JP5046501B2 - Tablets that hold multiple drugs separately - Google Patents
Tablets that hold multiple drugs separately Download PDFInfo
- Publication number
- JP5046501B2 JP5046501B2 JP2005237371A JP2005237371A JP5046501B2 JP 5046501 B2 JP5046501 B2 JP 5046501B2 JP 2005237371 A JP2005237371 A JP 2005237371A JP 2005237371 A JP2005237371 A JP 2005237371A JP 5046501 B2 JP5046501 B2 JP 5046501B2
- Authority
- JP
- Japan
- Prior art keywords
- layer
- drug
- tablet
- divided
- drugs
- 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.)
- Expired - Fee Related
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- Medicinal Preparation (AREA)
Description
本発明は、複数の薬物保持部位をもつ医薬用の錠剤に関する。さらに詳しくは、接触を避けるべき複数の薬物であってもひとつの錠剤中に分離して安定的に保持できる錠剤に関する。また、分割後も接触を避けるべき複数の種類の薬物を安定的に保持している断片が得られる割線錠に関する。また、本発明は一錠中に複数の種類の薬物を保持しているが、分割により一種類の薬物のみを含む断片が容易に得られる割線錠に関する。 The present invention relates to a pharmaceutical tablet having a plurality of drug holding sites. More specifically, the present invention relates to a tablet that can stably hold a plurality of drugs that should not be contacted in one tablet. The present invention also relates to a scored tablet from which a fragment stably holding a plurality of types of drugs that should not be contacted even after division is obtained. The present invention also relates to a scored tablet in which a plurality of types of drugs are held in one tablet, but a fragment containing only one type of drug can be easily obtained by division.
割線錠は服用量に応じて薬剤師または患者によって分割される錠剤であり、服用量管理を最適にし、処方の際の融通性を高めるために用いられている（例えば特開平９−１０４６１９、米国特許第５５２０９２９号参照）。 A secant tablet is a tablet divided by a pharmacist or patient according to the dose, and is used to optimize dose management and increase flexibility in prescribing (for example, JP-A-9-104619, US Patent). No. 5520929).
本発明の第一の目的は、同種あるいは異種の複数の薬物、例えば接触を避けるべき異種の複数の薬物を安定的に保持できる錠剤を提供することである。 The first object of the present invention is to provide a tablet capable of stably holding a plurality of drugs of the same kind or different kinds, for example, a plurality of kinds of different drugs to avoid contact.
本発明の第二の目的は、接触を避けるべき複数の薬物がひとつの錠剤中に分離して保持されていて、分割後も接触を避けるべき複数の薬物を安定的に保持している断片が得られる割線錠を提供することである。 A second object of the present invention is that a plurality of drugs that should avoid contact are separated and held in one tablet, and a fragment that stably holds a plurality of drugs that should avoid contact even after splitting. It is to provide the resulting scored lock.
本発明の第三の目的は、複数の薬物（接触を避けるべきものを含む）がひとつの錠剤中に分離して保持されているが、分割後は一種の薬物のみを含む断片が得られる割線錠を提供することである。 A third object of the present invention is a secant line in which a plurality of drugs (including those that should be avoided from contact) are separately held in one tablet, but after dividing, a fragment containing only one kind of drug is obtained. Is to provide a lock.
本発明のさらなる目的は、上記のいずれかの錠剤であり、分割後も口腔内もしくは食道での薬物の接触が患者の不利益になることを避ける機能が維持される被覆錠を提供することである。 A further object of the present invention is to provide a coated tablet that is any of the above-mentioned tablets and that maintains the function of preventing the contact of the drug in the oral cavity or the esophagus with the patient even after splitting. is there.
本発明は、Ａ層とＢ層とからなる二層錠、またはＡ層、Ｂ層、Ｃ層の順に三層をなしている三層錠であって、
該Ｂ層は、薬物を含んでいてもよい医薬添加物層であり、
該Ａ層は医薬添加物を含んでいてもよい薬物層であって、Ｂ層上で分断されており、
該Ａ層の分断された各部分はＢ層に固着していることにより保持されていて、それぞれ同一もしくは異なる薬物を含有しており、
さらにＣ層を有する場合の該Ｃ層も医薬添加物を含んでいてもよい薬物層であって、Ｂ層上で分断されており、
該Ｃ層の分断された各部分はＢ層に固着していることにより保持されていて、それぞれ同一もしくは異なる薬物を含有している錠剤である。そしてＡ層またはＣ層の少なくとも一つの領域に含まれる薬物は、Ａ層またはＣ層の他の領域に含まれる薬物と接触すべきでない他の薬物であってもよい（第一発明）。
The present invention is a two-layer tablet consisting of A layer and B layer, or a three-layer tablet comprising three layers in the order of A layer, B layer, C layer,
The layer B is a pharmaceutical additive layer that may contain a drug,
The A layer is a drug layer that may contain a pharmaceutical additive, and is divided on the B layer,
Each divided part of the A layer is retained by being fixed to the B layer, and each contains the same or different drug,
Furthermore, when it has C layer, this C layer is a drug layer which may contain a pharmaceutical additive, and is divided on B layer,
Each divided part of the C layer is held by being fixed to the B layer, and is a tablet containing the same or different drug. The drug contained in at least one region of the A layer or the C layer may be another drug that should not come into contact with the drug contained in the other region of the A layer or the C layer (first invention).
また、本発明は上記第一発明において、さらにＢ層の片面もしくは両面に一つ以上の割線があり、
Ａ層、およびＣ層がある場合のＣ層の分断部位がＢ層上の割線のある部位もしくはその裏面の対応部位である錠剤である（第二発明）。
In the first invention, the present invention further includes one or more dividing lines on one side or both sides of the B layer.
In the case where there are the A layer and the C layer, the divided part of the C layer is a part having a dividing line on the B layer or a corresponding part on the back surface thereof (second invention).
さらに本発明は、Ａ層とＢ層とからなる二層錠、またはＡ層、Ｂ層、Ｃ層の順に三層をなしている三層錠であって、
該Ｂ層は、薬物を含んでいてもよい医薬添加物層であって、その片面もしくは両面に一つ以上の割線を有しており、
該Ａ層は医薬添加物を含んでいてもよい薬物層であって、Ｂ層上の割線のある部位もしくはその裏面の対応部位によって分断されており、
該Ａ層の分断された各部分はＢ層に固着していることにより保持されていて、それぞれ同一もしくは異なる薬物を含有しており、
さらにＣ層を有する場合の該Ｃ層も医薬添加物を含んでいてもよい薬物層であって、Ｂ層上の割線のある部位もしくはその裏面の対応部位によって分断されており、
該Ｃ層の分断された各部分はＢ層に固着していることにより保持されていて、それぞれ同一もしくは異なる薬物を含有しており、
Ａ層またはＣ層の少なくとも一つの領域に含まれる薬剤は、同じ層の他の領域に含まれる薬剤と同一ではなく、かつ少なくとも一つの割線に従って錠剤を分割すれば、一種類の薬物のみを含む断片が得られるようＡ層またはＣ層の薬物が配置された錠剤である（第三発明）。
Furthermore, the present invention is a two-layer tablet comprising A layer and B layer, or a three-layer tablet comprising three layers in the order of A layer, B layer, C layer,
The B layer is a pharmaceutical additive layer that may contain a drug, and has one or more secant lines on one or both sides thereof,
The A layer is a drug layer that may contain a pharmaceutical additive, and is divided by a part having a secant on the B layer or a corresponding part on the back surface thereof,
Each divided part of the A layer is retained by being fixed to the B layer, and each contains the same or different drug,
In addition, the C layer in the case of having the C layer is a drug layer that may contain a pharmaceutical additive, and is divided by a part having a dividing line on the B layer or a corresponding part on the back surface thereof,
Each divided portion of the C layer is retained by being fixed to the B layer, and each contains the same or different drug,
The drug contained in at least one region of the A layer or C layer is not the same as the drug contained in other regions of the same layer, and contains only one kind of drug if the tablet is divided according to at least one secant. It is a tablet in which drugs of layer A or layer C are arranged so that fragments can be obtained (third invention).
