A stable traditional Chinese medicine compound gel for anti-skin aging and its preparation method

Abstract

The present invention belongs to the field of pharmaceutical technology and relates to a stable traditional Chinese medicine compound gel for anti-skin aging. The present invention uses a novel CBSP-CP as a gel matrix, combines it with an anti-aging traditional Chinese medicine extract to prepare a gel preparation, which has better stability, better rheological properties, higher transdermal absorption effect, and stronger skin adaptability compared with traditional Chinese medicine compound gels for anti-skin aging prepared with different types of matrices such as Carbopol 940, modified Carbopol ETD 2020, and polyacrylate cross-linked polymer-6 (Zen).

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine preparations, and particularly to a stable traditional Chinese medicine compound gel for anti-skin aging, which has better stability, better rheological properties, higher transdermal absorption effect, and stronger skin adaptability. Background Art

[0002] CN 1943707B discloses a traditional Chinese medicine extract for anti-aging and its preparation method, which is prepared from rehmannia root, red ginseng, ophiopogon root, asparagus root, cortex lycii radicis, and poria cocos by a specific process, and has an obvious therapeutic effect on treating symptoms such as fatigue, palpitation, shortness of breath, listlessness, dizziness, hot flashes and sweating, tinnitus and amnesia, restlessness and insomnia caused by qi and yin deficiency in the middle-aged and elderly, and delays aging.

[0003] Aging is a process in which the body gradually loses its functions and moves towards death. As the largest organ of the body, the skin is the defense barrier between the body and the external environment, and can reflect aging more intuitively and obviously than other organs. Our research shows that the anti-aging traditional Chinese medicine extract has a definite effect in anti-skin aging, but currently there are only oral dosage forms such as tablets, pills, and capsules, and there is no report on topical preparations suitable for direct skin administration.

[0004] Gels refer to thick liquids or semi-solid preparations with gel characteristics prepared from raw material drugs and excipients (also called gel matrices) that can form gels. According to the different gel matrices, gels are divided into aqueous gels and oily gels. Aqueous gels have the characteristics of easy spreading, good comfort, no greasy feeling, easy to wash off, can absorb tissue exudate, do not interfere with the normal physiological functions of the skin, have a certain water retention effect, and can promote the transdermal absorption of traditional Chinese medicine extracts, etc., and are widely used in the fields of medicine, daily chemicals, etc., and are favored by patients and consumers. Preparing the anti-aging traditional Chinese medicine extract into an aqueous gel expands its application range, increases the drug concentration in the skin at the site of action, and can better achieve its anti-skin aging effect.

[0005] Carbomer is the most commonly used matrix for aqueous gels, with important uses such as thickening and suspension. It has the advantages of simple preparation process, good rheological properties, and no irritation to the skin and mucosa. It is widely used in emulsions, creams, and gels, and is an excellent gel matrix material. Although the process of preparing gels with carbomer is simple and can endow the gels with good rheological properties, its disadvantage is that carbomer has a relatively strong sensitivity to the gel environment. This is manifested in that the presence of ions will significantly reduce its thickening efficiency; trace amounts of iron or other transition metals will cause the gel to irreversibly decrease in viscosity, seriously damaging the stability of the system; in addition, high shear, ultraviolet irradiation, or prolonged stirring will also cause a loss of the viscosity of carbomer gels, reducing the gel viscosity. The sensitivity of carbomer, especially ion sensitivity, is the main problem in its application. Acid components and mineral ions cannot be added to gels based on carbomer, and certain bacteriostatic agents need to be avoided or can only be used at low concentrations, otherwise the consistency will decrease sharply or even disappear. In order to improve the ion tolerance of the carbomer matrix, companies have developed modified gel matrices, namely Carbopol ETD 2020, but its ion tolerance is still relatively low. As a gel matrix material with excellent rheological properties, the instability of the matrix properties, especially the lack of ion tolerance, limits the application of the carbomer matrix.

[0006] The anti-aging traditional Chinese medicine extract is composed of six traditional Chinese medicines: Rehmannia glutinosa, Panax ginseng, Ophiopogon japonicus, Asparagus cochinchinensis, Cortex Lycii, and Poria cocos. Its extract components are complex, and it is a huge challenge to prepare stable preparations, especially stable gel products, which cannot be achieved by simply using the carbomer matrix.

[0007] Explanation of related entries:

[0008] Anti-aging traditional Chinese medicine extract: In the present invention, it is the total extract of six traditional Chinese medicines: Rehmannia glutinosa, Panax ginseng, Ophiopogon japonicus, Asparagus cochinchinensis, Cortex Lycii, and Poria cocos; it can be a mixture after separate extraction or co-extraction.

[0009] CBSP: Cationized Bletilla striata polysaccharide;

[0010] CP: Carbomer;

[0011] CBSP-CP: A complex formed by cationized Bletilla striata polysaccharide and carbomer in a certain proportion, which can be used as a gel matrix.

[0012] CBSP-CP(2∶1): A complex formed by cationized Bletilla striata polysaccharide and carbomer in a 2∶1 ratio, used as a gel matrix. Summary of the Invention

[0013] The object of the present invention is to provide a novel gel for the current anti-aging traditional Chinese medicine extracts, which only have oral dosage forms such as tablets, pills, capsules, etc., and there is no report on external preparations suitable for direct skin administration. This novel gel has the advantages of high drug content, good stability, excellent rheological properties, good transdermal absorption effect, and strong skin adaptability.

[0014] The object of the present invention is achieved by the following technical means:

[0015] The present invention provides a novel gel matrix material, especially a novel gel matrix that is stable, resistant to ions, resistant to complex components of traditional Chinese medicine, and has good rheological properties. The gel matrix is composed of cationized Bletilla striata polysaccharide (CBSP) and CP that can form a composition with CBSP, where CP is Carbopol, also known as Carbopo. By weight ratio, the ratio of cationized Bletilla striata polysaccharide to Carbopol is 2:1.

