JP2003261439A - Preparation disintegrating in oral cavity - Google Patents
Preparation disintegrating in oral cavityInfo
- Publication number
- JP2003261439A JP2003261439A JP2002062978A JP2002062978A JP2003261439A JP 2003261439 A JP2003261439 A JP 2003261439A JP 2002062978 A JP2002062978 A JP 2002062978A JP 2002062978 A JP2002062978 A JP 2002062978A JP 2003261439 A JP2003261439 A JP 2003261439A
- Authority
- JP
- Japan
- Prior art keywords
- drug
- orally disintegrating
- disintegrating preparation
- preparation
- drying
- 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.)
- Granted
Links
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、服用に適した排尿
障害及びそれに関連する疾患の治療活性を有する薬物を
含有する口腔内崩壊製剤に関する。TECHNICAL FIELD The present invention relates to an orally disintegrating preparation containing a drug having a therapeutic activity for dysuria and related diseases suitable for taking.
【０００２】[0002]
【従来の技術】排尿障害及びそれに関連する疾患の治療
活性を有する薬物としてはアドレナリンα１受容体遮断
薬などが知られている。アドレナリンα１受容体遮断薬
は、本態性高血圧症、腎性高血圧症、褐色細胞腫による
高血圧症、または前立腺肥大に伴う排尿障害の治療薬と
して広く使用されている。アドレナリンα１受容体遮断
薬を必要とする適応症は、慢性疾患のため、長期服用す
る場合が多く、患者の生活状況に応じた、飲みやすく取
り扱いやすい剤型の製剤は必要性が極めて高い。2. Description of the Related Art Adrenergic α1 receptor blockers and the like are known as drugs having therapeutic activity for dysuria and related diseases. Adrenergic α1 receptor blockers are widely used as therapeutic agents for essential hypertension, renal hypertension, hypertension due to pheochromocytoma, or dysuria associated with prostatic hypertrophy. Since the indication requiring an adrenergic α1 receptor blocker is a chronic disease, it is often taken for a long period of time, and there is an extremely high need for a formulation having a dosage form that is easy to swallow and easy to handle, depending on the living conditions of the patient.
【０００３】従来、排尿障害及びそれに関連する疾患の
治療活性を有する薬物として用いられる医薬品は、錠剤
やカプセル剤の形態が広く用いられている。例えば、ア
ドレナリンα１受容体遮断薬である、ナフトピジル、塩
酸テラゾシン、塩酸ブナゾシンおよび塩酸プラゾシン
は、それぞれを有効成分として含有する錠剤が治療に用
いられている。また、塩酸タムスロシンやウラピジルを
有効成分とするカプセル剤も市販されている。[0003] Conventionally, tablets and capsules have been widely used as pharmaceuticals used as drugs having therapeutic activity for dysuria and related diseases. For example, tablets containing naphthopidil, terazosin hydrochloride, bunazosin hydrochloride and prazosin hydrochloride, which are adrenergic α1 receptor blockers, are used for treatment. Also, capsules containing tamsulosin hydrochloride or urapidil as active ingredients are commercially available.
【０００４】これらの治療を必要とする患者の大多数は
高齢者であり、錠剤あるいはカプセル剤が飲み込み難
く、服用の際に喉等につかえる等の不快感を感じるな
ど、嚥下力の弱い患者が存在する。また、夜間の排尿の
問題から就寝前の水分の摂取は控えなければならない患
者も存在する。さらに日常生活において常に水を携帯す
ることは困難であって、状況によっては水が入手困難と
なるケースも有り、従来の錠剤あるいはカプセル剤で
は、不便な場合もある。さらに、その他の剤型、例え
ば、散剤、顆粒剤では口腔内に残留し嚥下しずらく、口
中に不快感が残るケースもある。また、シロップ剤で
は、高齢者用に好ましいとされる剤型とも考えられる
が、携帯性が悪く、計量による服用は、困難性が高く、
正しい量の服用が期待できない問題点もある。The majority of patients in need of these treatments are elderly people, and patients with weak swallowing ability, such as difficulty in swallowing tablets or capsules and feeling discomfort such as sticking to throat when taking, Exists. In addition, there are patients who have to refrain from drinking water before bed due to problems of urination at night. In addition, it is difficult to carry water in daily life, and it may be difficult to obtain water depending on the situation. Conventional tablets or capsules may be inconvenient. Further, in other dosage forms such as powders and granules, they may remain in the oral cavity and may be difficult to swallow, and discomfort may remain in the mouth. In addition, the syrup is considered to be a dosage form that is said to be suitable for elderly people, but it is poor in portability, and it is difficult to take it by weighing,
There are also problems that you cannot expect to take the correct amount.
【０００５】口中に含んだ時、速やかに崩壊もしくは溶
解する剤型の従来技術もいくつか知られている。例え
ば、特開平６−２１８０２８号公報には、湿潤した練合
物を鋳型に充填し、圧縮して成型することを特徴とする
湿製錠の成型方法、湿製錠の圧縮成型の前に、湿製錠の
圧縮面もしくは、圧縮部表面に粉末を塗布して湿製錠の
圧縮時の張り付きを防止した湿製錠の成型方法が記載さ
れている。特開平８−１９５８９号公報には、湿潤粉体
を錠剤成型用の穴に充填し、湿潤粉体を張り付き防止フ
ィルムを介して、錠剤の形に成型する錠剤製造法が記載
されている。国際公開番号ＷＯ９３／１２７６９号公報
には、医薬物質と乳糖及びマンニトールを寒天水溶液に
懸濁させ、ポリプロピレン製のＰＴＰシートの成型ポケ
ット等に充填してゼリー状に固化させ、減圧乾燥した
後、アルミ箔をシールしてＰＴＰ包装品とする口腔内崩
壊性製剤が記載されている。There are some known prior art formulations which rapidly disintegrate or dissolve when contained in the mouth. For example, in Japanese Unexamined Patent Publication No. 6-218028, a method for molding a wet tablet characterized in that a wet kneaded product is filled in a mold and compressed to be molded, and before compression molding of the wet tablet, A method for molding a wet tablet is described in which powder is applied to the compression surface or the surface of the compression portion of the wet tablet to prevent sticking during compression of the wet tablet. JP-A-8-19589 describes a tablet manufacturing method in which a wet powder is filled in a hole for tablet formation and the wet powder is formed into a tablet shape through an anti-sticking film. International Publication No. WO93 / 12769 discloses that a medicinal substance, lactose, and mannitol are suspended in an agar aqueous solution, and the suspension is filled in a polypropylene PTP sheet molding pocket or the like to be solidified in a jelly form and dried under reduced pressure. An orally disintegrating preparation for sealing a foil into a PTP packaged article is described.
【０００６】国際公開番号ＷＯ９８／０２１８５号公報
や特開平１０−１８２４３６号公報には、糖アルコール
のエリスリトールと結晶セルロース乃至崩壊剤との圧縮
により成型する方法が記載されている。これらの方法の
原理は、成型時に水に濡れやすい糖アルコールのような
湿潤する担体を含有し、低い圧力で成型し錠剤としてい
るため、適度の空隙率を有する多孔性の錠剤とすること
を基本原理とし、また、撥水性に富む滑沢剤を従来法よ
り低減もしくは、使用することを避け、錠剤への吸水力
を向上させることにより速崩壊性の獲得を目指してい
る。International Publication No. WO98 / 02185 and Japanese Unexamined Patent Publication No. 10-182436 describe a method of molding by compressing sugar alcohol erythritol and crystalline cellulose or a disintegrant. The principle of these methods is to form a porous tablet having an appropriate porosity because it contains a moistening carrier such as sugar alcohol that is easily wetted by water at the time of molding and is molded into a tablet at a low pressure. In principle, the aim is to obtain fast disintegration by reducing the use of lubricants with high water repellency or avoiding the use of such lubricants, and improving the water absorption of tablets.
