Mosquito repellent slow-release system, preparation method and application

Abstract

The invention discloses a mosquito repellent slow-release system, a preparation method and application. The mosquito repellent slow-release system comprises deet and an adsorbent, and the adsorbent is selected from one or more of porous silica and polyester; the surface of the porous silica is modified with one or more of a hydroxyl siloxane group, a methyl siloxane group, an amino siloxane group and a methoxy amino-terminated polydimethylsiloxane / silsesquioxane copolymer; the mass ratio of the deet to the adsorbent can be (0.001 to 30): (0.001 to 30). According to the mosquito repellent sustained-release system, by optimizing the formula design and combining the sustained-release technology, the mosquito repelling time of deet can be remarkably prolonged on the basis of the conventional mosquito repellent content, and meanwhile, the irritation to skin is greatly reduced.

Description

Technical Field

[0001] This application relates to the technical field of daily chemical products, and particularly relates to a mosquito repellent sustained-release system, a preparation method and an application thereof. Background Art

[0002] Mosquitoes are an important type of medical insect. They are not only widely distributed around the world, but also have a wide variety of species and reproduce rapidly. The harm they bring to humans is not only the bites, swelling, itching caused by blood-sucking, but also the possibility of spreading a variety of diseases, including dengue fever, malaria, epidemic encephalitis B, yellow fever, Zika virus disease, etc., seriously endangering public health.

[0003] Currently, the most common indoor mosquito prevention strategies are using mosquito nets, insecticides or mosquito coils. In outdoor scenarios, which are actually the hardest hit areas for mosquito bites, mosquito prevention measures are scarce, and mainly mosquito repellents are used for protection. The mechanism of mosquito repellents is to induce the repellent behavior of mosquitoes by affecting their olfactory perception mechanism. Common mosquito repellents include: DEET (N,N-Diethyl-meta-toluamide), Picaridin, IR3535 (KBR 3023), lemon eucalyptus oil, etc. Mosquito repellent forms include mosquito repellent stickers, mosquito repellent bracelets, mosquito repellent sprays, mosquito repellent creams, etc. However, mosquito repellent stickers are easy to fall off and have a small protection range; mosquito repellent bracelets have low volatility and a small repellent range; mosquito repellent sprays cannot ensure effective and uniform coverage of the skin, most contain alcohol, which increases irritation, and there is a risk of inhalation during use. Only mosquito repellent creams can achieve uniformity and have a low inhalation risk. But most mosquito repellent creams have a low efficacy and rely on the addition of high-content mosquito repellents, which increases irritation accordingly.

[0004] Therefore, there is a need in this field to develop an effective mosquito repellent sustained-release system rather than improving the mosquito repellent efficacy by increasing the content of mosquito repellents. The advantages of the sustained-release system are as follows: 1. Reducing irritation; 2. Prolonging the mosquito repellent efficacy; 3. Improving the waterproof performance to adapt to outdoor scenarios of encountering water / sweating, thereby solving the pain points of mosquito bites for the majority of consumers and outdoor workers and improving the quality of life and work efficiency. Summary of the Invention

[0005] Based on this, it is necessary to provide a mosquito repellent sustained-release system, a preparation method and an application thereof.

[0006] In the first aspect of this application, a mosquito repellent sustained-release system is provided. The mosquito repellent sustained-release system includes DEET and an adsorbent. Among them, the adsorbent includes one or more of porous silica and polyester; the surface of the porous silica is modified with one or more of hydroxy siloxanyl, methyl siloxanyl, amino siloxanyl and methoxy amino-terminated polydimethylsiloxane / silsesquioxane copolymer; the mass ratio of DEET to the adsorbent is (0.001~30):(0.001~30).

[0007] In some embodiments, the polyester includes one or more of polyester-5, polyurethane, and polymethyl methacrylate.

[0008] In some embodiments, the porous silica is porous silica microspheres, and the average particle size of the porous silica microspheres is 0.1 μm to 100 μm.

[0009] In some embodiments, the adsorbent includes porous silica and polyester, and the mass ratio of DEET, the porous silica, and the polyester is (0.001 to 30):(0.001 to 20):(0.001 to 10).

[0010] In some embodiments, the mass ratio of DEET, the porous silica, and the polyester is (15 to 25):(0.5 to 2):(0.5 to 1).

[0011] In some embodiments, the mosquito repellent sustained-release system further includes one or more of a chelating agent, a thickening agent, an emulsifying agent, an emollient, an oil, a preservative, a soothing active ingredient, a neutralizing agent, and an aqueous solvent.

[0012] In some embodiments, the mosquito repellent sustained-release system includes a chelating agent, and the weight percentage of the chelating agent in the mosquito repellent sustained-release system is 0.001% - 0.1%.

[0013] In some embodiments, the mosquito repellent sustained-release system includes a thickening agent, and the weight percentage of the thickening agent in the mosquito repellent sustained-release system is 0.001% - 5%.

[0014] In some embodiments, the mosquito repellent sustained-release system includes an emulsifying agent, and the weight percentage of the emulsifying agent in the mosquito repellent sustained-release system is 0.001% - 10%.

[0015] In some embodiments, the mosquito repellent sustained-release system includes an emollient, and the weight percentage of the emollient in the mosquito repellent sustained-release system is 0.001% - 10%.

[0016] In some embodiments, the mosquito repellent sustained-release system includes an oil, and the weight percentage of the oil in the mosquito repellent sustained-release system is 0.01% - 10%.

[0017] In some embodiments, the mosquito repellent sustained-release system includes a preservative, and the weight percentage of the preservative in the mosquito repellent sustained-release system is 0.001% - 3%.

[0018] In some embodiments, the mosquito repellent sustained-release system includes a soothing active ingredient, and the weight percentage of the soothing active ingredient in the mosquito repellent sustained-release system is 0.001% - 20%.

[0019] In some embodiments, the mosquito repellent sustained-release system includes a neutralizing agent, and the weight percentage of the neutralizing agent in the mosquito repellent sustained-release system is 0.001% - 5%.

