JPH08503703A - Syrup containing N-acetyl cysteine - Google Patents

Abstract

  (57) [Summary] A syrup containing N-acetylcysteine, which is stable for at least 2 years and has a good taste and odor, consists of an aqueous solution of NAC, sweetener and thickener. The solution can also include seasonings and preservatives. The pH is 5-8.

Description

Detailed Description of the Invention                   Syrup containing N-acetyl cysteine   The present invention provides a composition in the form of a syrup containing N-acetylcysteine as an active ingredient About things.   N-acetyl cysteine (hereinafter simply referred to as NAC) is widely used as a drug Compounds with some pharmacological properties useful for   NAC may be useful in the treatment of colds due to its mucolytic properties. Was shown.   One of the widely used drug forms in the treatment of colds is syrup Yes, which is particularly suitable for pediatric use.   Although NAC is useful in some drug forms, it has high molecular reactivity, relative Due to instability and the characteristic sulfury odor and taste, time-stabl e) to achieve a liquid form for oral use that should be of good taste Has become extremely difficult.   The preparation of the syrup, especially in all cases, comprises a sweetener and an aqueous solution of the drug. It requires the use of disaccharides (sucrose) or simple sugars as thickeners. Shi However, due to the interaction of NAC with sugars, the solution produces an undesired brown coloration, NAC titer decreases.   Therefore, it is impossible to leave NAC in solution for a long time in the presence of sucrose. Is.   Similarly, a reaction that produces a brown coloration and gives off a malodor occurs between NAC and monosaccharides. Also occurs, this use of which results in French patent application No. 263 in the name of Calco Anstalt 1831.   To the best of our knowledge, the only syrup formulation on the market that contains NAC Comprises a composition prepared at the time of use by dissolving the granules in water.   After preparation, the syrup prepared in situ must be used within 3 weeks .   Surprisingly, the present inventors have found that, without sugar, they have a good flavor and are stable over time. It has been found that a sex NAC syrup can be prepared.   Therefore, the objects of the present invention are the following (in 100 ml): -N-acetyl cysteine 2-4.2 g / 100 ml -Sweetener 0.02-0.3g / 100ml -Sodium carboxymethyl cellulose and hydroxypropyl methylcell Thickening agent selected from the group consisting of loin or mixtures thereof 0.1-4 g / 100 ml And optionally: -Seasoning 0.1-0.4 g / 100 ml -Preservative 0.05-0.5 g / 100 ml (Containing water to make 100 ml), and the pH is between 5 and 8, It is a composition in the form of a lop.   The above solution should be stored in a closed bottle under inert gas under environmental conditions for at least 2 years. It is stable. When opened, the solution has a good taste and no offensive odor; NAC maintains the initial titer and the open syrup is stable for at least 5 weeks.   By sweetener is meant a substance that sweetens the solution but does not contain sugar. Special features of sweetener Common examples are saccharin, saccharin sodium salt and siku Lamate or a mixture thereof.   The amount of sweetener is the minimum amount sufficient to give the solution a good taste.   Thickener, sodium carboxymethyl cellulose and hydroxypropyl Selected from the group consisting of methylcellulose or mixtures thereof. Astonishing thing In addition, these substances are compatible with NAC and, in solution, in the usual taste of syrup. It has been shown that a suitable concentration can be given.   These three basic ingredients (NAC, sweetener and thickener) are optionally finalized. Adjust the pH so that it is maintained between 5 and 8 by adding water to the specified volume. It can be quantity. Preferably the pH is 6.5-7.   Syrup is generally manufactured in a non-sterile state, so the type of drug must always be preservative. Need to be present. In addition, preservatives may prevent microbiology during use by patients. It is necessary to ensure microbiological quality.   In this case, sodium benzoate, methyl 4-hydroxybenzoate, Selected from the group consisting of ropyl 4-hydroxybenzoate and mixtures thereof. It is preferable to use the preserved preservative.   Sodium EDTA, which has the dual functions of preservative and metal chelating agent, It may be used in addition to, or in part as an alternative to, the preservative.   The production of the syrups of the present invention consists in simply dissolving the substance in a given amount of water under an inert gas. By implementing.   The formed solution is dispensed into multiple dose bottles or single dose containers.   Adult (eg 10 milliliters) or children (eg. Providing progressive doses at the same time for precise doses in a single dose (eg 5 ml) Will be possible.   The following examples are provided to more fully illustrate the present invention. Example 1   The following (in 100 ml): NAC 2.1g Saccharin 0.04g Sodium carboxymethyl cellulose 0.2g Sodium benzoate 0.15g 0.1 g of sodium edetate Raspberry seasoning 0.25g (Add water to make 100 milliliters) Purified 10 liters of syrup containing the It was prepared by dissolving in.   The pH of the solution formed was adjusted to 6.5 by adding sodium hydroxide. Adjusted to the value.   The solution was dispensed at a rate of 150 milliliters per bottle.   The bottle was stored at room temperature for 2 years.   After this period, NAC titers were above 95% of the initial titers.   Such a titer is 90% or more of the initial titer even 5 weeks after opening the bottle. there were.   Also, the syrup after storage for 2 years has a good flavor and odor and a good It was shown to have general taste. Example 2   The following composition (in 100 ml): NAC 2.1g Saccharin sodium salt 0.04g Hydroxypropyl methylcellulose 0.2g Methyl 4-hydroxybenzoate 0.1 g Sodium edetate 0.1g Apricot seasoning 0.1g (Add water to make 100 milliliters) 10 liters of syrup containing 1 part of hydroxypropyl methylcellulose It was prepared by dispersing in boiling water and cooling to room temperature. Hydroxy After hydration of propylmethylcellulose, purify all remaining material under a nitrogen atmosphere. It was then poured into the solution obtained by dissolving in degassed water.   The pH of this solution was adjusted to 6.5 with sodium hydroxide.   Dispense the solution into 10 ml single dose sachets, each containing about 200 It contained mg NAC. Example 3   The following composition (in 100 ml): NAC 2.1g Saccharin sodium salt 0.04g Hydroxypropyl methylcellulose 0.2g Sodium edetate 0.1g Apricot seasoning 0.1g (Add water to make 100 milliliters) 10 liters of syrup containing 1 part of hydroxypropyl methylcellulose It was prepared by dispersing in boiling water and cooling to room temperature. Hydroxy After hydration of propylmethylcellulose, purify all remaining material under a nitrogen atmosphere. It was then poured into the solution obtained by dissolving in degassed water.   The pH of this solution was adjusted to 6.5 with sodium hydroxide.   Dispense the solution into a 10 ml single-dose glass bottle with a rubber stopper, Each contained about 200 mg NAC. Example 4   By repeating Example 1, the following composition (in 100 ml): NAC 4.2g Saccharin sodium salt 0.08g Sodium carboxymethyl cellulose 0.20g Sodium benzoate 0.15g Sodium edetate 0.10g Raspberry seasoning 0.4g (Add water to make 100 milliliters) 10 liters of syrup were prepared.   The pH of this solution was adjusted to 6.5 with sodium hydroxide.   The solution was dispensed into bottles at a rate of 150 milliliters per bottle. Example 5   By repeating Example 2, the following composition (in 100 ml): NAC 2.10g Saccharin 0.04g Hydroxypropyl methylcellulose 0.40g Methyl 4-hydroxybenzoate 0.10 g Banana seasoning 0.4g (Add water to make 100 milliliters) 10 liters of syrup were prepared.   The pH of this solution was adjusted to 7 with sodium hydroxide.   The solution was dispensed into bottles at a rate of 450 milliliters per bottle.

