TWM530653U - Liposome structure capable of improving transdermal penetration of effective ingredients - Google Patents

Description

Liposomal structure capable of improving transdermal absorption rate of active ingredient

The present invention relates to a liposome structure capable of improving the transdermal absorption rate of an active ingredient, which comprises an inner core comprising: an essence core comprising an active ingredient; and a lipoprotective layer having a hydrophilic property. The inner side surface facing the essence core and a hydrophilic outer surface away from the essence core, and a hydrophobic region between the inner side surface and the outer side surface. The liposome structure can increase the transdermal absorption rate of the active ingredient, so that the active ingredient can enter the skin quickly and completely, absorb and function through the skin tissue, and then the same or better effect can be achieved by using a smaller amount of the active ingredient.

Many anti-oxidant substances made from natural sources or artificially have been used to protect the skin by reducing the amount of free radicals in the skin tissue due to exposure to ultraviolet light, diet and work-and-rest, stress, and metabolism. Reduces dullness, spots, fine lines, dryness, loss of elasticity, etc. caused by free radical attack, and improves skin condition. These antioxidant-resistant substances can be eaten into health foods, or medicinal skin care products or cosmetics containing antioxidants can be applied to the skin, so that the antioxidant components are directly absorbed by the skin parts that are desired to be improved. Different antioxidant components have different properties and they are used directly on the skin surface. The efficiency of direct absorption by skin cells is also different. Therefore, how to make these active ingredients absorb well by the skin is the most critical problem at the application level.

In order to solve the above problems, the present invention provides a liposome structure capable of improving the transdermal absorption rate of an active ingredient, which comprises an inner core comprising: an essence core comprising an active ingredient; and a lipoprotective layer having A hydrophilic surface faces the inner side surface of the essence core and a hydrophilic outer surface away from the essence core, and has a hydrophobic region between the inner side surface and the outer side surface.

In the present liposome structure which can improve the transdermal absorption rate of the active ingredient, the particle diameter can be from 100 micrometers to 500 micrometers.

In the liposome structure of the present invention which improves the transdermal absorption rate of the active ingredient, the essence core may have a thickness of from 30 micrometers to 150 micrometers.

In the liposome structure of the present invention which improves the transdermal absorption rate of the active ingredient, the lipoprotective layer may have a thickness of from 30 micrometers to 200 micrometers.

In the liposome structure of the present invention which can improve the transdermal absorption rate of the active ingredient, the essence core may be in a homogeneous state, and the active ingredient may be at least one of astaxanthin and vitamin C.

The liposome structure of the present invention which can improve the transdermal absorption rate of the active ingredient can be in the form of a powder, a solution, a suspension, a gel, an emulsion, a cream, or a mask.

The effect of this new creation is that it can be improved by providing one The liposome structure of the percutaneous absorption rate of the component encapsulates the essence core containing the active ingredient in the protective layer of the liposome, and utilizes the characteristics of the liposome to enhance the transdermal absorption rate of the active ingredient, so that the active ingredient can be quickly and completely entered. The skin, absorbed and functioning through the skin tissue, can then achieve the same or better efficacy with a smaller amount of active ingredient. In the present creation, since the outer surface of the liposome structure is hydrophilic, the particles can be smoothly dispersed in the aqueous solution. Moreover, the hydrophilic component is soluble in the inner layer of the aqueous coating, and the hydrophobic component is soluble in the hydrophobic region of the protective layer of the liposome, and the active ingredient having different properties can be simultaneously delivered.

In addition, the liposome structure can protect the active ingredients contained therein, reduce the loss caused by the external environment (such as interaction with oxygen in the air), and the liposome particles themselves can provide lipid and water as cell repair. raw material. The liposome structure of the present invention can achieve a better effect than the direct application of the active ingredient.

