Application of active ingredient composition of brutal dragon liquid in preparation of freckle-removing product

Abstract

The invention discloses an application of a brutal dragon liquid active ingredient composition in preparation of a freckle-removing product, the weight ratio of epimedium polysaccharide to rehmannia and hyperoside in brutal dragon liquid active ingredients is 1: (2-4): (3-5), the invention discloses a preparation method of the brutal dragon liquid active ingredient composition, and the brutal dragon liquid active ingredient composition has a good freckle-removing effect.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical preparations, and more specifically, relates to the application of the effective ingredient composition of Manlong Liquid in the preparation of freckle-removing products. Background Art

[0002] Manlong Liquid is composed of male silkworm moths, acanthopanax senticosus, epimedium brevicornu, dodder seeds (processed with wine), prepared rehmannia root (processed with salt), psoralea corylifolia (processed with salt). It has the effects of tonifying the kidney and strengthening yang, replenishing essence and marrow. It is used for kidney deficiency and essence depletion, impotence and premature ejaculation, spermatorrhea, soreness of the waist and knees, and frequent urination.

[0003] Male silkworm moth is the whole body of the male of the domestic silkworm moth of the Bombycidae family. In summer, male silkworm moths are taken, scalded to death with boiling water, and dried in the sun. It tonifies the liver and kidney, strengthens yang and astringes sperm. It is used to treat impotence, spermatorrhea, leukorrhagia, hematuria, trauma, ulcers and burns. Male silkworm moths contain various amino acids, vitamins and trace elements. In particular, male silkworm moths contain a large amount of bioactive substances such as male hormones, juvenile hormones, brain hormones and molting hormones, and it is a "medicinal and edible homologous" good product that combines blood sugar lowering, elimination of complications, health preservation, health care and strengthening yang.

[0004] The main components of acanthopanax senticosus are glycosides, polysaccharides, etc. Among them, glycosides are its characteristic components and effective components. 1. Glycosides such as hyperoside, acanthoside A, B, B1, C, D, E, F, G, etc. 2. Polysaccharides The content of basic polysaccharides is generally 2% - 6%, and the content of water-soluble polysaccharides is 2.3% - 5.7%. 3. Other components such as isofraxidin, chlorogenic acid, sesamin, stearic acid, β-sitosterol, etc.

[0005] Epimedium brevicornu contains epimedoside, volatile oil, wax alcohol, phytosterol, tannin, vitamin E and other components. It can excite sexual function and has the effect of promoting semen secretion in animals. It also has the effects of lowering blood pressure (causing peripheral vasodilation), lowering blood sugar, diuresis, relieving cough and expelling phlegm, and the effect similar to vitamin E. Pharmacological experimental studies have shown that epimedium brevicornu can increase the blood flow of the heart and cerebrovascular, promote hematopoietic function, immune function and bone metabolism, and has the effects of anti-aging, anti-tumor, etc.

[0006] Dodder seeds contain alkaloids, anthraquinones, coumarins, flavonoids, glycosides, sterols, tannic acid, sugars, etc. Flavonoids include: quercetin, astragalin, hyperoside; Sterols include: cholesterol, campesterol, β-sitosterol, stigmasterol, β-amyrin.

[0007] The main components of prepared rehmannia root are various iridoids, monoterpenes and their glycosides, various sugar components, more than 20 kinds of amino acids (among which the contents of arginine and alanine are relatively high), various organic acids, and contain more than 20 elements such as iron, zinc, manganese, chromium, including psoralen, etc.

[0008] Psoralea contains coumarin components such as psoralen, isopsoralen, xanthotoxin, psoralidin, isopsoralidin, psoralen furanocoumarin, etc.; it also contains flavonoids, benzofuranoids, fatty acids and other components; secondly, it also contains psoralea polysaccharide, amino acids, etc.

[0009] Clinically, it has been found that Manlong Liquid has various therapeutic effects including freckle removal, but the mechanism is unclear. Summary of the Invention

[0010] The present invention provides the application of the composition of the active ingredients of Manlong Liquid in the preparation of freckle-removing products. The composition of the active ingredients of Manlong Liquid is composed of epimedium polysaccharide, rehmannioside and hyperoside.

[0011] When enterprise scientific and technical personnel were studying the active ingredients of Manlong Liquid, through a large number of experimental studies, it was unexpectedly found that epimedium polysaccharide, rehmannioside and hyperoside have a synergistic effect in freckle removal.

