WO2019158043A1 - Stable chloral hydrate solution, preparation method thereof, and use thereof - Google Patents

Abstract

Disclosed is a chloral hydrate solution, a preparation method thereof and use thereof. The chloral hydrate solution comprises chloral hydrate and a pharmaceutically acceptable acid and water. A mass concentration of the chloral hydrate ranges from 40% to 80%, and the pH value of the chloral hydrate solution ranges from 1.0 to 2.9.

Description

Stable hydrated chloral solution and preparation method and use thereof Field of invention

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a sedative and hypnotic pharmaceutical preparation, and more particularly to a chloral hydrate solution suitable for oral use in a child patient after dilution. Further, the present invention relates to a method for preparing the hydrated chloral solution and the use of the hydrated chloral solution in the preparation of a sedative and hypnotic drug.

Background of the invention

The diagnosis and treatment of childhood diseases usually requires a variety of medical examinations, such as nuclear magnetic resonance, CT, electrocardiogram, electroencephalography, ophthalmology, dental examination and so on. As a special group, children's psychological development is not yet mature. In the process of diagnosis and treatment, their ability to control their emotions and behaviors is far less than that of adults. It is prone to fear, anxiety, irritability, anxiety and even agitation, and then escape or refuse treatment. The process is difficult to carry out. Once the diagnosis and treatment of the disease cannot be carried out normally, it often affects the quality of diagnosis and treatment, delays the diagnosis and treatment of the disease, and causes harm to the child's physical and mental health. In severe cases, it may even affect the patient's life safety. Therefore, before the treatment, children are often required to take sedative hypnotics to keep them calm, reduce anxiety and fear, and ensure the smooth progress of the diagnosis and treatment process.

At present, there is no sedative and hypnotic preparation approved by the State Food and Drug Administration for child examination in China, and the hospital preparation of chloral hydrate oral solution is generally used as a sedative hypnotic for pediatric examination. Hydrated chloral hydrate mainly inhibits the up-regulation system of brainstem reticular structure, causing near-physiological sleep. It has a fast onset, long duration of action, does not shorten rapid eye movement sleep, has mild effect, no accumulation in the body, and less adverse reactions. Field investigation of many hospitals in China, chloral hydrate oral solution is the longest application, the most widely used, the most mature application, the largest amount of sedative and hypnotic drugs in pediatric examinations in China. It has become the drug of choice for sedation and hypnosis in clinical pediatric examination in China. There are no suitable alternatives.

However, the quality standards for chloral hydrate hospital preparations are generally lower than commercial products. According to reports in the literature, the stability of the product is very poor. The 5% concentration product needs to be refrigerated, and the effective period is only 30 days. The 10% concentration product is stored at room temperature (25 ° C), and the effective period is about 35 days. It has been reported in the literature that β-cyclodextrin is added to a chloral hydrate oral solution to prepare an inclusion compound to improve stability. However, the effective period of the product only increased to 46.63 days (Song Yongxi, Li Liying, Li Qianmei. Preparation and stability prediction of chloral hydrate syrup [J]. Tianjin Pharmaceutical, 2002, 14 (2): 48-48), without substance Sexual improvement. Therefore, effectively improving the stability of chloral hydrate oral solution has become a difficult problem, and there has been no effective method reported. In addition, hospital preparations are limited to the use of the preparation hospital, and may not be sold externally. For large and medium-sized hospitals and primary hospitals that do not have the preparation conditions, it is difficult to obtain chloral hydrate preparations, and clinicians often have to choose phenobarbital with high side effects. Sodium, propofol, ketamine injections and other drugs. Compared with oral drugs, injections require professional administration, which is inconvenient to use, increases children's fear and pain, and poor compliance.

Summary of invention

It is an object of the present invention to overcome the deficiencies of the prior art and to provide a chloral hydrate solution having high stability. Further, another object of the present invention is to provide a process for preparing the hydrated chloral solution.