1‧‧‧Liposome structure

2‧‧‧Essence core

3‧‧‧ liposome protective layer

4‧‧‧ inside surface

5‧‧‧ outside surface

6‧‧‧hydrophobic area

7‧‧‧phospholipid molecules

8‧‧‧Hydrophilic end

9‧‧‧hydrophobic end

10‧‧‧Essence containing the liposome structure of this creation

11‧‧‧ bottles

12‧‧‧ Caps with dropper

a, b‧‧‧ thickness

Figure 1a is a partial cross-sectional view of the liposome structure created in accordance with the present invention.

Figure 1b is a partially enlarged schematic view of the liposome protective layer of the novel liposome structure.

Figure 2 is a schematic representation of the use of one of the liposome structures created according to the present invention.

Figure 3a is a comparison of the cumulative diffusion amount of astaxanthin particles created according to the present invention and astaxanthin not produced according to the present invention within 12 hours.

Figure 3b compares the delay time and penetration coefficient of astaxanthin particles created according to the present invention with astaxanthin not produced according to the present invention.

Figure 4a is a comparison of the cumulative diffusion amount of vitamin C particles created according to the present invention and vitamin C not produced according to the present invention within 12 hours.

Figure 4b compares the delay time and penetration coefficient of vitamin C particles created according to the present invention with vitamin C not produced according to the present invention.

Figure 5a compares the skin properties measured with the serum containing the aspergillus microparticles according to the present invention and the serum of the comparative example for 8 weeks.

Fig. 5b is a photograph comparing the appearance of the skin after containing the essence of the astaxanthin particles according to the present invention and the serum of the comparative example for 8 weeks.

Fig. 6 is a comparison of the skin properties measured after using the serum containing the vitamin C microparticles according to the present invention and the comparative serum for 4 weeks, respectively.

Some of the implementations of the present invention will be described more fully hereinafter with reference to the accompanying drawings, and the present invention may be practiced in many different forms and should not be construed as being limited to the illustrated embodiments. In addition, in the drawings, the dimensions of the various items and regions may be exaggerated for clarity, and are not shown in actual scale. In the meantime, the terms "a", "an" and "the" are used in the singular and plural terms.

Referring to Figure 1a, a partial cross-sectional view of a liposome structure created in accordance with the present invention is shown. As shown in Figure 1a, the liposome structure 1 is packaged from the inside out. Including: an essence core 2 comprising an active ingredient; and a lipoprotective layer 3 having a hydrophilic inner side surface 4 facing the essence core and a hydrophilic outer side surface 5 away from the essence core, and on the inner side There is a hydrophobic region 6 between the surface and the outer surface.

Figure 1b shows a partial enlarged schematic view of the liposome protective layer 3. As shown in Fig. 1b, the liposome protective layer 3 is mainly composed of a plurality of phospholipid molecules 7 arranged to form a two-layer membrane structure, and the phospholipid molecule 7 has a hydrophilic end 8 and a hydrophobic end 9, which are arranged through the hydrophilic end 8. The inner side surface 4 and the outer side surface 5, while the hydrophobic end 9 form a hydrophobic area 6.

Phospholipid molecules suitable for use in the present invention may be selected, for example, from phosphatidic acid, phospholipid choline, phospholipid oxime ethanolamine, phospholipidylserine, phosphoinositides, sphingolipids ( Phosphosphingolipids), and any other natural or synthetic phospholipid molecule known to those skilled in the art to form a stable phospholipid bilayer membrane structure without adversely affecting the human body, and one or more different phospholipid molecules may be used. The phospholipid molecular species can be selected with reference to the technical literature in the art, for example, refer to the work of Betz G et al. In vivo comparison of various liposome formulations for cosmetic application (Int J Pharm. 2005 May 30; 296(1-2): 44-54); For example, lecithin obtained by extraction from egg yolk can be used.

