JPS60123426A - Secretin preparation for transnasal administration - Google Patents
Secretin preparation for transnasal administrationInfo
- Publication number
- JPS60123426A JPS60123426A JP58229820A JP22982083A JPS60123426A JP S60123426 A JPS60123426 A JP S60123426A JP 58229820 A JP58229820 A JP 58229820A JP 22982083 A JP22982083 A JP 22982083A JP S60123426 A JPS60123426 A JP S60123426A
- Authority
- JP
- Japan
- Prior art keywords
- secretin
- osmotic pressure
- aqueous solution
- preparation
- pressure ratio
- 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
Landscapes
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
【発明の詳細な説明】 本発明は経鼻投与用セクレチン製剤に関する。[Detailed description of the invention] The present invention relates to secretin preparations for nasal administration.
セクレチンは消化管ホルモンの一種、すなわち胚液分泌
ホルモンであり９月俗臓および胆嚢における疾患の治療
に使用される有用な物質である。ところでセクレチンは
、これを経口投与した場合には消化管内の加水分解酵素
により分解失活するために、経口投与以外の投与、具体
的には注射投与によって投与されてきた。しがしセクレ
チンがさらに広く使用されてその有用性を発揮するため
には、注射投与以外の簡便な方法によって投与されるこ
とがめられる。Secretin is a type of gastrointestinal hormone, ie, an embryonic fluid secretion hormone, and is a useful substance used in the treatment of diseases in the viscera and gallbladder. By the way, when secretin is orally administered, it is decomposed and inactivated by hydrolytic enzymes in the gastrointestinal tract. Therefore, secretin has been administered by administration other than oral administration, specifically by injection. In order for secretin to be used more widely and to demonstrate its usefulness, it is recommended that it be administered by a simple method other than injection.
かかる観点から本発明者はセクレチンを鼻粘膜を経由し
て吸収せしめる方法について検討を試みた。その結果、
セクレチンは鼻粘膜より速やかに吸収され、特にセクレ
チン水溶液として鼻粘膜に投与する場合に、当該水溶液
のｐＨが２乃至５であり、浸透圧比が１乃至５であると
きに速やかに吸収されることを知り２本発明を完成した
。From this point of view, the present inventor attempted to study a method for absorbing secretin via the nasal mucosa. the result,
Secretin is rapidly absorbed through the nasal mucosa, and especially when administered to the nasal mucosa as an aqueous solution of secretin, it is rapidly absorbed when the aqueous solution has a pH of 2 to 5 and an osmotic pressure ratio of 1 to 5. Completed two new inventions.
すなわち２本発明の目的はセクレチンを重粘るために２
本発明はセクレチンを経ｇ投匂用の水溶液とした場合に
、該水溶液のｐＨが２乃至５であり、かつ浸透圧比が１
乃至５であることを特徴とする技術手段を開示する。In other words, the purpose of the present invention is to make secretin thicker.
In the present invention, when secretin is made into an aqueous solution for oral administration, the aqueous solution has a pH of 2 to 5 and an osmotic pressure ratio of 1.
Disclosed are technical means characterized by the following.
以下に本発明を説明する。The present invention will be explained below.
本発明で使用されるセクレチンは哺乳類９例えばブタか
ら得られる天然セクレチンに限られず２合成セクレチン
あるいは特殊な方法によって９例えば醗酵によって得ら
れるセクレチンも含まれ、また精製物であっても粗製物
であってもよい。セクレチンの配合量は鼻粘膜投与のた
めの水溶液中において通常は０．０００４〜０．０４
Ｗ／Ｖ％であるのが好ましいが９本発明はセクレチンの
配合量によって特に限定されない。The secretin used in the present invention is not limited to natural secretin obtained from mammals, such as pigs, but also includes synthetic secretin or secretin obtained by special methods, such as fermentation, and may be purified or crude. It's okay. The amount of secretin blended in an aqueous solution for nasal mucosal administration is usually 0.0004 to 0.04.
W/V% is preferred, but the present invention is not particularly limited by the amount of secretin blended.
経鼻投与とは鼻粘膜を経由して薬物を吸収せしめようと
する投与の形態であり、具体的には主として水溶液を鼻
粘膜に噴霧あるいは点滴せしめることによって達成され
る。Nasal administration is a form of administration in which the drug is absorbed through the nasal mucosa, and is specifically achieved mainly by spraying or dripping an aqueous solution onto the nasal mucosa.
経鼻投与用の製剤は直接的には噴霧あるいは点滴に適す
るように水溶液であることが便利である。しかし間接的
には例えば製剤がセクレチンの凍結乾燥粉末と溶解液と
の組合せとして与えられ、同時溶解して使用される例も
含まれる。Preparations for nasal administration are conveniently in the form of aqueous solutions suitable for direct spraying or infusion. However, indirectly, for example, a preparation is provided as a combination of a freeze-dried powder of secretin and a solution, and examples are also included in which the preparation is used by simultaneous dissolution.