In order to achieve the above object, in one aspect, the present invention provides a hydrated chloral solution comprising chloral hydrate, a pharmaceutically acceptable acid and water, wherein the chloral hydrate has a mass concentration of 40% to 80%. The pH of the chloral hydrate solution is preferably from 1.0 to 2.9.

In another aspect, the present invention provides a stable chloral hydrate solution comprising the following components: chloral hydrate, monohydrate or anhydrous citric acid, and purified water, wherein the chloral hydrate The mass concentration is from 44% to 80%, and the pH of the chloral hydrate solution is from 1.0 to 2.9.

In another aspect, the present invention provides a method for preparing a chloral hydrate solution, characterized in that the preparation steps include:

1) mixing a pharmaceutically acceptable acid with water, stirring to dissolve to obtain an acid solution having a pH of 1.0 to 2.9;

2) adding chloral hydrate to the acid solution while stirring, stirring until completely dissolved, that is, the chloral hydrate solution is obtained, wherein the chloral hydrate has a mass concentration of 40% to 80%.

In another aspect, the present invention provides a method for preparing the stabilized chloral hydrate solution, the preparation steps of which include:

1) mixing monohydrate or anhydrous citric acid with purified water, and dissolving and dissolving to obtain a citric acid solution having a pH of 1.0 to 2.9;

2) adding chloral hydrate to the citric acid solution while stirring, and stirring until completely dissolved, that is, the chloral hydrate solution is obtained, wherein the chloral hydrate has a mass concentration of 44% to 80%.

In another aspect, the invention provides the use of a chloral hydrate solution of the invention in the manufacture of a medicament for use as a sedative hypnotic formulation.

In another aspect, the invention provides a chloral hydrate solution of the invention for use as a sedative hypnotic formulation.

In another aspect, the invention provides the use of sedative and hypnotic in a patient, particularly a pediatric patient, comprising administering to the patient an effective amount of a chloral hydrate solution of the invention.

The beneficial effects of the invention are that the chloral hydrate solution of the invention effectively improves the product stability of the chloral hydrate solution by reducing the pH value of the solution while increasing the concentration of chloral hydrate (for example, reducing the generation of degradants) The traits did not change after storage, no crystals were precipitated).

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 shows the effect of different pH values on the amount of chloroform formed in a chloral hydrate solution.

Detailed description of the invention

In some embodiments, the present invention provides a chloral hydrate solution comprising chloral hydrate, a pharmaceutically acceptable acid, and water (preferably purified water), wherein the chloral hydrate has a mass concentration of 40% to 80% (For example, 44%-80%, 44%-70%, 44%-60% or 44%-50%), the pH of the chloral hydrate solution is preferably 1.0-2.9.

In a preferred embodiment, the present invention provides a hydrated chloral solution, wherein the pharmaceutically acceptable acid is an inorganic or organic acid, wherein

The inorganic acid is selected from the group consisting of hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, boric acid, phosphoric acid, and any combination thereof;

The organic acid is selected from the group consisting of formic acid, acetic acid, acetic anhydride, acetoacetic acid, trifluoroacetic acid, propionic acid, pyruvic acid, butyric acid, caproic acid, heptanoic acid, undecanoic acid, lauric acid, stearic acid, palmitic acid, Oxalic acid, malonic acid, succinic acid (succinic acid), glutaric acid, adipic acid, maleic acid, fumaric acid, lactic acid, malic acid, citric acid, tartaric acid, tartaric acid, ascorbic acid, gallic acid, benzene Formic acid, salicylic acid, cinnamic acid, naphthoic acid, pamoic acid, nicotinic acid, orotic acid, phytic acid, methyl sulfuric acid, dodecyl sulfuric acid, methanesulfonic acid, trifluoromethanesulfonic acid, ethanedisulfonic acid, Isethionine, 1,5-naphthalenedisulfonic acid, 2-naphthalenesulfonic acid, camphorsulfonic acid, sulfamic acid, glutamic acid, aspartic acid, gluconic acid, glucuronic acid, and any combination thereof .