[0016] Specifically, in this composition, CP is preferably Carbopol ETD 2020 (abbreviated as CP 2020). That is, CBSP and Carbopol ETD 2020 form a composition, and the ratio of CBSP:CP is 2:1.

[0017] The cationized Bletilla striata polysaccharide (CBSP) described in the present invention can be prepared by the following method:

[0018] Dissolve BSP in a NaOH / urea solution to obtain a homogeneous system, then add NaOH to alkalize at room temperature, raise the temperature, add NaOH and the etherifying agent 3-chloro-2-hydroxypropyltrimethylammonium chloride (CTA) to the system. The molar ratio of alkali to ether in the system is 1:1, and etherify for 5 h, adjust the pH, and the etherification reaction ends; then place it in a dialysis bag and purify it with ultrapure water as the permeating medium; after purification, dry it to obtain cationized Bletilla striata polysaccharide (CBSP).

[0019] The novel gel matrix material CBSP-CP (2:1) described in the present invention can be prepared by the following method:

[0020] Disperse 0.5% (w / v) CP2020 in water, stir, and let stand to obtain phase A;

[0021] Disperse 1.0% (w / v) CBSP in water, stir to form a CBSP solution, which is phase B;

[0022] At room temperature of 25 °C, slowly add phase B to phase A, adjust the pH with a saturated solution of citric acid and triethanolamine, and freeze-dry to obtain the CBSP-CP composition matrix, that is, the novel gel matrix material CBSP-CP (2:1) described in the present invention.

[0023] The present invention provides a stable traditional Chinese medicine compound gel for anti-skin aging, and its composition includes: the gel matrix described in claim 1 and the traditional Chinese medicine extract, wherein the traditional Chinese medicine extract is prepared from the following raw materials in parts by weight:

[0024]

[0025] In the preparation of the traditional Chinese medicine extract, each medicinal material can be separately extracted by a conventional method and then mixed, or can be mixed and extracted by a conventional method.

[0026] The traditional Chinese medicine compound gel for anti-skin aging described in the present invention further includes a pH regulator;

[0027] The traditional Chinese medicine compound gel for anti-skin aging described in the present invention further includes additives, and is characterized in that the additives are selected from one or more of a humectant, a preservative, a transdermal absorption enhancer, an antioxidant, and a fragrance.

[0028] The present invention provides a stable traditional Chinese medicine compound gel for anti-skin aging, and the weight ratio of each component is:

[0029]

[0030] Further, the weight ratio of each component in the gel is:

[0031]

[0032] Further, the weight ratio of each component in the gel is:

[0033]

[0034]

[0035] Further, the weight ratio of each component in the gel is:

[0036]

[0037] Benefiting from the synergistic ratio among Rehmannia glutinosa, red ginseng, Ophiopogon japonicus, Asparagus cochinchinensis, Cortex Lycii, and Poria cocos, the good combination among the traditional Chinese medicine extracts, and the good ratio between the traditional Chinese medicine extract and the gel matrix, the beneficial effects of the traditional Chinese medicine compound gel for anti-skin aging of the present invention are:

[0038] The present invention relates to a traditional Chinese medicine compound gel preparation for anti-skin aging, which uses CBSP-CP as a gel matrix and combines with anti-aging traditional Chinese medicine extracts. Compared with anti-skin aging traditional Chinese medicine compound gels prepared by combining different types of matrices such as traditional Carbopol 940, modified Carbopol ETD 2020, and polyacrylate cross-linked polymer-6 (Zen) with anti-aging traditional Chinese medicine extracts, it has better stability, better rheological properties, higher transdermal absorption effect, and stronger moisturizing effect.

[0039] Stability. The anti-skin aging traditional Chinese medicine compound gel prepared by combining CBSP-CP as a matrix with anti-aging traditional Chinese medicine extracts has better stability (P < 0.01) in terms of the appearance, viscosity, and content of active index components of the gel under high temperature (40 °C), low temperature (-4 °C), and strong light (4500 Lx) conditions.

[0040] Rheological properties. The anti-skin aging traditional Chinese medicine compound gel prepared by combining CBSP-CP as a matrix with anti-aging traditional Chinese medicine extracts has the smallest decrease in steady-state apparent viscosity and has a better thickening and viscosity-maintaining effect on the system. In addition, the rheological curves of anti-skin aging traditional Chinese medicine compound gels prepared by combining different matrices with anti-aging traditional Chinese medicine extracts show that the anti-skin aging traditional Chinese medicine compound gel prepared with CBSP-CP as the matrix shows pseudoplastic fluidity, which is beneficial for spreading, and at the same time shows better shear resistance compared with the other three matrices.

