BM-Simlipid manufacturing method and cosmetic compositions manufactured by the method

Abstract

This invention provides a method for preparing BM-Simlipide, comprising the following steps: (a) in a first open tank, stirring a vernix caseosa-like component and a solvent, which are relatively stable at high temperatures, at 65-95°C using a mixer; (b) in a second open tank, stirring a heat-sensitive hydrogenated lecithin, glyceryl stearate (which needs to be premixed with hydrogenated lecithin), and stearic acid at room temperature using a mixer; (c) mixing the mixture from the first open tank and the mixture from the second open tank using an inline mixer to prepare a mixture; (d) solidifying the mixture from step (c), pulverizing it, and hydrating it to prepare a hydrate; and (e) nanoliposome-forming the hydrate from step (d) using a nanoliposome preparation device. BM-Simlipide prepared by the method of this invention significantly improves the emulsification stability of the cosmetic composition compared to conventional emulsification methods for dissolving vernix caseosa-like components.

Description

Technical Field

[0001] This invention relates to a method for manufacturing BM-simulipid and BM-simulipid manufactured by the method, and more specifically, to a method for manufacturing BM-simulipid comprising the step of mixing a vernix caseosa-like component with hydrogenated lecithin through a plurality of agitators including an in-line mixer and a disc mixer, and BM-simulipid manufactured by the method. Background Technology

[0002] Vernix caseosa is a sticky, white, creamy substance that typically forms in the final stages of pregnancy, covering the entire body of the fetus's skin. Vernix caseosa formation begins around 24 weeks of gestation, occurring simultaneously with the differentiation of the fetal epidermis and the formation of its protective barrier within the uterus.

[0003] Vernix caseosa is structurally simpler than the stratum corneum, consisting of a non-layered lipid matrix of fetal keratinocytes without intercellular desmosome connections. The keratinocytes of vernix caseosa are polygonal or oval, with a diameter of approximately 10-40 μm, and are composed of approximately 80% water, 10% protein, and 10% lipid.

[0004] Lipid composition analysis reveals that vernix caseosa possesses the following characteristics: it contains both nonpolar lipids derived from sebaceous glands (such as squalene, sterol esters, wax esters, and triglycerides) and barrier lipid components similar to those in the stratum corneum (such as cholesterol, free fatty acids, and ceramides). However, the content of barrier lipids in vernix caseosa is significantly lower than that in the stratum corneum.

[0005] The functions of vernix caseosa can be broadly categorized into those during the fetal period, the delivery process, and after birth. During the fetal period, due to its low surface tension, vernix caseosa can form a waterproof film inside the uterus. This film not only protects the fetal skin in the hot and humid aqueous environment but also promotes the maturation of the fetal stratum corneum and protects the fetus from inflammation inside and outside the amniotic membrane caused by bacterial infection.

[0006] During childbirth, vernix caseosa acts as a lubricant; after birth, it exhibits antioxidant, cleansing, thermoregulatory, and antibacterial properties. Furthermore, vernix caseosa can slowly release the high internal water content contained in keratinocytes, thereby enhancing the moisturizing and water-retention capacity of the skin. In addition, as an effective clinical therapeutic substance, vernix caseosa has been reported to promote the repair of the skin barrier in premature infants and help improve wound healing in adult skin.

[0007] Given the various skin barrier protective effects of vernix caseosa, it is worth considering using vernix caseosa or vernix caseosa-like substances as cosmetic ingredients. However, since vernix caseosa or vernix caseosa analogs contain a large number of poorly soluble substances, such as cholesterol esters and ceramides, their use as cosmetic ingredients requires mixing vernix caseosa or vernix caseosa analogs with an appropriate amount of surfactant to form an emulsion before application.

[0008] An emulsion is a liquid-liquid dispersion system in which one or more immiscible liquids are dispersed in another liquid, typically exhibiting a different particle size distribution ranging from tens of nanometers to tens of micrometers. Generally, when the average particle size of the dispersed phase is 20-500 nm, it is called a nanoemulsion; when the average particle size of the dispersed phase is 500 nm to 0.5 μm, it is called a microemulsion; and when the average particle size of the dispersed phase is greater than 0.5 μm, it is called a macroemulsion.

[0009] In the fields of pharmaceutical, food, or cosmetic compositions, the primary purpose of manufacturing emulsions is to dissolve poorly soluble substances in water to improve their absorption rate in the human body. A major advantage of this process is that when such emulsions are formulated into macroemulsions, the amount of poorly soluble substances trapped within the particles can be significantly increased, thereby substantially enhancing the absorption of these substances in the human body.

[0010] However, these macroemulsions are thermodynamically unstable and are prone to separation through various pathways such as flocculation, sedimentation, creaming, ostild ripening, and coalescence.

[0011] In order to manufacture the above emulsion, an emulsifier must be used, which can be a natural emulsifier or a synthetic emulsifier.

[0012] Natural emulsifiers include natural lecithin (such as soybean lecithin, egg yolk lecithin, hydrogenated soybean lecithin, and hydrogenated egg yolk lecithin), sphingosine, ganglioside, and phytosphingosine; while synthetic emulsifiers include diacylglycerol, phosphatidic acid, phosphocholine, phosphoethanolamine, phosphoglyceride, phosphoserine, mixed chain phospholipids, lysophospholipids, and PEGylated phosphol pids.