In a more preferred embodiment, the present invention provides a hydrated chloral solution, wherein the pharmaceutically acceptable acid is hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, lactic acid, malic acid, tartaric acid, fumaric acid, citric acid monohydrate Or anhydrous citric acid.

In a most preferred embodiment, the invention provides a hydrated chloral solution, wherein the pharmaceutically acceptable acid is monohydrate or anhydrous citric acid.

In some embodiments, the present invention provides a chloral hydrate solution comprising the following components: chloral hydrate, monohydrate or anhydrous citric acid, and purified water, wherein the quality of the chloral hydrate The concentration is from 44% to 80%, and the pH of the chloral hydrate solution is from 1.0 to 2.9.

In a preferred embodiment, the chloral hydrate solution has a pH of from 1.0 to 2.0.

In a preferred embodiment, the chloral hydrate solution has a pH of from 1.2 to 1.6.

In a preferred embodiment, the chloral hydrate has a mass concentration of 75%.

In a preferred embodiment, the pH of the chloral hydrate solution is from 1.31 to 2.0.

In a preferred embodiment, the chloral hydrate solution has a pH of from 1.61 to 2.0.

In a preferred embodiment, the monohydrate or anhydrous citric acid is present in a concentration of from 0.5% to 1%, preferably from about 0.7% to about 0.1%.

In some embodiments, the present invention provides a method for preparing a hydrated chloral solution, characterized in that the preparation steps include:

1) mixing a pharmaceutically acceptable acid with water, stirring to dissolve to obtain an acid solution having a pH of 1.0 to 2.9;

2) adding chloral hydrate to the acid solution while stirring, stirring until completely dissolved, that is, the chloral hydrate solution is obtained, wherein the concentration of chloral hydrate is 40%-80% (for example, 44%-80) %, 44%-70%, 44%-60% or 44%-50%).

In a preferred embodiment, the pH of the acid solution prepared in step 1) of the process is from 1.0 to 2.0, preferably from 1.2 to 1.6.

In a preferred embodiment, the pH of the acid solution prepared in step 1) of the process is from 1.31 to 2.0.

In a preferred embodiment, the pH of the acid solution prepared in step 1) of the process is from 1.61 to 2.0.

In other embodiments, the present invention provides a method for preparing the hydrated chloral solution, the preparation steps of which include:

1) mixing monohydrate or anhydrous citric acid with purified water, and stirring to obtain a citric acid solution having a pH of 1.0 to 2.9;

2) adding chloral hydrate to the citric acid solution while stirring, and stirring until completely dissolved, thereby obtaining a chloral hydrate solution of the present invention, wherein the chloral hydrate has a mass concentration of chloral hydrate of 44%. -80%, and the pH of the chloral hydrate solution is 1.0-2.9.

In a preferred embodiment, the pH of the citric acid solution prepared in step 1) of the process is from 1.0 to 2.0, preferably from 1.2 to 1.6.

In a preferred embodiment, the pH of the citric acid solution prepared in step 1) of the process is from 1.31 to 2.0.

In a preferred embodiment, the pH of the citric acid solution prepared in step 1) of the process is from 1.61 to 2.0.

In a preferred embodiment, in step 2) of the process, stirring is carried out at a rotational speed of from 100 to 500 r/min, preferably 300 r/min, to completely dissolve the chloral hydrate.

In the present application, the amount of the degradant (for example, chloroform or trichloroacetic acid) is expressed in the form of the amount (μg) of the degradation product per 1 g of chloral hydrate.