【０００７】[0007]
【発明が解決しようとする課題】本発明によって解決を
目指す課題は、高齢者等の服用に適した、生活の質を確
保する剤型であり、排尿障害及びそれに関連する疾患の
治療活性を有する薬物のための製剤技術である。The problem to be solved by the present invention is to provide a dosage form that secures quality of life and is suitable for ingestion for the elderly, etc., and has therapeutic activity for dysuria and related diseases. Formulation technology for drugs.
【０００８】[0008]
【課題を解決するための手段】本発明者らは前述の問題
点を解決するため、排尿障害及びそれに関連する疾患の
治療活性を有する薬物を用いて、且つ難溶性である薬物
について種々検討を行った結果、凍結乾燥により製する
方法を用いることで、高含有率でも速崩壊性が得られ、
且つ薬物の粒径を０．４〜１０５μｍとすると、ザラツ
キ感もなく、嚥下がスムーズであり、上述の方法ではな
しえない口腔内での崩壊時間が１０秒以内という製造方
法を発明するに至った。すなわち、本発明は、排尿障害
及びそれに関連する疾患の治療活性を有する薬物を含有
することを特徴とする口腔内崩壊製剤である。[Means for Solving the Problems] In order to solve the above-mentioned problems, the present inventors have conducted various investigations on drugs that are poorly soluble, using drugs having therapeutic activity for dysuria and related diseases. As a result, by using the method of producing by freeze-drying, fast disintegration is obtained even at a high content rate,
Moreover, when the particle size of the drug is 0.4 to 105 μm, there is no feeling of roughness, swallowing is smooth, and a disintegration time in the oral cavity that can not be achieved by the above-mentioned method is within 10 seconds, leading to the invention of a manufacturing method. It was That is, the present invention is an orally disintegrating preparation containing a drug having therapeutic activity for dysuria and related diseases.
【０００９】本発明の口腔内崩壊製剤は、特別に水を服
用することなしに、口腔内で迅速に崩壊し、唾液ととも
に嚥下される製剤であり、舌下において吸収される舌下
剤とは区別され、該有効成分自体は口腔内において実質
的には吸収されないことが必要とされる。例えば、舌の
上等の口腔内において、特別に水を服用することなく、
早期に崩壊するものであれば特に限定されないが、例え
ば、３０秒以内に崩壊することが好ましく、さらに好ま
しくは、２０秒以内、特に好ましくは１０秒以内、最も
好ましくは５秒以内に崩壊する例が挙げられる。これら
の有効成分は、実質的に唾液中では溶解せず、その後唾
液とともに飲みこまれる。The orally-disintegrating preparation of the present invention is a preparation that rapidly disintegrates in the oral cavity and is swallowed with saliva without especially taking water, and is distinguished from a sublingual drug which is absorbed under the tongue. However, it is required that the active ingredient itself is not substantially absorbed in the oral cavity. For example, in the oral cavity, such as on the tongue, without taking special water,
Although it is not particularly limited as long as it disintegrates early, for example, it is preferable to disintegrate within 30 seconds, more preferably within 20 seconds, particularly preferably within 10 seconds, and most preferably within 5 seconds. Is mentioned. These active ingredients are practically insoluble in saliva and then swallowed with saliva.
【００１０】しかしながら、ヒトの唾液は、個人差があ
り、客観的な評価とする場合には、例えば、試験液に水
を用いた日本薬局方崩壊試験で崩壊時間が３０秒以内が
好ましく、さらに２０秒以内であることがさらに好まし
く、１０秒以内であることが特に好ましい例として挙げ
られる。本発明の口腔内崩壊製剤は、固形製剤であり、
水分量は通常１０％以下であることが適当であるが、よ
り好ましくは８％以下、さらに好ましくは４％以下が例
示される。However, human saliva has individual differences, and in the case of objective evaluation, for example, the disintegration time is preferably 30 seconds or less in the Japanese Pharmacopoeia disintegration test using water as the test liquid. It is more preferably 20 seconds or less, and particularly preferably 10 seconds or less. The orally disintegrating preparation of the present invention is a solid preparation,
It is suitable that the water content is usually 10% or less, more preferably 8% or less, and further preferably 4% or less.
【００１１】本発明の口腔内崩壊製剤の形状は特に限定
しないが、円盤状などの放射状の形状であれよく、サイ
ズは指でつかみ易く、かつ口に含み易ければよく、さら
に、飲み込まないために若干大きめであることが好まし
い。例えば、長径（円盤状であれば直径）７〜２２ｍｍ
で厚みが１〜８ｍｍが適当であり、より好ましくは長径
８〜２０ｍｍで、厚みが１．５〜６ｍｍであり、さらに
好ましくは長径９〜１８ｍｍで厚みが２〜５ｍｍで例示
される。The shape of the orally disintegrating preparation of the present invention is not particularly limited, but it may be a radial shape such as a disc shape, and the size thereof should be easy to grasp with a finger and easy to hold in the mouth, and further it should not be swallowed. It is preferably slightly larger. For example, the major axis (diameter if disk-shaped) is 7 to 22 mm
The thickness is preferably 1 to 8 mm, more preferably 8 to 20 mm in major axis, 1.5 to 6 mm in thickness, and further preferably 9 to 18 mm in major axis and 2 to 5 mm in thickness.
【００１２】排尿障害及びそれに関連する疾患の治療活
性を有する薬物としてはアドレナリンα１受容体遮断活
性を有する薬物、コリン作動薬、ムスカリン受容体拮抗
作用を有する薬物（ＹＭ−９０５）などが知られてい
る。アドレナリンα１受容体遮断活性を有する薬物と
は、アドレナリンα１受容体に支配される臓器機能を抑
制するもので、さらに詳しくは、前立腺のアドレナリン
α１受容体に対して高い親和性を示す有効なアンタゴニ
ストであり、尿道及び前立腺に分布する交感神経の緊張
を緩和することにより、前立腺及び尿道平滑筋の収縮を
抑制するものである。As drugs having therapeutic activity for dysuria and related diseases, drugs having adrenergic α1 receptor blocking activity, cholinergic drugs, drugs having muscarinic receptor antagonistic action (YM-905) and the like are known. There is. A drug having an adrenergic α1 receptor blocking activity suppresses an organ function governed by an adrenergic α1 receptor, and more specifically, an effective antagonist showing a high affinity for the adrenergic α1 receptor of the prostate. By suppressing the tension of the sympathetic nerves distributed in the urethra and prostate, the contraction of the prostate and urethral smooth muscle is suppressed.
【００１３】具体的には、例えば、ナフトピジル、タム
スロシン、テラゾシン、ブナゾシン、ウラピジル、モキ
シシリト、ドキサゾシン、アルフゾシン、ウピドシン、
メタゾシン、フィデュクソシン、インドラゾシン、ＫＭ
Ｄ−３２１３及びこれらの塩類等が挙げられる。本発明
において特に好ましいのは、ナフトピジル、塩酸プラゾ
シン、ウラピジルである。さらにナフトピジルが特に好
ましい例として挙げられる。Specifically, for example, naphthopidil, tamsulosin, terazosin, bunazosin, urapidil, moxicilito, doxazosin, alfuzosin, upidosine,
Metazocine, fiduxocine, indrazocine, KM
D-3213 and salts thereof may be mentioned. Particularly preferred in the present invention are naphthopidil, prazosin hydrochloride, and urapidil. Further, naphthopidil is mentioned as a particularly preferable example.
【００１４】ナフトピジルは、化学名［４−（２−メト
キシフェニル）ピペラジニル］−３−（１−ナフチロキ
シ）プロパン−２−オールであり、また、ナフトピジル
の日本における特許は特許出願公告昭６０−２９７１２
に「１−［３−（ナフト−イル−オキシ）−２−ヒドロ
キシ−プロピル］−ピペラジン−誘導体の製法」として
開示している。また、特公平６−２６７３号公報に、ナ
フトピジル及びその塩を用いた前立腺肥大における排尿
困難治療の用途で開示している。Naftopidil has a chemical name of [4- (2-methoxyphenyl) piperazinyl] -3- (1-naphthyloxy) propan-2-ol, and the patent of naphthopidil in Japan is JP-A-60-29712.