[0013] Natural lecithin is a mixture of diacylglycerols linked to phosphatidylcholine, consisting of stearic acid, palmitic acid, and oleic acid, commonly known as phosphatidylcholine. It can be extracted from various sources, including eggs and soybeans. Soy lecithin and egg yolk lecithin (including hydrogenated lecithin) have long been considered safe in biological systems, possessing emulsifying and soluble properties, and decomposing into harmless substances more quickly than most synthetic emulsifiers.

[0014] However, when using the aforementioned lecithin as an emulsifier to emulsify poorly soluble substances, problems such as high interfacial tension, long-time stability, and difficulty in controlling viscosity arise.

[0015] To address the aforementioned problems, Korean Patent Application No. 10-2002-0085832 (Invention Title: Liquid Crystal Film Emulsified Cosmetic Composition and Manufacturing Method Thereof) discloses a liquid crystal film emulsified cosmetic composition comprising an oil phase, an aqueous phase, and additives. In this liquid crystal film emulsified cosmetic composition, the oil phase comprises the following components: a plant-derived polysorbate surfactant having 16-18 carbon chains, 1-10% by weight; a fatty acid having 16-18 carbon chains, 0.1-10% by weight; a higher alcohol having 16-18 carbon chains, 0.1-10% by weight; and a nonpolar oil having 16-18 carbon chains, 1.0-10% by weight.

[0016] However, the aforementioned literature still suffers from insufficient emulsification stability and inadequate viscosity control.

[0017] Numerous academic papers and patent documents have been cited and clearly marked in this specification. The content of the cited papers and patent documents has been incorporated into this specification in its entirety to illustrate the level of the technical field to which this invention pertains and to more clearly explain the content of this invention. Summary of the Invention

[0018] Technical issues

[0019] The inventors discovered that when vernix caseosa-like ingredients used in cosmetic compositions are formulated into water-soluble emulsion-like cosmetic compositions, although the poorly soluble substance—the vernix caseosa-like ingredient—can be water-soluble, the recrystallization caused by van der Waals forces between emulsion particles leads to a significant decrease in emulsion stability. To address this problem, the inventors conducted extensive research. The results showed that by adding surfactants and poorly soluble compounds (such as vernix caseosa-like ingredients) used in conventional emulsion manufacturing, and then using a homogenization device incorporating a shear-mixing concept to manufacture emulsion-like cosmetic compositions, the homogeneity between emulsion particles was significantly improved, thereby significantly improving emulsion stability, thus completing this invention.

[0020] Therefore, the object of the present invention is to provide a method for manufacturing BM-Simlipid.

[0021] Furthermore, another object of the present invention is to provide BM-Simlipide manufactured by the above-described manufacturing method.

[0022] Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, the claims and the accompanying drawings.

[0023] Technical solution

[0024] This invention provides a method for manufacturing a cosmetic composition.

[0025] The inventors have discovered that when vernix caseosa analogs used in cosmetic compositions are formulated into water-soluble emulsion-like cosmetic compositions, although the poorly soluble vernix caseosa analogs can be water-soluble, the recrystallization caused by van der Waals forces between emulsion particles leads to a significant decrease in the stability of the emulsion. To address this problem, the inventors have conducted extensive research.

[0026] The results show that when surfactants and poorly soluble compounds (such as vernix caseosa-like ingredients) used in conventional emulsion manufacturing are added, the homogeneity between emulsion particles is significantly improved when a homogenization device incorporating the concept of shear mixing is used to manufacture cosmetic compositions in emulsion form, thereby significantly improving the stability of the emulsion.

[0027] The present invention provides a method for manufacturing BM-Simlipide, the method comprising the following steps: (a) in a first open tank, a vernix-like component with relative stability to high temperature is stirred with a solvent at 65-95°C by a stirrer;

[0028] (b) In the second open tank, the heat-sensitive hydrogenated lecithin, the glyceryl stearate to be premixed with the hydrogenated lecithin, and stearic acid are stirred at room temperature using a stirrer.

[0029] (c) The mixture in the first open tank and the mixture in the second open tank are mixed together by using an in-line mixer;

[0030] (d) After the mixture in step (c) is solidified, it is pulverized and hydrated to prepare a hydrate;

[0031] (e) The hydrate from step (d) is nanoliposomed using a nanoliposome preparation device.

[0032] As used in this specification, the term "emulsion" can refer to a state in which one of two immiscible liquids is dispersed in the other liquid in the form of small particles.

[0033] The term "macro-emulsion" as used in this specification can refer to an emulsion with an average particle size greater than 0.5 μm.

[0034] The term "BM-simulipids" as used in this specification may refer to a cosmetic composition containing ingredients that are the same as or similar to vernix caseosa.

[0035] The term "water-soluble, dissolved, or made to dissolve" as used in this specification can include dissolution, emulsification, liposome form in the general sense, and the fluorine-free surfactant state described in Korean Patent Application No. 10-2012-0027176 (Invention Title: Fluorine-free Surfactant and Method for Manufacturing Anhydrous and Fluorine-free Surfactant), Korean Patent Application No. 10-2012-0027177 (Invention Title: Anhydrous and Fluorine-free Surfactant Containing Linear Alkyl Chain Fatty Acids), Korean Patent Application No. 10-2012-0027174 (Invention Title: Fluorine-free Surfactant), and Korean Patent Application No. 10-2012-0027175 (Invention Title: Anhydrous and Fluorine-free Surfactant).

