JPH11335295A - Stable aqueous solution preparation of calcium-controlling polypeptide hormone for parenteral administration - Google Patents
Stable aqueous solution preparation of calcium-controlling polypeptide hormone for parenteral administrationInfo
- Publication number
- JPH11335295A JPH11335295A JP10158513A JP15851398A JPH11335295A JP H11335295 A JPH11335295 A JP H11335295A JP 10158513 A JP10158513 A JP 10158513A JP 15851398 A JP15851398 A JP 15851398A JP H11335295 A JPH11335295 A JP H11335295A
- Authority
- JP
- Japan
- Prior art keywords
- aqueous solution
- parenteral administration
- calcium
- solution preparation
- polypeptide hormone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
【0001】背景技術 カルシトニンは哺乳類甲状腺および非哺乳類の外側甲状
腺から分泌されるアミノ酸残基32を含むポリペプチド
からなるカルシウム調節ホルモンである。エルカトニン
はウナギカルシトニンの合成類縁体であり、サケカルシ
トニンに似たアミノ酸配列を持っている。また合成サケ
カルシトニンはサルカトニン等の名称で知られている。
これらポリペプチドホルモンは、高カルシウム血症、骨
粗鬆症における疼痛、骨ページェット病に非経口的に投
与される。[0001] BACKGROUND Calcitonin is a calcium regulatory hormone consisting of a polypeptide comprising amino acid residues 32 secreted from mammalian thyroid and non-mammalian outer thyroid. Elcatonin is a synthetic analog of eel calcitonin and has an amino acid sequence similar to salmon calcitonin. Synthetic salmon calcitonin is known by a name such as sarcatonin.
These polypeptide hormones are administered parenterally for hypercalcemia, pain in osteoporosis, and Paget's disease of the bone.
【0002】水溶液中にこれらポリペプチドホルモンを
含む製剤を常法によりガラス製のアンプルやバイアルに
充填し、貯蔵すると経時的に該ホルモンの活性が低下す
る。これは溶出したガラス成分(主としてナトリウム)
によって溶液のpHが安定性にとって不利な域へシフト
するためと推測される。[0002] When a preparation containing these polypeptide hormones in an aqueous solution is filled in a glass ampoule or vial by a conventional method and stored, the activity of the hormone decreases with time. This is the eluted glass component (mainly sodium)
It is presumed that the pH of the solution shifts to a disadvantageous region for stability.
【0003】本発明はこの問題を克服する。[0003] The present invention overcomes this problem.
【0004】本発明の開示 本発明は、エルカトニンおよび合成カルシトニン(サ
ケ)よりなる群から選ばれたカルシウム調節ポリペプチ
ドホルモンの無菌水溶液を、少なくとも内面がSiO2
の薄い膜でコートされたガラス製アンプルもしくはバイ
アルに無菌充填してなる非経口投与用水溶液製剤を提供
する。DISCLOSURE OF THE INVENTION The present invention provides a sterile aqueous solution of a calcium-regulating polypeptide hormone selected from the group consisting of elcatonin and synthetic calcitonin (salmon), wherein at least the inner surface is SiO 2
The present invention provides an aqueous preparation for parenteral administration which is aseptically filled in a glass ampoule or vial coated with a thin film of
【0005】ガラス表面にSiO2 の薄い膜をコートす
る処理はシリコート処理として知られ、ガラス中の可溶
性成分の溶出を殆ど減らし、かつガラスの光学的性質に
殆ど影響しないため、内面をシリコート処理したアンプ
ルまたはバイアルを使用することにより、ポリペプチド
ホルモンの水溶液を安定にその中に貯蔵することができ
る。[0005] The process of coating a thin film of SiO 2 on a glass surface is known as a silycoat process. Since the elution of soluble components in the glass is substantially reduced and the optical properties of the glass are hardly affected, the inner surface is subjected to a silycoat process. By using an ampoule or vial, an aqueous solution of the polypeptide hormone can be stably stored therein.
【0006】該水溶液は、慣用の注射剤用添加剤を含む
ことができる。その例は等張化剤として塩化ナトリウム
がある。シリコート処理したアンプルまたは他のガラス
容器に密閉して充填する限り、pH調節剤、安定剤、保
存剤等の他の添加剤は通常添加しなくても良い。[0006] The aqueous solution may contain conventional injectable additives. An example is sodium chloride as a tonicity agent. Other additives such as a pH adjuster, a stabilizer, and a preservative need not usually be added as long as the ampoules or other glass containers that have been subjected to the silicide treatment are hermetically filled.
【0007】製剤の一般的製法は、始めに適量の注射用
蒸留水に最終濃度が等張濃度となる量の塩化ナトリウム
を溶解し、次にエルカトニンまたは合成サケカルシトニ
ンを静かに攪拌しながら加えて完全に溶解する。次に注
射用蒸留水を加え、静かに攪拌して所望の最終濃度とす
る。このようにして得た溶液を無菌濾過し、あらかじめ
滅菌処理した、内面シリコート処理アンプルまたはバイ
アルに無菌的に分注し、溶閉または密閉して製品とす
る。勿論安定性に悪影響しない限り、適宜変更を加える
ことができる。[0007] A general method for preparing a preparation is to first dissolve an appropriate amount of sodium chloride in an appropriate amount of distilled water for injection so that the final concentration is isotonic, and then add ercatonin or synthetic salmon calcitonin with gentle stirring. Dissolve completely. Then add distilled water for injection and gently stir to the desired final concentration. The solution thus obtained is aseptically filtered, aseptically dispensed into pre-sterilized ampoules or vials with an internal silicate treatment, and sealed or sealed to obtain a product. Of course, changes can be made appropriately as long as the stability is not adversely affected.
