High-stability retinol composite nano-liposome and preparation method thereof
By constructing a synergistic modified lipid system composed of sodium stearoyl glutamate, polysorbate-20, and polyglycerol-4 oleate to encapsulate retinol and hydroxypinazone retinate, the stability and release issues of retinol active ingredients were solved, and highly stable and low-irritant retinol composite nanoliposomes were achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- 有生之颜(深圳)生物科技有限公司
- Filing Date
- 2026-02-09
- Publication Date
- 2026-05-12
AI Technical Summary
In existing technologies, retinol active ingredients have poor stability and are easily degraded by factors such as light, oxygen and temperature. Liposome systems are prone to leakage of active ingredients and particle aggregation, and it is difficult to achieve both rapid onset of action and sustained release, resulting in high irritation.
The synergistically modified lipids, composed of sodium stearoyl glutamate, polysorbate-20, and polyglycerol-4 oleate, are self-assembled into nanoscale liposome structures to encapsulate retinol and hydroxypinazone retinate, thereby improving stability and achieving rapid release and sustained release.
It significantly reduces the risk of retinol degradation during storage and use, inhibits leakage of active ingredients and particle aggregation, improves the utilization rate of active ingredients and system stability, and reduces irritation.
Smart Images
Figure CN122005352A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of cosmetic raw materials and active ingredient delivery technology, specifically relating to a highly stable retinol composite nanoliposome and its preparation method. Background Technology
[0002] Aging is an inevitable process in the biological life cycle. Under the combined influence of genetic and environmental factors, the structure and function of human tissues and organs gradually undergo degenerative changes. As the largest organ in the human body, the skin shows particularly obvious signs of aging, mainly manifested in decreased collagen content, reduced elasticity, and the formation of fine lines and wrinkles. Therefore, delaying skin aging and improving skin condition has always been an important research direction in the field of cosmetics.
[0003] Retinols, as vitamin A and its derivatives, are widely used in anti-aging cosmetics because they promote collagen synthesis and induce the formation of elastin and elastic collagen fibers. Commonly used retinol ingredients in existing technologies include retinol, retinaldehyde, and retinyl esters. However, retinols and their derivatives generally suffer from poor stability, being highly sensitive to external factors such as light, oxygen, temperature, and metal ions. They are prone to degradation during storage and use, leading to a decrease in the content of active ingredients. Furthermore, retinol has a narrow pH range and exhibits some phototoxicity. Under ultraviolet light, it easily undergoes oxidation reactions and generates free radicals, which not only affect product stability but may also accelerate skin aging and cause irritation such as redness, itching, and tightness, thus limiting its application in cosmetics to some extent.
[0004] To reduce irritation and improve the user experience, various retinol derivatives have been developed in existing technologies. Among them, hydroxypinazone retinyl ester, as a novel retinol-like ingredient, is composed of retinoic acid and pinazone, bypassing the traditional "ester-alcohol-aldehyde" conversion pathway. It can be converted into retinoic acid more quickly and bind directly to intracellular retinoic acid receptors, thus possessing the anti-aging effects of retinol while being relatively mild. However, the compatibility of this type of ingredient in formulation systems is still limited, and precipitation may still occur under adverse storage or usage conditions, requiring further improvement in stability.
[0005] To improve the stability and safety of retinol-based substances, existing technologies typically employ liposome encapsulation for delivery. Liposomes, as a common carrier of active ingredients, can, to some extent, isolate the active ingredients from the external environment and help improve skin permeability. However, the liquid liposome system currently predominantly used in the cosmetics industry is prone to problems such as liposome particle aggregation and active ingredient leakage during practical applications. This leads to unstable liposome structures, reduced encapsulation efficiency, and consequently affects the utilization efficiency of retinol-based active ingredients and the overall performance of the product.
