Citron essential oil nanolipid carrier and its preparation and application

Abstract

The present invention discloses a method for preparing citron essential oil nanolipid carrier (NLC), comprising: (a) mixing an emulsifier and fatty acid glycerides and heating until a homogeneous mixture is obtained; (b) adding a moisturizer, active ingredient, and citron extract to the mixture in (a), stirring and emulsifying to form a homogeneous mixture; and (c) homogenizing the mixture obtained in (b) at high speed using a homogenizer to obtain a transparent liquid citron essential oil nanolipid carrier. The raw material in (a) further contains 0-20 wt% coenzyme Q10. This citron essential oil nanolipid carrier can be further formulated into a face cream, exhibiting excellent moisturizing and antioxidant properties, demonstrating significant skincare value and industrial applicability.

Description

Technical Field

[0001] The present invention discloses a method for preparing citron essential oil nanolipocarrier (NLC), comprising: (a) mixing an emulsifier and fatty acid glycerides and heating until a homogeneous mixture is obtained; (b) adding a moisturizer, active ingredient, and citron extract to the mixture in (a), stirring and emulsifying to form a homogeneous mixture; and (c) homogenizing the mixture obtained in (b) at high speed using a homogenizer to obtain a transparent liquid citron essential oil nanolipocarrier. The raw material in (a) further contains 0-20 wt% coenzyme Q10. This citron essential oil nanolipocarrier can be further formulated into a face cream, exhibiting excellent moisturizing and antioxidant properties, demonstrating significant skincare value and industrial applicability. Prior Technology

[0002] In recent years, with the rise of environmental awareness, people have begun to pay attention to the importance of natural plant-based cosmetics. Natural plant-based cosmetics are not only safer for people's skin, but also help the sustainable development of the environment. The formula of citron essential oil nano lipid carrier is in line with the modern green and environmentally friendly concept.

[0003] This novel nano-drug delivery system has expanded from pharmaceutical research to the cosmetic field. On one hand, embedding active ingredients within the microporous structure of a nano-structured lipid carrier improves the photostability of the active ingredients. On the other hand, it enables controlled release of active ingredients, thus solving problems such as high concentrations and short durations of action of active ingredients on the skin surface in the initial stages of cosmetic application. Recent studies have shown that solid particles themselves scatter ultraviolet light, and formulations encapsulating sunscreen agents exhibit a synergistic effect on sun protection. Simultaneously, it can reduce the penetration of sunscreen agents and their derivatives into the skin, improving the safety of sunscreen formulations. Therefore, NLC is a highly promising encapsulation carrier.

[0004] The technology of nanoliposomes was first proposed by Alec D. Bangham in the 1960s, and it attracted widespread attention from researchers as a nanoscale drug carrier. With further research, in the 1990s, more researchers turned their attention to preparing nanoparticles from solid lipids, namely solid lipid nanoparticles. Subsequently, based on solid lipid nanoparticles, nanostructured lipid carriers were developed, and both are collectively referred to as solid nanoliposomes. Currently, the focus of research on the application of solid nanoliposomes has shifted to topical drugs and cosmetics, and this technology provides new research ideas for improving the efficacy of cosmetics.

[0005] The aim was to develop a carrier-based formulation technology using a high-pressure homogenization method to address the poor compatibility and photochemical stability of OMC and BP3. Notably, there are currently no NLC formulations that simultaneously encapsulate two sunscreen agents, and studies on the interaction between sunscreen agents and excipients using differential scanning calorimetry are rarely reported. Furthermore, the physicochemical properties of the lipid nanoparticles, such as particle size, morphology, potential, and encapsulation efficiency, were investigated in detail, and the UV absorption performance and photostability of the optimized formulation were evaluated.

[0006] Essential oils are secondary metabolites of plants, extracted from various parts of the plant. They emit pleasant aromas and possess various physiological functions; their antioxidant and antibacterial properties have been applied to food. Currently, there are numerous methods for essential oil extraction, including steam distillation, water distillation, ester extraction, solvent extraction, and cold pressing. Different extraction methods result in different compositions of essential oils. Plant essential oils are composed of multiple components, and due to these differences, their physiological functions also vary. Research analyzing various commercially available essential oils has revealed that citrus essential oils widely possess antioxidant capabilities. The complexity of their composition leads to synergistic and antagonistic effects between components, resulting in variations in their antioxidant capacity. In aromatherapy, peppermint oil can improve gastrointestinal motility, eucalyptus oil can improve upper respiratory tract infections, and grapefruit oil can stimulate the sympathetic nervous system and inhibit the parasympathetic nervous system, thereby increasing plasma glycerol levels and blood pressure, and reducing appetite. The main compound limonene in grapefruit oil exhibits similar effects. Limonene, a major compound in citrus essential oils, has also been shown to have anti-cancer effects by regulating liver enzyme activity.

[0007] The variety, maturity, and tissue composition of different parts of the plant are all major factors influencing the differences in essential oil composition. Therefore, this study mainly explores the changes in maturity of citron fruit as its color changes from green to yellow, and the distribution of essential oil in the peel and pulp is also a factor under investigation. Therefore, this study will extract the essential oil using steam distillation, analyze its structure and composition using GC and GC / MS, and assess its antioxidant capacity. Furthermore, column chromatography will be used to differentiate the essential oil and explore whether the differentiating agents can increase antioxidant capacity.

