Method for preparing nano-emulsion with uniform particle size distribution

Abstract

The invention provides a method for preparing a nano-emulsion with uniform particle size distribution, which comprises the following steps: a mixture comprising an oil phase, a water phase and an emulsifier is subjected to jet mixing, the emulsifier at least comprises an emulsifier in a solid state at normal temperature, and the molding hardness of the emulsifier in the solid state at normal temperature at normal temperature is more than 40N; the jet mixing is carried out at a temperature lower than the melting point of the emulsifier that is solid at room temperature. According to the method provided by the invention, the particle size distribution uniformity of the emulsion can be improved, so that the Ostwald ripening phenomenon of the nano-emulsion is improved, and the stability and skin feeling of the nano-emulsion are improved.

Description

Technical Field

[0001] The present application relates to a method for preparing a product, and in particular, to a method for preparing a nanoemulsion with uniform particle size distribution. Background Art

[0002] Ostwald ripening, or Ostwald ripening for short, is a unique phenomenon observed in solid solutions or liquid sol materials. It describes a non-uniform structural evolution process over time: tiny crystals or sol particles originally dispersed in the solute undergo dissolution and then redeposition onto larger crystals or sol particles.

[0003] There are usually droplets of different sizes in the emulsion system. The more uneven the particle size distribution is, the more likely it is to undergo Ostwald ripening, which affects the stability and skin feel of the product. In particular, cream products with higher viscosity are more likely to undergo Ostwald ripening than emulsion products with lower viscosity.

[0004] Therefore, the stability problem is one of the most important factors limiting the widespread application of emulsion systems, especially nanoemulsions. How to improve the uniformity of particle size distribution of nanoemulsions to reduce the transfer of small droplets to large droplets and improve the Ostwald ripening phenomenon is still a technical problem that needs to be solved. Summary of the invention

[0005] In view of the problems existing in the prior art, the present application provides a method for preparing a nanoemulsion with uniform particle size distribution.

[0006] Specifically, this application involves the following aspects:

[0007] 1. A method for preparing a nanoemulsion with uniform particle size distribution, comprising:

[0008] The mixture including oil phase, water phase and emulsifier is jet mixed.

[0009] The emulsifier at least includes an emulsifier that is solid at room temperature.

[0010] The emulsifier which is solid at room temperature has a molding hardness of 40N or more at room temperature.

[0011] The jet mixing temperature is lower than the melting point of the emulsifier which is solid at room temperature.

[0012] 2. The method according to item 1, wherein the emulsifier which is solid at room temperature has a molding hardness of 40N to 80N at room temperature.

[0013] 3. The method according to item 1 or 2, wherein the melting point of the emulsifier which is solid at room temperature is 30°C or higher, preferably 35°C to 80°C.

[0014] 4. The method according to any one of items 1 to 3, wherein the pressure of the jet mixing is 30 to 300 bar.

[0015] 5. The method according to any one of items 1 to 4, wherein the temperature of the jet mixing is -20°C to 20°C.

[0016] 6. A method according to any one of items 1 to 5, wherein the method comprises heating the substance before the jet mixing into a liquid state.

[0017] 7. A method according to any one of items 1 to 6, wherein the method comprises heating the jet-mixed substance into a liquid state.

[0018] 8. The method according to any one of items 1 to 7, wherein in the mixture, the mass content of the emulsifier that is solid at room temperature is 0.5 to 5%, and the mass content of the oil phase is 1 to 10%.

[0019] 9. The nanoemulsion prepared by the method described in any one of items 1 to 8.

[0020] The method provided in the present application can improve the uniformity of the particle size distribution of the emulsion, thereby reducing the probability of Ostwald ripening of the nanoemulsion, which is beneficial for improving the skin feel of the product and increasing the stability of the nanoemulsion product. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is a schematic diagram of the molding hardness test of the emulsifier;

[0022] Figure 2 Schematic diagram of the jet mixing experiment. DETAILED DESCRIPTION

[0023] The present application is further described below in conjunction with examples. It should be understood that the examples are only used to further describe and illustrate the present application and are not used to limit the present application.