[0020] In some embodiments, the chelating agent includes one or more of disodium ethylenediaminetetraacetate and tetrasodium ethylenediaminetetraacetate.

[0021] In some embodiments, the thickening agent includes one or more of acrylate / steareth-20 methacrylate copolymer, acrylate / steareth-20 methacrylate copolymer, sodium polyacryloyldimethyltaurate, sodium polyacrylate, acrylate / C10-30 alkyl acrylate crosslinked polymer, sodium polyacrylate and acrylate / C10-30 alkyl acrylate crosslinked polymer.

[0022] In some embodiments, the emulsifying agent includes one or more of sucrose poly stearate, cetearyl alcohol, olive oil unsaponifiables, sodium stearoyl glutamate and potassium cetyl phosphate.

[0023] In some embodiments, the emollient includes one or more of glycerin, butylene glycol and propylene glycol.

[0024] In some embodiments, the soothing active ingredient includes one or more of purslane extract, bisabolol, ginger root extract and dipotassium glycyrrhizinate.

[0025] In some embodiments, by weight percentage, the mosquito repellent sustained-release system includes 0.001% - 30% of DEET, 0.001% - 20% of porous silica, 0.001% - 0.1% of chelating agent, 0.001% - 10% of polyester, 0.001% - 5% of thickening agent, 0.001% - 10% of emulsifying agent, 0.001% - 10% of emollient, 0.01% - 10% of oil, 0.001% - 3% of preservative, 0.001% - 20% of soothing active ingredient, 0.001% - 5% of neutralizing agent, and the balance of water.

[0026] The second aspect of the present application provides a method for preparing a mosquito repellent sustained-release system, including the following steps: stirring and mixing DEET and an adsorbent under high temperature conditions to prepare a mosquito repellent sustained-release system; wherein, the adsorbent is the adsorbent in the mosquito repellent sustained-release system described in the first aspect of the present application; the mass ratio of the DEET to the adsorbent is (0.001~30):(0.001~30); the high temperature conditions are 80°C~85°C.

[0027] The third aspect of the present application provides the use of the mosquito repellent sustained-release system described in the first aspect of the present application or the mosquito repellent sustained-release system prepared by the preparation method described in the second aspect of the present application in the preparation of mosquito repellent products; optionally, the mosquito repellent products include one or more of mosquito repellent creams, mosquito repellent sprays, and mosquito repellent liquids.

[0028] The aforementioned mosquito repellent sustained-release system does not rely on increasing the content of mosquito repellent to improve the mosquito repellent effect. By optimizing the formulation design and combining the sustained-release technology, the mosquito repellent time of DEET can be significantly extended on the basis of the conventional mosquito repellent content, while greatly reducing the irritation to the skin.

[0029] In addition, this system also has excellent waterproof and sweatproof performance, can effectively cope with various complex environments, and meet the long-term mosquito repellent needs of ordinary residents' daily protection and special fields such as the military. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the technical solutions in the embodiments and implementations of the present application and to more fully understand the present application and its beneficial effects, the following will briefly introduce the drawings required for the description of the embodiments or implementations. Obviously, the following described drawings are only some embodiments of the present application, and those skilled in the art can obtain other drawings based on these drawings without creative efforts.

[0031] Figure 1 It is a scanning electron microscope image of porous silica in an embodiment of the present application;

[0032] Figure 2 It is a comparison diagram of the states of a mosquito repellent emulsion with and without a film-forming agent on the skin in an embodiment of the present application;

[0033] Figure 3 It is the structural formula of polyester-5 in an embodiment of the present application. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0034] To facilitate the understanding of the present application, the present application will be described more comprehensively with reference to the relevant drawings. The preferred embodiments of the present application are given in the drawings. However, the present application can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure content of the present application more thorough and comprehensive.

[0035] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the technical field to which the present application belongs. The terms used in the description of the present application in this specification are only for the purpose of describing specific embodiments and are not intended to limit the present application. The term "and / or" used herein includes any and all combinations of one or more of the related listed items.

[0036] In this application, "optionally", "optional", and "option" mean that something is either present or absent, that is, any one of two alternative options, namely "present" or "absent". If the term "optional" appears multiple times in a technical solution, without special instructions, and without contradictions or mutual constraints, each "optional" is independent of the others.

[0037] In this application, "preferred", "better", "more preferable", and "should preferably" are only used to describe embodiments or examples with better effects. It should be understood that they do not constitute a limitation on the scope of protection of this application.

[0038] The terms "have", "contain", "include", and "comprise" used in this application are synonyms. They are inclusive or open-ended and do not exclude additional, unmentioned members or features. Members or features include, for example, materials or components, structures, elements, instruments, etc.; non-limiting examples of members or features also include actions, conditions under which actions occur, timing, states, etc.

[0039] In this application, in a technical feature or technical solution described in an open language, a closed technical feature or technical solution composed of the listed content is also included, as well as an open technical feature or technical solution that includes the listed content.

[0040] In this application, for units related to data ranges, if a unit is only attached to the right endpoint, it means that the units of the left endpoint and the right endpoint are the same. For example, 10~20 μL means that the units of both the left endpoint "10" and the right endpoint "20" are μL, which has the same meaning as 10 μL~20 μL. In addition, the above understanding method also applies to similar descriptions involving other parameters.

[0041] In this application, for a method process involving multiple steps, unless there are clear different instructions in this article, the execution of these steps has no strict order limit, and they can be executed in an order other than the described one. Moreover, any one step can include multiple sub-steps or multiple stages. These sub-steps or stages do not necessarily need to be executed at the same moment, but can be executed at different moments. Their execution order does not necessarily need to be sequential, but can be executed alternately or simultaneously with other steps or a part of the sub-steps or stages of other steps.