[0008] Nanostructured lipid carriers (NLCs) can disrupt the regular crystal structure of solid lipids, increasing the proportion of irregular crystal forms in the microparticle structure. Different encapsulation morphologies can improve the drug loading capacity, stability, and permeability of the carriers; for example, carriers smaller than 200 nm can improve skin hydration and elasticity (Pardeike et al., 2009). According to Zhong et al. (2011), using high-shear homogenization followed by 15 minutes of ultrasonic dispersion during NLC preparation helps stabilize the NLCs. Adding an appropriate amount of surfactant during NLC preparation can help reduce the average particle size of the sample; however, adding excessive surfactant can broaden the particle size distribution and increase the particle size.

[0009] Nanostructured lipid carriers (NLCs) are a novel type of carrier developed based on SLNs, overcoming the aforementioned shortcomings of SLNs. NLCs replace solid lipids with a mixture of solid and liquid lipids, resulting in a more irregular, defective structure. This creates more space to accommodate more active substances, effectively improving encapsulation efficiency and the stability of active substances during long-term storage. NLCs exist in an incomplete crystalline and amorphous state, making them more suitable for encapsulating active ingredients compared to SLNs. Currently, there are three main structures for encapsulating active ingredients using NLCs: amorphous, imperfect, and multiple.

[0010] Amorphous NLCs are prepared by adding a certain amount of special lipids during the process. The lipids undergo melting, dispersion, and cooling to form a solid matrix. This type of NLC matrix does not crystallize but forms an amorphous state, composed of rectangles with many gaps and vacancies. The amorphous matrix not only increases the space for accommodating bioactive substances, but its non-crystallization also avoids the leakage problems caused by crystal transformation. Defective NLCs use a mixture of solid and liquid lipids with significantly different chemical properties as the matrix, increasing the distance between fatty acid chains and disrupting the regular arrangement of molecules to form larger spaces to accommodate active ingredients; therefore, they are also called imperfect NLCs. They are obtained by homogenizing and cooling special oils, and are solid but do not crystallize at room temperature. Since the solubility of active ingredients in liquid lipids is usually higher than that in solid lipids, a third type of composite NLC was developed. When the content of liquid lipids in the solid-liquid mixed lipids increases to a certain level, the lipid matrix undergoes phase separation, forming a large number of oily nanodroplets. These oily nanodroplets are dispersed in a solid lipid phase, which in turn is dispersed in an aqueous phase. Therefore, the composite NLC is also considered an O / F / W (liquid lipid / solid lipid / water complex) system. Simultaneously, the solid lipid surrounding these droplets immobilizes the oily nanocompartments. That is, tiny liquid nanocompartments are contained within the solid lipid matrix and separated from it. This model allows for controlled release of the active ingredient, and the lipid matrix prevents burst release of the active ingredient, thereby significantly increasing the loading capacity of the active ingredient. Summary of the Invention

[0011] The present invention discloses a method for preparing citron essential oil nanolipid carrier (NLC), comprising: (a) mixing an emulsifier and fatty acid glycerides and heating until a homogeneous mixture is obtained; (b) adding a moisturizer, active ingredient, and citron extract to the mixture in (a), stirring and emulsifying to form a homogeneous mixture; and (c) homogenizing the mixture obtained in (b) at high speed using a homogenizer to obtain a transparent liquid citron essential oil nanolipid carrier.

[0012] Among them, (a) the raw materials contain 0-20 wt% coenzyme Q10. Among them, lecithin is the best emulsifier.

[0013] A face cream containing citron essential oil nanolipid carrier (NLC) comprises: 0.5-15% citron extract nanolipid carrier, 0.5-5 wt% emulsifier, 0-20 wt% active ingredient, 0.1-5 wt% preservative, 60-95 wt% water, 0-20 wt% other moisturizer, and 0-5 wt% water-soluble polymer.

[0014] Citron (Citrus medica L.), also known as Medicinal citron, and Buddha's hand (Citrus medica L. var. sarcodactylis Hort.), also known as Fingeredcitron, are both fruits of Citron medica L., belonging to the same subspecies, but with a difference in fruit morphology. Buddha's hand fruit is finger-cleft or fist-shaped, while citron fruit is simply oval. Furthermore, citron pulp contains seeds, while Buddha's hand pulp does not. Both are primarily sold in the market as medicinal materials, sharing similar pharmacological effects such as soothing the liver, regulating qi, and protecting the stomach. However, citron is more effective in relieving coughs and phlegm than Buddha's hand. The two cannot be distinguished by aroma or the appearance of the processed fruit, leading to confusion and difficulty in accurate identification.

