CN115501178A - Stable liquid composition containing minoxidil and preparation method thereof - Google Patents

Abstract

The invention discloses a stable liquid composition containing minoxidil and a preparation method thereof, wherein the composition contains the minoxidil and a pharmaceutically acceptable solvent, and further controls the content of carbon dioxide in a solution. The invention provides a method for preventing color change of a minoxidil solution by isolating direct contact between carbon dioxide and minoxidil, and the color change of the product solution is avoided during long-term storage by removing and isolating the carbon dioxide in the preparation process of the minoxidil solution; the method is simple to implement, does not need to introduce other buffer solutions and other reagents, is suitable for the existing preparation process of the minoxidil solution consisting of multiple components, and provides a new idea for developing a stable minoxidil preparation.

Description

Stable liquid composition containing minoxidil and preparation method thereof

Technical Field

The invention relates to the technical field of medicinal preparations, in particular to a stable minoxidil-containing liquid composition and a preparation method thereof.

Background

Minoxidil is an effective pharmaceutical ingredient for treating alopecia, oral administration of minoxidil causes systemic reactions including hirsutism and cardiovascular reactions, and topical application is a better way of administration. The currently commonly used dosage forms include sprays, tinctures, liniments, gels and the like. The currently approved minoxidil solution concentration is 2% or 5%.

The color of the minoxidil solution type product can be gradually deepened to be dark yellow in the long-term storage process, so that impurities which are unfavorable for the product quality are possibly formed; previous studies have had a number of explanations for this phenomenon, one view being related to the effect of light, so light-shielding containers have been used to hold the product, but the problem of discoloration has not been completely solved; the factors influencing the stability of the minoxidil solution reported by Marvin seal et al in the text of Minoxidil solution for treating alopecia and alopecia areata are related to the dosage of antioxidant and the pH value of the solution besides temperature and light. Textbook "pharmacy" (Shenyang pharmaceutical institute, beijing; national institutes of health, 1980, 213-217) describes that the addition of EDTA-disodium increases the effectiveness of antioxidants. The patent publication "a minoxidil-containing composition for external use and a method for preparing the same" (publication No. CN 109431996A) provides a method for preventing a minoxidil-containing liquid preparation from discoloration by adding a phosphate buffer, but the action principle thereof is not explained, and the introduced phosphate buffer increases the complexity of the ingredients of the preparation, thereby placing an additional burden on the quality control of the preparation. The patent publication "minoxidil leave-on gel" (publication No. CN 113599351A) proposes that minoxidil easily reacts with aldehydes due to its structure to generate yellow water-soluble substances, which causes the gel to discolor. In order to avoid the phenomenon, common ethanol is oxidized and filtered to remove aldehyde, and then activated carbon is used for absorbing peculiar smell to obtain odorless ethanol (dealdehyding and deodorizing ethanol) for the minoxidil gel.

However, in the research of the inventor, the phenomenon of discoloration can still occur during the storage process even if ethanol is not added into the product. At present, the color change mechanism of minoxidil is not clear, and no effective solution exists for avoiding the color change of the minoxidil preparation once and for all.

Disclosure of Invention

In order to solve the above problems of the prior art, the present invention provides a stable liquid composition containing minoxidil and a method for preparing the same.

The invention finds that the stability of the minoxidil solution in long-term storage can be ensured by removing carbon dioxide in the minoxidil preparation process and carrying out air-tight packaging on the product, and the problem of color change is solved. Meanwhile, during the preparation process and long-term storage, the degree of discoloration is measured by a first solution color inspection method specified in Chinese pharmacopoeia, and compared with a yellow standard colorimetric solution, the degree of discoloration does not exceed No. 3.

Based on previous researches, the color of the external solution type product turns yellow due to oxidation, and in order to isolate the oxidation effect of oxygen, the inventor adopts a nitrogen charging method to remove the influence of oxygen in the air. In the research process of the inventor, the fact that the solubility of carbon dioxide in a solution is far higher than that of nitrogen is considered to be probably more remarkable in removing oxygen in the solution, but in experiments, the product after carbon dioxide charging is unexpectedly found to be darker in color, and presumably, the carbon dioxide has an influence on the color change process.