[0042] In this application, "greater than or equal to", "more than or equal to", and "≥" have the same meaning and can be used interchangeably; "less than or equal to", "less than or equal to", and "≤" have the same meaning and can be used interchangeably; "greater than" can be equivalently expressed as ">", and "less than" can be equivalently expressed as "<". In this application, unless otherwise specified, "greater than or equal to" and "≥" can be regarded as also providing two options of "greater than" and "equal to". In this application, unless otherwise specified, "less than or equal to" and "≤" can be regarded as also providing two options of "less than" and "equal to".

[0043] In this application, for exemplary descriptions such as "in some embodiments" or "in one embodiment", etc., the following meanings can be covered but are not limited to: These solutions can be combined with other solutions in a suitable manner to form new technical solutions.

[0044] In this application, in "the first aspect", "the second aspect", etc., the terms "first", "second", etc. are only used for descriptive purposes and cannot be understood as indicating or implying relative importance or quantity, nor can they be understood as implicitly indicating the importance or quantity of the indicated technical features. Moreover, "first", "second", etc. only serve the purpose of non-exhaustive enumeration and description, and it should be understood that they do not constitute a closed limitation on quantity.

[0045] In this application, regarding numerical intervals (i.e., numerical ranges), unless otherwise specified, the distribution of the optional numerical values within this numerical interval is considered continuous and includes the two numerical endpoints of this numerical interval (i.e., the minimum value and the maximum value), as well as each numerical value between these two numerical endpoints. Unless otherwise specified, when the numerical interval only refers to the integers within this numerical interval, it includes the two endpoint integers of this numerical range, as well as each integer between the two endpoints, which is equivalent to directly listing each integer. When multiple numerical ranges are provided to describe features or characteristics, these numerical ranges can be combined. In other words, unless otherwise specified, the numerical ranges disclosed herein should be understood to include any and all sub-ranges subsumed therein. The "numerical values" in this numerical interval can be any quantitative values, such as numbers, percentages, ratios, etc. "Numerical intervals" are allowed to broadly include numerical interval types such as percentage intervals, ratio intervals, and ratio value intervals.

[0046] Currently, traditional mosquito repellent products have a short mosquito repellent duration (generally about 4 - 6h), are not waterproof or sweatproof, and when exposed to water outdoors, the mosquito repellent effect is greatly reduced. Or two dosage forms need to be used in combination to improve the duration, which is not convenient to use. They have a poor skin feel, are mostly sticky, and consumers have an extremely poor use experience in hot and humid outdoor weather.

[0047] Based on this, the embodiments of this application at least provide a mosquito repellent sustained-release system and its application.

[0048] In some embodiments, the mosquito repellent slow-release system provided by the present application mainly includes two components: silica and / or polyester. When both silica and polyester are included, the slow-release mechanism is as follows:

[0049] 1) The silica is modified with surface siloxane. The functionalized silyl groups in the siloxane chain can form hydrogen bonds with the amide bonds in the structure of DEET, increasing the binding effect, thereby firmly binding DEET, reducing its evaporation rate, increasing the evaporation time, and prolonging the mosquito repellent time.

[0050] 2) The silica particles are rigid and will not release oil under pressure like some polymer powders, enabling the persistence of the oil control performance.

[0051] 3) Polyester is added. The ester bonds in the polyester / the functionalized siloxane on the silica surface / the amide bonds of DEET form hydrogen bonds with each other to form a large three-dimensional network structure. There is also a van der Waals force between the silica particles and the polyester, which plays an adhesive role. This "binding" between molecules further reduces the evaporation rate of DEET.

[0052] 4) The polyester has very good film-forming properties. As Figure 2 shown, after the formulated product made of the slow-release system is applied to the skin, the polyester can quickly form a uniform protective film on the skin surface, sealing the silica microspheres / DEET on the skin surface and reducing the dropping of silica. Thereby further prolonging the mosquito repellent time.

[0053] In the present application, unless otherwise specified, Polyester-5 mainly includes the following monomers: Isophthalic acid, 1,4-Cyclohexanedimethanol (CHDM), 2,2'-Oxybis[ethanol], and 5-Sulfoisophthalic acid, sodium salt; the above monomers form Polyester-5 through a polymerization reaction, and its molecular structure contains characteristic groups such as benzene rings, sulfonic acid groups, and ether bonds. The structural formula of Polyester-5 is as Figure 3 shown; where w, x, y, and z are positive integers, and the molecular weight of Polyester-5 and the cooperative effect between each block can be regulated by adjusting w, x, y, and z.

[0054] In the first aspect of the present application, a mosquito repellent sustained-release system is provided. The mosquito repellent sustained-release system includes DEET and an adsorbent. Among them, the adsorbent is selected from one or more of porous silica, polyester, starch, methacrylate cross-linked polymer, talc, kaolin, cellulose, polydimethylsiloxane, and vinyl polydimethylsiloxane cross-linked polymer; the surface of the porous silica is modified with one or more of hydroxy siloxanyl group, methyl siloxanyl group, amino siloxanyl group, and methoxy amino-terminated polydimethylsiloxane / silsesquioxane copolymer; optionally, the mass ratio of DEET to the adsorbent can be (0.001~30):(0.001~30).

[0055] In some embodiments, the adsorbent includes at least one of porous silica and polyester.

[0056] In the present application, unless otherwise specified, the term "modification" refers to treating the surface of a material by a specific method to change its structure, properties or functions, so as to endow the material with new properties or improve its original properties. The specific ways of modification can include surface coating, chemical coating, precipitation reaction, mechanochemistry and chemical intercalation, etc.

[0057] In some embodiments, the polyester is a commonly used polyester in the art, for example, it can include but is not limited to one or more of polyester-5, polyurethane, and polymethyl methacrylate. Without limitation, the average molecular weight (such as weight average molecular weight) of the polyester can be 1000 Dalton to 1 million Dalton; further, the average molecular weight of the polyester can be but is not limited to 1000 Dalton, 10000 Dalton, 100000 Dalton, 1000000 Dalton, or a value or range between any two of the above values; furthermore, the average molecular weight of the polyester can be 10000 Dalton.