[0015] The preparation of NLCs typically utilizes high-pressure homogenizers. During operation, pre-emulsification is necessary, followed by high-pressure acceleration of the emulsion through a narrow opening, miniaturizing the particles under high shear and cavitation forces. Simultaneously, factors such as pressure and cycle time during operation alter the rheological properties and particle size of NLCs. Homogenization can be categorized into hot and cold homogenization methods. However, lipids are difficult to keep warm during high-pressure homogenization, and waxy raw materials solidify upon cooling, causing wear and damage to the high-pressure homogenizer, and preventing the sample from achieving the desired homogenization effect. Besides improving the stability of encapsulated active ingredients, NLCs exhibit excellent skin adhesion, which increases with decreasing particle size. When particles adhere to the skin surface, their aggregation creates an encapsulation effect, reducing moisture loss and increasing skin hydration. The type, ratio, molecular weight, melting point, and hydrophilicity of lipids all affect the average particle size and distribution of NLCs. A wide variety of lipids can be used in the preparation of NLCs, including triglycerides, gycerides, fatty acids, steroids, and waxes, all of which can be used as solid lipid raw materials. Studies by J. Volkhard et al. have shown that different lipids can affect the release rate of the active ingredient.

[0016] Preparation of Citron Extract of the Invention

[0017] Citron slices were placed in serum bottles and soaked in solvents such as methanol, ethyl acetate, and acetone for two weeks. After soaking, the fruit residue was filtered out as the first filtration. After the first filtration, a Buchner funnel was used for a second filtration. The solution from the second filtration was then concentrated in a vacuum concentrator to obtain the sample extract. The extraction yield is shown in Table 1. The antioxidant capacity of the extract was then tested.

[0018] Determination of the basic properties of citron extract of the present invention:

[0019] DPPH antioxidant capacity test

[0020] 1. Take 7.5 mL of DPPH test solution, add 5 mL of pure water and 1.5 mL of 95% ethanol, ultrasonically shake for 10 minutes, shake evenly, keep at room temperature in the dark for 30 minutes, put it in a centrifuge set to 3500 rpm, centrifuge for 3 minutes, and set the spectrophotometer wavelength to 517 nm to test the blank absorbance value of the DPPH test solution.

[0021] 2. Prepare sample extract solutions with concentrations of 1%, 10%, 30%, 50%, and 70%, take 5 mL of each, add 1.5 mL of 95% ethanol to each, ultrasonically shake for 10 minutes, shake evenly, add 7.5 mL of DPPH test solution, mix well, incubate at room temperature in the dark for 30 minutes, and centrifuge at 3500 rpm for 3 minutes.

[0022] 3. Place the prepared sample groups into the colorimetric cell, put them into the colorimetric tube holder of the spectrophotometer, measure and record the absorbance at a wavelength of λ=517nm.

[0023] 4. Prepare the vitamin C control group. Prepare vitamin C concentrations of 1%, 0.5%, 0.1%, 0.05%, and 0.01%. Take 1 mL of each concentration, add 1.5 mL of 95% ethanol, ultrasonically shake for 10 minutes, shake evenly, add 7.5 mL of DPPH test solution, mix well, and incubate at room temperature in the dark for 30 minutes.

[0024] 5. Place the prepared control group into the colorimetric cell, put it into the colorimetric tube holder of the spectrophotometer, measure the absorbance at wavelength λ=517nm and record it.

[0025] DPPH. Free radical scavenging calculation formula % = (blank group - sample group) ÷ blank group x 100%.

[0026] The results of the DPPH antioxidant capacity test of the extract are shown in Table 2.

[0027] The present invention discloses a method for preparing citron essential oil nanolipid carriers (NLCs), comprising: (a) mixing an emulsifier and fatty acid glycerides and heating until a homogeneous mixture is obtained; (b) adding a humectant, active ingredient, and citron extract to the mixture in (a), stirring and emulsifying to form a homogeneous mixture; and (c) homogenizing the mixture obtained in (b) at high speed using a homogenizer to obtain a transparent liquid citron essential oil nanolipid carrier. The raw materials in (a) further contain 0-20 wt% coenzyme Q10. The preferred emulsifier is lecithin. The nanolipid carrier formulations are shown in Tables 3 and 4.

[0028] A face cream containing citron essential oil nanolipid carrier (NLC) comprises: 0.5-15% citron extract nanolipid carrier, 0.5-5 wt% emulsifier, 0-20 wt% active ingredient, 0.1-5 wt% preservative, 60-95 wt% water, 0-20 wt% other moisturizer, and 0-5 wt% water-soluble polymer.

[0029] Preparation of face cream containing citron essential oil nanolipid carriers (NLC)

[0030] 1. First, dissolve the oil phase raw material A and the water phase raw material B separately in containers by heating and stirring in a water bath.

[0031] 2. Slowly pour B into A and react in a water bath until emulsification is complete. Remove the mixture and stir while cooling.

[0032] 3. After cooling to 35℃, add the ingredients in item C: citron essential oil nanolipid carrier (NLC) and preservative in sequence, and stir to complete the face cream.

[0033] The formulation of a face cream containing citron essential oil nanolipid carriers (NLC) is shown in Table 5.

[0034] Determination of basic properties of citron oil-containing nanolipid carriers (NLC)

[0035] Particle size analysis (Partica mini LA-350)

[0036] The particle size of the citron essential oil nanolipid carrier (NLC) in this experiment was measured using a particle size analyzer. The prepared citron essential oil nanolipid carrier (NLC) was injected into a four-sided transparent quartz tube, placed in the particle size analyzer, and the parameters (including viscosity, refractive index, and light incident angle) were set for measurement.