[0036] The term "poorly soluble" as used in this instruction manual refers to the property of a pharmacologically active preparation that it cannot be dissolved in an aqueous solution (such as water, physiological saline, injectable glucose solution, etc.). According to the United States Pharmacopeia (USP) / National Formulary (NF), solubility is typically expressed as the volume of solvent required to dissolve 1 gram of a drug at a specific temperature (e.g., 1 gram of aspirin in 300 ml of H₂O or 5 ml of ethanol at 25°C).

[0037] The term "in-line mixer" as used in this specification refers to a device that significantly improves the uniformity of emulsion particles, wherein interfacial separation and rotational circulation or radial mixing steps of the input material can be performed sequentially or simultaneously through the device's internal structure.

[0038] Although there are already mixers or homogenizing devices such as microfluidizers or high-pressure homogenizers that have similar stirring or homogenizing capabilities to the aforementioned inline mixers, the cosmetic compositions of the present invention can only be prepared by the aforementioned inline mixers and cannot be prepared by ordinary mixers, or even by mixers or homogenizing devices such as microfluidizers or high-pressure homogenizers.

[0039] The reason for this is that, generally, high-pressure homogenizers or microfluidizers typically break down and agitate specific substances by applying strong physical forces to one or more areas. While these devices can indeed achieve powerful breaking down and agitation at the point of force application, the transmitted physical force gradually weakens with increasing distance from the point of force application, resulting in less effective breaking down and agitation at locations farther from the point of force application. Therefore, although they can achieve fine particle breaking down and agitation, it is difficult to maintain consistent particle uniformity and ensure the formation of a stable emulsion.

[0040] However, for the aforementioned inline mixer, the hydrogenated lecithin and higher alcohols are subjected to a mixing process that is quantitatively divided into 1 / 2 to 1 / 10 each time as they pass through the unit blades contained inside the inline mixer pipe.

[0041] Furthermore, the more times a unit leaf passes through, the more the amount and proportion of hydrogenated lecithin and higher alcohols it binds to can be quantified according to the initial amount and proportion of hydrogenated lecithin and higher alcohols added.

[0042] Even in the initial stirring stage, the proportion and / or amount of hydrogenated lecithin and higher alcohols bound together may not yet be quantified, but as stirring continues, the proportion and amount bound together with hydrogenated lecithin and higher alcohols will gradually be quantified. Ultimately, as mentioned above, when hydrogenated lecithin and higher alcohols are bound together on the basis of quantified proportion and amount, their particle size tends to be uniform, thus significantly improving the uniformity of the product.

[0043] Therefore, the use of an inline mixer in this invention can be considered the most crucial component.

[0044] While the use of an inline mixer is an essential component in the manufacture of cosmetic compositions by the method of the present invention, it is not limited to the use of other agitators or homogenizing equipment in conjunction with the use of an inline mixer.

[0045] According to a preferred embodiment of the invention, the inline mixer comprises elements fixed within a pipe and twisted at 45-180° to the left and right or up and down, these elements being interconnected at angles of 30-150°. As fluid passes through and is transported, continuous flow division, rotational circulation, and radial mixing effects can be generated.

[0046] As used in this specification, the term "grind mixer" can refer to a mixer that generates stirring or homogenizing power through continuous face-to-face contact between two objects.

[0047] According to a preferred embodiment of the present invention, the vernix caseosa-like component in step (a) is preferably a mixture comprising ceramide, cholesterol, cholesterol ester-like components and phytosphingosine;

[0048] More preferred mixtures include ceramide NP as a ceramide; phytosteryl / octyldodecyllauroyl glutamate as a cholesterol or cholesterol ester-like component; and phytosphoprotein;

[0049] Further preferred mixtures include ceramide NP as a ceramide; phytosteryl / octyldodecyl lauroyl glutamate as a cholesterol or cholesterol ester-like component; phytosphingosine; triglyceride; and squalane;

[0050] The preferred mixture comprises 100 parts by weight of ceramide, and based on 100 parts by weight of ceramide, contains 30-100 parts by weight of cholesterol, 100-300 parts by weight of cholesterol ester analogs, 30-60 parts by weight of phytosphingosine, 100-200 parts by weight of triglycerides and 20-50 parts by weight of squalane.

[0051] In this invention, the various types of lipids and phospholipids contained in the above proportions are very important components. This is because extensive experiments have shown that when ceramide NP, cholesterol, phytosteryl / octyldodecyl lauroyl glutamate, phytosphingosine, triglycerides, and squalane are contained in the above proportions, the user experience and moisturizing effect of the cosmetic composition can be significantly improved.

[0052] According to a preferred embodiment of the present invention, the solvent in step (a) is preferably a substance selected from the group consisting of: glycerin, butylene glycol, propylene glycol, dipropylene glycol, diethylene glycol, benzyl alcohol, ethanol, ethoxydiglycol, polypropylene glycol, polyethylene glycol, sunflower oil, olive oil, corn oil, soybean oil, hydrogenated polyisobutene, octyldodecanol, isopropyl myristate, and isostearic acid.

