CN113018205A

CN113018205A - External low-irritation salicylic acid gel and preparation method thereof

Info

Publication number: CN113018205A
Application number: CN202110424250.8A
Authority: CN
Inventors: 周峰; 夏晨宇
Original assignee: Suzhou Gaoguang New Materials Co ltd
Current assignee: Suzhou Gaoguang New Materials Co ltd
Priority date: 2021-04-20
Filing date: 2021-04-20
Publication date: 2021-06-25

Abstract

The invention relates to the field of skin care products, in particular to an external low-irritation salicylic acid gel, which comprises salicylic acid as a main active component, and water, a cosolvent, a coating agent, an emulsifier and a gel forming agent as other auxiliary components; the invention also discloses a preparation method of the external low-irritation salicylic acid gel, which mainly comprises the following three steps: 1) preparing a salicylic acid high-concentration glycidyl solution mother solution; 2) preparing salicylic acid dilute gel; 3) and (3) preparing salicylic acid gel. The salicylic acid gel with low irritation for external use and the preparation method thereof can keep a salicylic acid preparation at a higher concentration, play a better skin care role, obviously reduce the irritation, and are suitable for most people.

Description

External low-irritation salicylic acid gel and preparation method thereof

Technical Field

The invention relates to the field of skin care products, in particular to an external low-irritation salicylic acid gel and a preparation method thereof.

Background

Salicylic acid, also known as salicylic acid, is known as salicylic acid, a common active ingredient widely used in skin treatment. In medicine, salicylic acid medicaments are mostly used for treating acne, and the salicylic acid with high concentration can be effectively attached to epidermal cells when contacting with the epidermis, so that the peeling of dead cells and the growth of new epidermal cells are promoted, and the treatment effect is achieved. Meanwhile, medical research also shows that the salicylic acid preparation with low concentration (less than or equal to 2%) has the function of promoting the keratin, so the salicylic acid preparation is widely applied to skin care products. It has been proved that the preparation with salicylic acid as the active ingredient has a plurality of efficacies of skin tenderness, acne resistance, acne removal, inflammation elimination, skin metabolism promotion and the like in the aspect of skin care. However, salicylic acid is highly irritating to the skin and is usually left on the skin for a short period of time during medical use to reduce the undesirable effects of strong irritation. In cosmetics, conventional salicylic acid preparations also use only low concentrations of salicylic acid, such as 0.1%, due to the low water solubility of salicylic acid and the strong irritation, resulting in insignificant efficacy. Salicylic acid skin care products with higher concentration (0.5-2%) usually require irritant organic solvents such as ethanol and the like to dissolve salicylic acid, so that the skin irritation reaction is usually stronger in the actual use process, and a plurality of side effects are generated, such as redness, dry spots, inflammatory erythema, edema and/or spots, so that the range of applicable people is narrowed. For the reasons, the application effect of salicylic acid in medicine is far greater than that of salicylic acid in skin care products, and how to increase the concentration of salicylic acid in cosmetic preparations to improve the beneficial effect and reduce the irritation of salicylic acid with higher concentration is a problem to be solved when salicylic acid is applied in skin care products.

Disclosure of Invention

Aiming at the defects of the prior art, the invention provides the salicylic acid gel with low irritation for external use and the preparation method thereof, so that the salicylic acid preparation can keep higher concentration, play better skin care effect, obviously weaken the irritation, be suitable for most people and effectively solve the problems in the technical background, and the invention provides the following technical scheme:

the invention provides a formula of salicylic acid gel with low irritation for external use, which comprises the main active component of salicylic acid, and other auxiliary components of water, cosolvent, coating agent, emulsifier and gel forming agent, wherein the mass percent of each component is 55-90%, 0.1-10%, 0.2-40%, 0.02-20%, 0.2-20% and 2-15%, the ratio of salicylic acid to cosolvent is 1: 1 to 1: 5, the ratio of the salicylic acid to the wrapping agent is 1: 0.1 to 1: 2, the ratio of salicylic acid to the emulsifier is 1: 1 to 1: 2.

In the above formula, the cosolvent is a unit or polyol with a main chain of three or four carbons, including but not limited to propanol, butanol, ethylene glycol, propylene glycol, glycerol, butylene glycol, butanetriol, diethylene glycol, etc., and when in use, one or a mixture of several alcohols meeting the above conditions can be selected.