[0037] step:

[0038] (a) Select the option via computer connection.

[0039] (b) Take 100 ml of the sample dispersion and 1 g of the sample.

[0040] (c) Set the measurement speed to approximately 10 seconds, wait for the measurement results and record them.

[0041] microscope.

[0042] (1) Observe using the magnification of an optical microscope.

[0043] (2) Optical microscopes can be divided into reflection microscopes and transmission microscopes depending on the sample. Reflection microscopes are generally used on opaque objects. Light shines on the object and is reflected before entering the microscope. They are mostly used in engineering and materials science. Transmission microscopes are generally used on transparent or very thin objects. Light can pass through the object and enter the microscope.

[0044] Stability

[0045] The prepared citron essential oil nanolipid carriers (NLCs) were placed into centrifuge tubes, each about eight-tenths full. The tubes were then placed in a centrifuge and centrifuged at 3000 rpm for 5 minutes and 10 minutes, respectively, and their layering was observed.

[0046] The rheological behavior of each face cream was determined using a viscometer (Brookfield Viscometer-MODEL DV-III+) with an appropriate spindle.

[0047] step:

[0048] (1) The drum is attached to the viscometer and can be held with one hand or placed on a special stand. (The instrument must be kept horizontal in all situations).

[0049] (2) Immerse the rotary drum in the solution to be measured, turn on the power, and select the rotary drum number.

[0050] (3) The viscosity can be measured immediately after pressing the start button.

[0051] Multifunctional skin test for face cream containing citron essential oil nanolipid carrier

[0052] Using the MPA580 skin analyzer

[0053] (a) Black and red pigment measurement probe.

[0054] (b) Probe Tewameter-TM300 for measuring transdermal water loss capacity.

[0055] (c) Skin moisture measurement probe (Probe of Corneometer-CM825).

[0056] Steps: Set the lens to the detection position of the surface skin (upper texture). After attaching the black moisture test paper to the moisture test probe, lightly touch the test paper end of the probe to the skin to be tested, and then take an image of the test paper end of the moisture test probe with the lens.

[0057] The emulsifiers described in this invention are selected from: esterified carboxylic acids and their salts, sodium alkyl polyoxyethylene ether carboxylate, phosphate ester salts, nonionic surfactants, and lecithin. Based on their structural formulas, they can be broadly classified into four types: (1) ethers, (2) esters, (3) alkyl alcohol amides, and (4) amides. Ethers - Span series: Sorbitan fatty acid esters, sorbitan monopalmitate, sorbitan monostearate, sorbitan monooleate; Ethers - Tween series: Polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan tristearate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan trioleate, fatty alcohol polyoxyethylene ethers, alkylphenol polyoxyethylene ethers, polyethers, polyethylene glycol fatty acid esters, ethoxylated glycerol esters, ethylene glycol esters and their derivatives, fatty acid monoglycerides, polyglycerol esters, sorbitan esters, sucrose esters and glucose esters, triphosphate esters, N-alkylpyrrolidone, etc., whose main function is emulsification.

[0058] The emulsifiers described in this invention are selected from hydrophilic emulsifiers and nonionic surfactants, such as: POE-sorbitol fatty acid esters (e.g., POE-sorbitol monooleate, POE-sorbitol monostearate, POE-sorbitol tetraoleate, etc.); POE-sorbitol fatty acid esters (POE-sorbitol monolaurate, POE-sorbitol monooleate, POE-sorbitol pentaoleate, POE-sorbitol monostearate, etc.); POE-glycerol fatty acid esters (e.g., POE... - POE monoisostearate, POE-glyceryl isostearate, POE-glyceryl triisostearate, etc., and POE monooleate, etc.; POE-fatty acid esters (e.g., POE distearate, POE monodioleate, ethylene distearate, etc.); POE-alkyl ethers (e.g., POE lauryl ether, POE oleyl ether, POE stearyl ether, POE behenyl ether, POE-2-octyldodecane ether, POE-cholestanol ether, etc.); Pluronic polyoxyalkylene oxides (e.g., Pl... uronic, etc.); POE‧POP-alkyl ethers (e.g., POE‧POP-cetyl ether, POE‧POP-2-decyltetradecane ether, POE‧POP-monobutyl ether, POE‧POP-hydrogenated lanolin, POE‧POP-glycerol ether, etc.); tetra-POE‧tetra-POP-ethylenediamine condensates (e.g., polyalkyloxyethylenediamine (Tetronic™), etc.); POE-caster oil hardened castor oil derivatives (e.g., POE-caster oil, POE-hardened castor oil, POE-hardened castor oil monoisostearate, etc.). POE-hardened castor oil triisostearate, POE-hardened castor oil monopyroglutamic acid monoisostearate, POE-hardened castor oil maleate, etc.; POE-beeswax / lanolin derivatives (e.g., POE-sorbitol beeswax); alkanolamides (e.g., coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide, etc.); POE-propylene glycol fatty acid esters; POE-alkylamines; POE-fatty acid amides; sucrose fatty acid esters; alkylethoxydimethylamine oxides; trioleyl phosphate, etc.

