A traditional Chinese medicine gel and its preparation method and application

Abstract

The present invention relates to the technical field of Chinese medicine preparations, and in particular to a Chinese medicine gel and a preparation method and application thereof. The Chinese medicine water extract obtained by using lithospermum officinale, peony bark, sophora flavescens, oldenlandia diffusa and honeysuckle as preparation raw materials has the effects of clearing away heat and detoxifying, cooling blood and clearing rashes, and anti-inflammatory and antipruritic, and can be used to treat skin itching and the like; by compounding appropriate amounts of carbomer 940, propylene glycol, triethanolamine and preservatives, the obtained Chinese medicine gel has a uniform and fine texture, moderate viscosity, moderate fluidity, is easy to spread and apply evenly, has good anti-inflammatory and antipruritic activities, is non-toxic and non-skin irritating, and has a long drug action time.

Description

Technical Field

[0001] The present invention relates to the technical field of Chinese medicine preparations, and in particular to a Chinese medicine gel and a preparation method and application thereof. Background Art

[0002] Skin diseases are the most common, the most morbid, and the most contagious diseases in human history in the 21st century. There are many causes of skin diseases, such as infection factors, the patient's own physical condition and eating habits, dust, mosquito bites, etc. [Jing Wenxi. Analysis of the causes and preventive measures of skin diseases in spring [J]. Chinese Rural Health, 2021, 13(10): 12+14.], which not only affect the patient's physical and mental health, but also endanger their lives, and even cause social panic and discrimination. Symptoms such as itching, pain, numbness, and changes in appearance are often associated with skin diseases. The pathogenesis of skin diseases is unclear and they are prone to recurrence. In clinical practice, they are often treated with analgesics, antihistamines, or hormone drugs, but these drugs have great side effects, are difficult to cure, cannot be used for a long time, are prone to dependence, and are limited to pregnant women, the elderly, and people in special occupations. Commonly used drugs such as dermatitis cream and hydrocortisone butyrate cream can be used to treat itching, neurodermatitis, chronic eczema, etc., but long-term use can cause skin atrophy, capillary dilation, pigmentation, and secondary infection [Xiao Wei. Skin often suffers in summer, so be cautious when purchasing drugs yourself [J]. Adolescent Health, 2019(16):52-53.].

[0003] Traditional Chinese medicine has a long history, definite therapeutic effects, fewer adverse reactions, low recurrence rate, and high acceptance. It has great advantages in the treatment of skin diseases. However, traditional topical preparations such as ointments and powders have problems such as poor spreadability, uneven coating, short drug action time, and easy to cause redness and swelling. Summary of the invention

[0004] In order to solve the above problems, the present invention provides a Chinese medicine gel and a preparation method and application thereof. The Chinese medicine gel provided by the present invention has a uniform and fine texture, is easy to spread, has good anti-inflammatory and antipruritic activity, is non-toxic and has no skin irritation, and has a long drug action time.

[0005] In order to achieve the above object, the present invention provides the following technical solutions:

[0006] The invention provides a traditional Chinese medicine gel. The traditional Chinese medicine gel comprises the following components in concentrations: 3.75wt.%-5wt.% of traditional Chinese medicine water extract, 9405wt.%-7.5wt.% of carbomer, 18.75wt.%-31.25wt.% of propylene glycol, 1.25-2.5mL / kg of triethanolamine, 0.125wt.% of a preservative and the remainder of water; the raw materials for preparing the traditional Chinese medicine water extract comprise: lithospermum officinale, moutan bark, sophora flavescens, oldenlandia diffusa and honeysuckle.

[0007] Preferably, the mass ratio of Lithospermum officinale, Paeonia suffruticosa, Sophora flavescens, Oldenlandia diffusa and Honeysuckle is 1:1:1:1:1:1.

[0008] Preferably, the pH value of the traditional Chinese medicine gel is 6.5-7.5.

[0009] Preferably, the preservative comprises ethylparaben and / or ethylparaben.

[0010] The present invention also provides a method for preparing the traditional Chinese medicine gel described in the above technical solution, comprising the following steps:

[0011] Mixing lithospermum officinale, peony bark, sophora flavescens, oldenlandia diffusa and honeysuckle, boiling in water and filtering to obtain a filtrate;

[0012] Drying the filtrate to obtain the Chinese medicine water extract;

[0013] Mixing the Carbomer 940 with a portion of water to obtain a swollen Carbomer 940 matrix;

[0014] Dissolving the Chinese medicine water extract and mixing it with the swollen Carbomer 940 matrix to obtain a drug-containing matrix;

[0015] The drug-containing matrix is ​​mixed with propylene glycol, a preservative, triethanolamine and remaining water to obtain the traditional Chinese medicine gel.

[0016] Preferably, the decoction is performed 1 to 3 times, and the decoction time for each time is 50 to 70 minutes.

[0017] Preferably, the drying temperature is ≤65°C.

[0018] Preferably, the mass ratio of Carbomer 940 to part of water in the swollen Carbomer 940 matrix is ​​1:5-10.

[0019] Preferably, the drug-containing matrix, propylene glycol, preservative, triethanolamine and remaining water are mixed in the following manner: dissolving the preservative in the propylene glycol to obtain an excipient solution; and mixing the drug-containing matrix, the excipient solution, triethanolamine and remaining water.

[0020] The present invention also provides the use of the traditional Chinese medicine gel described in the above technical solution or the traditional Chinese medicine gel prepared by the preparation method described in the above technical solution in the preparation of anti-inflammatory and / or antipruritic products.