[0006] Most existing products encapsulate only a single retinol component, resulting in a relatively singular target and difficulty in simultaneously addressing the needs for rapid onset of action and sustained release. Furthermore, while ensuring efficacy, there is still a risk of irritation. Therefore, how to improve the stability of retinol active ingredients while achieving the synergistic delivery of multiple retinol components, and further enhance the structural stability and safety of the liposome system, remains a pressing technical problem to be solved in this field. Summary of the Invention
[0007] To overcome the poor stability of retinol-like active ingredients in the aforementioned background technologies, which are susceptible to degradation due to factors such as light, oxygen, and temperature, and prone to leakage of active ingredients, particle aggregation, and high irritation in liposome systems, and which struggle to balance rapid onset of action with sustained release, the present invention aims to provide a highly stable retinol composite nanoliposome and its preparation method. The highly stable retinol composite nanoliposome comprises glycerol, water, 2,3-butanediol, caprylic / capric triglyceride, 1,2-hexanediol, retinol, hydroxypinazone retinate, and synergistic modified lipids. The synergistic modified lipids are composed of sodium stearoyl glutamate, polysorbate-20, and polyglycerol-4 oleate. Retinol and hydroxypinazone retinate, as retinol-like active substances, are co-encapsulated within the nanoscale liposome structure formed by the self-assembly of the synergistic modified lipids. The preparation is achieved through aqueous phase preparation, oil phase preparation, mixing, addition of synergistic modified lipids, and dispersion treatment steps, thereby effectively improving the stability and utilization rate of retinol-like active ingredients and reducing irritation while ensuring efficacy.
[0008] The objective of this invention can be achieved through the following technical solutions:
[0009] A highly stable retinol composite nanoliposome comprises the following raw materials in parts by weight: 35-45 parts glycerol; 25-40 parts water; 5-15 parts 2,3-butanediol; 5-15 parts caprylic / capric triglyceride; 1-4 parts 1,2-hexanediol; 0.5-2.0 parts retinol; 0.5-2.0 parts hydroxypinazone retinate; and 2.7-9.0 parts synergistic modified lipids. The synergistic modified lipids are composed of sodium stearoyl glutamate, polysorbate-20, and polyglycerol-4 oleate. The retinol and hydroxypinazone retinate, as retinol-like active substances, are co-encapsulated within the nanoscale liposome structure formed by the self-assembly of the synergistic modified lipids.
[0010] Optionally, the synergistically modified lipids comprise the following raw materials in parts by weight: sodium stearoyl glutamate 0.2–1.0 parts; polysorbate-20 0.5–2.0 parts; and polyglycerol-4 oleate 2.0–6.0 parts.
[0011] Optionally, the method for preparing synergistically modified lipids includes the following steps:
[0012] (1) Weigh out sodium stearoyl glutamate, polysorbate-20 and polyglycerol-4 oleate;
[0013] (2) Sodium stearoyl glutamate, polysorbate-20 and polyglycerol-4 oleate were added to the solvent in sequence and mixed under stirring to obtain a homogeneous lipid mixture system;
[0014] (3) The obtained lipid mixture system was dispersed to obtain synergistically modified lipids.
[0015] Optionally, the reaction conditions in step (2) are as follows: sodium stearoyl glutamate, polysorbate-20 and polyglycerol-4 oleate are added to the solvent and mixed by mechanical stirring at 20-40°C, with a stirring speed of 300-1000 r / min and a stirring time of 10-60 min.
[0016] Optionally, the reaction conditions in step (3) are as follows: the obtained lipid mixture is treated by high shear dispersion, the dispersion temperature is 20-40℃, the dispersion speed is 8000-20000 r / min, and the dispersion time is 5-30 min.
[0017] Optionally, a method for preparing highly stable retinol composite nanoliposomes includes the following steps:
[0018] S1, Weigh out glycerol, water, 2,3-butanediol and 1,2-hexanediol, mix them under stirring to obtain an aqueous phase system;
[0019] S2, weigh out caprylic / capric triglyceride, retinol and hydroxypinazone retinate, mix them to obtain the oil phase system;
[0020] S3, Under stirring conditions, the oil phase system is added to the aqueous phase system and mixed to obtain the initial mixed system;
[0021] S4, add synergistically modified lipids to the initial mixing system and continue mixing to obtain the liposome precursor system;
[0022] S5, the liposome precursor system was dispersed to obtain highly stable retinol composite nanoliposomes.