[0012] The application of the composition of the active ingredients of Manlong Liquid in the preparation of freckle-removing products. The composition of the active ingredients of Manlong Liquid is composed of epimedium polysaccharide, rehmannioside and hyperoside.

[0013] The application of the composition of the active ingredients of Manlong Liquid in the preparation of freckle-removing products. In the composition of the active ingredients of Manlong Liquid, the weight ratio of epimedium polysaccharide, rehmannioside and hyperoside is 1:2 - 4:3 - 5.

[0014] The application of the composition of the active ingredients of Manlong Liquid in the preparation of freckle-removing products. In the composition of the active ingredients of Manlong Liquid, the weight ratio of epimedium polysaccharide, rehmannioside and hyperoside is 1:3:4.

[0015] The application of the composition of the active ingredients of Manlong Liquid in the preparation of freckle-removing products. The freckle-removing product is a granule, which is composed of epimedium polysaccharide, rehmannioside, hyperoside and excipients.

[0016] The application of the composition of the active ingredients of Manlong Liquid in the preparation of freckle-removing products. The excipients are polyethylene glycol 400, calcium chloride, and siliconized microcrystalline cellulose, and the weight ratio is 1:2:1.

[0017] The application of the composition of the active ingredients of Manlong Liquid in the preparation of freckle-removing products. The preparation method of the freckle-removing product is: take epimedium polysaccharide, rehmannioside, hyperoside and excipients, and use an ethanol aqueous solution as a binder to make granules.

[0018] The application of the composition of the active ingredients of Manlong Liquid in the preparation of products for inhibiting tyrosinase activity.

[0019] The application of the composition of the active ingredients of Manlong Liquid in the preparation of products for inhibiting tyrosinase activity. The preparation method of the product for inhibiting tyrosinase activity is: take epimedium polysaccharide, rehmannioside, hyperoside and excipients, and use an ethanol aqueous solution as a binder to make granules.

[0020] The structure of epimedium polysaccharide is composed of polysaccharides such as glucose, galactose and mannose, with glucose being the main component. It is easily soluble in water, ethanol and ethyl acetate, and insoluble in organic solvents such as ether, benzene and chloroform. Rehmannioside belongs to iridoid compounds, is easily soluble in water or ethanol, is yellowish to brownish in color, and some derivatives have a special bitter taste. Hyperoside is chemically named quercetin-3-O-galactoside, and its molecular formula is C 21 H 20 O 12 , and is easily soluble in water or ethanol. It can be seen that the water solubility of the three is very good, but if prepared into granules, they are prone to moisture absorption. Through a large number of experimental studies, the present invention unexpectedly finds that using polyethylene glycol 400, calcium chloride, and silicified microcrystalline cellulose as excipients can well solve the problem of moisture absorption.

[0021] Compared with the prior art, the beneficial effects of the present invention are:

[0022] The freckle-removing product of the present invention is compounded with epimedium polysaccharide, rehmannioside and hyperoside, and has excellent whitening and freckle-removing effects; through synergistic effects, the whitening and freckle-removing composition maintains excellent whitening and freckle-removing effects, and uses polyethylene glycol 400, calcium chloride, and silicified microcrystalline cellulose as excipients. Due to the good hygroscopicity and moisture retention of polyethylene glycol 400, it can combine with water molecules through hydrogen bonds to form a stable hydrated film, thereby reducing the sensitivity of the traditional Chinese medicine extract to environmental humidity and avoiding the loss or caking of components caused by water evaporation. Calcium chloride forms a gel by chemically combining with water molecules during the moisture absorption process, completely locking the water and not evaporating. Silicified microcrystalline cellulose is formed by combining microcrystalline cellulose (MCC) and colloidal silica (silicon dioxide) through spray drying technology, and colloidal silica is evenly distributed on the surface and inside of MCC. This structure enhances the hydrophobicity and porosity of the material, forms a physical barrier to reduce water adsorption, and the porous structure can absorb the free water in the extract and fix it through hydrogen bonds to prevent water aggregation from causing adhesion. The combination of the three can well solve the problem of moisture absorption of epimedium polysaccharide, rehmannioside and hyperoside. Specific embodiments

[0023] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. In addition, it should be understood that after reading the content recorded in the present invention, those skilled in the art can make various changes or modifications to the present invention, but these equivalent forms also fall within the scope defined by the appended claims of this application.