[0024] Unless otherwise defined, the technical and scientific terms in this specification have the same meaning as those generally understood by those skilled in the art. Although similar or identical methods and materials as described herein may be used in experiments or practical applications, materials and methods are described herein below. In the event of a conflict, the present specification including the definitions therein shall prevail. In addition, materials, methods and examples are provided for illustration only and are not restrictive. The present application is further described below in conjunction with specific embodiments, but is not intended to limit the scope of the present application.

[0025] In view of the problems existing in the prior art, the present application provides a method for preparing a nanoemulsion with uniform particle size distribution, comprising: jet mixing a mixture including an oil phase, an aqueous phase, and an emulsifier. Jet mixing refers to mixing a mixture including an oil phase, an aqueous phase, and an emulsifier by the action of a jet to achieve emulsification of the mixture, which can also be called jet emulsification.

[0026] Wherein, the emulsifier at least includes an emulsifier that is solid at room temperature. That is, the emulsifier may include one or more emulsifiers, at least one of which is a solid emulsifier at room temperature. When the emulsifier contains only one emulsifier, the emulsifier is a solid emulsifier at room temperature. When the emulsifier contains more than two emulsifiers, it may contain only one emulsifier that is solid at room temperature, or it may contain more than two emulsifiers that are solid at room temperature.

[0027] In this application, "normal temperature" is also called general temperature or room temperature, which refers to the temperature range of 20°C-25°C, for example, it can be 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, and any value between these values.

[0028] The emulsifier which is solid at room temperature has a molding hardness of 40N or more at room temperature. When the molding hardness of the solid emulsifier at room temperature is lower than 40N, the uniformity of the particle size distribution of the formed emulsion will be reduced. For a solid emulsifier having a molding hardness of 40N or more at room temperature, it can be selected from the types of emulsifiers allowed to be added to skin external preparations. For example, a solid emulsifier having a hardness of 40N, 42N, 45N, 48N, 50N, 52N, 55N, 58N, 60N, 62N, 65N, 68N, 70N, 72N, 75N, 78N, 80N, 82N, 85N, 88N, 90N, 100N, and any values ​​between these values ​​can be selected.

[0029] In some specific embodiments, the emulsifier which is solid at room temperature preferably has a molding hardness of 40N to 80N at room temperature.

[0030] The molding hardness of the emulsifier can be tested using methods and equipment known in the art, for example, using a texture analyzer.

[0031] In some specific embodiments, the emulsifier that is solid at room temperature can be an oil-soluble emulsifier or a water-soluble emulsifier.

[0032] In some more specific embodiments, the emulsifier that is solid at room temperature is an oil-soluble emulsifier.

[0033] In some more specific embodiments, the emulsifier that is solid at room temperature may have a melting point of 30°C or more, illustratively 30°C, 32°C, 35°C, 38°C, 40°C, 42°C, 45°C, 48°C, 50°C, 52°C, 55°C, 58°C, 60°C, 62°C, 65°C, 68°C, 70°C, 72°C, 75°C, 78°C, 80°C, 82°C, 85°C, 88°C, 90°C, 92°C, 95°C, and any values ​​therebetween. Preferably, the melting point of the emulsifier that is solid at room temperature is 35°C to 80°C.

