融させた水不溶性物質中に分散
させ、噴霧冷却造粒によりカプセル化を行っているた
め、熱変性しやすい薬効剤を用いてのカプセル化は困難
である。またこの方法では、水不溶性物質の膜厚を制御
することは難しく、核材に対して均一な膜厚のカプセル
は得ることが困難である。さらに、工業化する場合に装
置が大きくなるという欠点を有する。また、流動層を用
いたカプセルの製造方法として、特開平３−１８５０９
９号公報において開示されたワックスカプセル製造方法
があるが、無溶剤系であるため緻密で薄い被覆層を得難
いという欠点を有する。As a method for producing such a capsule for stabilizing a water-soluble drug for a long time, Japanese Patent Publication No. 50-25 / 1975
Japanese Patent No. 011 discloses a method of encapsulating a medicinal agent for toothpaste. However, in this manufacturing method, the core (medicinal agent) is dispersed in a water-insoluble substance that has been heated and melted, and encapsulation is performed by spray cooling granulation. Therefore, encapsulation using a medicinal agent that is easily heat-denatured It is difficult. Further, with this method, it is difficult to control the film thickness of the water-insoluble substance, and it is difficult to obtain a capsule having a uniform film thickness with respect to the core material. Further, there is a drawback that the device becomes large when industrialized. Further, as a method for producing a capsule using a fluidized bed, Japanese Patent Laid-Open No. 3-18509
Although there is a method for producing a wax capsule disclosed in Japanese Patent No. 9, it has a drawback that it is difficult to obtain a dense and thin coating layer because it is a solventless system.
【０００５】[0005]
【発明が解決しようとする課題】一方、前記のような薬
効剤含有粒子に対して、使用時の適度な外圧により、機
械的崩壊を起こさせて薬効剤含有粒子から薬効剤が放出
されるような機能が要求される場合がある。即ち、歯磨
き、シャンプー等のペースト状、液状等の含水製品に薬
効剤含有粒子を配合して使用する際に、ブラッシング等
による外圧の作用で使用時にカプセルの機械的崩壊を生
じさせることができれば、安定化により薬効が維持され
た水溶性薬効剤により、十分な薬効が得られる。このよ
うな機能を薬効剤含有粒子に持たせるためには、カプセ
ルの被覆層を薄層化等して粒子の機械的強度を小さくす
ればよいが、前述の薬効剤の長期安定化をも実現するた
めには、生成する薬効剤含有粒子からの薬効剤の溶出抑
制と機械的強度とのバランスを考慮してその膜厚等を設
定する必要がある。即ち、被覆層の膜厚が小さすぎると
溶出抑制が不十分となり、一方、膜厚が大きすぎると機
械的強度も大きくなり崩壊しにくくなる。On the other hand, the drug-containing particles as described above are mechanically disintegrated by moderate external pressure during use so that the drug-containing particles are released from the drug-containing particles. Functions may be required. That is, when toothpaste, a paste-like product such as shampoo, or a water-containing product such as a liquid is mixed with the medicinal agent-containing particles and used, if it is possible to cause mechanical collapse of the capsule at the time of use by the action of external pressure due to brushing or the like, Sufficient efficacy is obtained by the water-soluble drug, whose efficacy is maintained by stabilization. In order to impart such a function to the drug-containing particles, it is sufficient to reduce the mechanical strength of the particles by thinning the capsule coating layer, etc., but also realizing the long-term stabilization of the drug as described above. In order to do so, it is necessary to set the film thickness and the like in consideration of the balance between the suppression of elution of the drug and the mechanical strength from the drug-containing particles that are generated. That is, when the film thickness of the coating layer is too small, the dissolution suppression is insufficient, while when the film thickness is too large, the mechanical strength increases and it becomes difficult to disintegrate.
【０００６】以上のように、薬効剤含有粒子に対して、
カプセル化により水溶性薬効剤を長期間安定化させるこ
とと、使用時の各種用途に応じた適度な外圧により、機
械的崩壊を起こすような機能を持たせることとは、相反
するものであり、当業界では、両者を兼ね備えた薬効剤
含有粒子の出現が望まれていた。本発明の目的は、以上
の課題を解決すべく、薬効剤含有粒子中の水溶性薬効剤
を長期間安定化させつつ、使用時の適度な外圧により、
機械的崩壊を起こすような機能を有する薬効剤含有粒
子、およびその製造方法を提供することにある。[0006] As described above, for the drug-containing particles,
Stabilizing the water-soluble drug for a long time by encapsulation and having a function of causing mechanical disintegration by moderate external pressure according to various uses at the time of use are contradictory, In the art, the emergence of particles containing a medicinal agent having both of them has been desired. The object of the present invention is to solve the above problems, while stabilizing the water-soluble drug efficacy agent in the drug efficacy-containing particles for a long period of time, by an appropriate external pressure during use,
(EN) It is intended to provide a medicinal agent-containing particle having a function of causing mechanical disintegration, and a method for producing the same.
