Slow-release permeation-enhancing composition based on water-in-oil system as well as preparation method and application of slow-release permeation-enhancing composition

Abstract

The invention belongs to the technical field of cosmetics, and particularly relates to a slow-release permeation-enhancing composition based on a water-in-oil system as well as a preparation method and application of the slow-release permeation-enhancing composition. The slow-release permeation-enhancing type composition is prepared from the following components in parts by weight: 1 to 6 parts of polydimethylsiloxane PEG-10 / 15 cross-linked polymer, 0.1 to 2 parts of PEG-10 polydimethylsiloxane, 2 to 15 parts of polydimethylsiloxane, 2 to 15 parts of glycerol tri (ethylhexoic acid) ester and 0.01 to 2 parts of squalane. The sustained-release permeation-promoting composition has excellent wrapping capacity on active ingredients, oxidation and decomposition of the active ingredients are reduced, and therefore the activity retention rate of the active ingredients is remarkably increased. Moreover, the composition formed by the specific compound components has unique molecular structure and physical properties, and a wrapping system of the composition can effectively control the release rate of the active components, so that the durability and effectiveness of the application effect of the composition are improved, and the permeation promoting effect of the composition is further enhanced.

Description

Technical Field

[0001] This invention belongs to the field of cosmetic technology, and particularly relates to a sustained-release and penetration-enhancing composition based on a water-in-oil system, its preparation method, and its application. Background Technology

[0002] Currently, the mainstream system for cosmetic emulsions is an oil-in-water (O / W) structure, where the aqueous phase acts as the outer phase, encapsulating the oil phase inside. Water-soluble active ingredients (such as PDRN, vitamin C, hyaluronic acid, and peptides) are typically dissolved in the aqueous outer layer. While this type of system offers advantages such as a light texture and ease of application, it still suffers from the following significant problems:

[0003] (1) Active ingredients are easily deactivated: Water-soluble active ingredients are directly exposed to the external environment (such as oxygen, light, microorganisms), which leads to chemical decomposition or oxidation and reduces efficacy; (2) Release rate is too fast: Because the active ingredients are located in the external phase, they are released quickly when used, lacking a sustained release effect and having a short duration of action, which cannot meet consumers' demand for long-lasting efficacy; (3) Formulation stability challenge: Some sensitive active ingredients (such as vitamin C) require additional stabilizers or antioxidants, which increases the complexity and cost of the formulation.

[0004] Therefore, given the shortcomings of existing oil-in-water systems in terms of active ingredient stability, release efficiency, and formulation stability, developing a novel cosmetic composition that can solve these problems has significant practical importance and application value. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the prior art and provide a sustained-release and permeation-enhancing composition based on a water-in-oil system, its preparation method and application, so as to effectively improve the stability of water-soluble active ingredients while achieving a sustained-release and permeation-enhancing effect, thereby enhancing the persistence of product efficacy and bioavailability.

[0006] To achieve the above objectives, the technical solution adopted by the present invention includes:

[0007] In a first aspect, the present invention provides a sustained-release permeation-enhancing composition based on a water-in-oil system, the sustained-release permeation-enhancing composition comprising the following components in parts by weight: 1-6 parts of polydimethylsiloxane PEG-10 / 15 crosslinked polymer, 0.1-2 parts of PEG-10 polydimethylsiloxane, 2-15 parts of polydimethylsiloxane, 2-15 parts of glycerol tri(ethylhexanoate), and 0.01-2 parts of squalane.