[0059] The fatty acid glycerides described in this invention are mono-fatty acid glycerides, particularly those with 12 to 32 carbon atoms. Examples include glyceryl laurate, glyceryl myristate, glyceryl palmitate, glyceryl stearate, glyceryl betaine, glyceryl oleate, glyceryl undecenoate, tall oil fatty acid glycerides, glyceryl isostearate, glyceryl linoleate, glyceryl linoleate, glyceryl alpha-linolenic acid, glyceryl eicosapentaenoate, glyceryl docosahexaenoate, and coconut oil fatty acid glycerides, which can be used alone or in combination of two or more. In particular, in this invention, straight-chain fatty acid glycerides with 16 or more carbon atoms are preferred, and straight-chain fatty acids such as glyceryl palmitate, glyceryl stearate, and glyceryl betaine are particularly suitable.

[0060] The moisturizer described in this invention is selected from: glycerol, propylene glycol, butylene glycol, methyl propylene glycol, hexanediol, dipropylene glycol, pentanediol, hexanediol, low molecular weight polyethylene glycol, xylitol, amino acids, vinylpyrrolidone carboxylic acid (PCA) and / or its sodium salt, lactic acid, sodium lactate, hyaluronic acid, collagen, or mixtures thereof, and is mainly used as a moisturizer for skin and hair.

[0061] The active ingredients described in this invention include: skin-soothing, skin cell-promoting, antioxidant, whitening, anti-allergic, anti-inflammatory, thickening, astringent, hair-promoting, and blood circulation-promoting agents, which may be aloe vera extract or red and green algae extracts, with the main function of soothing the skin; nicotinic acid and epidermal growth factor, whose main functions are to promote skin cell proliferation, anti-oxidation, and inhibit melanin accumulation; allantoin and vitamin B3 anti-inflammatory agents (such as glycyrrhizin derivatives, licorice extract, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, zinc oxide, allantoin, etc.), whose main functions are anti-inflammatory, soothing, and skin tissue regeneration-aiding functions; arbutin and tranexamic acid. Azelaic acid), azelaic acid, salicylic acid, kojic acid, Atractylodes macrocephala extract, chamomile extract and its derivatives, sodium vitamin C phosphate, magnesium vitamin C phosphate, vitamin C glucoside, Saxifraga stolonifera extract, arbutin, etc.; various extracts (such as Phellodendron amurense, Coptis chinensis, Lithospermum erythrorhizon, Paeonia lactiflora, Swertia japonica, birch, Sage corydalis).Officinalis), loquat, ginseng, aloe vera, mallow (Malva sylvestris), iris, grape, coix seed, loofah, lily, saffron, chuanxiong, raw scallion, licorice, alfalfa, garlic, chili, dried tangerine peel, angelica, seaweed, etc.; activators (such as royal jelly, photosensitizers, cholesterol derivatives, etc.) are used to provide skin whitening; anti-inflammatory agents (such as tranexamic acid, thiotaurine, hypotaurine, etc.); aromatic alcohols (benzyl alcohol, benzyloxyethanol, etc.), potassium glycyrrhizate, sodium glycyrrhizate, ammonium glycyrrhizate, mainly used for anti-allergy and anti-inflammatory purposes; vitamin E and its derivatives, mainly used for anti-oxidation; placental extract and whey protein, mainly used to promote skin cell proliferation and reduce wrinkles; nonoyl acid The main functions of substances such as vanillylamide, benzyl nicotinate, β-butoxyethyl nicotinate, capsicin, zingerone, cantharis tincture, ichthammol, tannic acid, α-borneol, tocopheryl nicotinate, inositol hexanicotinic acid, cyclandelate, cinnarizine, tolazoline, acetylcholine, verapamil, cepharanthine, and γ-oryzanol are blood circulation promoters.

[0062] The water-soluble polymer described in this invention primarily functions to increase viscosity, retain moisture, and improve product quality stability. Examples of such polymers include starch-based polymers (e.g., carboxymethyl starch, etc.). Methyl hydroxypropyl starch, etc.; cellulose-based polymers (methylcellulose, ethylcellulose, methyl hydroxypropylcellulose, hydroxyethylcellulose, sodium cellulose sulfate, dialkyl dimethylammonium cellulose sulfate, hydroxypropylcellulose, carboxymethylcellulose, sodium carboxymethyl cellulose, crystalline cellulose, cellulose powder, and hydrophobically modified compounds of these polymers <e.g., some modified with stearyl groups> and cationic modified compounds of these polymers, etc.); alginate-based polymers (e.g., sodium alginate, propylene glycol alginate, etc.); sodium pectate, chitosan, gum arabic, guar gum, cyclodextrin, tartaric acid, gelatin, polyvinylpyrrolidone, polyvinyl alcohol or mixtures thereof, polyacrylic acid, cross-linked polymers of acrylic acid, copolymers of acrylic acid with hydrophobic monomers, copolymers of carboxylic acid monomers with acrylates, cross-linked copolymers of acrylic acid and acrylates, heteropolysaccharide gums, and crystalline long-chain amide derivatives. These long-chain amide derivatives are preferably selected from ethylene glycol stearate, alkanolamides of fatty acids having 16 to 22 carbon atoms, and mixtures thereof. Distearate and polyethylene distearate 3 are preferred long-chain acetal derivatives because they provide a pearlescent luster to the composition. Polyacrylic acid is commercially available as Carbopol 420, Carbopol 488, or Carbopol 493. Polymers of acrylic acid crosslinked with polyfunctional agents can also be used; these are commercially available as Carbopol 910, Carbopol 934, Carbopol 941, and Carbopol 980. An example of a suitable copolymer containing carboxylic acid monomers and acrylates is Carbopol 1342. All Carbopol (trade name) materials are available from Goodrich. Suitable crosslinking polymers of acrylic acid and acrylates are Pemulen TR1 or Pemulen TR2. A suitable heteropolysaccharide gum is xanthan gum, for example, available from Kelzanmu. Mixtures of any of the above thickeners can be used.

