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TWI748207B - Sunblock liposome, and method for preparing the same - Google Patents

Sunblock liposome, and method for preparing the same Download PDF

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TWI748207B
TWI748207B TW108124758A TW108124758A TWI748207B TW I748207 B TWI748207 B TW I748207B TW 108124758 A TW108124758 A TW 108124758A TW 108124758 A TW108124758 A TW 108124758A TW I748207 B TWI748207 B TW I748207B
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sunscreen
liposome
solution
resveratrol
liposomes
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TW108124758A
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TW202102197A (en
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吳姵萱
蔡素珍
郭億清
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靜宜大學
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Abstract

The present disclosure provides a sunblock liposome prepared by the following steps. A first solution is provided, wherein the first solution is used as a water phase and includes resveratrol and at least one sunscreen. A second solution is provided, wherein the second solution is used as an oil phase and includes lecithin and cholesterol, wherein the lecithin and the surfactant are contained in a weight percentage of 10:1 to 30:1. A water-in-oil emulsification is performed, wherein the water-in-oil emulsification is for mixing the first solution and the second solution so as to obtain an emulsion. A homogenization step is performed, wherein the homogenization step is for homogenizing the emulsion so as to obtain the sunblock liposome. Therefore, the sunblock liposome can increase effectiveness of sunscreen and reduce the amount of chemical sunscreen, so that the sunblock liposome has a marketing potential in the related fields.

Description

防曬脂質體及其製備方法 Sunscreen liposome and preparation method thereof

本發明係關於一種脂質體及脂質體的製備方法,特別是關於一種防曬脂質體及防曬脂質體的製備方法。 The present invention relates to a liposome and a preparation method of liposomes, in particular to a sun-protecting liposome and a preparation method of the sun-protecting liposome.

紫外線對皮膚造成許多嚴重的傷害,包括皮膚紅腫、曬傷、色素沉澱、老化、失去彈性及產生皺紋等,甚至會造成皮膚免疫系統受損及增加皮膚癌發生機率。加上近年來環境的破壞使得紫外線的入侵日趨嚴重,所以對於防曬工作更加不容忽視。 Ultraviolet rays cause many serious damage to the skin, including skin redness, sunburn, pigmentation, aging, loss of elasticity and wrinkles, etc., and even damage the skin's immune system and increase the chance of skin cancer. Coupled with the destruction of the environment in recent years, the invasion of ultraviolet rays has become more and more serious, so the work of sun protection cannot be ignored.

防曬劑常被添加於化妝品中,用來濾除有害的紫外線輻射。依作用機轉的不同,可將防曬劑分為化學性防曬劑和物理性防曬劑。化學性防曬劑也是所謂的紫外線吸收劑,多為人工合成的吸光性化合物,是以吸收紫外線能量來達到防曬的功效,這些化合物可依其化學結構不同,而能吸收特定波長的紫外線。物理性防曬劑主要是藉由固體顆粒對陽光的反射和散射來阻抗陽光,不讓陽光直接與皮膚接觸,故一般習用皆使用無機物顆粒作為物理性防曬劑。 Sunscreens are often added to cosmetics to filter out harmful ultraviolet radiation. Depending on the mechanism of action, sunscreens can be divided into chemical sunscreens and physical sunscreens. Chemical sunscreens are also so-called ultraviolet absorbers. Most of them are synthetic light-absorbing compounds that absorb ultraviolet energy to achieve sun protection. These compounds can absorb ultraviolet rays of specific wavelengths depending on their chemical structure. Physical sunscreens mainly resist sunlight through the reflection and scattering of sunlight by solid particles, and prevent sunlight from directly contacting the skin. Therefore, inorganic particles are generally used as physical sunscreens.

防曬劑雖然有助於抵抗紫外線的傷害,但是它們也有許多副作用存在,包括對皮膚造成刺激、發炎、光過敏及光毒性的反應。其中化學性防曬劑是利用能量轉移的方式來達到防曬的效果,但是有些防曬劑會因為紫外線所提供的能量發生光降解,產生有害的自由基及光毒性物質,也會使產品的防曬能力降低。此外,國人發生接觸性過敏的原因中,有18.1%是由於使用防曬劑後所造成的不適,且近年來也有不少防曬成份被提出具有內分泌活性作用。 Although sunscreens help resist the damage of ultraviolet rays, they also have many side effects, including skin irritation, inflammation, photosensitivity, and phototoxic reactions. Among them, chemical sunscreens use energy transfer to achieve the effect of sun protection, but some sunscreens will photodegrade due to the energy provided by ultraviolet rays, produce harmful free radicals and phototoxic substances, and also reduce the sunscreen ability of the product. . In addition, 18.1% of Chinese people's contact allergies are caused by discomfort after using sunscreens. In recent years, many sunscreen ingredients have been proposed to have endocrine activity.

因此,如何發展一種防曬原料,其可有效地達到防曬效果且能降低對皮膚副作用和降低對環境造成負荷,實為本領域之技術人員所共同努力的目標。 Therefore, how to develop a sunscreen material that can effectively achieve the sunscreen effect, reduce the side effects on the skin and reduce the load on the environment, is the goal of the joint efforts of those skilled in the art.

本發明之一態樣在於提供一種防曬脂質體的製備方法,包含下述步驟:提供一第一溶液、提供一第二溶液、進行一油包水型乳化反應以及進行一均質步驟。第一溶液用以作為水相並包含一白藜蘆醇和至少一防曬劑。第二溶液用以作為油相並包含一卵磷脂及一膽固醇,其中卵磷脂與膽固醇係以重量百分比10:1至30:1的比例混合。油包水型乳化反應係混合第一溶液與第二溶液,以形成一乳化物。均質步驟係以一均質機均質乳化物,以製得一防曬脂質體。 One aspect of the present invention is to provide a method for preparing sunscreen liposomes, which includes the following steps: providing a first solution, providing a second solution, performing a water-in-oil emulsification reaction, and performing a homogenization step. The first solution is used as an aqueous phase and contains a resveratrol and at least one sunscreen. The second solution is used as an oil phase and contains a lecithin and a cholesterol, wherein the lecithin and the cholesterol are mixed in a ratio of 10:1 to 30:1 by weight. The water-in-oil type emulsification reaction system mixes the first solution and the second solution to form an emulsion. The homogenization step is to homogenize the emulsion with a homogenizer to prepare a sunscreen liposome.

依據前述之防曬脂質體的製備方法,其中至少一防曬劑可選自由對氨基苯甲酸類防曬劑、二苯甲酮類防曬 劑、桂皮酸鹽類防曬劑和水楊酸鹽類防曬劑所組成之一群組。 According to the aforementioned method for preparing sunscreen liposomes, at least one sunscreen can be selected from para-aminobenzoic acid sunscreens and benzophenone sunscreens. A group consisting of cinnamate sunscreens and salicylate sunscreens.

依據前述之防曬脂質體的製備方法,其中至少一防曬劑可為甲氧基肉桂酸辛酯、二苯酮-3或丁基甲氧基二苯甲醯基甲烷。 According to the aforementioned method for preparing sunscreen liposomes, at least one sunscreen agent can be octyl methoxycinnamate, benzophenone-3 or butylmethoxybenzylmethane.

依據前述之防曬脂質體的製備方法,其中油包水型乳化反應中,第一溶液和第二溶液可以超音波震盪和攪拌進行混合。 According to the aforementioned preparation method of sunscreen liposomes, in the water-in-oil type emulsification reaction, the first solution and the second solution can be mixed by ultrasonic vibration and stirring.