[0021] Beneficial effects:

[0022] The invention provides a traditional Chinese medicine gel. The traditional Chinese medicine gel comprises the following components in concentrations: 3.75wt.%-5wt.% of traditional Chinese medicine water extract, 9405wt.%-7.5wt.% of carbomer, 18.75wt.%-31.25wt.% of propylene glycol, 1.25-2.5mL / kg of triethanolamine, 0.125wt.% of a preservative and the remainder of water; the raw materials for preparing the traditional Chinese medicine water extract comprise: lithospermum officinale, moutan bark, sophora flavescens, oldenlandia diffusa and honeysuckle. The Chinese medicine water extract prepared by taking lithospermum officinale, peony bark, sophora flavescens, oldenlandia diffusa and honeysuckle as preparation raw materials has the effects of clearing away heat and detoxifying, cooling blood and clearing away rash, and anti-inflammatory and antipruritic, and can be used to treat skin itching and the like; by compounding appropriate amounts of carbomer 940, propylene glycol, triethanolamine and preservatives, the obtained Chinese medicine gel has uniform and fine texture, moderate viscosity and fluidity, is easy to spread and apply evenly, has good anti-inflammatory and antipruritic activities, is non-toxic and has no skin irritation, and has a long drug action time. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required to be used in the embodiments are briefly introduced below.

[0024] Figure 1 This is a finished product picture of the traditional Chinese medicine gel prepared in Example 1;

[0025] Figure 2 The results of the effects of different doses of Chinese medicine gel on the swelling of the mouse ear.

[0026] Figure 3 The results of the effects of different doses of Chinese medicine gel on the itch threshold of guinea pigs;

[0027] Figure 4 This is a picture showing the effect of applying Chinese medicine gel on normal skin and damaged skin;

[0028] Figure 5 The results of single-dose skin irritation test on normal skin and damaged skin;

[0029] Figure 6 Results of skin irritation tests on normal skin and damaged skin after multiple administration;

[0030] Figure 7 The results of the effects of Chinese medicine gels prepared with different formulas on the swelling of the mouse ear;

[0031] Figure 8 The results of the effects of Chinese herbal gels prepared with different formulas on the itch threshold of guinea pigs;

[0032] Compared with the model control group, ** means p < 0.01, * means p < 0.05; compared with the gel matrix control group, ## p<0.01,# p<0.05;. DETAILED DESCRIPTION

[0033] The invention provides a traditional Chinese medicine gel. The traditional Chinese medicine gel comprises the following components in concentrations: 3.75wt.%-5wt.% of traditional Chinese medicine water extract, 9405wt.%-7.5wt.% of carbomer, 18.75wt.%-31.25wt.% of propylene glycol, 1.25-2.5mL / kg of triethanolamine, 0.125wt.% of a preservative and the remainder of water; the raw materials for preparing the traditional Chinese medicine water extract comprise: lithospermum officinale, moutan bark, sophora flavescens, oldenlandia diffusa and honeysuckle.

[0034] Unless otherwise specified, the present invention has no special requirements on the sources of the components or raw materials of the traditional Chinese medicine gel, and commercially available products known to those skilled in the art may be used.

[0035] The Chinese medicine gel of the present invention comprises 3.75wt.% to 5wt.%, preferably 4.375wt.% of Chinese medicine water extract; the raw materials for preparing the Chinese medicine water extract preferably comprise: lithospermum officinale, peony bark, sophora flavescens, white flower oldenlandia diffusa and honeysuckle; the mass ratio of lithospermum officinale, peony bark, sophora flavescens, white flower oldenlandia diffusa and honeysuckle is preferably 1:1:1:1:1. The raw materials for preparing the Chinese medicine water extract of the present invention are compounded with lithospermum officinale, peony bark, sophora flavescens, white flower oldenlandia diffusa and honeysuckle, and have the effects of clearing away heat and detoxifying, cooling blood and clearing rash, and anti-inflammatory and antipruritic, and can be used to treat skin itching and the like.

[0036] The preparation method of the Chinese medicine water extract of the present invention preferably comprises the following steps: mixing lithospermum officinale, peony bark, sophora flavescens, oldenlandia diffusa and honeysuckle, decocting in water and filtering to obtain a filtrate; and drying the filtrate to obtain the Chinese medicine water extract.

[0037] In the present invention, the number of water decoctions is preferably 1 to 3 times, more preferably 2 times; when the number of water decoctions is 2 or 3 times, the filtrate is preferably the sum of the filtrates filtered after 2 or 3 decoctions; the time for each water decoction is preferably 50 to 70 minutes, more preferably 1 hour; the material-liquid ratio for each water decoction is preferably 1 g:10 to 15 mL, more preferably 1 g:10 mL.

[0038] In the present invention, the filtrate is preferably concentrated before drying; the concentration is preferably concentrated to a paste, that is, the relative density at 65° C. is 1.1 to 1.3; the drying temperature is preferably ≤ 65° C., more preferably 65° C. The present invention has no special requirements for the concentration method, and a method well known to those skilled in the art can be used.

[0039] The Chinese medicine gel of the present invention comprises 5wt.% to 7.5wt.%, preferably 6.25wt.%. The Carbomer 940 of the present invention as the matrix material of the Chinese medicine gel can increase the retention time of the drug in the affected area, improve the bioavailability, and solve the solubility and dispersibility problems of the drug in the gel. The Carbomer 940 described in the embodiment of the present invention is preferably purchased from Henan Wanbang Chemical Technology Co., Ltd., batch number 20171206.

[0040] The Chinese medicine gel of the present invention comprises propylene glycol 18.75wt.% to 31.25wt.%, preferably 25wt.%. The propylene glycol of the present invention is a humectant, which can dissolve and disperse other auxiliary materials such as preservatives, and is convenient for mixing and dispersing with the drug-containing matrix. The purity of the propylene glycol in the embodiment of the present invention is preferably analytically pure, and is preferably purchased from Shanghai Zhanyun Chemical Technology Co., Ltd., batch number 20220112.