In the liposome protective layer, in addition to the phospholipid molecule, molecules which are compatible with the phospholipid bilayer membrane structure and have no negative influence on the human body, such as proteins, glycolipids, sterols, etc., may be added as needed; Need to adjust. The physical and chemical properties of the liposome protective layer can be adjusted by the ingredients added, thereby adjusting the rate at which the liposome structure is absorbed by human tissue, or facilitating the liposome particles to be readily absorbed by a particular type of cell. For example, those skilled in the art will appreciate that the addition of a suitable ratio of sterols to the liposome protective layer may result in a property of the liposome protective layer that is more similar to cell membrane properties, since the biological cell membrane contains a portion of the sterol molecules.

In the liposome structure 1 of the present invention which can improve the transdermal absorption rate of the active ingredient, the particle diameter can be from 100 μm to 500 μm, preferably from 120 μm to 250 μm. The thickness a of the essence core 2 is usually from 30 μm to 150 μm, preferably from 40 μm to 120 μm, more preferably from 50 μm to 100 μm; and the thickness b of the lipoprotective layer 3 is usually from 30 μm to 200 μm, preferably It is from 50 micrometers to 160 micrometers, more preferably from 70 micrometers to 120 micrometers. The particle size of the liposome structure and the thickness of the essence core and the liposome protective layer which can improve the transdermal absorption rate of the active ingredient can also be adjusted by the skilled person after viewing the contents of the present specification without departing from the present invention. The scope of creation.

In the liposome structure 1 of the present invention, the essence core 2 containing the active ingredient may be in a homogeneous state. The actual composition and content of the essence core 2 can be adjusted by the skilled person as needed, for example, selecting one or more active ingredients according to the desired effect and adjusting the ratio between the active ingredients, and adjusting the active ingredients according to the physicochemical properties of the selected active ingredients. The concentration in the essence core, as well as the adjustment of the amount and proportion of other components, make the essence core stable and not easy to deteriorate. The active ingredient and other components in the core of the essence are not limited to the source and type, and any liposome structure which is compatible with the present invention and which can improve the transdermal absorption rate of the active ingredient can be used.

In one embodiment of the liposome structure according to the present invention, at least one of astaxanthin and vitamin C is used as an active ingredient.

Astaxanthin is a carotenoid found in nature in a variety of organisms such as salmon, trout, plankton, krill, yeast, algae, especially Haematococcus pluvialis. A large amount of astaxanthin is produced, and the astaxanthin molecule can also be synthesized. Vitamin C, also known as ascorbic acid, is widely found in plants and animals and is an important factor in many biochemical reactions. However, since humans cannot make vitamin C in the body, they must be supplemented from food or nutrients to maintain good physiology. function. For example, the lack of vitamin C will lead to the inability to function properly in the synthesis of collagen in the body, the collagen in the tissue is gradually reduced, the skin is tarnished and easily lost in moisture and becomes slack, and those who are severely deficient in vitamin C are more likely to suffer from soft tissue bleeding. Symptoms that are difficult to heal, eventually leading to scurvy. Both astaxanthin and vitamin C have antioxidant capacity, reducing skin damage caused by free radical attack by reducing the amount of free radicals in the skin tissue due to exposure to ultraviolet light, diet and work disorders, life stress, and metabolism. Problems such as dullness, spots, fine lines, dryness, loss of elasticity, etc., improve skin condition. In addition, astaxanthin and vitamin C have low toxicity to the human body, and are suitable for general daily maintenance, and can also be reused in areas where it is desired to strengthen the focus.

The liposome structure of the present invention may be in the form of a powder, a solution, a suspension, a gel, an emulsion, a cream, or a mask, but is not limited thereto. The liposome structure of the present invention can also be stored in a powder form, and the user can use it in a liquid form by adding an appropriate amount of solvent and mixing it well before use.