[0058] In some embodiments, the porous silica is porous silica microspheres.

[0059] In some embodiments, the porous silica microspheres are observed at 25000 times magnification using a scanning electron microscope Helios5hydra CX, as Figure 1 shown.

[0060] In some embodiments, the average particle size of the porous silica microspheres is 0.1μm to 100μm. Further, the particle size of the porous silica microspheres can be but is not limited to 0.1μm, 1μm, 50μm, 100μm, or a value or range between any two of the above values.

[0061] In some embodiments, the adsorbent comprises porous silica and polyester, and the mass ratio of porous silica to polyester is (0.001~20):(0.001~10); further, the mass ratio of porous silica to polyester is (1~20):(1~10). By weight, based on 1 part of polyester, the number of parts of porous silica can be 0.1 part, 1 part, 5 parts, 10 parts, 15 parts, 20 parts, or the number of parts or range between any two of the above.

[0062] In some embodiments, the mass ratio of DEET, porous silica and polyester is (0.001~30):(0.001~20):(0.001~10); further, the mass ratio of DEET, porous silica and polyester is (1~30):(1~20):(1~10).

[0063] Non-limitingly, by weight, based on 1~30 parts of DEET, the number of parts of porous silica can be 1 part, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, or the number of parts or range between any two of the above, and the number of parts of polyester can be 1 part, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, or the number of parts or range between any two of the above.

[0064] Non-limitingly, by weight, based on M parts of DEET, the number of parts of porous silica can be 1 part, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, or the number of parts or range between any two of the above, and M can be 1 part, 5 parts, 10 parts, 15 parts, 20 parts, 25 parts, 30 parts, or the number of parts or range between any two of the above.

[0065] Non-limitingly, by weight, based on M parts of DEET, the number of parts of polyester can be 1 part, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, or the number of parts or range between any two of the above, and M can be 1 part, 5 parts, 10 parts, 15 parts, 20 parts, 25 parts, 30 parts, or the number of parts or range between any two of the above.

[0066] In some embodiments, the mass ratio of DEET, porous silica and polyester is (15~25):(0.5~2):(0.5~1); further still, the mass ratio of DEET, porous silica and polyester can be but is not limited to 20:1.5:0.8, 20:1:1, 20:0.5:0.5 or 20:0.5:1.

[0067] In some embodiments, DEET (N,N-Diethyl-meta-toluamide) is a highly effective mosquito repellent active ingredient that achieves the repellent effect by interfering with the olfactory receptors of mosquitoes (such as blocking the perception of lactic acid and carbon dioxide). However, it has limitations such as high volatility, strong skin irritation, and short action time (requiring frequent re-application); porous silica (such as MCM-41, SBA-15, etc.) is an inorganic porous material with a high specific surface area, adjustable pore size, and adsorption capacity, and is commonly used to load active ingredients and achieve slow release; polyesters (such as polylactic acid PLA, polycaprolactone PCL, or modified polyesters) are polymer materials that can be used as embedding or film-forming matrices to control the release of active ingredients through physical barriers and degradation rates.

[0068] In some embodiments, through the synergistic effect of DEET, porous silica, and polyester, the following effects can be achieved:

[0069] (1) Slow release and enhanced efficacy: Prolong the mosquito repellent time

[0070] Among them, the role of porous silica is to load DEET into the pores through physical adsorption, and use its high specific surface area and pore confinement effect to reduce the evaporation rate of DEET. For example: after DEET molecules enter the nanopores of porous silica, evaporation needs to overcome the diffusion resistance in the pores, thereby slowing down the release.

[0071] Polyester can be used as an outer coating material (such as through electrospinning or microencapsulation technology) to form a physical barrier to further delay the release of the DEET and porous silica complex. For example: when the polyester film degrades, the internal porous silica-DEET complex is gradually released, achieving "secondary slow release".

[0072] Example of the synergistic effect: Porous silica adsorption + polyester coating form a dual slow release system, significantly prolonging the effective mosquito repellent time of DEET (for example, from 4 hours to more than 8 hours).

[0073] (2) Improved stability: Reduce the decomposition and irritation of DEET

[0074] Among them, porous silica plays a protective role: the inert surface of porous silica can reduce the direct contact of DEET with the external environment (such as oxygen, ultraviolet light), reducing the risk of its oxidation and decomposition.

[0075] The isolation effect of polyester: The polyester matrix can reduce the contact concentration of DEET with the skin, reducing irritation (such as avoiding direct irritation of the skin by high-concentration DEET at the initial stage through slow release).

[0076] Example of the synergistic effect: Improve the chemical stability and use safety of DEET, while reducing the need for frequent re-application due to rapid evaporation.

[0077] (3) Complementary functions: Enhance the mosquito repellent efficacy

[0078] Among them, the additional functions of porous silica: Some modified porous silica can carry other auxiliary components (such as plant essential oils, antibacterial agents), and cooperate with DEET to enhance the mosquito repellent or antibacterial effect.

[0079] Physical property regulation of polyester: By selecting different polyesters (such as hydrophobic PLA or hydrophilic PEG-PCL), the skin adhesion, sweat resistance and air permeability of the mosquito repellent are adjusted.

[0080] Synergistic effects of examples: Achieve multi-mechanism mosquito repellent (such as DEET + natural ingredients) and more adaptable product forms (such as patches, sprays or lotions).

[0081] In some embodiments, the mosquito repellent sustained-release system further includes one or more of a chelating agent, a thickening agent, an emulsifying agent, an emollient, an oil, a preservative, a soothing active ingredient, a neutralizing agent and a water solvent. In some embodiments, the mosquito repellent sustained-release system includes a chelating agent. The functions of the chelating agent include: ① binding to metal ions (such as calcium, magnesium, iron, etc.) to prevent the oxidation and decomposition of the active ingredient (such as DEET) catalyzed by metal ions; ② maintaining the stability of the formulation and avoiding turbidity or precipitation of the system due to ionic reactions. Non-limitingly, the weight percentage of the chelating agent in the mosquito repellent sustained-release system can be 0.001% - 0.1%; non-limitingly, the weight percentage of the chelating agent in the mosquito repellent sustained-release system can be but is not limited to 0.001%, 0.005%, 0.01%, 0.05%, 0.1% or the value or range between any two of the above values.