【０００７】[0007]
【課題を解決するための手段】本発明者らは、水を含む
系において水および他の配合物により分解、変性を受け
易い水溶性薬効剤の安定化を鋭意研究したところ、水不
溶性物質の有機溶剤溶液を薬効剤に噴霧し有機溶剤を乾
燥させて薬効剤を水不溶性物質で被覆することにより、
従来法に比べ薬効剤の溶出が著しく抑制され薬効剤が長
期安定化されるとともに適度な機械的崩壊性を有するこ
とを見い出し本発明を完成するに至った。Means for Solving the Problems The inventors of the present invention have earnestly studied the stabilization of a water-soluble drug which is susceptible to decomposition and modification by water and other compounds in a system containing water. By spraying an organic solvent solution on the drug and drying the organic solvent to coat the drug with a water-insoluble substance,
The inventors have found that the elution of the medicinal agent is significantly suppressed as compared with the conventional method, that the medicinal agent is stabilized for a long period of time, and that it has an appropriate mechanical disintegration property, and thus completed the present invention.
【０００８】すなわち、本発明の要旨は、水溶性薬効剤
の固体粒子及び該固体粒子を被覆する水不溶性物質の被
覆層からなる薬効剤含有粒子において、該被覆層の膜厚
が１０〜９５μｍであり、かつ、得られる薬効剤含有粒
子を２０℃の水中に３０日間放置した際の水溶性薬効剤
の溶出量が５％以下であるか、または９０日間放置した
際の水溶性薬効剤の溶出量が１０％以下であることを特
徴とする薬効剤含有粒子に関し、並びに水溶性薬効剤の
固体粒子を流動させながら水不溶性物質の有機溶剤溶液
を噴霧し、溶剤を蒸発させることにより該固体粒子表面
に水不溶性物質の被覆層を形成させることを特徴とする
前記の薬効剤含有粒子の製造方法に関する。That is, the gist of the present invention is a drug-containing particle comprising a solid particle of a water-soluble drug and a coating layer of a water-insoluble substance coating the solid particle, wherein the coating layer has a thickness of 10 to 95 μm. And the elution amount of the water-soluble drug is 5% or less when the obtained drug-containing particles are allowed to stand in water at 20 ° C for 30 days, or the water-soluble drug is allowed to elute when left to stand for 90 days The amount of the solid particles is 10% or less, and the solid particles of the water-insoluble substance are sprayed with an organic solvent solution of a water-insoluble substance while the solid particles of the water-soluble pharmaceutical agent are made to flow, and the solid particles are evaporated. The present invention relates to the method for producing particles containing a medicinal agent, which comprises forming a coating layer of a water-insoluble substance on the surface.
【０００９】本発明の薬効剤含有粒子は、水溶性薬効剤
の固体粒子及び該固体粒子を被覆する水不溶性物質の被
覆層からなるが、使用される水溶性薬効剤としては、特
に限定されることなく、例えば酵素、ビタミン類、殺菌
剤、生理活性物質等が挙げられる。また、単一あるいは
二種以上の薬効剤を使用することも可能である。更に、
単一あるいは二種以上の薬効剤を予め造粒成形したもの
を使用することも可能であり、その場合の造粒法として
は、攪拌転動造粒をはじめとする公知の方法で行うこと
ができる。The medicinal agent-containing particles of the present invention are composed of solid particles of a water-soluble medicinal agent and a coating layer of a water-insoluble substance that coats the solid particles, but the water-soluble medicinal agent to be used is not particularly limited. However, for example, enzymes, vitamins, bactericides, physiologically active substances and the like can be mentioned. It is also possible to use a single drug or two or more drugs. Furthermore,
It is also possible to use a single or two or more types of medicinal agents that have been previously granulated, and in that case, the granulation method may be carried out by a known method such as stirring rolling granulation. it can.
【００１０】水溶性薬効剤および該造粒物の形状は特に
限定されないが、球形、立方体およびこれらに類似した
ものの方が、薬効剤粒子全体を水不溶性物質で均一に被
覆しやすく水溶性薬効剤の溶出抑制に効果的である。水
溶性薬効剤の平均粒径は、通常５〜１００００μｍ、好
ましくは、２０〜５０００μｍである。５μｍ未満の微
粉末では薬効剤粉末同士の付着凝集が起こり易くなり収
率低下を招く。また、１００００μｍより大きいと良好
な粒子流動が難しく、各粒子を均一に被覆することが困
難である。The shape of the water-soluble drug and the granules are not particularly limited, but spherical particles, cubes and the like are more likely to uniformly coat the whole drug particles with the water-insoluble substance. It is effective in suppressing elution. The average particle size of the water-soluble drug is usually 5 to 10000 μm, preferably 20 to 5000 μm. If the fine powder is less than 5 μm, adhesion and agglomeration of the drug powder tend to occur, resulting in a decrease in yield. On the other hand, if it is larger than 10000 μm, it is difficult for the particles to flow well, and it is difficult to coat each particle uniformly.