In order to study the relationship between the pH value of the chloral hydrate solution and the amount of chloroform produced by the degradation product, the present invention dissolves chloral hydrate in an aqueous solution of citric acid of different pH values to prepare chloral hydrate having the same concentration. Solution (concentration of about 10%), but chloral hydrate solution with different pH values, and potting in a clear glass bottle, placed in an environment of 60 ° C ± 2 ° C for 5 days, after testing its degradation product chloroform The amount generated. Figure 1 shows the relationship of this change. According to the results shown in Fig. 1, the amount of the degradation product chloroform increased as the pH of the chloral hydrate solution increased, and the pH at the critical point of the change was about 2.9. When the pH of the chloral hydrate solution is greater than 2.9, the amount of chloroform formed increases sharply as the pH of the chloral hydrate solution increases. It can be seen that a lower pH value is beneficial to improve the stability of chloral hydrate, but simply lowering the pH of the chloral hydrate solution does not reduce the amount of chloroform produced, and the pH is too low. It is not conducive to the commercial production, storage and use of the chloral hydrate solution. For this reason, in the present invention, the chloral hydrate solution preferably has a pH of 1.0 to 2.9.

In addition, in order to study the stability of different concentrations of chloral hydrate solution, the present invention prepares a chloral hydrate solution having a pH of 2.0 with different concentrations of chloral hydrate, and potting in a transparent glass bottle, placed at 60 ° C After 5 days in an environment of ±2 ° C, the contents of the degradation products of chloroform and trichloroacetic acid in the solution were measured, and the results are shown in Table 1.

Table 1 Stability test results of different concentrations of chloral hydrate solution

It can be seen from the test results in Table 1 that as the concentration of chloral hydrate increases, the formation of the degradation products chloroform and trichloroacetic acid decreases significantly, and the stability of the chloral hydrate solution is significantly improved.

In view of the fact that the chloral hydrate solution of the present invention has a lower pH value and a higher concentration, this will result in a poor mouthfeel of the product and a certain irritation, which is not suitable for direct administration. Therefore, before taking the chloral hydrate solution of the present invention, it can be diluted with a single syrup, water or juice as a diluent to improve the mouthfeel and reduce irritation.

Example

Specific embodiments of the present invention are further described below in conjunction with specific embodiments. Unless otherwise stated, the components used in the present invention are commercially available.

In the experimental examples, the chloral hydrate content refers to the percentage relative to the labeled amount (i.e., the theoretical content of chloral hydrate per label or the labeling content of each formulation unit).

Example 1

Add 12 g of anhydrous citric acid and a certain amount of purified water to a glass beaker, stir to dissolve to obtain a citric acid solution having a pH of 1.64, and then add 738 g of chloral hydrate (14-24 mesh) with stirring at 300 r. Stir at a speed of /min until completely dissolved, that is, a chloral hydrate solution having a mass concentration of 44%.

Example 2

Add 12g of anhydrous citric acid and a certain amount of purified water to a glass beaker, stir to dissolve to obtain a citric acid solution with a pH of 1.61, and then add 1007g of chloral hydrate (14-24 mesh) with stirring at 300r. Stir at a speed of /min until completely dissolved, that is, a chloral hydrate solution having a mass concentration of 60%.

Example 3

Add 12g of anhydrous citric acid and a certain amount of purified water to a glass beaker, stir to dissolve to obtain a citric acid solution with a pH of 1.31, and then add 1342g of chloral hydrate (14-24 mesh) with stirring at 300r. Stir at a speed of /min until completely dissolved, that is, a chloral hydrate solution having a mass concentration of 80%.

Example 4

Add 1.7 ml of phosphoric acid and a certain amount of purified water to a glass beaker, stir to dissolve to obtain a phosphoric acid solution with a pH of 2.03, and then add 745.7 g of chloral hydrate (14-24 mesh) with stirring at 300 r/min. The mixture was stirred until completely dissolved, that is, a chloral hydrate solution having a mass concentration of 44.44% was obtained.

According to a method similar to the above, a chloral hydrate solution (pH 2.00) having a mass concentration of 50% was prepared.

Example 5

Add 4.2 ml of hydrochloric acid and a certain amount of purified water to a glass beaker, stir to dissolve to obtain a hydrochloric acid solution having a pH of 1.99, and then add 1118.7 g of chloral hydrate (14-24 mesh) with stirring at 300 r/min. The mixture was stirred until completely dissolved, that is, a chloral hydrate solution having a mass concentration of 66.67% was obtained.