[0082] In some embodiments, the chelating agent includes one or more of disodium ethylenediaminetetraacetate and tetrasodium ethylenediaminetetraacetate.

[0083] In some embodiments, the mosquito repellent sustained-release system includes a thickening agent. The functions of the thickening agent include: ① adjusting the viscosity of the product, improving the spreadability and adhesion, and prolonging the residence time of the mosquito repellent component on the skin surface; ② slowing down the volatilization rate of the active ingredient and enhancing the sustained-release effect; ③ preventing the emulsion from separating (cooperating with the emulsifying agent). Non-limitingly, the weight percentage of the thickening agent in the mosquito repellent sustained-release system can be 0.001% - 5%; non-limitingly, the weight percentage of the thickening agent in the mosquito repellent sustained-release system can be but is not limited to 0.001%, 0.01%, 0.1%, 1%, 5% or the value or range between any two of the above values.

[0084] In some embodiments, the thickener includes one or more of acrylate / steareth-20 methacrylate copolymer, acrylate / steareth-20 methacrylate copolymer, sodium polyacryloyldimethyl taurate, sodium polyacrylate, and acrylic acid / C10-30 alkyl acrylate cross-linked polymer, sodium polyacrylate, and acrylic acid / C10-30 alkyl acrylate cross-linked polymer; wherein the molecular weight of the acrylate / steareth-20 methacrylate copolymer is about 2.1 million Daltons.

[0085] In some embodiments, the mosquito repellent sustained-release system includes an emulsifier. The functions of the emulsifier include: ① mixing the aqueous phase and the oil phase (such as mosquito repellent ester components and emollient oils) to form a stable emulsion; ② maintaining the uniform dispersion of the active ingredient in the system to prevent precipitation or layering; ③ affecting the release rate (such as non-ionic emulsifiers may form micelles to encapsulate the active ingredient). Without limitation, the weight percentage of the emulsifier in the mosquito repellent sustained-release system can be 0.001%-10%; without limitation, the weight percentage of the emulsifier in the mosquito repellent sustained-release system can be but is not limited to 0.001%, 0.01%, 0.1%, 1%, 5%, 10%, or a value or range between any two of the above values.

[0086] In some embodiments, the emulsifier includes one or more of sucrose poly stearate, cetearyl alcohol, olive oil unsaponifiables, sodium stearoyl glutamate, and potassium cetyl phosphate.

[0087] In some embodiments, the mosquito repellent sustained-release system includes an emollient. The functions of the emollient include: ① reducing the dry irritation of the mosquito repellent (such as alcohol or ester solvents) to the skin; ② improving the skin feel and enhancing the smoothness and extensibility of the product; ③ some emollients (such as silicone oil) can form a hydrophobic film to assist in delaying the release of the active ingredient. Without limitation, the weight percentage of the emollient in the mosquito repellent sustained-release system can be 0.001%-10%; without limitation, the weight percentage of the emollient in the mosquito repellent sustained-release system can be but is not limited to 0.001%, 0.01%, 0.1%, 1%, 5%, 10%, or a value or range between any two of the above values.

[0088] In some embodiments, the emollient includes one or more of glycerin, butylene glycol, and propylene glycol.

[0089] In some embodiments, the mosquito repellent sustained-release system includes an oil. The functions of the oil include: ① acting as a solvent to dissolve fat-soluble mosquito repellent components (such as picaridin and ethyl hexanediol); ② regulating the spreadability and film-forming property of the formulation and affecting the release rate of the active ingredient; ③ some oils (such as castor oil) may enhance the skin permeability of the mosquito repellent component. Without limitation, the weight percentage of the oil in the mosquito repellent sustained-release system can be 0.01%-10%; without limitation, the weight percentage of the oil in the mosquito repellent sustained-release system can be but is not limited to 0.01%, 0.1%, 1%, 5%, 10% or a value or range between any two of the above values.

[0090] In some embodiments, the oil includes one or more of cyclopentasiloxane, polydimethylsiloxane, glyceryl trioctanoate, and isononyl isononanoate.

[0091] In some embodiments, the mosquito repellent sustained-release system includes a preservative. The functions of the preservative include: ① inhibiting the growth of microorganisms and preventing the formulation from spoiling; ② extending the shelf life of the product, which is particularly indispensable in aqueous systems; ③ attention should be paid to the compatibility with the active ingredient (such as some preservatives may accelerate the degradation of DEET). Without limitation, the weight percentage of the preservative in the mosquito repellent sustained-release system can be 0.001%-3%; without limitation, the weight percentage of the preservative in the mosquito repellent sustained-release system can be but is not limited to 0.001%, 0.01%, 0.1%, 1%, 3% or a value or range between any two of the above values.

[0092] In some embodiments, the emollient includes one or more of glycerin, butylene glycol, and propylene glycol.

[0093] In some embodiments, the mosquito repellent sustained-release system includes a soothing active ingredient. The functions of the soothing active ingredient include: ① relieving skin irritation or itching that may be caused by the mosquito repellent or solvent; ② enhancing the mildness and consumer acceptance of the formulation; ③ some components (such as bisabolol) have both anti-inflammatory and antibacterial functions. Without limitation, the weight percentage of the soothing active ingredient in the mosquito repellent sustained-release system can be 0.001%-20%; without limitation, the weight percentage of the soothing active ingredient in the mosquito repellent sustained-release system can be but is not limited to 0.001%, 0.01%, 0.1%, 1%, 10%, 20% or a value or range between any two of the above values.

[0094] In some embodiments, the soothing active ingredient includes one or more of purslane extract, bisabolol, ginger root extract, and dipotassium glycyrrhizinate.