[0024] Example 1:

[0025] Weigh 100 g of epimedium polysaccharide, 300 g of rehmannioside and 400 g of hyperoside according to the weight ratio, add 10 g of polyethylene glycol 400, 20 g of calcium chloride and 10 g of silicified microcrystalline cellulose, granulate with 50% ethanol solution, and prepare into granules.

[0026] Example 2:

[0027] Weigh 100 g of epimedium polysaccharide, 200 g of rehmannioside and 300 g of hyperoside according to the weight ratio, add 10 g of polyethylene glycol 400, 20 g of calcium chloride and 10 g of silicified microcrystalline cellulose, granulate with 50% ethanol solution, and prepare into granules.

[0028] Example 3:

[0029] Weigh 100 g of epimedium polysaccharide, 400 g of rehmannioside and 500 g of hyperoside according to the weight ratio, add 10 g of polyethylene glycol 400, 20 g of calcium chloride and 10 g of silicified microcrystalline cellulose, granulate with 50% ethanol solution, and prepare into granules.

[0030] Comparative Example 1:

[0031] Weigh 100 g of epimedium polysaccharide by weight, add 10 g of polyethylene glycol 400, 20 g of calcium chloride and 10 g of silicified microcrystalline cellulose, granulate with 50% ethanol solution, and prepare into granules.

[0032] Comparative Example 2:

[0033] Weigh 300 g of rehmannioside by weight, add 10 g of polyethylene glycol 400, 20 g of calcium chloride and 10 g of silicified microcrystalline cellulose, granulate with 50% ethanol solution, and prepare into granules.

[0034] Comparative Example 3:

[0035] Weigh 300 g of hyperoside by weight, add 10 g of polyethylene glycol 400, 20 g of calcium chloride and 10 g of silicified microcrystalline cellulose, granulate with 50% ethanol solution, and prepare into granules.

[0036] Comparative Example 4:

[0037] Weigh 100 g of epimedium polysaccharide and 300 g of rehmannioside according to the weight ratio, add 10 g of polyethylene glycol 400, 20 g of calcium chloride and 10 g of silicified microcrystalline cellulose, granulate with 50% ethanol solution, and prepare into granules.

[0038] Comparative Example 5:

[0039] Weigh 300 g of rehmannioside and 400 g of hyperoside according to the weight ratio, add 10 g of polyethylene glycol 400, 20 g of calcium chloride and 10 g of silicified microcrystalline cellulose, granulate with 50% ethanol solution, and prepare into granules.

[0040] Comparative Example 6:

[0041] Weigh 100 g of epimedium polysaccharide and 400 g of hyperoside according to the weight ratio, add 10 g of polyethylene glycol 400, 20 g of calcium chloride, and 10 g of silicified microcrystalline cellulose, and granulate with 50% ethanol solution to prepare a granule.

[0042] Comparative Example 7:

[0043] Weigh 100 g of epimedium polysaccharide, 300 g of rehmannioside, and 400 g of hyperoside according to the weight ratio, add 10 g of polyethylene glycol 400, and granulate with 50% ethanol solution to prepare a granule.

[0044] Comparative Example 8:

[0045] Weigh 100 g of epimedium polysaccharide, 300 g of rehmannioside, and 400 g of hyperoside according to the weight ratio, add 20 g of calcium chloride, and granulate with 50% ethanol solution to prepare a granule.

[0046] Comparative Example 9:

[0047] Weigh 100 g of epimedium polysaccharide, 300 g of rehmannioside, and 400 g of hyperoside according to the weight ratio, add 10 g of silicified microcrystalline cellulose, and granulate with 50% ethanol solution to prepare a granule.

[0048] Comparative Example 10:

[0049] Weigh 100 g of epimedium polysaccharide, 300 g of rehmannioside, and 400 g of hyperoside according to the weight ratio, add 10 g of polyethylene glycol 400 and 20 g of calcium chloride, and granulate with 50% ethanol solution to prepare a granule.

[0050] Comparative Example 11:

[0051] Weigh 100 g of epimedium polysaccharide, 300 g of rehmannioside, and 400 g of hyperoside according to the weight ratio, add 20 g of calcium chloride and 10 g of silicified microcrystalline cellulose, and granulate with 50% ethanol solution to prepare a granule.