[0034] The jet mixing is carried out at a temperature lower than the melting point of the emulsifier that is solid at room temperature. That is, the jet mixing needs to ensure that the emulsifier is carried out in a solid state. The temperature of the jet mixing can be selected accordingly according to the different melting points of the emulsifier that is solid at room temperature used. The selectable temperature range is exemplarily lower than 30°C, 32°C, 35°C, 38°C, 40°C, 42°C, 45°C, 48°C, 50°C, 52°C, 55°C, 58°C, 60°C, 62°C, 65°C, 68°C, 70°C, 72°C, 75°C, 78°C, 80°C, 82°C, 85°C, 88°C, 90°C, 92°C, 95°C, etc. Among them, it is preferred to use a temperature below room temperature for jet mixing, and such a temperature is exemplarily below 20°C to 25°C, for example, 25°C, 22°C, 20°C, 18°C, 15°C, 12°C, 10°C, 8°C, 5°C, 2°C, 0°C, -2°C, -5°C, -8°C, -10°C, -12°C, -15°C, -18°C, -20°C, -22°C, and any values ​​and ranges between these values.

[0035] In some more specific embodiments, the temperature of the jet mixing is -20°C to 20°C.

[0036] In some specific embodiments, the pressure of the jet mixing is 30 to 300 bar, for example, it can be 30 bar, 40 bar, 50 bar, 60 bar, 70 bar, 80 bar, 90 bar, 100 bar, 110 bar, 120 bar, 130 bar, 140 bar, 150 bar, 160 bar, 170 bar, 180 bar, 190 bar, 200 bar, 210 bar, 220 bar, 230 bar, 240 bar, 250 bar, 260 bar, 270 bar, 280 bar, 290 bar, 300 bar, and any value and range between these values.

[0037] Those skilled in the art will appreciate that the jet mixing described in the present application can be performed using a jet mixing device known in the art.

[0038] In some specific embodiments, the jet mixing device includes a storage tank, a high-pressure plunger pump, a heating unit, a jet mixing chamber, a cooling unit, and a pipeline. The storage tank, the high-pressure plunger pump, the heating unit, the jet mixing chamber, the cooling unit, and the pipeline can be conventionally selected according to needs.

[0039] In some specific embodiments, the hydraulic diameter of the jet mixing chamber in the jet mixing device is 0.5-2.0 mm, for example, it can be 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1.0 mm, 1.1 mm, 1.2 mm, 1.3 mm, 1.4 mm, 1.5 mm, 1.6 mm, 1.7 mm, 1.8 mm, 1.9 mm, 2.0 mm, and any value and range between these values.

[0040] In a specific embodiment, the jet mixing chamber can be prepared by itself or purchased, for example, the ATS-Z chamber can be purchased from Antos Nanotechnology (Suzhou) Co., Ltd.

[0041] The oil phase in the present application has oil and fat, and may further include other oil-soluble components.

[0042] The oil is selected according to the physical properties of the product. For example, when used to form a liquid emulsion, the oil is a grease that is conducive to forming a liquid emulsion. When used to form a solid or semi-solid emulsion such as an ointment or cream, the oil is a grease that is conducive to forming an ointment or cream, and such oil at least includes an oil that is solid at room temperature. Oils that are liquid at room temperature can be added according to product needs. The above oils can be selected according to the types of oils listed in skin topical products.

[0043] The oils and fats may include, for example, triglycerides, diglycerides, monoglycerides, wax esters, hydrocarbons, etc. The triglycerides may include, for example, caprylic / capric triglyceride, meadowfoam seed oil, etc.; the wax esters may include, for example, octyldodecyl myristate, etc.

[0044] The aqueous phase of the present application may be water only, or may further include other water-soluble components.

[0045] In a specific embodiment, the mixture consists of an oil phase, an aqueous phase and the above-mentioned emulsifier.

[0046] In a specific embodiment, in the mixture, the mass content of the emulsifier which is solid at room temperature is 0.5-5%, for example, it can be 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, and any value in between these values; the mass content of the oil phase is 1-10%, for example, it can be 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, and any value and range in between these values.

[0047] Furthermore, the method of the present application may also include heating the substance before the jet mixing into a liquid state, that is, heating the emulsifier and / or oil that is solid at room temperature before the jet mixing into a liquid state.

