CN113372581A

CN113372581A - Sprayable hydrogel, preparation method and application thereof

Info

Publication number: CN113372581A
Application number: CN202110680423.2A
Authority: CN
Inventors: 葛贝尔; 赵洲; 王一诺
Original assignee: Hebei Ruinuocheng Biotechnology Co ltd
Current assignee: Hebei Ruinuocheng Biotechnology Co ltd
Priority date: 2021-06-18
Filing date: 2021-06-18
Publication date: 2021-09-10

Abstract

The invention belongs to the field of hydrogel materials and preparations, and discloses a sprayable hydrogel which comprises the following raw materials in percentage by mass: 0.2-0.5% of gellan gum, 0.4-0.5% of alkali metal salt, 0.8-1.5% of glycerol and the balance of water; the invention also provides a preparation method of the sprayable hydrogel and application of the sprayable hydrogel as a carrier in the fields of medicines and cosmetics. The invention is suitable for preparing a sprayable hydrogel, has good compatibility with most antibiotics, disinfectants, skin conditioners, antiseptics, rhinitis soothing agents and the like, can be widely used in the fields of medicines, cosmetics and the like, and can be used as a carrier for preparing medicines and cosmetics.

Description

Sprayable hydrogel, preparation method and application thereof

Technical Field

The invention belongs to the field of hydrogel materials and preparations, and particularly relates to a sprayable hydrogel, a preparation method and application thereof.

Background

The hydrogel is a multi-element system consisting of a high molecular three-dimensional network and water, is a substance form commonly existing in nature, and is a semisolid formed by swelling and crosslinking a plurality of high polymers or copolymers after absorbing a large amount of water. And is a "soft and wet" class of materials with unique physical properties (soft, aqueous and tunable porous structures) and a 3D network structure of good biocompatibility. Therefore, the hydrogel is widely used in the fields of cosmetics, tissue engineering and regenerative medicine, diagnosis, drug delivery, wound dressing, medical devices, and the like. For example, patent 200480023378.8 discloses a temperature-sensitive state-changing hydrogel composition which is transformed into a fluid state at 10 ℃ to 50 ℃ and transformed into a fluid state by body temperature when brought into contact with the skin, and a method for producing the same. Patent 201210485804.6 mentions a temperature sensitive hydrogel as a nutritional mask and a preparation method thereof, wherein the hydrogel is a temperature sensitive hydrogel, and the water absorption saturation of the hydrogel decreases with the increase of temperature in the temperature range of 10-50 ℃, and the water is released from the interior of the hydrogel.

At present, the hydrogel can be divided into two types according to the response condition of the hydrogel to external stimulation: one is conventional hydrogel which is not particularly sensitive to environmental changes, and the other is environmentally sensitive hydrogel which is intelligent, namely in-situ gel, which is mainly classified into temperature sensitive in-situ gel, pH sensitive in-situ gel and ion sensitive in-situ gel.

The temperature sensitive in-situ gel is a pseudoplastic fluid and is characterized in that phase change is generated when the critical temperature is reached. However, the greatest disadvantage of temperature-sensitive in-situ gel is that a large amount of high molecular gel substances are required, which is represented by poloxamer, the usage amount is usually up to more than 15%, and the critical phase transition temperature is negatively related to the content of the high molecular substances; meanwhile, in order to prevent the problem of drug burst release during the phase transition, a certain amount of rheology modifier and the like is usually added. This brings great inconvenience to the manufacturing process, thereby limiting its application in practical production.

pH sensitive in situ gels are a class of systems represented by the gel substance carbomer, characterized by the need to adjust the pH to a specific value to achieve a phase transition. It is well known that the pH of human body fluids is maintained in a relatively stable range, and that either too high or too low can cause serious problems. This therefore limits the application of pH sensitive in situ gels in the field of pharmaceutical carriers.

The ion sensitive in-situ gel is a system which changes according to the concentration of environmental ions and then undergoes phase change, and typical substances comprise gel substances such as sodium alginate, gellan gum and the like. The application of such systems in the medical field is typically ocular administration, due to the amount of metal cations contained in the tear fluid. If applications in other fields are desired, it is desirable to present the gel in AB bottles, i.e., A bottles containing gellable materials and B bottles containing ionic modifiers. This causes great inconvenience, and in order to achieve a certain strength of the gel, it is essential to select divalent metal cations as the ion modifier, and the in-situ gel prepared from the divalent metal cations is generally used as a plastic fluid, and it is difficult to form a spray having a certain strength after the gel is formed.