さらに本発明は、上記第一、第二、または第三発明の錠剤において錠剤全体が被覆され、該被覆層が、口腔内もしくは食道での薬物の接触が患者の不利益になることを避ける機能を有しており、分割しても上記被覆層の機能が維持される錠剤である。 Furthermore, the present invention provides the tablet according to the first, second, or third invention, wherein the whole tablet is coated, and the coating layer prevents the contact of the drug in the oral cavity or the esophagus from being a disadvantage for the patient. It is a tablet in which the function of the coating layer is maintained even when divided.
第一発明の錠剤は、同種あるいは異種の複数の薬物、例えば接触を避けるべき異種の複数の薬物をひとつの錠剤中に分離して、したがって安定的に保持できるという効果を有する。 The tablet of the first invention has an effect that a plurality of drugs of the same kind or different kinds, for example, a plurality of kinds of different drugs to avoid contact, can be separated in one tablet and thus stably held.
第二発明の割線錠は、接触を避けるべき複数の薬物がひとつの錠剤中に分離して安定に保持されているが、分割後もそれら接触を避けるべき複数の薬物が各断片に分離して安定に保持されている状態が維持されるという効果を有する。 In the scored tablet of the second invention, a plurality of drugs that should avoid contact are separated and retained stably in one tablet, but even after the division, the plurality of drugs that should avoid contact are separated into each fragment. It has the effect that the state maintained stably is maintained.
第三発明の割線錠は、複数の薬物（接触を避けるべきものを含む）がひとつの錠剤中に分離して安定に保持されているが、分割後はその一種の薬物のみを含む断片が得られるという効果を有する。これらの効果は処方の際の融通性を増す。 In the scored tablet of the third invention, a plurality of drugs (including those that should not be contacted) are stably held in a single tablet, but after splitting, a fragment containing only that kind of drug is obtained. Has the effect of being These effects increase flexibility during formulation.
さらに、上記第一ないし第三発明の錠剤において、口腔内もしくは食道での薬物の接触が患者の不利益になることを避ける機能を有する被覆層をさらに有する錠剤は、割線錠の場合にそれを分割した後の断片も含め、当該被覆の効果が付加される。 Furthermore, in the tablet of the first to third inventions, the tablet further having a coating layer having a function of preventing the contact of the drug in the oral cavity or the esophagus from being disadvantageous to the patient is obtained when it is a scored tablet. The effect of the covering is added including the fragments after the division.
また、本発明のなかでも割線錠は、分割時に薬物量のばらつきを生ぜず、正確に分割することができる効果がある。
本発明は、これらの効果を簡便な構造により達成する。したがって、その製造コストが低い利点をもつ。
In addition, among the present invention, the scored tablet has an effect that it can be accurately divided without causing variation in the amount of drug at the time of division.
The present invention achieves these effects with a simple structure. Therefore, there is an advantage that the manufacturing cost is low.
第一発明は、Ａ層とＢ層とからなる二層錠、またはＡ層、Ｂ層、Ｃ層の順に三層をなしている三層錠であって、
該Ｂ層は、薬物を含んでいてもよい医薬添加物層であり、
該Ａ層は医薬添加物を含んでいてもよい薬物層であって、Ｂ層上で分断されており（以下、「分断領域」ともいう。）、
該Ａ層の分断された各部分はＢ層に固着していることにより保持されていて、それぞれ同一もしくは異なる薬物を含有しており、
さらにＣ層を有する場合の該Ｃ層も医薬添加物を含んでいてもよい薬物層であって、Ｂ層上で分断されており（以下、「分断領域」ともいう。）、
該Ｃ層の分断された各部分はＢ層に固着していることにより保持されていて、それぞれ同一もしくは異なる薬物を含有している錠剤である。
The first invention is a two-layer tablet consisting of A layer and B layer, or a three-layer tablet comprising three layers in the order of A layer, B layer, C layer,
The layer B is a pharmaceutical additive layer that may contain a drug,
The A layer is a drug layer that may contain a pharmaceutical additive, and is divided on the B layer (hereinafter also referred to as “divided region”).
Each divided part of the A layer is retained by being fixed to the B layer, and each contains the same or different drug,
Further, when the layer C is provided, the layer C is also a drug layer that may contain a pharmaceutical additive, and is divided on the layer B (hereinafter also referred to as “divided region”).
Each divided part of the C layer is held by being fixed to the B layer, and is a tablet containing the same or different drug.
かかる錠剤の大きさは、錠剤として服用するのに不都合でなく、上記構成を実現しうるものである限り、問題とならない。形状についても、通常の製造装置により、またはそれに手を加えた製造装置により困難なく製造できるものである限り特に限定されないが、一般的な錠剤の概念である、円盤状のものが典型例として例示できる。他に、高さの低い三ないし六角柱状のもの、直方体状のものも典型例として挙げることができるが、以下に述べるような各層の基本的機能が害されない限り、形状は特に問題とならない。 The size of the tablet is not inconvenient for taking as a tablet, and does not cause a problem as long as the above configuration can be realized. The shape is not particularly limited as long as it can be produced without difficulty by an ordinary production apparatus or a production apparatus that has been modified, but a typical example of a general tablet concept is a disk-like shape. it can. In addition, low-height three or hexagonal prisms and rectangular parallelepipeds can be given as typical examples, but the shape is not particularly problematic as long as the basic functions of each layer as described below are not impaired.
Ｂ層の形状は、基本的には上下面が平面的であることが望ましいが、Ａ層やＣ層の各分断領域を保持しうるような形態である限り、起伏や凹凸があってもよい。特に、二層錠の場合におけるＡ層と反対側の面は、保持すべき層がないから錠剤の片面として採用できるものである限り、何ら限定はない。 As for the shape of the B layer, it is basically desirable that the upper and lower surfaces are planar, but as long as it can hold each segmented region of the A layer and the C layer, there may be undulations and irregularities. . In particular, the side opposite to the A layer in the case of a bilayer tablet is not limited as long as it can be employed as one side of a tablet because there is no layer to be held.
Ａ層やＣ層は、活性成分たる薬物のみで構成されていても、医薬添加物を含んでいてもよいが、本発明錠剤の一部をなすものであり、一定の形状を保つ固形のものでなければならない。なお、医薬添加物が含まれる場合にも、当該薬物は均一に分散していることが望ましい。 The A layer and the C layer may be composed of only a drug as an active ingredient or may contain a pharmaceutical additive. However, the A layer and the C layer are part of the tablet of the present invention and are solid solids that maintain a certain shape. Must. Even when a pharmaceutical additive is contained, it is desirable that the drug is uniformly dispersed.
Ｂ層に含まれる医薬添加物やＡ層やＣ層が含んでいてもよい医薬添加物は、製薬学的に許容されるものであり、錠剤の形状を安定に保つことを妨げないものである限り、特に限定されない。具体的には、苦みや刺激等のマスキングの目的のためには、例えば、結晶セルロース、乳糖、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、部分アルファー化デンプン、デンプン、エリスリトール、マンニトール、ソルビトール、トレハロース、軽質無水珪酸またはこれらの混合物や造粒物が用いられ、さらに製造性、成形性、製剤機能を向上させる目的で、滑沢剤、崩壊剤、流動化剤などを含んでもよい。腸溶機能の維持または発現の目的のためには、メタアクリル酸コポリマー、酢酸フタル酸セルロース、カルボキシメチルエチルセルロース、ヒドロキシプロピルメチルセルロースフタレート、ヒドロキシプロピルメチルセルロースアセテートサクシネート、ヒドロキシプロピルメチルセルロースまたはこれらの混合物に可塑剤が添加されたものが用いられ、徐放機能の維持または発現の目的のためには、ヒドロキシエチルセルロース、エチルセルロース、ヒドロキシプロピルメチルセルロースフタレート、ヒドロキシプロピルメチルセルロースアセテートサクシネート、カルボキシビニルポリマーまたはこれらの混合物に可塑剤が添加されたものが用いられる。また、分割後の光安定性の維持を目的として、酸化チタンなどを上記Ｂ層の成分に加えてもよい。 The pharmaceutical additive contained in the B layer and the pharmaceutical additive that may be contained in the A layer and the C layer are pharmaceutically acceptable and do not prevent keeping the tablet shape stable. As long as it is not particularly limited. Specifically, for masking purposes such as bitterness and irritation, for example, crystalline cellulose, lactose, hydroxypropylcellulose, hydroxypropylmethylcellulose, partially pregelatinized starch, starch, erythritol, mannitol, sorbitol, trehalose, light anhydrous Silicic acid or a mixture or granulated product thereof is used, and may further contain a lubricant, a disintegrant, a fluidizing agent, etc. for the purpose of improving the manufacturability, moldability and formulation function. For the purpose of maintaining or developing enteric function, a plasticizer may be added to methacrylic acid copolymer, cellulose acetate phthalate, carboxymethyl ethyl cellulose, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose or mixtures thereof. In order to maintain or develop the sustained release function, a plasticizer is added to hydroxyethyl cellulose, ethyl cellulose, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, carboxyvinyl polymer or a mixture thereof. Is used. Further, for the purpose of maintaining the light stability after the division, titanium oxide or the like may be added to the component of the B layer.