Add 6.4 ml of hydrochloric acid and a certain amount of purified water to a glass beaker, stir to dissolve to obtain a hydrochloric acid solution having a pH of 2.00, and then add 745.7 g of chloral hydrate (14-24 mesh) with stirring at 300 r/min. The mixture was stirred until completely dissolved, that is, a chloral hydrate solution having a mass concentration of 44.44% was obtained.

A chloral hydrate solution (pH 1.98) having a mass concentration of 50% was prepared in a manner similar to the above.

Example 6

Add 14.0 ml of acetic acid and a certain amount of purified water to a glass beaker, stir to dissolve to obtain an acetic acid solution with a pH of 2.03, and then add 1118.7 g of chloral hydrate (14-24 mesh) with stirring at 300 r/min. The mixture was stirred until completely dissolved, that is, a chloral hydrate solution having a mass concentration of 66.67% was obtained.

Add 21.3 ml of acetic acid and a certain amount of purified water to a glass beaker, stir to dissolve to obtain an acetic acid solution with a pH of 2.04, and then add 745.7 g of chloral hydrate (14-24 mesh) with stirring at 300 r/min. The mixture was stirred until completely dissolved, that is, a chloral hydrate solution having a mass concentration of 44.44% was obtained.

According to a method similar to the above, a chloral hydrate solution (pH 2.02) having a mass concentration of 50% was prepared.

Example 7

Add 3.2 ml of sulfuric acid and a certain amount of purified water to a glass beaker, stir to dissolve to obtain a sulfuric acid solution with a pH of 2.00, and then add 745.7 g of chloral hydrate (14-24 mesh) with stirring at 300 r/min. The mixture was stirred until completely dissolved, that is, a chloral hydrate solution having a mass concentration of 44.44% was obtained.

A chloral hydrate solution (pH 2.01) having a mass concentration of 50% was prepared according to a method similar to the above.

Example 8

Add 21.3 ml of lactic acid and a certain amount of purified water to a glass beaker, stir to dissolve to obtain a lactic acid solution having a pH of 2.04, and then add 745.7 g of chloral hydrate (14-24 mesh) with stirring at 300 r/min. The mixture was stirred until completely dissolved, that is, a chloral hydrate solution having a mass concentration of 44.44% was obtained.

According to a method similar to the above, a chloral hydrate solution (pH 2.02) having a mass concentration of 50% was prepared.

Experimental example

Experimental Example 1 Stability Test

The chloral hydrate preparations of different hospitals in China and the chloral hydrate solution prepared in Example 1 - Example 3 of the present invention are respectively placed under high temperature (60 ° C ± 2 ° C) and illumination (4500 lx ± 500 lx). The product traits were observed on day 0 and day 10, respectively, and the pH, degradation products and contents were examined. The results are shown in Table 2.

Table 2 Stability test results

From the results in Table 2, it can be seen that under high temperature or light conditions, the properties of the preparations of the hospitals did not change significantly, but the pH value decreased, the main drug had different degrees of degradation, and different amounts of chloroform and trichloroacetic acid were produced. In particular, the degradation is accelerated under high temperature conditions, and the content does not reach 90% of the labeled amount. However, the chloral hydrate solution prepared in Examples 1 to 3 of the present invention has no significant change in product properties, pH value and content under the same conditions, and the production amount of chloroform and trichloroacetic acid is far lower. In hospital preparations. It can be seen that the stability of the chloral hydrate solution of the present invention is significantly higher than that of existing hospital preparations.

The chloral hydrate solution prepared in Examples 4-8 was placed under high temperature (60 ° C ± 2 ° C), and the chloral hydrate content and the degradation product content were observed on the 0th day and the 5th day, and the results are shown in the following table. .

