JPH01132514A - Stable vitamin complex freeze-dried pharaceutical - Google Patents

Abstract

PURPOSE:To obtain the title pharmaceutical, suitable for applying to patients incapable of nutritional oral intake, such as postoperative patients, and having improved blending stability of mutual vitamins, by using at least 9 kinds of water-soluble essential vitamins with a basic amino acid in combination. CONSTITUTION:The above-mentioned pharmaceutical, obtained by blending a basic amino acid, such as histidine, arginine or lysine, and/or inorganic acid salt thereof, such as hydrochloride, sulfate or phosphate, in an amount of about 7-150wt.%, preferably about 20-100wt.% based on the total amount of the vitamins in the above-mentioned pharmaceutical containing at least 9 kinds of water-soluble essential vitamins, e.g., vitamins B1, B2, B6, B12, folic acid, nicotinic acid, nicotinamide, pantothenic acid, pantothenyl alcohol, biotin and vitamin C or further fat-soluble vitamins containing a suitable solubilizing agent added thereto, e.g. vitamins A, D, E and/or K, capable of suppressing reduction in contents of the various vitamins in the same container and having excellent blending stability.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a lyophilized multivitamin preparation suitable for use as a sprig to high-calorie infusions applied to patients who are unable to take nutritional supplements orally, such as after internal eczema surgery.

[Conventional technology]

In recent years, nutritional management for patients who are unable to take nutrients orally after surgery, etc. has improved dramatically with the development of high-calorie infusion therapy using central parenteral nutrition, and various essential vitamins have been added to this high-calorie infusion. is also becoming commonplace.

To this end, various forms of multivitamin supplements have been developed to be added to high-calorie infusions.

In order for the vitamins in the mold to be effectively and safely administered to the human body, the required performance in formulating this multivitamin is stability during market distribution from manufacture to use, as well as the addition of vitamins. Convenience in use is important in order to minimize bacterial contamination during the preparation of high-calorie infusions. Many vitamins are unstable on their own, and there are many combinations that become even more unstable when they are combined with each other. The formulation is divided into containers and formulated (Japanese Patent Application Laid-open Nos. 56-77222 and 1982-116413).

[Problem that the invention seeks to solve]

However, in order to improve the ease of use, it is desirable to reduce the number of containers for the layered agent as much as possible, and the development of multivitamin preparations with good formulation stability is expected.

[Means for solving problems]

As a result of intensive research aimed at stabilizing multivitamin cleavage agents, the present inventors discovered that the use of basic amino acids as stabilizers suppresses the decrease in vitamin content in multivitamins.

The present invention has been completed based on the above findings. The nine water-soluble essential vitamins include vitamin Bll B2.
86.81°1 Folic acid, nicotinic acid or nicotinamide, pantothenic acid or pantothenyl alcohol, biotin and vitamin C. Furthermore, fat-soluble vitamins obtained by adding a suitable solubilizer to these vitamins may be added. Fat-soluble vitamins include vitamins A, D, E and/or vitamin K. Although there are no particular limitations on the amounts of these vitamins, it is preferable to mix them in amounts that are close to the amount that can supplement the daily intake of humans. An example of the amount of each vitamin is vitamin 821.
10 ■, Vitamin B61-10mg, pantothenic acid 5-25rr@, vitamin CC50-250ff1.
Vitamin YB, 1-10”'g, Vitamin B121
30 μg 1 folic acid 100-1000 μg 1 piotin 20-
300 μg 1 nicotinic acid 10-50 ■, vitamin A 20
00-5000IU, vitamin D200-1000IU
, vitamin E5-20IU, vitamin I (0,2-1o
It is desirable that it be blended at the same ratio as Tan.

Specific examples of the blending amounts are shown in Table 1.

Table 1: Falling Tree of Vitamin Components and Amounts of Multivitamin Preparations Examples of the basic amino acids used in the invention include histidine, arginine, and lysine.