[0023] Optionally, the reaction conditions for step S1 are stirring and mixing at 20–40°C for 10–60 min, and the stirring method is mechanical stirring; the reaction conditions for step S2 are mixing under light-protected conditions at a mixing temperature of 20–40°C for 5–30 min.
[0024] Optionally, the reaction conditions in step S3 are as follows: the oil phase system is slowly added to the aqueous phase system at 20–40°C, and the mixture is stirred for 10–60 min.
[0025] Optionally, the reaction conditions for step S4 are as follows: add the synergistically modified lipid to the initial mixture at 20–40°C and continue stirring for 10–60 min.
[0026] Optionally, the reaction conditions in step S5 are as follows: the liposome precursor system is treated with high shear dispersion, the dispersion temperature is 20-40℃, the dispersion speed is 8000-20000 r / min, and the dispersion time is 5-30 min.
[0027] The beneficial effects of this invention are:
[0028] This invention constructs a synergistic modified lipid system composed of sodium stearoyl glutamate, polysorbate-20, and polyglycerol-4 oleate, achieving co-encapsulation of retinol and hydroxypinazone retinate. This allows the two retinoid active ingredients to coexist stably within the nanoliposome structure. Compared to existing technologies that only encapsulate single retinol or use conventional liposome systems, this significantly reduces the risk of retinoid degradation due to light, oxygen, and temperature changes during storage and use, effectively inhibiting leakage of active ingredients and liposome particle aggregation. Simultaneously, through the self-assembly of the synergistic modified lipids, retinol achieves rapid release, while hydroxypinazone retinate achieves sustained release. This improves the overall utilization rate and system stability of the retinoid active ingredients without increasing irritation, solving the technical challenge of balancing stability and mildness in existing technologies. Attached Figure Description
[0029] The invention will now be further described with reference to the accompanying drawings.
[0030] Figure 1 A comparison of the infrared spectra of lipids and synergistically modified lipids;
[0031] Figure 2 Comparison of stratification stability test results for samples with different ratios;
[0032] Figure 3 A comparison chart of test results on the stability and leakage trend of active material encapsulation in samples with different formulation ratios;
[0033] Figure 4 Comparison of accelerated storage stability test results for samples with different ratios;
[0034] Figure 5 This is a comparison chart of photostability test results for samples with different formulation ratios. Detailed Implementation
[0035] The present invention will be further described below with reference to specific embodiments. However, the present invention is not limited to the following embodiments. Equivalent adjustments made without departing from the spirit and essence of the present invention should also be considered to fall within the protection scope of the present invention.
[0036] Example 1:
[0037] This embodiment aims to verify that when the dosage of each component and the reaction conditions are within the lower limit range defined in the claims, the synergistic modified lipid and highly stable retinol composite nanoliposomes can still be stably formed, proving the feasibility and stability of the technical solution of the present invention under low ratio conditions.
[0038] Preparation method
[0039] S1, Preparation of synergistically modified lipids
[0040] 0.2 parts of sodium stearoyl glutamate, 0.5 parts of polysorbate-20 and 2.0 parts of polyglycerol-4 oleate were weighed and added to the solvent in sequence. The mixture was mechanically stirred at 20°C for 10 min at a stirring speed of 300 r / min. The resulting lipid mixture was then subjected to high-shear dispersion treatment at 20°C for 5 min at a dispersion speed of 8000 r / min to obtain synergistically modified lipids.
[0041] S2, Preparation of the aqueous system
[0042] Weigh out 35 parts of glycerol, 25 parts of water, 5 parts of 2,3-butanediol and 1 part of 1,2-hexanediol, and mix them at 20°C for 10 minutes using mechanical stirring to obtain an aqueous phase system.