依據前述之防曬脂質體的製備方法,其中前述均質機可為一高壓均質機,且高壓均質機之一高壓均質壓力可為400巴至1500巴。 According to the aforementioned method for preparing sunscreen liposomes, the aforementioned homogenizer can be a high-pressure homogenizer, and the high-pressure homogenization pressure of one of the high-pressure homogenizers can be 400 bar to 1500 bar.

本發明之另一態樣在於提供一種防曬脂質體,其係利用前述之製備方法製得。 Another aspect of the present invention is to provide a sunscreen liposome, which is prepared by the aforementioned preparation method.

依據前述之防曬脂質體,其中前述之防曬脂質體的一平均粒徑可為200nm至400nm。 According to the aforementioned sunscreen liposome, an average particle size of the aforementioned sunscreen liposome can be 200nm to 400nm.

依據前述之防曬脂質體,其中防曬脂質體的一界面電位(zeta potential)可為-60mV至-40mV。 According to the aforementioned sunscreen liposome, a zeta potential of the sunscreen liposome can be -60mV to -40mV.

依據前述之防曬脂質體,其中白藜蘆醇的包覆率可為45%至60%。 According to the aforementioned sunscreen liposome, the coating rate of resveratrol can be 45% to 60%.

依據前述之防曬脂質體,其中至少一防曬劑的包覆率可為35%至60%。 According to the aforementioned sunscreen liposome, the coating rate of at least one sunscreen agent can be 35% to 60%.

藉此,本發明之防曬脂質體之製備方法的製程簡單,且所製備出之防曬脂質體可增加化學性防曬劑的防曬效能,以減少化學性防曬劑的用量,以及降低化學性防曬劑 經皮吸收所造成的刺激反應,具有應用於化妝品市場之潛能。 Thereby, the preparation process of the sunscreen liposome of the present invention is simple, and the prepared sunscreen liposome can increase the sunscreen performance of chemical sunscreen agents, reduce the amount of chemical sunscreen agents, and reduce chemical sunscreen agents The irritation caused by transdermal absorption has the potential to be applied to the cosmetics market.

100‧‧‧防曬脂質體的製備方法 100‧‧‧Preparation method of sunscreen liposome

110‧‧‧提供一第一溶液 110‧‧‧Provide a first solution

120‧‧‧提供一第二溶液 120‧‧‧Provide a second solution

130‧‧‧進行一油包水型乳化反應 130‧‧‧Perform a water-in-oil type emulsification reaction

140‧‧‧進行一均質步驟 140‧‧‧Perform a homogenization step

300‧‧‧防曬脂質體 300‧‧‧Sunscreen Liposome

為讓本發明之上述和其他目的、特徵、優點與實施例能更明顯易懂,所附圖式之說明如下:第1圖係繪示本發明一實施方式之防曬脂質體的製備方法的步驟流程圖;第2圖係繪示本發明另一實施方式之防曬脂質體之穿透式電子顯微鏡之影像圖;第3圖和第4圖係繪示本發明實施例1之防曬脂質體之體外經皮傳輸之穿透量曲線圖;第5圖和第6圖係繪示本發明實施例2之防曬脂質體之體外經皮傳輸之穿透量曲線圖;第7圖係繪示本發明實施例3之含防曬脂質體之防曬製劑的防曬能力分析結果圖;以及第8圖係繪示本發明實施例4之含防曬脂質體之防曬製劑的防曬能力分析結果圖。 In order to make the above and other objectives, features, advantages and embodiments of the present invention more comprehensible, the description of the accompanying drawings is as follows: Figure 1 shows the steps of a method for preparing sunscreen liposomes according to an embodiment of the present invention Flow chart; Figure 2 shows a penetrating electron microscope image of a sunscreen liposome according to another embodiment of the present invention; Figures 3 and 4 show the in vitro sunscreen liposome of Example 1 of the present invention The penetration curve of transdermal delivery; Figures 5 and 6 show the penetration curve of the sunscreen liposome of Example 2 of the present invention for transdermal delivery in vitro; Figure 7 shows the implementation of the present invention The results of the analysis of the sun protection ability of the sunscreen preparation containing sunscreen liposomes of Example 3; and Fig. 8 is a graph showing the results of the analysis of the sun protection ability of the sunscreen preparation containing sunscreen liposomes of Example 4 of the present invention.

以下為本說明書中所用特定名詞的說明:說明書中所述之「對氨基苯甲酸類防曬劑」係指含有對氨基苯甲酸(para aminobenzoic acid)或其衍生物的防曬劑,其為一種化學性防曬劑。對氨基苯甲酸類防曬 劑可吸收波長200~313nm的紫外線,先前研究顯示,對氨基苯甲酸類防曬劑經由紫外線照射後,會讓使用者的皮膚發炎及產生光過敏現象,此外它光裂解後的產物,被認為是一種致癌物。 The following is an explanation of the specific terms used in this specification: The " para- aminobenzoic acid sunscreen" mentioned in the specification refers to a sunscreen containing para aminobenzoic acid or its derivatives, which is a chemical Sunscreen. Para-aminobenzoic acid sunscreens can absorb ultraviolet rays with a wavelength of 200~313nm. Previous studies have shown that para-aminobenzoic acid sunscreens can cause skin inflammation and photosensitivity after being irradiated with ultraviolet rays. In addition, after photolysis, The product is considered a carcinogen.

說明書中所述之「二苯甲酮類防曬劑」係指含有二苯甲酮類(benzophenones)的防曬劑,為一種化學性防曬劑,二苯酮-3(benzophenone-3,BP-3)為其中一種二苯甲酮類防曬劑。二苯甲酮類防曬劑是一類重要的紫外線吸收劑,以結構上分類有兩種類型,一種為只有一個部位羥基,能吸收波長290~380nm的紫外線。另一種含有兩個部位羥基,吸收的波段向長波方向偏移,能吸收波長300~400nm的紫外線。所以二苯甲酮類紫外線吸收對UVA和UVB區段兼能吸收,是一類廣譜紫外線吸收劑。但易發生氧化反應。與皮膚和黏膜有良好的親合性,易有光過敏反應等情形。 The "benzophenone sunscreen agent" mentioned in the manual refers to a sunscreen agent containing benzophenones, which is a chemical sunscreen agent, benzophenone-3 (BP-3) It is one of the benzophenone sunscreens. Benzophenone sunscreens are an important class of ultraviolet absorbers. There are two types based on structural classification. One has only one hydroxyl group and can absorb ultraviolet rays with a wavelength of 290-380nm. The other contains two hydroxyl groups, the absorption band shifts to the long-wave direction, and can absorb ultraviolet light with a wavelength of 300 to 400 nm. Therefore, benzophenone ultraviolet absorption can absorb both UVA and UVB sections, and it is a kind of broad-spectrum ultraviolet absorber. But it is prone to oxidation reaction. It has good affinity with the skin and mucous membranes, and is prone to light allergic reactions.