Based on the above findings, as a first aspect of the present invention, there is provided a stable minoxidil-containing liquid composition comprising minoxidil and a pharmaceutically acceptable solvent, wherein the mass ratio of carbon dioxide to minoxidil in the liquid composition is not higher than 2.6 x 10 ^-5 :1。

In the research, control measures for simultaneously removing oxygen and carbon dioxide are adopted, and as a result, the product color is unexpectedly found not to be changed in the long-term storage process.

In order to further investigate this discoloration process, in a further study, only carbon dioxide-removing measures were used, as a result of which it was found, even more surprisingly, that the product color did not undergo any change over the course of long-term storage. This result suggests that oxygen in the air is not a previously thought critical contributor to this discoloration process. For analysis, the minoxidil has the following structural formula:

analyzing the structure of the minoxidil, wherein the minoxidil is an oxidation product, and unless the forced degradation test is carried out through strong oxidation reaction, oxygen in the air is not enough to generate oxidation effect on the minoxidil; meanwhile, under the strong acid condition, the minoxidil is relatively stable.

It can be seen that the color change problem of minoxidil can be solved by controlling the amount of carbon dioxide alone.

Preferably, the mass ratio of the carbon dioxide to the minoxidil is controlled to be not higher than 2.0 x 10 ^-5 :1。

At present, the minoxidil solution type products sold in the market mostly adopt HDPE (high density polyethylene) bottles, and plastic bottles made of the materials have certain permeability to all gas components in the air.

In a typical embodiment, the method for isolating carbon dioxide is to adopt airtight packaging, and comprises adding a composite film bag outside an HDPE bottle, and replacing the air in the bag with nitrogen or other inert gases to completely isolate the influence of the outside air; or a composite film bag is added outside the HDPE bottle, and a carbon dioxide adsorption device is placed in the composite film bag to eliminate the influence of carbon dioxide gas in the air; or packaging the liquid composition in airtight container such as aluminum can or glass bottle. Through the mode, the contact between carbon dioxide and minoxidil is isolated, and the effect of avoiding color change of the minoxidil solution is achieved.

Preferably, the composite film bag may be a composite film of aluminum foil and various plastic materials, including PE, EVA, CPP, EMA, EAA, or the like.

Preferably, the carbon dioxide adsorption device can adopt a carbon dioxide adsorbent containing alkaline earth metal hydroxide or alkaline earth metal oxide and a gas-permeable material bag wrapping the carbon dioxide adsorbent. Specifically, the alkaline earth metal hydroxide is selected from calcium hydroxide, magnesium hydroxide, lithium hydroxide or sodium hydroxide; the alkaline earth metal oxide is selected from calcium oxide or magnesium oxide. The air-permeable material bag for wrapping the carbon dioxide adsorbent can be selected from non-woven bag, gauze bag, cotton bag, etc.

Furthermore, the carbon dioxide adsorption device comprises a carbon dioxide adsorbent and a non-woven fabric bag wrapping the carbon dioxide adsorbent.

Preferably, the stable liquid composition comprises minoxidil and a solvent, wherein the content of minoxidil is 2% -5%; the solvent is one or a mixture of two or more of propylene glycol, ethanol or purified water.

As a second aspect of the present invention, a method for preparing the stable liquid composition comprises the steps of:

(1) Weighing the minoxidil and the solvent according to the prescription amount, and stirring and mixing uniformly;

(2) Vacuumizing to not more than-0.03 MPa, introducing nitrogen into the solution, keeping the nitrogen pressure not less than 0.03MPa for not less than 5min, and repeating the vacuumizing and nitrogen introducing operations for three times; maintaining the liquid medicine under the protection of positive pressure of nitrogen, wherein the pressure of nitrogen is not lower than 0.03MPa;

(3) Stirring until the minoxidil is completely dissolved;

(4) And packaging by adopting an air-tight material.

Further, the preparation method of the stable liquid composition comprises the following steps:

(1) Weighing the minoxidil and the solvent according to the prescription amount, and stirring and mixing uniformly;

(2) Vacuumizing to-0.03 MPa, charging nitrogen into the solution, keeping the nitrogen pressure not less than 0.03MPa for 5min, and repeating vacuumizing and nitrogen charging operations for three times; maintaining the liquid medicine under the protection of positive pressure of nitrogen, wherein the pressure of the nitrogen is about 0.03MPa;

(3) Stirring until the minoxidil is completely dissolved;

(4) And packaging by adopting an air-tight material.