Ａ層やＣ層は、Ｂ層上で分断されている。その分断の幅は、隣接する分断領域との接触が実質的に避けられる程度以上であればよい。すなわち、接触すべきでない複数の薬物が、保存中やＰＴＰシートから取り出すときに、または服用のために手にとったときに互いに接触しない程度以上である。Ａ層やＣ層は分断されているが、各分断領域はいずれもＢ層に固着していることによりＢ層に保持されていて剥離することはない。 The A layer and the C layer are divided on the B layer. The width of the division may be greater than or equal to a degree at which contact with the adjacent division region is substantially avoided. That is, it is more than the extent that a plurality of drugs that should not come into contact do not come into contact with each other during storage, when taken out from a PTP sheet, or when taken for hand. Although the A layer and the C layer are divided, each divided region is held by the B layer because it is fixed to the B layer and does not peel off.
一方、Ａ層やＣ層の各分断領域におけるＢ層との接合面以外の部分の形状は、製造に支障がない限り、全く自由といってよい。例えば直方体状や半球状である。各分断領域の形状は同一である必要はない。またＡ層とＣ層の分断領域の形状は一致する必要はない。 On the other hand, the shape of the portion other than the joint surface with the B layer in each divided region of the A layer and the C layer can be said to be completely free as long as there is no problem in production. For example, a rectangular parallelepiped or hemispherical shape. The shape of each segmented region need not be the same. Further, the shape of the divided regions of the A layer and the C layer need not match.
さらに、図面に沿って本発明錠剤の具体的形態を説明するが、これはあくまでも例示である。図１には、Ｂ層の形状が円盤状で、Ａ層およびＣ層の分断領域の形状は半円柱状である３層錠が示されている。図２の錠剤は、それに対応する２層錠である。図３には、Ｂ層の形状が正四角柱状で、Ａ層の分断領域の形状が直方体状である２層錠が示されている。図４には図３と類似する形状の３層状が示されているが、Ａ層およびＣ層の分断部分の形状が、Ｂ層上の割線と一体化した形状になっている点に特徴がある。図５には、図３の２分割２層錠に対応する４分割２層錠が示されている。ここでは、Ａ層の４つの分断領域は同一形状の正方形柱となっている。図６には、それに対応する３層状が示されている。図７には、図６の錠剤におけるＡ層およびＣ層の分断領域が半球状のものが示されている。なお、図１から図７まではいずれも割線錠が示されているが、それらに対応する割線のない錠剤も本発明に含まれる（第一発明）。 Furthermore, although the specific form of this invention tablet is demonstrated along drawing, this is an illustration to the last. FIG. 1 shows a three-layer tablet in which the shape of the B layer is a disc shape, and the shape of the divided regions of the A layer and the C layer is a semi-cylindrical shape. The tablet of FIG. 2 is a corresponding two-layer tablet. FIG. 3 shows a two-layer tablet in which the shape of the B layer is a regular quadrangular prism and the shape of the segmented region of the A layer is a rectangular parallelepiped shape. FIG. 4 shows a three-layer shape similar to that in FIG. 3, but the feature is that the shape of the divided portions of the A layer and the C layer is integrated with the dividing line on the B layer. is there. FIG. 5 shows a 4-split 2-layer tablet corresponding to the 2-split 2-layer tablet of FIG. Here, the four divided areas of the A layer are square pillars having the same shape. FIG. 6 shows a corresponding three-layer shape. FIG. 7 shows that the divided regions of the A layer and the C layer in the tablet of FIG. 6 are hemispherical. In addition, although FIG. 1 to FIG. 7 all show a scored tablet, a tablet without a scored line corresponding to them is also included in the present invention (first invention).
Ａ層の薬物と、Ｂ層が薬物を含む場合の薬物と、Ｃ層がある場合のＣ層の薬物はそれぞれ異なっていてもよい。かかる活性成分たる薬物は、通常の製造方法で本発明の錠剤となしうるものである限り、特に限定はないが、例えば中枢神経系用薬、末梢神経系用薬、循環器官用薬、消化器官用薬、ホルモン剤、泌尿生殖器官用薬、血液・体液用薬、代謝性医薬品、痛風治療薬、腫瘍用薬、アレルギー用薬、気管支拡張剤、抗生物質、抗細菌薬、抗ウイルス薬、創傷治癒物質、鎮痙剤、抗コリン作用剤、抗ヒスタミン剤、抗炎症剤、抗コレステロール血剤、抗脂質剤、食欲抑制剤、興奮剤、凝血剤、制酸剤、化学療法剤、栄養補給剤、診断薬、麻薬・覚醒剤、鎮痛剤、鎮咳剤、喀痰剤等から選ばれる１種または２種以上の活性成分が挙げられる。さらに具体的には、例えば、アスコルビン酸、アセトアミノフェン、エテンザミド、塩酸アンブロキソール、アレンドロネート、フェブキソスタット、塩酸クレンブテロール、イコサペント酸エチル、タカルシトール、ピコスルファート、アルファカルシドール、国際公開ＷＯ９９／２６９１８号記載の化合物、国際公開ＷＯ０１／５３２９１記載の化合物、国際公開ＷＯ９９／２５６８６号記載の化合物およびこれらの塩および／または水和物からなる群から選ばれる１種または２種以上の活性成分が挙げられる。ここで、Ａ層の薬物とＢ層が薬物を含む場合のＢ層の薬物、あるいはＣ層がある場合のＣ層の薬物とＢ層が薬物を含む場合のＢ層の薬物は、相互に接触しても不都合を生じない組合せであることが望ましい。なお、典型的には、Ｂ層は薬物を含まない。 The drug in the A layer, the drug in the case where the B layer contains the drug, and the drug in the C layer in the case where the C layer is present may be different from each other. The drug as the active ingredient is not particularly limited as long as it can be made into the tablet of the present invention by a usual production method. For example, drugs for central nervous system, drugs for peripheral nervous system, drugs for cardiovascular organs, digestive organs Drugs, hormone drugs, urogenital drugs, blood and body fluid drugs, metabolic drugs, gout treatment drugs, tumor drugs, allergy drugs, bronchodilators, antibiotics, antibacterial drugs, antiviral drugs, wounds Healing substance, antispasmodic agent, anticholinergic agent, antihistamine, anti-inflammatory agent, anticholesterolemia agent, antilipid agent, appetite suppressant, stimulant agent, coagulant agent, antacid, chemotherapeutic agent, nutritional supplement, diagnostic agent, Examples thereof include one or more active ingredients selected from narcotics / stimulants, analgesics, antitussives, antiepileptics and the like. More specifically, for example, ascorbic acid, acetaminophen, etenzaamide, ambroxol hydrochloride, alendronate, febuxostat, clenbuterol hydrochloride, ethyl icosapentate, tacalcitol, picosulfate, alphacalcidol, international publication WO99 One or two or more kinds of active ingredients selected from the group consisting of compounds described in Japanese Patent No./26918, compounds described in International Publication WO01 / 53291, compounds described in International Publication WO99 / 25686, and salts and / or hydrates thereof Is mentioned. Here, the drug in the B layer when the drug in the A layer and the B layer contain the drug, or the drug in the B layer when the B layer contains the drug and the drug in the B layer when the C layer is in contact with each other It is desirable that the combination does not cause any inconvenience. Typically, layer B does not contain a drug.