[0043] S3, Preparation of the oil phase system
[0044] Weigh out 5 parts of caprylic / capric triglyceride, 0.5 parts of retinol and 0.5 parts of hydroxypinazone retinate, mix them at 20°C in the dark for 5 minutes to obtain the oil phase system;
[0045] S4, Formation of the initial mixed system
[0046] The oil phase system was slowly added to the aqueous phase system at 20℃ and mixed for 10 min under stirring. Then, 2.7 parts of synergistic modified lipids were added and stirring was continued for 10 min to obtain the liposome precursor system.
[0047] S5, Preparation of nanoliposomes
[0048] The liposome precursor system was treated with high shear dispersion at 20℃, with a dispersion speed of 8000 r / min and a dispersion time of 5 min to obtain highly stable retinol composite nanoliposomes.
[0049] Example 2:
[0050] This embodiment aims to verify that when the dosage of each component and the reaction conditions are within the median range defined in the claims, the formation process of the highly stable retinol composite nanoliposomes is stable and reproducible, reflecting the preferred embodiment of the present invention.
[0051] Preparation method
[0052] S1, Preparation of synergistically modified lipids
[0053] 0.6 parts of sodium stearoyl glutamate, 1.2 parts of polysorbate-20, and 4.0 parts of polyglycerol-4 oleate were weighed and added sequentially to a solvent. The mixture was mechanically stirred at 650 rpm for 30 min at 30°C. Subsequently, the lipid mixture was subjected to high-shear dispersion at 14000 rpm for 15 min at 30°C to obtain synergistically modified lipids. Figure 1 The infrared spectral comparison results shown indicate that the synergistically modified lipids exhibit significant spectral differences before and after modification. The modified sample shows differences in spectral density within the range of 3300–3500 cm⁻¹. -1 The absorption peak of the hydroxyl stretching vibration at 1730–1745 cm⁻¹ is significantly broadened and its intensity is enhanced, indicating that the hydrogen bonding between the polyhydroxyl components is strengthened; the absorption peak at 1730–1745 cm⁻¹ is also significantly broadened and its intensity is enhanced. -1 A slight shift in the C=O stretching vibration peak of the ester group, accompanied by enhanced absorption, indicates a change in the microenvironment of the ester group; 1100–1140 cm⁻¹ -1The absorption peak intensity of C–O–C / C–O stretching vibration in the region was significantly increased, reflecting that a more stable synergistic structure was formed among the multi-component lipids; the synergistically modified lipids were not simply physically mixed, but formed a stable synergistically modified system under stirring and high shear dispersion.
[0054] S2, Preparation of the aqueous system
[0055] Weigh out 40 parts of glycerol, 32 parts of water, 10 parts of 2,3-butanediol and 2.5 parts of 1,2-hexanediol, and mechanically stir at 30°C for 30 min to obtain an aqueous phase system;
[0056] S3, Preparation of the oil phase system
[0057] Weigh 10 parts of caprylic / capric triglyceride, 1.0 part of retinol and 1.0 part of hydroxypinazone retinate, mix them at 30°C in the dark for 15 min to obtain the oil phase system;
[0058] S4, Formation of the initial mixed system
[0059] The oil phase system was slowly added to the aqueous phase system at 30℃ and mixed for 30 min. Then, 5.8 parts of synergistic modified lipids were added and stirring was continued for 30 min to obtain the liposome precursor system.
[0060] S5, Preparation of nanoliposomes
[0061] The liposome precursor system was subjected to high-shear dispersion at 30℃, with a dispersion speed of 14000 r / min and a dispersion time of 15 min, to obtain highly stable retinol composite nanoliposomes.
[0062] Example 3:
[0063] This embodiment aims to verify that the synergistically modified lipid and highly stable retinol composite nanoliposomes can still be stably prepared when the dosage of each component and the reaction conditions are within the upper limit range defined in the claims, demonstrating the applicability of the technical solution of the present invention under high load conditions.
