Natural mosquito repellent and anti-itching compound ointment containing lygodium and cold-pressed coconut oil

Abstract

The present application relates to the technical field of compound ointment, in particular to a natural mosquito-repelling and itching-relieving compound ointment containing Lyginia and cold-pressed coconut oil. The ointment comprises Lyginia extract, cold-pressed coconut oil, natural beeswax, natural modifier, natural synergist, menthol and vitamin E. In the natural mosquito-repelling and itching-relieving compound ointment containing Lyginia and cold-pressed coconut oil, the natural modifier and the cold-pressed coconut oil form a stable fat-soluble combination system, and the natural beeswax forms a semi-solid matrix network, which can optimize the bearing environment of the Lyginia extract in the matrix, reduce the stratification of active ingredients due to density difference, improve the dispersion uniformity and retention stability of active ingredients in the oil matrix, and improve the stable bearing capacity of unit ointment for active ingredients, thereby solving the problems of uneven dispersion of active ingredients and insufficient bearing capacity of unit ointment, and making the ointment more stably exert mosquito-repelling and itching-relieving effects during use.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of compound ointment, in particular to a natural mosquito repellent and itching-relieving compound ointment containing Lyginia and cold-pressed coconut oil. BACKGROUND

[0002] At present, in the research and development of natural mosquito repellent and itching-relieving compound ointment, plant extracts are often used as core active ingredients, and natural oils are used as substrates, aiming to combine the mosquito repellent and itching-relieving effects of plant ingredients and the skin compatibility of natural oils to meet the needs of consumers for safe and mild external preparations. Lyginia is often selected as the source of active ingredients due to its traditional application basis, and cold-pressed coconut oil becomes an important part of the substrate due to its moisturizing properties. The combination of the two is a common approach to developing natural compound ointments to achieve the dual effects of mosquito repellent and itching relief.

[0003] In the prior art, Lyginia-related components and cold-pressed coconut oil are combined through simple mixing or conventional emulsification to achieve basic formulation molding and function loading. However, there are still some deficiencies in the compatibility and stability between the two and the carrying efficiency of active ingredients. For example, the lack of close interaction between the components not only reduces the uniformity of active substances in Lyginia in the cold-pressed coconut oil substrate, causing problems such as enrichment of active ingredients in some areas and insufficient content in other areas, but also affects the retention of active ingredients in the substrate, reduces the total amount of active ingredients that can be stably carried per ointment, and affects the mosquito repellent and itching-relieving effects of the ointment, thereby reducing the overall application value and user experience of the natural mosquito repellent and itching-relieving compound ointment.

[0004] Therefore, there is an urgent need for a natural mosquito repellent and itching-relieving compound ointment containing Lyginia and cold-pressed coconut oil. SUMMARY

[0005] The present application aims to provide a natural mosquito repellent and itching-relieving compound ointment containing Lyginia and cold-pressed coconut oil to solve the problems raised in the background.

[0006] To achieve the above-mentioned purpose, the present application provides a natural mosquito repellent and itching-relieving compound ointment containing Lyginia and cold-pressed coconut oil, which comprises Lyginia extract 8-12 parts, cold-pressed coconut oil 30-40 parts, natural beeswax 6-10 parts, natural modifier 2-4 parts, natural synergist 3-5 parts, menthol 2-3 parts, and vitamin E 1-2 parts.

[0007] The natural modifier adopts phytosterol, which is purchased from Zhejiang Kangyi Biotechnology Co., Ltd., batch number KY-PS230315, for forming a stable fat-soluble binding system with cold-pressed coconut oil, which is purchased from Zhejiang Tropical Crop Technology Co., Ltd., batch number ZJTR231028; and optimizing the matrix carrying environment of the extract of Scytalidium, which can improve the dispersion stability of the extract of Scytalidium in the oil matrix;

[0008] The natural synergist adopts patchouli extract, which is purchased from Xi'an Tianyi Biotechnology Co., Ltd., batch number TY-POG230810, for forming a synergistic system with flavonoids and saponins in the extract of Scytalidium, for strengthening the functional complementation effect between active ingredients, which can enhance the mosquito-repelling and itching-relieving effect of the compound ointment, and the combination of phytosterol and cold-pressed coconut oil can also assist in improving the compatibility of the extract of Scytalidium and the extract of Scytalidium in the matrix, promoting the uniform dispersion of the extract of Scytalidium in the cold-pressed coconut oil matrix, reducing the problem of active ingredient enrichment or insufficient content, and further improving the stable carrying capacity of active ingredients per unit ointment.

[0009] The natural beeswax forms a semi-solid matrix network with fatty acid glycerides in cold-pressed coconut oil and polar components in the extract of Scytalidium, which is used to build a stable ingredient carrying structure, can fix the fluidity of cold-pressed coconut oil and wrap the extract of Scytalidium, avoiding the stratification of active ingredients due to density difference, and the fat-soluble nature of beeswax assists phytosterol in optimizing the matrix environment, further improving the dispersion uniformity and retention stability of the extract of Scytalidium in the oil system;

[0010] The vitamin E forms a weak hydrogen bond binding system with fatty acid glycerides in cold-pressed coconut oil and flavonoid components in the extract of Scytalidium, which is used to build an ingredient protection and stability auxiliary structure, can reduce the loss of active ingredients in the extract of Scytalidium due to oxidation, and the fat-soluble nature of vitamin E synergizes with natural beeswax and phytosterol to optimize the compatibility of the oil matrix, assisting in improving the dispersion persistence of the extract of Scytalidium in the cold-pressed coconut oil system, and increasing the long-acting nature of the mosquito-repelling and itching-relieving effect of the compound ointment;

[0011] The menthol forms a fat-soluble dispersion system with fatty acid glycerides in cold-pressed coconut oil and polar components in the extract of Scytalidium, which is used to build a cooling and soothing active ingredient synergistic structure, can integrate into the oil matrix through its fat-soluble nature, complement the itching-relieving effect of the extract of Scytalidium, quickly relieve skin itching and discomfort, and the volatile components of menthol can assist in enhancing the mosquito-repelling effect of the compound ointment, and the uniform dispersion of menthol in the matrix can further diffuse the extract of Scytalidium in the cold-pressed coconut oil system, reduce the local aggregation of active ingredients, and assist in improving the effective action range of active ingredients per unit ointment.