[0041] The Chinese medicine gel of the present invention includes triethanolamine 1.25-2.5mL / kg, preferably 1.875mL / kg. The triethanolamine of the present invention can keep the Chinese medicine gel at a suitable pH value to avoid irritation to the skin. The purity of the triethanolamine described in the embodiment of the present invention is preferably analytically pure, preferably purchased from Shanghai Zhanyun Chemical Technology Co., Ltd., batch number 220112. The triethanolamine of the present invention has the effects of thickening, moisturizing, humidifying, thickening, and pH balance. It is a neutralizer for acidic polymer gels containing carbomer, etc., and forms a stable polymer structure by neutralizing with carboxyl groups such as carbomer, thereby achieving the application effects of thickening and moisturizing.

[0042] The Chinese medicine gel of the present invention includes 0.125wt.% of preservative. In the present invention, the preservative preferably includes ethyl hydroxybenzoate and / or ethyl paraben, more preferably ethyl hydroxybenzoate. The purity of ethyl hydroxybenzoate in the embodiment of the present invention is preferably analytically pure, preferably purchased from Tianjin Bodi Chemical Co., Ltd., batch number 100106.

[0043] The solvent of the traditional Chinese medicine gel of the present invention is preferably water.

[0044] The pH value of the traditional Chinese medicine gel of the present invention is preferably 6.5-7.5, more preferably 7.0.

[0045] The traditional Chinese medicine gel of the invention is not only beautiful and uniform, easy to clean and stable, but also has anti-inflammatory and antipruritic effects and has no skin irritation effect.

[0046] The present invention also provides a method for preparing the traditional Chinese medicine gel described in the above technical solution, comprising the following steps:

[0047] Mixing the Carbomer 940 with a portion of water to obtain a swollen Carbomer 940 matrix;

[0048] Dissolving the Chinese medicine water extract and mixing it with the swollen Carbomer 940 matrix to obtain a drug-containing matrix;

[0049] The drug-containing matrix is ​​mixed with propylene glycol, a preservative, triethanolamine and remaining water to obtain the traditional Chinese medicine gel.

[0050] The present invention mixes the carbomer 940 with part of water to obtain a swollen carbomer 940 matrix. In the present invention, the mass ratio of carbomer 940 to part of water in the swollen carbomer 940 matrix is ​​preferably 1:5-10, more preferably 1:10; after the carbomer 940 and part of water are mixed, it is preferably further included to stand overnight and / or heat at 60°C. The present invention allows carbomer 940 to fully absorb water and swell by standing overnight and / or heating at 60°C. The present invention first performs a swelling treatment on carbomer 940 to avoid the agglomeration phenomenon of direct mixing, thereby facilitating the dispersion of materials.

[0051] After obtaining the swollen Carbomer 940 matrix, the present invention dissolves the traditional Chinese medicine water extract and mixes it with the swollen Carbomer 940 matrix to obtain a drug-containing matrix.

[0052] In the present invention, the propylene glycol is preferably used to dissolve the preservative to obtain an auxiliary material solution. In the present invention, the preservative and other auxiliary materials can be fully dissolved in the propylene glycol by using propylene glycol.

[0053] After obtaining the drug-containing matrix and the auxiliary material solution, the present invention preferably mixes the drug-containing matrix, the auxiliary material solution, triethanolamine and the remaining water to obtain the traditional Chinese medicine gel.

[0054] The present invention also provides the use of the Chinese medicine gel described in the above technical solution or the Chinese medicine gel prepared by the preparation method described in the above technical solution in the preparation of anti-inflammatory and / or antipruritic products. The Chinese medicine gel described in the present invention has good anti-inflammatory and antipruritic activity, is non-toxic and non-skin irritating, has a long drug action time, and can be used to prepare anti-inflammatory and / or antipruritic products.

[0055] In order to further illustrate the present invention, a Chinese medicine gel provided by the present invention and its preparation method and application are described in detail below in conjunction with the accompanying drawings and examples, but they should not be construed as limiting the scope of protection of the present invention.

[0056] Example 1

[0057] A Chinese medicine water extract is prepared by the following steps: taking 50 g each of lithospermum officinale, moutan bark, sophora flavescens, oldenlandia diffusa and honeysuckle crude powder, adding water and decocting twice, adding 500 ml of water each time, each time for 60 minutes, combining the filtrates after the two decoctions, concentrating to a thick paste, and drying at 65°C to obtain the Chinese medicine water extract; the lithospermum officinale, moutan bark, sophora flavescens, oldenlandia diffusa and honeysuckle are all purchased from Beijing Huaishuntang Pharmaceutical Co., Ltd. with batch number 20220115.

[0058] Example 2

[0059] A Chinese medicine gel with anti-inflammatory and / or antipruritic effects, comprising the following components in the following concentrations: 4.375 wt.% of the Chinese medicine water extract prepared in Example 1, 9406.25 wt.% of carbomer, 2.5 wt.% of propylene glycol, 1.875 mL / kg of triethanolamine, 0.125 wt.% of ethylparaben, and the remainder of water;

[0060] The Chinese medicine gel is prepared by the following steps:

[0061] 0.5 g of Carbomer 940 was added with 5 mL of water (i.e., the mass ratio of Carbomer 940 to water was 1:10) and soaked overnight to obtain a swollen Carbomer 940 matrix;

[0062] Dissolving 0.35 g of the Chinese medicine water extract and mixing with the swollen Carbomer 940 matrix, stirring evenly to obtain a drug-containing matrix;

[0063] 0.01 g of ethyl hydroxybenzoate was dissolved in 2 g of propylene glycol, and mixed evenly with the drug-containing matrix, and then 15 μL of triethanolamine was added, stirred evenly, and finally water was added to make up to 8 g to obtain the traditional Chinese medicine gel.