說明書中所述之「桂皮酸鹽類防曬劑」係指含有桂皮酸鹽類(cinnamates)的防曬劑,為一種化學性防曬劑,甲氧基肉桂酸辛酯(octyl methoxycinnamate,OMC)是其中一種桂皮酸鹽類防曬劑。桂皮酸鹽類防曬劑屬於紫外線UVB型吸收劑,為提高其防曬效果,常與其他紫外線吸收劑配合使用,是目前使用量最廣、用量最大的一類防曬劑。常與UVA紫外線吸收劑配合使用,以達到全效防曬效果。在純化合物狀態下,OMC的光穩定性較高,但在防曬化妝品的乳化體系中,特別是在水及表面活性劑的存在下,OMC在紫外線下的光穩定性不太高,通常在經過10 MED 最小紅斑劑量的陽光輻射後,約有一半以上的活性成分被降解。OMC的光降解產物會對皮膚產生一定的刺激作用。近年來更有一些動物研究指出,OMC可能是一種類雌激素的作用成分。 The "cinnamate sunscreens" mentioned in the instructions refer to sunscreens containing cinnamates, which are chemical sunscreens. Octyl methoxycinnamate (OMC) is one of the cinnamates. Salt sunscreens. Cinnamic acid salt sunscreens are ultraviolet UVB absorbers. In order to improve their sunscreen effect, they are often used in conjunction with other ultraviolet absorbers. They are currently the most widely used and the largest amount of sunscreens. It is often used in conjunction with UVA ultraviolet absorbers to achieve full sun protection. In the pure compound state, the light stability of OMC is relatively high, but in the emulsification system of sunscreen cosmetics, especially in the presence of water and surfactants, the light stability of OMC under ultraviolet light is not very high. 10 MED After the minimum erythema dose is irradiated with sunlight, more than half of the active ingredients are degraded. The photodegradation products of OMC will have a certain irritation effect on the skin. In recent years, some animal studies have pointed out that OMC may be an estrogen-like component.

說明書中所述之「水楊酸鹽類防曬劑」係指含有水楊酸鹽類(salicylates)的防曬劑,為一種化學性防曬劑,是較老的一類紫外線吸收劑,其特點是價格便宜,毒性低,與其他成分相容性好。其缺點是紫外線吸收率低,其吸收波段較窄(340nm下),本身對紫外線不甚穩定,長時間光照以後發生重排反應,而明顯地吸收可見光使其帶有顏色。 The "salicylate sunscreens" mentioned in the instructions refer to sunscreens containing salicylates. It is a chemical sunscreen and is an older type of ultraviolet absorber, which is characterized by its low price. , Low toxicity, good compatibility with other ingredients. The disadvantage is that the ultraviolet absorption rate is low, and its absorption band is relatively narrow (under 340nm), and it is not very stable to ultraviolet rays. After long-term exposure, the rearrangement reaction occurs, and the visible light is obviously absorbed to make it colored.

說明書中所述之「丁基甲氧基二苯甲醯基甲烷(butyl methoxydibenzylmethane,B-MDM)」又稱為Avobenzone或Parsol 1789,是一種主要的紫外線UVA防曬劑,屬於化學性防曬劑,可以吸收UVA 320~400波段,可以阻隔一些UVA-I,但對於UVA-II效果微弱,因此常與BP-3混合使用,易引發過敏等皮膚不適。此外,丁基甲氧基二苯甲醯基甲烷的主要缺點是光穩定性不高,經過紫外線的照射後會漸漸被分解而失去防曬效果。 The "butyl methoxydibenzylmethane (B-MDM)" described in the manual is also known as Avobenzone or Parsol 1789. It is a major ultraviolet UVA sunscreen. It is a chemical sunscreen and can absorb UVA. The 320~400 band can block some UVA-I, but the effect on UVA-II is weak, so it is often mixed with BP-3, which can easily cause skin discomfort such as allergies. In addition, the main disadvantage of butylmethoxydibenzamethane is its low light stability, and it will gradually be decomposed after being irradiated by ultraviolet rays and lose its sunscreen effect.

<本發明之防曬脂質體的製備方法><Preparation method of sunscreen liposome of the present invention>

請參照第1圖,其係繪示本發明一實施方式之防曬脂質體的製備方法100的步驟流程圖。防曬脂質體的製備方法100包含步驟110、步驟120、步驟130以及步驟140。 Please refer to Fig. 1, which is a flowchart of the steps of a method 100 for preparing sunscreen liposomes according to an embodiment of the present invention. The method 100 for preparing sunscreen liposomes includes step 110, step 120, step 130, and step 140.

步驟110為提供一第一溶液,其中第一溶液用以作為水相並包含一白藜蘆醇和至少一防曬劑。前述之白藜 蘆醇和至少一防曬劑係溶於一極性溶液中,以形成前述之第一溶液。詳細而言,前述之白藜蘆醇(resveratrol)為一種非黃酮類的酚類物質,屬於芪類化合物的植物抗毒素,天然白藜蘆醇的來源有葡萄、藍莓、樹莓及桑葚的果皮以及決明屬植物。至少一防曬劑可選自由對氨基苯甲酸類防曬劑、二苯甲酮類防曬劑、桂皮酸鹽類防曬劑和水楊酸鹽類防曬劑所組成之一群組,較佳地,至少一防曬劑可為甲氧基肉桂酸辛酯、二苯酮-3或丁基甲氧基二苯甲醯基甲烷。 Step 110 is to provide a first solution, wherein the first solution is used as an aqueous phase and contains a resveratrol and at least one sunscreen. White Chenopodium The retinol and at least one sunscreen are dissolved in a polar solution to form the aforementioned first solution. In detail, the aforementioned resveratrol (resveratrol) is a non-flavonoid phenolic substance, which belongs to the phytoantitoxin of stilbene compounds. The natural sources of resveratrol are grape, blueberry, raspberry and mulberry peels and Cassia plant. The at least one sunscreen can be selected from a group consisting of para-aminobenzoic acid sunscreens, benzophenone sunscreens, cinnamate sunscreens, and salicylate sunscreens. Preferably, at least one The sunscreen may be octyl methoxycinnamate, benzophenone-3 or butylmethoxybenzoylmethane.

步驟120為提供一第二溶液,其中第二溶液用以作為油相並包含一卵磷脂及一膽固醇,其中卵磷脂與膽固醇係以體積百分比10:1至30:1的比例混合。詳細而言,前述之卵磷脂將會形成防曬脂質體的磷脂雙層膜結構,以將白藜蘆醇和至少一防曬劑包覆於其中,而膽固醇的分子則會均勻分布於磷脂雙層膜結構的內膜與外膜中,以改變防曬脂質體的相變溫度,進而控制防曬脂質體的磷脂雙層膜的通透性和流動性。較佳地,前述卵磷脂可為Emulmetik 900。 Step 120 is to provide a second solution, wherein the second solution is used as an oil phase and contains a lecithin and a cholesterol, wherein the lecithin and the cholesterol are mixed in a ratio of 10:1 to 30:1 by volume. In detail, the aforementioned lecithin will form the phospholipid bilayer membrane structure of the sunscreen liposome, so that resveratrol and at least one sunscreen agent are coated therein, and the cholesterol molecules will be evenly distributed in the phospholipid bilayer membrane structure In the inner and outer membranes of the sunscreen liposomes, the phase transition temperature of the sunscreen liposomes can be changed to control the permeability and fluidity of the phospholipid bilayer membrane of the sunscreen liposomes. Preferably, the aforementioned lecithin may be Emulmetik 900.

步驟130為進行一油包水型乳化反應,其係混合第一溶液與第二溶液,以形成一乳化物。較佳地,前述第一溶液和第二溶液係以超音波震盪和攪拌進行混合,使第一溶液和第二溶液能均勻分散混合。 Step 130 is to perform a water-in-oil type emulsification reaction, which involves mixing the first solution and the second solution to form an emulsion. Preferably, the first solution and the second solution are mixed by ultrasonic vibration and stirring, so that the first solution and the second solution can be uniformly dispersed and mixed.