As "1- [3- (naphtho-yl-oxy) -2-hydroxy-propyl] -piperazine-derivative preparation". Further, Japanese Patent Publication No. 6-2673 discloses the use of naphthopidil and its salt for treating dysuria in prostatic hypertrophy.
【００１５】ナフトピジルはヒト前立腺のα１受容体に
対して高い親和性を示す有効なアンタゴニストであり、
尿道及び前立腺に分布する交感神経の緊張を緩和するこ
とにより、前立腺及び尿道平滑筋の収縮を抑制する。ま
たナフトピジルは多数の臨床的研究において、前立腺肥
大に伴う排尿障害に対して改善作用を示すことが証明さ
れ、経口用錠剤すなわち、ナフトピジル錠として既に発
売されている。ナフトピジル錠は前立腺肥大症に伴う排
尿障害の成人に、ナフトピジルとして１日１回２５ｍｇ
より投与を始め、効果が不十分な場合は１〜２週間の間
隔をおいて５０〜７５ｍｇに漸増し、１日１回服用する
ことが臨床的試験結果から設定されている。塩酸プラゾ
シンは、化学名１−（４−アミノ−６，７−ジメトキシ
−２−キナゾリニル）−４−（２−フラニルカルボニ
ル）ピペラジン ヒドロクロライドである。第２回αブ
ロッカー研究会誌Ｐ．１２１，１９８４，メディカル・
ジャーナル社に前立腺肥大における排尿障害治療の効果
が記載されており、前立腺肥大症に伴う排尿障害の成人
１日１〜１．５ｍｇ（１回０．５ｍｇ １日２〜３回）
より投与を始め、効果が不十分な場合は１〜２週間の間
隔をおいて１．５〜６ｍｇまで漸増し、１日２〜３回服
用することが設定されている。Naftopidil is an effective antagonist showing a high affinity for the α1 receptor of human prostate,
It suppresses the contraction of the prostate and urethral smooth muscle by relaxing the sympathetic tone distributed in the urethra and prostate. Further, naphthopidil has been proved to have an improving effect on urinary disorders associated with benign prostatic hyperplasia in numerous clinical studies, and has already been released as an oral tablet, that is, naphthopidil tablet. Naftopidil tablets 25mg once daily as naphthopidil for adults with dysuria associated with benign prostatic hyperplasia
From the clinical test results, it is set that the administration is started more, and when the effect is insufficient, the dose is gradually increased to 50 to 75 mg at intervals of 1 to 2 weeks and the dose is taken once a day. Prazosin hydrochloride has the chemical name 1- (4-amino-6,7-dimethoxy-2-quinazolinyl) -4- (2-furanylcarbonyl) piperazine hydrochloride. The 2nd α Blocker Study Group P. 121,1984, Medical
The effect of urination disorder treatment on benign prostatic hyperplasia is described in Journal, and adults with urinary disorders associated with benign prostatic hyperplasia 1 to 1.5 mg daily (0.5 mg once, 2 to 3 times daily)
If the effect is insufficient after administration, the dose is gradually increased to 1.5 to 6 mg at intervals of 1 to 2 weeks, and the dose is to be taken 2 to 3 times a day.
【００１６】ウラピジルは、化学名６−［［３−［４−
（ο−メトキシフェニル）−１−ピペラゾニル］プロピ
ル］アミノ］−１，３−ジメチルウラシルである。泌尿
器外科Ｐ．２６７，６（３），１９９３、に前立腺肥大
における排尿障害治療の効果が記載されており、前立腺
肥大症に伴う排尿障害の成人１日３０ｍｇより投与を始
め、効果が不十分な場合は１〜２週間の間隔をおいて１
日６０〜９０ｍｇまで漸増し、１日２回に服用すること
が設定されている。Urapidil has a chemical name of 6-[[3- [4-
(Ο-methoxyphenyl) -1-piperazonyl] propyl] amino] -1,3-dimethyluracil. Urological Surgery P. 267, 6 (3), 1993, describes the effect of treating dysuria on benign prostatic hyperplasia, and when the effect of urination disorder associated with benign prostatic hyperplasia is started from 30 mg per day, the effect is 1 1 every 2 weeks
The dose is gradually increased to 60 to 90 mg per day, and it is set to be taken twice a day.
【００１７】前立腺肥大症に伴う排尿障害は、特に成人
男子にみられ、その発生は４０歳頃からみられ、加齢と
ともに増加して７０歳代でピークに達し、６５歳以上の
高齢者においては約２０％が治療の対象とされている。
また、本発明において難溶性としては、１５０μｍふる
いを通過する粉末を、１０００ｍｌの精製水中に入れ、
２０±５℃で、５分ごとに強く３０秒間振り混ぜると
き、３０分以内に１ｇ未満しか溶解しないものが好まし
い例として挙げられる。特に、難溶性の物質は懸濁して
用いることができ、凍結乾燥し錠剤様のマトリックスを
形成するには有用な性質である。Urinary dysfunction associated with benign prostatic hyperplasia is observed especially in adult males, the incidence of which has been observed since about 40 years old, increased with aging and peaked in the 70s, and in elderly people over 65 years old. About 20% are targeted for treatment.
Further, in the present invention, as a poorly soluble substance, a powder that passes through a 150 μm sieve is put in 1000 ml of purified water,
A preferable example is one which dissolves less than 1 g within 30 minutes when shaken vigorously at 20 ± 5 ° C. every 5 minutes for 30 seconds. In particular, a sparingly soluble substance can be used by suspending it, which is a property useful for freeze-drying to form a tablet-like matrix.
【００１８】本発明のアドレナリンα１受容体遮断活性
を有し、且つ難溶性である薬物としては、さらに、不快
な味を有する薬物である場合に、その不快な味をより感
じない製剤となすことが出来る点で、さらに好ましい効
果を与える。不快な味としては、代表的には、苦味が例
示され、例えば、ナフトピジルが代表的な例として挙げ
ることができる。ナフトピジルに関しては１錠中の含量
は２５ｍｇ〜７５ｍｇが好適である。As the poorly soluble drug having an adrenergic α1 receptor-blocking activity of the present invention, when it is a drug having an unpleasant taste, a preparation in which the unpleasant taste is less felt It is possible to obtain a more preferable effect. The unpleasant taste is typically exemplified by bitterness, and, for example, naphthopidil can be mentioned as a typical example. The content of naphthopidil in one tablet is preferably 25 mg to 75 mg.
【００１９】前述の薬物の粒径は、口中でのザラツキ感
や、違和感等を感じ難い効果を達成するためには、例え
ば、薬物の実質的に全てが１０５μｍ以下の粒径である
こと、より好ましくは８９μｍ以下、さらに好ましくは
７４μｍである。ザラツキ感や違和感の低減の効果から
すれば、特に下限は問題とされないが、特に、薬物が不
快な味を有する場合には、粒径が小さすぎると問題を生
ずることが確認された。The particle size of the above-mentioned drug is, for example, that substantially all of the drug has a particle size of 105 μm or less in order to achieve the effect of making the mouth feel less rough or uncomfortable. It is preferably 89 μm or less, more preferably 74 μm. From the viewpoint of the effect of reducing the feeling of roughness and discomfort, the lower limit is not particularly a problem, but it has been confirmed that when the drug has an unpleasant taste, if the particle size is too small, a problem occurs.
【００２０】したがって、通常は０．４μｍ以上、好ま
しくは０．８μｍ以上、さらに好ましくは１．２μｍ以
上が例示される。実質的とは、粉砕物の粒径分布を測定
したときにその殆どが含まれることを意味し、例えば粉
砕機の条件を適切に選択して粉砕した後に得られた粉砕
物などが含まれる。また、薬物の粒子の平均粒径として
は、１〜４０μｍの範囲内であることが好ましく、より
好ましくは３〜３５μｍである、さらに好ましくは４〜
３０μｍである。Therefore, the thickness is usually 0.4 μm or more, preferably 0.8 μm or more, more preferably 1.2 μm or more. The term “substantially” means that most of them are contained when the particle size distribution of the pulverized product is measured, and includes, for example, a pulverized product obtained after pulverizing by appropriately selecting the conditions of the pulverizer. The average particle size of the drug particles is preferably in the range of 1 to 40 μm, more preferably 3 to 35 μm, and further preferably 4 to
It is 30 μm.