[0063] The preservatives described in this invention are selected from: benzyl alcohol, phenoxyethanol, imizoleyl urea, p-hydroxybenzoic acid esters, benzoic acid, 1,3-dihydroxymethyl-5,5-dimethylhydantoin, triclosan, 1,2-alkyldiol (carbon chain length 6 to 14) and its derivatives, and methylchloroisothiazolinone. Their main function is to inhibit foreign microorganisms. Simple Explanation of the Diagram

[0064] Figure 1. Extraction rate trend of various citron extracts

[0065] Figure 2. Trend chart of antioxidant capacity (DPPH) and free radical scavenging capacity of various citron extracts.

[0066] Figure 3. Viscosity comparison of face cream samples containing citron essential oil nanolipid carriers (NLC). Implementation

[0067] Preparation method of citron extract

[0068] This invention uses cleaned and sliced ​​citron, soaking it in solvents such as methanol, ethyl acetate, and acetone for two weeks. After first filtration, second filtration, concentration, and weighing, the resulting citron extracts are shown in Table 1 and Figure 1, which shows the citron extraction rate trend. As can be seen from Table 1, the extraction rate of citron using acetone is the lowest among the three solvents, possibly due to the low compatibility between the solvent and citron. Overall, ethyl acetate has the highest extraction rate at 16.25%, while acetone has the lowest at only 12.02%.

[0069] Extraction rate formula = (Weight after concentration / Weight before extraction) * 100%

[0070]

[0071] Antioxidant capacity test

[0072] DPPH Radical Scavenging Capacity Test

[0073] This invention tested the antioxidant capacity of citron extract at five different concentrations, as shown in Table 2 and Figure 2, which illustrates the trend of DPP free radical scavenging capacity of citron extract. Comparing the scavenging rates at different concentrations using the same solvent, the highest antioxidant capacity was observed at these concentrations: methanol (30 mg / mL) at 92.7%, ethyl acetate (70 mg / mL) at 85.8%, and acetone (70 mg / mL) at 86.5%. Overall, methanol showed the highest antioxidant capacity at 30 mg / mL, reaching 92.7%. On average, methanol outperformed ethyl acetate at all five concentrations, and ethyl acetate outperformed acetone. Citron is a fruit with excellent antioxidant capacity, possibly because its antioxidants have similar polarity to methanol, making them easier to extract. This explains why methanol outperformed the other two solvents in the antioxidant capacity test.

[0074] Free radical scavenging formula = (blank value - sample value) / blank value * 100%

[0075]

[0076] Preparation method of citron essential oil nanolipid carrier (NLC)

[0077] The mixture was divided into two groups: one with Q10 and one without. The proportions of each component were as follows: 1% soybean lecithin, 1% caprylic acid glyceride, and 1% Q10 were stirred at 50°C to form a homogeneous mixture. Then, 94% glycerol and 3% deionized water were added to the mixture and stirred to form a homogeneous emulsion. Finally, the emulsion was processed by a high-pressure homogenizer at 500br pressure for 8 cycles to obtain a transparent citron essential oil nanolipid carrier (NLC).

[0078] Then, based on the existing conditions, change it to

[0079] (1) The ratio of Q10 is 1% lecithin, 1% caprylic acid glyceride and 1% Q10. Stir at 50°C to form a homogeneous mixture. Then add 94% glycerol and 3% extract to the mixture and stir to form a homogeneous emulsion. Finally, the emulsion is homogenized at 8000 rpm for 3 hours to obtain a transparent NLC formulation as shown in Table 3.

[0080] (2) The Q10-free formulation consists of 1% soybean lecithin and 1% caprylic / capric triglyceride, stirred at 50°C to form a homogeneous mixture. Then, 94% glycerol and 4% extract are added to the mixture and stirred to form a homogeneous emulsion. Finally, the emulsion is homogenized at 8000 rpm for 3 hours to obtain transparent NLC. The NLC formulation is shown in Table 4.

[0081]

[0082]

[0083] 1. Stir the raw materials in item A to form a homogeneous mixture.

[0084] 2. Add ingredient B to mixture A and stir to form a homogeneous emulsion.