Due to the defects of the existing temperature-sensitive in-situ gel, pH-sensitive in-situ gel and ion-sensitive in-situ gel, the use is inconvenient, and the application of the gel in the actual production is limited. Therefore, the development of the sprayable hydrogel which is well compatible with most antibiotics, disinfectants, skin conditioners and the like has important significance.

Disclosure of Invention

The invention aims to provide a sprayable hydrogel, which forms a spray by utilizing the shear thinning principle of a pseudoplastic fluid, gels again after being sprayed, improves the strength of the hydrogel by utilizing alkali metal salt to combine gellan gum with different concentration, and increases the strength of the hydrogel through natural evaporation;

it is another object of the present invention to provide a process for the preparation of the sprayable hydrogel described above;

it is a third object of the present invention to provide the use of the sprayable hydrogel described above.

In order to achieve the purpose, the invention adopts the following technical scheme:

a sprayable hydrogel comprises the following raw materials in percentage by mass: 0.2-0.5% of gellan gum, 0.4-0.5% of alkali metal salt, 0.8-1.5% of glycerol and the balance of water.

The material comprises the following raw materials in percentage by mass: 0.25-0.4% of gellan gum, 0.45-0.48% of alkali metal salt, 1-1.2% of glycerol and the balance of water.

As a second limitation, the composition comprises the following raw materials in percentage by mass: 0.25% of gellan gum, 0.475% of alkali metal salt, 1% of glycerin and the balance of water.

As a third limitation, the gellan gum is a low acyl gellan gum.

As a fourth limitation, the alkali metal salt is at least one of sodium chloride, potassium chloride, lithium chloride, sodium sulfate, potassium sulfate, lithium sulfate, sodium nitrate, potassium nitrate, lithium nitrate, sodium oxalate, potassium oxalate, lithium oxalate, sodium phosphate, potassium phosphate, and lithium phosphate.

The invention also provides a preparation method of the sprayable hydrogel, which comprises the following steps:

s1, heating and dissolving gellan gum and water to obtain a solution A;

s2, heating and dissolving the alkali metal salt, the glycerol and the rest water to obtain a solution B;

s3, mixing and stirring the solution A and the solution B to obtain sprayable hydrogel;

the water is used in two parts, and the mass sum of gellan gum and water is as follows: the ratio of the sum of the masses of alkali metal salt, glycerol and remaining water is 1: 0.25 to 4.

In the step S1, the heating temperature of the gellan gum is 80-90 ℃ and the heating time is 30-50 min.

In the second limitation, in step S2, the alkali metal salt and glycerin are heated at 70-90 deg.C for at least 15 min.

And as a third limitation, in the step S3, stirring the solution A and the solution B for 10-40 min, and cooling to 55-75 ℃ after stirring to obtain the sprayable hydrogel.

In another aspect, the invention also provides an application of the sprayable hydrogel, which is characterized in that the sprayable hydrogel is used for preparing medicinal products and cosmetics.

Due to the adoption of the technical scheme, compared with the prior art, the invention has the technical progress that:

(1) the sprayable hydrogel prepared by the invention has strong applicability, is well compatible with most antibiotics, disinfectants, skin conditioners, antiseptics, rhinitis soothing agents and the like, can be widely used for preparing medical products and cosmetics, and can be used in the fields of medicine, cosmetics and the like.

(2) The sprayable hydrogel prepared by the invention is convenient to spray after being filled;

(3) according to the invention, the nature that the pseudoplastic fluid and the plastic fluid can be converted by combining the alkali metal salt with the gellan gum with different mass percentages is utilized, the principle that the pseudoplastic fluid can be sheared and thinned is utilized, and the hydrogel can be formed again after spraying; as the water evaporates, the pseudoplastic fluid formed by gellan gum and alkali metal salt is converted into a plastic fluid, thereby forming a gel with a certain strength.