[0064] Example 3

[0065] A Chinese medicine gel with anti-inflammatory and / or antipruritic effects is composed of the following components in concentrations: 3.75wt.% of the Chinese medicine water extract prepared in Example 1, 9407.5wt.% of carbomer, 18.75wt.% of propylene glycol, 1.875mL / kg of triethanolamine, 0.125wt.% of ethylparaben and the remainder of water; the preparation method of the Chinese medicine gel is similar to that of Example 2, except that the amount of each component is adaptively adjusted according to the concentration, wherein the amount of the Chinese medicine water extract is 0.3g.

[0066] Example 4

[0067] A Chinese medicine gel similar to Example 3, except that the concentration of the Chinese medicine water extract prepared in Example 1 is 4.375wt.%, and the amount of the Chinese medicine water extract used in preparing the Chinese medicine gel is 0.35g.

[0068] Example 5

[0069] A Chinese medicine gel similar to Example 3, except that the concentration of the Chinese medicine water extract prepared in Example 1 is 5wt.%, and the amount of the Chinese medicine water extract used in preparing the Chinese medicine gel is 0.4g.

[0070] Comparative Example 1

[0071] A Chinese medicine gel similar to Example 3, except that the concentration of the Chinese medicine water extract prepared in Example 1 is 5wt.%, and the amount of the Chinese medicine water extract used in preparing the Chinese medicine gel is 0.45g.

[0072] Comparative Example 2

[0073] A Chinese medicine gel similar to Example 3, except that the concentration of the Chinese medicine water extract prepared in Example 1 is 6.25wt.%, and the amount of the Chinese medicine water extract used in preparing the Chinese medicine gel is 0.5g.

[0074] Comparative Example 3

[0075] A Chinese medicine gel similar to Example 3, except that the concentration of the Chinese medicine water extract prepared in Example 1 is 8.75wt.%, and the amount of the Chinese medicine water extract used in preparing the Chinese medicine gel is 0.7g.

[0076] Example 6

[0077] A Chinese medicine gel similar to Example 4, except that the concentration of Carbomer 940 is 5wt.%, and the amount of Carbomer 940 used in preparing the Chinese medicine gel is 0.4g.

[0078] Example 7

[0079] A Chinese medicine gel similar to Example 4, except that the concentration of Carbomer 940 is 6.25wt.%, and the amount of Carbomer 940 used in preparing the Chinese medicine gel is 0.5g.

[0080] Comparative Example 4

[0081] A Chinese medicine gel similar to Example 4, except that the concentration of Carbomer 940 is 8.75wt.%, and the amount of Carbomer 940 used in preparing the Chinese medicine gel is 0.7g.

[0082] Comparative Example 5

[0083] A Chinese medicine gel similar to Example 4, except that the concentration of Carbomer 940 is 10wt.%, and the amount of Carbomer 940 used in preparing the Chinese medicine gel is 0.8g.

[0084] Example 8

[0085] A Chinese medicine gel similar to Example 7, except that the concentration of propylene glycol is 25wt.%, and the amount of propylene glycol used in preparing the Chinese medicine gel is 2g.

[0086] Example 9

[0087] A Chinese medicine gel similar to Example 7, except that the concentration of propylene glycol is 31.25wt.%, and the amount of propylene glycol used in preparing the Chinese medicine gel is 2.5g.

[0088] Comparative Example 6

[0089] A Chinese medicine gel similar to Example 7, except that the concentration of propylene glycol is 6.25wt.%, and the amount of propylene glycol used in preparing the Chinese medicine gel is 0.5g.

[0090] Comparative Example 7

[0091] A Chinese medicine gel similar to Example 7, except that the concentration of propylene glycol is 12.5wt.%, and the amount of propylene glycol used in preparing the Chinese medicine gel is 1g.

[0092] Example 10

[0093] A Chinese medicine gel similar to Example 8, except that the concentration of triethanolamine is 1.25 mL / kg, and the amount of triethanolamine used in preparing the Chinese medicine gel is 10 μL.

[0094] Embodiment 11

[0095] A Chinese medicine gel similar to Example 8, except that the concentration of triethanolamine is 2.5 mL / kg, and the amount of triethanolamine used in preparing the Chinese medicine gel is 20 μL.

[0096] Comparative Example 8

[0097] A Chinese medicine gel similar to Example 8, except that the concentration of triethanolamine is 0.625 mL / kg, and the amount of triethanolamine used in preparing the Chinese medicine gel is 5 μL.

[0098] Comparative Example 9

[0099] A Chinese medicine gel similar to Example 8, except that the concentration of triethanolamine is 3.125 mL / kg, and the amount of triethanolamine used in preparing the Chinese medicine gel is 25 μL.

[0100] Comparative application example 1

[0101] A comprehensive evaluation method for gel prescriptions was established based on the three indicators of appearance, viscosity and spreadability. The formability of the Chinese medicine gels prepared in Examples 2 to 11 and Comparative Examples 1 to 9 was compared. The scoring criteria are shown in Table 1, and the scoring results are shown in Tables 2 to 5.