步驟140為進行一均質步驟,其係以一均質機均質前述乳化物,以製得一防曬脂質體。較佳地,前述之均質機可為一高壓均質機,且高壓均質機之一高壓均質壓力可 為400巴至1500巴,以進一步調整包含防曬脂質體的平均粒徑、包覆率與界面電位(zeta potential)。 Step 140 is to perform a homogenization step, which is to homogenize the aforementioned emulsion with a homogenizer to prepare a sunscreen liposome. Preferably, the aforementioned homogenizer can be a high-pressure homogenizer, and one of the high-pressure homogenizers can be a high-pressure homogenizer. It is 400 bar to 1500 bar to further adjust the average particle size, coating rate and zeta potential of the sunscreen liposome.

藉此,本發明之防曬脂質體的製備方法100透過第二溶液所包含的卵磷脂及膽固醇以重量百分比10:1至30:1的比例混合的方式,可有效地對白藜蘆醇和至少一防曬劑進行包覆,進而使本發明之防曬脂質體的製備方法100所製得之防曬脂質體具有高可變性、易於吸收之特性,並具有適當的平均粒徑、界面電位與包覆率,可增加化學性防曬劑的防曬效能,以減少化學性防曬劑的用量,以及降低化學性防曬劑經皮吸收所造成的刺激反應。較佳地,經由前述防曬脂質體的製備方法100所製得的防曬脂質體,其平均粒徑可為200nm至400nm,其界面電位可為-60mV至-40mV,其中白藜蘆醇的包覆率可為45%至60%,至少一防曬劑的包覆率可為35%至60%。 Thereby, the preparation method 100 of sunscreen liposomes of the present invention can effectively treat resveratrol and at least one sunscreen by mixing the lecithin and cholesterol contained in the second solution in a ratio of 10:1 to 30:1 by weight. The sunscreen liposome is coated with the sunscreen liposome, so that the sunscreen liposome prepared by the method 100 of the present invention has the characteristics of high variability, easy absorption, and appropriate average particle size, interface potential, and coating rate. Increase the sunscreen efficacy of chemical sunscreens to reduce the amount of chemical sunscreens and reduce the irritation caused by the transdermal absorption of chemical sunscreens. Preferably, the sunscreen liposome prepared by the aforementioned method 100 for preparing sunscreen liposome has an average particle size of 200nm to 400nm, and its interface potential can be -60mV to -40mV, wherein the coating of resveratrol The rate may be 45% to 60%, and the coating rate of at least one sunscreen agent may be 35% to 60%.

茲以下列具體試驗例進一步示範說明本發明,用以有利於本發明所屬技術領域通常知識者,可在不需過度解讀的情形下完整利用並實踐本發明,而不應將這些試驗例視為對本發明範圍的限制,但用於說明如何實施本發明的材料及方法。 The following specific test examples are used to further illustrate the present invention, so as to facilitate those who are generally knowledgeable in the technical field of the present invention to fully utilize and practice the present invention without excessive interpretation. These test examples should not be regarded as It limits the scope of the present invention, but is used to illustrate how to implement the materials and methods of the present invention.

<本發明之防曬脂質體><Sunscreen liposome of the present invention>

為確認防曬脂質體的製備方法100確實能製備防曬脂質體300,本試驗例中將經由步驟110至步驟140製備防曬脂質體300,並以穿透式電子顯微鏡確認其結構。 In order to confirm that the sunscreen liposome preparation method 100 can indeed prepare the sunscreen liposome 300, in this test example, the sunscreen liposome 300 will be prepared through step 110 to step 140, and its structure will be confirmed with a penetrating electron microscope.

請參照第2圖,為本發明另一實施方式之防曬脂質體300之穿透式電子顯微鏡之影像圖。結果顯示,本發明之防曬脂質體300為一大小均勻的微球體結構,顯示經由防曬脂質體的製備方法100確實能製備防曬脂質體300。 Please refer to FIG. 2, which is a transmission electron microscope image of the sunscreen liposome 300 according to another embodiment of the present invention. The results show that the sunscreen liposome 300 of the present invention is a uniform microsphere structure, which shows that the sunscreen liposome 300 can indeed be prepared by the method 100 for preparing the sunscreen liposome.

<高壓均質壓力對於脂質體的物理性質影響評估><Evaluation of the effect of high-pressure homogenization pressure on the physical properties of liposomes>

於本試驗例中,先製備不添加膽固醇和至少一防曬劑的包含白藜蘆醇之脂質體(測試例1至測試例5),以測試於均質步驟所使用之高壓均質機的最佳高壓均質壓力,並利用雷射粒徑分析儀(Laser Particle Size Analyzer,Malvern)分析測試例1至測試例5之平均粒徑和界面電位,並以高效液相層析儀(HPLC)系統評估白藜蘆醇的包覆率。 In this test example, first prepare liposomes containing resveratrol without adding cholesterol and at least one sunscreen (test example 1 to test example 5) to test the best high pressure of the high pressure homogenizer used in the homogenization step Homogenize the pressure, and analyze the average particle size and interface potential of Test Example 1 to Test Example 5 with a Laser Particle Size Analyzer (Malvern), and use a high-performance liquid chromatography (HPLC) system to evaluate Chenopodium album The coating rate of Retrol.

在包含白藜蘆醇之脂質體的平均粒徑測試實驗方面,首先將包含白藜蘆醇之脂質體以去離子水進行稀釋並以超音波振盪5分鐘,接著取1ml的樣品以雷射粒徑分析儀測量三次,並將三次結果進行平均,以得包含白藜蘆醇之脂質體的平均粒徑及其界面電位。 In the test of the average particle size of the liposomes containing resveratrol, first the liposomes containing resveratrol were diluted with deionized water and ultrasonically shaken for 5 minutes, and then a 1ml sample was taken as laser particles The diameter analyzer measures three times, and averages the three results to obtain the average particle diameter and the interface potential of the liposome containing resveratrol.

在白藜蘆醇的包覆率測試實驗方面,首先將包含白藜蘆醇之脂質體以10000rpm轉速離心15分鐘後,取上清液以甲醇稀釋,並以過濾膜(PhreeTM Phospholipid Removal,Phenomenex)過濾後,將濾液利用高效液相層析儀進行分析,而高效液相層析儀的檢測條件如下:注入體積為50μL,偵測波長以待測物(於本試驗例即為白藜蘆醇)作調整,以88%甲醇+11%水+1%醋酸作為移動相等位(isocratic)沖提,移動相流速1.0mL/分鐘。採用濃度1 ppm~100ppm的白藜蘆醇標準溶液建立檢量線,每種濃度都做3次重複偵測並取平均值。訊號擷取與處理採peak-ABC層析數據處理系統軟體(Great Tide Instruments,Taiwan),以公式I計算包覆率。 In the test of the coating rate of resveratrol, first the liposomes containing resveratrol were centrifuged at 10,000 rpm for 15 minutes, and then the supernatant was diluted with methanol and filtered with a membrane (PhreeTM Phospholipid Removal, Phenomenex) After filtration, the filtrate is analyzed by high performance liquid chromatograph, and the detection conditions of high performance liquid chromatograph are as follows: the injection volume is 50μL, and the detection wavelength is based on the test substance (in this test example, it is resveratrol). ) For adjustment, use 88% methanol + 11% water + 1% acetic acid as a mobile isocratic extraction, and the mobile phase flow rate is 1.0 mL/min. Adopt concentration 1 Resveratrol standard solution of ppm~100ppm establishes a calibration line, and each concentration is detected 3 times and the average value is taken. The signal acquisition and processing adopts peak-ABC tomography data processing system software (Great Tide Instruments, Taiwan), and formula I is used to calculate the coverage rate.