[0008] This invention utilizes a specific compound combination of polydimethylsiloxane PEG-10 / 15 cross-linked polymer, PEG-10 polydimethylsiloxane, polydimethylsiloxane, triglyceride (ethylhexanoate), and squalane to form a sustained-release, penetration-enhancing composition with excellent encapsulation capabilities for water-soluble active ingredients. This encapsulation structure effectively isolates the active ingredients from the influence of external environmental factors (such as oxygen, light, temperature changes, and pH fluctuations), reducing their oxidation, decomposition, or denaturation, thereby significantly prolonging the retention rate of water-soluble active ingredients. Furthermore, the composition formed by the above-mentioned specific compound components possesses a unique molecular structure and physical properties, and its encapsulation system effectively controls the release rate of water-soluble active ingredients, thereby improving the durability and effectiveness of the composition's application effect and further enhancing its penetration-enhancing effect. In addition, the sustained-release, penetration-enhancing composition of this invention is well-compatible with various water-soluble active ingredients (such as vitamins and peptides) and can be widely used in cosmetics, pharmaceuticals, health products, and other fields, providing an efficient carrier solution for the application of water-soluble active ingredients in different scenarios.

[0009] The sustained-release and permeation-enhancing composition comprises the following components in parts by weight: 3-5 parts of polydimethylsiloxane PEG-10 / 15 crosspolymer, 0.2-1 part of PEG-10 polydimethylsiloxane, 4-10 parts of polydimethylsiloxane, 3-8 parts of glycerol tri(ethylhexanoate), and 0.1-1 part of squalane.

[0010] The sustained-release and permeation-enhancing composition comprises the following components in parts by weight: 4 parts of polydimethylsiloxane PEG-10 / 15 crosspolymer, 0.4 parts of PEG-10 polydimethylsiloxane, 6 parts of polydimethylsiloxane, 5 parts of glycerol tri(ethylhexanoate) ester, and 1 part of squalane.

[0011] Experimental studies have revealed that the proportions of the five components significantly influence the sustained-release effect and stability of the final composition. By precisely controlling the five components to their optimal values, each component interacts and influences the others in terms of compatibility, interfacial activity, and structural support, thereby synergistically forming a composite carrier with both stable encapsulation and sustained-release permeation regulation functions. This effect is significantly superior to that achieved by a single component or other non-specific combinations.

[0012] The sustained-release and permeation-enhancing composition also includes 0.001-1 part of the active ingredient.

[0013] The active ingredients include at least one of sodium DNA, vitamin C ethyl ether, hyaluronic acid, polypeptide, and 3-o-ethyl ascorbic acid.

[0014] Secondly, the present invention provides the application of the sustained-release and penetration-enhancing composition in cosmetics.

[0015] Preferably, the cosmetic dosage form includes lotion and cream.

[0016] Thirdly, the present invention provides a method for preparing the aforementioned sustained-release permeation-enhancing composition, comprising the following steps:

[0017] S1. Mix polydimethylsiloxane PEG-10 / 15 crosslinked polymer, PEG-10 polydimethylsiloxane, polydimethylsiloxane, triglyceride (ethylhexanoate) and squalane evenly to obtain the oil phase;

[0018] S2. Mix the water-soluble active ingredient with water until homogeneous to obtain the aqueous phase;

[0019] S3. The aqueous phase is added to the oil phase for mixing to obtain the slow-release permeation-enhancing composition.

[0020] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0021] (1) The present invention uses a specific compound system of polydimethylsiloxane PEG-10 / 15 cross-linked polymer, PEG-10 polydimethylsiloxane, polydimethylsiloxane, glyceryl tri(ethylhexanoate) ester and squalane to form a highly efficient encapsulation and protection for water-soluble active ingredients, which solves the problem that water-soluble active ingredients are easily degraded and ineffective due to environmental factors, and effectively extends the shelf life of active ingredients.

[0022] (2) The composition of the present invention constructs a unique sustained-release structure through the synergistic effect between the components, which can effectively regulate the release rate of water-soluble active ingredients, prolong the action time, enhance the persistence of product efficacy, and exert a good penetration-promoting effect, further improving the bioavailability of active ingredients.

[0023] (3) The sustained-release and permeation-enhancing composition of the present invention can be well compatible with a variety of water-soluble active ingredients and can be widely used in cosmetics, pharmaceuticals, health products and other fields. It provides an efficient carrier solution for the application of water-soluble active ingredients in different scenarios. Moreover, the sustained-release and permeation-enhancing composition of the present invention can be prepared by a simple compounding process without relying on additional coating technology. The production process is easy to control and the cost is low. Attached Figure Description

[0024] Figure 1 The graph shows the results of sustained-release verification experiments of the sustained-release and permeation-enhancing compositions prepared in Example 6 and Comparative Example 11 at different times.