【００２１】薬物を前述の粒径にするためには、例え
ば、篩により粒径を揃える方法、メンブランフィルター
により粒径を揃える方法、また適宜の方法により粉砕す
る方法等が例示される。粉砕する方法や、その際に使用
される粉砕機は特に限定されないが、例えば、ピンミル
粉砕機、ボールミル粉砕機、ハンマーミル粉砕機の使用
が好適である。運転条件等は、適宜作成される粒径を測
定して決定すればよい。本発明に関する口腔内速崩製剤
は、有効成分である薬剤が製剤中に含まれる量は、薬剤
の重量により適宜調整すればよいが口腔内崩壊製剤の１
〜９５％が好ましい。特に、ナフトピジルに関しては有
効成分を高含有率にせしめることができ、製剤の含有率
が３０〜９５％が好ましく、より好ましくは４０〜９５
％であり、更に好ましくは５０〜９５％で口腔内速崩剤
の特徴を保持し、さらにナフトピジルの製剤が服用し易
い製剤を製することが可能である。この高含有量の口腔
内崩壊製剤は、後述の通り、ナフトピジルを凍結乾燥方
法により調整する場合に、より容易に調製することがで
きる。In order to make the drug have the above-mentioned particle size, for example, a method of making the particle size uniform by a sieve, a method of making the particle size uniform by a membrane filter, and a method of pulverizing by an appropriate method are exemplified. The method of crushing and the crusher used at that time are not particularly limited, but for example, use of a pin mill crusher, a ball mill crusher, or a hammer mill crusher is suitable. The operating conditions and the like may be determined by measuring the particle size that is appropriately created. In the rapidly disintegrating buccal preparation according to the present invention, the amount of the drug as an active ingredient contained in the formulation may be appropriately adjusted depending on the weight of the drug.
~ 95% is preferred. In particular, for naphthopidil, the active ingredient can have a high content, and the content of the preparation is preferably 30 to 95%, more preferably 40 to 95.
%, More preferably 50 to 95%, the characteristics of the oral disintegrant can be maintained, and the naphthopidil preparation can be easily taken. This high content orally disintegrating preparation can be more easily prepared when naphthopidil is prepared by a freeze-drying method, as described below.
【００２２】本発明の口腔内崩壊製剤の製造方法は、製
剤が上述の用件に包含されていればよく特に限定されな
いが、薬物に担体を加えて均一に混合し、溶媒で懸濁さ
せた懸濁液を一定の型に流し込んで成型した後、減圧乾
燥、通風乾燥またはマイクロウエーブ照射して製造され
る方法が挙げられる。特に、薬物に担体を加えて均一に
混合し、溶媒で懸濁させた懸濁液を一定の型に流し込ん
で成型した後、凍結乾燥して製造される方法で調製され
た本発明の口腔内崩壊製剤は、製剤密度が小さい方が、
口腔内での易崩壊性が達成されやすいため、製剤密度は
８０〜３００ｍｇ／ｍｌが適当であり、より好ましくは
１００〜２８０ｍｇ／ｍｌであり、さらに好ましくは１
２０〜２５０ｍｇ／ｍｌである。The method for producing the orally-disintegrating preparation of the present invention is not particularly limited as long as the preparation is included in the above-mentioned requirements, but a carrier is added to the drug and the mixture is uniformly mixed and suspended in a solvent. Examples include a method in which the suspension is poured into a predetermined mold to be molded, and then dried under reduced pressure, ventilation drying or microwave irradiation to produce the suspension. In particular, an oral cavity of the present invention prepared by a method in which a carrier is added to a drug and uniformly mixed, and a suspension suspended in a solvent is poured into a certain mold to be molded, and then freeze-dried to be produced. For disintegrated formulations, the smaller the formulation density,
Since easy disintegration in the oral cavity is easily achieved, the formulation density is suitably 80 to 300 mg / ml, more preferably 100 to 280 mg / ml, and further preferably 1
20-250 mg / ml.
【００２３】また本法により調製された本発明の口腔内
崩壊製剤は、崩壊時間が非常に短い製剤が調製可能であ
り、その崩壊時間としては、例えば３０秒以内、好まし
くは１０秒以内、非常に好ましくは５秒以内、または２
秒以内が例示される。唾液のｐＨは個人差や、体調によ
って変動が多く、中性〜弱アルカリ性（ｐＨ６〜７）で
変動することが言われている（医学大辞典、南山堂）
が、本発明の口腔内崩壊製剤は、崩壊したとき、唾液の
ｐＨでは溶解しない性質の薬物が好適である。The orally disintegrating preparation of the present invention prepared by this method can be prepared as a preparation having a very short disintegration time. The disintegration time is, for example, 30 seconds or less, preferably 10 seconds or less. Preferably within 5 seconds, or 2
It is exemplified within seconds. It is said that saliva pH varies a lot depending on individual differences and physical condition, and varies from neutral to weakly alkaline (pH 6 to 7) (Medical University Dictionary, Nanzando).
However, the orally disintegrating preparation of the present invention is preferably a drug having a property of not being dissolved at the pH of saliva when disintegrated.
【００２４】本発明の口腔内崩壊製剤は、排尿障害及び
それに関連する疾患への薬効が期待される薬剤であれば
特に限定されない。排尿障害は尿の排出が障害される排
出障害と、尿の貯留が障害される蓄尿障害に分けられ
る。また排尿障害に関連する疾患としては、例えば、腎
不全等の腎機能障害等があげられる。また薬剤がアドレ
ナリンα１受容体遮断活性薬であれば、本態性高血圧
症，腎性高血圧症，褐色細胞腫による高血圧症及び前立
腺肥大に伴う排尿障害等の治療、または予防剤としての
用途も例示される。アドレナリンα１受容体遮断活性薬
がナフトピジルのときには、特に、前立腺肥大に伴う排
尿障害等の治療、または予防剤が例示される。The orally disintegrating preparation of the present invention is not particularly limited as long as it is a drug which is expected to be effective against dysuria and related diseases. Urination disorders are divided into drainage disorders in which urine output is impaired and urine storage disorders in which urine retention is impaired. Examples of diseases related to dysuria include renal dysfunction such as renal failure. If the drug is an adrenergic α1 receptor blocker, it is also used as a therapeutic or preventive agent for essential hypertension, renal hypertension, hypertension due to pheochromocytoma and urinary disorders associated with benign prostatic hyperplasia. It When the adrenergic α1 receptor blocker is naphthopidil, a therapeutic or prophylactic agent for urinary disorders associated with prostatic hypertrophy is particularly exemplified.
【００２５】本発明の口腔内崩壊製剤の製造法として
は、薬物に適当な担体を加えて均一に混合し、溶媒で懸
濁させた懸濁液を一定の型に流し込んで成型した後、乾
燥して製造される方法が挙げられる。溶媒としては、容
易に除去が可能であり、且つ薬学的に許容される物質で
あることが好ましく、例えば、水、エタノール、アセト
ン、イソプロピルアルコールが挙げられる。より好まし
くは、水が好適である。本法における乾燥方法として
は、好ましくは、真空凍結乾燥法が例示される。As a method for producing the orally disintegrating preparation of the present invention, a suitable carrier is added to the drug and the mixture is uniformly mixed, and the suspension suspended in the solvent is poured into a fixed mold to be molded, and then dried. The method manufactured by The solvent is preferably a substance which can be easily removed and is pharmaceutically acceptable, and examples thereof include water, ethanol, acetone and isopropyl alcohol. More preferably, water is suitable. As a drying method in this method, a vacuum freeze-drying method is preferably exemplified.