Compared with the prior art, the invention has the beneficial effects that:

1. the invention provides a method for avoiding color change of a minoxidil solution by isolating direct contact of carbon dioxide and minoxidil, and the color of the product solution is not changed during the two-year shelf life of long-term storage by removing and isolating the carbon dioxide in the process of preparing the minoxidil solution;

2. the method is simple to implement, does not need to introduce other buffer solutions and other reagents, is suitable for the existing preparation process of the minoxidil solution consisting of multiple components, and provides a new idea for developing a stable minoxidil preparation.

Drawings

The accompanying drawings, which are incorporated in and constitute a part of this specification, are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the invention and together with the description serve to explain the invention and not to limit the invention.

FIG. 1 is a graph showing the discoloration of the product (exposed to carbon dioxide) in example 5.1 when allowed to stand at room temperature for 30 days.

FIG. 2 is a graph showing the discoloration of the product (exposed to carbon dioxide) in example 5.2 when allowed to stand at room temperature for 30 days.

FIG. 3 is a graph showing the discoloration of the product (exposed to carbon dioxide in air) in example 5.3 when allowed to stand at room temperature for 30 days.

FIG. 4 is a graph of the discoloration of the product of example 5.4 when left at room temperature for 24 months (with carbon dioxide exclusion).

FIG. 5 is a graph of the discoloration of the product of example 5.5 when left at room temperature for 24 months (with carbon dioxide exclusion).

Detailed Description

It is to be understood that the following detailed description is exemplary and is intended to provide further explanation of the invention as claimed. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the invention. As used herein, the singular forms "a", "an", and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof, unless the context clearly indicates otherwise.

In the examples, the discoloration test was carried out by referring to the first method (visual colorimetry) in the solution color detection method of the Chinese pharmacopoeia 0901. The specific method comprises the following steps: taking the product to detect, the solution should be clear and colorless, if it is developed, according to the examination of the method (the first method of the color examination method of the solution 0901 in the general rules of the four parts of the Chinese pharmacopoeia 2020 edition), the color of the solution should not be darker than No. 0.5 compared with yellow standard colorimetric solution.

Example 1: liquid minoxidil composition

Prescription 1 (Specification: 2%)

Prescription 2 (Specification: 5%)

The solvent in the above formula can be replaced by similar components, including hydrophilic solvent such as glycerol, liquid PEG, etc.

Example 2: a method of preparing a minoxidil liquid composition comprising the steps of:

(1) Weighing the formula amount of propylene glycol, ethanol and purified water, stirring and mixing uniformly, and adding the formula amount of minoxidil;

(2) Vacuumizing to not more than-0.03 MPa, introducing nitrogen into the solution, keeping the nitrogen pressure not less than 0.03MPa, maintaining for 5min, and repeating vacuumizing and nitrogen introducing for three times; maintaining the liquid medicine under the protection of positive pressure of nitrogen, wherein the pressure of the nitrogen is about 0.03MPa;

(3) Stirring until the minoxidil is completely dissolved;

(4) And packaging the product by adopting an air-tight packaging material.

The airtight package in the invention has the effect of isolating the gas inside and outside the package after the product is packaged. The packaging mode can adopt various modes, such as:

(1) directly packaging by adopting an HDPE (high-density polyethylene) bottle, adding a composite film bag outside the HDPE bottle, and replacing air in the bag with nitrogen to completely isolate the influence of outside air;

the composite film bag can be selected from composite films of aluminum foil and various plastic materials, wherein the plastic materials comprise PE, EVA, CPP, EMA, EAA and the like.

(2) Directly packaging by adopting an HDPE (high-density polyethylene) bottle, adding a composite film bag outside the HDPE bottle, and placing a carbon dioxide adsorption device in the bag to eliminate the influence of carbon dioxide gas in the air;

the carbon dioxide adsorption means may comprise a carbon dioxide adsorbent selected from alkaline earth metal hydroxides such as calcium hydroxide, magnesium hydroxide, lithium hydroxide, sodium hydroxide and the like and/or alkaline earth metal oxides such as calcium oxide, magnesium oxide and the like.

The carbon dioxide adsorption device comprises a carbon dioxide adsorbent and a non-woven fabric bag wrapping the carbon dioxide adsorbent.

(3) And (3) filling the minoxidil liquid medicine into an aluminum pot or a glass bottle for packaging.