[0041] Transdermal penetration characteristics. Using catalpol in Rehmannia glutinosa and ginsenoside Re in Panax ginseng as index components, the 24-hour cumulative penetration rates of catalpol and ginsenoside Re in the anti-skin aging traditional Chinese medicine compound gel samples prepared by combining each matrix with anti-aging traditional Chinese medicine extracts are the highest with CBSP-CP. At the same time, the 24-hour skin retention amounts of catalpol and ginsenoside Re in the anti-skin aging traditional Chinese medicine compound gel samples with CBSP-CP as the matrix are also the largest, which is beneficial for forming a drug reservoir on the skin and playing a long-term effect. Description of the Drawings

[0042] Figure 1 is the γ-η rheological curve of the gel prepared by combining CBSP-CP and commercially available matrices with anti-aging traditional Chinese medicine extracts;

[0043] Figure 2 is the transdermal penetration curve of the gel prepared by combining CBSP-CP and commercially available matrices with anti-aging traditional Chinese medicine extracts ( , n = 3);

[0044] Figure 3 is the result of the skin retention rate of the gel prepared by combining CBSP-CP and commercially available matrices with anti-aging traditional Chinese medicine extracts ( , n = 3); Detailed Implementation Modes

[0045] Bletilla striata polysaccharide (BSP, provided by Xi'an Panier Biotechnology Co., Ltd., Shaanxi, China); Carbopol (CP): Carbopol 940 (CP940, supplied by Lubrizol Corporation, USA), Carbopol ETD 2020 (CP2020, supplied by Lubrizol Corporation, USA), Carbopol Ultrez 20 (CP U20, supplied by Lubrizol Corporation, USA), polyacrylate cross-linked polymer - 6 (Zen, provided by Seppic, France).

[0046] Example 1 Preparation of cationized Bletilla striata polysaccharide (CBSP)

[0047] Dissolve BSP in NaOH / urea solution to obtain a homogeneous system, then add NaOH to alkalize at room temperature, raise the temperature, add NaOH to the system and slowly dropwise add the etherifying agent 3-chloro-2-hydroxypropyltrimethylammonium chloride (CTA). The molar ratio of alkali to ether in the system is 1:1. Carry out etherification in a constant temperature water bath for 5 h, adjust the pH to neutral, and the etherification reaction ends. Subsequently, place it in an activated dialysis bag with a molecular weight cut-off of 8 - 14 KD, use ultrapure water as the permeation medium for purification, and change the exudate every 3 h; after purification, filter by suction, rotary evaporate, freeze-dry, and pulverize to obtain cationized Bletilla striata polysaccharide (CBSP).

[0048] Example 2 Preparation of the novel gel matrix material CBSP-CP (2:1)

[0049] Disperse 0.5% (w / v) CP2020 in deionized water at 70 °C, stir at 400 rpm until uniform, and let stand for 12 h until a uniform, lump-free sol is formed, designated as Phase A;

[0050] Disperse 1.0% (w / v) CBSP in deionized water at room temperature of 25 °C, stir at 400 rpm until uniform to form a CBSP solution, designated as Phase B;

[0051] At room temperature of 25 °C, slowly drop Phase B into Phase A, and adjust the pH to 6.5 with a saturated solution of citric acid and triethanolamine, then freeze-dry to obtain the CBSP-CP composition matrix.

[0052] Example 3 Preparation of the anti-aging traditional Chinese medicine extract (Rehmannia glutinosa: Panax ginseng: Ophiopogon japonicus: Asparagus cochinchinensis: Lycium chinense: Poria cocos = 409:167:26:26:26:77)

[0053] Take 409g of Rehmannia root, 167g of red ginseng, 26g of Ophiopogon japonicus, 26g of Asparagus cochinchinensis, 26g of Lycium bark, and 77g of Poria cocos, decoct three times with 3 times the amount of water, combine the decoctions extracted three times, filter, and concentrate the filtrate to a relative density of 1.30-1.40 at 80°C: take 500mL of the supernatant and store it at low temperature and away from light, which is an anti-aging Chinese medicine extract.

[0054] Example 4 Preparation of anti-aging Chinese herbal extract (raw rehmannia root: red ginseng: ophiopogon japonicus: asparagus cochinchinensis: lycium bark: poria cocos = 409: 167: 26: 26: 26: 77)

[0055] Take 409g of raw rehmannia, 167g of red ginseng, 26g of ophiopogon, 26g of asparagus, 26g of lycium bark, and 77g of poria, and decoct each medicinal material separately with appropriate amount of water. After decocting each material three times, combine all the decoctions, filter, and concentrate the filtrate to a relative density of 1.30-1.40 when the filtrate is concentrated to 80°C; take 500mL of the supernatant and store it at low temperature and away from light to obtain the anti-aging Chinese medicine extract.

[0056] Example 5 Gels prepared by combining different gel matrices with anti-aging Chinese herbal extracts

[0057] Four anti-skin aging Chinese herbal compound gels were prepared under different matrix conditions using commercially available CP 940, CP 2020, Zen and CBSP-CP as matrix materials, with other components and preparation methods being the same. The preparation performance quality of the anti-skin aging Chinese herbal compound gel prepared with CBSP-CP as the matrix was investigated.

[0058] Prescription composition:

[0059]

[0060] Take an appropriate amount of glycerin as a wetting agent, fully swell the four matrices of CP940, CP2020, Zen and CBSP-CP (Example 2), add antioxidants and anti-aging Chinese medicine extracts, and stir until uniform; then add penetration enhancers, surfactants, preservatives, etc. and stir thoroughly, add deionized water to a certain amount, adjust the pH, and add a certain amount of flavor to prepare an anti-skin aging Chinese medicine compound gel combining different matrices with anti-aging Chinese medicine extracts.

[0061] Example 6 Gels prepared by combining different gel matrices with anti-aging Chinese herbal extracts

[0062] Four anti-skin aging Chinese herbal compound gels were prepared under different matrix conditions using commercially available CP940, CP2020, Zen and CBSP-CP as matrix materials, with other components and preparation methods being the same. The preparation performance quality of the anti-skin aging Chinese herbal compound gel prepared with CBSP-CP as the matrix was investigated.

[0063] Prescription composition:

[0064]

[0065]

[0066] Take an appropriate amount of glycerol as a wetting agent, and fully swell it with four matrices of CP940, CP2020, Zen, and CBSP-CP (Example 2) respectively. Add an antioxidant and an anti-aging traditional Chinese medicine extract, and stir until uniform; then add a penetration enhancer, a surfactant, a preservative, etc., and stir well. Supplement deionized water to a fixed volume, adjust the pH, and add a fixed amount of essence to prepare an anti-skin-aging traditional Chinese medicine compound gel combined with different matrices and an anti-aging traditional Chinese medicine extract.