The invention belongs to the field of hydrogel materials and preparations, and is suitable for preparing a sprayable hydrogel.

Detailed Description

The present invention is further described with reference to the following examples, but it should be understood by those skilled in the art that the present invention is not limited to the following examples, and any modifications and variations based on the specific examples of the present invention are within the scope of the claims of the present invention.

EXAMPLE 1 preparation of sprayable hydrogel

The embodiment comprises the following steps:

s1, heating 0.2kg of low acyl gellan gum and 79.8kg of water at 85 ℃ for 35min, stirring and dissolving to obtain a solution A;

s2, heating 0.5kg of alkali metal salt, 1.2kg of glycerol and 18.3kg of the rest water at 70 ℃ for 15min, stirring and dissolving to obtain a solution B;

and S3, mixing and stirring the solution A and the solution B for 40min, cooling to 65 ℃, and filling to obtain the sprayable hydrogel. The obtained sprayable hydrogel is convenient to spray after being filled, and has good compatibility with most antibiotics, disinfectants, skin conditioners, antiseptics, rhinitis soothing agents and the like.

Example 2 preparation of sprayable hydrogel

Examples 2-11 are processes for preparing sprayable hydrogels, respectively, and they are substantially the same as example 1 except for the amount of raw materials and process parameters used to prepare 100kg of sprayable hydrogel, respectively, as detailed in table 1. The composition of the alkali metal salt is shown in table 2.

Table 1 examples 2-11 raw material compositions

TABLE 2 composition of alkali metal salts of step S2

In practical applications, the alkali metal salt of this embodiment may be one or more of sodium chloride, potassium chloride, lithium chloride, sodium sulfate, potassium sulfate, lithium sulfate, sodium nitrate, potassium nitrate, lithium nitrate, sodium oxalate, potassium oxalate, lithium oxalate, sodium phosphate, potassium phosphate, and lithium phosphate.

Example 12 comparative test

Comparative example 1 poloxamer gel

Preparing 17% poloxamer F407 aqueous solution, wherein the phase transition temperature is similar to the body surface temperature, and obtaining poloxamer gel marked as M1.

Comparative examples 2 to 4

Preparing gellan gum solutions with the concentrations of 0.2%, 0.4% and 0.6%, and adding calcium chloride solutions with the concentrations of 0.1% respectively to gelatinize the gellan gum solutions, wherein the obtained gel products are marked as M2-M4.

The gel products of comparative examples 1 to 4 were filled in spray bottles and spray-compared with the sprayable hydrogel prepared in example 11, and gel strength comparison and a residual test after skin application were performed, and the obtained results are shown in table 3.

TABLE 3 comparative results

As can be seen from Table 3, the sprayable hydrogel prepared in example 11 of the present invention can be used in a spray form, and after being sprayed, a hydrogel having a certain strength can be formed. The skin care product does not generate residue and any uncomfortable feeling after being smeared on the skin, and the formula and the preparation process are simple, so that the skin care product has wide application prospect and application range.

EXAMPLE 13 use of a sprayable hydrogel

The sprayable hydrogel prepared by the invention can be used for preparing medical products and cosmetics, and can be used for disinfecting wound surfaces, treating fungal infection, relieving rhinitis, nursing skin and the like after antibiotics, disinfectants, skin conditioners, rhinitis soothing agents and the like are respectively added.

Application example 1 sprayable hydrogel having dermal fungal infection treatment

The sprayable hydrogel prepared by the invention is taken as a carrier, and is matched with an antifungal medicament (miconazole nitrate) to prepare the sprayable hydrogel with the function of treating skin fungal infection, and the specific preparation method comprises the following steps:

s1, weighing 0.6kg of gellan gum and 99.4kg of sterile water, heating at 90 ℃ for 35min, stirring and dissolving to obtain a solution A;

s2, weighing 0.95kg of sodium chloride and 2kg of glycerin, dissolving in 97.05kg of the rest sterile water, heating at 70 ℃ for 15min, stirring and dissolving to obtain a solution B;

s3, mixing and stirring the solution A and the solution B for 40min, cooling to 70 ℃, and aging for 60min to obtain 200kg of sprayable hydrogel;

s4, adding 0.02kg of miconazole nitrate into 99.98kg of aged sprayable hydrogel, dissolving, stirring until the mixture is clear and transparent, filling the mixture into a bottle, and finally sterilizing to obtain the sprayable hydrogel with the effect of treating dermatophyte infection.