Example 3: a method for preparing minoxidil liquid composition comprises the following steps:

(1) Weighing the formula amount of propylene glycol, ethanol and purified water, stirring and mixing uniformly, and adding the formula amount of minoxidil;

(2) Stirring until the minoxidil is completely dissolved;

(3) The liquid medicine is packaged by HDPE bottles.

Example 4: and (3) investigating influence factors of the minoxidil solution samples obtained by different preparation methods.

Example 4-1: according to the formula 1 of the example 1, the preparation method from the step (1) to the step (3) in the example 2 is adopted, and the product is packaged by a glass bottle.

Example 4-2: according to the formula 2 of the example 1, the preparation method from the step (1) to the step (3) in the example 2 is adopted, and the product is packaged by a glass bottle.

Examples 4 to 3: according to the formula 1 of the example 1, the preparation method from the step (1) to the step (3) in the example 3 is adopted, and the product is packaged by a glass bottle.

Examples 4 to 4: according to the formula 2 of the embodiment 1, the preparation methods of the steps (1) to (3) in the embodiment 3 are adopted, and the product is packaged by a glass bottle.

The above samples were subjected to the influence factor examination, and the results are as follows.

4.1 Effect of light on Minoxidil solutions

The prepared solutions were subjected to stability tests under two different illumination conditions. Wherein, the degradation is carried out for 10 days under the condition of forced degradation illumination (4500 lx +/-500 lx); simulating the production illumination condition, and placing the product under the illumination condition of a fluorescent lamp for 72 hours. The results were as follows:

TABLE 1 results of stability studies of the product (in clear glass bottles) under light conditions

The results show that no matter whether the process for removing the carbon dioxide is adopted by the minoxidil solution or not, the related substances are slightly increased and the color of the solution is slightly changed into yellowish under the condition of forced degradation illumination (4500 lx +/-500 lx) for 10 days. The production conditions are simulated, and the color of related substances and solution is not obviously changed after the device is placed under the illumination condition of a fluorescent lamp for 72 hours. It is seen that under high light conditions, the solution color changes slightly, but the effect of light on the product can be eliminated by using opaque packaging.

4.2 Effect of high temperature on Minoxidil solutions

The solutions prepared in examples 4-1 to 4-4 were left at a high temperature of 60 ℃ for 30 days to observe the change in color, and the results are shown in Table 2.

TABLE 2 stability of the product (in clear glass bottles) at high temperature

The results show that no matter whether the process for removing the carbon dioxide is adopted in the minoxidil solution, the color of related substances and the color of the solution have no obvious change under the high-temperature condition. It can be seen that high temperatures have substantially no effect on the product.

Example 5 testing of the Effect of carbon dioxide on the color of minoxidil solutions

According to the formula 2 in the example 1, the minoxidil solution is prepared by the process from the step (1) to the step (3) in the example 2. The liquid medicine was packed as required in each test described below.

Test 5.1 the solution was filled into HDPE bottles and placed into 1000ml aluminum plastic composite bags filled with carbon dioxide gas (saturated). The sample is placed at normal temperature for 30 days, at least two samples are taken out respectively at 10 days, 20 days and 30 days to observe the change condition of the color, one sample at the same time point is used for opening at the time point to observe the color, the other sample is taken out from an aluminum-plastic composite bag and placed at normal temperature, all samples are opened and poured into a test tube to be placed side by side for taking a picture at 30 days, the color is compared with a reference preparation placed at normal temperature, and the reference preparation is packaged by an HDPE bottle. The result is shown in fig. 1, which is from left to right in fig. 1: reference formulation, self-preparation (day 0), self-preparation (day 10), self-preparation (day 20), self-preparation (day 30).

The results show that the yellowish clear liquid of the comparative reference preparation changes in color from the preparation to a deep yellowish clear liquid over the period of investigation and that the color deepens over time.

Test 5.2 the liquid medicine was filled into HDPE bottles, charged with carbon dioxide (at an inflation pressure of 0.08MPa, a flow rate of about 5L per minute, for 5 min), sealed and placed into aluminum-plastic composite bags filled with compressed air. The sample was left at room temperature for 30 days, and the color change was observed by sampling for 10 days, 20 days, and 30 days, respectively, in the same manner as in test 5.1. The result is shown in fig. 2, which is from left to right in fig. 2: reference formulation, self-preparation (no carbon dioxide), self-preparation (10 days), self-preparation (20 days), self-preparation (30 days).