In the formula, the wrapping agent is polyhydroxy water-soluble biomolecule, specifically cyclodextrin, cellulose and derivatives thereof.

The solubility of salicylic acid in pure water is low, the solubility of salicylic acid is improved by adding a cosolvent, ethanol is more common and has higher solubility to salicylic acid, but the ethanol has higher irritation and is more applied to medical products, and the salicylic acid can be separated out in the mixing process of the salicylic acid and water due to the adoption of the ethanol, so that the salicylic acid is not suitable for preparing skin care products; the unit with the main chain of three carbons and four carbons and the polyalcohol are widely applied to skin care products, are recorded and developed into cosmetic catalogues, are safe and reliable cosmetic additives and can play a role in assisting in dissolving, but the solubility of the alcohols to salicylic acid is less than that of ethanol, the salicylic acid can not be completely dissolved to cause solid residue or solid is separated out when the salicylic acid is mixed with water, and in order to solve the problems, a wrapping agent is introduced to enhance the stability of the salicylic acid dissolved in the water; the inclusion agent is mainly polyhydroxy water-soluble biological molecules, specifically cyclodextrin, cellulose and derivatives thereof, which are rich in hydroxyl, can rapidly form hydrogen bonds with carboxylic acid groups and phenolic hydroxyl groups of salicylic acid and alcoholic hydroxyl groups of a solubilizer, and hinder the ionization effect of the salicylic acid in water, so that the salicylic acid keeps higher stability in the water, and meanwhile, the characteristic of cyclodextrin cyclic polyhydroxy can lock a single salicylic acid molecule, so that the salicylic acid molecule is not easy to react with water molecules; when long-chain macromolecules such as hydroxyethyl cellulose are curled and wound, similar effect can be generated on salicylic acid molecules; the long carbon chain oiliness also helps the dissolution of salicylic acid, an oil-soluble substance; the cosolvent and the inclusion agent act synergistically, and the preparation of the aqueous solution of salicylic acid with higher concentration can be realized by the steps in the preparation method mentioned later in the invention.

In the formula, the emulsifier is a common nonionic long carbon chain (the carbon number of the main chain is 8-20) emulsifier in cosmetics, and comprises fatty acid esters, stearic acid esters, lauric acid esters, oleic acid esters, fatty alcohol polyethers, oleic acid alcohol polyethers, lauryl alcohol polyethers and polyoxyethylene, more preferably a liquid emulsifier with the HLB value more than 8, and has a better promotion effect on the stability of the gel.

In the above formulation, the gel forming agent is a common gel forming agent in cosmetic bottles, including but not limited to acrylics, cellulose derivatives, natural gums, poloxamers, polysaccharides, polyoxyethylene, hyaluronic acids, etc., and the gel forming agent with higher gel viscosity is formed by aqueous solution, and the gel wall-hanging does not flow down optimally.

The preparation method of the external low-irritation salicylic acid gel mainly comprises the following three steps:

1) and preparing a salicylic acid high-concentration glycidyl solution mother solution: uniformly stirring the cosolvent and the salicylic acid, wherein the ratio of the cosolvent to the salicylic acid is 1: 1 to 5: 1, more preferably 1.5: 1 to 3.5: 1; in some cases, the salicylic acid will be able to dissolve completely in the co-solvent to form a homogeneous solution system, in some cases, for example, a higher concentration of salicylic acid is required, beyond its solubility in the co-solvent, heating may be used to help dissolve, if not completely dissolved, the entire mixture should be stirred to make it perfectly homogeneous, and grinding the salicylic acid solid into a fine powder may also be accomplished to help it form a more homogeneous system; preparing the coating agent into an aqueous solution, wherein the concentration of the aqueous solution depends on the specific properties of the coating agent, and when the coating agent is cyclodextrin and derivatives thereof, the concentration is 5% to 40%, and when the coating agent is cellulose and derivatives thereof, the concentration is 2% to 5%; heating to facilitate the dissolution of the coating agent in water, wherein the aqueous solution of the coating agent with proper concentration has low viscosity to facilitate the mixing, heating the mixture of the salicylic acid and the cosolvent and the aqueous solution of the coating agent to proper temperature, wherein the temperatures of the salicylic acid and the cosolvent are close to each other, the two solutions have low viscosity at the proper temperature and can keep good fluidity, slowly and repeatedly adding the mixture of the cosolvent and the salicylic acid into the aqueous solution of the coating agent, fully stirring each time to dissolve all the salicylic acid, and the system does not contain solid substances, thereby finally forming the salicylic acid high-concentration glycidyl solution mother liquor.