The antifungal agent in this application example may be selected from polyenes (polyenes), fluorocytosines (flucytosine), azoles (azoles), echinocandins (echinocandins), and the like.

(II) Performance verification test

The application example uses trichophyton rubrum (ATCC28188) to verify the treatment effect of the prepared sprayable hydrogel with the function of treating skin fungal infection on fungal infection.

Firstly, picking a colony with large sesame grains and no pollution from an activated trichophyton rubrum strain, dissolving the colony in 0.9% sodium chloride injection, placing the colony in a micro-oscillator to shake for 2-3 min, fully shaking to elute spores, uniformly mixing, and adjusting the turbidity of the bacterial suspension to 0.5-1 McLeod turbidity which is equivalent to 5 x 10⁶-10*10⁶cfu/ml。

Then 0.5ml of the inoculum was measured by pipette and transferred to Sabouraud agar medium and spread evenly with a spreader. Three of the test groups and two of the control groups. In the process of performance verification, a control group is directly placed into an incubator at 28 ℃ for 5 days; each test group was sprayed with 1.5ml of the sample prepared in this application example, and cultured in an incubator at 28 ℃ for 5 days. The colony growth was observed after 5 days, and the results are shown in Table 4.

TABLE 4

As can be seen from Table 4, the colonies of the control group grew well, and no colonies appeared on the petri dish in the test group, so that the application example had a good inhibitory effect on the growth of Trichophyton rubrum (ATCC28188), and was easy to use. Therefore, the sprayable hydrogel with the function of treating dermatophyte infection prepared by the application example has good antifungal effect, and the application example shows that the hydrogel prepared by the application example can be applied in a spraying mode, forms hydrogel at the affected part, and gives sufficient time for antibiotics to act on the affected part while being convenient to use.

Application example 2 sprayable hydrogel with wound and vaginal disinfectant effects

In the embodiment, the skin disinfectant adopts chlorhexidine acetate which is a cationic surface active preservative and has the characteristics of wide antibacterial spectrum and strong antibacterial effect. The action mechanism is to change the permeability of the bacterial cell membrane, has quite strong broad-spectrum bacteriostasis and sterilization effects, and is effective to gram-positive bacteria and gram-negative bacteria. Can be used for hand, instrument, wound surface and skin disinfection, etc., and can kill staphylococcus aureus, escherichia coli and candida albicans, and its aqueous solution is a medicine for treating mycotic vaginitis and cervical erosion, and has the function of sterilization.

The sprayable hydrogel prepared by the invention is used as a carrier to prepare the sprayable hydrogel with wound and vagina disinfection effects, and the specific preparation method comprises the following steps:

s4, adding 0.2kg of chlorhexidine acetate into 99.8kg of aged sprayable hydrogel, dissolving, stirring until the mixture is clear and transparent, filling into a bottle, and finally sterilizing to obtain the sprayable hydrogel with wound and vagina disinfection effects.

The skin disinfectant in the present application example may further include, but is not limited to, quaternary ammonium salt disinfectant, biguanide antibacterial agent, iodine-containing disinfectant, triclosan, and the like.

(II) Performance verification test

(1) Sterilization effect verification

Coli (ATCC25922), staphylococcus aureus (ATCC6538), and candida albicans c. albicans (ATCC10231) were used to verify the bactericidal and disinfectant effects of the sprayable hydrogel having wound and vaginal disinfectant effects.

First, one bead of Escherichia coli, Staphylococcus aureus, Candida albicans from a frozen stock solution was placed in separate flasks with 100ml of Muellar-Hinton Broth (MHB) using an inoculating loop, and cultured overnight in an orbital incubator at 37 ℃. Meanwhile, three bottles of broth containing 20ml of MHB were placed in an incubator at 37 ℃ and heated overnight for preheating. The following day, 500ul of overnight grown culture was transferred from each individual flask to a corresponding 20ml preheated broth bottle and placed in an orbital incubator for continued growth until logarithmic growth phase was reached.