[0085] 3. Finally, the emulsion was homogenized at 8000 rpm for 3 hours to obtain a transparent citron essential oil nanolipid carrier (NLC).

[0086] Preparation method of face cream containing citron essential oil nanolipid carrier (NLC)

[0087] Table 5. Ingredients of face creams containing citron essential oil nanolipid carriers (NLC)

[0088] (1) Weigh the raw material in item A into a beaker, heat it in a water bath, and stir until it is completely dissolved. Weigh the raw material in item B into another beaker, heat it in a water bath, and stir until it is completely dissolved.

[0089] (2) Slowly pour B into A and react in a water bath for several minutes until emulsification is complete. Take out the mixture and stir while cooling.

[0090] (3) After cooling to 35°C, weigh in the raw materials in item C in sequence and stir evenly.

[0091] Physical properties and shape of citron essential oil nanolipid carriers (NLC)

[0092] Particle size analysis (Partica mini LA-350)

[0093] step:

[0094] (a) Select the option via computer connection.

[0095] (b) Take 100 ml of the sample dispersion and 1 g of the sample.

[0096] (c) Set the measurement speed to approximately 10 seconds, wait for the measurement results and record them.

[0097] This invention uses particle size variation to infer coating and aggregation. The particle size of the coated product is approximately between 5 and 25 nm. After several hours of Brownian motion, collisions occur between particles, leading to aggregation. If the particles are too large, they will settle, resulting in stratification or deposition. Therefore, the particle size of the coated product should have a normal distribution to ensure its stability; that is, the narrower the particle size distribution, the better the stability.

[0098] The particle size of each citron essential oil nanolipid carrier (NLC) is shown to be as follows: acetone-extracted NLC without Q10 < methanol-extracted NLC with Q10 < ethyl acetate-extracted NLC without Q10 < ethyl acetate-extracted NLC with Q10 < acetone-extracted NLC with Q10 < methanol-extracted citron essential oil nanolipid carrier (NLC).

[0099] Stability of Citron essential oil nanolipid carriers (NLC)

[0100] This invention uses pre-prepared citron essential oil nanolipid carriers (NLCs) to test their stability. The results are shown in Table 6. The NLCs were centrifuged at 3000 rpm. After 5 minutes, the NLCs were removed. The NLCs with Q10 extracted by methanol, those without Q10 extracted by methanol, and those without Q10 extracted by acetone showed clear stratification after 5 minutes of centrifugation. The NLCs with Q10 extracted by ethyl acetate, those without Q10 extracted by ethyl acetate, and those with Q10 extracted by acetone did not show clear stratification after 5 minutes of centrifugation. After another 10 minutes of centrifugation, the NLCs with Q10 extracted by methanol, those without Q10 extracted by methanol, and those without Q10 extracted by acetone showed even more clear stratification after 10 minutes of centrifugation. The NLCs with Q10 extracted by ethyl acetate, those without Q10 extracted by ethyl acetate, and those with Q10 extracted by acetone showed slight stratification after 10 minutes of centrifugation.

[0101] 0: No stratification; 1: Slight stratification; 2: Obvious stratification; 3: Severe stratification

[0102] microscope

[0103] Under a microscope, it can be seen that the citron essential oil nanolipid carrier (NLC) has successfully coated spherical substances, but there are still some uneven substances with small black dots due to differences in equipment. Microscopic images of the citron essential oil nanolipid carrier (NLC) synthesized in this case show the following: Microscopic images of NLC with methanol and Q10 show only a few large successfully coated NLC particles, and one or two small black dots of uneven substance. Microscopic images of NLC without methanol and Q10 show many successfully coated NLC particles, but one or two small black dots of uneven substance. Microscopic images of NLC with ethyl acetate and Q10 show a moderate amount of NLC, but they are all small particles, and one or two small black dots of uneven substance. Microscopic images of NLC without ethyl acetate and Q10 show a moderate amount of NLC, but they are all small particles, and one or two small black dots of uneven substance. The microscopic images of NLC with Q10 in acetone show that the coated NLC contains more small black dots of uneven material compared to the NLC with Q10 in methanol. The microscopic images of NLC without Q10 in acetone show scattered but large coated NLC particles, as well as a noticeable small black dot of uneven material.

[0104] The basic properties of face cream containing citron essential oil nanoliposome carriers (NLC) were investigated and tested, including viscosity and moisturizing properties.

[0105] The viscosity of face creams containing citron essential oil nanolipid carriers (NLC)

[0106] Viscosity is a measure of the resistance to liquid flow. For face creams, which are substances between solid and liquid states, viscosity has a significant impact on their structure and stability. Face creams formed from high-viscosity liquids typically have lower porosity and a relatively dense structure due to stronger intermolecular forces; at the same time, high viscosity can effectively inhibit phase separation and improve the stability of the face cream.