一方、第一発明にはＡ層またはＣ層の少なくとも一つの分断領域に含まれる薬物が、Ａ層またはＣ層の他の領域に含まれる薬物と接触すべきでない他の薬物である実施態様がある。 On the other hand, the first invention has an embodiment in which the drug contained in at least one divided region of the A layer or the C layer is another drug that should not come into contact with the drug contained in the other region of the A layer or the C layer. is there.
これを図８の錠剤について説明する。仮に、薬物Ｐと薬物Ｑが接触すべきでないものとする。図８の錠剤ではＡ層の二つの分断領域に薬物Ｐが配置され、他の二つの分断領域に薬物Ｑが配置されている。すなわち、これらの薬物は錠剤中に分離されて安定的に保持されている。３層錠である図９の錠剤の右半分では、薬物Ｐと薬物ＱがＢ層を隔ててＡ層とＣ層の対応する分断領域に位置しており、同様な効果を奏している。 This will be described for the tablet of FIG. Suppose that drug P and drug Q should not contact. In the tablet of FIG. 8, the drug P is arranged in the two divided areas of the A layer, and the drug Q is arranged in the other two divided areas. That is, these drugs are separated and retained stably in the tablet. In the right half of the tablet of FIG. 9 which is a three-layer tablet, the drug P and the drug Q are located in the corresponding divided regions of the A layer and the C layer across the B layer, and the same effect is exhibited.
ここで、接触すべきでない薬物の組合せとしては、例えばコデインとアスピリン、トリメタジオンとエトトインがある。その理由はそれぞれ、エステル転移反応、湿潤・液化、という不都合を生じるからである。また、これ以外のも加水分解や酸化を受けやすい薬物は、酸性薬物や塩基性薬物に触媒されることにより変質する。加水分解されやすい薬物としては、塩酸プロカイン、ワルファリン、ベンジルペニシリン、フェノバルビタール、ジアゼパムなどがあり、酸化されやすいものとしては、エピネフリン、アスコルビン酸、トコフェロール、カプトリル、スルピリンなどがある。
かかる第一発明の構成により、配合性の悪い２種類以上の薬物を相互に接触することなく１錠中に配合できるという効果が得られる。
Here, examples of combinations of drugs that should not be contacted include codeine and aspirin, and trimetadione and etotoin. The reason is that inconveniences such as transesterification, wetting and liquefaction occur. In addition, other drugs that are susceptible to hydrolysis and oxidation are altered by being catalyzed by acidic drugs and basic drugs. Drugs that are easily hydrolyzed include procaine hydrochloride, warfarin, benzylpenicillin, phenobarbital, diazepam, and the like, and those that are easily oxidized include epinephrine, ascorbic acid, tocopherol, captolyl, and sulpyrine.
According to the configuration of the first invention, an effect that two or more drugs having poor compoundability can be formulated in one tablet without contact with each other is obtained.
第二発明は上記第一発明において、さらにＢ層の片面もしくは両面に一つ以上の割線があり、Ａ層、およびＣ層がある場合のＣ層の分断部位がＢ層上の割線のある部位もしくはその裏面の対応部位である割線錠である。 The second invention is the above-mentioned first invention, wherein there is one or more secant lines on one or both sides of the B layer, and when the A layer and the C layer are present, the segmented part of the C layer is the part with the secant line on the B layer Or it is a scored lock which is a corresponding part of the back surface.
ここで、錠剤の大きさや形状はこの場合であっても基本的に第一発明について前述した通りであるが、大きさが割線錠として分割するのに不適当なほど小さくなく、厚みについても分割を妨げるほどでない必要がある。Ｂ層の形状や、Ａ層やＣ層の各分断領域におけるＢ層との接合面以外の部分の形状も第一発明について前述した通りであるが、いずれも割線部位のみでの切断に支障があるものであってはならない。 Here, the size and shape of the tablet is basically the same as described above for the first invention even in this case, but the size is not small enough to be divided as a scored tablet, and the thickness is also divided. It should not be so high as to interfere. The shape of the B layer and the shape of the portion other than the joint surface with the B layer in each segmented region of the A layer and the C layer are also as described above for the first invention. It must not be.
第二発明においては、Ｂ層の片面もしくは両面には一つ以上の割線がつけてある。割線は割溝と表現されることもあるが、本明細書では割溝も含めて「割線」と総称する。錠剤に割線をつけること、およびその一般的形状は既にこの分野の技術常識となっている。したがって、患者や薬剤師らが錠剤全体を困難なく分割できるものである限り本発明における割線の形状は特に限定されず、当業者であれば技術常識に基づき容易に形成することができる。具体的には上記特許文献中に開示された割線の形状を例示することができる。なお、複数の割線を有する錠剤の場合には、分割を意図した割線のみで分割できるように構成する必要があるが、これも当業者にとって格別の困難はない。 In the second invention, one or more secant lines are attached to one side or both sides of the B layer. Although the dividing line may be expressed as a dividing groove, in this specification, the dividing line and the dividing line are collectively referred to as a “dividing line”. Making a score line on a tablet and its general shape are already common technical knowledge in this field. Therefore, as long as patients and pharmacists can divide the whole tablet without difficulty, the shape of the secant in the present invention is not particularly limited, and those skilled in the art can easily form it based on common technical knowledge. Specifically, the shape of the secant disclosed in the above patent document can be exemplified. In the case of a tablet having a plurality of secant lines, it is necessary to configure the tablet so that it can be divided only by the dividing line intended to be divided, but this is also not particularly difficult for those skilled in the art.
Ａ層やＣ層は、Ｂ層上の割線のある部位もしくはその裏面の対応部位によって分断されている。「その裏面の対応部位」とは、Ｂ層上のある割線が片面にのみ刻まれている場合において、Ｂ層上の当該割線のない面における対応部位を意味する。 The A layer and the C layer are divided by a part having a dividing line on the B layer or a corresponding part on the back surface thereof. The “corresponding portion on the back surface” means a corresponding portion on the surface without the dividing line on the B layer when a certain dividing line on the B layer is carved only on one side.
図１０の左上には割線のない２層錠が、左下にはＡ層が割線のある部位によって分断されている２層錠が、右上にはＡ層が割線のある部位の裏面の対応部位によって分断されている２層錠が、右下にはＢ層の両面に割線があり、Ａ層がその部位で分断されている２層錠が示されている。
なお、Ａ層やＣ層の分断領域は、Ｂ層上、割線よって区切られる領域（割線が片面のみにある場合における割線のない面の対応部位によって区切られる領域を含む）すべてに存在しなくてもよい。
In the upper left of FIG. 10 is a two-layer tablet without a dividing line, in the lower left is a two-layer tablet in which the A layer is divided by a part with a dividing line, and in the upper right is a corresponding part on the back of the part with a dividing line. The two-layer tablet which is divided is shown in the lower right, and there are secant lines on both sides of the B layer, and the two-layer tablet in which the A layer is divided at that site.
In addition, the division | segmentation area | region of A layer and C layer does not exist in all the area | regions (including the area | region divided by the corresponding part of the surface without a dividing line in the case where a dividing line exists only on one side) on the B layer. Also good.