[0053] More preferred solvents are substances selected from the group consisting of: glycerin, butylene glycol, propylene glycol, dipropylene glycol, diethylene glycol, benzyl alcohol, and ethanol.

[0054] The preferred solvent is butylene glycol.

[0055] According to a preferred embodiment of the present invention, the mixer in step (a) is preferably a millstone-type mixer.

[0056] In this invention, the use of a millstone-type mixer in step (a) is a crucial component. This invention mixes various poorly soluble substances, including ceramide, cholesterol, cholesterol ester analogs, and phytosphingosine, all of which have different particle sizes. Therefore, by thoroughly pulverizing these poorly soluble substances using a millstone-type mixer followed by homogenization using an inline mixer, the stability of the emulsion particles and the user experience are significantly improved compared to simply mixing with a paddle mixer and then homogenizing using an inline mixer.

[0057] According to a preferred embodiment of the present invention, the content of hydrogenated lecithin relative to 100 parts by weight of vernix caseosa-like components is preferably 10-200 parts by weight, more preferably 20-80 parts by weight, and most preferably 40-60 parts by weight. In conventional liposomes, 5-10% hydrogenated lecithin is typically used to dissolve 1.0% of vernix caseosa-like components. However, the cosmetic composition of the present invention containing vernix caseosa oily components requires only 0.2-1.0% hydrogenated lecithin to easily dissolve 1% of vernix caseosa-like components in water, which is a significant advantage.

[0058] According to a preferred embodiment of the present invention, the particle size of the hydrate in step (d) is preferably 0.5-30 μm, more preferably 1-10 μm, and most preferably 1.5-5 μm.

[0059] In this invention, the particle size of the hydrate in step (d) is crucial in its ability to dissolve poorly soluble substances. This is because particle size is a significant factor determining the amount of poorly soluble substances that the hydrophobic groups of a surfactant can accommodate.

[0060] According to a preferred embodiment of the present invention, the average range of BM-Simlipide particle size (based on the overall diameter) is preferably -200% to 200%, more preferably -30% to 30%, and most preferably -10% to 10%. Achieving high uniformity is a very important component in significantly delaying the recrystallization of BM-Simlipide.

[0061] The exact mechanism by which high uniformity can delay recrystallization has not yet been fully elucidated. However, it is speculated that the van der Waals force between BM-Simlipide particles manufactured by the method of this invention is counteracted by the repulsive force caused by the zeta potential between the particles, thereby delaying recrystallization.

[0062] As described above, in order to significantly improve the homogeneity of the hydrate in step (d), the present invention must use an inline mixer that includes a mixing blade structure with a shear mixing concept.

[0063] The term "shear mixing" as used in this specification refers to, as Figure 2 As shown, a fixed pipe contains 10 or fewer blades, preferably 4 or fewer, arranged in a fixed manner. The blades repeatedly change direction at regular intervals, continuously cutting the passing liquid into 2... n 3 n 4 n and 5 n Such as or a mixture thereof, thereby achieving micronization and homogenization. The solution is conceptually cut and mixed countless times each time it passes through individual blade units.

[0064] According to another embodiment of the present invention, the vernix caseosa-like component of the BM-Simlipide comprises: 100 parts by weight of ceramide; based on the 100 parts by weight of ceramide, it comprises 30-100 parts by weight of cholesterol, 100-300 parts by weight of cholesterol ester-like component, 30-60 parts by weight of phytosphingosine, and 20-50 parts by weight of squalane. The BM-Simlipide also comprises 10-200 parts by weight of hydrogenated lecithin based on the 100 parts by weight of vernix caseosa-like component. The average particle size of the BM-Simlipide is 0.5-30 μm, and the average particle size range is within ±200% of the diameter reference. Furthermore, the BM-Simlipide is manufactured using the vernix caseosa-like component and hydrogenated lecithin and employing an inline mixer.

[0065] Invention Effects

[0066] The features and advantages of this invention are summarized as follows:

[0067] (1) The present invention provides a method for manufacturing BM-Simlipide, comprising the following steps: (a) in a first open tank, a vernix caseosa-like component and a solvent that are relatively stable to high temperatures are stirred by a mixer at 65-95°C; (b) in a second open tank, hydrogenated lecithin that is sensitive to high temperatures, glyceryl stearate that needs to be premixed with hydrogenated lecithin and stearic acid are stirred by a mixer at room temperature; (c) the mixture in the first open tank and the mixture in the second open tank are mixed by an inline mixer; (d) the mixture in step (c) is solidified, pulverized and hydrated to prepare a hydrate; (e) the hydrate in step (d) is nanoliposomed by a nanoliposome preparation device.

[0068] (2) BM-Simlipide prepared by the method of the present invention has significantly superior user experience and moisturizing power.

[0069] (3) Compared with the traditional method of water-soluble vernix caseosa-like components by emulsification, BM-Simlipide prepared by the method of the present invention has the advantage of significantly improved emulsification stability in cosmetic compositions. Attached Figure Description

[0070] Figure 1 A system diagram of an inline mixer according to an embodiment of the present invention is shown.

[0071] Figure 2 Showing Figure 1 A partial cross-sectional view of the inline mixer shown.

[0072] Figure 3 Showing the illustration Figure 2 A three-dimensional view of the blade structure shown.