[0052] Comparative Example 12:

[0053] Weigh 100 g of epimedium polysaccharide, 300 g of rehmannioside, and 400 g of hyperoside according to the weight ratio, add 10 g of polyethylene glycol 400 and 10 g of silicified microcrystalline cellulose, and granulate with 50% ethanol solution to prepare a granule.

[0054] Example 4: Stability Experiment

[0055] Place at 40 ± 2 °C and RH 75% ± 5% for 6 months. Take samples monthly for the accelerated experiment. Determine the water content according to the requirements of the water determination method in the Chinese Pharmacopoeia (2020 Edition), and observe its properties. The results are shown in Table 1.

[0056] Table 1 Accelerated Stability Experiment Study of the Invention

[0057]

[0058]

[0059] The results show that after placing Examples 1 - 3 under accelerated conditions for 6 months, the water content of the granules is still lower than 5%, and there is no caking. In contrast, for Comparative Examples 7 - 12, using single excipients or combinations of two, the water content increases and caking occurs after 6 months of placement. This shows that using polyethylene glycol 400, calcium chloride, and silicified microcrystalline cellulose as excipients in specific combinations and ratios can effectively prevent the moisture absorption problems of icariin, rehmannioside, and hyperoside.

[0060] Example 5: Determination of Tyrosinase Activity

[0061] Tyrosinase is the key enzyme in melanin synthesis and participates in multiple processes of melanin synthesis, including catalyzing the formation of dopa from monophenol and oxidizing dopa to form dopaquinone, etc. By measuring the absorbance of the enzyme-catalyzed product at a wavelength of 475 nm, it can be determined whether the activity of tyrosinase is inhibited.

[0062] Tyrosinase solution: Take tyrosinase and prepare a 100 U / mL tyrosinase solution with PBS (pH = 6.8) buffer solution. L-Dopa solution: Take L-Dopa and prepare a tyrosine solution with a concentration of 1 mg / mL with PBS (pH = 6.8) buffer solution.

[0063] Preparation of the sample solution to be measured: Take the samples of Examples 1 - 3 and Comparative Examples 1 - 6, add distilled water, and prepare a 1 mg / mL sample solution for standby.

[0064] Determination of tyrosinase activity: Take 0.47 mL of tyrosine solution, 0.5 mL of the sample solution to be tested, and 0.28 mL of PBS (pH = 6.8) buffer solution. After preheating at 37 °C for 10 min, add 0.25 mL of tyrosinase solution and mix well. Incubate in a constant temperature water bath at 37 °C for 10 min. Measure the absorbance value at a wavelength of 475 nm. Use PBS buffer solution instead of the sample to be tested as the blank group, and use vitamin C (0.5 mg / mL) as the positive control. The experiment was repeated three times, and the average value was taken. The data was expressed as the average value ± standard deviation. (Absorbance value of the sample group / Absorbance value of the blank group) × 100% represents the tyrosinase activity. Tyrosinase inhibition rate = [1 - (Average value of the test sample group - Average value of the blank control group) / (Average value of the negative control group - Average value of the blank control group)] × 100%. The results are shown in Table 2.

[0065] Table 2 Effects of the present invention on tyrosinase activity

[0066] Group Tyrosinase activity / % Positive drug group 68.5±6.8 Example 1 73.7±6.7 Example 2 68.9±2.3 Example 3 70.6±5.4 Comparative Example 1 32.9±4.7 Comparative Example 2 35.1±5.2 Comparative Example 3 34.5±4.9 Comparative Example 4 46.9±5.1 Comparative Example 5 37.1±4.0 Comparative Example 6 36.2±3.4

[0067] The results showed that the sample groups of Examples 1 - 3 all exhibited a certain effect of inhibiting tyrosinase activity. Among them, Example 1 had the best effect, comparable to the positive drug group. Compared with Comparative Examples 1 - 6, the inhibitory effect of Examples 1 - 3 was significantly increased, indicating that epimedium polysaccharide, rehmannioside, and hyperoside have a synergistic effect on the inhibition of tyrosinase.