第二発明における分断の幅は、前述した第一発明のそれでは必ずしも足りない。錠剤を割線部位で分割すると必ずしも一定の割れ方とはならず、若干のばらつきが生ずるのを避けられない。したがって、Ａ層やＣ層の分断領域は、割線の機能の妨げにならないのみならず、分割のばらつきの影響を受けない程度に割線のある部位もしくはその裏面の対応部位から離れている必要がある。「Ｂ層上の割線のある部位もしくはその裏面の対応部位によって分断」とは、そのために十分な幅をもって分断されていることを意味する。このことが、分割時に薬物量のばらつきを生ぜず、正確に分割できる効果につながる。 The width of the division in the second invention is not necessarily sufficient as that of the first invention described above. When a tablet is divided at a secant part, it does not necessarily become a certain cracking method, and it is inevitable that some variation occurs. Therefore, the dividing regions of the A layer and the C layer need not only interfere with the function of the dividing line but also need to be separated from the part having the dividing line or the corresponding part on the back surface thereof so as not to be affected by the variation in division. . “Divided by a part having a dividing line on the B layer or a corresponding part on the back surface thereof” means that the material is divided with a sufficient width. This leads to an effect that the drug amount can be accurately divided without causing variations in the drug amount at the time of division.
かかる第二発明によれば、分割することにより、分割前の錠剤が保持していた複数の薬物のうち一部を保持する断片を与える割線錠が得られる。
特に一組以上の接触すべきでない２種の薬物が、各組ともＢ層を隔ててＡ層とＣ層の対応する分断領域に位置している三層の割線錠を作成すれば、分割後も、接触すべきでない２種の薬物が、Ｂ層を隔ててＡ層とＣ層の対応する分断領域に位置している状態が維持される。すなわち、分割後の断片中でもそれらの接触すべきでない２種の薬物が安定的に保持される効果を奏するのである。
According to the second invention, a scored tablet is obtained that gives a fragment that holds a part of a plurality of drugs held by the tablet before the division by dividing.
In particular, if one set or more of two types of drugs that should not be contacted, each group is separated from the B layer and a three-layer scored tablet is located in the corresponding split region of the A and C layers. However, the state in which the two kinds of drugs that should not be in contact with each other are located in the corresponding divided regions of the A layer and the C layer across the B layer is maintained. That is, there is an effect that the two kinds of drugs that should not be brought into contact with each other in the fragments after the division are stably maintained.
これを図１１の錠剤について説明する。仮に、薬物Ｐと薬物Ｑが接触すべきものでなく、薬物Ｒと薬物Ｓも接触すべきものでないとする。図１１の錠剤では、２組の接触すべきでない２種の薬物が、各組ともＢ層を隔ててＡ層とＣ層の対応する分断領域に位置しており、分割後もその状態が維持される。なお、図１１の錠剤では、薬物Ｐは二つの分断領域に存在しているが、いずれも同一の層（Ａ層）に位置している。 This will be described for the tablet of FIG. Assume that the drug P and the drug Q are not to be contacted, and the drug R and the drug S are not to be contacted. In the tablet of FIG. 11, two sets of two types of drugs that should not be contacted are located in the corresponding divided regions of the A layer and the C layer with the B layer separated from each other, and the state is maintained even after the division. Is done. In the tablet of FIG. 11, the drug P exists in two divided regions, but both are located in the same layer (A layer).
一方、第二発明の他の実施態様は、接触すべきでない各組の２種の薬物がいずれも同じ層に位置している割線錠である。この場合には、Ａ層やＣ層における薬物の配置と割線との位置関係により、分割すると接触すべきでない２種の薬物が異なる断片に分離される割線錠が得られる。この中には、Ｃ層の分断領域のすべてにおいて、Ｂ層を隔てて対応するＡ層の薬物と同一の薬物を含有している三層の割線錠が含まれる。典型的には、第二発明における接触すべきでない２種の薬物の組数は一組であり、なかでも錠剤中にかかる一組の薬物以外の薬物を含まない割線錠がさらに典型的である。このような割線錠は、処方の際の融通性を高める効果がある。 On the other hand, another embodiment of the second invention is a scored tablet in which each of two sets of two drugs that should not be contacted is located in the same layer. In this case, it is possible to obtain a scored tablet in which two types of drugs that should not be contacted when separated are separated into different fragments depending on the positional relationship between the arrangement of the drugs in the A layer and the C layer and the score line. This includes a three-layer scored tablet containing the same drug as the corresponding drug in the A layer across the B layer in all of the divided regions of the C layer. Typically, the number of sets of two kinds of drugs that should not be contacted in the second invention is one set, and among them, a scored tablet that does not contain any drug other than the set of drugs in the tablet is more typical. . Such a scored tablet has the effect of increasing flexibility during prescription.
その一例が図１２に示される錠剤である。この錠剤では、薬物Ｐと薬物Ｑはいずれも同じ層（Ａ層およびＣ層）に位置している。そして、Ｃ層の分断領域のすべてにおいて、Ｂ層を隔てて対応するＡ層の薬物と同一の薬物が配置されている。この錠剤では接触すべきでない２種の薬物の組数は一組である。そして、Ａ層およびＣ層には接触すべきでない薬物以外の薬物を含まない。この錠剤を図面上で上下方向の割線に従って分割すると、薬物Ｐのみを含む断片と、薬物Ｑのみを含む断片が得られる。一方、この錠剤を図面上で左右方向の割線に従って分割すると、薬物Ｐと薬物Ｑのそれぞれ半量が分離されて安定的に保持されている断片が得られる。 One example is the tablet shown in FIG. In this tablet, both drug P and drug Q are located in the same layer (A layer and C layer). And in all the division | segmentation area | regions of C layer, the drug same as the drug of A layer which respond | corresponds across B layer is arrange | positioned. In this tablet, there is one set of two drugs that should not be contacted. The A layer and the C layer do not contain drugs other than drugs that should not be contacted. When this tablet is divided according to the vertical dividing line in the drawing, a fragment containing only drug P and a fragment containing only drug Q are obtained. On the other hand, when this tablet is divided according to the secant line in the left-right direction on the drawing, a half of each of the drug P and drug Q is separated and stably held.
第三発明はＡ層とＢ層とからなる二層錠、またはＡ層、Ｂ層、Ｃ層の順に三層をなしている三層錠であって、
該Ｂ層は、薬物を含んでいてもよい医薬添加物層であって、その片面もしくは両面に一つ以上の割線を有しており、
該Ａ層は医薬添加物を含んでいてもよい薬物層であって、Ｂ層上の割線のある部位もしくはその裏面の対応部位によって分断されており、
該Ａ層の分断された各部分はＢ層に固着していることにより保持されていて、それぞれ同一もしくは異なる薬物を含有しており、
さらにＣ層を有する場合の該Ｃ層も医薬添加物を含んでいてもよい薬物層であって、Ｂ層上の割線のある部位もしくはその裏面の対応部位によって分断されており、
該Ｃ層の分断された各部分はＢ層に固着していることにより保持されていて、それぞれ同一もしくは異なる薬物を含有しており、
Ａ層またはＣ層の少なくとも一つの領域に含まれる薬剤は、同じ層の他の領域に含まれる薬剤と同一ではなく、かつ少なくとも一つの割線に従って錠剤を分割すれば、一種類の薬物のみを含む断片が得られるようＡ層またはＣ層の薬物が配置された錠剤である。
The third invention is a two-layer tablet consisting of A layer and B layer, or a three-layer tablet comprising three layers in the order of A layer, B layer, C layer,
The B layer is a pharmaceutical additive layer that may contain a drug, and has one or more secant lines on one or both sides thereof,
The A layer is a drug layer that may contain a pharmaceutical additive, and is divided by a part having a secant on the B layer or a corresponding part on the back surface thereof,
Each divided part of the A layer is retained by being fixed to the B layer, and each contains the same or different drug,
In addition, the C layer in the case of having the C layer is a drug layer that may contain a pharmaceutical additive, and is divided by a part having a dividing line on the B layer or a corresponding part on the back surface thereof,
Each divided portion of the C layer is retained by being fixed to the B layer, and each contains the same or different drug,
The drug contained in at least one region of the A layer or C layer is not the same as the drug contained in other regions of the same layer, and contains only one kind of drug if the tablet is divided according to at least one secant. It is a tablet in which drugs of layer A or layer C are arranged so that fragments can be obtained.
