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 view of the problem that water-soluble salicylic acid cannot be dissolved at high concentration, the invention provides a preparation process of liquid sustained-release salicylic acid with the concentration of 30%.
The invention provides a typical embodiment of a preparation process of liquid slow-release salicylic acid, which comprises the steps of adding salicylic acid into a glycerol aqueous solution under the condition of a first set temperature, uniformly mixing, cooling to a second set temperature, homogenizing until the solution is transparent, heating to a third set temperature, sequentially adding poloxamer and polyethylene glycol, uniformly mixing, cooling to a fourth set temperature, adding a skin feel regulator, and uniformly mixing; wherein the first set temperature is not lower than 60 ℃, the second set temperature is lower than 60 ℃, the third set temperature is not lower than 60 ℃, and the fourth set temperature is higher than 40 ℃.
In the experimental process, the inventor of the invention finds that the solubility of salicylic acid can be greatly improved through a specific dissolving process (feeding sequence and temperature change) in a specific proportioning combination of the three specific components, and the concentration of the prepared liquid sustained-release salicylic acid can reach as high as 30%.
In one or more embodiments of this embodiment, the glycerol in the aqueous glycerol solution is present in an amount of 15 to 20% by weight.
In the series of embodiments, the mass fraction of glycerol in the glycerol aqueous solution is 17-18%.
In one or more embodiments of this embodiment, the aqueous glycerol solution is prepared by: heating glycerol and water to 60-100 ℃, and stirring until the glycerol and the water are dissolved and transparent. When the temperature is 88-92 ℃, the dissolving effect is better.
In the series of embodiments, the stirring time is 10-50 min. When the stirring time is 29-31 min, the stirring time is shortened on the premise that the solution is completely dissolved and transparent.
In one or more embodiments of this embodiment, the first set temperature is 60 to 100 ℃. When the temperature is 88-92 ℃, the dissolving effect is better.
In one or more embodiments of the present disclosure, the time for stirring and mixing after adding salicylic acid is 40 to 80 min. When the stirring and mixing time is 59-61 min, the salicylic acid can be ensured to be dissolved, and the stirring time is shortened.
In one or more embodiments of this embodiment, the second set temperature is 30 to 60 ℃. When the temperature is 44-46 ℃, the dissolving effect is better.
In one or more embodiments of the present invention, the homogenizing method is to homogenize for 1-5 times by using a high-pressure homogenizer. The effect is better when homogenizing for 3 times.
In one or more embodiments of this embodiment, the third set point temperature is 60 to 100 ℃. When the temperature is 88-92 ℃, the effect is better.
In one or more embodiments of the embodiment, poloxamer and polyethylene glycol are sequentially added, mixed uniformly and then kept warm for 20-100 min. When the heat preservation time is 58-62 min, the effect is better.
In one or more embodiments of this embodiment, the polyethylene glycol is polyethylene glycol 400.
In one or more embodiments of this embodiment, the fourth set temperature is between 80 ℃ and 40 ℃. When the temperature is 63-67 ℃, the effect is better.
In one or more embodiments of this embodiment, the skin feel modifier is menthol.
In one or more embodiments of the embodiment, the adding mass ratio of the glycerol, the salicylic acid, the poloxamer and the polyethylene glycol is 1:3: 0.4-1: 0.2-0.6.
In one or more embodiments of the embodiment, the adding mass ratio of the salicylic acid to the skin feeling modifier is 3: 0.1-0.4.
The invention also provides a preparation process of the liquid slow-release salicylic acid with the concentration of 30%, which comprises the step of preparing the liquid slow-release salicylic acid with the concentration of 30% by adopting the preparation process of the liquid slow-release salicylic acid.
In a third embodiment of the invention, the liquid sustained-release salicylic acid is obtained by the preparation process.
In one or more embodiments of the present disclosure, the salicylic acid is 15 to 30% by mass, the poloxamer is 7.5 to 8.5% by mass, and the glycerol is 9.5 to 10.5% by mass.
In order to make the technical solution of the present invention more clearly understood by those skilled in the art, the technical solution of the present invention will be described in detail below with reference to specific examples and comparative examples.
Example 1
The preparation process of the liquid slow-release salicylic acid comprises the following steps:
1: 460 parts of water and 100 parts of glycerol are mixed, heated to 90 ℃, and stirred for 30min under the condition of heat preservation until the materials are completely dissolved and transparent.
2: adding 300 parts of salicylic acid, continuously stirring until the salicylic acid is completely dissolved, and keeping the temperature at 90 ℃ and stirring for 60 minutes.