1ml of the bacterial liquid was evenly spread on five Muellar Hinton Agar (MHA) culture dishes, three culture dishes for each bacterium were set as a test group, and two culture dishes were set as a control group. The control group was placed directly at 37 ℃ in 5% CO₂Culturing in an incubator overnight; 2ml of sprayable hydrogel with wound surface and vagina disinfection functions prepared by the application example is uniformly sprayed in a test group, exposed in the air for 15min under a super clean bench condition, and then put into the incubator for overnight culture. The colony number of each culture dish was measured using a colony measuring instrument, and the average of the colonies of escherichia coli, staphylococcus aureus, and candida albicans in the test group and the control group was determined, and the specific results are shown in table 5.

TABLE 5

As can be seen from Table 5, the growth of microorganisms was normal in the culture dishes of the control group to which the disinfectant was not sprayed, and no growth of colonies was observed in the culture dishes of the test group to which the disinfectant was sprayed. From this, it is considered that the present application example has a good sterilization effect.

(2) Verification of irritation to mucous membranes and wounds

To evaluate the irritation of the application examples to mucous membranes and wounds, eye irritation experiments were performed using new zealand white rabbits. Taking three 2.5KG New Zealand white rabbits, taking the left eye of each white rabbit as a test eye, and adding 0.1ml of sprayable hydrogel with wound surface and vagina disinfection functions, which is prepared by the application example, into the eye conjunctival sac; the right eye of each rabbit was a control eye, and 0.1ml of physiological saline was added for the control experiment. After the hydrogel of the application example is dropped, the eyes are passively closed for 4s, and after 30s, the eyes are washed by physiological saline. And the conjunctival injury status was examined 1h, 24h, 48h, and 72h after instillation. After tests, the product prepared by the application example has no irritation.

Application example 3 sprayable hydrogel with rhinitis symptom relieving effect

The sprayable hydrogel prepared by the invention is used as a carrier, and is matched with glucocorticoid (mometasone furoate) and preservative (chlorhexidine acetate) to prepare the sprayable hydrogel with the effect of treating rhinitis symptoms, and the specific preparation method comprises the following steps:

s1, weighing 0.5kg of gellan gum and 99.5kg of sterile water, heating at 90 ℃ for 35min, stirring and dissolving to obtain a solution A;

s3, mixing and stirring the solution A and the solution B for 40min, cooling to 60 ℃, and aging for 60min to obtain 200kg of sprayable hydrogel;

s4, adding 0.05kg of mometasone furoate and 0.01kg of chlorhexidine acetate into 99.94kg of aged sprayable hydrogel, dissolving, stirring until the mixture is clear and transparent, filling into a bottle, and finally sterilizing to obtain the sprayable hydrogel with the effect of relieving rhinitis symptoms.

The glucocorticoid in the present application can also be selected from, but not limited to, budesonide, fluticasone propionate, beclomethasone propionate, triamcinolone acetonide, and the like.

(II) Performance verification test

30 wistar rats were divided randomly into two groups, with males and females in half each. One group of rats were administered with the sprayable hydrogel prepared in this application example daily at a dose of 10 ul/nostill each. The other group of rats was given daily blank saline in an amount of 10 ul/nostill. Dripping into nose for 20 days. After the test, the nasal mucosa tissue of the rat was taken out and the presence of congestion, red swelling and the like was observed. The nasal mucosa tissue is fixed with formalin, sliced, stained with hematoxylin-eosin, and examined under an optical microscope for pathological section of the nasal mucosa.

After microscopic examination, the nasal mucosa of the two groups of rats has complete structure, and no obvious vasodilation and inflammatory cell infiltration are observed in the submucosa. Therefore, after the continuous administration for 20 days, no obvious abnormality of nasal mucosa tissues of the sprayable hydrogel with the effect of relieving rhinitis symptoms and the normal saline prepared by the application example is seen, which indicates that the sprayable hydrogel with the effect of relieving rhinitis symptoms prepared by the application example has no local irritation effect on the nasal mucosa after long-term administration.