【００１１】本発明において、前記の薬効剤への水不溶
性物質の被覆量は、用途により生成する薬効剤含有粒子
からの水溶性薬効剤の溶出抑制と機械的強度とのバラン
スを考慮して設定する必要がある。つまり、薬効剤含有
粒子の製造、輸送、保存の際には水溶性薬効剤の溶出を
抑制し安定化を図る必要があり、使用時には機械的崩壊
により薬効剤含有粒子から薬効剤が放出され十分な薬効
が認められる被覆量でなければならない。従って、水不
溶性物質の被覆量は、水溶性薬効剤１００重量部に対し
て通常１〜１００００重量部である。１重量部未満の被
覆量では水溶性薬効剤の溶出を抑制することが困難であ
る。また、１００００重量部より多いと溶出抑制に対し
て過剰な被覆量となり、薬効剤の含有量の調節範囲も狭
くなるとともに、被覆層が厚くなるため適度な崩壊性が
得られない。実用上、溶出抑制、機械的強度、コスト、
生産性等の点から被覆量は５〜２０００重量部がより好
ましい。In the present invention, the coating amount of the water-insoluble substance on the medicinal agent is set in consideration of the balance between the suppression of elution of the water-soluble medicinal agent from the medicinal agent-containing particles produced depending on the use and the mechanical strength. There is a need to. In other words, it is necessary to suppress the elution of the water-soluble drug efficacy agent during production, transportation, and storage of the drug efficacy agent-containing particles for stabilization, and during use, the drug efficacy agent-containing particles release the drug agent sufficiently by mechanical disintegration. The amount of coating must be such that a sufficient medicinal effect is observed. Therefore, the coating amount of the water-insoluble substance is usually 1 to 10000 parts by weight with respect to 100 parts by weight of the water-soluble drug. If the coating amount is less than 1 part by weight, it is difficult to suppress the elution of the water-soluble drug. On the other hand, if the amount is more than 10,000 parts by weight, the coating amount becomes excessive for suppressing dissolution, the control range of the content of the medicinal agent is narrowed, and the coating layer becomes thick, so that appropriate disintegration cannot be obtained. In practical use, dissolution suppression, mechanical strength, cost,
From the viewpoint of productivity and the like, the coating amount is more preferably 5 to 2000 parts by weight.
【００１２】また、水不溶性物質の被覆量について膜厚
の点からは、膜厚がより薄い方が薬効剤の配合量を広範
囲に調節でき、生産性も高くなるという利点を有する。
好ましい膜厚としては１０〜９５μｍ、より好ましくは
２０〜８０μｍである。１０μｍより小さいと溶出抑制
が不十分であり、機械的強度も小さくなり過ぎて、輸
送、保存中のわずかな外圧により崩壊し易くなる。９５
μｍより大きいと薬効剤に対して水不溶性物質量が非常
に大きくなるため生成粒子中の薬効剤含有量の少ないも
のしか得られず、機械的強度が大きくなりすぎて使用時
に崩壊しにくくなる。さらに、被覆量が多いため生産性
も低下するといった欠点を有する。Further, from the viewpoint of the film thickness of the coating amount of the water-insoluble substance, the thinner film thickness has an advantage that the compounding amount of the medicinal agent can be adjusted in a wide range and the productivity is increased.
The preferable film thickness is 10 to 95 μm, more preferably 20 to 80 μm. If it is less than 10 μm, the dissolution suppression is insufficient, the mechanical strength becomes too small, and it tends to collapse due to a slight external pressure during transportation and storage. 95
If it is larger than μm, the amount of the water-insoluble substance becomes very large with respect to the medicinal agent, so that only particles having a small medicinal agent content in the produced particles can be obtained, and the mechanical strength becomes too large, and it becomes difficult to disintegrate during use. Further, there is a drawback that productivity is reduced due to the large amount of coating.
【００１３】膜厚を薄くするためには、水不溶性物質を
有機溶剤に溶解した溶液を薬効剤に噴霧し被覆する方法
が有用である。有機溶剤により水不溶性物質を希釈し粘
度を低下させることにより、形成される被覆層は均一で
緻密な薄膜となる。このとき、有機溶剤としては、使用
する水不溶性物質を溶解するものであれば特に限定され
るものでなく、例えばメタノール、エタノール、プロパ
ノール、ヘキサン、シクロヘキサン、キシレン、塩化メ
チレン等が挙げられるが、安全性、蒸気圧の点から塩化
メチレン、エタノール等が好ましい。水不溶性物質溶液
中の有機溶剤量としては、通常１０〜９９．５重量％、
好ましくは５０〜９８重量％である。１０重量％より小
さいと水不溶性物質溶液の粘度が高いこと、噴霧溶液量
が少なくなること等の理由により、均一で薄い被覆層が
形成されにくくなり、９９．５重量％より大きいと水不
溶性物質の濃度が低すぎて生産性が低下する。In order to reduce the film thickness, a method of spraying a solution of a water-insoluble substance in an organic solvent onto a drug and coating it is useful. By diluting the water-insoluble substance with the organic solvent to reduce the viscosity, the formed coating layer becomes a uniform and dense thin film. At this time, the organic solvent is not particularly limited as long as it dissolves the water-insoluble substance used, and examples thereof include methanol, ethanol, propanol, hexane, cyclohexane, xylene, and methylene chloride. Methylene chloride, ethanol and the like are preferable from the viewpoints of properties and vapor pressure. The amount of the organic solvent in the water-insoluble substance solution is usually 10 to 99.5% by weight,
It is preferably 50 to 98% by weight. If it is less than 10% by weight, it is difficult to form a uniform and thin coating layer because the viscosity of the water-insoluble substance solution is high and the amount of the sprayed solution is small. Is too low, resulting in reduced productivity.