[0073] Figure 4 SEM images of the crystal structures of poorly soluble substances, including ceramides and other poorly soluble substances, in a cosmetic composition prepared by the method of this invention, serving as a control group. In the images, "1000" and "7000" represent the SEM magnification. Detailed Implementation

[0074] The present invention will be described in more detail below through embodiments. These embodiments are only used to describe the invention more specifically, and their scope is not limited by these embodiments, as will be apparent to those skilled in the art.

[0075] Example

[0076] In this specification, unless otherwise stated, the percentage used to express the concentration of a particular substance is: solid / solid (weight / weight)%, solid / liquid (weight / volume)%, liquid / liquid (volume / volume)%.

[0077] Preparation Example 1: Preparation of BM-Simlipide

[0078] Preparation Example 1-1: Preparation of Fine Powder

[0079] Following the formulations shown in Table 1 and the mixing conditions shown in Table 2, in a first open tank, a relatively high-temperature stable vernix caseosa-like component and dipropylene glycol were mixed by stirring using a first mixer. In a second open tank, high-temperature sensitive hydrogenated lecithin, glyceryl stearate (which needs to be premixed with hydrogenated lecithin), and stearic acid were mixed by stirring using a second mixer. Subsequently, the solutions in the first and second open tanks were mixed by stirring using a third mixer, then solidified and micronized to prepare a finely powdered mixture.

[0080] Preparation Examples 1-2: Nanoliposome Formation Process

[0081] The finely powdered mixture prepared by the method in Example 1-1 was hydrated to prepare a hydrate (5% by weight). Subsequently, the hydrate was nanoliposomed using a microfluidizer to prepare nanoliposomes with a particle size of 50-500 nm. Thus, BM-Simlipid was prepared for the following examples and control examples.

[0082] Table 1

[0083]

[0084]

[0085] Table 2

[0086]

[0087] Experiment Example 1: Temperature Control Bath Preservation Test

[0088] BM-Simlipide prepared by the methods of Comparative Examples 1 to 4 was stored in constant temperature baths at 4°C, 20°C, 38°C, and 50°C for 1 to 90 days to confirm its long-term stability. The results showed that at 38°C and 50°C, fine powder floated to the surface of the liquid after approximately 15 days of storage. However, BM-Simlipide prepared by the methods of Examples 1 and 2, as shown in Table 3, remained stable after 90 days of storage in constant temperature baths at 4°C, 20°C, 38°C, and 50°C.

[0089] Table 3

[0090]

[0091] Experiment Example 2: Cyclic Test (4-50℃)

[0092] BM-Simlipide, prepared by the methods of Comparative Examples 1 to 4, was alternately stored in constant temperature baths at 4°C and 50°C for one day at a time to confirm its long-term stability. The results showed that fine powder appeared to float on the liquid surface after about 3 days of storage.

[0093] However, the BM-Simlipide prepared by the methods of Examples 1 and 2, as shown in Table 4, still showed stable results even after being stored for 14 days.

[0094] Table 4

[0095] 1st 2nd 5th 7th 14th 30th 60 days 90 days Cyclic testing (4–50℃) Stablize Stablize Stablize Stablize Stablize - - -

[0096] Experiment Example 3: Low Temperature (-10℃) Test

[0097] To confirm the long-term stability of BM-Simlipide prepared by the methods of Comparative Examples 1 to 4, a low-temperature test was conducted at -10°C. The results showed that after storage at -10°C for approximately 3 days, fine powder particles floated to the surface of the liquid. However, BM-Simlipide prepared by the methods of Examples 1 and 2, as shown in Table 5, still exhibited stable results even after storage at -10°C for 7 days.

[0098] Table 5

[0099] 1st 2nd 5th 7th 15th 30th 60 days 90 days Result (-10℃) Stablize Stablize Stablize Stablize - - - -

[0100] Experiment Example 4: Phase Separation Test Using a Centrifuge

[0101] BM-Simlipide was prepared according to the methods of Examples 1 and 2. 1 mL of the preparation liquid was transferred into 1.5 mL tubes and sealed to prepare each sample. Subsequently, each sample was placed in a centrifuge, and phase separation was confirmed at different speeds (RPM: 3000, 5000, 7000, and 9000) and times. The control group used BM-Simlipide prepared according to the method of the control example. As shown in Table 6, no phase separation was observed in the hydrate prepared by the method of Example 1 at any speed; however, phase separation was observed in the hydrate prepared by the method of Example 2 after running at 7000 RPM for 20 minutes. In contrast, phase separation was observed in the hydrate prepared by the method of the control example after running at 3000 RPM for 10 minutes.

[0102] Table 6

[0103]

[0104]

[0105] Experiment Example 5: Experiment on Skin Barrier Improvement

[0106] To evaluate the irritation-relieving efficacy of BM-Simlipide in this invention, related experiments were conducted. Two emulsion formulations were used: one containing 10% by weight of BM-Simlipide prepared according to the method in Example 1, and the other a formulation without BM-Simlipide (control group). Six volunteers were recruited and completed the clinical trial. The volunteers were aged 26 to 41 years, and were all men and women with healthy skin. Volunteers meeting the experimental criteria were selected, and the test substance was applied to both the test area and the untreated control area on their forearms. The test substance was applied twice daily (8 hours apart) at a dose of 2 μL / cm². Tape stripping was performed before application, and transepidermal water loss (TEWL) was measured at various time points on days 1, 2, 3, and 5 after application. The results showed that transepidermal water loss increased in all treatment groups after tape stripping. However, compared to the untreated group, the experimental group treated with the emulsion recovered transdermal moisture loss more quickly. In particular, the emulsion formulation containing BM-Simlipide prepared by the method of Example 1 exhibited a faster transdermal moisture loss recovery effect.