[0012] Further comprising the following preparation steps:

[0013] S1, raw material pretreatment and active ingredient activation: place the extract of goldthread and natural synergist in a first sterile stirring container, add one-third of cold-pressed coconut oil, and stir at a constant temperature of 35-40°C and a speed of 500-600 r / min for 15-20 min, so that the active ingredients (flavonoids, saponins) in the two extracts are fully dissolved and dispersed in the oil, forming a preliminary active ingredient-oil dispersion system. At the same time, place the natural modifier and the remaining two-thirds of cold-pressed coconut oil in a second sterile stirring container, and stir at a constant temperature of 45-50°C and a speed of 800-900 r / min for 10-12 min, so that the natural modifier fully combines with the fatty acid glycerides in the cold-pressed coconut oil, forming a stable fat-soluble modified matrix system;

[0014] S2, preliminary construction of matrix network: add the active ingredient-oil dispersion system to the modified matrix system, and continuously stir at a constant temperature of 40-45°C and a speed of 700-800 r / min for 24-30 min. During this period, add natural beeswax in stages to obtain a matrix intermediate in which the active ingredients are preliminarily wrapped, reducing the tendency of stratification due to density differences, and at the same time, the natural modifier and beeswax optimize the matrix structure and enhance the preliminary carrying capacity of the system for active ingredients;

[0015] S3, synergistic system compounding and function enhancement: add menthol and vitamin E to the matrix intermediate, and continuously stir at a constant temperature of 38-42°C and a speed of 600-700 r / min for 18-22 min. During this process, menthol is incorporated into the oil matrix to form a fat-soluble dispersion system with the polar components of the goldthread extract, driving the active ingredients to further diffuse; vitamin E forms a weak hydrogen bond system with the fatty acid glycerides and flavonoids in the system, and at the same time, it optimizes the matrix compatibility with the natural modifier and beeswax, obtaining a composite matrix system that not only enhances the uniformity of active ingredient dispersion, but also constructs a dual-function system of component protection and cooling and soothing;

[0016] S4, constant temperature maturation and structure stabilization: use a low-temperature and low-speed stirring compounding maturation method to process the composite system, obtaining a pre-product of ointment with a dense structure, uniform component dispersion, and stable active ingredient carrying capacity;

[0017] S5, low temperature shaping and quality control: the ointment pre-product is cooled to 20-25 DEG C, and then is placed in a closed environment for 25-30 min to make the semi-solid matrix network fully shaped, and the active ingredients can be stably wrapped and not layered; then, the shaped ointment is homogenized, and the pH value of the ointment is detected to be 6.0-7.0, so that the natural mosquito-repelling and itching-relieving compound ointment containing kelp and cold-pressed coconut oil is obtained.

[0018] The present application, firstly, constructs a stable fat-soluble combination system by a natural modifier (phytosterol) and cold-pressed coconut oil, and forms a semi-solid matrix network by means of natural beeswax, which can not only optimize the bearing environment of the kelp extract in the matrix, reduce the layering of active ingredients due to density difference, improve the dispersion uniformity and retention stability of the active ingredients in the oil matrix, but also form a synergistic system with the natural synergist (pachouli extract) and the kelp extract, construct a component protection structure with vitamin E, and drive the diffusion of active ingredients with menthol, which not only strengthens the mosquito-repelling and itching-relieving effect and long-acting property of the compound ointment, but also effectively improves the stable bearing capacity of the unit ointment to the active ingredients, improves the efficacy fluctuation problem caused by uneven dispersion of components, and improves the overall use experience.

[0019] Further, the extraction of the kelp extract comprises the following steps:

[0020] S1.1, dry kelp whole plant is taken, impurities are removed, and then is crushed to 80-100 mesh and placed in an extraction tank, 8-10 times of purified water of the mass of the kelp powder is added, 0.5-1% of natural pectinase of the mass of the kelp powder is added, and then is stirred and treated at 40-45 DEG C for 2-3 h, the pectin substances in the cell wall of the kelp are decomposed by the pectinase, the cell wall structure is destroyed, then the temperature is raised to 85-90 DEG C for 15-20 min to inactivate the pectinase to avoid interference with the subsequent extraction process;

[0021] S1.2, then, 6-8 times of 70-75% ethanol solution of the mass of the kelp powder is added, the pH of the system is adjusted to 5.0-5.5, and then is extracted at 60-65 DEG C under the conditions of constant temperature and 0.1-0.12 MPa micro-pressure for 2-2.5 h, during which the system is stirred every 25-30 min for 10-15 min, the ethanol solution is improved to improve the dissolution efficiency of the active ingredients in the micro-pressure environment, and the pH and temperature are controlled to reduce the degradation loss of flavonoids and saponins in the extraction process;

[0022] S1.3, after extraction, filter the extraction liquid while hot, collect the primary filtrate, repeat the above ethanol extraction step once on the residue, combine the two filtrates, and place the combined filtrate in a rotary evaporator, concentrate to 1 / 5-1 / 4 of the original volume under the conditions of 50-55℃ and -0.08 to -0.09 MPa vacuum, obtain the concentrated liquid of gold-threaded moss, ensure the full recovery of active ingredients through secondary extraction, and avoid the destruction of active ingredients by high temperature through low-temperature vacuum concentration;

[0023] S1.4, add 1-1.5 times the volume of ethyl acetate to the concentrated liquid of gold-threaded moss, stir and extract at 25-30℃ for 20-25 min, collect the upper organic phase after standing and separating, repeat the extraction 2-3 times, combine the organic phases, add anhydrous sodium sulfate to the combined organic phase for drying until the anhydrous sodium sulfate no longer clumps, then filter to remove the anhydrous sodium sulfate, and vacuum concentrate the filtered organic phase again to remove solvent residues, obtain a viscous gold-threaded moss extract, enrich flavonoids and saponins through directional extraction with ethyl acetate, improve the purity of target active ingredients in the extract, and ensure that the extract is free of water residues through anhydrous sodium sulfate drying to avoid phase separation when mixed with cold-pressed coconut oil later.