[0102] Table 1 Comprehensive scoring criteria for gel prescriptions

[0103] score Appearance Viscosity Spreadability 20～40 Poor surface smoothness, uneven texture, and rough texture Too thick or too thin Poor coating properties 41～60 The surface is generally smooth, the texture is generally uniform and not fine enough Slightly thick or slightly thin General coating properties 61～80 The surface is smooth and the texture is uniform, but not delicate enough Not thick or thin enough Good coating properties 81～100 The surface is smooth and shiny, the texture is uniform and delicate Moderate Good spreadability, easy to spread

[0104] Note: Full score is 100 points; comprehensive score of gel prescription = appearance score × 0.3 + viscosity score × 0.3 + spreadability score × 0.4.

[0105] Table 2 Effect of the dosage of Chinese herbal medicine extract on gel forming properties

[0106] Group Extract dosage / g Appearance Viscosity Spreadability Example 3 0.3 Smooth surface, uniform and fine texture Slightly rare Good coating properties Example 4 0.35 Smooth surface, uniform and fine texture Moderate Good coating properties Example 5 0.4 Smooth surface and uniform texture Slightly thick Good coating properties Comparative Example 1 0.45 Smooth surface and uniform texture Slightly thick Good coating properties Comparative Example 2 0.5 Smooth surface and uniform texture Slightly thick Slightly difficult to apply Comparative Example 3 0.7 Smooth surface and uniform texture Slightly thick Slightly difficult to apply

[0107] As shown in Table 2, when the amount of extract exceeds 0.4g, the viscosity of the gel is too high, and when the amount of extract is less than 0.3g, the viscosity of the gel is too low and the fluidity is too strong. Therefore, the amount of extract is more suitable at 0.3-0.4g.

[0108] Table 3 Effect of Carbomer 940 dosage on gel forming properties

[0109]

[0110]

[0111] As shown in Table 3, when the amount of Carbomer 940 exceeds 0.6 g, the gel viscosity is high and the spreadability is poor, while when the amount of Carbomer 940 is less than 0.4 g, the gel viscosity is low and the fluidity is too strong. Therefore, the amount of Carbomer 940 is more suitable between 0.4 and 0.6 g.

[0112] Table 4 Effect of propylene glycol dosage on gel forming properties

[0113] Group Propylene glycol dosage / g Appearance Viscosity Spreadability Comparative Example 6 0.5 Smooth surface and uniform texture Very thick Difficult to apply Comparative Example 7 1 Smooth surface and uniform texture Thick Difficult to apply Example 7 1.5 Smooth surface and uniform texture Slightly thick Good coating properties Example 8 2 Smooth surface, uniform and fine texture Moderate Good coating properties Example 9 2.5 Smooth surface, uniform and fine texture Slightly rare Good coating properties

[0114] As shown in Table 4, when the amount of propylene glycol exceeds 2.5g, the viscosity of the gel is too low and the fluidity is too strong, while when the amount of propylene glycol is less than 1.5g, the viscosity of the gel is too high and the spreadability is poor. Therefore, the amount of propylene glycol is more suitable between 1.5 and 2.5g.

[0115] Table 5 Effect of triethanolamine dosage on gel forming properties

[0116] Group Triethanolamine dosage / μL Appearance Viscosity Spreadability Comparative Example 8 5 Smooth surface, uniform and fine texture Slightly rare Good coating properties Example 10 10 Smooth surface, uniform and fine texture Slightly rare Good coating properties Example 8 15 Smooth surface, uniform and fine texture Moderate Good coating properties Embodiment 11 20 Smooth surface, uniform and fine texture Slightly thick Good coating properties Comparative Example 9 25 Smooth surface, uniform and fine texture Slightly thick Good coating properties

[0117] As shown in Table 5, when the amount of triethanolamine exceeds 20 μL, the pH value of the gel is greater than 7.5, the viscosity is too high, and the spreadability is poor. When the amount of triethanolamine is less than 10 μL, the pH value of the gel is less than 6.5, the viscosity is too low, and the fluidity is too strong. When the amount of triethanolamine is between 10 and 20 μL, the pH is just between 6.5 and 7.5, so the amount of triethanolamine between 10 and 20 μL is more appropriate.

[0118] Based on the appearance, viscosity and spreadability of Examples 2 to 11 of the present invention, the optimal preparation process is the Chinese medicine gel prepared in Example 2. Three batches of Chinese medicine gel (ZSGA) were prepared according to the method described in Example 2, and scored according to the scoring criteria in Table 1. The scoring results are shown in Table 6.

[0119] Table 6 Verification test results

[0120]

[0121] As shown in Table 6, the three batches of gels all had good appearance and spreading properties, and the average comprehensive score of the three batches of preparations was 94.9 points, with good process reproducibility and stability.

[0122] The quality stability of the three batches of samples prepared in Example 2 was evaluated by a confirmatory test according to the method described in the reference [Su Ting, Zhao Yan, Bi Ye, et al. Study on the preparation process of liposome gel of total flavonoids from Ula herb [J]. Drug Evaluation Research, 2021, 44(05): 990-996.], and the evaluation criteria were as follows:

[0123] (1) Properties: Observe the smoothness of the surface, clarity and fluidity of the three batches of ZSAG to see if they meet the requirements;

[0124] (2) Determination of pH value: Take 3 portions of ZSAG, 0.5 g each, dissolve in 10 mL of distilled water with sonication, and measure the pH value after dissolution;

[0125] (3) Spreadability: Apply an appropriate amount of ZSAG on your hands and observe whether the gel can be easily and evenly spread;

[0126] (4) Centrifugation test: Weigh 5 g of ZSAG into a centrifuge tube, centrifuge at 4000 r / min for 30 min, and observe whether there is stratification and color change;

[0127] (5) Low temperature test: Weigh 5 g of ZSAG and place it in a -20°C refrigerator for 72 h. Then take it out and observe whether it has stratification and color change.