[0048] Furthermore, the method of the present application may also include heating the substance mixed by the jet into a liquid state, that is, heating the emulsifier and / or fat which is solid at room temperature after the jet mixing into a liquid state.

[0049] In a specific embodiment, the method for preparing a nanoemulsion with uniform particle size distribution of the present application comprises: jet mixing a mixture including an oil phase, an aqueous phase, and an emulsifier, wherein the emulsifier comprises at least an emulsifier that is solid at room temperature, the emulsifier that is solid at room temperature has a molding hardness of 40N or more at room temperature, the emulsifier that is solid at room temperature has a melting point of 30°C or more, the temperature of the jet mixing is lower than the melting point of the emulsifier that is solid at room temperature, and the pressure is 30 to 300 bar.

[0050] In a specific embodiment, the method for preparing a nanoemulsion with uniform particle size distribution of the present application comprises: jet mixing a mixture including an oil phase, an aqueous phase, and an emulsifier, wherein the emulsifier comprises at least an emulsifier that is solid at room temperature, the emulsifier that is solid at room temperature has a molding hardness of 40N to 80N at room temperature, the emulsifier that is solid at room temperature has a melting point of 35°C to 80°C, the temperature of the jet mixing is below room temperature, and the pressure is 30 to 300 bar.

[0051] In a specific embodiment, the method for preparing a nanoemulsion with uniform particle size distribution of the present application comprises: jet mixing a mixture including an oil phase, an aqueous phase, and an emulsifier, wherein the emulsifier comprises at least an emulsifier that is solid at room temperature, the emulsifier that is solid at room temperature has a molding hardness of 40N to 80N at room temperature, the emulsifier that is solid at room temperature has a melting point of 35°C to 80°C, the temperature of the jet mixing is -20 to 20°C, and the pressure is 30 to 300 bar.

[0052] In a specific embodiment, the method for preparing a nanoemulsion with uniform particle size distribution of the present application comprises: jet mixing a mixture including an oil phase, an aqueous phase, and an emulsifier, wherein the emulsifier comprises at least an emulsifier that is solid at room temperature, the emulsifier that is solid at room temperature has a molding hardness of 40N or more at room temperature, the emulsifier that is solid at room temperature has a melting point of 30°C or more, the temperature of the jet mixing is lower than the melting point of the emulsifier that is solid at room temperature, and the pressure is 30 to 300 bar; in the mixture, the mass content of the emulsifier that is solid at room temperature is 0.5 to 5%, and the mass content of the oil phase is 1 to 10%.

[0053] In a specific embodiment, the method for preparing a nanoemulsion with uniform particle size distribution of the present application comprises: jet mixing a mixture including an oil phase, an aqueous phase, and an emulsifier, wherein the emulsifier comprises at least an emulsifier that is solid at room temperature, the emulsifier that is solid at room temperature has a molding hardness of 40N to 80N at room temperature, the emulsifier that is solid at room temperature has a melting point of 35°C to 80°C, the temperature of the jet mixing is below room temperature, and the pressure is 30 to 300 bar; in the mixture, the mass content of the emulsifier that is solid at room temperature is 0.5 to 5%, and the mass content of the oil phase is 1 to 10%.

[0054] The present application also provides a nanoemulsion prepared by any of the methods described above.

[0055] In some specific embodiments, the particle size distribution standard deviation of the nanoemulsion is less than 120nm, for example, it can be 119nm, 118nm, 117nm, 116nm, 115nm, 114nm, 113nm, 112nm, 111nm, 110nm, 109nm, 108nm, 107nm, 106nm, 105nm, 104nm, 103nm, 102nm, 101nm, 100nm, 99nm, 98nm, 97nm, 96nm, 95nm, 94nm, 93nm, 92nm 20nm, 15nm, 10nm, 5nm, 1nm, etc., as well as any values ​​and ranges between these values.

[0056] The nanoemulsion prepared by the method of the present application has a uniform particle size distribution, and the standard deviation of the particle size distribution of the emulsion can be less than 120 nm.