Figure 108124758-A0101-12-0010-19
Figure 108124758-A0101-12-0010-19

於本試驗例中,測試例1至測試例5的製備條件係根據本發明之防曬脂質體的製備方法進行製備,但其第一溶液中不包含至少一防曬劑,第二溶液中不包含膽固醇,測試例1至測試例5所使用的詳細試驗條件列於表一。 In this test example, the preparation conditions of Test Example 1 to Test Example 5 are prepared according to the method for preparing sunscreen liposomes of the present invention, but the first solution does not contain at least one sunscreen agent, and the second solution does not contain cholesterol , The detailed test conditions used in Test Example 1 to Test Example 5 are listed in Table 1.

Figure 108124758-A0101-12-0010-1
Figure 108124758-A0101-12-0010-1

測試例1至測試例5的包含白藜蘆醇之脂質體的平均粒徑、兩週後平均粒徑、白藜蘆醇的包覆率、兩週後白藜蘆醇的包覆率及界面電位結果列於表二。 The average particle size of the liposomes containing resveratrol of Test Example 1 to Test Example 5, the average particle size after two weeks, the coating rate of resveratrol, the coating rate and interface of resveratrol after two weeks The potential results are listed in Table 2.

Figure 108124758-A0101-12-0010-2
Figure 108124758-A0101-12-0010-2

由表二的結果可見,當高壓均質壓力越大,包含白藜蘆醇之脂質體的平均粒徑越小,但包含白藜蘆醇之脂質體對於白藜蘆醇的包覆率的結果差距甚小,顯示高壓均質機的高壓均質壓力在400巴至1500巴的條件範圍下皆可有效地包覆白藜蘆醇,是以本發明之防曬脂質體的製備方法可使用高壓均質壓力為400巴至1500巴的高壓均質機進行均質,以獲得平均粒徑、白藜蘆醇的包覆率與界面電位皆優的防曬脂質體。然由表二的結果顯示,當高壓均質壓力為600巴時,可獲得最佳白藜蘆醇的包覆率的含白藜蘆醇之脂質體(包覆率為43.93±0.37%),是以後續試驗條件中的高壓均質壓力均使用600巴進行防曬脂質體的製備。 It can be seen from the results in Table 2 that the higher the high-pressure homogenization pressure, the smaller the average particle size of the liposomes containing resveratrol, but the result of the difference in the coating rate of the liposomes containing resveratrol to resveratrol It is very small, showing that the high-pressure homogenizing pressure of the high-pressure homogenizer can effectively coat resveratrol under the condition of 400 bar to 1500 bar. Therefore, the method for preparing sunscreen liposomes of the present invention can use a high-pressure homogenizing pressure of 400 bar. The high-pressure homogenizer of bar to 1500 bar performs homogenization to obtain sunscreen liposomes with excellent average particle size, resveratrol coating rate and interface potential. However, the results in Table 2 show that when the high-pressure homogenization pressure is 600 bar, the best resveratrol coating rate can be obtained with resveratrol-containing liposomes (the coating rate is 43.93±0.37%). The high-pressure homogenization pressure in the subsequent test conditions was used to prepare sunscreen liposomes at 600 bar.

<膽固醇添加比例對於脂質體的物理性質影響評估><Evaluation of the effect of cholesterol addition ratio on the physical properties of liposomes>

於本試驗例中,先製備未加入至少一防曬劑的白藜蘆醇脂質體(測試例6至測試例8),以測試第二溶液中卵磷脂和膽固醇的最佳混合比例,並利用雷射粒徑分析儀分析測試例6至測試例8之平均粒徑和界面電位,並以高效液相層析儀(HPLC)系統評估白藜蘆醇的包覆率。白藜蘆醇的包覆率、平均粒徑及其界面電位的分析方法請參考前段所述,在此則不再贅述。 In this test example, first prepare resveratrol liposomes without adding at least one sunscreen agent (test example 6 to test example 8) to test the optimal mixing ratio of lecithin and cholesterol in the second solution, and use the lecithin The particle size analyzer analyzes the average particle size and interface potential of Test Example 6 to Test Example 8, and uses a high performance liquid chromatography (HPLC) system to evaluate the coating rate of resveratrol. For the analysis method of the coating rate, average particle size and interface potential of resveratrol, please refer to the previous paragraph, so I will not repeat it here.

於本試驗例中,測試例6至測試例8的製備條件係根據本發明之防曬脂質體的製備方法進行製備,且均質步驟中的高壓均質壓力為600巴,但其第一溶液中不包含至少一防曬劑,測試例6至測試例8所使用的詳細試驗條件列於表三。 In this test example, the preparation conditions of Test Example 6 to Test Example 8 are prepared according to the method for preparing sunscreen liposomes of the present invention, and the high-pressure homogenization pressure in the homogenization step is 600 bar, but the first solution does not contain At least one sunscreen, and the detailed test conditions used in Test Example 6 to Test Example 8 are listed in Table 3.

Figure 108124758-A0101-12-0012-3
Figure 108124758-A0101-12-0012-3

測試例6至測試例8的白藜蘆醇脂質體的平均粒徑、兩週後平均粒徑、白藜蘆醇的包覆率、兩週後白藜蘆醇的包覆率及界面電位結果列於表四。 Results of the average particle size of the resveratrol liposomes of Test Example 6 to Test Example 8, the average particle size after two weeks, the coating rate of resveratrol, the coating rate of resveratrol and the interface potential after two weeks Listed in Table 4.

Figure 108124758-A0101-12-0012-4
Figure 108124758-A0101-12-0012-4

由表四的結果可見,測試例6至測試例8的白藜蘆醇脂質體在平均粒徑、白藜蘆醇的包覆率和界面電位的結果差距甚小,顯示第二溶液中卵磷脂與膽固醇的重量百分比為10:1至30:1的比例混合的條件範圍下皆可有效地包覆白藜蘆醇,是以本發明之防曬脂質體的製備方法中卵磷脂與膽固醇的重量百分比可為10:1至30:1的比例進行混合,可以獲得平均粒徑、白藜蘆醇的包覆率與界面電位皆優的防曬脂質體。然由表四的結果顯示,當卵磷脂與膽固醇的重量百分比為15:1時,可獲得最佳白藜蘆醇包覆率的白藜蘆醇脂質體(包覆率為42.25±0.47%),且於室溫條件儲放兩週後,其白藜蘆醇的包覆率仍大致維持恆定,是以後續試驗條件中,第二溶液中的卵磷脂與膽固醇的重量百分比均使用15:1進行防曬脂質體的製備。 It can be seen from the results in Table 4 that the results of the resveratrol liposomes of Test Example 6 to Test Example 8 in the average particle size, the coating rate of resveratrol and the interface potential are very small, indicating that the lecithin in the second solution Resveratrol can be effectively coated under the conditions of mixing with a ratio of 10:1 to 30:1 by weight of cholesterol, which is the weight percentage of lecithin and cholesterol in the method for preparing sunscreen liposomes of the present invention It can be mixed in a ratio of 10:1 to 30:1, and a sunscreen liposome with excellent average particle size, resveratrol coating rate and interface potential can be obtained. However, the results in Table 4 show that when the weight percentage of lecithin and cholesterol is 15:1, resveratrol liposomes with the best resveratrol coating rate can be obtained (the coating rate is 42.25±0.47%) And after two weeks of storage at room temperature, the coating rate of resveratrol remains roughly constant. Therefore, in the subsequent test conditions, the weight percentage of lecithin and cholesterol in the second solution is 15:1 The preparation of sunscreen liposomes is carried out.