【００１４】本発明で使用される水不溶性物質として
は、融点３０℃以上の脂肪酸、脂肪酸誘導体、油脂、樹
脂等が挙げられる。さらに好ましくは融点３０℃以上、
炭素数１６〜２２の脂肪酸、脂肪酸誘導体（ワックス、
高級アルコール、界面活性剤）、油脂等を使用すること
ができる。融点が３０℃より低い水不溶性物質で薬効剤
を被覆した場合には、製造および保存時に外気温により
水不溶性物質の軟化、溶融が起こり、薬効剤の露出や粒
子同士の凝集が生じやすくなるなどの欠点を有する。Examples of the water-insoluble substance used in the present invention include fatty acids having a melting point of 30 ° C. or higher, fatty acid derivatives, fats and oils, resins and the like. More preferably, the melting point is 30 ° C. or higher,
Fatty acids having 16 to 22 carbon atoms, fatty acid derivatives (wax,
Higher alcohols, surfactants), fats and oils can be used. When the drug is coated with a water-insoluble substance having a melting point lower than 30 ° C, the water-insoluble substance is softened or melted due to the ambient temperature during production and storage, and the drug is exposed or the particles are easily aggregated. Has the drawback of.
【００１５】融点３０℃以上、炭素数１６〜２２の脂肪
酸としては、例えばパルミチン酸、ステアリン酸、エイ
コサン酸、ベヘン酸等が、脂肪酸誘導体としては、ジス
テアリルケトン、蜜ろう、鯨ろう等のワックス、セチル
アルコール、ステアリルアルコール、ベヘニルアルコー
ル等の高級アルコール、エチレングリコールジステアレ
ート、ソルビタントリステアレート、ソルビタントリオ
レート等の界面活性剤が、油脂としては硬化ナタネ油、
硬化ヒマシ油等が挙げられる。樹脂としてはエチルセル
ロース、ポリエチレン、ポリプロピレン等が挙げられ
る。何れの水不溶性物質とも精製されたものでもよく、
また未精製のものでもよい。水溶性薬効剤を被覆する際
の水不溶性物質としては上記の中から選ばれる一種ある
いは二種以上の混合物を使用する。さらに、二種以上の
異なる水不溶性物質を用いて二重あるいは三重以上の多
層の被覆を行ってもよい。Fatty acids having a melting point of 30 ° C. or higher and 16 to 22 carbon atoms include, for example, palmitic acid, stearic acid, eicosanoic acid, behenic acid, etc., and fatty acid derivatives such as distearyl ketone, beeswax and spermaceti wax. , Higher alcohols such as cetyl alcohol, stearyl alcohol and behenyl alcohol, surfactants such as ethylene glycol distearate, sorbitan tristearate and sorbitan trioleate, hardened rapeseed oil as fats and oils,
Hardened castor oil and the like can be mentioned. Examples of the resin include ethyl cellulose, polyethylene, polypropylene and the like. Any water-insoluble substance may be purified,
It may also be unpurified. As the water-insoluble substance for coating the water-soluble drug, one or a mixture of two or more selected from the above is used. Further, two or more different water-insoluble substances may be used to perform double or triple or more multilayer coating.