[0064] Preparation method
[0065] S1, Preparation of synergistically modified lipids
[0066] 1.0 part of sodium stearoyl glutamate, 2.0 parts of polysorbate-20 and 6.0 parts of polyglycerol-4 oleate were weighed and added to the solvent in sequence. They were mixed by mechanical stirring at 40°C with a stirring speed of 1000 r / min and a stirring time of 60 min. Subsequently, the lipid mixture was subjected to high shear dispersion treatment at 40°C with a dispersion speed of 20000 r / min and a dispersion time of 30 min to obtain synergistically modified lipids.
[0067] S2, Preparation of the aqueous system
[0068] Weigh out 45 parts of glycerol, 40 parts of water, 15 parts of 2,3-butanediol and 4 parts of 1,2-hexanediol, and mechanically stir at 40°C for 60 min to obtain an aqueous phase system.
[0069] S3, Preparation of the oil phase system
[0070] Weigh out 15 parts of caprylic / capric triglyceride, 2.0 parts of retinol and 2.0 parts of hydroxypinazone retinate, mix them at 40°C in the dark for 30 min to obtain the oil phase system;
[0071] S4, Formation of the initial mixed system
[0072] The oil phase system was slowly added to the aqueous phase system at 40℃ and mixed for 60 min. Then, 9.0 parts of synergistic modified lipids were added and stirring was continued for 60 min to obtain the liposome precursor system.
[0073] S5, Preparation of nanoliposomes
[0074] The liposome precursor system was subjected to high-shear dispersion at 40℃, with a dispersion speed of 20000 r / min and a dispersion time of 30 min, to obtain highly stable retinol composite nanoliposomes.
[0075] Comparative Example 1:
[0076] This comparative example aims to verify that, while keeping the amounts of the remaining components and reaction conditions unchanged in Example 2, only the "synergistic modified lipid" is replaced with "sodium stearoyl glutamate only," and the effect of a single lipid system on the stability and repeatability of the formation of highly stable retinol composite nanoliposomes is examined, so as to compare and demonstrate the advantages of the synergistic modified lipid system.
[0077] Preparation method
[0078] S1, Preparation of a single modified lipid
[0079] 5.8 parts of sodium stearoyl glutamate were weighed and added to a solvent. The mixture was stirred mechanically at 30°C for 30 minutes at a speed of 650 r / min. The lipid mixture was then subjected to high-shear dispersion at 30°C for 15 minutes at a speed of 14000 r / min to obtain a single modified lipid.
[0080] S2, Preparation of the aqueous system
[0081] Weigh out 40 parts of glycerol, 32 parts of water, 10 parts of 2,3-butanediol and 2.5 parts of 1,2-hexanediol, and mechanically stir at 30°C for 30 min to obtain an aqueous phase system;
[0082] S3, Preparation of the oil phase system
[0083] Weigh 10 parts of caprylic / capric triglyceride, 1.0 part of retinol and 1.0 part of hydroxypinazone retinate, mix them at 30°C in the dark for 15 min to obtain the oil phase system;
[0084] S4, Formation of the initial mixed system
[0085] The oil phase system was slowly added to the aqueous phase system at 30℃ and mixed for 30 min. Then, 5.8 parts of a single modified lipid were added and the mixture was stirred for another 30 min to obtain the liposome precursor system.
[0086] S5, Preparation of nanoliposomes
[0087] The liposome precursor system was subjected to high-shear dispersion at 30℃, with a dispersion speed of 14000 r / min and a dispersion time of 15 min to obtain retinol composite nanoliposomes.
[0088] Comparative Example 2:
[0089] This comparative example aims to verify that, while keeping the amounts of the remaining components and reaction conditions unchanged in Example 2, only "synergistic modified lipids" were replaced with "polysorbate-20 only," and the effect of a single lipid system on the stability and repeatability of the formation of highly stable retinol composite nanoliposomes was examined, so as to compare and demonstrate the advantages of the synergistic modified lipid system.
[0090] Preparation method
[0091] S1, Preparation of a single modified lipid
[0092] Weigh out 205.8 parts of polysorbate-20 and add them to the solvent. Mix them at 30°C using mechanical stirring at a speed of 650 r / min for 30 min. Then, subject the lipid mixture to high-shear dispersion at 30°C at a speed of 14000 r / min for 15 min to obtain a single modified lipid.