第三発明における、錠剤全体の大きさや形状、「Ａ層」、「Ｂ層」、「Ｃ層」、「医薬添加物」、「割線」、「割線のある部位もしくはその裏面の対応部位によって分断」の意義は、割線錠について前述したものと同様である。薬物については、「接触すべきでない」といった制限はないが、接触すべきでない複数の薬物を異なる分断領域、例えば同じ層の他の分断領域に含んでいてもよい。この場合には、分割前であっても配合性の悪い２種類以上の薬物を相互に接触することなく１錠中に配置できるという効果が加わる。 In the third invention, the size and shape of the whole tablet, “A layer”, “B layer”, “C layer”, “pharmaceutical additive”, “secant”, “part with the secant or corresponding part on the back side thereof The meaning of “” is the same as that described above for the scored lock. The drug is not limited to “not to be contacted”, but a plurality of drugs that should not be contacted may be included in different divided regions, for example, other divided regions in the same layer. In this case, there is an effect that two or more kinds of drugs having poor compoundability can be arranged in one tablet without contacting each other even before division.
ここで、「Ａ層またはＣ層の少なくとも一つの領域に含まれる薬剤は、同じ層の他の領域に含まれる薬剤と同一ではなく、かつ少なくとも一つの割線に従って錠剤を分割すれば、一種類の薬物のみを含む断片が得られるようＡ層またはＣ層の薬物が配置」することは、当業者であれば容易に定めうることである。典型的にはＢ層は薬物を含まない。かかる薬剤は、分割前には複数種類の薬剤を同時に服用できる錠剤であるのに対し、分割後には一種類の薬物のみを含む断片が得られるなど、処方の際の融通性を高める効果を奏する。
その具体例としては、前述した図８、図９、図１２の錠剤が挙げられる。
Here, “the drug contained in at least one region of the A layer or the C layer is not the same as the drug contained in the other region of the same layer and if the tablet is divided according to at least one secant, It can be easily determined by those skilled in the art that the drug of the A layer or the C layer is arranged so that a fragment containing only the drug can be obtained. Typically, layer B contains no drug. Such a drug is a tablet that can be used simultaneously with a plurality of types of drugs before splitting, whereas a fragment containing only one type of drug can be obtained after splitting, which has the effect of increasing flexibility during prescription. .
Specific examples thereof include the tablets shown in FIGS. 8, 9 and 12 described above.
さらに、本発明の錠剤は、被覆層を有していてもよい。かかる被覆層は、例えば、口腔内もしくは食道での薬物の接触が患者の不利益になることを避ける機能を有する。かかる患者の不利益としては、例えば苦み等の不快な味や不快臭、刺激、口腔内での意図しない薬物吸収による副作用、または口腔内もしくは食道での薬物の溶解による副作用が挙げられる。このほか、被覆は不溶性、速溶性、速崩壊性、腸溶性、徐放性、時限放出性といった薬物放出制御機能の付与、水分や湿気に対する安定化、投与後に接する胃液や酵素等の生体内成分に対する安定化、あるいは光安定性の目的でも施される。 Furthermore, the tablet of the present invention may have a coating layer. Such a covering layer has a function of avoiding a disadvantage of the patient from contacting the drug in the oral cavity or the esophagus, for example. Such patient disadvantages include, for example, unpleasant tastes and unpleasant odors such as bitterness, irritation, side effects due to unintentional drug absorption in the oral cavity, or side effects due to dissolution of the drug in the oral cavity or esophagus. In addition, the coating is insoluble, fast-dissolving, fast-disintegrating, enteric, sustained-release, timed-release drug release control function, stabilization against moisture and moisture, in vivo components such as gastric juice and enzymes that come into contact after administration It is also applied for the purpose of stabilization against light or light stability.
不快な味や不快臭のマスキングのためには、例えばヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロースが、腸溶性の付与のためには、例えばメタアクリル酸コポリマー、酢酸フタル酸セルロース、カルボキシメチルエチルセルロース、ヒドロキシプロピルメチルセルロースフタレート、ヒドロキシプロピルメチルセルロースアセテートサクシネート、ヒドロキシプロピルメチルセルロースまたはこれらの混合物に可塑剤が添加されたものが、徐放性の付与のためには、例えばヒドロキシエチルセルロース、エチルセルロース、ヒドロキシプロピルメチルセルロースフタレート、ヒドロキシプロピルメチルセルロースアセテートサクシネート、カルボキシビニルポリマーまたはこれらの混合物に可塑剤が添加されたものが、水分等に対する安定化のためにはエチルセルロース、メタアクリル酸コポリマー、セラック、ポリビニルアセタールジエチルアミノアセテートが用いられる。また、胃液や酵素などの生体内成分に対する安定化のためにはマスキング、腸溶性、徐放性機能をもつ医薬品添加物を単独あるいは組合せて使用し、光安定性の目的のためにはこれらのコーティング基材の中に酸化チタンなどを添加する。かかる被覆層は種類の異なるもの複数層であってもよい。 For masking unpleasant taste and unpleasant odor, for example, hydroxypropyl cellulose and hydroxypropyl methylcellulose are used, and for providing enteric properties, for example, methacrylic acid copolymer, cellulose acetate phthalate, carboxymethylethyl cellulose, hydroxypropyl methylcellulose. For example, hydroxyethyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose, which is obtained by adding a plasticizer to phthalate, hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose, or a mixture thereof. A plasticizer added to acetate succinate, carboxyvinyl polymer or a mixture thereof, Ethylcellulose For stabilization against minute, etc., methacrylic acid copolymer, shellac, polyvinyl acetal diethylamino acetate is used. In addition, pharmaceutical additives with masking, enteric, and sustained-release functions can be used alone or in combination for stabilization of in vivo components such as gastric juice and enzymes, and for the purpose of photostability, these additives can be used. Titanium oxide or the like is added into the coating substrate. Such a coating layer may be a plurality of different types of layers.
なお、被覆層を有する割線錠の場合において、被覆層のもつ効果の維持のためには、分割後も割線のある部位もしくはその裏面の対応部位近傍のＢ層上に被覆層が残り、Ａ層やＣ層の分断された各部分がＢ層または被覆層に接していて露出することがない程度に、割線のある部位もしくはその裏面の対応部位から離れていることが望ましい。そのような被覆状態の一例が、図１３に示されている。さらに、分割後に露出するＢ層の医薬添加物の特性は、不溶性であるか、または当該被覆層と同種の特性であることが、分割後における被覆層の効果維持のためには望ましい。 In the case of a scored tablet having a coating layer, in order to maintain the effect of the coating layer, the coating layer remains on the B layer in the vicinity of the part with the dividing line or the corresponding part on the back side after the division, and the A layer In addition, it is desirable that the divided portions of the C layer and the C layer are separated from the part where the secant line is located or the corresponding part on the back surface thereof so that the portions which are in contact with the B layer or the coating layer are not exposed. An example of such a covering state is shown in FIG. Furthermore, it is desirable for maintaining the effect of the coating layer after the division that the properties of the pharmaceutical additive of the B layer exposed after the division are insoluble or the same kind of properties as the coating layer.
図１４、図１５、図１６、図１７、図１８、図１９は、それぞれ前記の図１、図２、図３、図４、図５、図６の錠剤の被覆錠を示す。図２０には前記の図７の錠剤に対応する２層錠の被覆錠を示す。
なお、本発明の効果に類似する効果をもつ錠剤は、いわゆる有核錠とすることでも得られる場合がある。しかしながら、本発明の錠剤と同様の効果を有する有核錠を製造するためにはより高度な製造技術を要する。また、有核錠の製造工程ではロスが多く、速度を上げられない。したがって、有核錠では高コストの問題を避けることができない。
14, FIG. 15, FIG. 16, FIG. 17, FIG. 18, and FIG. 19 show the coated tablets of the tablets of FIG. 1, FIG. 2, FIG. 3, FIG. FIG. 20 shows a two-layered coated tablet corresponding to the tablet of FIG.
In addition, the tablet which has an effect similar to the effect of this invention may be obtained also by using what is called a dry-coated tablet. However, in order to produce a dry-coated tablet having the same effect as the tablet of the present invention, a more advanced production technique is required. In addition, the manufacturing process of the dry-coated tablet is lossy and the speed cannot be increased. Therefore, high cost problems cannot be avoided with dry tablets.