【００１６】本発明の薬効剤含有粒子の製造法は、水溶
性薬効剤の固体粒子を流動させながら水不溶性物質の有
機溶剤溶液を噴霧し、溶剤を蒸発させることにより固体
粉末表面に水不溶性物質の被覆層を形成させることを特
徴とする。より具体的には、水溶性薬効剤の固体粉末を
装置内で流動させながら、水不溶性物質の有機溶剤溶液
をスプレーノズルより薬効剤表面に噴霧し、噴霧された
溶液は薬効剤表面上で温風により有機溶剤が蒸発し水不
溶性物質が残留付着して被覆層を形成する。このとき、
所定量の水不溶性物質で薬効剤表面全体を均一に被覆す
ることができるため、薬効剤の溶出が抑制された薬効剤
含有粒子を得ることができる。このとき用いられる一般
的な装置としては、温風の供給および水不溶性物質溶液
のスプレーが可能な攪拌転動型あるいは流動層型の造粒
・コーティング装置が挙げられる。攪拌転動型としては
スパイラルフロー（フロイント産業製）、ハイコーター
（フロイント産業製）、グラニュレックス（フロイント
産業製）、ニューマルメライザー（不二パウダル製）、
ドリアコーター（パウレック製）等が挙げられる。ま
た、流動層型としては、フローコーター（フロイント産
業製）、ニューマルメライザーＮＱ−ＧＭ（不二パウダ
ル製）、パウダーコーター（Ｇｌａｔｔ、パウレック
製）、スプレーグラニュレーター（エアロマティック
製）等が挙げられる。The method for producing particles containing a medicinal agent according to the present invention comprises spraying an organic solvent solution of a water-insoluble substance while flowing solid particles of a water-soluble medicinal agent, and evaporating the solvent to evaporate the solvent. The coating layer is formed. More specifically, while a solid powder of a water-soluble drug is flown in the device, an organic solvent solution of a water-insoluble substance is sprayed from the spray nozzle onto the drug surface, and the sprayed solution is heated on the drug surface. The organic solvent is evaporated by the wind and the water-insoluble substance remains attached to form a coating layer. At this time,
Since the entire surface of the medicinal agent can be uniformly coated with a predetermined amount of the water-insoluble substance, the medicinal agent-containing particles in which the elution of the medicinal agent is suppressed can be obtained. As a general apparatus used at this time, there is a stirring rolling type or fluidized bed type granulating / coating apparatus capable of supplying hot air and spraying a water-insoluble substance solution. As a stirring rolling type, spiral flow (made by Freund Sangyo), high coater (made by Freund Sangyo), granurex (made by Freund Sangyo), new marmelizer (made by Fuji Paudal),
Doria coater (manufactured by Paulec) and the like can be mentioned. Examples of the fluidized bed type include a flow coater (manufactured by Freund Industrial Co., Ltd.), a Numemalizer NQ-GM (manufactured by Fuji Paudal), a powder coater (manufactured by Glatt and Paulec), and a spray granulator (manufactured by Aeromatic). .
【００１７】さらに本発明においては、得られた薬効剤
含有粒子を水不溶性物質の融点より１０℃低い温度から
該融点までの温度範囲で加熱し、被覆層の表面を軟化・
溶融させて被覆層表面を更に緻密化し薬効剤の溶出抑制
効果を高めることも可能である。ここでの加熱温度は、
水不溶性物質の種類により異なるが、被覆材として使用
した水不溶性物質の融点より１０℃低い温度から該融点
までの温度範囲で加熱する必要がある。融点より１０℃
低い温度を下回る温度では、水不溶性物質の軟化が起こ
らず、また融点より高い温度では水不溶性物質が融解
し、薬効剤含有粒子同士の付着凝集や粒子の崩壊が生じ
るからである。加熱処理に用いる装置は、一定の温度に
調節できる機器であればよく、棚乾燥機等の恒温槽、又
は流動槽等が挙げられる。Further, in the present invention, the obtained drug-containing particles are heated in a temperature range from a temperature lower than the melting point of the water-insoluble substance by 10 ° C. to the melting point to soften the surface of the coating layer.
It is also possible to melt and further densify the surface of the coating layer to enhance the elution suppressing effect of the medicinal agent. The heating temperature here is
Although it depends on the type of the water-insoluble substance, it is necessary to heat in a temperature range from a temperature 10 ° C. lower than the melting point of the water-insoluble substance used as the coating material to the melting point. 10 ℃ from melting point
This is because the softening of the water-insoluble substance does not occur at a temperature lower than the low temperature, and the water-insoluble substance melts at a temperature higher than the melting point, resulting in adhesion and aggregation of the drug-effect-containing particles and disintegration of the particles. The device used for the heat treatment may be any device that can adjust the temperature to a constant temperature, and examples thereof include a constant temperature tank such as a shelf dryer or a fluidized tank.
【００１８】以上のようにして得られる本発明の薬効剤
含有粒子の薬効剤の溶出性は、生成した薬効剤含有粒子
を２０℃の水中に３０日間放置した際に、その溶出率が
５％以下、好ましくは３％以下であり、あるいは同様に
２０℃の水中に９０日間放置した場合にはその溶出率が
１０％以下好ましくは５％以下である。また、３０日間
放置および９０日間放置の両方でこれらの溶出性を満足
するものが、さらに好ましいが、薬効剤の種類、薬効剤
配合製品の用途等によっては、いずれか一方のみを満足
するものであってもよい。このような溶出性を実現する
ことにより、薬効剤含有粒子中の水溶性薬効剤を長期間
安定化させることができる。また、本発明の薬効剤含有
粒子は、水不溶性物質の種類、被覆層の膜厚等を適宜選
択することにより、各種の用途に応じて適度な機械的崩
壊性を持たせるように機械的強度を設定することが可能
である。The elution property of the medicinal agent of the medicinal agent-containing particles of the present invention obtained as described above is such that when the produced medicinal agent-containing particles are allowed to stand in water at 20 ° C. for 30 days, the elution rate is 5%. Hereinafter, it is preferably 3% or less, or similarly, when left in water at 20 ° C. for 90 days, the elution rate is 10% or less, preferably 5% or less. Further, it is more preferable that these dissolution properties are satisfied after both standing for 30 days and 90 days, but depending on the kind of the medicinal agent, the use of the medicinal agent-containing product, etc., either one may be satisfied. It may be. By realizing such dissolution property, the water-soluble drug effect in the drug effect-containing particles can be stabilized for a long period of time. Further, the medicinal agent-containing particles of the present invention, by appropriately selecting the type of the water-insoluble substance, the film thickness of the coating layer, etc., mechanical strength so as to have appropriate mechanical disintegration according to various uses. Can be set.