[0095] In some embodiments, the mosquito repellent sustained-release system includes a neutralizing agent. The functions of the neutralizing agent include: ① adjusting the pH value of the formulation to a skin-friendly range (usually pH 5.5 - 7.0); ② neutralizing the alkaline environment required by the thickening agent (such as carbomer) to form a gel; ③ avoiding inactivation of the active ingredient or skin irritation caused by extreme pH values. Without limitation, the weight percentage of the neutralizing agent in the mosquito repellent sustained-release system can be 0.001% - 5%; without limitation, the weight percentage of the neutralizing agent in the mosquito repellent sustained-release system can be but is not limited to 0.001%, 0.01%, 0.1%, 1%, 5% or a value or range between any two of the above values.

[0096] In some embodiments, the neutralizing agent includes one or more of sodium hydroxide, potassium hydroxide, and triethanolamine.

[0097] In some embodiments, the mosquito repellent sustained-release system includes an aqueous solvent. The functions of the aqueous solvent include: ① serving as a solvent for water-soluble components (such as certain chelating agents and soothing agents); ② adjusting the fluidity of the formulation and reducing costs; ③ serving as the continuous phase or dispersed phase in the emulsion system and affecting the release kinetics of the active ingredient.

[0098] In some embodiments, by weight percentage, the mosquito repellent sustained-release system includes 0.001% - 30% of DEET, 0.001% - 20% of porous silica, 0.001% - 0.1% of chelating agent, 0.001% - 10% of polyester, 0.001% - 5% of thickening agent, 0.001% - 10% of emulsifier, 0.001% - 10% of emollient, 0.01% - 10% of oil, 0.001% - 3% of preservative, 0.001% - 20% of soothing active ingredient, 0.001% - 5% of neutralizing agent, and the balance of water.

[0099] The mosquito repellent sustained-release system provided in the embodiments of the present application, through optimizing the formulation design and combining the sustained-release technology, can extend the mosquito repellent time of DEET on the basis of the conventional mosquito repellent content when the adsorbent includes any one of porous silica and polyester. When both porous silica and polyester are present, the mosquito repellent sustained-release system can not only significantly extend the mosquito repellent time of DEET on the basis of the conventional mosquito repellent content, but also greatly reduce the irritation to the skin, and also endow it with excellent waterproof and sweatproof properties, being able to effectively cope with various complex environments and meet the long-term mosquito repellent needs of ordinary residents' daily protection and special fields such as the military industry.

[0100] In the second aspect of the present application, a preparation method of a mosquito repellent sustained-release system is provided, including the following steps: stirring and mixing DEET with an adsorbent under high-temperature conditions to prepare the mosquito repellent sustained-release system;

[0101] Among them, the adsorbent is the adsorbent in the mosquito repellent slow-release system of the first aspect of the present application; the mass ratio of DEET to the adsorbent is (0.001~30):(0.001~30);

[0102] The high-temperature condition can be 80°C to 85°C.

[0103] In some embodiments, the adsorbent and DEET are first mixed evenly by high-speed shearing (physical mixing), and then added to a formulation containing a thickener, an emulsifier, a skin emollient, and an oil, etc. for emulsification. The formulation is an oil-in-water type, and DEET, as a kind of "oil", enters the inner phase.

[0104] In the third aspect of the present application, there is provided the use of the mosquito repellent slow-release system of the first aspect of the present application or the mosquito repellent slow-release system prepared by the preparation method of the second aspect of the present application in the preparation of mosquito repellent products; further, the mosquito repellent products include one or more of mosquito repellent creams, mosquito repellent sprays, and mosquito repellent liquids.

[0105] Some examples are provided below.

[0106] The embodiments of the present application will be described in detail below in conjunction with the examples. It should be understood that these examples are only used to illustrate the present application and not to limit the scope of the present application. For the experimental methods without specified conditions in the following examples, the guidance given in the present application is preferably referred to, and it can also be carried out according to the experimental manuals or conventional conditions in the art, or according to the conditions recommended by the manufacturer, or by referring to the experimental methods known in the art.

[0107] In the following embodiments, for the measurement parameters of the raw material components, if there is no special description, there may be slight deviations within the weighing accuracy range. For the temperature and time parameters, acceptable deviations caused by instrument test accuracy or operation accuracy are allowed.

[0108] The porous silica involved in the following examples was purchased from Keno (trade name: Silica Shells-SH), and its surface was modified with a methoxyamino-terminated polydimethylsiloxane / silsesquioxane copolymer. The porous silica was observed at 25,000 times using a scanning electron microscope Helios5hydra CX, as Figure 1 shown, the average particle size of the porous silica microspheres is 0.1μm to 100μm.

[0109] The acrylic acid (ester) / stearyl alcohol polyether-20 methacrylate copolymer involved in the following examples was purchased from Shanghai Qianfei (Novmer CS).

[0110] The emulsifier involved in the following examples was purchased from Shanghai Boshuo. The emulsifier contains sucrose poly stearate, cetearyl alcohol, and olive (OLEA EUROPAEA) oil unsaponifiables, as shown in Table 1 below.

[0111] Table 1

[0112]

[0113] The preservatives involved in the following examples were purchased from Shanghai Boshuo. The preservatives include octanoyl hydroxamic acid, glycerol caprylate, 1,2 - hexanediol, and ethylhexylglycerin, as shown in Table 2 below.

[0114] Table 2

[0115]

[0116] The purslane extract involved in the following examples was purchased from Huiwen Biologics. It contains purslane extract, 1,2 - hexanediol, and p - hydroxyacetophenone, as shown in Table 3 below.

[0117] Table 3

[0118]

[0119] The main components of SymRelief® 100 involved in the following examples are bisabolol and ginger root extract, as shown in Table 4 below.