[0067] The gel prepared in Example 7 by combining different gel matrices with an anti-aging traditional Chinese medicine extract

[0068] Take commercially available CP940, CP2020, Zen, and CBSP-CP as matrix materials respectively, with the other components and preparation methods being the same, to prepare anti-skin-aging traditional Chinese medicine compound gels under four different matrix conditions, and investigate the preparation performance and quality of the anti-skin-aging traditional Chinese medicine compound gel prepared with CBSP-CP as the matrix.

[0069] Prescription composition:

[0070]

[0071]

[0072] Take an appropriate amount of glycerol as a wetting agent, and fully swell it with four matrices of CP940, CP2020, Zen, and CBSP-CP (Example 2) respectively. Add an antioxidant and an anti-aging traditional Chinese medicine extract, and stir until uniform; then add a penetration enhancer, a surfactant, a preservative, etc., and stir well. Supplement deionized water to a fixed volume, adjust the pH, and add a fixed amount of essence to prepare an anti-skin-aging traditional Chinese medicine compound gel combined with different matrices and an anti-aging traditional Chinese medicine extract.

[0073] The gel prepared in Example 8 by combining different gel matrices with an anti-aging traditional Chinese medicine extract

[0074] Take commercially available CP940, CP2020, Zen, and CBSP-CP as matrix materials respectively, with the other components and preparation methods being the same, to prepare anti-skin-aging traditional Chinese medicine compound gels under four different matrix conditions, and investigate the preparation performance and quality of the anti-skin-aging traditional Chinese medicine compound gel prepared with CBSP-CP as the matrix.

[0075] Prescription composition:

[0076]

[0077] Take an appropriate amount of glycerol as a wetting agent, and fully swell it with four matrices of CP940, CP2020, Zen, and CBSP-CP (Example 2) respectively. Add an antioxidant and an anti-aging traditional Chinese medicine extract, and stir until homogeneous. Then add a penetration enhancer, a surfactant, a preservative, etc., and stir well. Add deionized water to a fixed volume, adjust the pH, and add a fixed amount of essence to prepare an anti-skin aging traditional Chinese medicine compound gel combined with different matrices and an anti-aging traditional Chinese medicine extract.

[0078] The gel prepared in Example 9 by combining different gel matrices with an anti-aging traditional Chinese medicine extract

[0079] Take commercially available CP940, CP2020, Zen, and CBSP-CP as matrix materials respectively, with the same other components and preparation methods, and prepare anti-skin aging traditional Chinese medicine compound gels under four different matrix conditions, and investigate the preparation performance and quality of the anti-skin aging traditional Chinese medicine compound gel prepared with CBSP-CP as the matrix.

[0080] Prescription composition:

[0081]

[0082] Take an appropriate amount of glycerol as a wetting agent, and fully swell it with four matrices of CP940, CP2020, Zen, and CBSP-CP (Example 2) respectively. Add an antioxidant and an anti-aging traditional Chinese medicine extract, and stir until homogeneous. Then add a penetration enhancer, a surfactant, a preservative, etc., and stir well. Add deionized water to a fixed volume, adjust the pH, and add a fixed amount of essence to prepare an anti-skin aging traditional Chinese medicine compound gel combined with different matrices and an anti-aging traditional Chinese medicine extract.

[0083] The gel prepared in Example 10 by combining different gel matrices with an anti-aging traditional Chinese medicine extract

[0084] Take commercially available CP940, CP2020, Zen, and CBSP-CP as matrix materials respectively, with the same other components and preparation methods, and prepare anti-skin aging traditional Chinese medicine compound gels under four different matrix conditions, and investigate the preparation performance and quality of the anti-skin aging traditional Chinese medicine compound gel prepared with CBSP-CP as the matrix.

[0085] Prescription composition:

[0086]

[0087]

[0088] Take an appropriate amount of glycerol as a wetting agent, and swell it with four matrices of CP940, CP2020, Zen, and CBSP-CP (Example 2) respectively. Add an antioxidant and an anti-aging traditional Chinese medicine extract, and stir until homogeneous. Then add a penetration enhancer, a surfactant, a preservative, etc., stir well, supplement deionized water to a fixed volume, adjust the pH, and add a fixed amount of essence to prepare an anti-skin aging traditional Chinese medicine compound gel combined with different matrices and an anti-aging traditional Chinese medicine extract.

[0089] The gel prepared in Example 11 by combining different gel matrices with an anti-aging traditional Chinese medicine extract

[0090] Take commercially available CP940, CP2020, Zen, and CBSP-CP as matrix materials respectively, with the same other components and preparation methods, prepare anti-skin aging traditional Chinese medicine compound gels under four different matrix conditions, and investigate the preparation performance and quality of the anti-skin aging traditional Chinese medicine compound gel prepared with CBSP-CP as the matrix.

[0091] Prescription composition:

[0092]

[0093]

[0094] Take an appropriate amount of glycerol as a wetting agent, and swell it with four matrices of CP940, CP2020, Zen, and CBSP-CP (Example 2) respectively. Add an antioxidant and an anti-aging traditional Chinese medicine extract, and stir until homogeneous. Then add a penetration enhancer, a surfactant, a preservative, etc., stir well, supplement deionized water to a fixed volume, adjust the pH, and add a fixed amount of essence to prepare an anti-skin aging traditional Chinese medicine compound gel combined with different matrices and an anti-aging traditional Chinese medicine extract.