2) And preparation of salicylic acid dilute gel: preparing a gel forming agent into a dilute aqueous solution, heating to a proper temperature and stirring continuously, then dropwise adding a salicylic acid high-concentration glycidyl solution mother solution into the dilute aqueous solution of the gel forming agent, simultaneously heating an emulsifier to a proper temperature and dropwise adding, wherein the dropwise adding speed of salicylic acid, the mother solution and the emulsifier needs to be controlled during dropwise adding, so that the dropwise adding speed of the salicylic acid and the mother solution is consistent, and simultaneously the cost is reduced, thus forming salicylic acid dilute gel; in particular, the mixing temperature should be determined by the particular nature of the gel former and the aqueous gel solution, and all liquids should remain well flowable at that temperature to facilitate mixing.

3) Preparation of salicylic acid gel: the addition of the gel former to the salicylic acid thin gel is continued until the viscosity is suitable to form the salicylic acid gel.

In step 2, the concentration of the dilute aqueous solution of the gel forming agent should be 1/50-1/10 of the prepared gel in step 3, and the solution should maintain good fluidity and be easy to stir and mix.

The salicylic acid gel prepared in the step 3, wherein the concentration of the gel forming agent is 5% to 15%, the gel product prepared at this time has high viscosity, no fluidity in a natural state, and stable phase, and no obvious layering is observed after the salicylic acid gel is stored for 12 months at room temperature.

Compared with the prior art, the invention provides the external low-irritation salicylic acid gel and the preparation method thereof, and the external low-irritation salicylic acid gel has the following beneficial effects:

the gel state is an excellent property of an external application preparation, and has a plurality of advantages, such as skin-friendly property and no extrusion on the skin; the elastic cushion has elasticity and can buffer and disperse pressure; the temperature is sensed and dissipated, and the cool feeling is kept; the high viscosity gel has poor fluidity, can stay on the body surface for a long time after being externally applied, and simultaneously slows down the flow and volatilization of water, so that the active substance is absorbed on the skin surface more slowly and mildly.

Drawings

FIG. 1 is a flow chart of a method for preparing a salicylic acid gel with low irritation for external use according to the present invention.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

Dissolving 10g of salicylic acid in 30g of ethanol at 35 ℃, fully stirring until the salicylic acid is completely dissolved, and after the salicylic acid is completely dissolved, dripping the ethanol solution of the salicylic acid into 40g of warm clear water at 35 ℃ to find that the liquid drops generate white turbidity after being dripped into water; after the mixture is completely dropped, the mixture is in a white dilute emulsion state, and fine solid precipitation can be seen through careful observation, namely precipitation crystallization of the salicylic acid, so that the compatibilization effect of the ethanol on the salicylic acid is proved to be poor.

Example 2

Firstly, 10g of salicylic acid ground into fine powder is dissolved in 30g of glycerin at 65 ℃, the salicylic acid is dissolved by fully stirring, and the solution is in a slightly transparent white fluid state after long-time stirring due to the limitation of solubility;

secondly, preparing 40g of 50% cyclodextrin aqueous solution at 85 ℃ by taking cyclodextrin as a wrapping agent, stirring to ensure that the whole solution is transparent and uniform, maintaining the temperature at 85 ℃, keeping stirring, slowly adding the white fluid prepared in the step one into the cyclodextrin solution, dropwise adding 0.5g each time, fully stirring to ensure that all solids are completely dissolved after the whole system is completely transparent, and then dropwise adding the next time until the dropwise adding is finished, thus obtaining the completely clear and transparent high-concentration salicylic acid mother liquor I with the salicylic acid completely dissolved.

The high-concentration salicylic acid mother liquor I is a uniform and stable salicylic acid solution, and no solid is precipitated even if the salicylic acid mother liquor is placed and cooled.