[0120] Table 4

[0121]

[0122] Example 1

[0123] I. Prepare blank sample A, sample B, sample C, and sample D respectively according to the components and contents (by mass ratio, unit: %) shown in Table 5 below. The preparation method is as follows:

[0124] (1) Heat the film - forming agent (polyester - 5) and water to about 85°C. After stirring and dissolving, add the thickener, emollient, and chelating agent, stir and disperse evenly, add the neutralizing agent, and keep warm;

[0125] (2) Heat the mosquito repellent, oil, emulsifier, powder (porous silica) to about 85°C and stir evenly;

[0126] (3) Add the components in (2) to (1) under stirring, homogenize, accelerate emulsification, and then start to cool down;

[0127] (4) Add the preservative and soothing active ingredient at about 45°C;

[0128] (5) When the temperature drops below 40°C, filter, discharge, and defoam to obtain the microsphere - sustained - release mosquito repellent cream.

[0129] Table 5

[0130]

[0131] II. Use each of the blank sample A, sample B, sample C, and sample D for testing respectively.

[0132] 1. Mosquito repellent efficacy test:

[0133] (1) Experimental basis: GB / T 13917.9-2009 Hygienic insecticides for pesticide registration - Indoor efficacy test and evaluation - Part 9: Repellents

[0134] (2) Test method: Select 4 or more testers with qualified attack ability (half male and half female, and should not drink alcohol, tea, or coffee before and during the test, and should not use products containing fragrances). Draw a skin area of 50 mm × 50 mm on the back of each hand of both hands. Apply the repellent to be tested evenly on one hand at a dose of 1.5 mg / cm 2 ², expose 40 mm × 40 mm of the skin, and tightly cover the rest. The other hand is the blank control. 2 hours after applying the repellent, put the hand into a mosquito cage with qualified attack ability for 2 minutes, and observe whether mosquitoes come to land and suck blood. Then test once every 1 hour. As long as one mosquito comes to suck blood, it is judged that the repellent has failed. Record the effective protection time (h) of the repellent. Each time, the control hand is tested first, and the test insects with qualified attack ability can continue the test. If the attack ability of the test insects is unqualified, qualified test insects need to be replaced for the test.

[0135] (3) Test samples: Blank sample A, sample B, sample C, and sample D.

[0136] (4) Test results: See Table 6 below

[0137] Table 6

[0138]

[0139] (5) Experimental conclusion: Compared with the base material without any slow-release components, after adding silica microspheres to increase slow-release (sample B), the mosquito repellent efficacy can reach 7.5 hours, and the mosquito repellent efficacy increases by 25% compared with the blank sample A, indicating that porous silica does have an adsorption effect on DEET and can effectively reduce the volatilization of DEET. Sample C is a formulated sample with only a film-forming agent (polyester-5) added. Compared with the blank sample A, the mosquito repellent efficacy is extended by one hour because the film-forming agent can help the mosquito repellent material form a more uniform protective film on the skin surface, providing more complete protection. Sample D added both slow-release components and a film-forming agent, and the two are compounded synergistically. The mosquito repellent efficacy can reach 9.8 hours. It is speculated that the mechanism is that the slow-release microspheres that adsorb DEET are evenly distributed on the skin surface with the help of the film-forming agent to form a mosquito repellent protective film with a uniform thickness. Due to the addition of the film-forming agent, the slow-release microspheres can be firmly fixed on the skin surface and will not fall off with movement. Therefore, the mosquito repellent efficacy is extended by more than 60%.

[0140] 2. Waterproof Test:

[0141] (1)Experimental basis: GB / T 13917.9-2009 Indoor Efficacy Test and Evaluation of Sanitary Insecticides for Pesticide Registration - Part 9: Repellents

[0142] (2)Experimental method: Select 4 or more testers with qualified attack ability (half male and half female, and they should not drink alcohol, tea or coffee before and during the test, and should not use products containing fragrances). Draw a skin area of 50mm×50mm on the back of each hand of them. Apply the repellent to be tested evenly on one hand at a dose of 1.5mg / cm 2 . Expose 40mm×40mm of the skin and cover the rest tightly. The other hand is the blank control. After applying the repellent for 10 minutes, rinse it with artificial sweat at a speed of 15mL / s for 10 seconds, then put the hand into a mosquito cage with qualified attack ability for 2 minutes, and observe whether mosquitoes come to land and suck blood. Then test once every 1 hour. As long as one mosquito comes to suck blood, it is judged that the repellent fails. Record the effective protection time (h) of the repellent. Each time, the control hand is tested first. The test insects with qualified attack ability can continue the test. If the attack ability of the test insects is unqualified, qualified test insects need to be replaced for the test.

[0143] (3)Test sample: Sample D

[0144] (4)Test result: The protection effect reaches more than 6 hours (Grade A)

[0145] (5)Experimental conclusion: Sample D has certain waterproof performance and can also achieve Grade A mosquito repellent effect under the condition of simulated sweating (According to GB / T 13917.9-2009, the Grade A of the repellent efficacy result: effective protection time ≥ 6h)

[0146] Example 2

[0147] Prepare the microsphere sustained-release mosquito repellent cream sample E according to the method of Example 1, with the only difference being that the mass percentages of DEET, porous silica, and polyester-5 in the formula are 20%, 0.5%, and 0.5% respectively. Test sample E, and the mosquito repellent time is 7 hours, with a slight improvement in the mosquito repellent time.

[0148] Example 3

[0149] Prepare the microsphere sustained-release mosquito repellent cream sample F according to the method of Example 1, with the only difference being that the mass percentages of DEET, porous silica, and polyester-5 in the formula are 20%, 1%, and 0.5% respectively. Test sample F, and the mosquito repellent time is 8.5 hours.

[0150] Comparative Example 1

[0151] Prepare the microsphere sustained-release mosquito repellent cream according to the method of Example 1, with the only difference being that nylon-12 (average particle size of 5 µm to 12.5 µm, purchased from Keno, trade name SP-500 polyamide) is used as the adsorbent. Test the microsphere sustained-release mosquito repellent cream of Comparative Example 1, and the mosquito repellent time effect is 6 hours, with almost no extension of the mosquito repellent effect.