【００２６】他に乾燥方法として、減圧乾燥や通風乾
燥、マイクロウエーブ照射することもできる。使用され
る担体としては、賦形剤、マトリックス成形助剤、若し
くはその他の担体等が例示される。賦形剤としては、水
に対する溶解性が高く且つ凍結乾燥後の成形状態が良好
である糖類あるいは糖アルコールが適当な例として挙げ
られ、さらに具体的には、例えば、ブドウ糖、果糖、乳
糖、白糖、マンニトール、ソルビトール、キシリトー
ル、エリスリトール、トレハロース等が挙げられる。Other drying methods include vacuum drying, ventilation drying, and microwave irradiation. Examples of the carrier used include excipients, matrix forming aids, and other carriers. Examples of suitable excipients include sugars and sugar alcohols, which have high solubility in water and are well formed after freeze-drying, and more specifically, for example, glucose, fructose, lactose, sucrose. , Mannitol, sorbitol, xylitol, erythritol, trehalose and the like.
【００２７】マトリックスを保持するためのマトリック
ス成形助剤としては、例えば水溶性高分子が適当であ
り、ゼラチンや、寒天、アルギン酸、アルギン酸ナトリ
ウム、キタンサンガム、アラビアゴム末、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、ポリビニルピロリドン、部分けん化ポリビニルアル
コール、メチルセルロース、プルラン、部分α化デンプ
ン等が挙げられる。本発明に用いるゼラチンは、牛、
豚、魚由来等がありいずれも使用可能であるが、安全上
の点からは魚由来のものが好ましい。As the matrix forming aid for holding the matrix, for example, a water-soluble polymer is suitable, and gelatin, agar, alginic acid, sodium alginate, xanthan gum, gum arabic powder, hydroxypropylcellulose, hydroxypropylmethylcellulose, Examples thereof include polyvinylpyrrolidone, partially saponified polyvinyl alcohol, methyl cellulose, pullulan, and partially pregelatinized starch. Gelatin used in the present invention is cow,
There are pigs and fish derived from them, and any of them can be used, but from the viewpoint of safety, those derived from fish are preferable.
【００２８】また酸性領域で加水分解処理されたＡタイ
プ、アルカリ性領域で加水分解処理されたＢタイプの何
れであってよい。甘味剤としては、アスパルテーム（登
録商標）、サッカリン、グリチルリチン等があげられ、
香料としては、レモン、オレンジ、パイン、ミント、メ
ントール等があげられる。また、懸濁液の分散性の改善
目的で、アルキル硫酸ナトリウムなどのアニオン系界面
活性剤、ショ糖脂肪酸エステル、ポリオキシエチレンソ
ルビタン脂肪酸エステル、ポリオキシエチレン脂肪酸エ
ステルおよびポリオキシエチレンヒマシ油誘導体などの
非イオン系界面活性剤などの界面活性剤を添加すること
ができる。Further, it may be either A type hydrolyzed in the acidic region or B type hydrolyzed in the alkaline region. Examples of the sweetener include aspartame (registered trademark), saccharin, glycyrrhizin, and the like.
Examples of the fragrance include lemon, orange, pine, mint, menthol and the like. Further, for the purpose of improving the dispersibility of the suspension, such as anionic surfactants such as sodium alkylsulfate, sucrose fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester and polyoxyethylene castor oil derivative A surfactant such as a nonionic surfactant can be added.
【００２９】さらに、唾液のｐＨは個人差や、体調によ
って変動が多く、中性〜弱アルカリ性（ｐＨ６〜７）で
変動することが言われている（医学大辞典、南山堂）
が、本発明の口腔内崩壊製剤は、崩壊したとき唾液のｐ
Ｈでは溶解しない性質の薬物が好適であるため、場合に
よっては、グリシン、炭酸水素ナトリウム、リン酸水素
カルシウム、リン酸水素ナトリウム、酢酸、コハク酸、
酒石酸およびクエン酸等の有機酸またはその塩類などの
ｐH調整剤を使用することもできる。本製法には上記の
担体１種もしくはそれ以上を使用することができる。Furthermore, the pH of saliva varies a lot depending on individual differences and physical condition, and it is said that it varies from neutral to weakly alkaline (pH 6 to 7) (Dictionary of Medicine, Nanzando).
However, the orally disintegrating preparation of the present invention has a p
Since a drug having a property of not dissolving in H is suitable, in some cases, glycine, sodium hydrogen carbonate, calcium hydrogen phosphate, sodium hydrogen phosphate, acetic acid, succinic acid,
It is also possible to use pH regulators such as organic acids such as tartaric acid and citric acid or salts thereof. One or more of the above carriers can be used in the present production method.
【００３０】[0030]
【発明の実施の形態】以下に実施例をあげて本発明を詳
しく説明するがこれらは本発明を限定するものではな
い。BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in detail below with reference to examples, but these do not limit the present invention.
【００３１】[0031]
【実施例１】ナフトピジル原末を、目開き１０６μｍの
篩（ＪＩＳ１４０メッシュ）を用い、振動式ふるい分器
（ＭＳ−２００、ＩＴＯＨ）でふるい分け、篩を通過し
たナフトピジル分級末を得た。本分級末に水を加え２０
％の懸濁液とし、孔径０．４μｍのメンブランフィルタ
ー（アイソポアHＴ、ミリポア社製）用いろ過した。孔
径０．４μｍのメンブランフィルター上の残留物を取
り、真空乾燥機（ＶＯＣ−４００Ｄ、ＥＹＥＬＡ社製）
を用い乾燥し、０．４〜１０５μｍナフトピジル分級末
を得た。Example 1 Naphtopidil bulk powder was sieved with a vibrating sieving machine (MS-200, ITOH) using a sieve (JIS140 mesh) having a mesh size of 106 μm to obtain a naphthopidil classified powder that passed through the sieve. Add water to the end of this classification 20
% Suspension and filtered using a membrane filter (Isopore HT, Millipore) with a pore size of 0.4 μm. The residue on the membrane filter with a pore size of 0.4 μm is removed, and the vacuum dryer (VOC-400D, manufactured by EYELA) is used.
To obtain 0.4-105 μm naphthopidil classified powder.
【００３２】１０ｍｌビーカーに入れた精製水５．７６
ｇにゼラチン０．１４ｇ（Ｓ−Ｂ１７５、ニッピ社製）
とD−マンニトール０．１ｇ（マンニットＰ、東和化成
社製）を添加し、スターラーで攪拌しながら約５０℃に
加熱し溶解した。溶解後、２５℃に冷却した。本溶液を
スターラーで攪拌しながら、０．４〜１０５μｍナフト
ピジル分級末１ｇを徐々にスパーテルで添加した。スタ
ーラーで攪拌し均一に分散させながら、塩化ビニール樹
脂を内膜にしたブリスターパックのポケット中に分散液
３５０ｍｇを手動分注機で添加した。分注後−７０℃で
凍結後、真空凍結乾燥機（トリオマスターＡ０４、共和
真空技術社製）を用いて乾燥を行い製剤を得た。5.76 of purified water in a 10 ml beaker
0.14 g of gelatin in g (S-B175, manufactured by Nippi)
And 0.1 g of D-mannitol (Mannitol P, manufactured by Towa Kasei Co., Ltd.) were added, and the mixture was heated to about 50 ° C. with stirring with a stirrer and dissolved. After dissolution, it was cooled to 25 ° C. While stirring this solution with a stirrer, 1 g of 0.4-105 μm naphthopidil classified powder was gradually added with a spatula. While stirring with a stirrer and uniformly dispersing, 350 mg of the dispersion liquid was added by a manual dispenser into a pocket of a blister pack having a vinyl chloride resin as an inner film. After dispensing, it was frozen at −70 ° C. and dried using a vacuum freeze dryer (Triomaster A04, manufactured by Kyowa Vacuum Technology Co., Ltd.) to obtain a preparation.