[0025] Figure 2 The diagram shows the permeation effect of the sustained-release permeation-enhancing compositions prepared in Example 1, Comparative Example 10, and Comparative Example 8. Detailed Implementation

[0026] To better illustrate the objectives, technical solutions, and advantages of this invention, the invention will be further described below with reference to specific embodiments. Those skilled in the art should understand that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

[0027] Unless otherwise specified, all raw materials used in the following examples and comparative examples are commercially available general-purpose materials.

[0028] Examples 1-5

[0029] Examples 1-5 provide a sustained-release, permeation-enhancing composition based on a water-in-oil system, with specific formulations shown in Table 1 (total parts by weight: 100 parts). The preparation method of the sustained-release, permeation-enhancing composition includes the following steps:

[0030] S1. Mix polydimethylsiloxane PEG-10 / 15 crosslinked polymer, PEG-10 polydimethylsiloxane, polydimethylsiloxane, triglyceride (ethylhexanoate) and squalane evenly to obtain the oil phase;

[0031] S2. Mix the active ingredients with water until homogeneous to obtain the aqueous phase;

[0032] S3. The aqueous phase is added to the oil phase for mixing to obtain the slow-release permeation-enhancing composition.

[0033] Table 1. Formulation table (parts by weight) of the sustained-release and permeation-enhancing compositions described in Examples 1-5.

[0034]

[0035] Example 6

[0036] This embodiment provides a sustained-release permeation-enhancing composition based on a water-in-oil system. The only difference between this composition and Example 1 is that an equal amount of the water-soluble active ingredient 3-o-ethyl ascorbic acid is used to replace sodium DNA, while the remaining components and their amounts remain unchanged.

[0037] Comparative Examples 1-9

[0038] Comparative Examples 1-9 provide a sustained-release permeation-enhancing composition based on a water-in-oil system, which differs from Example 1 only in its formulation. The specific formulations of the sustained-release permeation-enhancing compositions described in Comparative Examples 1-9 are shown in Table 2 (total parts by weight: 100 parts).

[0039] Table 2. Formulation table (parts by weight) of the sustained-release and permeation-enhancing compositions described in Comparative Examples 1-9.

[0040]

[0041]

[0042] Comparative Example 10

[0043] This comparative example provides a sustained-release permeation-enhancing composition based on a water-in-oil system. The only difference between this composition and Example 1 is that equal amounts of sorbitan oleate and cetearyl oleate are used to replace polydimethylsiloxane PEG-10 / 15 crosspolymer and PEG-10 polydimethylsiloxane, respectively, while the remaining components and amounts remain unchanged.

[0044] Comparative Example 11

[0045] This comparative example provides a sustained-release permeation-enhancing composition based on a water-in-oil system. The only difference between this composition and Comparative Example 10 is that an equal amount of the water-soluble active ingredient 3-o-ethyl ascorbic acid is used to replace sodium DNA, while the remaining components and their amounts remain unchanged.

[0046] Example of effect 1

[0047] This example uses the sustained-release and permeation-enhancing compositions prepared in Example 6 and Comparative Example 11 as test samples to verify the sustained-release effect of the active ingredients. The specific method is as follows:

[0048] Two dispensing bottles were taken, and 10g of Example 6 and Comparative Example 11 were filled into each bottle. At the same time, 2g of povidone-iodine solution was added. After stirring, the fading of the povidone-iodine solution in the dispensing bottles was observed over time to observe the antioxidant properties of the water-soluble active ingredient 3-o-ethyl ascorbic acid in the formulation, thereby determining the sustained-release effect of the composition.

