JPS63313734A - syrup - Google Patents

Abstract

PURPOSE:To obtain a syrup stable with time and capable of being compounded with other drug active components, by using lysozyme or its salt optionally in combination with bromhexine or its salt as active components and adding maltitol as a sugar component. CONSTITUTION:The aging stability of a syrup containing 0.03-0.3wt.% of lysozyme or its salt and optionally 0.01-0.4wt.% of bromhexine or its salt can be improved by adding 20-70g of maltitol as a sugar component per 100ml of the syrup. The syrup prepared by the above process is resistant to discoloration with time and can be compounded with other drug active components. The pH of the syrup is preferably adjusted to 3-5. The syrup has excellent anti-inflammatory and hemostatic actions and can be easily administered even to aged person and child.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a syrup containing lysozyme or a salt thereof, or lysozyme or a salt thereof, and bromhexine or a salt thereof as active ingredients, and more specifically, a syrup containing lysozyme or a salt thereof, or bromhexine or a salt thereof as active ingredients. Concerning stable syrups.

[Conventional technology]

Lysozyme is a basic protein discovered as a bacteriolytic enzyme, and has excellent anti-inflammatory and hemostatic effects, and is therefore used in a wide range of medicines.

Lysozyme or its salts are administered orally, and are often in the form of syrups, which are easy to take even for the elderly and young children. Conventionally, lysozyme syrup preparations have been prepared by using refined white sugar as the syrup base carbohydrate. However, lysozyme syrup preparations containing refined white sugar as the carbohydrate have the disadvantage that lysozyme or its salts become deactivated and colored over time.

For this reason, a method has been proposed in which D-sorbitol, xylitol, etc. are used as carbohydrates instead of refined white sugar (Japanese Patent Publications No. 16609/1982 and No. 16126/1986), but these carbohydrates have a It has the disadvantage of causing diarrhea symptoms. The pH of the syrup is adjusted using refined white sugar.
A method of keeping the temperature at 4.7~6 has also been proposed (Unexamined Japanese Patent Publication No. 1983
-19535). However, in this method, the target syrup contains medicinal ingredients other than lysozyme.
In particular, when a basic compound is blended, the solubility of the compound is lowered, so there is a drawback that the types and amounts of the ingredients to be blended are limited.

Furthermore, in the treatment of common colds, lysozyme or its salts are often used in combination with bromhexine or its salts, which are antitussive and expectorant drugs that promote mucus secretion and dissolve mucus. [Problems to be solved by the invention] Therefore, syrups that use refined white sugar as the carbohydrate have the problem of decreasing bromhexine content and coloring over time. [Problems to be solved by the invention] Therefore, lysozyme or its salt It has been eagerly awaited to develop a syrup containing this and bromhexine or its salt as an active ingredient, which is stable over time and can also be combined with other medicinal ingredients.

[Means for solving problems]

Therefore, the present inventors conducted various studies in order to solve the above problems, and found that if maltitol was used as the carbohydrate in the syrup, it would be possible to create a syrup that is stable over time and can be mixed with other medicinal ingredients. The inventors have discovered that the present invention can be obtained and completed the present invention.

That is, the present invention provides a syrup containing lysozyme or a group thereof and bromhexine or a salt thereof as active ingredients, which is characterized in that maltitol is used as the carbohydrate.

Maltitol used in the present invention is a disaccharide sugar alcohol also called reduced maltose, and is produced by reducing maltose. This product is commercially available, for example, as reduced maltose starch syrup (containing 75 to 80% by weight of maltitol in dry matter), powdered reduced maltose starch syrup (powder containing 93% or more by weight of maltitol), etc. The object of the present invention can also be achieved using the following.

Since lysozyme, which is the active ingredient of the syrup of the present invention, is a basic protein, the free protein can be used as it is, but it is particularly preferable to use lysozyme chloride if it contains no salts. Although bromhexine is a basic compound having a primary amino group, it is preferably used as a salt with an acid, particularly as a hydrochloride.

The blended amount of maltitol is 100mA! 10 to 75 g, especially 20 to 70 g is preferable (7 g).

For example, when lysozyme chloride is used, the amount of lysozyme to be blended is preferably 0.01 to 2.0% by weight, particularly 0.03 to 0.3% by weight, based on the total amount of the syrup. For example, when bromhexine hydrochloride is used, the blending amount of bromhexine is preferably 0.01 to 0.4% by weight based on the total amount of the syrup.

Although it is not necessary to particularly adjust the pH of the syrup of the present invention, it is preferable to adjust the pH as appropriate depending on the properties of the ingredients other than the above-mentioned active ingredients. Generally, it is preferable to adjust the pH to about 3 to 5. To adjust the pH, use citric acid, sodium citrate, malic acid, phosphoric acid, sodium phosphate, hydrochloric acid,
This can be done using conventional pH adjusters such as sodium hydroxide.

