Use of toad oil cream in preparing medicine for treating dermatitis

Abstract

The present invention provides the use of a toad oil cream in preparing a drug for treating dermatitis, and relates to the field of medical technology. The toad oil cream is composed of toad oil and a matrix, and the toad oil is prepared according to the method of Chinese invention patent application CN117126696 A, and the matrix is ​​composed of cetostearyl alcohol, glyceryl monostearate, liquid paraffin, dimethicone, propylparaben, carbomer, glycerol, potassium lauryl phosphate, hyaluronic acid, methylparaben, triethanolamine and water. The toad oil cream obtained by the present invention can reduce the irritation of toad oil to the skin, improve the spreadability of toad oil, show good therapeutic effects on atopic dermatitis and contact dermatitis, and can be used to treat dermatitis.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines, and in particular relates to application of toad oil cream in preparing medicines for treating dermatitis. Background Art

[0002] At present, the main toads used as medicine are toad venom and toad skin. After collecting toad venom and peeling toad skin, toad bones, meat and internal organs become waste materials, resulting in a great waste of resources. Chinese invention patent application CN117126696A discloses a toad oil and its preparation method and application, using toad internal organs after collecting toad venom and peeling toad skin as raw materials, extracting and processing to make toad oil, turning waste into treasure; the toad oil obtained by the invention has obvious effects on skin diseases (inflammation, eczema, etc.), and according to its component analysis, the toad oil obtained by the invention also has anti-tumor function; in the patent application, toad oil comes from toad internal organs, but only involves the preparation of toad oil, and does not involve information on making toad oil into an ointment for deep utilization, and the obtained toad oil is sticky and not easy to be evenly applied on the skin, and according to the efficacy research, it has a certain irritation to the skin.

[0003] Regarding creams, the research progress of cream preparation methods [J] (Nie Jihong, Wang Ping, Jia Ziyi La. Xinjiang Medicine, 2004, (06): 173-177) reviewed the optimization of cream bases and the emulsification methods of creams. The ideal cream should be uniform, delicate, stable and have appropriate viscosity, adhesion and spreadability.

[0004] In order to facilitate the clinical application of the above-mentioned toad oil, it is urgently necessary to develop a toad oil cream, so that the toad oil can be easily and evenly applied on the skin, easily absorbed and less irritating, and the prepared cream has a better therapeutic effect on dermatitis, especially atopic dermatitis and contact dermatitis. Summary of the invention

[0005] The invention aims at the problems existing in the prior art and provides use of a toad oil cream in preparing a drug for treating dermatitis. By preparing the toad oil into the cream, the irritation of the toad oil to the skin is reduced and the spreadability of the toad oil is improved. The toad oil cream has a better therapeutic effect on dermatitis, especially atopic dermatitis and contact dermatitis. While turning the toad oil into treasure, the toad resource utilization system is improved, and the toad oil cream is a breakthrough resource reserve for external use of traditional Chinese medicine to treat skin diseases.

[0006] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0007] The invention provides use of a toad oil cream in preparing a medicament for treating dermatitis. The toad oil cream comprises toad oil and a matrix, wherein the toad oil is prepared according to the method of Chinese invention patent application CN117126696 A, and the matrix comprises cetostearyl alcohol, glyceryl monostearate, liquid paraffin, dimethicone, propylparaben, carbomer, glycerin, potassium lauryl phosphate, hyaluronic acid, methylparaben, triethanolamine and water.

[0008] Preferably, the method for preparing toad oil comprises the following steps:

[0009] S1: crushing the toad viscera to obtain toad viscera paste;

[0010] S2: heating the minced toad viscera obtained in step S1 and then centrifuging and separating the mixture to obtain toad oil;

[0011] In the step S2, the heating method includes heating the toad viscera paste in water, heating with water, and heating with a weak alkali; the heating temperature is ≤95°C, preferably 65°C; the heating time is ≤60min, preferably 30min.

[0012] Further preferably, in the step S1, the particles are crushed to a size of ≤5 mm; in the step S2, a solvent is added when the toad viscera mince is heated in water, and the solvent is distilled water; NaCl is added for salting out when the toad viscera mince is heated in water, and the amount of NaCl added is within 2% of the mass of the toad viscera mince, and more preferably 1%.