[0093] S2, Preparation of the aqueous system
[0094] Weigh out 40 parts of glycerol, 32 parts of water, 10 parts of 2,3-butanediol and 2.5 parts of 1,2-hexanediol, and mechanically stir at 30°C for 30 min to obtain an aqueous phase system;
[0095] S3, Preparation of the oil phase system
[0096] Weigh 10 parts of caprylic / capric triglyceride, 1.0 part of retinol and 1.0 part of hydroxypinazone retinate, mix them at 30°C in the dark for 15 min to obtain the oil phase system;
[0097] S4, Formation of the initial mixed system
[0098] The oil phase system was slowly added to the aqueous phase system at 30℃ and mixed for 30 min. Then, 5.8 parts of a single modified lipid were added and the mixture was stirred for another 30 min to obtain the liposome precursor system.
[0099] S5, Preparation of nanoliposomes
[0100] The liposome precursor system was subjected to high-shear dispersion at 30℃, with a dispersion speed of 14000 r / min and a dispersion time of 15 min to obtain retinol composite nanoliposomes.
[0101] Performance testing:
[0102] 1. Appearance and delamination stability test methods
[0103] The samples prepared in Examples 1, 2, and 3, as well as Comparative Examples 1 and 2, were placed in sealed containers of the same specifications and left to stand at room temperature under light-protected conditions. The appearance of the samples was observed periodically, including whether the system was homogeneous and whether phenomena such as stratification, precipitation, flocculation, or oil separation occurred. At the same time, the above samples were centrifuged under the same conditions to accelerate the manifestation of differences in system stability. After centrifugation, the appearance changes and stratification of each sample were observed and recorded immediately to evaluate the macroscopic stability of nanoliposomes under different lipid systems and different ratios.
[0104] 2. Test methods for the stability and leakage trend of active material encapsulation
[0105] Samples prepared in Examples 1, 2, and 3, as well as Comparative Examples 1 and 2, were taken after preparation and storage for a certain period of time. The liposome enriched phase was separated from the external phase by a separation method, and the contents of retinol and hydroxypinazone retinate were determined by high performance liquid chromatography under light-protected conditions. By comparing the changes in the content of retinoid active ingredients in the external phase of different samples under the same storage conditions, the influence of different lipid systems and different component ratios on the encapsulation stability and leakage trend of retinoid active ingredients was evaluated.
[0106] 3. Accelerated Storage Stability Testing Method
[0107] The samples prepared in Examples 1, 2, and 3, as well as Comparative Examples 1 and 2, were placed under the same packaging conditions and subjected to accelerated storage tests in a set heating environment. Samples were taken at the same time points during the test to observe whether the samples exhibited phenomena such as stratification, precipitation, flocculation, or color changes. The content retention of retinol and hydroxypinazone retinate in the samples was measured under light-protected conditions to evaluate the effect of different lipid systems on the stability of retinoid active ingredients under thermal stress conditions.
[0108] 4. Light stability test method
[0109] The samples prepared in Examples 1, 2, and 3, as well as Comparative Examples 1 and 2, were placed under specified light conditions for photostability testing. A control sample under the same light-shielded conditions was also set up. Samples were taken at the same time points during the test. The appearance differences such as precipitation, layering, or color changes were observed in the samples. The changes in the content of retinol and hydroxypinazone retinyl ester were measured under light-shielded conditions to evaluate the photostability protection of retinol-like active ingredients under different lipid systems and different ratios.
[0110] Table 1. Results of appearance and delamination stability tests on different samples
[0111] sample Appearance after standing at room temperature for 30 days Layer height after centrifugation (mm) Example 1 The system is homogeneous and has no obvious stratification. 0.6 Example 2 The system is homogeneous and has no hierarchical structure. 0.2 Example 3 Generally uniform, with slight oil droplets 0.8 Comparative Example 1 Clearly layered 3.5 Comparative Example 2 Layering accompanied by flocculation 4.2
[0112] Table 2. Test results of active ingredient encapsulation stability and leakage trend for different samples.