In the process of making the aforementioned forms, the skilled artisan can select the ingredients of the finished product comprising the liposome structure of the present invention as needed, such as suitable other active ingredients, emulsifiers, diluents, thickeners, moisturizers. Agents, antibacterial agents, and other suitable ingredients commonly used by people skilled in the art. The skilled person can adjust various physical and chemical properties of the finished product as needed, so that the liposome structure of the present invention can be stably existed and distributed in a desired manner (for example, evenly distributed), and the finished product does not be used on the user's skin. Cause any discomfort. Natural or synthetic pigments and/or fragrances, essential oils, etc. may also be added as appropriate to allow the user to feel happy during use.

After being manufactured into a finished product, the finished product containing the liposome structure of the present invention can be packaged and subsequently stored, transported, sold and used by the packaging method commonly used by the skilled person; the skilled person can select an appropriate packaging method according to the nature of the finished product, The protection product is not easily affected by external influences and is detrimental to the user. For example, it may be packaged by, for example, a glass bottle, a plastic bottle, a pneumatic spray bottle, a sterile sealed bag, a hose, a capsule, a soft capsule, or the like, but is not limited thereto. For example, solutions in the form of solutions, suspensions, and emulsions are mostly highly fluid, and are generally placed in bottles with narrow openings to avoid dumping and spillage, and can be easily used with a dropper or indenter; gelatinous Most of the cream-like products are more viscous. They are usually used in large-open bottles for excavation or in hoses. The mask-like products are often packaged in aseptic sealed bags.

Referring to Fig. 2, there is shown a schematic diagram showing the use of one of the liposome structures according to the present invention, in which the liposome structure of the present invention which improves the transdermal absorption rate of the active ingredient is used in liquid form. As shown in Figure 2, including this creation The liposome-structured essence 10 is packaged in a bottle 11, and the bottle 11 is provided with a bottle cap 12 with a dropper, and the bottle cap 12 with a dropper is normally tightened to seal the bottle 11 to avoid the essence 10 for a long time. It is in contact with the outside air and prevents spillage. When the user wants to use the essence 10, the bottle cap 12 with the dropper can be unscrewed, and the appropriate amount is taken out by the dropper, and it is applied to the skin part to be improved. The bottle 11 can be designed as an opaque bottle to prevent the essence 10 in the bottle from being exposed to ultraviolet rays for a long time, thereby reducing the deterioration or the failure of the active ingredient.

In addition to the essence form shown in Figure 2, the liposome structure of the present invention can also be adjusted as described above to adjust the components of the finished product and various physical and chemical properties to make a lotion and gel known to the skilled person. Products in the form of lotions, creams, and masks are not mentioned here.

The effect of the present creation is further illustrated by the following examples. The embodiments are provided for illustrative purposes only and are not intended to limit the scope of the invention. The scope of this creation is as shown in the attached patent application.

Example

In the following examples, the coated active ingredients (ie, astaxanthin, vitamin C) having the liposome structure of the present invention were prepared by using astaxanthin and vitamin C as active ingredients, respectively, and being effective without coating. Ingredients, the transdermal absorption rate of the two is compared; the two are separately made into an essence to apply the subject to the skin, and the effects of the two on the skin are compared.

[Transdermal absorption rate]

The transdermal absorption rate of the active ingredient is determined using a Franz vertical diffusion system, reference to the work of Kim KW et al. Terahertz dynamic imaging of skin drug absorption (Opt Express. 2012 Apr 23; 20(9): 9476- The description in 84) is carried out. Specifically, a buffer solution containing an active ingredient or a buffer solution containing microparticles of the active ingredient having the present liposome structure is placed in the upper supply end, and a buffer solution containing no active ingredient is placed in the lower receiving end and a stirrer is placed in the middle. Separated by a permeable membrane such as pig skin, nude mouse skin, or artificial skin. The time during which the active ingredient is measured from the supply end through the permeable membrane to the receiving end, and the active ingredient can be measured in the solution at the receiving end is referred to as the delay time t _lag . Moreover, the measurement of the permeation amount per unit area and unit time is called flux J, and its unit is mass/area time (Q/At); the penetration coefficient K _p is defined as the flux per unit concentration of active ingredient. The unit is distance/time, and the penetration coefficient is proportional to the penetration rate of the active ingredient. The higher the coefficient, the greater the penetration rate. The penetration coefficient can be calculated by the following equation, where J _ss represents the flux in the steady state, C _d represents the concentration of the active ingredient in the supply end, and C _a represents the concentration of the active ingredient in the receiving end.