<實施例><Example>

實施例係以前述最佳製備條件製備本發明之防曬脂質體,且於實施例1中至少一防曬劑為OMC,實施例2中至少一防曬劑為OMC和B-MDM。此外,試驗上另製備未添加膽固醇的比較例1作為對照組。所製得的實施例1、實施例2和比較例1之防曬脂質體進一步進行平均粒徑分析、界面電位分析、白藜蘆醇的包覆率分析和防曬劑的包覆率分析。其中白藜蘆醇的包覆率、平均粒徑及其界面電位的分析方法請參考前段所述,在此則不再贅述。而防曬劑的包覆率分析方法與白藜蘆醇的包覆率分析方法相同,但將待測物由白藜蘆醇置換為防曬劑。 The example is to prepare the sunscreen liposome of the present invention under the aforementioned optimal preparation conditions, and in Example 1, at least one sunscreen is OMC, and in Example 2, at least one sunscreen is OMC and B-MDM. In addition, Comparative Example 1 with no cholesterol added was prepared as a control group. The prepared sunscreen liposomes of Example 1, Example 2 and Comparative Example 1 were further subjected to average particle size analysis, interface potential analysis, resveratrol coating rate analysis, and sunscreen coating rate analysis. For the analysis methods of the coating rate, average particle size and interface potential of resveratrol, please refer to the previous paragraph, which will not be repeated here. The analysis method of the coating rate of sunscreen is the same as that of resveratrol, but the analyte is replaced with a sunscreen from resveratrol.

詳細試驗步驟如下:秤取不同比例的白藜蘆醇、OMC和B-MDM溶於重量百分比為5%之乙醇水溶液中,即為本發明之第一溶液。接著秤取不同比例的卵磷脂和膽固醇溶於重量百分比為5%之乙醇水溶液中,即為本發明之第二溶液。接著,將第二溶液與第一溶液以體積百分比1:1混合,以直流攪拌機(EURO-ST D S1 So,IKA,Germany)以轉速500rpm均勻攪拌,以及超音波震盪(DC300H,DELTA,Taiwan)小時,使第一溶液和第二溶液均勻分散以形成一乳化物,並將前述之乳化物以間歇性超音波振盪2分鐘後,以高壓均質機(APV-2000,SPXFLOW,Germany)於高壓均質壓力為600巴的條件下均質5次,以製得本發明之防曬脂質體。而本發明之實施例1、實施例2和比較例1的詳細製備條件列於表五。 The detailed test procedure is as follows: weigh different proportions of resveratrol, OMC and B-MDM and dissolve them in 5% by weight ethanol aqueous solution, which is the first solution of the present invention. Then weigh different proportions of lecithin and cholesterol and dissolve them in 5% by weight ethanol aqueous solution, which is the second solution of the present invention. Next, mix the second solution and the first solution at a volume percentage of 1:1, stir evenly with a DC mixer (EURO-ST D S1 So, IKA, Germany) at 500 rpm, and ultrasonic vibration (DC300H, DELTA, Taiwan) After hours, the first solution and the second solution were uniformly dispersed to form an emulsion, and the aforementioned emulsion was oscillated with intermittent ultrasound for 2 minutes, and then homogenized at high pressure with a high-pressure homogenizer (APV-2000, SPXFLOW, Germany) The homogenization was performed 5 times under the condition of a pressure of 600 bar to prepare the sunscreen liposome of the present invention. The detailed preparation conditions of Example 1, Example 2 and Comparative Example 1 of the present invention are listed in Table 5.

Figure 108124758-A0101-12-0013-5
Figure 108124758-A0101-12-0013-5
Figure 108124758-A0101-12-0014-6
Figure 108124758-A0101-12-0014-6

請參照表六,其係實施例1、實施例2和比較例1之防曬脂質體的平均粒徑、兩週後平均粒徑、白藜蘆醇的包覆率、兩週後白藜蘆醇的包覆率、界面電位、OMC的包覆率、兩週後的OMC包覆率、B-MDM的包覆率和兩週後的B-MDM包覆率測試結果。 Please refer to Table 6, which is the average particle size of the sunscreen liposomes of Example 1, Example 2 and Comparative Example 1, the average particle size after two weeks, the coating rate of resveratrol, and the resveratrol after two weeks. Test results of the coverage rate, interface potential, OMC coverage rate, OMC coverage rate after two weeks, B-MDM coverage rate and B-MDM coverage rate after two weeks.

Figure 108124758-A0101-12-0014-7
Figure 108124758-A0101-12-0014-7

由表六的結果可見,實施例1和實施例2之防曬脂質體的白藜蘆醇的包覆率均達50%以上(分別為50.07±0.67%和55.09±0.98%),且在室溫條件儲放兩週後,其白藜蘆醇的包覆率依然維持在40%以上。此外,實施例1和實施例2之防曬脂質體的OMC的包覆率約為40%(分別為39.77±0.51%和40.10±0.08%),且在室溫條件儲放兩週後,其OMC的包覆率依然維持在30%以上。而同時包覆OMC和B-MDM的實施例2,其B-MDM的包覆率亦高達50.45±0.21%。顯示以本發明之防曬脂質體的製備方法不 僅可有效包覆白藜蘆醇和至少一防曬劑,其所製得之防曬脂質體亦具有良好的穩定性,有利於後續的應用。 From the results in Table 6, it can be seen that the coating rate of resveratrol in the sunscreen liposomes of Example 1 and Example 2 reached more than 50% (50.07±0.67% and 55.09±0.98%, respectively), and at room temperature After two weeks of storage, the coating rate of resveratrol remained above 40%. In addition, the OMC coating rate of the sunscreen liposomes of Example 1 and Example 2 is about 40% (39.77±0.51% and 40.10±0.08%, respectively), and after two weeks of storage at room temperature, the OMC The coverage rate is still maintained at more than 30%. In Example 2, where OMC and B-MDM are simultaneously coated, the coverage rate of B-MDM is also as high as 50.45±0.21%. Shows that the preparation method of sunscreen liposomes of the present invention is not It can only effectively coat resveratrol and at least one sunscreen, and the sunscreen liposomes prepared therefrom also have good stability, which is conducive to subsequent applications.

<防曬脂質體的經皮傳輸的能力測定><Measurement of the transdermal delivery ability of sunscreen liposomes>

本試驗例進一步以體外經皮傳輸分析,測試本發明之防曬脂質體是否具影響人體之穿透特性,以評估本發明之防曬脂質體對皮膚的致敏疑慮。 This test example further used in vitro transdermal transmission analysis to test whether the sunscreen liposome of the present invention has the penetrating properties that affect the human body, so as to evaluate the skin sensitization doubt of the sunscreen liposome of the present invention.