[0049] Figure 1 The results showed that the compositions prepared in Example 6 and Comparative Example 11 were both milky white emulsions. When iodine was added to the compositions and stirred, Comparative Example 11 immediately regained its white appearance, indicating that the water-soluble active ingredient 3-o-ethyl ascorbic acid was rapidly released and reacted with iodine, exhibiting almost no sustained-release ability. The active ingredient was released in a concentrated manner within a short time, meaning the composition had no sustained-release effect. In contrast, the composition prepared in Example 6 gradually regained its white appearance within 15 minutes, indicating that the composition prepared in Example 6 could slowly and continuously release the active substance. The color gradually faded through gradual reaction with iodine, demonstrating significant sustained-release characteristics. These results prove that the sustained-release and permeation-enhancing compositions prepared using the specific components of this invention can successfully achieve sustained-release control of the encapsulated active substances, which is of great significance for applications such as prolonging the action time of active substances, improving their stability, or reducing irritation.

[0050] Example 2

[0051] This effect example uses the sustained-release and permeation-enhancing compositions prepared in Examples 1-5 and Comparative Examples 1-10 as test samples. The permeation effect of the compositions is tracked and quantified by testing the permeation depth of the sustained-release and permeation-enhancing compositions indicated by sodium fluorescein. The specific test method is as follows:

[0052] (1) Sample preparation: Mix 0.1% sodium fluorescein with the test sample to ensure uniform dispersion of sodium fluorescein and store in the dark;

[0053] (2) Fix the pigskin between the supply chamber and the receiving chamber of the Franz cell diffusion cell, with the stratum corneum of the pigskin facing the supply chamber and the dermis facing the receiving chamber.

[0054] (3) Add 7.0 mL of receiving solution to the receiving chamber, tighten and fix the pigskin, add 1 mL of receiving solution (PBS) to the receiving chamber through the sampler, remove the air, and make the dermal layer of the skin in close contact with the receiving solution.

[0055] (4) Sample loading: Add the sample to the skin surface in the supply chamber. The effective penetration area S is approximately 3.14 cm². 2 Apply the sample to the surface of the pigskin, spreading it evenly radially from the center of the skin towards the edges. Perform three replicates and parallels for each sample.

[0056] (5) Infiltration: Turn on the electromagnetic stirrer and stir at 300 rpm, maintain a constant temperature water bath of (32±1)℃, and ensure that there are no air bubbles in the water bath jacket.

[0057] (6) Skin samples were collected at 0h and 24h time points. The skin surface was washed 5 times with PBS. The residual liquid on the surface was wiped dry with a cotton swab. The skin was circumferentially cut with a blade and fixed in 4% paraformaldehyde solution (fixation time > 24h). The samples were then frozen and sectioned.

[0058] (7) Gently wipe the matrix surface with a cotton swab soaked in physiological saline until no sample residue is visible to the naked eye. Cut the sample into 5-10 μm thick sections using a cryostat, place them on a glass slide, and allow them to air dry. Observe and image the sample using a fluorescence microscope. Use image analysis software to measure the vertical distance from the matrix surface (marked boundary) to the fluorescence front. Measure three times for each field of view and take the average value as the penetration depth of the sample. Calculate the relative penetration depth of the sample using the penetration depth: Relative penetration depth = (Average penetration depth of sample group / Average penetration depth of control group) * 100%. The control group uses a mixture of 0.1% sodium fluorescein and water as the control sample. The specific test results are shown in Table 3.

[0059] Table 3 Relative Permeability Results

[0060]

[0061] Table 3 shows that the sustained-release permeation-enhancing composition prepared by the technical solution of the present invention has a better permeation effect. In particular, the relative permeation of the composition described in Example 1 reaches 214%, which shows excellent permeation performance. This further illustrates that the sustained-release properties of the composition can promote the penetration of sodium fluorescein into the deep matrix.