The results show that the yellowish clear liquid of the comparative reference formulation changes in color from the preparation to a deep yellowish clear liquid over the duration of the investigation. Since the HDPE bottle of 100ml is charged with carbon dioxide for a long time, after sufficient dissolution, excess carbon dioxide overflows, and this operation ensures that the HDPE bottle contains saturated carbon dioxide.

Experiment 5.3 the liquid medicine was filled into HDPE bottles, left at room temperature, and sampled at 6, 12, and 24 months to observe the color change. The result is shown in fig. 3, which is from left to right in fig. 3: reference formulation, self-preparation (30 days), self-preparation (6 months), self-preparation (12 months), self-preparation (24 months).

The results show that the light yellow clear liquid of the comparative reference formulation gradually changed in color from the product to the light yellow clear liquid over the study period, comparable to the reference formulation.

Test 5.4 the solution was filled into HDPE bottles with a capacity of 100ml and placed in aluminium plastic composite bags with a volume of 1000 ml. The aluminum-plastic composite bag is filled with compressed air, and a sodium hydroxide non-woven cloth bag capable of adsorbing carbon dioxide is placed in the aluminum-plastic composite bag. The sample is placed at normal temperature for 24 months, and is sampled and observed for color change in 6 months, 12 months and 24 months. The result is shown in fig. 4, which is from left to right in fig. 4: reference formulation, self-preparation (day 0), self-preparation (month 6), self-preparation (month 12), self-preparation (month 24).

The results show that the yellowish clear liquid of the comparative reference preparation, which has no color change during the investigation period from the preparation, is a colorless clear liquid.

Carbon dioxide in the visible liquid medicine is removed, and meanwhile, the liquid medicine is packaged in an airtight mode, the situation that no carbon dioxide in the packaging bag migrates into the HDPE bottle is guaranteed, and the color of the liquid medicine is unchanged within two years.

Because 100ml of air in the HDPE bottle for containing the liquid medicine also contains 0.03-0.04% of carbon dioxide by volume, and the carbon dioxide has higher solubility in water, the amount of the carbon dioxide introduced into the liquid medicine due to the HDPE bottle can be calculated as follows:

the minimum is: 100ml 0.03%/Vm M =0.059mg;

the highest is: 100ml 0.04%/Vm M =0.079mg;

wherein Vm is the gas molar volume, and under the standard condition, the gas molar volume is 22.4L/mol; m is the molar mass of carbon dioxide, 44g/mol.

60ml of the liquid medicine is put into a 100ml HDPE bottle. The minoxidil in the liquid medicine is 3g, the maximum carbon dioxide in the air in the bottle is 0.079mg, and the proportion of the minoxidil to the carbon dioxide in the air in the bottle is 1g:0.026mg; the minimum is 0.059mg, and the ratio of the two is 1g:0.026mg.

Carbon dioxide in the aluminum-plastic composite membrane bag outside the bottle reacts with the adsorbent, and only the carbon dioxide in the HDPE bottle exists.

Therefore, the color of the liquid medicine can be ensured to be unchanged within two years by controlling the amount of carbon dioxide contacting with the minoxidil in the solution to be less than 1g of carbon dioxide in the range of 0.026mg.

Test 5.5 the liquid medicine was filled in 100ml aluminum bottles and left at room temperature. The sample is placed at normal temperature for 24 months, and is sampled and observed for color change in 6 months, 12 months and 24 months. The result is shown in fig. 5, which is from left to right in fig. 5: reference formulation, self-preparation (day 0), self-preparation (month 6), self-preparation (month 12), self-preparation (month 24). The aluminum bottle can ensure the air tightness, and even if a carbon dioxide adsorbent is not adopted outside the bottle, the carbon dioxide content of not higher than 0.026mg. The results show that the yellowish clear liquid of the comparative reference preparation, which has no color change during the investigation period from the preparation, is a colorless clear liquid.

In another embodiment, a 1000ml aluminum bottle is vacuumized, 600ml of liquid medicine is filled, then carbon dioxide with the total amount of about 0.4ml is filled, the liquid medicine is placed at room temperature for 30 days, the color of the liquid medicine is observed, and the result is colorless clear liquid, so that when the mass ratio of the carbon dioxide to the minoxidil in a container is 0.026mg.