[0024] Further, in S2, the segmented addition of natural beeswax is divided into 3-4 times, and after each addition, stirring is performed for 5-6 min to allow the beeswax to gradually melt and interact with the fatty acid glycerol esters and polar components of the gold-threaded moss extract in the system, and a semi-solid matrix network is initially formed.

[0025] Further, in S4, the complex maturation method includes the following steps:

[0026] Transfer the complex system to a constant-temperature maturation tank, increase the temperature in the tank to 35-38℃ at a rate of 1℃ / min to avoid local shrinkage of the matrix network formed by the cold-pressed coconut oil and natural beeswax due to sudden temperature rise, and at the same time, start the stirring device to pre-stir at an initial speed of 80-100 r / min for 5-8 min to ensure uniformity of the surface and internal temperature of the system;

[0027] Next, increase the stirring speed to 300-400 r / min and maintain a constant temperature of 35-38℃ for 20-24 min, during which the ester components in the natural beeswax further crosslink with the fatty acid glycerol esters of the cold-pressed coconut oil, causing the semi-solid matrix network to transition from initial formation to densification, and the phytosterols more fully fuse with the cold-pressed coconut oil in a stable temperature environment, enabling the gold-threaded moss extract and patchouli extract to penetrate deeper into the system, avoiding the accumulation of active ingredients on the surface.

[0028] Finally, the stirring speed is reduced to 120-150 r / min, and constant temperature stirring at 35-38 DEG C is continued for 10-12 min, at this time, the weak hydrogen bond combination system of vitamin E fully acts in the low-speed stable environment, and forms a closer molecular association with the flavonoid components of the extract of gold thread and the fatty acid glyceride of cold-pressed coconut oil, reduces the oxidative loss of active ingredients due to stirring impact, and at the same time, the menthol gradually diffuses to each region of the system with the help of the mild force of low-speed stirring, and drives the active ingredients to form a global uniform distribution.

[0029] Further, in the S5, the homogenization treatment includes the following steps:

[0030] First, the shaped ointment is placed in a double screw homogenizer with a temperature controllable interlayer, the interlayer circulating water temperature is 22-24 DEG C, so that the ointment is maintained in a stable state close to the shaping temperature, avoiding the destruction of the matrix network structure due to temperature fluctuation;

[0031] Then start the double screw homogenizer, first at a speed of 800 r / min for 4-6 min of pre-shearing, and initially disperse the invisible small aggregate particles;

[0032] Then gradually increase the speed to 1200 r / min, and at the same time, start the pulse shear function of the homogenizer, pause for 10 s every 2 min of continuous shearing, so that the ointment forms an alternating extrusion and relaxation state in the screw cavity through the pulse force, and promotes the further diffusion of active ingredients (such as gold thread extract and patchouli extract) in the matrix;

[0033] Finally, the speed is 600 r / min for 3 min of finishing shearing, so that the ointment texture is restored to be fine and uniform, forming a temperature constant-gradient shear-pulse dispersion composite homogenization system, which not only avoids the destruction of active ingredients by high temperature, but also realizes the deep dispersion of active ingredients through differential shear force, so that the uniformity of active ingredient content in the ointment is improved.

[0034] Compared with the prior art, the beneficial effects of the present application are:

[0035] 1. In the natural mosquito-repelling and itching-relieving compound ointment containing gold thread and cold-pressed coconut oil, a stable fat-soluble combination system is constructed by a natural modifier and cold-pressed coconut oil, and a semi-solid matrix network is formed by natural beeswax, which can optimize the bearing environment of the gold thread extract in the matrix, reduce the stratification of active ingredients due to density difference, improve the dispersion uniformity and retention stability of active ingredients in the oil matrix, and improve the stable bearing capacity of active ingredients per ointment, solve the problem of uneven dispersion of active ingredients and insufficient bearing capacity per ointment, so that the ointment can more stably play the role of mosquito-repelling and itching-relieving.

[0036] 2、The natural mosquito repellent and itching relieving compound ointment containing Lygodium japonicum and cold-pressed coconut oil forms a synergistic system with natural synergists and Lygodium japonicum extract, strengthens the functional complementary effect between active ingredients, and reduces the oxidation loss of active ingredients by constructing a component protection structure with vitamin E. The combination of menthol drives active ingredients, further spreads and provides cooling and soothing effects, not only enhances the long-acting and comfortable use of the mosquito repellent and itching relieving compound ointment, but also optimizes the stability and application value of the whole preparation through the synergistic effect of multiple components, thereby improving the comprehensive application performance of the natural mosquito repellent and itching relieving compound ointment. BRIEF DESCRIPTION OF DRAWINGS

[0037] Figure 1 A flowchart for preparing the natural mosquito repellent and itching relieving compound ointment containing Lygodium japonicum and cold-pressed coconut oil of the present application;

[0038] Figure 2 A line graph of the duration of the mosquito repellent rate of the present application being greater than or equal to 80%;

[0039] Figure 3 A line graph of the time for the scratching frequency to return to the initial level of the present application;

[0040] Figure 4 A line graph of the average irritation score of the present application;

[0041] Figure 5 A line graph of the spreadability score of the present application;

[0042] Figure 6 A line graph of the skin feel score of the present application;

[0043] Figure 7 A line graph of the odor score of the present application;

[0044] Figure 8 A line graph of the average itching relieving time of the present application. DETAILED DESCRIPTION

[0045] The technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the drawings in the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0046] Example 1