3: cooling to 45 deg.C, homogenizing for 3 times with high pressure homogenizer until it is completely transparent.
4: heating to 90 deg.C, adding 80 parts of poloxamer, adding 40 parts of PEG-400, dissolving completely, and keeping the temperature for 60 min.
5: cooling to 65 ℃, adding 20 parts of menthol, and stirring uniformly.
6: cooling to 40 ℃, and discharging.
Example 2
The preparation process of the liquid slow-release salicylic acid comprises the following steps:
1: 460 parts of water and 100 parts of glycerol are mixed, heated to 80 ℃, and stirred for 50min under the condition of heat preservation until the materials are completely dissolved and transparent.
2: adding 300 parts of salicylic acid, continuously stirring until the salicylic acid is completely dissolved, and keeping the temperature at 80 ℃ and stirring for 100 minutes.
3: cooling to 40 deg.C, homogenizing for 5 times with high pressure homogenizer until it is completely transparent.
4: heating to 80 deg.C, adding 70 parts of poloxamer and 40 parts of PEG-400, dissolving completely, and keeping the temperature for 60 min.
5: cooling to 65 ℃, adding 20 parts of menthol, and stirring uniformly.
6: cooling to 40 ℃, and discharging.
Example 3
The preparation process of the liquid slow-release salicylic acid comprises the following steps:
1: 460 parts of water and 100 parts of glycerol are mixed, heated to 80 ℃, and stirred for 50min under the condition of heat preservation until the materials are completely dissolved and transparent.
2: adding 300 parts of salicylic acid, continuously stirring until the salicylic acid is completely dissolved, and keeping the temperature at 70 ℃ and stirring for 180 minutes.
3: cooling to 40 deg.C, homogenizing for 5 times with high pressure homogenizer until it is completely transparent.
4: heating to 80 deg.C, adding 70 parts of poloxamer and 40 parts of PEG-400, dissolving completely, and keeping the temperature for 60 min.
5: cooling to 65 ℃, adding 20 parts of menthol, and stirring uniformly.
6: cooling to 40 ℃, and discharging.
The experimental results are as follows: the water-soluble slow-release salicylic acid can be obtained in three ways, and the water-soluble slow-release salicylic acid obtained in example 1 is used as the optimal effect.
Comparative example 1
This comparative example is the same as example 1, except that: the glycerol was omitted.
Comparative example 2
This comparative example is the same as example 1, except that: the poloxamer is omitted.
Comparative example 3
This comparative example is the same as example 1, except that: PEG-400 is omitted.
Comparative example 4
This comparative example is the same as example 1, except that: step 1, adding poloxamer; and 4, adding glycerol and then adding PEG-400.
Comparative example 5
This comparative example is the same as example 1, except that: step 1, adding PEG-400; and 4, adding glycerol and then adding poloxamer.
Comparative example 6
This comparative example is the same as example 1, except that: step 1, adding glycerol; and 4, adding PEG-400 and then adding poloxamer.
The solubility of the liquid sustained-release salicylic acid prepared in example 1 and comparative examples 1 to 3 is shown in Table 1.
TABLE 1 solubility of liquid sustained-release salicylic acids prepared in example 1 and comparative examples 1 to 3
|
Glycerol
|
Poloxamers
|
PEG-400
|
Solubility in water
|
Example 1
|
√
|
√
|
√
|
30%
|
Comparative example 1
|
×
|
√
|
√
|
5%
|
Comparative example 2
|
√
|
×
|
√
|
10%
|
Comparative example 3
|
√
|
√
|
×
|
5% |
The solubility of the liquid sustained-release salicylic acid prepared in example 1 and comparative examples 4 to 6 is shown in Table 2.
TABLE 2 solubility of liquid sustained-release salicylic acids prepared in example 1 and comparative examples 4 to 6
|
Glycerol
|
Poloxamers
|
PEG-400
|
Solubility in water
|
Example 1
|
Frist
|
Second
|
Third
|
30%
|
Comparative example 4
|
Second
|
Frist
|
Third
|
10%
|
Comparative example 5
|
Second
|
Third
|
Frist
|
10%
|
Comparative example 6
|
Frist
|
Third
|
Second
|
20% |
As is apparent from tables 1 and 2, the solubility of the liquid sustained-release salicylic acid is affected by the composition of the solubilizer in example 1 and the addition sequence of the solubilizer, and the solubility of the liquid sustained-release salicylic acid can be increased only when glycerol, poloxamer and PEG-400 are selected as the solubilizers and added in the order of glycerol, poloxamer and PEG-400.
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.