【００３３】[0033]
【実施例２】ナフトピジル原末をピンミル粉砕機（６３
C、アルピネ社製）を用いて粉砕した。本品を、目開き
７５μｍのふるい（ＪＩＳ２００メッシュ）を用い、振
動式ふるい分器（ＭＳ−２００、ＩＴＯＨ）でふるい分
け、篩を通過したナフトピジル分級末を得た。本分級末
に水を加え２０％の懸濁液とし、孔径１．２μｍのメン
ブランフィルター（アイソポアＲＴ、ミリポア社製）用
いろ過した。孔径１．２μｍのメンブランフィルター上
の残留物を取り、真空乾燥機（ＶＯＣ−４００Ｄ、ＥＹ
ＥＬＡ社製）を用い乾燥し、１．２〜７４μｍナフトピ
ジル分級末を得た。以下実施例１の方法で製剤を得た。[Example 2] Raw powder of naphthopidil was crushed with a pin mill (63
C, manufactured by Alpine Company). This product was sieved with a vibrating sieve (MS-200, ITOH) using a sieve (JIS200 mesh) with an opening of 75 μm to obtain a naphthopidil classified powder that passed through a sieve. Water was added to the end of this classification to make a 20% suspension, and the suspension was filtered using a membrane filter (Isopore RT, Millipore) with a pore size of 1.2 μm. Remove the residue on the membrane filter with a pore size of 1.2 μm and use a vacuum dryer (VOC-400D, EY).
(Manufactured by ELA) to obtain 1.2-74 μm naphthopidil classified powder. The preparation was obtained by the method of Example 1 below.
【００３４】[0034]
【比較例１】ナフトピジル原末に水を加え２０％の懸濁
液とし、ビーズミル粉砕機（ＤＹＮＯ−ＭＩＬＬ ＰＩ
ＬＯＴ型、Ｗｉｌｌｙ Ａ．Ｂａｃｈｏｆｅｎ社製）を
用いて６０分間粉砕した。この懸濁液を、孔径０．４μ
ｍのメンブランフィルター（アイソポアHＴ、ミリポア
社製）用いろ過した。このろ液を孔径０．１μｍのメン
ブランフィルター（アイソポアVC、ミリポア社製）を用
いろ過した。孔径０．１μｍのメンブランフィルターメ
ンブランフィルター上の残留物を取り、真空乾燥機（Ｖ
ＯＣ−４００Ｄ、ＥＹＥＬＡ社製）を用い乾燥し、０．
１〜０．３μｍナフトピジル分級末を得た。以下実施例
１の方法で製剤を得た。[Comparative Example 1] Water was added to bulk naphthopidil powder to prepare a 20% suspension, and a bead mill grinder (DYNO-MILL PI
LOT type, Willy A. It was crushed for 60 minutes using Bachofen's). This suspension has a pore size of 0.4μ
m membrane filter (Isopore HT, Millipore) was filtered. This filtrate was filtered using a membrane filter (Isopore VC, Millipore) having a pore size of 0.1 μm. Membrane filter with a pore size of 0.1 μm Remove the residue on the membrane filter and use a vacuum dryer (V
OC-400D, manufactured by EYELA), and dried.
A 1-0.3 μm naphthopidil classified powder was obtained. The preparation was obtained by the method of Example 1 below.
【００３５】[0035]
【比較例２】ナフトピジル原末を、目開き１５０μｍの
ふるい（ＪＩＳ１００メッシュ）と目開き１０６μｍの
ふるい（ＪＩＳ１４０メッシュ）を用い、振動式ふるい
分器（ＭＳ−２００、ＩＴＯＨ）でふるい分け、１０６
〜１４９μｍナフトピジル分級末を得た。以下実施例１
の方法で製剤を得た。[Comparative Example 2] Naftopidil bulk powder was sieved with a vibrating screen sifter (MS-200, ITOH) using a sieve with a mesh size of 150 μm (JIS100 mesh) and a sieve with a mesh size of 106 μm (JIS140 mesh).
˜149 μm naphthopidil classified powder was obtained. Example 1 below
The preparation was obtained by the method of.
【００３６】[0036]
【試験例】本発明の効果をより詳しく説明するために、
実施例で得られた製剤について、下記のような錠剤特性
を測定した。
日局崩壊試験による崩壊時間：日本薬局方第１４改正に
記載されている崩壊試験法に従い測定した。製剤６個を
取り、試験液を水とし製剤の崩壊時間を測定した。（補
助板は使用しない）
口腔内崩壊時間：健康な成人男子１０名をパネラーとし
て選び、口腔内でかまずに、舌で軽く触れた状態で製剤
が崩壊するまでの時間（秒）
味の評価：健康な成人男子１０名をパネラーとして選
び、製剤を服用後、口腔内でかまずに、舌で軽く触れた
状態での苦味を評価した。
苦い：２ポイント、やや苦い：１ポイント、苦味を感じ
ない：０ポイント
ザラツキ感の評価：健康な成人男子１０名をパネラーと
して選び、口腔内でかまずに、舌で軽く触れた状態での
ザラツキ感を評価した。
ざらつく：２ポイント、ややざらつく１ポイント、ざら
つき無し：０ポイント
得られた結果を平均し表１に示す。[Test Example] In order to explain the effect of the present invention in more detail,
The following tablet characteristics were measured for the formulations obtained in the examples. Disintegration time by Japanese Pharmacopoeia disintegration test: Measured according to the disintegration test method described in the 14th revision of the Japanese Pharmacopoeia. Six preparations were taken, the test solution was water, and the disintegration time of the preparation was measured. (Auxiliary plate is not used) Oral disintegration time: Time until the preparation disintegrates when 10 healthy adult males were selected as panelists, without chewing in the oral cavity and lightly touching with tongue (seconds) Taste evaluation : 10 healthy adult males were selected as panelists, and after taking the preparation, the bitterness was evaluated in a state where the tongue was lightly touched without chewing in the oral cavity. Bitterness: 2 points, Slightly bitterness: 1 point, No bitterness: 0 points Evaluation of rough feeling: 10 healthy adult males were selected as panelists, and rough without touching with the tongue without chewing in the oral cavity. The feeling was evaluated. Roughness: 2 points, slightly grainy 1 point, no graininess: 0 points The averaged results are shown in Table 1.
【００３７】[0037]
【表１】 [Table 1]
【００３８】[0038]
【発明の効果】以上説明したように、本発明は、口中で
速に崩壊し、口中でのザラツキ感や、違和感及び苦味を
感じることなく、排尿障害及びそれに関連する疾患の治
療活性を有する薬物が、唾液とともに速やかに飲みこま
れることができる、優れた口腔内崩壊製剤である。INDUSTRIAL APPLICABILITY As described above, the present invention is a drug that rapidly disintegrates in the mouth and has therapeutic activity for dysuria and related diseases without feeling a feeling of roughness, discomfort and bitterness in the mouth. However, it is an excellent orally disintegrating preparation that can be swallowed quickly with saliva.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ テーマコート゛(参考） Ａ６１Ｐ 13/02 Ａ６１Ｐ 13/02 43/00 １１１ 43/00 １１１ ─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. 7 Identification code FI theme code (reference) A61P 13/02 A61P 13/02 43/00 111 43/00 111
Claims (12)
活性を有する薬物を含有する口腔内崩壊製剤。1. An orally disintegrating preparation containing a drug having therapeutic activity for dysuria and related diseases.
活性を有する薬物が難溶性であり、有効成分とする薬物
に、担体を添加せしめ、該薬物が溶解しない溶媒にて該
薬物を縣濁せしめ、型に流し込んで成型した後、凍結乾
燥法により乾燥することにより得られる請求項１に記載
の口腔内崩壊製剤。2. A drug having therapeutic activity for dysuria and related diseases is poorly soluble, a carrier is added to the drug as an active ingredient, and the drug is suspended in a solvent in which the drug is insoluble. The orally disintegrating preparation according to claim 1, which is obtained by pouring into a mold, molding, and then drying by a freeze-drying method.
薬物であることを特徴とする請求項２に記載の口腔内崩
壊製剤。3. The orally disintegrating preparation according to claim 2, wherein the poorly soluble drug is a drug having an unpleasant taste.
活性を有する薬物がＹＭ−９０５であることを特徴とす
る請求項１に記載の口腔内崩壊製剤。4. The orally disintegrating preparation according to claim 1, wherein the drug having a therapeutic activity on dysuria and related diseases is YM-905.
活性を有する薬物がナフトピジルであることを特徴とす
る請求項１に記載の口腔内崩壊製剤。5. The orally disintegrating preparation according to claim 1, wherein the drug having a therapeutic activity for dysuria and related diseases is naphthopidil.