[0047] Take sea gold sand extract 8 parts, cold pressed coconut oil 30 parts, natural beeswax 6 parts, phytosterol 2 parts, broadleaf perilla extract 3 parts, menthol 2 parts, vitamin E 1.4 parts; first, the sea gold sand extract and broadleaf perilla extract are placed in a first sterile stirring container, 10 parts of cold pressed coconut oil is added, and stirring is carried out at a constant temperature of 35°C and a rotating speed of 500 r / min for 15 min to form an active ingredient-oil dispersion system; at the same time, phytosterol and 20 parts of cold pressed coconut oil are placed in a second sterile stirring container, stirring is carried out at a constant temperature of 45°C and a rotating speed of 800 r / min for 10 min to form a modified matrix system; then, the active ingredient-oil dispersion system is added to the modified matrix system, and continuous stirring is carried out at a constant temperature of 40°C and a rotating speed of 700 r / min for 24 min, during which natural beeswax is added in three times, and stirring is carried out for 5 min after each addition to obtain a matrix intermediate; then, menthol and vitamin E are added to the matrix intermediate, and continuous stirring is carried out at a constant temperature of 38°C and a rotating speed of 600 r / min for 18 min to obtain a composite matrix system; the composite matrix system is transferred to a constant temperature maturation tank, the temperature is raised to 35°C at a rate of 1°C / min, pre-stirring is carried out at an initial rotating speed of 80 r / min for 5 min, then stirring is carried out at a rotating speed of 300 r / min for 20 min, and finally stirring is carried out at a rotating speed of 120 r / min for 10 min to obtain a ointment pre-product; the ointment pre-product is cooled to 20°C, and is placed in a double-screw homogenizer with a circulating water temperature of 22°C, pre-shearing is carried out at a rotating speed of 800 r / min for 4 min, then the rotating speed is raised to 1200 r / min to open the pulse type shearing (pause for 10 s every 2 min of shearing), and finally, finishing shearing is carried out at a rotating speed of 600 r / min for 3 min, and the pH value is detected to be 6.0, and the target ointment is obtained.

[0048] Example 2

[0049] Take 11 parts of the extract of Sargassum, 35 parts of cold-pressed coconut oil, 8 parts of natural beeswax, 3 parts of phytosterol, 4.5 parts of the extract of Pogostemonis Herba, 2.5 parts of menthol, and 1 part of vitamin E. First, place the extract of Sargassum and the extract of Pogostemonis Herba in a first sterile stirring container, add 11.7 parts of cold-pressed coconut oil, and stir at a constant temperature of 38℃ and a speed of 550 r / min for 18 min to form an active ingredient-oil dispersion system. At the same time, place phytosterol and 23.3 parts of cold-pressed coconut oil in a second sterile stirring container, stir at a constant temperature of 48℃ and a speed of 850 r / min for 11 min to form a modified matrix system. Then, add the active ingredient-oil dispersion system to the modified matrix system, continuously stir at a constant temperature of 42℃ and a speed of 750 r / min for 27 min, and add natural beeswax four times during the stirring, with 5.5 min of stirring after each addition, to obtain a matrix intermediate. Add menthol and vitamin E to the matrix intermediate, continuously stir at a constant temperature of 40℃ and a speed of 650 r / min for 20 min to obtain a composite matrix system. Transfer the composite matrix system to a constant-temperature maturation tank, increase the temperature to 36℃ at a rate of 1℃ / min, pre-stir at an initial speed of 90 r / min for 6 min, then stir at a speed of 350 r / min for 22 min, and finally stir at a speed of 135 r / min for 11 min to obtain a ointment pre-product. Cool the ointment pre-product to 22℃, seal and stand for 28 min, then place it in a double-screw homogenizer with a circulating water temperature of 23℃. First, pre-shear at a speed of 800 r / min for 5 min, then increase the speed to 1200 r / min and open the pulse-type shearing (pause for 10 s every 2 min of shearing), finally finish the shearing at a speed of 600 r / min for 3 min. The pH value is 6.5, and the target ointment is obtained.

[0050] Example 3

[0051] Take sea gold sand extract 9 parts, cold-pressed coconut oil 38 parts, natural beeswax 9 parts, phytosterol 3.5 parts, patchouli extract 4 parts, menthol 3 parts, vitamin E 1.8 parts; first, place the sea gold sand extract and patchouli extract in a first sterile stirring container, add 12.7 parts of cold-pressed coconut oil, and stir at a constant temperature of 39°C and a rotation speed of 580 r / min for 19 min to form an active ingredient-fat dispersion system; at the same time, place the phytosterol and 25.3 parts of cold-pressed coconut oil in a second sterile stirring container, stir at a constant temperature of 49°C and a rotation speed of 880 r / min for 11.5 min to form a modified matrix system; then, add the active ingredient-fat dispersion system to the modified matrix system, continuously stir at a constant temperature of 44°C and a rotation speed of 780 r / min for 29 min, and add the natural beeswax four times during the stirring, with 5.8 min of stirring after each addition, to obtain a matrix intermediate; further add the menthol and vitamin E to the matrix intermediate, continuously stir at a constant temperature of 41°C and a rotation speed of 680 r / min for 21 min to obtain a composite matrix system; transfer the composite matrix system to a constant-temperature maturation tank, increase the temperature to 37°C at a rate of 1°C / min, pre-stir at an initial rotation speed of 95 r / min for 7 min, then stir at 380 r / min for 23 min, and finally stir at 145 r / min for 11.5 min to obtain a ointment pre-product; cool the ointment pre-product to 24°C, seal and stand for 29 min, and then place it in a double-screw homogenizer with a circulating water temperature of 23.5°C, pre-shear at 800 r / min for 5.5 min, then increase the rotation speed to 1200 r / min to open the pulse-type shearing (pause for 10 s every 2 min of shearing), and finally finish the shearing at 600 r / min for 3 min, and the pH value is 6.8, thus obtaining the target ointment.