[Acquisition of active ingredients]

The astaxanthin used was obtained by crushing algae cells containing astaxanthin and extracting with dichloromethane to obtain a red solid powder. Vitamin C is commercially available from the market.

[Preparation example: Preparation of liposome structure]

Astaxanthin, phospholipid, ethanolamine, and water are mixed and stirred to form a uniform dispersion. After that, use ultrasonic to oscillate the dispersion to form An aqueous solution of a liposome structure comprising an elite core containing astaxanthin and a liposome protective layer of phospholipid ethanolamine. Further, vitamin C, phospholipid, ethanolamine, and water were mixed to prepare a liposome structure containing the core of vitamin C in the same manner.

[Example 1a: Transdermal absorption rate of astaxanthin]

The transdermal absorption rate of both the liposome structure (Example) containing the astaxanthin core according to the present invention and the uncoated striamycin (Comparative Example) was compared. Referring to Fig. 3a, which shows the cumulative diffusion amount (microgram) of astaxanthin in 12 hours, it can be seen that the delay time T _lag of uncoated astaxanthin reaching the receiving end through the permeable membrane is 5.46 hours. The sample can be shortened to a period of 5.03 hours, i.e., reduced by about 7.9%; the cumulative amount of diffusion after 12 hours is higher than that of uncoated astaxanthin. Referring further to Figure 3b, the penetration coefficient K _{p of} the uncoated astaxanthin is calculated to be 1.50 × 10 ^-9 cm / sec, and the present aspect can increase the penetration coefficient to 2.20 × 10 ^-9 The centimeter/second is increased to about 1.5 times. From this, it was confirmed that the liposome structure according to the present invention can significantly increase the transdermal absorption rate of astaxanthin.

[Example 1b: Transdermal absorption rate of vitamin C]

The transdermal absorption rate of the liposome structure (Example) containing the vitamin C essence core according to the present invention and the uncoated vitamin C (Comparative Example) were compared. Referring to Figure 4a, which shows the cumulative amount of diffusion (mg) of vitamin C in 12 hours, it can be seen that the delay time T _lag of uncoated vitamin C passing through the permeable membrane to the receiving end is 5.57 hours, while the creative aspect is The delay time can be shortened to 3.23 hours, ie, by about 42%; the cumulative amount of diffusion after 12 hours is higher than that of uncoated vitamin C. Referring further to Figure 4b, the penetration coefficient K _{p of} the uncoated vitamin C is calculated to be 2.43 × 10 ^-7 cm / sec, and the present aspect can increase the penetration coefficient to 6.63 × 10 ^-7 cm. / sec, that is, up to about 2.7 times. From this, it was confirmed that the liposome structure according to the present invention can significantly increase the transdermal absorption rate of vitamin C.

[Example 2a: Effect of astaxanthin on facial skin]

The liposome structure (ie, astaxanthin particles) of the present invention containing the astaxanthin core prepared in the preparation example was uniformly dispersed in water to prepare an essence containing the astaxanthin particles having the present liposome structure. . Further, an astaxanthin extract was prepared in which untreated astaxanthin was uniformly dispersed in water as a comparative example.