[0107] Table 7

[0108]

[0109]

[0110] Structure and function of inline mixer

[0111] The emulsifying device and inline mixer in the embodiments of the present invention will be described in detail below with reference to the accompanying drawings.

[0112] Figure 1 A system diagram of an emulsification apparatus according to an embodiment of the present invention is shown.

[0113] like Figure 1 As shown, an emulsification apparatus (1) according to an embodiment of the present invention includes: an inline mixer (10), an emulsification tank (20), a feed pipe (30), a circulation pipe (40, 50), a circulation valve (41), a pump (60), a discharge pipe (70), a discharge valve (71), and a mixer (80).

[0114] The emulsifying tank (20) contains the mixture (C) to be emulsified. In order to feed the mixture (C) and other substances into the emulsifying tank (20), a feed pipe (30) is connected to the upper part of the emulsifying tank (20).

[0115] The lower and upper parts of the emulsifying tank (20) are connected to circulation pipes (40, 50), respectively. An inline mixer (10), a circulation valve (41) and a pump (60) are installed on the circulation pipes (40, 50).

[0116] The circulation valve (41) is installed on the circulation pipe (40) connected to the lower part of the emulsifying tank (20). By controlling the opening and closing of the circulation valve (41), the mixture (C) can flow through the circulation pipe (40) or stop flowing.

[0117] The mixer (80) can be positioned below the emulsifying tank (20) as shown in the figure. When the mixture (C) fed into the emulsifying tank (20) through the feed pipe (30) has a low degree of homogenization, for example, when there are large solid or liquid particles in the mixture (C), the mixer (80) can be used to reduce the size of these particles.

[0118] A discharge pipe (70) is connected to the lower part of the emulsification tank (20), and a discharge valve (71) is installed on the discharge pipe (70). When the emulsification process of the mixture (C) is completed, the discharge valve (71) is opened, and the emulsified mixture (C) can be discharged from the emulsification tank (20) through the discharge pipe (70).

[0119] When the circulation valve (41) is open and the pump (60) is running, the mixture (C) is introduced into the inline mixer (10) through the circulation pipe (40) connecting the lower part of the emulsifying tank (20) to one side of the inline mixer (10). The mixture (C) processed by the inline mixer (10) is then returned to the emulsifying tank (20) through the circulation pipe (50) connecting the upper part of the emulsifying tank (20) to the other side of the inline mixer (10).

[0120] The inline mixer (10) reduces the particle size of the particles contained in the passing mixture (C) while homogenizing the particle size after reduction. To this end, the inline mixer (10) induces flow division, rotational circulation and radial mixing during the flow of the mixture (C).

[0121] As described above, the operation process of the emulsifying device (1) with the above connection relationship is as follows:

[0122] First, the mixture (C) to be emulsified is introduced into the emulsification tank (20) through the feed pipe (30). If necessary, the mixer (80) can be activated to improve the mixing degree of the mixture (C) and reduce the size of the particles contained in the mixture (C).

[0123] Subsequently, the circulation valve (41) is opened and the pump (60) is started, allowing the mixture (C) to enter the inline mixer (10) through the circulation pipe (40) for processing, and then return to the emulsification tank (20) through the circulation pipe (50). In this way, the mixture (C) repeatedly passes through the inline mixer (10), and the degree of emulsification gradually increases.

[0124] When it is determined that the mixture (C) has been fully emulsified, stop the operation of the pump (60) and close the circulation valve (41), and then open the discharge valve (71) to discharge the emulsified mixture (C) through the discharge pipe (70).

[0125] Through the above process, the mixture (C) can achieve a very high homogenization and emulsification effect using the emulsification device (1).

[0126] In addition, in order to allow sufficient flow division, rotational circulation and radial mixing to occur during the flow of the mixture (C) within the inline mixer (10), the inline mixer (10) needs to have a certain level of pipe resistance.

[0127] Therefore, the pump (60) needs to be able to apply sufficient output pressure to the mixture (C) flowing into the inline mixer (10) through the circulation pipe (40) and prevent backflow. For this purpose, a plunger pump or a gear pump can be used. Plunger pumps and gear pumps are common technologies and will not be described in detail here.

[0128] Figure 2 Showing Figure 1 The diagram shows a partial cross-sectional view of the inline mixer. Figure 3 To explain Figure 2 The diagram shows a three-dimensional representation of the blade structure. The following will combine... Figure 2 and Figure 3 Please provide an explanation.

[0129] First, refer to Figure 2 The inline mixer (10) includes blades (11) and pressure-resistant tubes (12).

[0130] The pressure-resistant pipe (12) is a hollow pipe capable of withstanding high pressure, with its two ends as follows: Figure 1 The connection to the circulation pipe is shown. In order to facilitate operation when the inline mixer (10) needs to be replaced due to aging or other reasons, the inline mixer (10) can be detachably connected to the circulation pipe.

[0131] The blade (11) is located inside the pressure-resistant tube (12).