[0107] This invention uses a prepared face cream containing citron essential oil nanolipid carriers (NLCs). A type R needle, size 6, was used at a speed of 10 RPM. The viscosity range of each face cream sample was between 21,000 cP and 26,000 cP. Figure 3 shows a comparison of the viscosity of the face cream samples containing citron essential oil nanolipid carriers (NLCs) of this invention. As shown in Table 7, the highest viscosity was found in the NLC sample containing ethyl acetate without Q10, reaching 26,000 cP, demonstrating its stability. The viscosity ranking of each face cream is as follows: NLC containing ethyl acetate without Q10 > NLC containing acetone without Q10 > NLC containing methanol without Q10 > NLC containing pure ethyl acetate > NLC containing acetone with Q10 > NLC containing ethyl acetate with Q10 > NLC containing methanol with Q10 > NLC containing pure methanol > NLC containing pure acetone.

[0108]

[0109] Moisturizing effect test of face cream containing citron essential oil nanolipid carrier (NLC)

[0110] The multifunctional skin test was conducted using the MPA 580 skin analyzer. The test environment conditions were: humidity 52.5% and temperature 24.7℃. The test measured transepidermal water loss and moisture content before and after applying face cream.

[0111] (1) Moisturizing test. Transdermal water loss

[0112] The transepidermal moisture data were mostly higher after applying face cream than before. After investigation, the reason was found to be that the testing interval was not long enough. The test was conducted only 20 minutes after applying face cream, which meant that the face cream was not fully absorbed. Therefore, the data after applying face cream was mostly higher than before applying face cream.

[0113] (2) Moisture retention test. Water content

[0114] The water content values ​​all showed a considerable increase, and the values ​​after applying the face cream were higher than before applying the face cream. The order of the increase rate of water content can be ranked as follows: NLC with Q10 in ethyl acetate extraction > NLC with Q10 in methanol extraction > NLC with Q10 in acetone extraction > NLC without Q10 in methanol extraction > NLC without Q10 in ethyl acetate extraction > NLC without Q10 in acetone extraction > NLC with ethyl acetate extraction > NLC with methanol extraction > NLC with acetone extraction.

[0115] (3) Moisturizing test. Adverse reactions.

[0116] During the moisturizing test, we observed whether the test subjects experienced any adverse reactions. We paid special attention to two areas: redness and itching, as most people pay attention to these two areas when judging whether a product is suitable for them. No adverse reactions occurred in this experiment.

[0117] Table 8 shows whether there were any adverse reactions in the moisturizing test. Redness and swelling: 0 - No redness and swelling; 1 - Slight redness; 2 - Moderate redness; 3 - Severe redness; 4 - Burning redness. Itching: (+) Itching present; (-) No itching.

[0118] The results of this invention show that, in terms of citron extraction, ethyl acetate extraction yielded the highest extraction rate, while acetone extraction yielded the lowest. In the DPPH antioxidant capacity test, methanol-extracted citron showed the best free radical scavenging ability, while acetone-extracted citron showed the worst. In particle size testing, the acetone-extracted NLC without Q10 had the smallest particle size, while the methanol-extracted NLC without Q10 had the largest. In the stability test, the ethyl acetate-extracted NLC with Q10, the ethyl acetate-extracted NLC without Q10, and the acetone-extracted NLC with Q10 performed relatively well. Regarding viscosity, the ethyl acetate-extracted NLC without Q10 had the highest viscosity, while the acetone-extracted NLC had the lowest. Regarding moisturizing properties, transdermal water loss was generally higher than before the test began, likely due to insufficient test intervals; it is recommended to extend the testing time.

[0119] Moisturizing properties: Ethyl acetate extraction with Q10 showed the best NLC effect, while acetone extraction showed the worst. Moisturizing properties: No adverse reactions were observed in any of the nine samples tested.

Claims

1. A citron essential oil nanolipid carrier, the preparation method of which includes steps (a) to (c): (a) mixing an emulsifier and fatty acid glycerides and heating until a homogeneous mixture is obtained; (b) adding a moisturizer, active ingredient, and citron extract to the mixture in (a), stirring and emulsifying to form a homogeneous mixture; and (c) stirring the mixture obtained in (b) at high speed with a homogenizer to obtain a transparent liquid citron essential oil nanolipid carrier.

2. As in claim 1, the citron essential oil nanolipid carrier, wherein, (a) The raw materials in the step further contain 0 to 20 wt% coenzyme Q10.

3. As in claim 1, the citron essential oil nanolipid carrier, wherein, This fatty acid glyceride is a mono-fatty acid glyceride.

4. As in claim 1, the citron essential oil nanolipid carrier, wherein, The emulsifier is lecithin.

5. A face cream containing citron essential oil nanolipid carrier, comprising: 0.5-15% citron essential oil nanolipid carrier, 0.5-5 wt% emulsifier, 0-20 wt% active ingredient, 0.1-5 wt% preservative, 60-95 wt% water, 0-20 wt% other moisturizer, and 0-5 wt% water-soluble polymer.

6. The face cream as described in claim 5, wherein the water-soluble polymer is used as a thickener.

7. The face cream of claim 5, wherein the emulsifier is selected from: esterified carboxylic acids and their salts, sodium alkyl polyoxyethylene ether carboxylate, phosphate salts, nonionic surfactants, which, according to their structural formula, can be broadly classified into (1) ethers, (2) esters, (3) alkyl alcohol amides, (4) amides, etc., or a combination thereof.

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