體外經皮傳輸分析之試驗步驟如下。先將豬耳皮以去離子水清理乾淨,以解剖刀取豬耳上皮(去除脂肪層),再裁切成面積1.5×1.5cm2、厚度650μm之穿透膜,以PBS浸濕封袋後冷凍備用。試驗前將穿透膜浸泡在PBS生理溶液中解凍至室溫,使角質細胞間隙回復膨潤之自然狀態,將穿透膜固定在Franz-type擴散槽(Franz-type diffusion cell,LOGAN FDC-6,USA),擴散面積為0.636cm2,為測試皮膚之完整性,先於擴散槽上下層填充50%乙醇+50%PBS,並去除下槽氣泡後,在上層施藥端(donor cell)重新放置0.5g樣品,測試之樣品包含實施例1、實施例2和比較例1,並以OMC、OMC-B-MDM和OMC-1789作為對照組。置入50%乙醇+50%PBS於下層受藥端(receptor cell,體積為5.3mL),使用恆溫水槽加熱器,控制水溫在35℃±1,並藉由磁石攪拌,平衡受藥端內藥物濃度分佈。每次實驗同時使用5個擴散槽測定,並取平均值,從受藥端取樣50μL以HPLC分析,並隨即回填相同體積的生理溶液,以確保受藥端內的體積不變。每次實驗同時使用5個擴散槽測定,並取平均值,從受藥端取樣50μL以 HPLC分析,並隨即回填相同體積的生理溶液,以確保受藥端內的體積不變。 The test procedure for in vitro transdermal transmission analysis is as follows. First clean the pig ear skin with deionized water, take the pig ear epithelium with a scalpel (to remove the fat layer), and then cut it into a penetrating membrane with an area of 1.5×1.5cm 2 and a thickness of 650 μm. After soaking the bag with PBS Frozen for later use. Before the test, the penetrating membrane was immersed in PBS physiological solution to thaw to room temperature to restore the natural state of swelling between the keratinocytes, and the penetrating membrane was fixed in the Franz-type diffusion cell (LOGAN FDC-6, USA), the diffusion area is 0.636cm 2 , in order to test the integrity of the skin, the upper and lower layers of the diffusion tank are filled with 50% ethanol + 50% PBS, and the bubbles in the lower tank are removed, and then placed on the upper donor cell. 0.5g sample, the tested samples include Example 1, Example 2 and Comparative Example 1, and OMC, OMC-B-MDM and OMC-1789 were used as the control group. Place 50% ethanol + 50% PBS in the lower drug-receiving end (receptor cell, volume 5.3mL), use a constant temperature water tank heater, control the water temperature at 35℃±1, and stir it with a magnet to balance the drug-receiving end Drug concentration distribution. In each experiment, 5 diffusion tanks were used for measurement at the same time, and the average value was taken. A sample of 50 μL from the drug-receiving end was analyzed by HPLC, and then the same volume of physiological solution was backfilled to ensure that the volume in the drug-receiving end remained unchanged. In each experiment, 5 diffusion tanks were used for measurement at the same time, and the average value was taken. A sample of 50 μL from the drug-receiving end was analyzed by HPLC, and then the same volume of physiological solution was backfilled to ensure that the volume in the drug-receiving end remained unchanged.

請參照第3圖、第4圖、第5圖和第6圖,其中第3圖和第4圖係繪示本發明實施例1之防曬脂質體之體外經皮傳輸之穿透量曲線圖,其中第3圖和第4圖的對照組為OMC。第5圖和第6圖係繪示本發明實施例2之防曬脂質體之體外經皮傳輸之穿透量曲線圖,其中第5圖的對照組為OMC-B-MDM,第6圖的對照組為OMC-1789。 Please refer to Figure 3, Figure 4, Figure 5 and Figure 6, where Figure 3 and Figure 4 are graphs showing the in vitro transdermal penetration curve of the sunscreen liposome of Example 1 of the present invention. The control group in Figures 3 and 4 is OMC. Figures 5 and 6 are graphs showing the penetration curve of the sunscreen liposomes in vitro for transdermal delivery of Example 2 of the present invention. The control group in Figure 5 is OMC-B-MDM, and the control in Figure 6 The group is OMC-1789.

第3圖和第4圖的結果顯示,OMC在試驗0.5小時後,即具有經皮穿透的情況,但不論是實施例1或比較例1在經皮穿透方面皆沒有破裂釋放的情形。而第5圖的結果顯示,OMC-B-MDM在試驗0.5小時後,即具有經皮穿透的情況,但實施例2在試驗6小時的累積通透量不到0.1μg/cm2。第6圖的結果顯示,OMC-1789在試驗1小時後,即具有經皮穿透的情況,但實施例2經皮穿透方面皆沒有破裂釋放的情形。上述結果顯示本發明之防曬脂質體確實能達到長效保護效果,並不會經皮吸收造成致敏。 The results in Figures 3 and 4 show that OMC has percutaneous penetration after 0.5 hours of the test, but neither Example 1 nor Comparative Example 1 has a rupture release in terms of percutaneous penetration. The results in Figure 5 show that OMC-B-MDM has percutaneous penetration after 0.5 hours of the test, but the cumulative permeability of Example 2 during the 6 hours of the test is less than 0.1 μg/cm 2 . The results in Figure 6 show that OMC-1789 has percutaneous penetration after 1 hour of the test, but there is no rupture and release in the percutaneous penetration of Example 2. The above results show that the sunscreen liposomes of the present invention can indeed achieve long-term protection, and will not cause sensitization due to transdermal absorption.

<防曬脂質體的防曬能力分析><Analysis of sunscreen ability of sunscreen liposomes>

本試驗例進一步本發明之防曬脂質體製備為防曬製劑,並利用體外紫外線防護能力分析對本發明之防曬脂質體的防曬能力進行分析。體外紫外線防護能力分析係利用Optomeric SPF-290S防曬係數測定儀,測定體外(in vitro)SPF值(sun protection factor),探討對紫外線的防禦力。體外試驗過程中,以3M(TransporeTM Tape)來當 作人造皮定量塗抹2mg/cm2防曬乳接受SPF儀之太陽模擬燈照射,測試結果計算出SPF評估參數。 In this test example, the sunscreen liposome of the present invention is further prepared as a sunscreen preparation, and the sunscreen ability of the sunscreen liposome of the present invention is analyzed by using in vitro ultraviolet protection ability analysis. The in vitro UV protection ability analysis system uses Optomeric SPF-290S sun protection factor tester to measure the in vitro SPF value (sun protection factor) and explore the defense against UV rays. During the in vitro test, 3M (Transpore TM Tape) was used as artificial leather to quantitatively apply 2mg/cm 2 sunscreen to receive the solar simulation lamp of the SPF meter, and the SPF evaluation parameters were calculated from the test results.

請參照表七,為包含本發明之防曬脂質體的防曬製劑的詳細的重量百分比配比。 Please refer to Table 7 for the detailed weight percentage ratio of the sunscreen preparation containing the sunscreen liposome of the present invention.

Figure 108124758-A0101-12-0017-8
Figure 108124758-A0101-12-0017-8

請參照第7圖、第8圖、表八和表九,第7圖係繪示本發明實施例3之含防曬脂質體之防曬製劑的防曬能力分析結果圖,第8圖係繪示本發明實施例4之含防曬脂質體之防曬製劑的防曬能力分析結果圖,表八為實施例3之含防曬脂質體之防曬製劑的防曬能力分析結果,表九為實施例4之含防曬脂質體之防曬製劑的防曬能力分析結果。 Please refer to Figure 7, Figure 8, Table 8 and Table 9. Figure 7 shows the results of the analysis of the sun protection ability of the sunscreen formulation containing sunscreen liposomes according to Example 3 of the present invention, and Figure 8 shows the present invention. The results of the analysis of the sunscreen ability of the sunscreen formulation containing sunscreen liposomes in Example 4. Table 8 shows the analysis results of the sunscreen ability of the sunscreen formulation containing sunscreen liposomes of Example 3, and Table 9 shows the results of the sunscreen liposome containing sunscreen of Example 4 The analysis result of sunscreen ability of sunscreen preparation.