The experiment was performed in a single-blind, controlled group control manner. Three subjects aged 40 to 60 years old were evenly applied to the left and right faces as a comparative group of astaxanthin extracts as a control group and aspergillus microparticle essence according to the present invention, which were applied once a day in the morning and evening for a period of 8 week. Skin properties were measured before and after the test, including skin melanin content, gloss, transepidermal water loss (TEWL), pores, texture, wrinkles and elasticity. The results are shown in Figure 5a. It can be seen from Fig. 5a that the skin melanin content, gloss, TEWL, pores, texture, wrinkles and elasticity can be improved after using the essence according to the present invention for 8 weeks, wherein the gloss, wrinkles and elasticity are improved compared with the control group. Especially obvious. In addition, it was observed from the face photograph of Fig. 5b that the crow's feet using the essence of the present example were significantly reduced after 8 weeks, while the crow's feet using the comparative essence did not change much. It can be confirmed that the astaxanthin particles having the liposome structure of the present invention can enhance the effects of astaxanthin on the skin, such as improving skin color, reducing wrinkles and increasing elasticity.

[Example 2b: Effect of vitamin C on facial skin]

The liposome structure (i.e., vitamin C microparticles) containing the vitamin C essence core of the present preparation prepared in the preparation example was uniformly dispersed in water to prepare an essence containing vitamin C microparticles having the present liposome structure. Further, a vitamin C essence was prepared in which untreated vitamin C was uniformly dispersed in water as a comparative example.

The experiment was performed in a single-blind, controlled group control manner. 25 subjects aged 30-60 years were evenly applied to one side of the face with the vitamin C microparticle essence according to the present invention, and 5 subjects were used as the control group on the other side of the face. Vitamin C essence is rubbed once a day for 4 weeks. Skin properties were measured before and after the test, including skin moisture content, gloss, yellow tone, spots, sunburn, texture, pores and wrinkles. The results are shown in Figure 6. It can be seen from Fig. 6 that the skin moisture content, gloss, yellow tone, spots, sun spots, texture, pores and wrinkles can be improved after using the essence according to the present creation example for 4 weeks, compared with the control group, wherein the spots, Texture and pore improvement are especially noticeable. It can be confirmed that the vitamin C particles having the liposome structure of the present invention can enhance the effect of vitamin C on the skin, such as whitening and increasing skin fineness.

The specific embodiments of the present invention have been described with reference to the accompanying drawings, but the present invention is not limited to the exact embodiment, and modifications or alterations may be made to those skilled in the art; such modifications or changes should include It is within the scope of this creation as defined in the scope of the appended patent application.

1‧‧‧Liposome structure

2‧‧‧Essence core

3‧‧‧ liposome protective layer

4‧‧‧ inside surface

5‧‧‧ outside surface

6‧‧‧hydrophobic area

a, b‧‧‧ thickness

Claims (6)

A liposome structure capable of improving the transdermal absorption rate of an active ingredient, comprising an inner core comprising: an essence core comprising an active ingredient; and a lipoprotective layer having a hydrophilic orientation toward the essence core The inner side surface is a hydrophilic away from the outer side surface of the essence core, and has a hydrophobic region between the inner side surface and the outer side surface. The liposome structure according to claim 1, which is capable of improving the transdermal absorption rate of the active ingredient, has a particle diameter of from 100 μm to 500 μm. The liposome structure according to claim 1, which is capable of improving the transdermal absorption rate of the active ingredient, wherein the essence core has a thickness of from 30 μm to 150 μm. The liposome structure according to claim 1, which is capable of improving the transdermal absorption rate of the active ingredient, wherein the liposome protective layer has a thickness of from 30 μm to 200 μm. The liposome structure according to claim 1, which is capable of improving the transdermal absorption rate of the active ingredient, wherein the essence core is in a homogeneous state, and the active ingredient is at least one of astaxanthin and vitamin C. The liposome structure according to any one of claims 1 to 5, which is capable of improving the transdermal absorption rate of the active ingredient, which can be prepared into a powder form, a solution form, a suspension form, a gel form, an emulsion form, a cream form, Or in the form of a mask.