[0128] (6) High temperature test: Weigh 5 g of ZSAG and seal it in a 55°C water bath for 5 h. Then take it out and observe whether it has stratification and color change.

[0129] The average results are as follows:

[0130] 1) Properties: The results show that the gel surface is smooth, light brown and transparent, with moderate fluidity. Figure 1; 2) Determination of pH value: The average pH value was measured to be 7.0±0.5; 3) Spreadability: The results showed that the gel had a uniform and fine texture, moderate viscosity, moderate fluidity, and was easy to spread evenly; 4) Centrifugation test, low temperature test, and high temperature test: The results all showed that the three batches of gel had no stratification or color change.

[0131] The above results show that the traditional Chinese medicine gel prepared in Example 2 has good stability and meets the quality standards.

[0132] Comparative Example 10

[0133] A Chinese medicine aqueous extract similar to Example 1, except that the preparation raw materials do not contain Lithospermum officinale.

[0134] Comparative Example 11

[0135] A Chinese medicine water extract similar to Example 1, except that the preparation raw materials do not contain peony bark.

[0136] Comparative Example 12

[0137] A Chinese medicine water extract similar to Example 1, except that the preparation raw materials do not contain Sophora flavescens.

[0138] Comparative Example 13

[0139] A Chinese medicine aqueous extract similar to Example 1, except that the preparation raw materials do not contain Hedyotis diffusa.

[0140] Comparative Example 14

[0141] A Chinese medicine aqueous extract similar to Example 1, except that the preparation raw materials do not contain honeysuckle.

[0142] Comparative Example 15

[0143] A traditional Chinese medicine gel similar to Example 2, except that the traditional Chinese medicine aqueous extract prepared in Example 1 is replaced by the traditional Chinese medicine aqueous extract prepared in Comparative Example 10.

[0144] Comparative Example 16

[0145] A Chinese medicine gel similar to Example 2, except that the Chinese medicine aqueous extract prepared in Example 1 is replaced by the Chinese medicine aqueous extract prepared in Comparative Example 11.

[0146] Comparative Example 17

[0147] A traditional Chinese medicine gel similar to Example 2, except that the traditional Chinese medicine aqueous extract prepared in Example 1 is replaced by the traditional Chinese medicine aqueous extract prepared in Comparative Example 12.

[0148] Comparative Example 18

[0149] A traditional Chinese medicine gel similar to Example 2, except that the traditional Chinese medicine aqueous extract prepared in Example 1 is replaced by the traditional Chinese medicine aqueous extract prepared in Comparative Example 13.

[0150] Comparative Example 19

[0151] A traditional Chinese medicine gel similar to Example 2, except that the traditional Chinese medicine aqueous extract prepared in Example 1 is replaced by the traditional Chinese medicine aqueous extract prepared in Comparative Example 14.

[0152] Comparative Example 20

[0153] A gel similar to Example 2, except that it does not contain the Chinese medicine aqueous extract prepared in Example 1.

[0154] Application Example 1

[0155] The anti-inflammatory and antipruritic effects of the traditional Chinese medicine gel prepared in Example 2 were verified by the following specific verification tests:

[0156] 36 SPF ICR mice, male, weight (20±2) g, 12 SPF SD rats, male, weight (200±20) g, 36 normal healthy DH guinea pigs, male, weight (350±20) g, provided by Henan Sikebes Biotechnology Co., Ltd., quality inspection unit is Shandong Provincial Experimental Animal Center, license number: SCXK (Yu) -2020-0005. The experiment has passed the animal experiment ethics review of Wanxi University.

[0157] 1. Effect of the traditional Chinese medicine gel prepared in Example 2 on xylene-induced ear swelling in mice

[0158] Thirty-six male ICR mice were randomly divided into a model control group, a positive control group, a high-dose gel group, a medium-dose gel group, a low-dose gel group, and a gel matrix control group, with 6 mice in each group. The model control group was not given any medicine; the positive control group, the high-dose gel group, the medium-dose gel group, the low-dose gel group, and the gel matrix control group were applied externally on the front and back of the right auricle of the mice twice a day for 7 consecutive days. The dosage for each administration is shown in Table 7. The smear drug of the positive control group was a compound dexamethasone acetate cream group (China Resources Sanjiu (Nanchang) Pharmaceutical Co., Ltd., batch number 2301012S), and the smear drugs of the high-dose gel group, the medium-dose gel group, and the low-dose gel group were all the traditional Chinese medicine gel prepared in Example 2, and the smear drug of the gel matrix control group was the gel prepared in Comparative Example 20;

[0159] 0.5 h after the last administration, 0.05 mL / animal xylene (analytical grade, Shanghai MacLean Biochemical Technology Co., Ltd., batch number 20150508) was evenly applied on both sides of the right ear of each group of animals to induce inflammation, and the animals were killed by dislocating the neck 30 min later. The two ears of the mice were cut along the auricle, and a disc was punched in the same part of both ears with a puncher with a diameter of 8 mm. The disc was weighed with an electronic balance, and the ear swelling degree, swelling rate and swelling inhibition rate were calculated.

[0160] Ear swelling (mg) = right ear piece weight - left ear piece weight;

[0161] Swelling rate (%) = ear swelling degree / left ear piece weight × 100%;

[0162] Swelling inhibition rate = (average swelling rate of model control group - average swelling rate of drug administration group) / average swelling rate of model control group × 100%. The results are shown in Table 7 and Figure 2 .

[0163] Table 7 Effect of ZSAG on ear swelling in mice ( n=6)

[0164]

[0165] Note: “—” indicates no such data; compared with the model control group, ** indicates p<0.01, * indicates p<0.05; compared with the gel matrix control group, # indicates p<0.05.