本発明は投与に当っては水溶液であることが必須の条件
であり、従って本発明製剤は最終的には水溶液となり得
る製剤であれば、いづれを選択してもよ（、上記例示に
よって特に限定されない。It is an essential condition for the present invention to be an aqueous solution for administration; therefore, any formulation of the present invention may be selected as long as it can ultimately become an aqueous solution (although this is not particularly limited by the above examples). Not done.
本発明において投与に当っての水溶液は、そのｐＨが２
乃至５であり、かつ浸透圧比が１乃至５であることが必
須の条件である。ｐＨを２乃至５に調節あるいは維持す
るために適当な緩衝剤。In the present invention, the aqueous solution for administration has a pH of 2.
The essential conditions are that the osmotic pressure ratio is between 1 and 5, and the osmotic pressure ratio is between 1 and 5. A suitable buffer for adjusting or maintaining pH between 2 and 5.
例えばクエン酸リン酸緩衝液等を加えることは自由であ
る。後記実験例によって示されるごと＜ｐＨを２乃至５
とすることによって経鼻吸収は促進され、膵外分泌増加
量の積算値が増大する。For example, it is free to add citrate phosphate buffer and the like. As shown in the experimental examples below, the pH is 2 to 5.
By doing so, nasal absorption is promoted and the cumulative value of increase in pancreatic exocrine secretion increases.
浸透圧比とは生理的浸透圧に対する相対比を言う。本発
明においては０．９％塩化ナトリウム水溶液の浸透圧比
を１として、塩化ナトリウムの濃度換算によって浸透圧
比を示すことにする。例えば水溶液の濃度が塩化ナトリ
ウム濃度に換算して１．８％であるならば浸透圧比を２
と定義する。Osmolarity ratio refers to the relative ratio to physiological osmotic pressure. In the present invention, the osmotic pressure ratio of a 0.9% sodium chloride aqueous solution is assumed to be 1, and the osmotic pressure ratio is expressed in terms of concentration of sodium chloride. For example, if the concentration of the aqueous solution is 1.8% in terms of sodium chloride concentration, the osmotic pressure ratio is 2.
It is defined as
従って、塩化ナトリウムの適宜量を添加して所定の浸透
圧比に調節することができる。後記実験例によって示さ
れるごとく浸透圧比が１乃至５において膵外分泌増加量
の積算値が対照に比して増大する。Therefore, the osmotic pressure ratio can be adjusted to a predetermined value by adding an appropriate amount of sodium chloride. As shown in the experimental examples described later, when the osmotic pressure ratio is 1 to 5, the integrated value of the increase in pancreatic exocrine secretion increases compared to the control.
本発明製剤の製法は相当する製剤を製造するための通常
の方法を選択すればよい。また本発明製剤中に緩衝剤、
浸透圧比調節剤、防腐剤等を適宜選択して加えることは
自由である。For the production of the formulation of the present invention, any conventional method for producing the corresponding formulation may be selected. In addition, a buffer in the formulation of the present invention,
It is free to select and add osmotic pressure ratio regulators, preservatives, etc. as appropriate.
実験例１
試料
合成セクレチン（協Ｑ’；；＋単位／ｍｙ’）を塩化ナ
トリウム水溶液に溶解して、浸透圧比を１，３および５
とした試料Ａ、ＢおよびＣを用意した。Experimental Example 1 Sample synthesis Secretin (Kyo Q'; + unit/my') was dissolved in an aqueous sodium chloride solution, and the osmotic pressure ratio was adjusted to 1, 3 and 5.
Samples A, B and C were prepared.
なお、いづれもセクレチン活性は１００単位／ｍｌであ
る。The secretin activity in each case was 100 units/ml.
仔、ｃｔｒ。child, ctr.
合成セクレチン（Ｊ２％０ＯＯ一単位／ＴｒｖＪ）を生
理的クエン酸−リン酸緩衝液に溶解してｐＨを２．０
、３．０ 。Synthetic secretin (1 unit of J2%0OO/TrvJ) was dissolved in physiological citrate-phosphate buffer to pH 2.0.
, 3.0.
３６８および４．８とした試料り、 Ｅ、 ＦおよびＧ
を用意した。なお、いづれもセクレチン活性は１００単
位／１ｎＬであり、浸透圧比は１である。368 and 4.8 samples, E, F and G
prepared. In addition, the secretin activity in each case is 100 units/1 nL, and the osmotic pressure ratio is 1.
別に合成セクレチン（２４；０００単位／ｍｇ）のみを
溶解した水溶液を用意し、対照とした。Separately, an aqueous solution in which only synthetic secretin (24,000 units/mg) was dissolved was prepared and used as a control.
方法
ＳＤ系雌雄性ラット体重２５０〜３００ｇ）にウレタン
１７０ｍｇ／１００ｇを腹腔内注射によって投与して麻
酔し、各試料６．２ｍＬ／ｈｙをマイクロシリンジで鼻
腔内に投与した。その後、あらかじめ膵管ニカニュレー
ションしたポリエチレンチューブの人工膵管から流出す
る膵液分泌量を経時的に測定した。Method Male and female SD rats (body weight 250-300 g) were anesthetized by intraperitoneal injection of urethane (170 mg/100 g), and 6.2 mL/hy of each sample was administered intranasally using a microsyringe. Thereafter, the amount of pancreatic juice secretion flowing out from the artificial pancreatic duct of the polyethylene tube in which the pancreatic duct had been nicannulated in advance was measured over time.