Figure 108124758-A0101-12-0017-20
Figure 108124758-A0101-12-0017-20

Figure 108124758-A0101-12-0017-10
Figure 108124758-A0101-12-0017-10

第7圖和表八結果顯示,實施例3的SPF值為8.45±0.06,優於比較例2和比較3的SPF值(分別為7.60±0.09和8.17±0.04)。再經由紫外線模擬儀照射破壞後,實施例3之防曬係數下降6.11%,比較例2和比較3的防曬係數分別下降8.91%和8.12%,實施例3可以有效保護OMC避免其降解,顯示本發明之實施例3的防曬效果以及持久性優於未包覆脂質體的OMC。 The results in Figure 7 and Table 8 show that the SPF value of Example 3 is 8.45±0.06, which is better than the SPF values of Comparative Examples 2 and 3 (7.60±0.09 and 8.17±0.04, respectively). After being damaged by the ultraviolet ray simulator, the sun protection factor of Example 3 decreased by 6.11%, and the sun protection factors of Comparative Example 2 and Comparative Example 3 decreased by 8.91% and 8.12%, respectively. Example 3 can effectively protect OMC from degradation, showing that the present invention The sun protection effect and durability of Example 3 are better than those of OMC without liposomes.

第8圖和表九結果顯示,實施例4的SPF值為15.59±0.32,優於比較例4的SPF值(14.55±0.18)。再經由紫外線模擬儀照射破壞後,實施例4之防曬係數下降38%,比較例4的防曬係數下降44.92%,實施例4可以有效保護OMC-B-MDM避免其降解,顯示本發明之實施例4的防曬效果以及持久性優於未包覆脂質體的OMC-B-MDM。 The results in Figure 8 and Table 9 show that the SPF value of Example 4 is 15.59±0.32, which is better than the SPF value of Comparative Example 4 (14.55±0.18). After being damaged by the ultraviolet ray simulator, the sun protection factor of Example 4 was reduced by 38%, and the sun protection factor of Comparative Example 4 was reduced by 44.92%. Example 4 can effectively protect OMC-B-MDM from degradation, showing an example of the present invention The sun protection effect and durability of 4 are better than that of OMC-B-MDM without liposomes.

綜上所述,本發明提供一種防曬脂質體及防曬脂質體之製備方法。本發明之防曬脂質體之製備方法的製程簡單,且所製備出之防曬脂質體是一種新穎的防曬原料。進一步地說,本發明之防曬脂質體的製備方法透過第二溶液所包含的卵磷脂及膽固醇以重量百分比10:1至30:1的比例混合的方式,可有效地對白藜蘆醇和至少一防曬劑進行包覆,進而使本發明之防曬脂質體的製備方法100所製得之防曬脂質體具有高可變性、易於吸收之特性,並具有適當的平均粒徑、界面電位與包覆率,可增加化學性防曬劑的防曬效能,以減少化學性防曬劑的用量,以及降低化學性防曬劑經皮吸收所造成的刺激反應,具有應用於化妝品市場之潛能。 In summary, the present invention provides a sunscreen liposome and a preparation method of the sunscreen liposome. The preparation method of the sunscreen liposome of the present invention has a simple process, and the prepared sunscreen liposome is a novel sunscreen material. Furthermore, the preparation method of sunscreen liposomes of the present invention can effectively treat resveratrol and at least one sunscreen by mixing the lecithin and cholesterol contained in the second solution in a ratio of 10:1 to 30:1 by weight. The sunscreen liposome is coated with the sunscreen liposome, so that the sunscreen liposome prepared by the method 100 of the present invention has the characteristics of high variability, easy absorption, and appropriate average particle size, interface potential, and coating rate. Increasing the sunscreen efficacy of chemical sunscreens, reducing the amount of chemical sunscreens, and reducing the irritation caused by the transdermal absorption of chemical sunscreens, has the potential to be applied to the cosmetics market.

然本發明已以實施方式揭露如上,然其並非用以限定本發明,任何熟習此技藝者,在不脫離本發明的精神和範圍內,當可作各種的更動與潤飾,因此本發明的保護範圍當視後附的申請專利範圍所界定者為準。 Although the present invention has been disclosed in the above embodiments, it is not intended to limit the present invention. Anyone who is familiar with the art can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the protection of the present invention The scope shall be subject to the scope of the attached patent application.

100‧‧‧防曬脂質體的製備方法 100‧‧‧Preparation method of sunscreen liposome

110‧‧‧提供一第一溶液 110‧‧‧Provide a first solution

120‧‧‧提供一第二溶液 120‧‧‧Provide a second solution

130‧‧‧進行一油包水型乳化反應 130‧‧‧Perform a water-in-oil type emulsification reaction

140‧‧‧進行一均質步驟 140‧‧‧Perform a homogenization step

Claims (7)

一種防曬脂質體的製備方法,包含下述步驟:提供一第一溶液,其中該第一溶液用以作為水相並包含一白藜蘆醇和甲氧基肉桂酸辛酯,其中該白藜蘆醇與該甲氧基肉桂酸辛酯以重量百分比1:100的比例混合;提供一第二溶液,該第二溶液用以作為油相並包含一卵磷脂及一膽固醇,其中該卵磷脂與該膽固醇係以重量百分比10:1至30:1的比例混合;進行一油包水型乳化反應,其係混合該第一溶液與該第二溶液,以形成一乳化物;以及進行一均質步驟,其係以一均質機均質該乳化物,以製得一防曬脂質體,其中該均質機為一高壓均質機,且該高壓均質機之一高壓均質壓力為400巴至1500巴。 A method for preparing sunscreen liposomes includes the following steps: providing a first solution, wherein the first solution is used as an aqueous phase and contains a resveratrol and octyl methoxycinnamate, wherein the resveratrol and The octyl methoxycinnamate is mixed in a ratio of 1:100 by weight; a second solution is provided, which is used as an oil phase and contains a lecithin and a cholesterol, wherein the lecithin and the cholesterol are Mix in a ratio of 10:1 to 30:1 by weight; perform a water-in-oil emulsification reaction, which is to mix the first solution and the second solution to form an emulsion; and perform a homogenization step, which is A homogenizer homogenizes the emulsion to prepare a sunscreen liposome, wherein the homogenizer is a high-pressure homogenizer, and a high-pressure homogenization pressure of the high-pressure homogenizer is 400 bar to 1500 bar. 如申請專利範圍第1項所述之防曬脂質體的製備方法,其中該油包水型乳化反應中,該第一溶液和該第二溶液係以超音波震盪和攪拌進行混合。 According to the method for preparing sunscreen liposomes as described in item 1 of the scope of patent application, in the water-in-oil emulsification reaction, the first solution and the second solution are mixed by ultrasonic vibration and stirring. 一種防曬脂質體,其係利用如申請專利範圍第1項至第2項任一項之製備方法製得。 A sunscreen liposome, which is prepared by the preparation method according to any one of items 1 to 2 of the scope of patent application. 如申請專利範圍第3項所述之防曬脂質體,其中該防曬脂質體的一平均粒徑為200nm至400nm。 The sunscreen liposome described in item 3 of the scope of patent application, wherein an average particle size of the sunscreen liposome is 200nm to 400nm. 如申請專利範圍第3項所述之防曬脂質體,其中該防曬脂質體的一界面電位為-60mV至-40mV。 The sunscreen liposome described in item 3 of the scope of patent application, wherein an interface potential of the sunscreen liposome is -60mV to -40mV. 如申請專利範圍第3項所述之防曬脂質體,其中該白藜蘆醇的包覆率為45%至60%。 The sunscreen liposome described in item 3 of the scope of patent application, wherein the coating rate of the resveratrol is 45% to 60%. 如申請專利範圍第3項所述之防曬脂質體,其中該甲氧基肉桂酸辛酯的包覆率為35%至60%。 The sunscreen liposome described in item 3 of the scope of patent application, wherein the coating rate of the octyl methoxycinnamate is 35% to 60%.
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