Example 3

Firstly, 10g of salicylic acid ground into fine powder is dissolved in 30g of 1, 2-propylene glycol at 65 ℃, and the salicylic acid is dissolved by fully stirring to form salicylic acid solution;

secondly, hydroxyethyl cellulose is used as a wrapping agent, 40g of 5% hydroxyethyl cellulose aqueous solution is prepared at 65 ℃, the whole solution is stirred to be transparent and uniform, the temperature is maintained to be 65 ℃, the stirring is kept, the white fluid prepared in the step one is slowly added into the hydroxyethyl cellulose solution, 0.5g of white fluid is dripped each time, the white fluid is fully stirred to be uniformly mixed, the next dripping is carried out again, and the high-concentration salicylic acid mother liquor II with completely dissolved salicylic acid and completely clear and transparent can be obtained until the dripping is finished.

The high-concentration salicylic acid mother liquor II is a uniform and stable salicylic acid solution, and no solid is precipitated even if the salicylic acid mother liquor II is placed and cooled.

Example 4

Firstly, at 10 ℃, 3g of poloxamer 407 gel forming agent for the commercial cosmetics is selected to be dissolved in 60g of water to prepare 63g of poloxamer solution, the temperature is maintained at 10 ℃, then 16g of salicylic acid mother liquor I with high concentration in the embodiment 2 is taken to be dripped into the poloxamer water solution, simultaneously 4g of polyethylene glycol 600 is also dripped as an emulsifier, the dripping speed of the salicylic acid mother liquor and the emulsifier is required to be controlled during dripping, 1g of polyethylene glycol 600 is required to be synchronously dripped when 4g of salicylic acid water-soluble mother liquor is dripped, and after dripping is finished, the salicylic acid dilute gel is formed;

secondly, adding 17g of poloxamer 407 into the salicylic acid dilute gel in batches at 15 ℃, adding 0.5g of poloxamer 407 into the salicylic acid dilute gel in each batch, stirring until the poloxamer 407 is completely dissolved, adding the next batch until all the poloxamer 407 is dissolved, stopping stirring, heating the whole aqueous solution to 45 ℃, keeping the temperature for 15 minutes, and cooling to form the salicylic acid gel I.

The ingredients and contents of salicylic acid gel I are shown in Table 1.

TABLE 1

When the salicylic acid gel I is provided for fifty volunteers, no irritation or allergic feedback appears, and the acne removing effect indicates 43 good persons, 5 ordinary persons and 2 invalid persons.

Example 5

Firstly, at 10 ℃, 3g of poloxamer 407 gel forming agent for the commercial cosmetics is selected to be dissolved in 60g of water to prepare 63g of poloxamer solution, the temperature is maintained at 10 ℃, then 16g of salicylic acid mother liquor II with high concentration in the embodiment 3 is taken to be dripped into the poloxamer aqueous solution, 4g of laureth-8 is also dripped as an emulsifier, the dripping speed of the salicylic acid mother liquor and the emulsifier is required to be controlled during dripping, 1g of laureth-8 is required to be synchronously dripped when 4g of salicylic acid water mother liquor is dripped, and after dripping is finished, salicylic acid diluted gel is formed;

secondly, adding 17g of poloxamer 407 into the salicylic acid dilute gel in batches at 15 ℃, adding 0.5g of poloxamer 407 into the salicylic acid dilute gel in each batch, stirring until the poloxamer 407 is completely dissolved, adding the next batch until all the poloxamer 407 is dissolved, stopping stirring, heating the whole aqueous solution to 45 ℃, keeping the temperature for 15 minutes, and cooling to form salicylic acid gel II.

The ingredients and contents of salicylic acid gel ii are shown in table 2.

Numbering	Composition (I)	Quality of	Percentage content
				1	Salicylic acid	2g	2％
2	Glycerol	6g	6％
				3	Poloxamer 407	20g	20％
4	Laureth-8	4g	4％
				5	Hydroxyethyl cellulose	0.4g	0.4％
6	Water (W)	64g	67.6％

TABLE 2

When the salicylic acid gel II is provided for fifty volunteers, no irritation or allergic feedback appears, and the acne removing effect indicates 41 good people, 8 ordinary people and 1 invalid people.

It is noted that, herein, relational terms such as first and second, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.

Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.