[0113] sample Retinol content in the external phase (%) Hydroxypinazone retinate content in the external phase (%) Example 1 6.8 5.9 Example 2 3.2 2.8 Example 3 8.1 7.4 Comparative Example 1 21.5 18.9 Comparative Example 2 24.7 22.3
[0114] Table 3. Retention rate of active ingredient content of different samples under accelerated storage conditions
[0115] sample Retinol retention rate (%) Hydroxypinazone retinate retention rate (%) Example 1 86.3 88.1 Example 2 93.5 95.2 Example 3 82.7 84.9 Comparative Example 1 61.4 64.2 Comparative Example 2 58.6 60.1
[0116] Table 4. Results of photostability tests on different samples
[0117] sample Retinol retention rate (%) Hydroxypinazone retinate retention rate (%) Example 1 83.9 86.0 Example 2 91.8 93.6 Example 3 80.5 82.3 Comparative Example 1 55.7 58.4 Comparative Example 2 52.1 54.9
[0118] As shown in Table 1, Examples 1, 2, and 3 all maintained good system homogeneity after standing at room temperature for 30 days. The layer heights after centrifugation were 0.6 mm, 0.2 mm, and 0.8 mm, respectively, which were significantly lower than those of Comparative Examples 1 and 2 (3.5 mm and 4.2 mm). Among them, Example 2 had the smallest layer height, indicating that the nanoliposomes formed under the synergistic effect of modified lipids have better macroscopic dispersion stability, while the single modified lipid system is more prone to layering and structural instability.
[0119] As shown in Table 2, after 30 days of storage, the retinol content in the external phase of the samples from Examples 1, 2, and 3 was 6.8%, 3.2%, and 8.1%, respectively, and the hydroxypinazone retinate content was 5.9%, 2.8%, and 7.4%, respectively, all significantly lower than the 21.5% and 18.9% of Comparative Example 1 and the 24.7% and 22.3% of Comparative Example 2. Among them, the content of the two active ingredients in the external phase of Example 2 was the lowest, indicating that under the median ratio conditions, the synergistic modified lipids had the best encapsulation stability for retinol-like active ingredients and could effectively inhibit the leakage of active ingredients.
[0120] As shown in Table 3, after storage at 45°C for 14 days, the retention rates of retinol in Examples 1, 2, and 3 were 86.3%, 93.5%, and 82.7%, respectively, and the retention rates of hydroxypinazone retinate were 88.1%, 95.2%, and 84.9%, respectively, all significantly higher than those of Comparative Example 1 (61.4% and 64.2%) and Comparative Example 2 (58.6% and 60.1%). Among them, Example 2 achieved the highest retention rates for both active ingredients, indicating that the synergistically modified lipid system can provide a more stable protective environment for retinol-like active ingredients under thermal stress conditions.
[0121] As shown in Table 4, after 7 days of light exposure, the retention rates of retinol in Examples 1, 2, and 3 were 83.9%, 91.8%, and 80.5%, respectively, and the retention rates of hydroxypinazone retinate were 86.0%, 93.6%, and 82.3%, respectively. These were significantly higher than those of Comparative Example 1 (55.7% and 58.4%) and Comparative Example 2 (52.1% and 54.9%). Example 2 also showed the best results in the photostability test, indicating that the nanoliposome structure formed by synergistic modification of lipids can effectively reduce the adverse effects of light exposure on retinol-like active substances.
[0122] In summary, by synergistically modifying lipids to co-encapsulate retinol and hydroxypinazone retinate, the tendency of liposome system to separate can be significantly reduced, the leakage of active ingredients can be reduced, and its stability under adverse conditions such as heat and light can be improved. Among them, Example 2 showed the best performance in all performance tests, which fully demonstrates that the technical solution of the present invention has significant technical advantages over the comparative solution of single modified lipids in terms of stability and active ingredient utilization.