【0008】実施例および比較例製剤の製造 注射用蒸留水約900mLに塩水ナトリウム9,855
mgを溶解し、次にエルカトニン7.0mgを静かに攪
拌しながら加えて完全に溶解する。これに注射用蒸留水
を加えて全量を1,000mLとし、静かに攪拌して均
一な溶液とする。得られた調製液を無菌濾過し、あらか
じめ滅菌処理した内面シリコート処理ガラスアンプル
(不二硝子社製)に1mLづつ充填、溶閉して注射剤を
得た。Examples and Comparative Examples Preparation of Preparations About 900 mL of distilled water for injection was added to 9,855 sodium salt water.
mg and then add 7.0 mg of elcatonin with gentle stirring to completely dissolve. To this is added distilled water for injection to make the total volume 1,000 mL, and the mixture is gently stirred to obtain a uniform solution. The prepared solution was aseptically filtered, filled into glass ampoules (manufactured by Fuji Glass Co., Ltd.), each of which had been sterilized beforehand, and filled and sealed to obtain injections.
【0009】比較例においては、同じ調製液をシリコー
ト処理していないガラスアンプルに充填、溶閉した。In the comparative example, the same preparation solution was filled in a glass ampoule that had not been subjected to a silicide treatment, and sealed.
【0010】安定性試験 実施例および比較例で製造したアンプルを45℃におい
て7日、1ケ月および3ケ月保存し、HPLC法により
エルカトニンの残存量を定量し、初期値に対する残存率
(%)を算出した。結果を表1に示す。 Stability Test The ampoules produced in Examples and Comparative Examples were stored at 45 ° C. for 7 days, 1 month and 3 months, and the residual amount of elcatonin was quantified by HPLC, and the residual ratio (%) to the initial value was determined. Calculated. Table 1 shows the results.
【0011】[0011]
【表1】 表1 45℃保存におけるエルカトニン残存率 実施例 ──────────────────────────── 初期値 7日後 1ケ月後 3ケ月後 ──── ───── ────── ────── 100% 97% 79% 77% ──────────────────────────── 比較例 ──────────────────────────── 初期値 7日後 1ケ月後 3ケ月後 ──── ───── ────── ────── 100% 98% 77% 41% ────────────────────────────[Table 1] Table 1 Residual ratio of elcatonin after storage at 45 ° C Example ──────────────────────────── Initial value 7 days later 1 month later 3 months later ──── ───── ────── ────── 100% 97% 79% 77% ────────────────── ────────── Comparative example ──────────────────────────── Initial value 7 days later 1 month later 3 months later ──── ───── ────── ────── 100% 98% 77% 41% ───────────────────── ───────
【0012】上の数値は、いずれも平均値(n=4)で
ある。The above numerical values are all average values (n = 4).
【0013】表1の結果から明らかなように、実施例の
製品は比較例の製品よりも安定性においてすぐれてい
る。As is evident from the results in Table 1, the products of the examples have better stability than the products of the comparative examples.
【0014】エルカトニンに代え、合成サケカルシトニ
ン(サルカトニン)を用いて同じ試験を繰り返し、同様
な結果を得た。The same test was repeated using synthetic salmon calcitonin (sarcatonin) in place of elcatonin, and similar results were obtained.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 藤田 茂樹 大阪府門真市一番町26番7号 東和薬品株 式会社研究所内 (72)発明者 今井 文人 大阪府門真市一番町26番7号 東和薬品株 式会社研究所内 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Shigeki Fujita 26-7 Ichibancho, Kadoma-shi, Osaka Towa Pharmaceutical Co., Ltd. (72) Inventor Fumito Imai 26-7 Ichibancho, Kadoma-shi, Osaka Towa Pharmaceutical Co., Ltd.
Claims (2)
ケ)よりなる群から選ばれたカルシウム調節ポリペプチ
ドホルモンの無菌水溶液を、少なくとも内面がSiO2
の薄い膜でコートされたガラス製アンプルもしくはバイ
アルに無菌充填してなる非経口投与用水溶液製剤。1. A sterile aqueous solution of a calcium-regulating polypeptide hormone selected from the group consisting of elcatonin and synthetic calcitonin (salmon), wherein at least the inner surface is SiO 2
An aqueous solution for parenteral administration which is aseptically filled in a glass ampoule or vial coated with a thin film.
製剤。2. The preparation according to claim 1, wherein said aqueous solution is an isotonic aqueous solution.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP10158513A JPH11335295A (en) | 1998-05-22 | 1998-05-22 | Stable aqueous solution preparation of calcium-controlling polypeptide hormone for parenteral administration |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP10158513A JPH11335295A (en) | 1998-05-22 | 1998-05-22 | Stable aqueous solution preparation of calcium-controlling polypeptide hormone for parenteral administration |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH11335295A true JPH11335295A (en) | 1999-12-07 |
Family
ID=15673386
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP10158513A Pending JPH11335295A (en) | 1998-05-22 | 1998-05-22 | Stable aqueous solution preparation of calcium-controlling polypeptide hormone for parenteral administration |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH11335295A (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012229230A (en) * | 2003-05-23 | 2012-11-22 | Novo Nordisk Health Care Ag | Protein stabilization in solution |
JP2013006811A (en) * | 2011-06-27 | 2013-01-10 | Fujifilm Corp | Formulation packed in container |
-
1998
- 1998-05-22 JP JP10158513A patent/JPH11335295A/en active Pending
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012229230A (en) * | 2003-05-23 | 2012-11-22 | Novo Nordisk Health Care Ag | Protein stabilization in solution |
JP2013006811A (en) * | 2011-06-27 | 2013-01-10 | Fujifilm Corp | Formulation packed in container |
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