日局崩壊試験法での崩壊時間が３０秒以内であることを
特徴とする請求項５に記載の口腔内崩壊製剤。6. The orally disintegrating preparation according to claim 5, wherein the orally disintegrating preparation has a disintegration time of 30 seconds or less in a Japanese disintegration test method using water as a test solution.
に０．４〜１０５μｍであり、且つ製剤中の水分が１０
％以内であることを特徴とする請求項５または６に記載
の口腔内崩壊製剤。7. The drug, naphthopidil, has a particle size of substantially 0.4 to 105 μm, and the formulation has a water content of 10 μm.
% Or less, The orally disintegrating preparation according to claim 5 or 6, wherein
ラチンの他、担体を含んでもよいことを特徴とする請求
項５に記載の口腔内崩壊製剤。8. The orally disintegrating preparation according to claim 5, wherein the orally disintegrating preparation may contain a carrier in addition to naphthopidil and gelatin.
物に、担体を添加せしめ、該薬物が溶解しない溶媒にて
該薬物を縣濁せしめ、型に流し込んで成型した後、乾燥
することにより得られる請求項７または８に記載の口腔
内崩壊製剤。9. An orally disintegrating preparation, which comprises adding a carrier to a drug as an active ingredient, suspending the drug in a solvent in which the drug is insoluble, pouring into a mold, molding, and then drying. The orally disintegrating preparation according to claim 7, which is obtained by
乾燥であることを特徴とする請求項９に記載の口腔内崩
壊製剤。10. The orally disintegrating preparation according to claim 9, wherein the method for drying the orally disintegrating preparation is freeze-drying.
腔内崩壊製剤の３０〜９５％であることを特徴とする請
求項５に記載の口腔内崩壊製剤。11. The orally disintegrating preparation according to claim 5, wherein the content of naphthopidil as a drug is 30 to 95% of the orally disintegrating preparation.
障害及びそれに関連する疾患の治療活性を有する薬物が
難溶性であり、有効成分とする薬物に、担体を添加せし
め、該薬物が溶解しない溶媒にて該薬物を縣濁せしめ、
型に流し込んで成型した後、凍結乾燥法により乾燥する
ことを特徴とする口腔内崩壊製剤の製法。12. A method for producing an orally disintegrating preparation, wherein a drug having therapeutic activity for dysuria and related diseases is poorly soluble, and a carrier is added to the drug as an active ingredient, and the drug is dissolved. Suspend the drug in a solvent that does not
A method for producing an orally disintegrating preparation, which comprises pouring into a mold and molding, followed by drying by a freeze-drying method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002062978A JP4173670B2 (en) | 2002-03-08 | 2002-03-08 | Orally disintegrating preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002062978A JP4173670B2 (en) | 2002-03-08 | 2002-03-08 | Orally disintegrating preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2003261439A true JP2003261439A (en) | 2003-09-16 |
| JP4173670B2 JP4173670B2 (en) | 2008-10-29 |
Family
ID=28670713
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002062978A Expired - Fee Related JP4173670B2 (en) | 2002-03-08 | 2002-03-08 | Orally disintegrating preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP4173670B2 (en) |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004066991A1 (en) * | 2003-01-27 | 2004-08-12 | Yamanouchi Pharmaceutical Co., Ltd. | Enteric sustained-release fine particles for tamsulosin or its salt and process for producing the same |
| WO2005092889A1 (en) * | 2004-03-25 | 2005-10-06 | Astellas Pharma Inc. | Composition for solid pharmaceutical preparation of solifenacin or salt thereof |
| JP2005325040A (en) * | 2004-05-13 | 2005-11-24 | Asahi Kasei Pharma Kk | Pharmaceutical containing naftopidil |
| JP2010132626A (en) * | 2008-12-08 | 2010-06-17 | Kyorin Pharmaceut Co Ltd | Tablet quickly disintegrating in oral cavity |
| CN1934109B (en) * | 2004-03-25 | 2010-06-23 | 安斯泰来制药株式会社 | Composition for solid pharmaceutical preparation of solifenacin or salt thereof |
| US7815939B2 (en) | 2005-07-20 | 2010-10-19 | Astellas Pharma Inc. | Coated fine particles containing drug for intrabuccally fast disintegrating dosage forms |
| JP2011012082A (en) * | 2010-10-18 | 2011-01-20 | Asahi Kasei Pharma Kk | Method for producing drug containing naftopidil |
| JP2013506683A (en) * | 2009-10-01 | 2013-02-28 | アプタリス ファーマテク，インコーポレイテッド | Oral corticosteroid composition |
| JP2014505098A (en) * | 2011-02-11 | 2014-02-27 | シーティーシー バイオ インコーポレイテッド | Sildenafil free base-containing film preparation and method for producing the same |
| US10105315B2 (en) | 2016-08-18 | 2018-10-23 | Adare Pharmaceuticals, Inc. | Methods of treating eosinophilic esophagitis |
| US10471071B2 (en) | 2013-09-06 | 2019-11-12 | Adare Pharmaceuticals, Inc. | Corticosteroid containing orally disintegrating tablet compositions for eosinophilic esophagitis |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4523265B2 (en) * | 2002-11-13 | 2010-08-11 | 旭化成ファーマ株式会社 | Orally disintegrating preparations for the treatment of urination disorders |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61118314A (en) * | 1976-10-06 | 1986-06-05 | ジヨン ワイス アンド ブラザ リミテツド | Package and manufacture |
| JPS6250445B2 (en) * | 1976-10-06 | 1987-10-24 | Wyeth John & Brother Ltd | |
| JPH09209822A (en) * | 1996-01-30 | 1997-08-12 | Suzuki Motor Corp | Manufacture of cylinder block |
| JPH09209821A (en) * | 1996-02-06 | 1997-08-12 | Suzuki Motor Corp | Joint structure of cylinder block and cylinder head |
| JP2000169364A (en) * | 1998-09-30 | 2000-06-20 | Taisho Pharmaceut Co Ltd | Granule for oral pharmaceutical preparation |
| JP2002029964A (en) * | 2000-07-11 | 2002-01-29 | Lion Corp | Solid medicine composition |
| WO2003009831A1 (en) * | 2001-07-27 | 2003-02-06 | Yamanouchi Pharmaceutical Co., Ltd. | Compositions containing sustained-release fine grains for tablets quickly disintegrable in the oral cavity and process for producing the same |
-
2002
- 2002-03-08 JP JP2002062978A patent/JP4173670B2/en not_active Expired - Fee Related
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61118314A (en) * | 1976-10-06 | 1986-06-05 | ジヨン ワイス アンド ブラザ リミテツド | Package and manufacture |
| JPS6250445B2 (en) * | 1976-10-06 | 1987-10-24 | Wyeth John & Brother Ltd | |
| JPH09209822A (en) * | 1996-01-30 | 1997-08-12 | Suzuki Motor Corp | Manufacture of cylinder block |
| JPH09209821A (en) * | 1996-02-06 | 1997-08-12 | Suzuki Motor Corp | Joint structure of cylinder block and cylinder head |
| JP2000169364A (en) * | 1998-09-30 | 2000-06-20 | Taisho Pharmaceut Co Ltd | Granule for oral pharmaceutical preparation |
| JP2002029964A (en) * | 2000-07-11 | 2002-01-29 | Lion Corp | Solid medicine composition |
| WO2003009831A1 (en) * | 2001-07-27 | 2003-02-06 | Yamanouchi Pharmaceutical Co., Ltd. | Compositions containing sustained-release fine grains for tablets quickly disintegrable in the oral cavity and process for producing the same |
| JP2004196829A (en) * | 2001-07-27 | 2004-07-15 | Yamanouchi Pharmaceut Co Ltd | Composition containing sustained-release fine partice for tablet quickly disintegrable in oral cavity and method for producing the same |
| JP2005206608A (en) * | 2001-07-27 | 2005-08-04 | Astellas Pharma Inc | Composition containing sustained-release fine particle for tablet quickly disintegrable in buccal cavity and process for producing the same |
Non-Patent Citations (2)
| Title |
|---|
| THE JAPANESE JOURNAL OF PHARMACOLOGY, vol. 86, JPN6008027612, 2001, pages 281 - 288, ISSN: 0001059420 * |
| 日本医薬品集２０００（第２３版）財団法人日本医薬情報センター編, JPN6008027611, 1999, pages １３３４, ISSN: 0001059419 * |