【００１９】本発明の薬効剤含有粒子の適用例として
は、例えば歯磨きペースト中に配合することにより、保
存時には薬効剤成分が変性することなく安定に保存さ
れ、使用時にはブラッシングにより生じる圧力により薬
効剤含有粒子が崩壊し放出された薬効剤成分の薬効が発
現される。また液状洗剤に配合すると同様に保存時には
安定で洗濯時に薬効が発現される。As an application example of the particles containing a medicinal agent of the present invention, for example, by compounding it in a toothpaste, the medicinal agent component can be stably stored without being modified during storage, and the medicinal agent can be used by pressure generated by brushing during use. The contained drug disintegrates and the drug efficacy of the released drug component is exhibited. Further, when blended in a liquid detergent, similarly, it is stable during storage and exhibits a medicinal effect during washing.
【００２０】[0020]
【実施例】以下に実施例を挙げ、本発明をさらに具体的
に説明するが、本発明はこれらに限定されるものではな
い。薬効剤含有粒子からの薬効剤溶出率は、次の方法に
より測定した。薬効剤含有粒子０．３ｇをイオン交換水
３０ｍｌ中に投入し、２０℃に保ちながら所定の期間放
置し水中に溶出してくる薬効剤量を測定し溶出率を求め
た。 溶出率（％）＝薬効剤溶出量（ｇ）／薬効剤含有粒子中
の薬効剤量（ｇ）×１００ 薬効剤量の測定は薬効剤中に含有される炭素濃度をＴＯ
Ｃ測定装置（ＴＯＣ−５００，島津（株）製）を使用し
て測定し、薬効剤の分子式から換算して薬効剤重量を求
めた。The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto. The elution rate of the medicinal agent from the medicinal agent-containing particles was measured by the following method. 0.3 g of the particles containing a medicinal agent was put into 30 ml of ion-exchanged water and allowed to stand for 20 minutes at 20 ° C. for a predetermined period of time to measure the amount of medicinal agent eluted in water to obtain the dissolution rate. Dissolution rate (%) = Elution amount of medicinal agent (g) / Amount of medicinal agent in medicinal agent-containing particles (g) x 100 The amount of medicinal agent is measured by measuring the concentration of carbon contained in the medicinal agent by TO.
It measured using the C measuring device (TOC-500, Shimadzu Co., Ltd. product), converted from the molecular formula of the drug, and calculated | required the drug weight.
【００２１】実施例１ ヒノキチオール造粒物（平均粒径４１０μｍ）１００ｇ
を流動層装置（スプレーグラニュレーターＳＴＲＥＡ−
１型、エアロマティック）内に仕込み、流動層下部より
３５℃の乾燥用空気および流動空気を９０ｍ3 ／ｈで吹
き込み粒子を流動させながら、流動層下部中央の二流体
ノズルより塩化メチレン９５重量部（８３６ｇ）にステ
アリルアルコール（融点：５８℃）５重量部（４４ｇ）
を溶解した溶液を６．１ｇ／ｍｉｎ、空気圧０．６ｋｇ
／ｃｍ2 で噴霧し、ヒノキチオール造粒物をステアリル
アルコールで被覆した。得られた本発明のヒノキチオー
ル含有粒子の組成はステアリルアルコール２６．８重
量％、ヒノキチオール造粒物７３．２重量％、平均粒径
４９０μｍ、膜厚４０μｍであった。Example 1 100 g of granulated hinokitiol (average particle size 410 μm)
Fluidized bed equipment (spray granulator STREA-
(Type 1, Aeromatic), and blowing air at 35 ° C. for drying and flowing air from the lower part of the fluidized bed at 90 m 3 / h to make the particles flow, and 95 parts by weight of methylene chloride from the two-fluid nozzle in the center of the lower part of the fluidized bed. (836 g) with stearyl alcohol (melting point: 58 ° C.) 5 parts by weight (44 g)
6.1g / min, air pressure 0.6kg
The hinokitiol granulation was coated with stearyl alcohol by spraying at / cm 2 . The composition of the obtained hinokitiol-containing particles of the present invention was 26.8% by weight of stearyl alcohol, 73.2% by weight of a granulated product of hinokitiol, an average particle size of 490 μm, and a film thickness of 40 μm.
【００２２】実施例２ 噴霧量以外は実施例１と同条件で、塩化メチレン９５重
量部（１１０２ｇ）にステアリルアルコール５重量部
（５８ｇ）を溶解した溶液を噴霧しヒノキチオール含有
粒子を得た。該生成粒子の組成は、ヒノキチオール
造粒物６５．４重量％、ステアリルアルコール３４．６
重量％であり、平均粒径５２０μｍ、膜厚５５μｍであ
った。実施例１〜２で得られたヒノキチオール含有粒子
についての２０℃の水中での溶出性を表１に示した。Example 2 A hinokitiol-containing particle was obtained by spraying a solution prepared by dissolving 5 parts by weight (58 g) of stearyl alcohol in 95 parts by weight (1102 g) of methylene chloride under the same conditions as in Example 1 except that the amount was sprayed. The composition of the produced particles was as follows: hinokitiol granulated product 65.4% by weight, stearyl alcohol 34.6.