[0095] The gel prepared in Example 12 by combining different gel matrices with an anti-aging traditional Chinese medicine extract

[0096] Take commercially available CP940, CP2020, Zen, and CBSP-CP as matrix materials respectively, with the same other components and preparation methods, prepare anti-skin aging traditional Chinese medicine compound gels under four different matrix conditions, and investigate the preparation performance and quality of the anti-skin aging traditional Chinese medicine compound gel prepared with CBSP-CP as the matrix.

[0097] Prescription composition:

[0098]

[0099] Take an appropriate amount of glycerol as a wetting agent, and swell it with four matrices of CP940, CP2020, Zen, and CBSP-CP (Example 2) respectively. Then add an antioxidant and an anti-aging traditional Chinese medicine extract, and stir until homogeneous. Next, add a penetration enhancer, a surfactant, a preservative, etc., and stir well. Add deionized water to a fixed volume, adjust the pH, and add a fixed amount of essence to prepare an anti-skin aging traditional Chinese medicine compound gel combined with different matrices and an anti-aging traditional Chinese medicine extract.

[0100] The gel prepared in Example 13 by combining different gel matrices with an anti-aging traditional Chinese medicine extract

[0101] Take commercially available CP940, CP2020, Zen, and CBSP-CP as matrix materials respectively, with the same other components and preparation methods, and prepare anti-skin aging traditional Chinese medicine compound gels under four different matrix conditions. Examine the preparation performance and quality of the anti-skin aging traditional Chinese medicine compound gel prepared with CBSP-CP as the matrix.

[0102] Prescription composition:

[0103]

[0104] Take an appropriate amount of glycerol as a wetting agent, and swell it with four matrices of CP940, CP2020, Zen, and CBSP-CP (Example 2) respectively. Then add an antioxidant and an anti-aging traditional Chinese medicine extract, and stir until homogeneous. Next, add a penetration enhancer, a surfactant, a preservative, etc., and stir well. Add deionized water to a fixed volume, adjust the pH, and add a fixed amount of essence to prepare an anti-skin aging traditional Chinese medicine compound gel combined with different matrices and an anti-aging traditional Chinese medicine extract.

[0105] The gel prepared in Example 14 by combining different gel matrices with an anti-aging traditional Chinese medicine extract

[0106] Take commercially available CP940, CP2020, Zen, and CBSP-CP as matrix materials respectively, with the same other components and preparation methods, and prepare anti-skin aging traditional Chinese medicine compound gels under four different matrix conditions. Examine the preparation performance and quality of the anti-skin aging traditional Chinese medicine compound gel prepared with CBSP-CP as the matrix.

[0107] Prescription composition:

[0108]

[0109] Take an appropriate amount of glycerol as a wetting agent, and fully swell it with four matrices of CP940, CP2020, Zen, and CBSP-CP (Example 2) respectively. Add an antioxidant and an anti-aging traditional Chinese medicine extract, and stir until uniform; then add a penetration enhancer, a surfactant, a preservative, etc., stir well, supplement deionized water to a fixed volume, adjust the pH, and add a fixed amount of essence to prepare an anti-skin aging traditional Chinese medicine compound gel combined with different matrices and anti-aging traditional Chinese medicine extracts.

[0110] Investigation on the stability of the anti-skin aging traditional Chinese medicine compound gel prepared by combining different gel matrices with anti-aging traditional Chinese medicine extracts in Example 15

[0111] The samples of Example 5 were evenly encapsulated in colorless transparent vials and placed under different temperatures and strong light (45001x) conditions respectively. The changes in the appearance properties, viscosity, and quality indexes such as the contents of the index components of Rehmannia glutinosa (catalpol) and red ginseng (ginsenoside Re) of the anti-skin aging traditional Chinese medicine compound gel prepared by combining different matrices with anti-aging traditional Chinese medicine extracts were investigated. The results are shown in Table 1. In the table, "↓" and "↑" represent the degree of decrease or increase compared with day 0. The results show that the anti-skin aging traditional Chinese medicine compound gel prepared with CBSP-CP as the matrix has better stability in terms of the appearance properties, viscosity, and content of active index components under low temperature, high temperature, and strong light conditions (P < 0.01).

[0112] Table 1 Stability of the traditional Chinese medicine compound gel prepared by combining different matrices with anti-aging traditional Chinese medicine extracts (low temperature -4°C) ( n = 3)

[0113]

[0114] Table 2 Stability of the traditional Chinese medicine compound gel prepared by combining different matrices with anti-aging traditional Chinese medicine extracts (high temperature 40°C) ( n = 3)

[0115]

[0116]

[0117] Table 3 Stability of the traditional Chinese medicine compound gel prepared by combining different matrices with anti-aging traditional Chinese medicine extracts (strong light 4500lx) ( n = 3)

[0118]

[0119]

[0120] Investigation on the steady-state viscosity in Example 16

[0121] Using a DV-III rheometer, mode 1, SC4-34# rotor, shear at a constant rate of 20 s -1 for 120 s at room temperature (25 °C) to measure the steady-state apparent viscosity of the gel sample. The steady-state viscosity results of the anti-skin aging traditional Chinese medicine compound gel prepared with different matrices are shown in Table 4. The anti-skin aging traditional Chinese medicine compound gel prepared with CBSP-CP (Example 5) has the smallest decrease in steady-state apparent viscosity, indicating that the combination of CBSP-CP and the traditional Chinese medicine extract results in the best maintenance of the viscosity of the anti-skin aging traditional Chinese medicine compound gel system.