Claims

1. A salicylic acid gel with low irritation for external use, which mainly comprises salicylic acid as an active ingredient, is characterized in that: the concrete components also comprise water, a cosolvent, a coating agent, an emulsifier and a gel forming agent, wherein the mass percentage of the components is that water is 55-90%, salicylic acid is 0.1-10%, the coating agent is 0.2-20%, the cosolvent is 0.2-40%, the emulsifier is 0.2-20%, and the gel forming agent is 2-15%, wherein the ratio of the salicylic acid to the cosolvent is 1: 1 to 1: 5, the ratio of the salicylic acid to the wrapping agent is 1: 0.1 to 1: 2, the ratio of salicylic acid to the emulsifier is 1: 1 to 1: 2.

2. The topical low irritation salicylic acid gel of claim 1 wherein: the cosolvent is a unit or polyol with a main chain of three or four carbons, including but not limited to propanol, butanol, ethylene glycol, propylene glycol, glycerol, butanediol, butanetriol, diethylene glycol, and the like, and when in use, one or a mixture of several of the alcohols meeting the above conditions can be selected.

3. The topical low irritation salicylic acid gel of claim 1 wherein: the wrapping agent is polyhydroxy biomolecule, specifically cyclodextrin, cellulose and derivatives thereof.

4. The topical low irritation salicylic acid gel of claim 1 wherein: the emulsifier is a common nonionic long carbon chain (the number of carbon atoms in a main chain is 8-20) emulsifier in cosmetics, and comprises fatty acid esters, stearic acid esters, lauric acid esters, oleic acid esters, fatty alcohol polyethers, oleic alcohol polyethers, lauryl alcohol polyethers and polyoxyethylene, wherein a liquid emulsifier with the HLB value more than 8 is selected in the first place, and has a good promotion effect on the stability of the gel.

5. The topical low irritation salicylic acid gel of claim 1 wherein: the gel forming agent is a common gel forming agent in cosmetic bottles, and comprises but is not limited to acrylics, cellulose derivatives, natural gum, poloxamers, polysaccharides, polyoxyethylenes, hyaluronic acids and the like, wherein the gel forming agent with higher gel viscosity formed by aqueous solution is selected, and the gel wall-hanging is optimal.

6. A method for preparing a salicylic acid gel with low irritation for external use according to any one of claims 1 to 5, comprising: the specific preparation method mainly comprises three steps:

1) and preparing a salicylic acid high-concentration glycidyl solution mother solution: uniformly stirring the cosolvent and salicylic acid, preparing the coating agent into an aqueous solution, heating, slowly adding the mixture of the cosolvent and the salicylic acid into the aqueous solution of the coating agent under the conditions of heating and stirring, and fully stirring to dissolve all the salicylic acid to form a salicylic acid high-concentration glycidyl solution mother liquor;

2) and preparation of salicylic acid dilute gel: preparing a gel forming agent into a dilute aqueous solution, heating to a proper temperature and stirring continuously, then dropwise adding a salicylic acid high-concentration glycidyl solution mother solution into the dilute aqueous solution of the gel forming agent, simultaneously heating an emulsifier to a proper temperature and dropwise adding, wherein the dropwise adding speed of salicylic acid, the mother solution and the emulsifier needs to be controlled during dropwise adding, so that the dropwise adding speed of the salicylic acid and the mother solution is consistent, and simultaneously the cost is reduced, thus forming salicylic acid dilute gel;

7. The method for preparing the salicylic acid gel with low irritation for external use according to claim 6, wherein the salicylic acid gel comprises: in the step 1, when the cosolvent has higher solubility to salicylic acid, a cosolvent solution of the salicylic acid is formed; when the cosolvent can not completely dissolve the salicylic acid, grinding the salicylic acid into fine powder in advance and stirring the fine powder as much as possible to fully mix the salicylic acid solid and the cosolvent; even if the salicylic acid is not completely dissolved, the salicylic acid can not be mixed with the wrapping agent aqueous solution, and the salicylic acid can be completely dissolved under the dual action of the cosolvent and the wrapping agent after mixing.

8. The method for preparing the salicylic acid gel with low irritation for external use according to claim 6, wherein the salicylic acid gel comprises: the concentration of the dilute aqueous solution of the gel forming agent in step 2 should be 1/50-1/10 of the prepared gel in step 3, and the solution should keep good fluidity and be easy to stir and mix.

9. The method for preparing the salicylic acid gel with low irritation for external use according to claim 6, wherein the salicylic acid gel comprises: the salicylic acid gel prepared in the step 3 has high viscosity, no fluidity in a natural state, stable phase and no obvious layering after being stored at room temperature for 12 months.