The syrup of the present invention may contain one or more other medicinal ingredients, if necessary. For example,
Antitussives such as dihydrocodine phosphate, methylephedrine hydrochloride, dextromethorphan hydrobromide, noscapine hydrochloride, phenylzolonoQ-nolamine hydrochloride, and methoxyphenamine hydrochloride; antipyretic analgesics such as acetaminophen and ethenzamide; glycerin monoguagycol, Expectorants such as potassium guaiacolsulfonate; chlorpheniramine maleate, carbinoxamine maleate, cyphenhydramine hydrochloride, 2-isopropylamino-hydrochloride
Antihistamines such as 6-methylhezotane; bactericidal agents such as chlorhexicine hydrochloride and benzethonium hydrochloride; hypnotic sedatives such as bromvalerylurea and bromdiethylacetylurea; vasoconstrictors such as naphazoline hydrochloride and phenylephrine hydrochloride; local anesthetics such as zobucaine hydrochloride;
Examples include vitamins such as thiamine nitrate, riboflavin, and sodium ascorbate.

Others 1. Preservatives such as methyl paraoxybenzoate, ethyl paraoxybenzoate, zolopyl paraoxybenzoate, sorbic acid, sodium benzoate; orange flavor, glacier flavor, strawberry flavor,
Flavoring agents such as vanilla essence can also be added as necessary.

The syrup of the present invention is manufactured by a conventional method, for example, the following method. That is, purified water is added to the calculated amount of maltitol, preservative, etc. to make about 90% of the total amount, and preferably dissolved by heating. Next, add and dissolve this solution KIJ zozyme, bromhexine, other medicinal ingredients, fragrances, etc.
Further, adjust the pH to a predetermined value using a pH adjuster, and add purified water to bring the total amount to a predetermined amount. The desired syrup is obtained by performing filtration operations such as diatomaceous earth filtration and membrane filter filtration, and sterilization operations such as plate sterilization and hot shower sterilization.

[Action and effect of the invention]

By using maltitol as the carbohydrate, the syrup of the present invention dramatically improves the stability of lysozyme or its salt, or this and bromhexine or its salt, and can also be combined with various other medicinal ingredients. It is something.

〔Example〕

Next, the present invention will be explained in detail with reference to Examples.

Example 1 Reduced maltose starch syrup (containing 75 to 80% by weight of maltitol in dry matter) 2 icg,) Q methyl hydroxybenzoate 0.
6 fl, IQ ethyl benzoate 0.9 g and Q
Add purified water to 0.6 g of Zoropyru laoxybenzoate and add 2
7001nl, heated to 80℃ and dissolved, 30
Cooled to ℃. Add and dissolve 6 g of lysozyme chloride in this solution, and adjust the pH to 4 with citric acid and sodium citrate.
, adjusted to 0. Furthermore, add purified water to this and make 300
omz, membrane filter filtration and plate sterilization were performed, and 60-ml bottles were filled into brown bottles to obtain lysozyme syrup.

Example 2 According to Example 1, the following formulation was applied to the zozyme syrup (p
H4,0) was obtained.

Lysozyme chloride 6.0.9 Bromhexine hydrochloride 1.2g Zohydrocodeine phosphate 3.0g dJ-methylephedrine hydrochloride 7.5g Chlorpheniramine maleate 1.2g Methyl oxybenzoate 0.6 g IQ Ethyl oxybenzoate 0 .99, Q zolovir oxybenzoate 0
．． 69 Citric acid Appropriate amount Sodium citrate Appropriate amount Purified water Total amount 300 (Hm)
H3,4) was obtained.

Lysozyme chloride 6.0g Acetaminophen 6.0!9 Anhydrous caffeine
0.259 Maltitol 1500. Og
IQ Methyl laoxybenzoate 0.6 g, Q Ethyl laoxybenzoate 0.9.9 Zolopyl laoxybenzoate 0.6 g Citric acid Appropriate amount Sodium citrate Appropriate amount Flavoring Appropriate amount Purified water Total amount 30001 nl Test example According to Example 1, Lysozyme chloride 0.6g, reduced maltose starch syrup 100.9. Dissolve 0.12 g of bromhexine hydrochloride and appropriate amounts of methyl no-9-oxybenzoate, ethyl no-9-oxybenzoate, citric acid and sodium citrate in purified water, adjust the pH to 3.4 to make the total amount 3001,
Sample 1 was obtained by sterilizing the plate. Sample 2 has the same composition as Sample 1 and has a pH adjusted to 4.6.
And so. Samples 3 and 4 were prepared in the same manner as above using 150 g of refined white sugar instead of reduced maltose.

These samples were filled into 301 brown bottles and stored at 40°C for 6 months, and the residual rate of lysozyme chloride (%) of each sample was determined.
and changes in appearance were investigated. The results are shown in Table 1.

Table 1 The above results clearly show that the stability of lysozyme chloride is dramatically improved by using maltitol as the carbohydrate in the syrup.

that's all

Claims (1)

[Claims] 1. A syrup containing lysozyme or a salt thereof as an active ingredient, characterized in that maltitol is used as the carbohydrate. 2. A syrup containing lysozyme or its salt and bromhexine or its salt as active ingredients, characterized in that maltitol is used as the carbohydrate.