[0122] Table 4 Steady-state viscosity results of anti-skin aging traditional Chinese medicine compound gels prepared by combining different matrices with anti-aging traditional Chinese medicine extracts

[0123]

[0124] Example 17 Investigation of ion resistance

[0125] The viscosity and viscosity retention rate μ of the anti-skin aging traditional Chinese medicine compound gels prepared with different matrix materials under deionized water, 1% NaCl, and 1% CaCl2 conditions are shown in Table 5. The compound gels prepared with the four matrices have stronger resistance to Na + than to Ca 2+ . After combining different matrices with anti-aging traditional Chinese medicine extracts, the ability to resist Na + , Ca 2+ is the strongest with CBSP-CP.

[0126] Table 5 Ion resistance of anti-skin aging traditional Chinese medicine compound gels prepared by combining different matrices with anti-aging traditional Chinese medicine extracts

[0127]

[0128]

[0129] Example 18 Investigation of rheological curves

[0130] The rheological curves of the anti-skin aging traditional Chinese medicine compound gels prepared by combining different matrices with anti-aging traditional Chinese medicine extracts are shown in Figure 1 . At room temperature (25 °C) and body surface temperature (37 °C), each gel shows a decrease in viscosity with an increase in shear rate, conforming to a shear-thinning pseudoplastic fluid, which is beneficial for spreading. In the shear range of 0.01 - 70 S -1 , the viscosity value of the anti-skin aging traditional Chinese medicine compound gel prepared with CBSP-CP as the matrix and combined with anti-aging traditional Chinese medicine extracts always remains at a relatively high level, and the terminal viscosity value is still greater than 1000 mPa·s, indicating that the anti-skin aging traditional Chinese medicine compound gel prepared by the combined action of CBSP-CP and the traditional Chinese medicine extract has better shear resistance.

[0131] Investigation on Percutaneous Penetration Characteristics of Example 19

[0132] Referring to the method in the literature, using excised rat skin as the barrier model, the prepared rat skin was washed with normal saline before the experiment, dried with absorbent paper and then fixed in the diffusion cell; using normal saline containing 20% ethanol as the receiving medium, rotation speed: 400 r / min, temperature: 37 ± 0.1 °C; using Rehmannia glutinosa (catalpol) and Red Ginseng (ginsenoside Re) as the index components, 1 g of the anti-skin aging traditional Chinese medicine compound gel samples prepared by combining CBSP-CP and commercially available matrix with anti-aging traditional Chinese medicine extracts were added to the supply cell respectively. Each group was paralleled 4 times, 2 mL of samples were taken at different times, and an equal volume of blank receiving liquid was supplemented at the same temperature. The contents of Rehmannia glutinosa (catalpol) and Red Ginseng (ginsenoside Re) were determined by HPLC method, and the cumulative penetration amounts (Q, μg·cm -2 ) and cumulative permeation rates (F, %) of Rehmannia glutinosa (catalpol) and Red Ginseng (ginsenoside Re) at different time points were calculated through the following formulas 1 and 2. After the 24-hour percutaneous penetration experiment, the rat skin was removed, washed with normal saline, the residual moisture was removed by suction, cut into pieces, 5 mL of methanol was added, homogenized for 5 min, sonicated for 30 min, centrifuged, and the supernatant was taken to determine the contents of Rehmannia glutinosa (catalpol) and Red Ginseng (ginsenoside Re), and the skin retention rate (Qs) was calculated according to formula 3.

[0133]

[0134]

[0135] In the formula, S is the effective diffusion area (3.14 cm 2 ); P n is the sampling concentration at the nth time point; V is the total volume of the receiving cell (8.1 mL); P i is the sampling concentration at the ith time point; C is the mass concentration of Rehmannia glutinosa (catalpol) and Red Ginseng (ginsenoside Re) in the anti-skin aging traditional Chinese medicine compound gel; V0 is the sampling volume (2 mL); V1 is the total volume of the extracted solution of the administered gel (10 mL).

[0136]

[0137] In the formula, C1 is the mass concentration of Rehmannia glutinosa (catalpol) and Red Ginseng (ginsenoside Re) in the skin extract, V1 is the volume of the skin extract (5 mL), C is the mass concentration of Rehmannia glutinosa (catalpol) and Red Ginseng (ginsenoside Re) in the anti-skin aging traditional Chinese medicine compound gel, and V is the total volume of the administered gel solution (10 mL).

[0138] The change curves of the cumulative permeation rates (F) of Rehmannia glutinosa (catalpol) and Red Ginseng (ginsenoside Re) with time (t) in the traditional Chinese medicine compound gel for anti-skin aging (Example 5) prepared by combining CBSP-CP and commercially available matrices with anti-aging traditional Chinese medicine extracts are as follows Figure 2 shown. The 24-hour cumulative permeation rates of the traditional Chinese medicine compound gel samples for anti-skin aging prepared by combining different matrices with anti-aging traditional Chinese medicine extracts are different, among which CBSP-CP is the highest. The skin retention results are shown in Figure 3 . In the traditional Chinese medicine compound gel sample for anti-skin aging prepared by using CBSP-CP as the matrix and combining it with anti-aging traditional Chinese medicine extracts, the 24-hour skin retention amounts of Rehmannia glutinosa (catalpol) and Red Ginseng (ginsenoside Re) are relatively large, which is beneficial to forming a drug reservoir on the skin and playing a long-term effect.

[0139] Investigation of the anti-skin aging effect of Example 20

[0140] The skin has a barrier function, which can resist external physical and chemical damages and defend against the invasion of substances such as microbial antigens. Skin hydration, that is, the water content of the stratum corneum of the skin, is an important parameter reflecting the skin barrier function. Long-term exposure of the skin to UV radiation will lead to too low skin hydration and damage to the barrier function, causing skin aging; there are abundant capillaries under the stratum corneum of the skin. When the skin is stimulated by the outside world for a long time, it will increase the skin sensitivity, cause capillary dilation, form skin erythema, and lead to aging. Long-term UV radiation will also cause the skin to synthesize a large amount of melanin; melanin is a biological pigment widely distributed in the skin and hair tissues of higher animals. Its excessive production will lead to disordered melanin metabolism and abnormal pigment deposition, forming age spots.