Application example 4 spray mask having moisturizing effect

The sprayable hydrogel prepared by the invention is matched with a skin conditioner (water-soluble lanolin, phenoxyethanol, cucumber extract, aloe extract and decarboxycarnosine) to prepare a spray mask with a moisturizing effect, and the specific preparation method comprises the following steps:

s1, weighing 0.5kg of gellan gum, 0.015kg of water-soluble lanolin, 1.6kg of phenoxyethanol and 97.885kg of deionized water, heating at 250rpm at 90 ℃ for 35min, and stirring for dissolving to obtain a solution A;

s2, weighing 0.95kg of sodium chloride, 2kg of glycerol, 3kg of cucumber extract and 1kg of aloe extract, dissolving in 93.05kg of the rest sterile water, heating at 250rpm at 70 ℃ for 30min, stirring and dissolving to obtain a solution B;

s3, mixing and stirring the solution A and the solution B for 40min, and cooling to 63 ℃ to obtain 200kg of sprayable hydrogel;

s4, mixing and stirring 0.05kg of decarbocreatine and 99.95kg of the mixed 63 ℃ sprayable hydrogel until the mixture is clear and transparent, filling, cooling to room temperature, packaging and sealing to obtain the spray mask with the moisturizing effect.

In the application example, the skin conditioner can also be selected from various plant and natural product extracts such as cucumber extract, aloe extract, propolis extract, seaweed extract and the like.

(II) Performance verification test

(1) Evaluation of safety

The spray mask with the moisturizing effect prepared in the application example is subjected to safety evaluation according to the item 3.1.2 in GB 7919-1987 cosmetic safety evaluation program and method. The experimental contents include an acute skin stimulation experiment, a multiple skin stimulation experiment and an eye stimulation experiment. Safety evaluation two new zealand white rabbits, male and female, at 2.5KG were selected for the experiment, with a test period of 14 days. In the experimental process, the experimental animals all have the conditions of skin red and swelling, blisters, eye and cornea congestion and the like. The samples prepared according to this method can be considered safe and non-irritating according to this standard.

(2) Evaluation of product quality

And (3) carrying out product quality inspection on the spray mask with the moisturizing effect prepared in the application example according to the QB/T2872-2017 mask standard. The product is transparent jelly product with natural cucumber and plant fragrance, and has pure fragrance and no foreign odor. The sensory index, the physicochemical index and the sanitary index of the sample all meet the standard requirements. By combining the two items, the sample can be subjected to a human body test to verify the efficacy of the product.

(3) Water supplement efficacy verification

In order to verify the moisturizing effect of the spray mask with the moisturizing effect prepared in the application example, 30 volunteers were recruited to perform an effect evaluation experiment. Volunteers had no past history of allergy and no major chronic disease, 10 men and 20 women. The volunteer age distribution is shown in table 6.

TABLE 6

The experiment is carried out for two weeks, three times per week and 15min each time. The difference of the skin water content 15min and 30min before and after the use is detected by using a skin water content measuring instrument to prove the water replenishing effect. Three positions (forehead, nasal wing and face) of the face are selected for data acquisition, each point is tested three times, and nine data average values are calculated. The overall average values after six experiments are tabulated and the test results are shown in table 7.

TABLE 7

As can be seen from Table 7, after 15 minutes of application, the moisture content of the skin of the volunteers increased significantly, and the moisture content of the skin remained at a higher value within 30 minutes, so that the skin was supplemented with a large amount of moisture and appeared white and ruddy.

Application example 5 spray mask with anti-allergy and soothing effects

The sprayable hydrogel prepared by the invention is matched with skin conditioners (water-soluble lanolin, phenoxyethanol, purslane extract and dandelion extract) to prepare the sprayable facial mask with anti-allergy and relieving effects, and the specific preparation method comprises the following steps:

s1, weighing 0.5kg of gellan gum, 0.015kg of water-soluble lanolin, 1.6kg of phenoxyethanol and 97.885kg of deionized water, heating at 90 ℃ for 35min, and stirring for dissolving to obtain a solution A;

s2, weighing 0.95kg of sodium chloride, 0.05kg of purslane extract powder, 0.01kg of dandelion extract powder, 2kg of glycerol and 96.99kg of deionized water, heating at the temperature of 70 ℃ at 250rpm, and stirring for dissolving to obtain a solution B;

s4, mixing 0.05kg of blueish copper peptide, 0.001kg of palmitoyl tetrapeptide-7 and 99.949kg of the mixed sprayable hydrogel at 63 ℃ and stirring until the mixture is clear and transparent, filling, cooling to room temperature, packaging and sealing to obtain the anti-allergy and soothing spray mask.