The results of the above sample examinations are summarized in Table 3.

TABLE 3 summary of color change results of sample room temperature storage inspection

From the above experimental results, it can be seen that when the liquid medicine is contacted with carbon dioxide during the preparation process or the storage process, the liquid medicine turns yellow, as in examples 5.1, 5.2 and 5.3; the liquid medicine is prevented from contacting with carbon dioxide in the preparation process or the storage process, and the liquid medicine does not turn yellow within 24 months as in example 5.4 and example 5.5. The specific analysis is as follows.

(1) The liquid medicine is filled in an HDPE bottle and placed in a composite membrane bag filled with carbon dioxide gas, as in example 5.1; or the liquid medicine is filled in an HDPE bottle and filled with carbon dioxide, and then is placed in a composite membrane bag filled with compressed air, as in example 5.2; the solution turns yellow after being stored for 30 days at normal temperature.

(2) The liquid medicine is filled in an HDPE bottle and is placed in the air as in example 5.3, and the color of the solution turns yellow after being stored for 24 months at normal temperature.

(3) Filling the liquid medicine into an HDPE bottle, placing the HDPE bottle in a composite membrane bag filled with air, and placing a carbon dioxide adsorbent in the composite membrane bag, as in example 5.4; or the liquid medicine is filled in an aluminum bottle as in example 5.5; the solution is stored for 24 months at normal temperature, and the color of the solution is almost unchanged.

The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

1. Stable liquid composition containing minoxidil, characterized by comprising minoxidil and a pharmaceutically acceptable solvent, wherein the mass ratio of carbon dioxide to minoxidil in the liquid composition is not higher than 2.6X 10 ^-5 :1。

2. The stable minoxidil-containing liquid composition according to claim 1, wherein the mass ratio of carbon dioxide to minoxidil in the liquid composition is not higher than 2.0 x 10 ^-5 :1。

3. The stable minoxidil-containing liquid composition according to claim 1, wherein said liquid composition is hermetically packaged, said hermetic packaging comprises adding a composite film bag outside HDPE bottle, filling inert gas in the composite film bag, or placing a carbon dioxide adsorption device; or the liquid composition is filled into a container of gas-tight material.

4. The stable minoxidil-containing liquid composition according to claim 3, wherein said container of airtight material comprises an aluminum can or a glass bottle.

5. The stable minoxidil-containing liquid composition according to claim 3, wherein said composite film pouch material is selected from the group consisting of a composite film of aluminum foil and a plastic material comprising PE, EVA, CPP, EMA or EAA.

6. The stable liquid composition containing minoxidil according to claim 3, wherein said carbon dioxide adsorption unit comprises carbon dioxide adsorbent and a pouch of gas permeable material encasing the carbon dioxide adsorbent.

7. The stable liquid composition containing minoxidil according to claim 6, wherein said carbon dioxide adsorbent is selected from alkaline earth metal hydroxides or alkaline earth metal oxides, or a mixture of both; the alkaline earth metal hydroxide is selected from calcium hydroxide, magnesium hydroxide, lithium hydroxide or sodium hydroxide; the alkaline earth metal oxide is selected from calcium oxide or magnesium oxide.

8. The stable minoxidil-containing liquid composition according to claim 6, wherein said carbon dioxide adsorbing means comprises a carbon dioxide adsorbent and a non-woven fabric bag enclosing the carbon dioxide adsorbent.

9. The stable liquid composition containing minoxidil according to claim 1, which comprises minoxidil and a solvent, wherein the content of minoxidil is 2-5%; the solvent is one or a mixture of two or more of propylene glycol, ethanol or purified water.

10. The stable minoxidil-containing liquid composition according to any one of claims 1 to 9, wherein said stable liquid composition is prepared by a method comprising the steps of:

(1) Weighing the minoxidil and the solvent according to the prescription amount, and stirring and mixing uniformly;

(2) Vacuumizing to not more than-0.03 MPa, introducing nitrogen into the solution, keeping the nitrogen pressure not less than 0.03MPa for not less than 5min, and repeating the vacuumizing and nitrogen introducing operations for three times; maintaining the liquid medicine under the protection of positive pressure of nitrogen, wherein the pressure of nitrogen is not lower than 0.03MPa;

(3) Stirring until the minoxidil is completely dissolved;

(4) And packaging by adopting air-tight packaging.

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