Experimental Example 2 Accelerated Stability Test

The chloral hydrate preparations of different hospitals in China and the chloral hydrate solution prepared in Examples 1 to 3 of the present invention are placed at 40±2 ° C according to the provisions of the accelerated stability test in the Chinese Pharmacopoeia 2015 edition. Accelerated stability test was carried out under the condition of RH 75%±5%, and samples were taken at 0, 1, 2, 3, and 6 months, respectively, and pH value, degradant and content were observed, and the results are shown in Table 3.

Table 3 Accelerated Stability Test Results

From the test results of Table 3, it was found that the pH and content of the chloral hydrate solution of the present invention did not change significantly after 6 months of acceleration. Although the amount of chloroform of the chloral hydrate solution of the present invention increased after an acceleration of 6 months, the value was lower than the 60 μg/g limit of ICH. In contrast, hospital preparations undergo significant degradation, producing large amounts of chloroform. It can be seen that the stability of the chloral hydrate solution of the invention is significantly better than that of the hospital preparation.

Experimental Example 3 Long-term stability test

The chloral hydrate preparations of different hospitals in China and the chloral hydrate solution prepared in Examples 1 to 3 of the present invention were placed at 25±2 ° C according to the provisions of the Chinese Pharmacopoeia 2015 edition medium- and long-term stability test. Long-term stability test was carried out under the condition of RH 60%±5%, and samples were taken at 0, 3, 6, 9, 12, 18, and 24 months, respectively, to detect pH, degradation products and contents, and the results are shown in Table 4.

Table 4 Long-term stability test results

From the results of Table 4, in the long-term stability test, the pH value of the chloral hydrate solution of the present invention, the content of chloroform and trichloroacetic acid did not change significantly, and the long-term stability was significantly better than the existing one. Hospital preparations.

Compared with the 30-day storage expiration date in the prior product, the chloral hydrate solution provided by the invention can be stored for a period of up to 24 months at room temperature, and the amount of the degradation product chloroform is less than 60 μg/g. It has excellent stability and controllability, effectively solves the problem of poor stability in conventional conventional preparations, and is suitable for commercial mass production.

Example 5: Pharmacodynamic test

Using a single syrup as a diluent, the present invention, Example 1, and Example 3 of the present invention were respectively prepared to prepare a chloral hydrate solution having a specification of 1 ml: 100 mg.

The chloral hydrate preparations of different hospitals in China and the chloral hydrate solution prepared by using the first embodiment of the present invention, the second embodiment of the present invention or the third embodiment of the present invention were used for clinical trials to observe the sedative and hypnotic effects.

A total of 360 children who underwent sedation were enrolled. The age ranged from 1 month to 3 years old. The children who were allergic to chloral hydrate and severe liver and kidney dysfunction were randomly divided into Nanjing *** hospital preparation group. The Xinjiang *** hospital preparation group, the Shanghai *** hospital preparation group, the first embodiment of the present invention, the second embodiment of the present invention, and the third embodiment of the present invention, each group of 60 cases. According to the weight of the children, the groups were fed according to the doctor's prescription before the examination. The sedative and hypnotic effects of each group were observed and compared. The sedative effect was expressed by efficiency (the ratio of the number of successful examinations to the total number of people). The results are shown in Table 5.

Table 5 Comparison of sedative and hypnotic effects of oral chloral hydrate solution

From the results of Table 5, it can be seen that the embodiments of the present invention have no significant difference in hypnotic sedation efficiency compared with different hospital preparations in China, and the effect is equivalent.

The specific embodiments described herein are only a detailed description of the specific embodiments of the chloral hydrate solution of the present invention, and are not intended to be limiting thereof. Any modification or modification of the embodiments of the present invention, the substitution and use of the same or similar substances within the scope or scope of the patents, are all within the scope of the invention.