─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Saudino Alessandro             Switzerland 6600 Muralto via bee             Lieri 10 (72) Inventor Gazaniga Annivale             Milan, Italy 20027 Rescalde             Ina Via Generale Polo 22

Claims (1)

[Claims] 1. In the composition in the form of syrup, The following (in 100 ml): -N-acetyl cysteine 2-4.2 g / 100 ml -Sweetener 0.02-0.3g / 100ml -Sodium carboxymethyl cellulose and hydroxypropyl methylcell Thickening agent selected from the group consisting of loin or mixtures thereof 0.1-4 g / 100 ml And optionally: -Seasoning 0.1-0.4 g / 100 ml -Preservative 0.05-0.5 g / 100 ml (Add water to make 100 milliliters) And the pH is between 5 and 8 A composition in the form of a syrup characterized by the following. 2. The sweetener is saccharin, saccharin sodium salt, cyclamate or Claim 1 characterized in that it is selected from the group consisting of mixtures of these. Composition. 3. Preservatives include sodium edetate, sodium benzoate, methyl 4-hydro Xybenzoate, propyl 4-hydroxybenzoate and mixtures thereof The composition according to claim 1, wherein the composition is selected from the group consisting of: 4. pH is 6.5-7, The composition of Claim 1 characterized by the above-mentioned.