[0141] An ICR mouse skin aging model induced by ultraviolet (UV) radiation was established to investigate the effects of the traditional Chinese medicine compound gel for anti-skin aging prepared by combining different matrices with anti-aging traditional Chinese medicine extracts on the skin water content, sensitivity, melanin and wrinkle formation of mice.

[0142] (1) Establishment of a photoaging animal model

[0143] First, use scissors and an electric shaver to remove the hair on the back of the mice. After fully exposing the back skin, fix the mice with a self-made mouse fixator, and then irradiate the mice with an SS-03AB type phototherapy instrument for modeling. Irradiate 5 days a week and rest for 2 days, and irradiate for a total of 3 weeks for modeling. The total radiation dose: the total dose of UVB is 9.45 J / cm 2 , and the total dose of UVA is 94.5 J / cm 2 . After the modeling is completed, the back skin of the successfully modeled mice is significantly thickened, the skin surface is rough, the skin is dry and hard, and obvious wrinkles can be seen.

[0144] (2) Experimental grouping

[0145] Randomly divided into 6 groups, namely: blank control group, 5 rats, skin preparation, device fixation, no irradiation; model group, 5 rats, skin preparation, device fixation, irradiation; compound gel group (anti-aging traditional Chinese medicine compound gel prepared by combining different matrices with anti-aging traditional Chinese medicine extracts in Example 4), 5 rats, skin preparation, device fixation, and the compound gel prepared with the corresponding matrix was topically applied to the back skin, irradiation.

[0146] (3) Effect of compound gel on skin moisture of UV-irradiated photoaging mice

[0147] The probe of the skin moisture content tester (Cornemeter CM 825, Courage and Khazaka, Germany) measures based on the principle of capacitance. The dielectric constant of water is 81, and the dielectric constants of other substances are usually less than 7. Water is the substance with the largest dielectric constant on the skin. When the moisture content changes, the capacitance value of the skin also changes. Therefore, the water content on the skin surface can be analyzed by measuring the skin capacitance value. The measured value is a relative value. The unit is expressed in C.U. (Corneometer Units).

[0148] In the experiment, the changes in skin moisture content after using different compound gels were tested. Specifically: the blank control group was not irradiated, the model group and different compound gel groups were all irradiated with ultraviolet light, and the irradiation conditions are shown in the establishment of the photoaging animal model. Irradiated 5 days a week, and the skin water content was measured on the 6th day (i.e., 6d, 12d, 18d) after the end of the 5-day irradiation every week. The skin MMV value of the test area was measured using a skin moisture content tester, and the average value was taken after testing 3 times in each test area. The change in the skin moisture content MMV value reflects the change law of the moisture content in the experimental area over time during the test period. The larger the value, the greater the moisture content, and vice versa, the smaller the moisture content. The measurement results are shown in Table 6.

[0149] Table 6 Effect of compound gel on skin moisture of UV-irradiated photoaging mice (n = 5)

[0150]

[0151] ### P < 0.001 vs blank control group ## P < 0.01 vs blank control group **P < 0.01 vs model group *P < 0.05 vs model group

[0152] It can be seen from Table 6 that during the test period, the skin moisture MMV value of the test area in the compound gel group was higher than that in the model group, and the anti-aging traditional Chinese medicine compound gel prepared by combining CBSP-CP with anti-aging traditional Chinese medicine extracts had the greatest effect on increasing the water content of photoaging skin and improving the dry symptoms of photoaging skin.

[0153] (4) Effect of compound gel on skin sensitivity of photoaged mice induced by UV irradiation

[0154] The Tissue Viability Imager TiVi 700 (WheelsBridge AB, Sweden) is based on the fact that linearly polarized light after passing through a polarization filter emitted by a white light illuminator reaches the skin surface to be analyzed. Most of the linearly polarized light is blocked by the filter of the detector after being directly reflected by the skin surface. Only part of the irregular polarized light passes through the lower layer of the skin, and the polarized light absorbed by red blood cells passes through the filter and enters the detector. Among the polarized light reaching the detector, the green light component is weakened due to the absorption of red blood cells in blood vessels, the red light component is hardly changed, and the other tissues around red blood cells absorb green light and red light basically the same. In this way, the microcirculation state of blood vessels in the deep layer of the skin can be obtained, and the red blood cell concentration value of each point in the image, that is, the TiVi value, can be obtained. The TiVi 700 system utilizes the characteristic that red blood cells in blood vessels absorb green light to obtain the distribution and aggregation image of red blood cells in skin tissue, and the content of red blood cells represents skin sensitivity.

[0155] In the experiment, the change of skin sensitivity after using the compound gel was tested. Specifically: the blank control group was not irradiated, the model group and different compound gel groups were all irradiated with ultraviolet light, and the irradiation conditions are shown in the establishment of the photoaging animal model. It was irradiated 5 days a week, and the skin sensitivity was measured on the 6th day (i.e., 6d, 12d, 18d) after the end of the 5-day irradiation every week. The measurement results are shown in Table 7.

[0156] Table 7 Effect of compound gel on skin sensitivity of photoaged mice induced by UV irradiation (n = 5)

[0157]

[0158] ### P < 0.001 vs blank control group ## P < 0.01 vs blank control group ***P < 0.001 vs model group **P < 0.01 vs model group *P < 0.05 vs model group

[0159] It can be seen from Table 7 that during the experimental period, the skin sensitivity values in the test areas of the groups using the compound gel were all lower than those of the model group, and the anti-skin aging traditional Chinese medicine compound gel prepared by combining CBSP-CP and anti-aging traditional Chinese medicine extracts had the strongest effect on reducing the sensitivity of photoaged skin and improving the high sensitivity of photoaged skin.