(II) Performance verification test

(1) Evaluation of safety

The spray mask with anti-allergy and relieving effects prepared by the application example is subjected to safety evaluation according to the item 3.1.2 in GB 7919-1987 cosmetic safety evaluation program and method. The experimental contents include an acute skin stimulation experiment, a multiple skin stimulation experiment and an eye stimulation experiment. Safety evaluation two new zealand white rabbits, male and female, at 2.5KG were selected for the experiment, with a test period of 14 days. In the experimental process, the experimental animals all have the conditions of skin red and swelling, blisters, eye and cornea congestion and the like. Samples prepared according to this method can be considered safe and non-irritating according to the GB 7919-1987 cosmetic safety evaluation procedure and method.

(2) Evaluation of product quality

The spray mask with the anti-allergy and soothing effects prepared by the application example is subjected to product quality inspection according to the QB/T2872-2017 mask standard. The product is a yellowish transparent jelly product with natural Chinese herbal medicine smell, and has pure fragrance and no foreign odor. The sensory index, the physicochemical index and the sanitary index of the sample all meet the standard requirements. By combining the two items, the sample can be subjected to a human body test to verify the efficacy of the product.

(3) Verification of anti-allergy and relieving efficacy

In order to verify the moisturizing effect of the spray mask with anti-allergy and soothing effects prepared in the application example, 30 volunteers were recruited for effect evaluation experiments. Volunteers had no past history of allergy and no major chronic disease, 10 men and 20 women. The volunteer age distribution is shown in table 8.

TABLE 8

The soothing and anti-allergy effects of the application example were verified by using the SDS patch method. The medial forearm skin was divided into A, B, C areas of 4 cm square each, with area C as a positive control. The area a was sprayed with the sample of this application example in advance, and the test was carried out 15 minutes later. A10% SDS patch was applied to the three regions, and 0.2ml of 10% SDS was added dropwise every 15 min. After 45 minutes, the untreated B, C area is found to be red and swollen obviously, and the area A sprayed with the application example only becomes slightly red and does not have symptoms such as pruritus and the like. At the moment, the sample prepared by the application example is sprayed to the area B, and after 15 minutes, the itching symptom of the area B is relieved, and the red swelling is improved. Thus, the application example is proved to have the effect of relieving.

Application example 6 spray mask with whitening effect

The sprayable hydrogel prepared by the invention is matched with skin conditioners (water-soluble lanolin, phenoxyethanol, bighead atractylodes rhizome extract, Japanese ampelopsis root extract, rose hydrosol, nonapeptide-1 and acetyl tetrapeptide-5) to prepare the spray mask with the whitening effect, and the specific preparation method comprises the following steps:

s1, weighing 0.55kg of gellan gum, 0.015kg of water-soluble lanolin, 1.6kg of phenoxyethanol and 97.835kg of deionized water, heating at 90 ℃ for 35min, and stirring for dissolving to obtain a solution A;

s2, weighing 0.95kg of sodium chloride, 0.1kg of white atractylodes rhizome extract powder, 0.1kg of ampelopsis japonica extract, 3kg of rose hydrosol, 2kg of glycerin and 93.85kg of deionized water, heating at the temperature of 70 ℃ at 250rpm, and stirring for dissolving to obtain a solution B;

s4, mixing 0.0001kg of nonapeptide-1, 0.0005kg of acetyl tetrapeptide-5 and 99.9994kg of the mixed sprayable hydrogel at 63 ℃, stirring until the mixture is clear and transparent, filling, cooling to room temperature, packaging and sealing to obtain the spray mask with the whitening effect.

In this embodiment, the skin conditioner may also be selected from, but not limited to, niacinamide, Vc and derivatives, hexapeptide-9, arbutin, and other natural extracts, chemically synthesized small molecules or polypeptides with whitening effect.