[0132] As shown in the figure, the blade (11) includes a series of unit blades (11a) arranged within the pressure-resistant tube (12). Each unit blade (11a) includes a first element (110) and a second element (120).

[0133] like Figure 3 As shown, the first element (110) includes a first element body (111). The first element body (111) has a front edge (112), a rear edge (113), and a pair of side edges (114).

[0134] Here, the terms "front" and "back" refer to the inline mixer ( Figure 1 The direction of flow of mixture (C) in (10) is defined. The direction in which mixture (C) flows in is called the forward direction, and the direction in which mixture (C) flows out is called the backward direction.

[0135] The first element body (111) is a rectangular component with a front edge (112), a rear edge (113), and a pair of opposite side edges (114) as its four sides. It is twisted in a single direction (A) around a first center line (not shown) connecting the center points of the front edge (112) and the rear edge (113) to form a curved shape.

[0136] In other words, the first element body (111) gradually twists along direction A as shown in the figure from the front edge (112) to the rear edge (113), forming a spiral shape.

[0137] Furthermore, when the first element body (111) is disposed inside the pressure-resistant tube (12), its side edge (114) contacts the inner wall of the pressure-resistant tube (12). Therefore, through the first element body (111), a flow channel with a spiral shape in the A direction is formed inside the pressure-resistant tube (12) along the flow direction of the mixture (C).

[0138] The second element (120) includes a second element body (121). The second element body (121) has a front edge (122), a rear edge (123), and a pair of side edges (124).

[0139] The second component body (121) is a rectangular component with four sides: a front edge (122), a rear edge (123), and a pair of side edges (124). It is twisted in another direction (B) around a second center line (not shown) connecting the center points of the front edge (122) and the rear edge (123) to form a curved shape.

[0140] In other words, the second element body (121) gradually twists along direction B as shown in the figure from the front edge (122) to the rear edge (123), forming a spiral shape.

[0141] Furthermore, when the second element body (121) is disposed inside the pressure-resistant tube (12), its side edge (124) contacts the inner wall of the pressure-resistant tube (12). Therefore, through the second element body (121), a flow channel with a spiral shape in the B direction is formed inside the pressure-resistant tube (12) along the flow direction of the mixture (C).

[0142] Furthermore, the first element (110) and the second element (120) can be combined with each other.

[0143] The first element (110) and the second element (120) are connected in the following manner: the first center line (not shown) of the first element (110) and the second center line (not shown) of the second element (120) are arranged on a straight line as shown in the figure, forming a common center line (CL). At the same time, the rear edge (113) of the body of the first element (111) contacts and joins the front edge (122) of the body of the second element (121).

[0144] During the bonding process, the rear edge (113) and the front edge (122) are intersecting each other. In other words, the rear edge (113) and the front edge (122) are not parallel, but intersect at a certain angle.

[0145] Here, the angle formed between the front edge (112,122) and the rear edge (113,123), that is, the degree of twist of the rear edge (113,123) relative to the front edge (112,122), can be arbitrarily selected as needed.

[0146] Experimental results show that the emulsification efficiency of the mixture (C) is high when the rear edge (113, 123) forms an angle of 90° to 180° relative to the front edge (112, 122); especially when the angle is 180°, the emulsification efficiency is the highest. Therefore, the torsion angle of the first element body (111) along the A direction and the torsion angle of the second element body (121) along the B direction can be set to 180° respectively.

[0147] Furthermore, when the first element (110) and the second element (120) are connected, the angle formed between the rear edge (113) and the front edge (122) can be arbitrarily selected as needed. However, experimental results show that the emulsification efficiency of the mixture (C) is highest when the angle is 90°, that is, when the rear edge (113) and the front edge (122) are perpendicular. Therefore, the first element (110) and the second element (120) can be connected in a way that forms a 90° angle between the rear edge (113) and the front edge (122), that is, in a perpendicular arrangement.

[0148] It should be noted that the terms "parallel" and "perpendicular" in this instruction manual do not refer to "parallel" and "perpendicular" in a strict mathematical sense, but rather to "parallel" and "perpendicular" that take into account various errors such as processing errors and assembly errors.

[0149] Furthermore, as previously mentioned, the blade (11) comprises multiple unit blades (11a). Thus, the blade (11) exhibits a structure in which the first element (110) and the second element (120) are arranged alternately in a row.

[0150] In other words, the rear edge (123) of the second element (120) is again connected to the front edge (112) of the first element (110), forming a continuous structure. Experimental results show that, in this case, the emulsification efficiency of the mixture (C) is highest when the front edge (112) connected to the rear edge (123) is perpendicular. Therefore, the blades (11) can be arranged as a continuous structure in which the rear edge (113) of the first element (110) and the front edge (122) of the second element (120), as well as the front edge (112) of the first element (110) and the rear edge (123) of the second element (120) are all orthogonally arranged.

[0151] Figure 2 The F represented by the dashed line is part of the flow of the mixture (C).

[0152] Here, F indicates that, under the arrangement of the first element (110) and the second element (120) described above, the flow is divided into F1 and F2. This division occurs continuously along the length of the blade (11) as the mixture (C) flows in the direction of the straight arrow.