In addition, salts of basic amino acids with inorganic acids such as hydrochlorides, sulfates, and phosphates can also be used. These basic amino acids or their salts with inorganic acids may be used alone, or
Two or more types may be used in combination.

The amount of basic amino acids to be used is about 7 to about 150 w/w%, preferably about 20 to about 100 w/w%, based on the total amount of vitamins to be mixed.

Furthermore, excipients may be added to form a freeze-dried cleaving agent.

Excipients include sugar alcohols such as mannitol, monosaccharides such as lactose and maltose, oligosaccharides, and polymers such as chondroitin sulfate and dextran. If excipients are used, the amount used should be 0.01% of the total amount of combined vitamins.
It is good to use up to 3 times, preferably 0.3 to 2.5 times.

Further, when adding fat-soluble vitamins, it is necessary to use a solubilizer, and for example, polyoxyethylene rubitan fatty acid ester such as polysorbate 80 can be used. The amount of solubilizer used is 3-10% of the fat-soluble vitamin.
By using double the amount, a clear solution can be obtained upon re-dissolving the lyophilized sticky agent.

The layer agent of the present invention can be prepared by a conventional method for producing an injection. That is, water-soluble vitamins are dissolved in distilled water for injection, and after further dissolving the stabilizer according to the present invention, the pH is adjusted to pH 4.5-6 using a pI-1 adjusting agent such as sodium hydroxide.
5 to obtain a chemical solution. This drug solution is divided into containers and then freeze-dried to obtain lacerated wounds. If fat-soluble vitamins are to be added, an aqueous solution of fat-soluble vitamins solubilized with a surfactant may be added to the above-mentioned drug solution, and the resulting mixture may be divided into containers and freeze-dried. The concentration of the solid content in the drug solution is not particularly limited, but is selected in consideration of the solubility of vitamins and excipients, the solubility of freeze-dried lacerations, and the difficulty and efficiency of freeze-drying. In other words, if the concentration is too high, the solubility during preparation of the drug solution and the resolubility due to crystal precipitation during freeze-drying will decrease, and if the concentration is too low, the drying efficiency will decrease due to the lack of water to be removed. Maneku.

In the range of vitamin compounding amount in the present invention, the solid content is 1 to 1.
It is desirable to include it in tomt.

〔Effect of the invention〕

After storing the sample group prepared according to the present invention and a sample prepared without adding a stabilizer as a control at 50° C. for 10 days, the content of vitamins in the samples was measured and the residual rate was determined. The sample used had the composition shown in Example 1.2 below. As a control, the formulation of Example 1 without the stabilizer was used. The results are shown in Table 2.

As is clear from this table, the formulation of the present invention has improved vitamin stability compared to the control example, and in particular, the stability of dianocobalamin has been greatly improved.

Table 2 As is clear from the above, according to the present invention, a stable lyophilized multivitamin preparation with reduced content of various vitamins can be obtained even in a single container.

Example 1 Water-soluble vitamins were dissolved in distilled water for injection according to the amounts of vitamins shown in Table 1. To this solution, 50 μm of histidine hydrochloride (monohydrate) was added as a stabilizer and dissolved. In addition, fat-soluble vitamins are solubilized in distilled water for injection using polysorbate 8060 to form an aqueous solution. These two solutions were mixed, and the pH was adjusted to about 5.0 using sodium hydroxide, so that the total volume was 2 ml. The obtained drug solution was filled into a vial, freeze-dried, and then sealed with a rubber stopper to obtain a product of the present invention.

Example 2 A product of the present invention was obtained by carrying out the same procedure as in Example 1, except that the amount of histidine hydrochloride was changed to 100 ml instead of 50 ml, and the total amount was 3 ml.

Example 3 A product of the present invention was obtained in the same manner as in Example 1 except that arginine hydrochloride was used instead of histidine hydrochloride.

Example 4 A control product was obtained in the same manner as in Example 1 except that lysine hydrochloride was used instead of histidine hydrochloride.

Claims (1)

[Claims] A lyophilized multivitamin preparation characterized by containing at least nine water-soluble essential vitamins and basic amino acids.