[0152] Comparative Example 2

[0153] Prepare the microsphere sustained-release mosquito repellent cream according to the method of Example 1, with the only difference being that the surface of the porous silica is not modified on the basis of Example 1. Test the microsphere sustained-release mosquito repellent cream of Comparative Example 2, and the mosquito repellent time effect is 6 hours, with almost no extension of the mosquito repellent effect.

[0154] The technical features of the above-described embodiments can be combined arbitrarily. For the sake of brevity of description, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered as the scope recorded in this specification.

[0155] The above-described embodiments only represent several implementation manners of the present application, and their descriptions are relatively specific and detailed, but they should not be construed as limiting the scope of the invention patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present application, several modifications and improvements can still be made, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application should be subject to the appended claims, and the specification and drawings can be used to explain the scope of the claims.

Claims

1. A mosquito repellent sustained-release system, characterized in that: The mosquito repellent slow-release system comprises DEET and an adsorbent, wherein the adsorbent comprises one or more of porous silica and polyester; the surface of the porous silica is modified with one or more of hydroxysiloxane, methylsiloxane, aminosiloxane and methoxyamino-terminated polydimethylsiloxane / silsesquioxane copolymer; The mass ratio of the DEET to the adsorbent is (0.001-30): (0.001-30).

2. The mosquito repellent sustained-release system according to claim 1, characterized in that: The polyester includes one or more of polyester-5, polyurethane and polymethyl methacrylate.

3. The mosquito repellent sustained-release system according to claim 1, characterized in that: The porous silica is porous silica microspheres, and the average particle size of the porous silica microspheres is 0.1 μm to 100 μm.

4. The mosquito repellent sustained-release system according to any one of claims 1 to 3, characterized in that: The adsorbent includes porous silica and polyester, and the mass ratio of the DEET, the porous silica and the polyester is (0.001-30): (0.001-20): (0.001-10).

5. The mosquito repellent sustained-release system according to claim 4, characterized in that: The mass ratio of the DEET, the porous silica and the polyester is (15-25): (0.5-2): (0.5-1).

6. The mosquito repellent sustained-release system according to any one of claims 1 to 3, characterized in that: The mosquito repellent sustained-release system further comprises one or more of a chelating agent, a thickener, an emulsifier, an emollient, a grease, a preservative, a soothing active substance, a neutralizer and an aqueous solvent.

7. The mosquito repellent sustained-release system according to claim 6, characterized in that: Meet one or more of the following characteristics: (a1) the mosquito repellent sustained-release system comprises a chelating agent, and the weight percentage of the chelating agent in the mosquito repellent sustained-release system is 0.001%-0.1%; (a2) the mosquito repellent sustained-release system comprises a thickener, and the weight percentage of the thickener in the mosquito repellent sustained-release system is 0.001%-5%; (a3) the mosquito repellent sustained-release system comprises an emulsifier, and the weight percentage of the emulsifier in the mosquito repellent sustained-release system is 0.001%-10%; (a4) the mosquito repellent sustained-release system comprises an emollient, and the weight percentage of the emollient in the mosquito repellent sustained-release system is 0.001%-10%; (a5) the mosquito repellent sustained-release system comprises oil, and the weight percentage of the oil in the mosquito repellent sustained-release system is 0.01%-10%; (a6) the mosquito repellent sustained-release system comprises a preservative, and the weight percentage of the preservative in the mosquito repellent sustained-release system is 0.001%-3%; (a7) the mosquito repellent sustained-release system comprises a soothing active substance, and the weight percentage of the soothing active substance in the mosquito repellent sustained-release system is 0.001%-20%; (a8) the mosquito repellent sustained-release system comprises a neutralizer, and the weight percentage of the neutralizer in the mosquito repellent sustained-release system is 0.001%-5%; (a9) the chelating agent includes one or more of ethylenediaminetetraacetic acid disodium salt and ethylenediaminetetraacetic acid tetrasodium salt; (a10) the thickener comprises one or more of acrylic acid / stearyl alcohol polyether-20 methacrylate copolymer, acrylic acid esters / stearyl alcohol polyether-20 methacrylate copolymer, sodium polyacryloyldimethyl taurate, sodium polyacrylate and acrylic acid / C10-30 alkyl acrylate crosspolymer, sodium polyacrylate and acrylates / C10-30 alkyl acrylate crosspolymer; (a11) the emulsifier comprises one or more of sucrose polystearate, cetearyl alcohol, unsaponifiable olive oil, sodium stearoyl glutamate and potassium cetyl phosphate; (a12) the emollient comprises one or more of glycerin, butylene glycol and propylene glycol; (a13) The soothing active ingredient comprises one or more of purslane extract, bisabolol, ginger root extract and dipotassium glycyrrhizinate.

8. The mosquito repellent sustained-release system according to claim 7, characterized in that: Calculated by weight percentage, it includes 0.001%-30% DEET, 0.001%-20% porous silica, 0.001%-0.1% chelating agent, 0.001%-10% polyester, 0.001%-5% thickener, 0.001%-10% emulsifier, 0.001%-10% emollient, 0.01%-10% oil, 0.001%-3% preservative, 0.001%-20% soothing active ingredient, 0.001%-5% neutralizer, and the balance water.

9. A method for preparing a mosquito repellent sustained-release system, characterized in that: The method comprises the following steps: stirring and mixing DEET and an adsorbent under high temperature conditions to prepare a mosquito repellent slow-release system; Wherein, the adsorbent is the adsorbent in the mosquito repellent sustained-release system according to any one of claims 1 to 8; the mass ratio of DEET to the adsorbent is (0.001 to 30): (0.001 to 30); The high temperature condition is 80°C~85°C.

10. Use of the mosquito repellent sustained-release system according to any one of claims 1 to 8 or the mosquito repellent sustained-release system prepared by the preparation method according to claim 9 in the preparation of mosquito repellent products; Optionally, the mosquito repellent product includes one or more of mosquito repellent cream, mosquito repellent spray and mosquito repellent liquid.

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