Cited By (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004066991A1 (en) * | 2003-01-27 | 2004-08-12 | Yamanouchi Pharmaceutical Co., Ltd. | Enteric sustained-release fine particles for tamsulosin or its salt and process for producing the same |
| JP5168711B2 (en) * | 2004-03-25 | 2013-03-27 | アステラス製薬株式会社 | Composition for solid formulation of solifenacin or a salt thereof |
| WO2005092889A1 (en) * | 2004-03-25 | 2005-10-06 | Astellas Pharma Inc. | Composition for solid pharmaceutical preparation of solifenacin or salt thereof |
| JPWO2005092889A1 (en) * | 2004-03-25 | 2008-02-14 | アステラス製薬株式会社 | Composition for solid formulation of solifenacin or a salt thereof |
| EP2156824A1 (en) * | 2004-03-25 | 2010-02-24 | Astellas Pharma Inc. | Composition of solifenacin or salt thereof for use in solid formulation |
| CN1934109B (en) * | 2004-03-25 | 2010-06-23 | 安斯泰来制药株式会社 | Composition for solid pharmaceutical preparation of solifenacin or salt thereof |
| JP2010163442A (en) * | 2004-03-25 | 2010-07-29 | Astellas Pharma Inc | Composition for solid pharmaceutical preparation of solifenacin or salt thereof |
| US8039482B2 (en) | 2004-03-25 | 2011-10-18 | Astellas Pharma Inc. | Composition of solifenacin or salt thereof for use in solid formulation |
| JP2013040193A (en) * | 2004-03-25 | 2013-02-28 | Astellas Pharma Inc | Composition of solifenacin or salt thereof for use in solid formulation |
| JP2005325040A (en) * | 2004-05-13 | 2005-11-24 | Asahi Kasei Pharma Kk | Pharmaceutical containing naftopidil |
| US7815939B2 (en) | 2005-07-20 | 2010-10-19 | Astellas Pharma Inc. | Coated fine particles containing drug for intrabuccally fast disintegrating dosage forms |
| JP2010132626A (en) * | 2008-12-08 | 2010-06-17 | Kyorin Pharmaceut Co Ltd | Tablet quickly disintegrating in oral cavity |
| US10632069B2 (en) | 2009-10-01 | 2020-04-28 | Adare Pharmaceuticals Us, L.P. | Orally administered corticosteroid compositions |
| JP2013506683A (en) * | 2009-10-01 | 2013-02-28 | アプタリス ファーマテク，インコーポレイテッド | Oral corticosteroid composition |
| US11266598B2 (en) | 2009-10-01 | 2022-03-08 | Ellodi Pharmaceuticals, L.P. | Orally administered corticosteroid compositions |
| US9387167B2 (en) | 2009-10-01 | 2016-07-12 | Adare Pharmaceuticals, Inc. | Orally administered corticosteroid compositions |
| US9486407B2 (en) | 2009-10-01 | 2016-11-08 | Adare Pharmaceuticals, Inc. | Orally administered corticosteroid compositions |
| US9849084B2 (en) | 2009-10-01 | 2017-12-26 | Adare Pharmaceuticals, Inc. | Orally administered corticosteroid compositions |
| US11246828B2 (en) | 2009-10-01 | 2022-02-15 | Ellodi Pharmaceuticals, L.P. | Orally administered corticosteroid compositions |
| JP2011012082A (en) * | 2010-10-18 | 2011-01-20 | Asahi Kasei Pharma Kk | Method for producing drug containing naftopidil |
| US9907759B2 (en) | 2011-02-11 | 2018-03-06 | Ctc Bio, Inc. | Sildenafil-free base-containing film preparation and method for producing same |
| JP2014505098A (en) * | 2011-02-11 | 2014-02-27 | シーティーシー バイオ インコーポレイテッド | Sildenafil free base-containing film preparation and method for producing the same |
| US10471071B2 (en) | 2013-09-06 | 2019-11-12 | Adare Pharmaceuticals, Inc. | Corticosteroid containing orally disintegrating tablet compositions for eosinophilic esophagitis |
| US11166961B2 (en) | 2013-09-06 | 2021-11-09 | Ellodi Pharmaceuticals, L.P. | Corticosteroid containing orally disintegrating tablet compositions for eosinophilic esophagitis |
| US11260061B2 (en) | 2013-09-06 | 2022-03-01 | Ellodi Pharmaceuticals, L.P. | Corticosteroid containing orally disintegrating tablet compositions for eosinophilic esophagitis |
| US10105315B2 (en) | 2016-08-18 | 2018-10-23 | Adare Pharmaceuticals, Inc. | Methods of treating eosinophilic esophagitis |
| US11026887B2 (en) | 2016-08-18 | 2021-06-08 | Ellodi Pharmaceuticals, L.P. | Methods of treating eosinophilic esophagitis |
| US11684571B2 (en) | 2016-08-18 | 2023-06-27 | Ellodi Pharmaceuticals, L.P. | Methods of treating eosinophilic esophagitis |
| US11896710B2 (en) | 2016-08-18 | 2024-02-13 | Ellodi Pharmaceuticals, L.P. | Methods of treating eosinophilic esophagitis |
Also Published As
| Publication number | Publication date |
|---|---|
| JP4173670B2 (en) | 2008-10-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Prajapati et al. | A review on recent patents on fast dissolving drug delivery system | |
| RU2193879C1 (en) | Pharmaceutical composition for treating acute disorders | |
| TWI288002B (en) | Orally disintegrating tablets and process for obtaining them | |
| JP4523265B2 (en) | Orally disintegrating preparations for the treatment of urination disorders | |
| KR100653568B1 (en) | Solid, quick dissolving cetirizine formulations | |
| JP5202856B2 (en) | Granular solid formulation containing tosfloxacin tosylate | |
| WO2005037254A1 (en) | Tablet quickly disintegrating in oral cavity | |
| ES2908977T3 (en) | Solid pharmaceutical dosage form for delivering at least two active pharmaceutical ingredients into the oral cavity | |
| JP5637624B2 (en) | Disintegrating particle composition and fast disintegrating compression molding using the same | |
| JP2009521523A (en) | Mouth-soluble pharmaceutical composition and method for producing the same | |
| JP2009114113A (en) | Intraorally disintegrable tablet and method for producing the same | |
| JP2001058944A (en) | Rapidly disintegrating solid formulation | |
| JP2002535269A (en) | Compositions and methods for mucosal distribution | |
| WO2005037319A1 (en) | Composition for tablet rapidly disintegrable in mouth | |
| JP2008531681A (en) | Fast disintegrating preparation containing magnesium carbonate heavy | |
| BRPI0620185B1 (en) | pharmaceutical formulation, tablets, and process for the preparation of a pharmaceutical formulation | |
| JP2006501233A (en) | Oral dosage form containing sildenafil with fast dissolution and occult taste | |
| JPWO2005055989A1 (en) | Drug-containing particles and solid preparation containing the particles | |
| JP2008260709A (en) | Intraoral disintegrator and method for producing the same | |
| JP4173670B2 (en) | Orally disintegrating preparation | |
| JP2003034655A (en) | Fast degradable solid tablet | |
| KR20070118247A (en) | Pranlukast hydrate-containing preparation having relieved bitterness | |
| JP3228335B2 (en) | Orally disintegrating composition and method for producing the same | |
| RU2426529C2 (en) | Orally decomposing powder, containing cilostazol and mannitol | |
| JP5204976B2 (en) | Fast disintegrating tablets containing iguratimod |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20041001 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20080610 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080709 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20080812 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20080814 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110822 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110822 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120822 Year of fee payment: 4 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130822 Year of fee payment: 5 |
|
| LAPS | Cancellation because of no payment of annual fees |