[0166] From Table 7 and Figure 2 It can be seen that compared with the model control group and the gel matrix control group, the positive control group and the high-, medium- and low-dose gel groups can alleviate the ear swelling of mice, and the difference is statistically significant (p<0.01, p<0.05); compared with the positive control group, there is no significant difference between the high-, medium- and low-dose gel groups and the positive control group (p>0.05), indicating that ZSAG can significantly inhibit xylene-induced ear inflammation in mice, and the effect is more obvious with increasing doses.

[0167] 2. Effect of the traditional Chinese medicine gel prepared in Example 2 on the itch reaction induced by histamine phosphate in guinea pigs

[0168] Take 36 guinea pigs and divide them into 6 groups at random, namely model control group, gel matrix control group, positive control group, gel high dose group, gel medium dose group and gel low dose group, 6 in each group, half male and half female. The left hind foot back of each group of guinea pigs was shaved 24h before administration to ensure that the skin was intact and undamaged. From the next day, local skin application was once a day for 7 consecutive days. The dosage of each administration is shown in Table 8. Each time, the test substance or gel matrix was directly applied to the depilated skin to make it naturally absorbed. The model control group was not administered. The smearing medicine of the positive control group was mometasone furoate gel group (China Resources Sanjiu (Nanchang) Pharmaceutical Co., Ltd., batch number 2301005J). The smearing medicine of the gel high dose group, gel medium dose group and gel low dose group was the Chinese medicine gel prepared by Example 2, and the smearing medicine of the gel matrix control group was the gel prepared by Comparative Example 20;

[0169] One hour after the last dose, gently scrape the shaved skin 1 cm with a No. 0 fine sandpaper. 2 , and drip 0.05 mL / guinea pig of increasing concentrations of 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.2, and 0.3% histamine phosphate (Sinopharm Chemical Reagent Co., Ltd., batch number 20150508) every 3 minutes. The total amount of histamine (μg) administered when the guinea pig turns back to lick the back of the left hind foot is the itch threshold. If the histamine concentration is increased to 0.3% and there is still no reaction of turning back to lick the back of the foot, the experiment will not be continued, that is, the total amount of histamine at this time will be calculated. The results are shown in Table 8 and Figure 3 .

[0170] Table 8 Effect of ZSAG on itch response induced by histamine phosphate in guinea pigs ( n=6)

[0171] Group <![CDATA[Dose (g / cm 2 )]]> Itch threshold (total amount of histamine phosphate) / μg Model control group — 87.50±30.62 Gel matrix control group 0.2 91.67±25.82 Positive control group 0.1 <![CDATA[166.67±66.46 * / # ]]> Low-dose gel group 0.1 125.00±54.77 Gel medium dose group 0.2 <![CDATA[150.00±61.24 * / # ]]> High-dose gel group 0.4 <![CDATA[191.67±51.64 ** / ## ]]>

[0172] Note: “—” indicates no such data. Compared with the model control group, ** indicates p < 0.01, * indicates p < 0.05; compared with the gel matrix control group, ## p<0.01, # p<0.05.

[0173] From Table 8 and Figure 3 It can be seen that compared with the model control group and the gel matrix control group, the itch thresholds of the positive control group, high-dose, medium-dose and low-dose gel groups were all increased. Except for the low-dose group, the differences in the other groups were statistically significant (p<0.01, p<0.05); compared with the positive control group, there was no significant difference between the high-dose, medium-dose and low-dose gel groups (p>0.05), indicating that ZSAG can increase the itch threshold of ammonium phosphate in guinea pigs, and the effect is more obvious with increasing doses.

[0174] 3. Single-dose skin irritation test

[0175] Twelve male SD rats were randomly divided into a normal skin group and a damaged skin group. Three rats in each of the two groups were given 3 g of blank matrix (i.e., the gel prepared in Comparative Example 20), and the other three rats were given 3 g of ZSAG gel (i.e., the traditional Chinese medicine gel prepared in Example 2, which was applied to the damaged skin). Figure 4 Before the experiment, the abdominal hair of the two groups of rats was shaved about 25 cm. 2 , divided equally into left and right, the left side was not treated, and the right side was treated; the treatment method of the damaged skin group was: rub the abdomen where hair was removed with No. 400 gauze to cause local abrasions, and the degree of damage to the stratum corneum and epidermal bleeding was considered. After administration, fix it with sterile gauze, and wash the skin with sterile warm water after 6 hours. The erythema, edema, etc. at the administration site were observed 1h, 24h, 48h, and 72h after drug withdrawal. The experimental results of 72h after drug withdrawal are shown in Figure 5 .

[0176] Depend on Figure 5 It can be seen that the traditional Chinese medicine gel provided by the present invention has no erythema, no eschar formation, no skin swelling, edema and other irritating manifestations after acting on the normal skin and damaged skin of rats, indicating that a single administration of blank matrix and ZSAG is non-irritating to the intact skin and damaged skin of rats.

[0177] 4. Repeated administration skin irritation test

[0178] Twelve male SD rats were selected, and the grouping method and animal skin treatment method were the same as those in the "single-dose skin irritation test". The drug was administered for 7 consecutive days, and the skin was washed with sterile warm water 24 hours after the last administration. The erythema and edema at the administration site were observed at 1 hour, 24 hours, 48 ​​hours, and 72 hours after drug withdrawal. The experimental results of 72 hours after drug withdrawal are shown in Figure 6 .

[0179] Depend on Figure 6 It can be seen that the traditional Chinese medicine gel provided by the present invention has no erythema, no eschar formation, no irritation phenotypes such as skin swelling and edema after acting on normal skin and damaged skin of rats, and the skin bleeding and damage are restored, indicating that multiple administrations of blank matrix and ZSAG are non-irritating to the intact skin and damaged skin of rats.

