JPH11335295A - Stable aqueous solution preparation of calcium-controlling polypeptide hormone for parenteral administration - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an elcatonin or synthetic salmon calcitonin aqueous solution preparation stable during its storage and used for parenteral administration. SOLUTION: A parenteral administration aqueous solution containing elcatonin or synthetic salmon calcitonin is aseptically charged into a glass ampoule or glass vial at least whose inner wall is coated with the thin film of SiO2 .

Description

DETAILED DESCRIPTION OF THE INVENTION

[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] 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] The present invention overcomes this problem.

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] 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] 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] 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.

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.

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.

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]

[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% ───────────────────── ───────

The above numerical values are all average values (n = 4).

As is evident from the results in Table 1, the products of the examples have better stability than the products of the comparative examples.

The same test was repeated using synthetic salmon calcitonin (sarcatonin) in place of elcatonin, and similar results were obtained.

 ──────────────────────────────────────────────────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)

[Claims] 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. 2. The preparation according to claim 1, wherein said aqueous solution is an isotonic aqueous solution.