次に、本発明を実施例を用いて説明するが、本発明はこれらによって限定されるものではない。 Next, although this invention is demonstrated using an Example, this invention is not limited by these.
実施例１：（多層錠法）上層充填 → 下層充填 → 圧縮成型
打錠機（畑鐵工製 ＨＴ−ＡＰ６ＳＳ−Ｕ）に楕円型杵臼（富士薬品機械製 Ｆ−Ｊ０３９２−１上杵割線入り）を装着した。この臼にダイラクトーズＲ（フロイント製）にステアリン酸マグネシウム０．５％を混合したものを８０ｍｇ充填し、上層にダイラクトーズＲ（フロイント製）にＨＰＣ−Ｌと青色１号で着色した粉体を３０ｍｇ充填した。これを、与圧杵先間隔１．５６ｍｍ 本圧杵先間隔１．３５から１．４０ｍｍで圧縮成型することにより特殊割線杵の割線部分で主薬層が分断された錠剤が得られた。
Example 1: (Multilayer tablet method) Upper layer filling-> Lower layer filling-> Compression molding Tablet press (HT-AP6SS-U, manufactured by Hata Seiko Co., Ltd.) Ellipse-shaped mortar (F-J0392-1, upper split line, manufactured by Fuji Pharmaceutical) Attached. This mill is filled with 80 mg of Dilacto's R (Freund) mixed with 0.5% magnesium stearate, and the upper layer is filled with 30 mg of powder colored with HPC-L and Blue No. 1 in Dilactos R (Freund). did. This was compression-molded at a pressure point distance of 1.56 mm and a pressure point distance of 1.35 to 1.40 mm to obtain a tablet in which the main drug layer was divided at the secant part of the special score line bar.
実施例２：（多層錠法）上層充填 → 下層充填 → 圧縮成型
打錠機（畑鐵工製 ＨＴ−ＡＰ６ＳＳ−Ｕ）に楕円型杵臼（富士薬品機械製 Ｆ−Ｊ０３９２−１上杵割線入り）を装着した。この臼にダイラクトーズＲ（フロイント製）にステアリン酸マグネシウム０．５％を混合したものを８０ｍｇ充填し、上層にダイラクトーズＲ（フロイント製）とアスコルビン酸ナトリウムとステアリン酸マグネシウムを混合した粉体を３０ｍｇ充填した。これを、与圧杵先間隔１．５６ｍｍ 本圧杵先間隔１．３５から１．４０ｍｍで圧縮成型することにより特殊割線杵の割線部分で主薬層が分断された錠剤が得られた。
Example 2: (Multi-layer tablet method) Upper layer filling → Lower layer filling → Compression molding Tablet press (HT-AP6SS-U, manufactured by Hata Seiko Co., Ltd.) with an elliptical tool (F-J0392-1, with an upper score line) Attached. This mill is filled with 80 mg of Dilacto's R (Freund) mixed with 0.5% magnesium stearate, and the upper layer is filled with 30 mg of powder mixed with Dilactos R (Freund), sodium ascorbate and magnesium stearate. did. This was compression-molded at a pressure point distance of 1.56 mm and a pressure point distance of 1.35 to 1.40 mm to obtain a tablet in which the main drug layer was divided at the secant part of the special score line bar.
実施例３
アスコルビン酸ナトリウム、乳糖、部分アルファー化デンプン、ヒドロキシプロピルセルロースからなる顆粒と乳糖、部分アルファー化デンプン、ヒドロキシプロピルセルロースからなる顆粒に、それぞれクロスカルメロースナトリウム、ステアリン酸マグネシウムを混合し打錠用粉体とした。
Example 3
Powder for tableting by mixing croscarmellose sodium and magnesium stearate into granules composed of sodium ascorbate, lactose, partially pregelatinized starch, hydroxypropylcellulose and granules composed of lactose, partially pregelatinized starch, and hydroxypropylcellulose. It was.
打錠機（畑鐵工製 ＨＴ−ＡＰ６ＳＳ−Ｕ）に特殊オーバル錠杵臼（富士薬品機械製 上杵Ｆ−Ｊ０３７５ 下杵Ｆ−Ｊ０３７４）を装着した。この臼の下層に、フェブキソスタットを含まない打錠用粉体を１２０ｍｇ充填し、さらに上層にフェブキソスタットを含む打錠用粉体を３０ｍｇ充填し、圧縮成型することにより特殊割線杵の割線部分で主薬層が分断された錠剤が得られた。 A special oval tablet mortar (upper F-J0375, lower punch F-J0374, manufactured by Fuji Yakuhin Kikai Co., Ltd.) was attached to a tableting machine (HT-AP6SS-U, manufactured by Hata Seiko). The lower part of this mortar is filled with 120 mg of tableting powder not containing febuxostat, and the upper layer is filled with 30 mg of tableting powder containing febuxostat and compression molded, so that the score line of the special scorer A tablet in which the main drug layer was divided at a part was obtained.
実施例４
フェブキソスタット、乳糖、部分アルファー化デンプン、ヒドロキシプロピルセルロースからなる顆粒と乳糖、部分アルファー化デンプン、ヒドロキシプロピルセルロースからなる顆粒に、それぞれクロスカルメロースナトリウム、ステアリン酸マグネシウムを混合し打錠用粉体とした。
Example 4
Powder for tableting by mixing croscarmellose sodium and magnesium stearate into granules of febuxostat, lactose, partially pregelatinized starch and hydroxypropylcellulose, and lactose, partially pregelatinized starch and hydroxypropylcellulose, respectively. It was.
打錠機（畑鐵工製 ＨＴ−ＡＰ６ＳＳ−Ｕ）に特殊オーバル錠杵臼（富士薬品機械製 上杵Ｆ−Ｊ０３７５ 下杵Ｆ−Ｊ０３７４）を装着した。この臼の下層に、フェブキソスタットを含まない打錠用粉体を１２０ｍｇ充填し、さらに上層にフェブキソスタットを含む打錠用粉体を３０ｍｇ充填し、圧縮成型することにより特殊割線杵の割線部分で主薬層が分断された錠剤が得られた。 A special oval tablet mortar (upper F-J0375, lower punch F-J0374, manufactured by Fuji Yakuhin Kikai Co., Ltd.) was attached to a tableting machine (HT-AP6SS-U, manufactured by Hata Seiko). The lower part of this mortar is filled with 120 mg of tableting powder not containing febuxostat, and the upper layer is filled with 30 mg of tableting powder containing febuxostat and compression molded, so that the score line of the special scorer A tablet in which the main drug layer was divided at a part was obtained.
実施例５：（多層錠法）上層充填 → 下層充填 → 圧縮成型 → コーティング
打錠機（畑鉄工製 ＨＴ−ＡＰ６ＳＳＵ）に楕円型杵臼（富士薬品機械製 Ｆ−Ｊ０３９２−１上杵割線入り）を装着した。この臼にダイラクトーズＲ（フロイント製）にステアリン酸マグネシウム０．５％を混合したものを８０ｍｇ充填し、上層にダイラクトーズＲ（フロイント製）にＨＰＣ−Ｌと青色１号で着色した粉体を３０ｍｇ充填した。これを、与圧杵先間隔１．５６ｍｍ 本圧杵先間隔１．３５から１．４０ｍｍで圧縮成型することにより特殊割線杵の割線部分で上層が分断された錠剤が得られた。
Example 5: (Multilayer tablet method) Upper layer filling → Lower layer filling → Compression molding → Coating A tableting machine (HT-AP6SSU made by Hata Tekko Co., Ltd.) with an elliptical mortar (F-J0392-1 made with an upper score line) Installed. This mill is filled with 80 mg of Dilacto's R (Freund) mixed with 0.5% magnesium stearate, and the upper layer is filled with 30 mg of powder colored with HPC-L and Blue No. 1 in Dilactos R (Freund). did. This was compression-molded at a pressing tip distance of 1.56 mm and a main pressing tip distance of 1.35 to 1.40 mm to obtain a tablet in which the upper layer was divided at the secant portion of the special scorer.