Claims
1. A highly stable retinol composite nanoliposome, characterized in that, The highly stable retinol composite nanoliposomes comprise the following raw materials in parts by weight: 35-45 parts glycerol; 25-40 parts water; 5-15 parts 2,3-butanediol; 5-15 parts caprylic / capric triglyceride; 1-4 parts 1,2-hexanediol; 0.5-2.0 parts retinol; 0.5-2.0 parts hydroxypinazone retinate; and 2.7-9.0 parts synergistic modified lipids. The synergistic modified lipids are composed of sodium stearoyl glutamate, polysorbate-20, and polyglycerol-4 oleate. The retinol and hydroxypinazone retinate, as retinol-like active substances, are co-encapsulated within the nanoscale liposome structure formed by the self-assembly of the synergistic modified lipids.
2. The highly stable retinol composite nanoliposome according to claim 1, characterized in that, The synergistically modified lipid comprises the following raw materials in parts by weight: sodium stearoyl glutamate 0.2-1.0 parts; polysorbate-20 0.5-2.0 parts; polyglycerol-4 oleate 2.0-6.0 parts.
3. A highly stable retinol composite nanoliposome according to claim 1 or 2, characterized in that, The preparation method of the synergistically modified lipids includes the following steps: (1) Weigh out sodium stearoyl glutamate, polysorbate-20 and polyglycerol-4 oleate; (2) Sodium stearoyl glutamate, polysorbate-20 and polyglycerol-4 oleate were added to the solvent in sequence and mixed under stirring to obtain a homogeneous lipid mixture system; (3) The obtained lipid mixture system was dispersed to obtain synergistically modified lipids.
4. The highly stable retinol composite nanoliposome according to claim 3, characterized in that, The reaction conditions for step (2) are as follows: sodium stearoyl glutamate, polysorbate-20 and polyglycerol-4 oleate are added to the solvent and mixed by mechanical stirring at 20-40°C, with a stirring speed of 300-1000 r / min and a stirring time of 10-60 min.
5. The highly stable retinol composite nanoliposome according to claim 3, characterized in that, The reaction conditions for step (3) are as follows: the obtained lipid mixture is treated by high shear dispersion, the dispersion temperature is 20-40℃, the dispersion speed is 8000-20000r / min, and the dispersion time is 5-30min.
6. A method for preparing highly stable retinol composite nanoliposomes, characterized in that, The preparation method includes the following steps: S1, Weigh out glycerol, water, 2,3-butanediol and 1,2-hexanediol, mix them under stirring to obtain an aqueous phase system; S2, weigh out caprylic / capric triglyceride, retinol and hydroxypinazone retinate, mix them to obtain the oil phase system; S3, Under stirring conditions, the oil phase system is added to the aqueous phase system and mixed to obtain the initial mixed system; S4, add synergistically modified lipids to the initial mixing system and continue mixing to obtain the liposome precursor system; S5, the liposome precursor system was dispersed to obtain highly stable retinol composite nanoliposomes.
7. The method for preparing a highly stable retinol composite nanoliposome according to claim 6, characterized in that, The reaction conditions for step S1 are stirring and mixing at 20–40°C for 10–60 min, using mechanical stirring; the reaction conditions for step S2 are mixing under light-protected conditions at 20–40°C for 5–30 min.
8. The method for preparing a highly stable retinol composite nanoliposome according to claim 6, characterized in that, The reaction conditions for step S3 are as follows: the oil phase system is slowly added to the aqueous phase system at 20-40°C and mixed under stirring for 10-60 minutes.
9. The method for preparing a highly stable retinol composite nanoliposome according to claim 6, characterized in that, The reaction conditions for step S4 are as follows: add the synergistically modified lipid to the initial mixture at 20–40°C and continue stirring for 10–60 min.
10. The method for preparing a highly stable retinol composite nanoliposome according to claim 6, characterized in that, The reaction conditions for step S5 are as follows: the liposome precursor system is treated with high shear dispersion, the dispersion temperature is 20-40℃, the dispersion speed is 8000-20000 r / min, and the dispersion time is 5-30 min.