[0160] (5) Effect of compound gel on the content of skin melanin in photoaged mice

[0161] Images were taken using the Tissue Viability Imager TiVi 700 (WheelsBridge AB, Sweden) in (4), and the melanin content was analyzed using the TiVi97 pigment analysis software.

[0162] In the experiment, the changes in the skin melanin content after using the compound gel were tested. Specifically: the blank control group was not irradiated, the model group and different compound gel groups were all irradiated with ultraviolet light, and the irradiation conditions are shown in the establishment of the photoaging animal model. It was irradiated 5 days a week, and the skin melanin content was measured on the 6th day (i.e., 6d, 12d, 18d) after the end of the 5-day irradiation every week. The measurement results are shown in Table 8.

[0163] Table 8 Effects of compound gel on the skin melanin content of photoaging mice induced by UV irradiation (n = 5)

[0164]

[0165]

[0166] ### P < 0.001 vs blank control group ## P < 0.01 vs blank control group **P < 0.01 vs model group *P < 0.05 vs model group

[0167] As can be seen from Table 8, during the experimental period, the melanin content in the test area of the compound gel group was lower than that of the model group, and the anti-skin aging traditional Chinese medicine compound gel prepared by combining CBSP-CP with the anti-aging traditional Chinese medicine extract had the best effect on reducing the melanin content of photoaging skin and improving the pigmentation problem of photoaging skin.

[0168] Experiments have proved that the anti-skin aging traditional Chinese medicine compound gel formed by combining the anti-aging traditional Chinese medicine extract with CBSP-CP can increase the water content of photoaging skin, reduce its sensitivity, reduce pigmentation, and play a clear role in anti-skin aging.

[0169] The above is only the specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention can easily think of changes or substitutions, which should all be covered within the protection scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the claimed rights.

Claims

1. A stable traditional Chinese medicine compound gel, which consists of a gel matrix and a traditional Chinese medicine extract. The gel matrix is composed of cationized bletilla striata polysaccharide and carbomer in a weight ratio of 2:

1. The traditional Chinese medicine extract is prepared from the following raw materials in parts by weight: Rehmannia glutinosa 409 g, Red ginseng 167 g, Ophiopogon japonicus 26 g, Asparagus cochinchinensis 26 g, Lycium chinense Mill. 26 g, Poria cocos 77 g.

2. The traditional Chinese medicine compound gel according to any one of claim 1, further comprising a pH regulator.

3. The traditional Chinese medicine compound gel preparation according to any one of claim 1, further comprising an additive, characterized in that, The additive is selected from one or more of a humectant, a preservative, a transdermal absorption enhancer, an antioxidant, and a fragrance.

4. The stable traditional Chinese medicine compound gel as claimed in any one of claims 1-3, characterized in that The gel is composed of the following components: Traditional Chinese medicine extract equivalent to 6 - 206 g of the total amount of compound Chinese medicinal materials Gel matrix 0.3 - 3 g Glycerol 0.1 - 20 ml 1,2 - propylene glycol 0.3 - 4 g PEG - 40 hydrogenated castor oil 0.1 - 5 g Phenoxyethanol 0.1 - 1.5 g Menthol 0.5 - 2 g Vitamin C ethyl ether 0.5 - 2 g D - panthenol 0.1 - 2 g Triethanolamine 0.01 - 2 g Fragrance 0.01 - 2 g Distilled water appropriate amount.

5. The stable traditional Chinese medicine compound gel as claimed in any one of claims 1 to 3, characterized in that, The weight ratio of each component is: Traditional Chinese medicine extract equivalent to 20 - 144 g of the total amount of compound Chinese medicinal materials Gel matrix 0.5 - 2 g Glycerol 1 - 15 ml 1,2 - propylene glycol 0.5 - 3 g PEG - 40 hydrogenated castor oil 0.2 - 2.5 g Phenoxyethanol 0.2 - 1 g Menthol 0.8 - 1.5 g Vitamin C ethyl ether 0.7 - 1.5 g D - panthenol 0.5 - 1.5 g Triethanolamine 0.05 - 1 g Fragrance 0.05 - 1.5 g Distilled water appropriate amount.

6. The stable traditional Chinese medicine compound gel as claimed in any one of claims 1 to 3, wherein The weight ratio of each component is: Traditional Chinese medicine extract equivalent to 60 - 110 g of the total amount of compound Chinese medicinal materials Gel matrix 0.8 - 1.5 g Glycerol 2 - 11 ml 1,2 - propylene glycol 0.8 - 1.5 g PEG - 40 hydrogenated castor oil 0.4 - 1 g Phenoxyethanol 0.4 - 0.8 g Menthol 0.9 - 1.2 g Vitamin C ethyl ether 0.9 - 1.2 g D - panthenol 0.8 - 1.2 g Triethanolamine 0.1 - 0.6 g Fragrance 0.2 - 1 g Distilled water appropriate amount.

7. The stable traditional Chinese medicine compound gel as claimed in any one of claims 1 to 3, wherein The weight ratio of each component is: Traditional Chinese medicine extract equivalent to 103 g of the total amount of compound Chinese medicinal materials Gel matrix 1 g Glycerol 10 ml 1,2 - propylene glycol 1 g PEG - 40 hydrogenated castor oil 0.5 g Phenoxyethanol 0.5 g Menthol 1 g Vitamin C ethyl ether 1 g D - panthenol 1 g Triethanolamine 0.5 g Fragrance 0.5 g Distilled water appropriate amount.

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