[0153] Therefore, the mixture (C) passes through the inline mixer ( Figure 1 When mixing and separating are performed multiple times (10), the emulsification degree of the mixture (C) is significantly improved, that is, the homogenization level of the mixed state.

[0154] In addition, such as Figure 3 As shown, directions A and B are opposite to each other, therefore, the mixture (C) will repeatedly experience rotation in both directions A and B as it flows (F) along the blade (11). In other words, the mixture (C) undergoes rotation in both directions as it passes through the inline mixer (F). Figure 1 When 10), it will rotate alternately in one direction and in the opposite direction around an axis parallel to the length direction of the blade (11).

[0155] Therefore, the mixture (C) not only undergoes multiple directional changes, but also radial mixing due to inertial effects, which significantly improves the emulsification degree of the mixture (C).

[0156] Thus, when the mixture (C) passes through the inline mixer (10), its components, such as the aforementioned insoluble organic substances, solvents that can dissolve insoluble substances, and surfactants, form a small and uniform particle structure. These particles have a very fine particle size, thereby giving the emulsion a high degree of uniformity and stability.

[0157] Symbol Explanation

[0158] 1: Emulsification device

[0159] 10: Inline Mixer

[0160] 11: Leaf blade

[0161] 11a: Single blade

[0162] 110: First Component

[0163] 111: First component body

[0164] 112: Leading edge

[0165] 113: Back edge

[0166] 114: Side edge

[0167] 120: Second Component

[0168] 121: Second component body

[0169] 122: Leading edge

[0170] 123: Back edge

[0171] 124: Side edge

[0172] 12: Pressure-resistant pipe

[0173] 20: Emulsifying tank

[0174] 30: Feed pipe

[0175] 40, 50: Circulation pipe

[0176] 41: Circulation valve

[0177] 60: Pump

[0178] 70: Discharge pipe

[0179] 71: Discharge valve

[0180] 80: Mixer

[0181] 200: Inline Mixer

[0182] 201: Blade

[0183] 201a: Single blade

[0184] 202: Pressure-resistant pipe

[0185] 210: First Component

[0186] 211: First component body

[0187] 212: Spacing protrusion

[0188] 213: Through hole

[0189] 214: Side edge

[0190] 220: Second Component

[0191] 221: Second component body

[0192] 222: Spacing protrusion

[0193] 223: Through hole

[0194] 224: Side edge

[0195] 300: Inline Mixer

[0196] 301: Blade

[0197] 302: Pressure-resistant pipe

[0198] 310: Blade body

[0199] 311: Mixed protrusions

[0200] 312: Leading edge

[0201] 313, 314: Dividing surfaces

[0202] 315: Support surface

Claims

1. A method for preparing BM-Simlipide, comprising the following steps: (a) In the first open tank, the vernix caseosa-like components and solvents that are relatively stable to high temperatures are stirred by a mixer at 65-95°C. (b) In a second open tank, hydrogenated lecithin, which is sensitive to high temperatures, glyceryl stearate, and stearic acid, which need to be premixed with hydrogenated lecithin, are stirred by a mixer at room temperature. (c) Using an inline mixer, the mixture in the first open tank and the mixture in the second open tank are combined to prepare a mixture; (d) The mixture from step (c) is solidified, pulverized, and hydrated to prepare a hydrate; and (e) Use a nanoliposome preparation apparatus to nanoliposome the hydrate from step (d).

2. The method according to claim 1, wherein the vernix caseosa analogue in step (a) comprises ceramide, cholesterol, cholesterol ester analogue and phytosphingosine.

3. The method according to claim 2, wherein the cholesterol ester analogue is phytosteryl / octyldodecyl lauroyl glutamate, and the ceramide is ceramide NP.

4. The method of claim 2, wherein the vernix caseosa-like component further comprises triglycerides and squalane.

5. The method according to claim 4, wherein the vernix caseosa analogue comprises 100 parts by weight of ceramide; and based on the 100 parts by weight of ceramide, it comprises 30-100 parts by weight of cholesterol, 100-300 parts by weight of cholesterol ester analogue, 30-60 parts by weight of phytosphingosine, 100-200 parts by weight of triglycerides and 20-50 parts by weight of squalane.

6. The method according to claim 1, wherein the solvent in step (a) is dipropylene glycol.

7. The method according to claim 1, wherein the mixer in step (a) is a disc mixer.

8. The method of claim 1, wherein the BM-Simlipide comprises 10-200 parts by weight of hydrogenated lecithin based on 100 parts by weight of a vernix caseosa-like component.

9. The method according to claim 1, wherein the average particle size of the BM-Simlipid is 0.5-30 μm, and the average particle size range is within ±200% of the diameter reference.

10. A BM-Simlipid, characterized in that: The vernix caseosa-like component includes 100 parts by weight of ceramide; based on the 100 parts by weight of ceramide, it contains 30-100 parts by weight of cholesterol, 100-300 parts by weight of cholesterol ester-like component, 30-60 parts by weight of phytosphingosine and 20-50 parts by weight of squalane. The BM-Simlipide further comprises 10-200 parts by weight of hydrogenated lecithin based on 100 parts by weight of a vernix caseosa-like component. The average particle size of the BM-Simlipid is 0.5-30 μm, and the average particle size range is within 200% of the diameter reference. The BM-Simlipide is prepared by processing vernix caseosa-like components and hydrogenated lecithin using an inline mixer.

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