[0180] Comparative Application Example 2

[0181] The anti-inflammatory and antipruritic effects of the traditional Chinese medicine gels prepared in Example 2 and Comparative Examples 15 to 19 were verified. The verification test method was similar to steps 1 and 2 in Application Example 1, except that no gel matrix control group and positive control group were set, and the dosage of each traditional Chinese medicine gel was 0.2 g / cm 2 The test results are shown in Table 9. Figure 7 , Table 10 and Figure 8 .

[0182] Table 9 Effects of the extract groups on ear swelling in mice ( n=6)

[0183]

[0184] Note: “—” indicates no such data; compared with the model control group, ** indicates p < 0.01, and * indicates p < 0.05.

[0185] From Table 9 and Figure 7 It can be seen that the swelling inhibition rate of each drug-treated group was improved to varying degrees compared with the model group. Except for the group without Hedyotis diffusa, the other extract groups showed extremely significant differences from the model group. In addition, the swelling inhibition rate of the formula without Hedyotis diffusa was quite different from that of the purple ginseng formula, which shows that Hedyotis diffusa has a greater impact on the anti-inflammatory activity of the formula.

[0186] Table 10 Effects of the extracts of the formula on the itch response of guinea pigs induced by histamine phosphate ( n=6)

[0187] Pharmacy Group <![CDATA[Dose (g / cm 2 )]]> Itch threshold (total amount of histamine phosphate) / μg No medication Model control group — 83.33±20.41 Comparative Example 15 No lithospermum group 0.2 100.00±27.39 Comparative Example 16 No peony bark group 0.2 91.67±25.82 Comparative Example 17 No Sophora flavescens group 0.2 <![CDATA[116.67±20.41 * <!-- 11 -->]]> Comparative Example 18 No Hedyotis diffusa group 0.2 108.33±25.82 Comparative Example 19 No honeysuckle group 0.2 <![CDATA[133.33±49.16 * ]]> Example 2 Purple ginseng formula group 0.2 <![CDATA[141.67±40.82 * ]]>

[0188] Note: “—” indicates no such data; compared with the model control group, ** indicates p < 0.01, and * indicates p < 0.05.

[0189] From Table 10 and Figure 8 It can be seen that the itch threshold of guinea pigs was increased to varying degrees in each drug-treated group compared with the model group. Among them, the purple ginseng formula, the group without sophora flavescens, and the group without honeysuckle were significantly different from the model group, and no significant differences were found in the other knockout groups. In addition, the itch threshold of the formula lacking peony bark was significantly different from that of the purple ginseng formula group, indicating that peony bark had a greater effect on the antipruritic activity of the formula.

[0190] In summary, the traditional Chinese medicine gel provided by the present invention has a uniform and fine texture, is easy to spread, has good anti-inflammatory and antipruritic activities, is non-toxic and has no skin irritation, and has a long drug action time.

[0191] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A Chinese medicine gel, characterized in that: The traditional Chinese medicine gel is composed of components with the following concentrations: 3.75wt.%~5wt.% of traditional Chinese medicine water extract, 5wt.%~7.5wt.% of carbomer 940, 18.75wt.%~31.25wt.% of propylene glycol, 1.25~2.5mL / kg of triethanolamine, 0.125wt.% of preservative and the balance of water; the raw materials for preparing the traditional Chinese medicine water extract are: lithospermum officinale, peony bark, sophora flavescens, oldenlandia diffusa and honeysuckle; the mass ratio of lithospermum officinale, peony bark, sophora flavescens, oldenlandia diffusa and honeysuckle is 1:1:1:1:

1.

2. The Chinese medicine gel according to claim 1, characterized in that: The pH value of the traditional Chinese medicine gel is 6.5-7.

5.

3. The Chinese medicine gel according to claim 1, characterized in that: The preservatives include ethylparaben and / or ethylparaben.

4. The method for preparing the Chinese medicine gel according to any one of claims 1 to 3, characterized in that: The following steps are involved: Mixing lithospermum officinale, peony bark, sophora flavescens, oldenlandia diffusa and honeysuckle, boiling in water and filtering to obtain a filtrate; Drying the filtrate to obtain the Chinese medicine water extract; Mixing the Carbomer 940 with a portion of water to obtain a swollen Carbomer 940 matrix; Dissolving the Chinese medicine water extract and mixing it with the swollen Carbomer 940 matrix to obtain a drug-containing matrix; The drug-containing matrix is ​​mixed with propylene glycol, a preservative, triethanolamine and remaining water to obtain the traditional Chinese medicine gel.

5. The preparation method according to claim 4, characterized in that: The decoction is performed 1 to 3 times, and the decoction time for each time is 50 to 70 minutes.

6. The preparation method according to claim 4, characterized in that: The drying temperature is ≤65°C.

7. The preparation method according to claim 4, characterized in that: The mass ratio of Carbomer 940 to part of water in the swollen Carbomer 940 matrix is ​​1:5-10.

8. The preparation method according to claim 4, characterized in that: The mixing method of the drug-containing matrix, propylene glycol, preservative, triethanolamine and remaining water comprises: dissolving the preservative in the propylene glycol to obtain an auxiliary material solution; and mixing the drug-containing matrix, the auxiliary material solution, triethanolamine and remaining water.

9. Use of the traditional Chinese medicine gel according to any one of claims 1 to 3 or the traditional Chinese medicine gel prepared by the preparation method according to any one of claims 4 to 8 in the preparation of anti-inflammatory and / or antipruritic drugs.

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