(II) Performance verification test

(1) Evaluation of safety

The spray mask with whitening effect prepared by the application example is subjected to safety evaluation according to the item 3.1.2 in GB 7919-1987 cosmetic safety evaluation program and method. The experimental contents include an acute skin stimulation experiment, a multiple skin stimulation experiment and an eye stimulation experiment. Safety evaluation two new zealand white rabbits, male and female, at 2.5KG were selected for the experiment, with a test period of 14 days. In the experimental process, the experimental animals all have the conditions of skin red and swelling, blisters, eye and cornea congestion and the like. Samples prepared according to this method can be considered safe and non-irritating according to the GB 7919-1987 cosmetic safety evaluation procedure and method.

(2) Evaluation of product quality

And (3) carrying out product quality inspection on the spray mask with the whitening effect prepared by the application example according to the QB/T2872-2017 mask standard. The product is transparent jelly with natural rose fragrance, and has pure fragrance and no foreign odor. The sensory index, the physicochemical index and the sanitary index of the sample all meet the standard requirements. By combining the two items, the sample can be subjected to a human body test to verify the efficacy of the product.

(3) Skin whitening efficacy verification

In order to verify the moisturizing effect of the spray mask with whitening effect prepared in the application example, 30 volunteers were recruited to perform an effect evaluation experiment. Volunteers had no past history of allergy and no major chronic disease, 10 men and 20 women. The volunteer age distribution is shown in table 9.

TABLE 9

The experiment is used for four weeks, once a day and ten minutes each time. During the experiment, other products with whitening efficacy are not used, and meanwhile, outdoor labor is not carried out. The volunteers were tested every 7 days using a minolta spectrophotometer, evaluated using the CIELab color system, and tabulated as the percentage of skin tone brightened.

Wherein the skin color whiteness degree is improved＝(L-L_{Original source})/L_{Original source}*100％。

Three positions (forehead, nasal wing and face) of the face of the volunteer are selected for data acquisition, each point is tested three times, nine data average values are obtained, the skin color is measured according to the average values, and the test results are shown in table 10.

Watch 10

Statistics of the table show that the skin color of all volunteers is improved after one month of experiments. The whitening effect is achieved, and no allergic signs such as pruritus, red swelling, blisters and the like appear in the experiment process. Therefore, the safety and the effectiveness of the application example are fully verified.

Although the present invention has been described in detail with reference to the above embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments described above, or equivalents may be substituted for elements thereof. 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

1. A sprayable hydrogel is characterized by comprising the following raw materials in percentage by mass: 0.2-0.5% of gellan gum, 0.4-0.5% of alkali metal salt, 0.8-1.5% of glycerol and the balance of water.

2. The sprayable hydrogel of claim 1, comprising the following raw materials in percentage by mass: 0.25-0.4% of gellan gum, 0.45-0.48% of alkali metal salt, 1-1.2% of glycerol and the balance of water.

3. The sprayable hydrogel of claim 2, comprising the following raw materials in percentage by mass: 0.25% of gellan gum, 0.475% of alkali metal salt, 1% of glycerin and the balance of water.

4. The sprayable hydrogel of any of claims 1 to 3, wherein the gellan gum is a low acyl gellan gum.

5. The sprayable hydrogel of any of claims 1 to 3, wherein the alkali metal salt is at least one of sodium chloride, potassium chloride, lithium chloride, sodium sulfate, potassium sulfate, lithium sulfate, sodium nitrate, potassium nitrate, lithium nitrate, sodium oxalate, potassium oxalate, lithium oxalate, sodium phosphate, potassium phosphate, and lithium phosphate.

6. A process for the preparation of a sprayable hydrogel of any of claims 1 to 5 comprising the steps of:

s1, heating and dissolving gellan gum and water to obtain a solution A;

7. The method of claim 6, wherein in step S1, the gellan gum is heated at 80-90 ℃ for 30-50 min.

8. The process of claim 7, wherein the alkali metal salt and glycerin are heated at 70-90 ℃ for at least 15min in step S2.

9. The preparation method of the sprayable hydrogel according to claim 8, wherein in step S3, the solution a and the solution B are stirred for 10-40 min, and then cooled to 55-75 ℃ after stirring to obtain the sprayable hydrogel.

10. A use of a sprayable hydrogel according to any of claims 1 to 5 for the preparation of pharmaceutical and cosmetic products.