[0062] In Comparative Examples 1-7, when one or more of the five specific components—polydimethylsiloxane PEG-10 / 15 crosslinked polymer, PEG-10 polydimethylsiloxane, polydimethylsiloxane, triglyceride (ethylhexanoate), and squalane—were missing, the permeability of the prepared compositions was significantly lower than that of the examples. This indicates that the five components selected in this invention are indispensable in the system; the absence of any one or more components will lead to a decrease in the system's permeability. The five components play a synergistic role in the compound system, working together to form a stable permeation-promoting system. The more components are missing, the more severely the synergistic effect of the system is disrupted, and the more obvious the decrease in permeability. In Comparative Examples 8-9, when the proportions of the above five components exceeded the limits defined in this invention, the permeability of the compositions also decreased, indicating that the proportions of the five components need to be within a specific range to achieve the best synergistic effect. An imbalance in the proportions will lead to a mismatch in the functions of the components, ultimately resulting in a decrease in permeability. In Comparative Example 10, when components with similar properties were used for component substitution, the relative permeability of the compositions also decreased to some extent, indicating that the five specific components selected in this invention cannot be conventionally substituted.

[0063] Figure 2 The images show the penetration effects of different sustained-release and penetration-enhancing compositions. The images demonstrate that the sustained-release and penetration-enhancing composition prepared in Example 1 exhibits trans-stratum corneum active epidermal diffusion, with a clear fluorescence signal penetrating the stratum corneum barrier. It displays a uniform and decreasing intensity diffuse distribution throughout the active epidermal layer and diffuses into the superficial dermis (papillary layer), demonstrating excellent penetration. In contrast, the penetration effects of the compositions prepared in Comparative Examples 10 and 8 are significantly reduced compared to Example 1.

[0064] Finally, it should be noted that the above embodiments are used to illustrate the technical solutions of the present invention and not to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A sustained-release, permeation-enhancing composition based on a water-in-oil system, characterized in that, The sustained-release and permeation-enhancing composition comprises the following components in parts by weight: 1-6 parts of polydimethylsiloxane PEG-10 / 15 crosslinked polymer, 0.1-2 parts of PEG-10 polydimethylsiloxane, 2-15 parts of polydimethylsiloxane, 2-15 parts of glycerol tri(ethylhexanoate), and 0.01-2 parts of squalane.

2. The sustained-release, permeation-enhancing composition according to claim 1, characterized in that, The sustained-release and permeation-enhancing composition comprises the following components in parts by weight: 3-5 parts of polydimethylsiloxane PEG-10 / 15 crosspolymer, 0.2-1 part of PEG-10 polydimethylsiloxane, 4-10 parts of polydimethylsiloxane, 3-8 parts of glycerol tri(ethylhexanoate), and 0.1-1 part of squalane.

3. The sustained-release, permeation-enhancing composition according to claim 2, characterized in that, The sustained-release and permeation-enhancing composition comprises the following components in parts by weight: 4 parts of polydimethylsiloxane PEG-10 / 15 crosspolymer, 0.4 parts of PEG-10 polydimethylsiloxane, 6 parts of polydimethylsiloxane, 5 parts of glycerol tri(ethylhexanoate) ester, and 1 part of squalane.

4. The sustained-release, permeation-enhancing composition according to any one of claims 1-3, characterized in that, The sustained-release and permeation-enhancing composition further includes 0.001-1 part of a water-soluble active ingredient.

5. The sustained-release, permeation-enhancing composition according to claim 4, characterized in that, The water-soluble active ingredient includes at least one of sodium DNA, vitamin C ethyl ether, hyaluronic acid, polypeptide, and 3-o-ethyl ascorbic acid.

6. The use of the sustained-release and penetration-enhancing composition according to any one of claims 1-5 in cosmetics.

7. The application as described in claim 6, characterized in that, The cosmetic dosage forms include lotions and creams.

8. The method for preparing the sustained-release and permeation-enhancing composition as described in claim 4 or 5, characterized in that, Includes the following steps: S1. Mix polydimethylsiloxane PEG-10 / 15 crosslinked polymer, PEG-10 polydimethylsiloxane, polydimethylsiloxane, triglyceride (ethylhexanoate) and squalane evenly to obtain the oil phase; S2. Mix the water-soluble active ingredient with water until homogeneous to obtain the aqueous phase; S3. The aqueous phase is added to the oil phase for mixing to obtain the slow-release permeation-enhancing composition.

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