[0057] Test example

[0058] 1. Mixture Preparation

[0059] According to the formulation in Table 1, the ingredients were added to a beaker and heated to 70-80° C. to dissolve all the ingredients. The mixture was then stirred at 200 rpm for 1 minute using a stirring paddle to form a preliminary mixture.

[0060] Table 1 Emulsion formula

[0061]

[0062]

[0063]

[0064] The "molding hardness" test method of the emulsifier is as follows:

[0065] Weigh 30g of solid emulsifier into a cylindrical heating mold, heat until the emulsifier is completely melted, and then cool naturally to room temperature (25°C). Take out the solidified cylinder for later use;

[0066] The hardness test is performed using a texture analyzer, where the texture analyzer can be "AMETEK-BOLEFIELD CT3" or equivalent. The probe of the texture analyzer adopts a conical probe with a top angle of 30 degrees. Figure 1 As shown, the solid emulsifier cylinder prepared above is placed horizontally directly below the probe, and the top angle of the probe is facing the center of the bottom surface of the cylinder. The probe is inserted into the sample to be tested at a speed of 0.5mm / s, the insertion depth is 6mm, and the peak force during the insertion process is recorded. Each solid emulsifier is measured 6 times in parallel as the hardness of the solid emulsifier.

[0067] 2. Jet mixing experiment

[0068] The mixture prepared in step 1 was introduced into the storage tank for the jet mixing experiment.

[0069] The jet emulsification conditions of each embodiment and comparative example are shown in Table 2.

[0070] The schematic diagram of the jet mixing experiment is shown in Figure 2 As shown, the jet mixing device includes a P0 storage tank, a P1 high-pressure plunger pump, a P2 heating unit (heated by constant temperature water), a P3 jet mixing chamber, a P4 cooling unit (cooled by circulating low-temperature antifreeze), a P5 heating unit (heated by constant temperature water), and a P6 pipeline. Among them, P3 adopts the ATS-Z chamber of Antos Nanotechnology (Suzhou) Co., Ltd.

[0071] 3. Particle size distribution test

[0072] The liquid after jet mixing was sampled in a beaker, and the particle size distribution was tested using the BT-9300ST laser particle size analyzer of Dandong Better Instrument Co., Ltd.: The particle size distribution test instrument was used to collect more than 200 particle size values, and the standard deviation of these values ​​was calculated. The test results are shown in Table 2.

[0073] Table 2 Emulsification conditions and particle size distribution results

[0074]

[0075]

Claims

1. A method for preparing a nanoemulsion with uniform particle size distribution, comprising: The mixture including oil phase, water phase and emulsifier is jet mixed. The emulsifier at least includes an emulsifier that is solid at room temperature. The emulsifier which is solid at room temperature has a molding hardness of 40N or more at room temperature. The jet mixing temperature is lower than the melting point of the emulsifier which is solid at room temperature.

2. The method according to claim 1, wherein the emulsifier which is solid at room temperature has a molding hardness of 40N to 80N at room temperature.

3. The method according to claim 1 or 2, wherein the melting point of the emulsifier which is solid at room temperature is above 30°C, preferably 35°C to 80°C.

4. The method according to any one of claims 1 to 3, wherein the pressure of the jet mixing is 30 to 300 bar.

5. The method according to any one of claims 1 to 4, wherein the temperature of the jet mixing is -20°C to 20°C.

6. The method according to any one of claims 1 to 5, wherein the method comprises heating the substance before the jet mixing to a liquid state.

7. The method according to any one of claims 1 to 6, wherein the method comprises heating the jet mixed substance into a liquid state.

8. The method according to any one of claims 1 to 7, wherein in the mixture, the mass content of the emulsifier which is solid at room temperature is 0.5-5%, and the mass content of the oil phase is 1-10%.

9. The nanoemulsion prepared by the method according to any one of claims 1 to 8.

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