[0052] Example 4

[0053] Take 12 parts of sea golden sand extract, 40 parts of cold-pressed coconut oil, 10 parts of natural beeswax, 4 parts of phytosterol, 5 parts of patchouli extract, 2.8 parts of menthol, and 2 parts of vitamin E. First, place the sea golden sand extract and the patchouli extract in a first sterile stirring container, add 13.3 parts of cold-pressed coconut oil, and stir at a constant temperature of 40℃ and a speed of 600r / min for 20 min to form an active ingredient-oil dispersion system. At the same time, place the phytosterol and 26.7 parts of cold-pressed coconut oil in a second sterile stirring container, stir at a constant temperature of 50℃ and a speed of 900r / min for 12 min to form a modified matrix system. Then, add the active ingredient-oil dispersion system to the modified matrix system, continuously stir at a constant temperature of 45℃ and a speed of 800r / min for 30 min, and add the natural beeswax in four portions, stirring for 6 min after each addition to obtain a matrix intermediate. Add the menthol and vitamin E to the matrix intermediate, continuously stir at a constant temperature of 42℃ and a speed of 700r / min for 22 min to obtain a composite matrix system. Transfer the composite matrix system to a constant-temperature maturation tank, increase the temperature to 38℃ at a rate of 1℃ / min, pre-stir at an initial speed of 100r / min for 8 min, then stir at a speed of 400r / min for 24 min, and finally stir at a speed of 150r / min for 12 min to obtain a ointment pre-product. Cool the ointment pre-product to 25℃, seal and stand for 30 min, then place it in a double-screw homogenizer with a circulating water temperature of 24℃, pre-shear at a speed of 800r / min for 6 min, then increase the speed to 1200r / min and open the pulse-type shearing (pause for 10 s every 2 min of shearing), and finally finish shearing at a speed of 600r / min for 3 min. The pH value is 7.0, and the target ointment is obtained.

[0054] Table 1: Dosage of each raw material in Examples 1-4

[0055]

[0056] In order to verify that the natural mosquito-repelling and itching-relieving compound ointment prepared in the examples of the present application has good active ingredient carrying stability and mosquito-repelling and itching-relieving efficacy persistence, the following test example is used to illustrate the natural mosquito-repelling and itching-relieving compound ointment provided in the examples of the present application.

[0057] Test Example

[0058] The purpose of this test group is to explore the influence of different ingredient proportions on the natural mosquito-repelling and itching-relieving compound ointment, and to detect the active ingredient carrying stability, mosquito-repelling and itching-relieving efficacy persistence, skin irritation, and comprehensive application performance of the natural mosquito-repelling and itching-relieving compound ointment of the present application.

[0059] Test objectives: Test group A, test group B, test group C and test group D respectively use the component proportion of natural mosquito repellent and itching compound ointment provided in examples 1-4; control examples use control group A, control group B, control group C, control group D, control group E, control group F, control group G and control group H, wherein:

[0060] Control group A

[0061] Take 8 parts of sea golden sand extract, 35 parts of cold-pressed coconut oil, 10 parts of vaseline, 2 parts of menthol and 1 part of vitamin E; mix the sea golden sand extract, menthol and vitamin E with the cold-pressed coconut oil and vaseline, stir at a constant temperature of 50°C at a speed of 500 r / min for 20 min, continuously stir during the period until the system becomes a uniform paste, then naturally cool to 25°C, stand for 30 min, and then stir at a speed of 800 r / min for 5 min. The pH value is 6.5, and the ointment is obtained.

[0062] Control group B

[0063] Take 10 parts of sea golden sand extract, 40 parts of cold-pressed coconut oil, 8 parts of lanolin, 2 parts of Tween 80 and 3 parts of menthol; first mix the sea golden sand extract and Tween 80 uniformly, add 20 parts of cold-pressed coconut oil, stir at a constant temperature of 45°C for 15 min, then add the remaining 20 parts of cold-pressed coconut oil, lanolin and menthol, continue to stir at a speed of 600 r / min for 25 min, cool to 22°C, stand for 25 min, and then homogenize at a speed of 1000 r / min for 5 min. The pH value is 6.8, and the ointment is obtained.

[0064] Control group C

[0065] Take 8 parts of sea golden sand extract, 30 parts of cold-pressed coconut oil, 6 parts of natural beeswax, 2 parts of glycerol, 3 parts of agastache extract, 2 parts of menthol and 1 part of vitamin E; the preparation steps are the same as in example 1, except that the phytosterol is replaced by glycerol, and the remaining operation parameters remain the same. The final pH value is 6.0, and the ointment is obtained.

[0066] Control group D

[0067] Take 8 parts of sea golden sand extract, 30 parts of cold-pressed coconut oil, 6 parts of natural beeswax, 2 parts of phytosterol, 2 parts of menthol and 1 part of vitamin E; the preparation steps are the same as in example 1, except that the agastache extract is removed, and the remaining operation parameters remain the same. The final pH value is 6.0, and the ointment is obtained.

[0068] Control group E

[0069] Take 8 parts of sea gold sand extract, 30 parts of cold-pressed coconut oil, 2 parts of phytosterol, 3 parts of patchouli extract, 2 parts of menthol, and 1 part of vitamin E; prepare according to the steps of Example 1, except that the natural beeswax is removed, and the rest of the operation parameters remain the same. The final pH value is 6.0, and the ointment is obtained.

[0070] Control group F

[0071] Take 8 parts of sea gold sand extract, 30 parts of cold-pressed coconut oil, 2 parts of phytosterol, 3 parts of patchouli extract, 2 parts of menthol, and 1 part of vitamin E; prepare according to the steps of Example 1, except that the natural beeswax is removed, and the rest of the operation parameters remain the same. The final pH value is 6.0, and the ointment is obtained.

[0072] Control group G

[0073] Take 8 parts of sea gold sand extract, 30 parts of cold-pressed coconut oil, 2 parts of phytosterol, 3 parts of patchouli extract, 2 parts of menthol, and 1 part of vitamin E; prepare according to the steps of Example 1, except that the natural beeswax is removed, and the rest of the operation parameters remain the same. The final pH value is 6.0, and the ointment is obtained.

[0074] Control group H

[0075] Take 8 parts of sea gold sand extract, 30 parts of cold-pressed coconut oil, 2 parts of phytosterol, 3 parts of patchouli extract, 2 parts of menthol, and 1 part of vitamin E; prepare according to the steps of Example 1, except that the natural beeswax is removed, and the rest of the operation parameters remain the same. The final pH value is 6.0, and the ointment is obtained.