The weight average was 520 μm, and the film thickness was 55 μm. Table 1 shows the elution properties of the hinokitiol-containing particles obtained in Examples 1 and 2 in water at 20 ° C.
【００２３】[0023]
【表１】 [Table 1]
【００２４】実施例３ アスコルビン酸造粒物（平均粒径１７０μｍ）５０ｇを
ワースター型流動層装置（ニューマルメライザーＮＱ−
ＧＭ型，不二パウダル製）に仕込み、流動層下部より３
５℃の乾燥用空気を、内塔下部中央のスプレーノズルよ
り流動および噴霧用空気を圧力２．０ｋｇ／ｃｍ2 で吹
き込み該造粒物粒子を流動させた。スプレー液としてエ
タノール９０重量部（１４０４ｇ）にステアリルアルコ
ール１０重量部（１５６ｇ）を加熱溶解した溶液を調製
後、スプレーノズルより１０ｇ／ｍｉｎの流速で噴霧し
アスコルビン酸造粒物をステアリルアルコールで被覆し
た。得られた本発明のアスコルビン酸含有粒子の組成は
ステアリルアルコール８０．３重量％、アスコルビン酸
造粒物１９．７重量％、平均粒径２５０μｍ、膜厚４０
μｍであった。さらにこのアスコルビン酸含有粒子を棚
乾燥器を用いて５８℃、１０分間加熱処理を行った。該
加熱処理粒子の水中でのアスコルビン酸溶出率は３０日
間で２．７％、９０日間で３．６％であった。Example 3 50 g of an ascorbic acid granulated product (average particle size 170 μm) was added to a Wurster type fluidized bed apparatus (New Malmerizer NQ-
GM type, made by Fuji Paudal), 3 from the bottom of the fluidized bed
Drying air at 5 ° C. was flown from a spray nozzle in the center of the lower part of the inner tower, and atomizing air was blown at a pressure of 2.0 kg / cm 2 to flow the granule particles. After preparing a solution of 10 parts by weight (156 g) of stearyl alcohol dissolved in 90 parts by weight of ethanol (1404 g) as a spray solution, it was sprayed from a spray nozzle at a flow rate of 10 g / min to coat the ascorbic acid granulated product with stearyl alcohol. .. The composition of the obtained ascorbic acid-containing particles of the present invention was as follows: stearyl alcohol 80.3% by weight, ascorbic acid granules 19.7% by weight, average particle size 250 μm, film thickness 40
was μm. Further, the ascorbic acid-containing particles were heat-treated at 58 ° C. for 10 minutes using a shelf dryer. The dissolution rate of ascorbic acid in the heat-treated particles in water was 2.7% in 30 days and 3.6% in 90 days.
【００２５】[0025]
【発明の効果】本発明によれば、水や他の配合物により
変性あるいは分解されやすい水溶性薬効剤を水不溶性物
質で被覆し薬効剤の溶出性を抑制することにより、薬効
剤を長期間安定化しつつ、更に使用時に薬効が発現する
ように各種用途に応じた適度な機械的崩壊性を達成する
ことができる。また、本発明の製造方法では薬効剤が長
時間高温にさらされないため熱に不安定な薬効剤もその
対象とすることができ、更に装置のコンパクト化も可能
となった。INDUSTRIAL APPLICABILITY According to the present invention, a water-soluble drug which is easily modified or decomposed by water or another compound is coated with a water-insoluble substance to suppress the elution of the drug, so that the drug can be treated for a long time. It is possible to achieve appropriate mechanical disintegration according to various applications while stabilizing and further exhibiting a drug effect during use. Further, in the production method of the present invention, the drug efficacy agent is not exposed to high temperature for a long time, so that the drug efficacy agent which is unstable to heat can be the target, and further the apparatus can be made compact.
Claims (9)
を被覆する水不溶性物質の被覆層からなる薬効剤含有粒
子において、該被覆層の膜厚が１０〜９５μｍであり、
得られる薬効剤含有粒子を２０℃の水中に３０日間放置
した際の水溶性薬効剤の溶出量が５％以下であることを
特徴とする薬効剤含有粒子。1. A drug-effect-containing particle comprising a solid particle of a water-soluble drug and a coating layer of a water-insoluble substance coating the solid particle, wherein the coating layer has a thickness of 10 to 95 μm.
The medicinal agent-containing particles, wherein the elution amount of the water-soluble medicinal agent is 5% or less when the obtained medicinal agent-containing particles are allowed to stand in water at 20 ° C. for 30 days.