[0068] Example 6: Test of whitening and freckle removal effect

[0069] Recruit 100 female volunteers aged 35 - 45 with darker facial skin color and having skin spots. Randomly divide them into two groups. When grouping, consider as much as possible the area and depth of facial chloasma, etc., as well as the outdoor activity conditions, age, gender, childbirth, etc. of each volunteer affecting the results, and conduct a balance test to ensure that there is no significant difference between the groups (P > 0.05). They are the Example 1 group of the present invention and the control group respectively. The Example 1 group of the present invention orally takes the granules prepared in Example 1 of the present invention, 500 mg per day, taken in two doses, and continuously used for 2 months; the control group orally takes Jiangzhong grape seed capsules (approval number: SC10644160200052), twice a day, one capsule each time, twice a day, and continuously used for 2 months. During the use of the two groups, the original eating habits are not changed.

[0070] Diagnostic criteria: Conduct a human feeding test on the product of the present invention in accordance with the "Specifications for Inspection and Evaluation of Health Foods". The subjects meet the following criteria: 1) Light brown to dark brown spots on the face, well-defined patches, without inflammatory manifestations; 2) The condition has a certain seasonality, being more severe in summer and milder in winter; 3) Pigmentation caused by no obvious other diseases except endocrine.

[0071] Effect evaluation method: Basically cured: The area of skin pigmentation has regressed by more than 90%, the color has basically disappeared, and the skin is clean, white and bright; Markedly effective: The area of skin pigmentation has regressed by more than 70%, the color has become significantly lighter, and the skin is fairer than before; Improved: The area of skin pigmentation has regressed by more than 30%, the color has become lighter, and the skin color has no obvious change. Ineffective: The area of skin pigmentation has regressed by less than 30%, and the color and skin color have no obvious change.

[0072] The test results are shown in Table 3 below:

[0073] Table 3 Clinical research

[0074] Group Basically cured Markedly effective Improved Ineffective Effective rate (%) Group of the present invention 16 18 12 4 92 Control group 8 17 13 12 76

[0075] As can be seen from Table 3, the freckle-removing composition of Example 1 has a significant effect compared with the control group, indicating that the formulation of the present invention is reasonable. Through the synergistic effect, the whitening and freckle-removing composition of the present invention maintains excellent whitening and freckle-removing effects.

[0076] Although the embodiments of the present invention have been shown and described, it will be understood by those of ordinary skill in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. The application of the Manlong liquid active ingredient composition in the preparation of freckle removal products, characterized in that: The effective ingredient composition of Manlong Liquid consists of epimedium polysaccharide, rehmannia glutinosa and hyperoside.

2. The use of the Manlong Liquid active ingredient composition as claimed in claim 1 in the preparation of a freckle removal product, characterized in that: The weight ratio of epimedium polysaccharide, rehmannia glutinosa and hyperoside in the effective ingredient composition of Manlong Liquid is 1:2-4:3-5.

3. The use of the Manlong Liquid active ingredient composition as claimed in claim 1 in the preparation of a freckle removal product, characterized in that: The weight ratio of epimedium polysaccharide, rehmannia glutinosa and hyperoside in the effective ingredient composition of Manlong Liquid is 1:3:

4.

4. The use of the Manlong Liquid active ingredient composition as claimed in claim 1 in the preparation of a freckle removal product, characterized in that: The freckle removal product is a granule composed of epimedium polysaccharide, rehmannia glutinosa, hyperoside and auxiliary materials.

5. The use of the Manlong Liquid active ingredient composition as claimed in claim 4 in the preparation of a freckle removal product, characterized in that: The excipients are polyethylene glycol 400, calcium chloride, and silicified microcrystalline cellulose in a weight ratio of 1:2:

1.

6. The use of the Manlong Liquid active ingredient composition as claimed in claim 4 in the preparation of a freckle removal product, characterized in that: The preparation method of the freckle removal product is as follows: epimedium polysaccharide, rehmannia glutinosa, hyperoside and auxiliary materials are taken, and granulated using ethanol aqueous solution as a binder.

7. Use of the Manlongye active ingredient composition as claimed in claim 1 in the preparation of a product for inhibiting tyrosinase activity.

8. The use of the Manlongye active ingredient composition as claimed in claim 7 in the preparation of a product for inhibiting tyrosinase activity, characterized in that: The preparation method of the product for inhibiting tyrosinase activity is as follows: epimedium polysaccharide, rehmannia glutinosa, hyperoside and auxiliary materials are taken, and granulated using ethanol aqueous solution as a binder.

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