[0076] Test method: According to the active ingredient carrying stability, mosquito repellent and itching relief efficacy persistence, skin irritation, and comprehensive application performance of the natural mosquito repellent and itching relief compound ointment of the application, tests are carried out respectively, and the specific test method is as follows:

[0077] Active ingredient carrying stability: Take 10 g of ointment samples from each test group and control group, respectively, and place them in 50 mL centrifuge tubes with stoppers. Place them in a constant temperature environment at 30°C for 30 days, and take samples every 5 days during this period. Each time the sample is taken, the ointment is evenly divided into upper, middle, and lower layers along the axis of the centrifuge tube, and 0.5 g of sample is taken from each layer. The content of sea gold sand extract flavonoid active ingredient in each layer is determined by high performance liquid chromatography (HPLC). The relative deviation of the content of each layer from the average content is calculated, and the formula is: relative deviation (%) = |single layer content-average content| / average content x 100%. At the same time, centrifuge all samples at a speed of 3000 r / min for 20 min, and observe whether there is stratification or precipitation after centrifugation. The relative deviation is ≤5% and there is no stratification and precipitation, which is considered to be active ingredient carrying stability.

[0078] Table 2 Active ingredient carrying stability detection index

[0079]

[0080] According to Table 2, the relative deviations of the flavonoid components of the upper, middle and lower three layers of the extract of Golden Thread in the four test groups after standing for 30 days are all within 1.5%-2.3%, and there is no stratification and no precipitation after centrifugation, and the stability of the active ingredient carrier is determined to be stable; while in the control group, the groups using traditional matrix (vaseline, lanolin) or lacking key components (phytosterols, natural beeswax) or changing the curing temperature all have relative deviations exceeding 5% (such as 8.5% in the upper layer and 9.1% in the lower layer of control group A), stratification and precipitation after centrifugation, etc., and only control group D lacking extract of Agastache rugosa reaches basic stability; this shows that the present application can effectively solve the problems of uneven distribution and unstable loading of active ingredients by constructing a fat-soluble binding system with phytosterols and cold-pressed coconut oil, forming a semi-solid matrix network with natural beeswax, and using a specific composite curing process, while the traditional matrix or the lack of key components makes it difficult to achieve stable loading of active ingredients, especially, control group G (lacking cold-pressed coconut oil) loses the ability to load active ingredients due to the lack of oil matrix, and cannot be effectively measured, which proves that cold-pressed coconut oil as a basic oil and solvent is indispensable; while the matrix of control group H (lacking extract of Golden Thread) itself shows good physical stability, but the relative deviation index of flavonoid components is not applicable due to the lack of target active ingredients, and its stability is only the physical property of the matrix, and this result together with control group G proves that the present application can effectively form a stable system of active ingredients and delivery matrix by the cooperation of Golden Thread extract and cold-pressed coconut oil, and at the same time, it is beneficial to maintain uniform distribution and continuous efficient release of mosquito-repelling and itching-relieving active ingredients during storage and use.

[0081] Mosquito repellent and itching relief efficacy persistence: 65 healthy female mice were selected and randomly divided into 13 groups (corresponding to 4 test groups, 8 control groups and 1 blank control group), 5 mice in each group; the mice were depilated on the back (depilation area 2 cm x 2 cm), and after 24 h, 0.2 g of the corresponding ointment was applied to the depilation area of the mice in the remaining groups except the blank control group; after application, the mice were placed in a closed mosquito cage (30 cm x 30 cm x 30 cm) containing 50 adult female Culex pipiens pallens for 10 min each time at 1 h, 3 h, 6 h, 9 h and 12 h; the number of bites of each group of mice at each time point was recorded, the mosquito repellent rate was calculated, and the formula was: mosquito repellent rate (%) = (blank control group bite times - sample group bite times) / blank control group bite times x 100%; at the same time, before applying the ointment, itching was induced on the depilation area of the mice with 0.5% histamine solution, and the scratching frequency of each group of mice within 10 min after applying the ointment was recorded, and then every 3 h, until the scratching frequency returned to the initial level after itching, to evaluate the persistence of efficacy, the duration of mosquito repellent rate ≥80% and the time for the scratching frequency to return to the initial level were evaluated;

[0082] Table 3 Mosquito repellent and itching relief efficacy persistence detection index

[0083]

[0084] According to Figures 2-3 As shown in Table 3, the mosquito repellent rate of the test group ointment was ≥80% for 9.5-10.5 h, and the time for the scratching frequency to return to the initial level was only 5.5-6.2 h; in contrast, the mosquito repellent effective duration of the control groups was less than 7 h (e.g. 4.2 h for control group A), and the itching relief recovery time was as long as 8.3-10.5 h. This difference shows that the synergistic system formed by the patchouli extract and the sea golden sand extract in the present application, combined with the protection of vitamin E for active ingredients and the diffusion driving effect of menthol, not only significantly prolongs the effective duration of mosquito repellent efficacy, but also speeds up the onset speed of itching relief effect, and the lack of synergistic components, the use of traditional process or matrix makes it difficult to improve the efficacy persistence; the results of control groups G and H are the most significant: the lack of cold-pressed coconut oil as a matrix and carrier makes the active ingredients unable to be effectively released and permeated, resulting in the loss of mosquito repellent and itching relief efficacy; and control group H, which lacks the core active substance sea golden sand extract, has only weak mosquito repellent effect due to patchouli and menthol, and the itching relief time is significantly longer than all test groups (> 12 min), which proves the core position of sea golden sand extract as a core efficacy component in the present application and the importance of its synergistic effect with the complete matrix system.

[0085] Skin irritation: Following the skin irritation test method in the "Cosmetic Safety Technical Specifications," 72 healthy New Zealand white rabbits were randomly divided into 12 groups of 6 rabbits each. 24 hours before the test, hair was removed from both sides of the spine on the back of each rabbit (3cm × 3cm area on each side). 0.5g of the ointment was applied evenly to the test area of ​​each rabbit in both the experimental and control groups. The area was covered and secured with sterile gauze, and left in contact for 4 hours. The ointment was then removed and the skin cleaned. Erythema and edema were observed in the test area at 1 hour, 24 hours, 48 ​​hours, and 72 hours after ointment removal. The scoring criteria were as follows (erythema: 0 points for no erythema, 1 point for mild erythema). Moderate erythema was scored as 2 points, severe erythema as 3 points; edema: no edema as 0 points, mild edema as 1 point, moderate edema as 2 points, severe edema as 3 points. The test area of ​​each rabbit was scored, and the average stimulus score for each group was calculated using the formula: Average stimulus score = (sum of erythema and edema scores for all animals at each time point) / (number of observations × number of animals); an average stimulus score < 0.5 was considered non-irritating, 0.5-2.0 was considered mildly irritating, and > 2.0 was considered moderate or more irritating.