この錠剤を、コーティング機（ハイコーターミニ フロイント製）を用いてフィルムコーティングを行った。運転条件は、吸気６８から７４℃、排気温度４４から５０℃、パン回転数２０から３０ｒｐｍ、アトマイズエアー６０ＮＬ／ｍｉｎ、パターンエアー３０ＮＬ／ｍｉｎで、コーティング液（６％ＨＰＭＣ ＴＣ−５ ０．１２％ＰＥＧ ６０００Ｐ水溶液）を２３３ｇ噴霧後、乾燥した。 The tablets were subjected to film coating using a coating machine (manufactured by Highcoater Mini Freund). The operating conditions were intake air 68 to 74 ° C., exhaust temperature 44 to 50 ° C., pan rotation speed 20 to 30 rpm, atomizing air 60 NL / min, pattern air 30 NL / min, and coating liquid (6% HPMC TC-5 0.12% PEG 6000P aqueous solution) was sprayed and dried.
実施例６：（多層錠法）上層充填 → 下層充填 → 圧縮成型 → コーティング
打錠機（畑鉄工製 ＨＴ−ＡＰ６ＳＳＵ）に楕円型杵臼（富士薬品機械製 Ｆ−Ｊ０３９２−１上杵割線入り）を装着した。この臼にダイラクトーズＲ（フロイント製）にステアリン酸マグネシウム０．５％を混合したものを８０ｍｇ充填し、上層にダイラクトーズＲ（フロイント製）とアスコルビン酸ナトリウムとステアリン酸マグネシウムを混合した粉体を３０ｍｇ充填した。これを、与圧杵先間隔１．５６ｍｍ 本圧杵先間隔１．３５から１．４０ｍｍで圧縮成型することにより特殊割線杵の割線部分で上層が分断された錠剤が得られた。
Example 6: (Multilayer tablet method) Upper layer filling → Lower layer filling → Compression molding → Coating A tableting machine (HT-AP6SSU made by Hata Tekko Co., Ltd.) with an elliptical tool (F-J0392-1 upper score line made by Fuji Pharmaceutical) Installed. This mill is filled with 80 mg of Dilacto's R (Freund) mixed with 0.5% magnesium stearate, and the upper layer is filled with 30 mg of powder mixed with Dilactos R (Freund), sodium ascorbate and magnesium stearate. did. This was compression-molded at a pressing tip distance of 1.56 mm and a main pressing tip distance of 1.35 to 1.40 mm to obtain a tablet in which the upper layer was divided at the secant portion of the special scorer.
この錠剤を、コーティング機（ハイコーターミニ フロイント製）を用いてフィルムコーティングを行った。運転条件は、吸気６８から７４℃、排気温度４４から５０℃、パン回転数２０から３０ｒｐｍ、アトマイズエアー６０ＮＬ／ｍｉｎ、パターンエアー３０ＮＬ／ｍｉｎで、コーティング液（６％ＨＰＭＣ ＴＣ−５ ０．１２％ＰＥＧ ６０００Ｐ水溶液）を２３３ｇ噴霧後、乾燥した。 The tablets were subjected to film coating using a coating machine (manufactured by Highcoater Mini Freund). The operating conditions were intake air 68 to 74 ° C., exhaust temperature 44 to 50 ° C., pan rotation speed 20 to 30 rpm, atomizing air 60 NL / min, pattern air 30 NL / min, and coating liquid (6% HPMC TC-5 0.12% PEG 6000P aqueous solution) was sprayed and dried.
本発明は、医薬品製造のために利用される。 The present invention is used for pharmaceutical manufacture.
Claims (14)
該Ｂ層は、薬物を含んでいてもよい医薬添加物層であり、その両面に一つ以上の割線を有しており、
該Ａ層は医薬添加物を含んでいてもよい薬物層であって、Ｂ層上の割線のある部位によって分断されており、
該Ａ層の分断された各部分はＢ層に固着していることにより保持されていて、それぞれ同一もしくは異なる薬物を含有しており、
さらに該Ｃ層も医薬添加物を含んでいてもよい薬物層であって、Ｂ層上の割線のある部位によって分断されており
該Ｃ層の分断された各部分はＢ層に固着していることにより保持されていて、それぞれ同一もしくは異なる薬物を含有している錠剤。 A three-layer tablet comprising three layers in the order of A layer, B layer and C layer,
The B layer is a pharmaceutical additive layer that may contain a drug, and has one or more secant lines on both sides thereof.
The A layer is a drug layer that may contain a pharmaceutical additive, and is divided by a part having a secant on the B layer,
Each divided part of the A layer is retained by being fixed to the B layer, and each contains the same or different drug,
Further, the C layer is a drug layer that may contain a pharmaceutical additive, and is divided by a part having a dividing line on the B layer, and each divided part of the C layer is fixed to the B layer. Tablets that contain the same or different drugs.
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2005237371A JP5046501B2 (en) | 2005-08-18 | 2005-08-18 | Tablets that hold multiple drugs separately |
| US12/063,951 US20090155361A1 (en) | 2005-08-18 | 2006-08-18 | Tablet with multiple drug-containing sections |
| CA002619745A CA2619745A1 (en) | 2005-08-18 | 2006-08-18 | Tablet with multiple drug-containing sections |
| PCT/JP2006/316660 WO2007021033A1 (en) | 2005-08-18 | 2006-08-18 | Tablet having multiple drug-containing segments |
| EP06783012A EP1915988A4 (en) | 2005-08-18 | 2006-08-18 | Tablet having multiple drug-containing segments |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2005237371A JP5046501B2 (en) | 2005-08-18 | 2005-08-18 | Tablets that hold multiple drugs separately |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007051094A JP2007051094A (en) | 2007-03-01 |
| JP5046501B2 true JP5046501B2 (en) | 2012-10-10 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2005237371A Expired - Fee Related JP5046501B2 (en) | 2005-08-18 | 2005-08-18 | Tablets that hold multiple drugs separately |
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| JP (1) | JP5046501B2 (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007078290A1 (en) * | 2005-12-30 | 2007-07-12 | Accu-Break Technologies, Inc. | Adhesively bonded dosage form |
| FR2928836B1 (en) * | 2008-03-21 | 2011-08-26 | Servier Lab | SECURE GALENIC FORM FOR MODIFIED RELEASE OF THE ACTIVE INGREDIENT |
| JP6106359B2 (en) * | 2010-12-13 | 2017-03-29 | 第一三共ヘルスケア株式会社 | Solid formulation containing loxoprofen sodium and vitamin B1 |
| JP6126780B2 (en) * | 2010-12-13 | 2017-05-10 | 第一三共ヘルスケア株式会社 | Solid formulation containing loxoprofen sodium and tranexamic acid |
| JP6112765B2 (en) * | 2010-12-13 | 2017-04-12 | 第一三共ヘルスケア株式会社 | Solid preparation containing loxoprofen sodium and dl-methylephedrine hydrochloride |
| JP6110589B2 (en) * | 2010-12-13 | 2017-04-05 | 第一三共ヘルスケア株式会社 | Solid formulation containing loxoprofen sodium and clemastine fumarate |
| WO2013021543A1 (en) * | 2011-08-08 | 2013-02-14 | パナソニック株式会社 | Medication package checking system |
| JP6160263B2 (en) * | 2012-06-07 | 2017-07-12 | 大正製薬株式会社 | Loxoprofen-containing pharmaceutical composition |
| CN111407734A (en) * | 2019-01-05 | 2020-07-14 | 厦门赛诺邦格生物科技股份有限公司 | Solid preparation of medicine for treating impotence and premature ejaculation |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4503031A (en) * | 1982-12-17 | 1985-03-05 | Glassman Jacob A | Super-fast-starting-sustained release tablet |
| JPH069375A (en) * | 1992-04-10 | 1994-01-18 | Takeda Chem Ind Ltd | Dividable connected tablet |
| WO2006038916A2 (en) * | 2004-05-21 | 2006-04-13 | Accu-Break Technologies, Inc. | Scored pharmaceutical tablets comprising a plurality of segments |
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| JP2007051094A (en) | 2007-03-01 |
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