結果
結果を表１に示す。表１の数値は膵液分泌量から自然に
流出する基礎分泌量を差引いた値すなわち膵外分泌増加
量の経時的な積算値を示す。なお、各数値はラット４〜
８匹の平均値で示した。Results The results are shown in Table 1. The numerical values in Table 1 indicate the value obtained by subtracting the basal secretion amount that naturally flows out from the amount of pancreatic juice secretion, that is, the cumulative value of the increase in pancreatic exocrine secretion over time. In addition, each value is rat 4~
The average value of 8 animals is shown.
表１
以下に記載する実施例をもって本発明を具体的に説明す
る。Table 1 The present invention will be specifically explained with reference to Examples described below.
実施例１
合成セクレチン（２４，０００単位／ｍｇ） ８３ｍ、
ｇを生理１−１４
的クエン酸リン酸緩衝液（皆） １０１に溶解し。Example 1 Synthetic secretin (24,000 units/mg) 83m,
1-14 g was dissolved in 101 g of physiological citrate phosphate buffer (all).
さらに塩化ナトリウム９０ｙおよびパラオキシ安息香酸
ブチル１ｇを加え２本発明経鼻投与用水溶液とした。Furthermore, 90 y of sodium chloride and 1 g of butyl paraoxybenzoate were added to form an aqueous solution for nasal administration of the present invention.
実施例２
合成セクレチン（２４，０００単位／ｍｙ） １６．６
■を水１１に溶解し、その１ ａｔを２ｒａ１点鼻用バ
イアルに分注して凍結乾燥し、粉末バイアルを用意した
。別に、生理用クエン酸リン酸緩衝液（り ２ ＴＬＬ
をアンプルに充填して溶解用溶液として添付して１本発
明経鼻投与用製剤とした。Example 2 Synthetic secretin (24,000 units/my) 16.6
(2) was dissolved in 11 parts of water, and 1 part of the solution was dispensed into 2 ra 1 nasal drop vials and freeze-dried to prepare powder vials. Separately, sanitary citrate phosphate buffer (RI 2 TLL
This was filled into an ampoule and attached as a dissolution solution to prepare a nasal preparation of the present invention.
特許出願人 工−ザイ株式会社patent applicant Ko-zai Co., Ltd.
Claims (3)
与用セクレチン製剤。(1) When made into an aqueous solution, the pH is 2 to 5. A secretin preparation for nasal administration, which has an osmotic pressure ratio of 1 to 5.
求の範囲第１項記載の経鼻投与用セクレチン製剤。(2) The secretin preparation for nasal administration according to claim 1, wherein the secretin preparation for nasal administration is an aqueous solution.
解液との組合せである特許請求の範囲第１項記載の経鼻
投与用セクレチン製剤。(3) The secretin preparation for nasal administration according to claim 1, wherein the secretin preparation for nasal administration is a combination of secretin powder and a solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58229820A JPS60123426A (en) | 1983-12-07 | 1983-12-07 | Secretin preparation for transnasal administration |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58229820A JPS60123426A (en) | 1983-12-07 | 1983-12-07 | Secretin preparation for transnasal administration |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60123426A true JPS60123426A (en) | 1985-07-02 |
| JPH0376291B2 JPH0376291B2 (en) | 1991-12-05 |
Family
ID=16898174
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58229820A Granted JPS60123426A (en) | 1983-12-07 | 1983-12-07 | Secretin preparation for transnasal administration |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60123426A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BG64919B1 (en) * | 1998-04-21 | 2006-09-29 | Teijin Ltd. | Pharmaceutical composition for mucous membrane application |
| JP2007532515A (en) * | 2004-04-07 | 2007-11-15 | アレス トレーディング ソシエテ アノニム | Growth hormone solution |
| KR20180066071A (en) | 2015-10-30 | 2018-06-18 | 데이진 화-마 가부시키가이샤 | Pharmaceutical composition for nasal administration |
-
1983
- 1983-12-07 JP JP58229820A patent/JPS60123426A/en active Granted
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BG64919B1 (en) * | 1998-04-21 | 2006-09-29 | Teijin Ltd. | Pharmaceutical composition for mucous membrane application |
| JP2007532515A (en) * | 2004-04-07 | 2007-11-15 | アレス トレーディング ソシエテ アノニム | Growth hormone solution |
| KR20180066071A (en) | 2015-10-30 | 2018-06-18 | 데이진 화-마 가부시키가이샤 | Pharmaceutical composition for nasal administration |
| US10849978B2 (en) | 2015-10-30 | 2020-12-01 | Teijin Pharma Limited | Pharmaceutical composition for administration to nasal mucosa |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0376291B2 (en) | 1991-12-05 |
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