Claims (14)

a chloral hydrate solution comprising chloral hydrate, a pharmaceutically acceptable acid and water (preferably purified water), wherein the chloral hydrate has a mass concentration of 40% to 80% (eg 44% to 80%, 44) The pH of the chloral hydrate solution is preferably from 1.0 to 2.9, %-70%, 44%-60% or 44%-50%). A chloral hydrate solution according to claim 1, wherein said pharmaceutically acceptable acid is an inorganic acid or an organic acid, wherein The inorganic acid is selected from the group consisting of hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, boric acid, phosphoric acid, and any combination thereof; The organic acid is selected from the group consisting of formic acid, acetic acid, acetic anhydride, acetoacetic acid, trifluoroacetic acid, propionic acid, pyruvic acid, butyric acid, caproic acid, heptanoic acid, undecanoic acid, lauric acid, stearic acid, palmitic acid, Oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, maleic acid, fumaric acid, lactic acid, malic acid, citric acid, tartaric acid, metatartaric acid, ascorbic acid, gallic acid, benzoic acid, salicin Acid, cinnamic acid, naphthoic acid, pamoic acid, nicotinic acid, orotic acid, phytic acid, methyl sulphate, lauryl sulphate, methanesulfonic acid, trifluoromethanesulfonic acid, ethanedisulfonic acid, hydroxyethyl sulfonate Acid, 1,5-naphthalenedisulfonic acid, 2-naphthalenesulfonic acid, camphorsulfonic acid, sulfamic acid, glutamic acid, aspartic acid, gluconic acid, glucuronic acid, and any combination thereof; Preferably, the pharmaceutically acceptable acid is hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, lactic acid, malic acid, tartaric acid, fumaric acid, monohydrate or anhydrous citric acid. A stable chloral hydrate solution, characterized in that the solution comprises the following components: chloral hydrate, monohydrate or anhydrous citric acid, and purified water, wherein the chloral hydrate has a mass concentration of 44 %-80%, and the pH of the chloral hydrate solution is 1.0-2.9. A stabilized chloral hydrate solution according to any one of claims 1 to 3, wherein the chloral hydrate solution has a pH of from 1.0 to 2.0, preferably from 1.2 to 1.6. A stabilized chloral hydrate solution according to any one of claims 1 to 4, wherein the chloral hydrate has a mass concentration of 75%. A stabilized chloral hydrate solution according to any one of claims 1 to 5, wherein the pH of the chloral hydrate solution is from 1.31 to 2.0. A stabilized chloral hydrate solution according to any one of claims 1 to 6, wherein the pH of the chloral hydrate solution is from 1.61 to 2.0. A method for preparing a chloral hydrate solution, characterized in that the preparation steps include: 1) mixing a pharmaceutically acceptable acid with water, stirring to dissolve to obtain an acid solution having a pH of 1.0 to 2.9; 2) adding chloral hydrate to the acid solution while stirring, stirring until completely dissolved, that is, the chloral hydrate solution is obtained, wherein the concentration of chloral hydrate is 40%-80% (for example, 44%-80) %, 44%-70%, 44%-60% or 44%-50%). A method for preparing a stable chloral hydrate solution, characterized in that the preparation steps include: 1) mixing monohydrate or anhydrous citric acid with purified water, and stirring to obtain a citric acid solution having a pH of 1.0 to 2.9; 2) adding chloral hydrate to the citric acid solution while stirring, stirring until completely dissolved, that is, the chloral hydrate solution is obtained, wherein the chloral hydrate has a mass concentration of 44% to 80%. A method for preparing a stable chloral hydrate solution according to claim 8 or 9, wherein the pH of the chloral hydrate solution is from 1.0 to 2.0, preferably from 1.2 to 1.6. A method for preparing a stable chloral hydrate solution according to any one of claims 8 to 10, wherein the chloral hydrate has a mass concentration of 75%. A method for preparing a stable chloral hydrate solution according to any one of claims 8-11, wherein the pH of the chloral hydrate solution is from 1.31 to 2.0. A stabilized chloral hydrate solution according to any one of claims 8 to 12, wherein the pH of the chloral hydrate solution is from 1.61 to 2.0. Use of a stabilized hydrated chloral solution according to any one of claims 1 to 5 for the preparation of a medicament for use as a sedative hypnotic formulation.

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