[0086] Table 4. Indicators for Skin Irritation Detection

[0087]

[0088] according to Figure 4 As shown in Table 4, the average irritation score of all experimental ointments was only 0.1-0.2, and they were all judged to be non-irritating. In the control groups, the average irritation scores of control groups A and B, which used traditional bases such as petrolatum or lanolin, reached 0.8-0.9, and they were judged to be slightly irritating. Although the other control groups that lacked a single ingredient or had modified processes were also non-irritating, the irritation scores of the experimental groups were even lower. This shows that the all-natural raw materials selected in this invention, combined with a mild preparation process (such as low-temperature curing and gradient homogenization), can minimize the irritation of the ointment to the skin. Traditional synthetic bases or non-optimized processes are prone to increasing the risk of skin irritation, which further increases the safety of the use of this invention. Furthermore, control group G (without cold-pressed coconut oil) showed moderate irritation, which proves the importance of cold-pressed coconut oil as the main mild carrier, emollient and stabilizer in the formulation. Its absence will lead to an imbalance in the proportion of beeswax and phytosterol components, directly causing skin irritation. Control group H (without Lygodium japonicum) remained non-irritating, indicating that the Lygodium japonicum extract itself is mild and the introduction of its efficacy did not bring additional safety risks.

[0089] Comprehensive application performance: 120 healthy volunteers (age 18-60 years old, half male and half female) were selected and randomly divided into 12 groups (4 test groups and 8 control groups), 10 people in each group; the volunteers applied 1 g of the corresponding ointment on the exposed arm outside (area 5 cm x 5 cm) during the active period of mosquitoes (18:00-21:00) for 7 consecutive days; after use every day, the volunteers scored the spreadability (whether easy to push away, no particle feeling), skin feel (whether greasy, refreshing), odor (whether easy to accept, no odor) of the ointment according to the score table (1-5 points, 1 point being the worst, 5 points being the best); at the same time, the number of times of being bitten by mosquitoes during use and the itching time (from application to obvious relief of itching) after being bitten were recorded; after the test, the average value of each score and the average value of the itching time were calculated, and the spreadability, skin feel, and odor scores were all ≥4 points and the itching time was ≤5 min were considered as excellent comprehensive application performance.

[0090] Table 5 Comprehensive application performance detection index

[0091]

[0092] According to Figures 5-8 As shown in Table 5, the four test groups had scores of 4.3-4.8 in the three sensory evaluations of spreadability, skin feel, and odor, and the average itching time was only 2.5-3.2 min, and the comprehensive application performance was all determined to be excellent; among the control groups, the three sensory scores of control groups A and B (traditional matrix) and control group E (missing beeswax) were all less than 4 points, and the itching time was more than 5.8 min, only control groups C (phytosterol instead of glycerol), D (missing pachouli), and F (changing the maturation temperature) reached the good level; this shows that the application greatly improves the use experience of the ointment by adjusting the consistency of the ointment with natural beeswax, optimizing the texture of the matrix with phytosterol, combining the cooling skin feel of menthol with the natural odor of pachouli extract, and at the same time, ensuring rapid itching relief with the efficient dispersion of active ingredients; while the traditional matrix or the lack of key ingredients and improper process have obvious shortcomings in sensory experience and itching efficiency; as seen from control groups G and H: control group G has a destroyed ointment structure due to the lack of cold-pressed coconut oil, and the spreadability and skin feel are very poor, which cannot be used normally, and the comprehensive performance is determined to be very poor; control group H maintains good spreadability and skin feel, but due to the lack of core itching component kelp extract, the average itching time is more than 10 min, and the efficacy is seriously insufficient, so the comprehensive performance is determined to be poor; it can be seen that the cold-pressed coconut oil and kelp extract are the core of the synergistic effect of the application, which together form a matrix stable- efficacy synergistic system.

[0093] In summary, the application can effectively solve the problems of limited active ingredient load, uneven distribution and unstable efficacy in natural mosquito-repelling and itching-relieving compound ointment. The plant sterol modified cold-pressed coconut oil is used to construct a fat-soluble system, and natural beeswax is used to form a semi-solid matrix network. The synergistic effect of patchouli extract and sea golden sand extract is combined, and the protection of vitamin E and the diffusion effect of menthol are added. Then, the compound is processed by compound curing and gradient homogenization process. The ointment not only has stable active ingredient load, long-lasting mosquito-repelling and itching-relieving effect (effective time is more than 9.5 hours), but also has the advantages of no skin irritation and excellent use experience. Compared with the traditional matrix or the scheme lacking key ingredients, the stability, efficacy and safety are significantly improved.

[0094] The basic principles, main features and advantages of the present application are shown and described above. Those skilled in the art should understand that the present application is not limited by the above examples, and the above examples and descriptions in the specification are only preferred examples of the present application and are not intended to limit the present application. Without departing from the spirit and scope of the present application, various changes and improvements can be made to the present application, and these changes and improvements all fall within the scope of the claimed present application. The scope of protection of the present application is defined by the appended claims and their equivalents.