を被覆する水不溶性物質の被覆層からなる薬効剤含有粒
子において、該被覆層の膜厚が１０〜９５μｍであり、
得られる薬効剤含有粒子を２０℃の水中に９０日間放置
した際の水溶性薬効剤の溶出量が１０％以下であること
を特徴とする薬効剤含有粒子。2. A drug-effect-containing particle comprising solid particles of a water-soluble drug and a coating layer of a water-insoluble substance coating the solid particles, wherein the coating layer has a thickness of 10 to 95 μm.
The medicinal agent-containing particles, wherein the elution amount of the water-soluble medicinal agent is 10% or less when the obtained medicinal agent-containing particles are allowed to stand in water at 20 ° C. for 90 days.
００重量部に対して１〜１００００重量部である、請求
項１または２記載の薬効剤含有粒子。3. A water-soluble drug 1 having a coating amount of a water-insoluble substance.
The medicinal agent-containing particle according to claim 1, which is 1 to 10000 parts by weight with respect to 00 parts by weight.
溶性物質である、請求項１または２記載の薬効剤含有粒
子。4. The medicinal agent-containing particles according to claim 1, wherein the water-insoluble substance is a water-insoluble substance having a melting point of 30 ° C. or higher.
ら水不溶性物質の有機溶剤溶液を噴霧し、溶剤を蒸発さ
せることにより該固体粒子表面に水不溶性物質の被覆層
を形成させることを特徴とする、該被覆層の膜厚が１０
〜９５μｍであって、２０℃の水中に３０日間放置した
際の水溶性薬効剤の溶出量が５％以下である薬効剤含有
粒子の製造方法。5. A method of forming a coating layer of a water-insoluble substance on the surface of the solid particles by spraying an organic solvent solution of a water-insoluble substance while flowing the solid particles of the water-soluble drug, and evaporating the solvent. And the film thickness of the coating layer is 10
The method for producing a drug-containing particle having a particle size of ˜95 μm, wherein the elution amount of the water-soluble drug is 5% or less when left in water at 20 ° C. for 30 days.
ら水不溶性物質の有機溶剤溶液を噴霧し、溶剤を蒸発さ
せることにより該固体粒子表面に水不溶性物質の被覆層
を形成させることを特徴とする、該被覆層の膜厚が１０
〜９５μｍであって、２０℃の水中に９０日間放置した
際の水溶性薬効剤の溶出量が１０％以下である薬効剤含
有粒子の製造方法。6. A coating layer of the water-insoluble substance is formed on the surface of the solid particles by spraying an organic solvent solution of the water-insoluble substance while flowing the solid particles of the water-soluble drug, and evaporating the solvent. And the film thickness of the coating layer is 10
A method for producing particles containing a drug, which has a particle size of ˜95 μm and has an elution amount of 10% or less of the water-soluble drug when left in water at 20 ° C. for 90 days.
１００重量部に対して１〜１００００重量部となるよう
水不溶性物質の有機溶剤溶液を噴霧することを特徴とす
る請求項５または６記載の薬効剤含有粒子の製造方法。7. The organic solvent solution of the water-insoluble substance is sprayed so that the coating amount of the water-insoluble substance is 1 to 10000 parts by weight with respect to 100 parts by weight of the water-soluble drug. 6. The method for producing particles containing a medicinal agent according to 6.
性物質である、請求項５または６記載の薬効剤含有粒子
の製造方法。8. The method for producing particles containing a medicinal agent according to claim 5, wherein the water-insoluble substance is a water-insoluble substance having a melting point of 30 ° C. or higher.
れる薬効剤含有粒子を水不溶性物質の融点より１０℃低
い温度から該融点までの温度範囲で更に加熱し、該水不
溶性物質の被覆層の表面を軟化させることを特徴とする
薬効剤含有粒子の製造方法。9. The drug-containing particles obtained by the production method according to claim 5 or 6 are further heated in a temperature range from a temperature 10 ° C. lower than the melting point of the water-insoluble substance to the melting point to coat the water-insoluble substance. A method for producing particles containing a medicinal agent, which comprises softening the surface of a layer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8324492A JPH05246840A (en) | 1992-03-04 | 1992-03-04 | Particle containing agent having medicinal action and its production |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8324492A JPH05246840A (en) | 1992-03-04 | 1992-03-04 | Particle containing agent having medicinal action and its production |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH05246840A true JPH05246840A (en) | 1993-09-24 |
Family
ID=13796921
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8324492A Pending JPH05246840A (en) | 1992-03-04 | 1992-03-04 | Particle containing agent having medicinal action and its production |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH05246840A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005343800A (en) * | 2004-05-31 | 2005-12-15 | Lion Corp | Coated caffeine particle, solid preparation and sleepiness-preventing medicine |
| US11215116B2 (en) | 2017-02-23 | 2022-01-04 | Mitsubishi Power, Ltd. | Turbine moving blade and gas turbine |
-
1992
- 1992-03-04 JP JP8324492A patent/JPH05246840A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005343800A (en) * | 2004-05-31 | 2005-12-15 | Lion Corp | Coated caffeine particle, solid preparation and sleepiness-preventing medicine |
| US11215116B2 (en) | 2017-02-23 | 2022-01-04 | Mitsubishi Power, Ltd. | Turbine moving blade and gas turbine |
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