Claims

1. A natural mosquito repellent and anti-itching compound ointment containing spikemoss and cold-pressed coconut oil, characterized in that, The natural mosquito repellent and itching relieving compound ointment containing sea gold sand and cold-pressed coconut oil comprises sea gold sand extract, cold-pressed coconut oil, natural beeswax, natural modifier, natural synergist, menthol and vitamin E. The preparation steps further comprise: S1, the sea gold sand extract and the natural synergist are placed in a first sterile stirring container, and after one-third of the cold-pressed coconut oil is added and mixed, a preliminary active ingredient-fat dispersion system is formed, at the same time, the natural modifier and the remaining two-thirds of the cold-pressed coconut oil are placed in a second sterile stirring container and stirred to form a stable fat-soluble modified matrix system; S2, the active ingredient-fat dispersion system is added to the modified matrix system and stirred, during which the natural beeswax is added in stages to obtain a matrix intermediate in which the active ingredient is preliminarily wrapped; S3, the menthol and vitamin E are added to the matrix intermediate and stirred to obtain a composite matrix system; S4, the composite matrix system is treated by a low-temperature and low-speed stirring compound curing method to obtain a medicinal ointment pre-product with a compact structure, uniformly dispersed components and stable active ingredient support; S5, after the medicinal ointment pre-product is placed and shaped, it is subjected to homogenization treatment; the medicinal ointment pH value is detected to be 6.0-7.0, and the natural mosquito repellent and itching relieving compound ointment containing sea gold sand and cold-pressed coconut oil is obtained; The natural modifier is phytosterol, and the natural synergist is patchouli extract; The amount of the sea gold sand extract is 8-12 parts; the amount of the cold-pressed coconut oil is 30-40 parts; the amount of the natural beeswax is 6-10 parts; the amount of the natural modifier is 2-4 parts; the amount of the natural synergist is 3-5 parts; the amount of the menthol is 2-3 parts; and the amount of the vitamin E is 1-2 parts; In S4, the compound curing method comprises the following steps: The composite matrix system is transferred to a constant-temperature curing tank, the temperature in the tank is increased to 35-38℃ at a rate of 1℃ / min, at the same time, the stirring device is started to pre-stir at an initial stirring speed of 80-100r / min for 5-8min to make the temperature of the system surface and the internal temperature uniform and consistent; Then, the stirring speed is increased to 300-400r / min, and the constant temperature of 35-38℃ is maintained for 20-24min of continuous stirring; Finally, the stirring speed is reduced to 120-150r / min, and the constant temperature of 35-38℃ is maintained for 10-12min of continuous stirring.

2. The natural mosquito repellent and anti-itching compound ointment containing Adiantium capillus-veneris and cold-pressed coconut oil according to claim 1, characterized in that, The extraction of the sea gold sand extract comprises the following steps: S1.1, the dried sea gold sand whole plant is removed from impurities, crushed to 80-100 mesh, and then placed in an extraction tank, 8-10 times the mass of pure water is added, and 0.5-1% of natural pectinase of the mass of the powder is added, and after stirring at a constant temperature of 40-45℃ for 2-3h, the temperature is increased to 85-90℃ for 15-20min to inactivate the pectinase; S1.2, then, 6-8 times the mass of 70-75% ethanol solution of the sea gold sand powder is added, the pH of the system is adjusted to 5.0-5.5, and the constant temperature extraction is carried out at a constant temperature of 60-65℃ and a micro-pressure of 0.1-0.12MPa for 2-2.5h, during which the system is stirred every 25-30min for 10-15min each time; S1.3, after extraction, filter the extraction liquid while hot, collect the primary filtrate, repeat the above ethanol extraction step once on the residue, combine the two filtrates, and concentrate the combined filtrate to 1 / 5-1 / 4 of the original volume under vacuum at 50-55°C and -0.08 to -0.09 MPa to obtain a concentrated liquid of Lyginia; S1.4, add 1-1.5 times the volume of ethyl acetate to the concentrated liquid of Lyginia, stir and extract at 25-30°C for 20-25 min, collect the upper organic phase after the liquid is separated, repeat the extraction 2-3 times, combine, dry with anhydrous sodium sulfate until it does not clump, filter, and vacuum concentrate the organic phase until no solvent remains to obtain a viscous Lyginia extract.

3. The natural mosquito repellent and anti-itching compound ointment containing Adiantium capillus-veneris and cold-pressed coconut oil according to claim 1, characterized in that, In the S1, the first sterile stirring container is stirred at 500-600 r / min for 15-20 min under constant temperature conditions of 35-40°C; the second sterile stirring container is stirred at 800-900 r / min for 10-12 min under constant temperature conditions of 45-50°C.

4. The natural mosquito repellent and anti-itching compound ointment containing Adiantium capillus-veneris and cold-pressed coconut oil according to claim 1, characterized in that, In the S2, the natural beeswax is added in 3-4 stages, and each time the beeswax is added and stirred for 5-6 min to gradually melt and interact with the fatty acid glycerol esters and polar components of the Lyginia extract in the system, and a semi-solid matrix network is initially formed.

5. The natural mosquito repellent and anti-itching compound ointment containing Adiantium and cold-pressed coconut oil according to claim 1, characterized in that, In the S2, the active ingredient-oil dispersion system and the modified matrix system are stirred at 700-800 r / min for 24-30 min under constant temperature conditions of 40-45°C; in the S3, the menthol and vitamin E are continuously stirred at 600-700 r / min for 18-22 min under constant temperature conditions of 38-42°C.

6. The natural mosquito repellent and anti-itching compound ointment containing Adiantium capillus-veneris and cold-pressed coconut oil according to claim 1, characterized in that, In the S5, before the ointment pre-product is placed, the temperature is reduced to 20-25°C, and then it is placed in a closed environment for 25-30 min.

7. The natural mosquito repellent and anti-itching compound ointment containing Adiantium and cold-pressed coconut oil according to claim 1, characterized in that, In the S5, the homogenization process includes the following steps: After shaping, the ointment is placed in a double-screw homogenizer with a temperature-controllable interlayer, and the circulating water temperature of the interlayer is 22-24°C; Then the double-screw homogenizer is started, and pre-shearing is performed at 800 r / min for 4-6 min to initially disperse the microscopic aggregated particles that are not visible to the naked eye; Then the speed is gradually increased to 1200 r / min, and the pulse shear function of the homogenizer is turned on, with a 10 s pause for every 2 min of continuous shearing. Through the pulse force, the ointment forms an alternating state of extrusion and relaxation in the screw cavity, promoting the further diffusion of active ingredients in the matrix; Finally, a finishing shear is performed at 600 r / min for 3 min to restore the texture of the ointment to be fine and uniform, forming a temperature-constant-gradient shear-pulse dispersion composite homogenization system.

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