[0013] Further preferably, in step S2, the salting-out time is ≤20 min, preferably 10 min; the centrifugal rate is ≤10000 r / min, preferably 6000 r / min; and the centrifugal time is <30 min, preferably 15 min.

[0014] Preferably, the dermatitis is atopic dermatitis or contact dermatitis.

[0015] Preferably, the medicament is used to improve erythema, crusting and skin erosion caused by atopic dermatitis.

[0016] Preferably, the medicament is used to improve the change of spleen index caused by atopic dermatitis.

[0017] Preferably, the medicament is used to improve ear swelling conditions, ie, inflammatory conditions, caused by contact dermatitis.

[0018] Preferably, the medicament is used to improve abnormal skin changes caused by contact dermatitis.

[0019] Preferably, the mass fraction of the toad oil in the toad oil cream is 5-20%.

[0020] Preferably, the toad oil cream matrix is ​​composed by weight: 1.5-2.5 parts of cetostearyl alcohol, 1-5 parts of glyceryl monostearate, 6-10 parts of liquid paraffin, 1-3.5 parts of dimethicone, 0.05-0.15 parts of propylparaben, 0.05-0.15 parts of carbomer, 6-10 parts of glycerol, 1.5-3 parts of potassium lauryl phosphate, 0.5-1.5 parts of hyaluronic acid, 0.15-0.25 parts of methylparaben, 0.05-0.15 parts of triethanolamine, and 50-60 parts of water.

[0021] Further preferably, the toad oil cream base is composed by weight: 2 parts of cetostearyl alcohol, 1 part of glyceryl monostearate, 8 parts of liquid paraffin, 2 parts of dimethicone, 0.1 part of propylparaben, 0.1 part of carbomer, 7 parts of glycerol, 2 parts of potassium lauryl phosphate, 1 part of hyaluronic acid, 0.2 parts of methylparaben, 0.1 part of triethanolamine, and 57 parts of water.

[0022] Preferably, the weight of the cetostearyl alcohol, potassium lauryl phosphate and hyaluronic acid in the matrix accounts for 4-8%.

[0023] Preferably, the weight ratio of cetostearyl alcohol, potassium lauryl phosphate and hyaluronic acid is 3-5:3-6:1-3.

[0024] Preferably, the weight ratio of cetostearyl alcohol, potassium lauryl phosphate and hyaluronic acid is 2:2:1.

[0025] Preferably, the preparation method of the toad oil cream base comprises the following steps:

[0026] (1) Mix cetostearyl alcohol, glyceryl monostearate, liquid paraffin, dimethyl silicone oil and propylparaben, and stir to obtain an oil phase;

[0027] (2) mixing carbomer, glycerin, potassium lauryl phosphate, hyaluronic acid, methylparaben and water, and stirring to obtain an aqueous phase;

[0028] (3) Add the oil phase to the water phase, heat, perform the first homogenization, keep warm, add triethanolamine, and perform the second homogenization to obtain.

[0029] More preferably, the stirring time in step (1) is 10-20 minutes, wherein 12 minutes is the best.

[0030] More preferably, the stirring time in step (2) is 10-20 minutes, wherein 15 minutes is the best.

[0031] More preferably, the heating temperature in step (3) is 85-100° C., with 85° C. being the best.

[0032] More preferably, in step (3), the first homogenization time and the second homogenization time are independently selected from 2-5 minutes, wherein the first homogenization time and the second homogenization time are both 3 minutes, which is the best.

[0033] More preferably, the insulation time in step (3) is 20-30 minutes, of which 25 minutes is the best.

[0034] Preferably, the preparation method of the toad oil cream is: adding the toad oil to the toad oil cream base and homogenizing to obtain the cream.

[0035] More preferably, the homogenization time is selected from 2-5 min, wherein 3 min is the best.

[0036] Compared with the prior art, the present invention has the following beneficial effects: by preparing toad oil into an ointment, the irritation of toad oil to the skin is reduced, the spreadability of toad oil is improved, and the obtained toad oil ointment has a better therapeutic effect on dermatitis, especially atopic dermatitis and contact dermatitis. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 The apparent changes of the skin of mice in each group during the atopic dermatitis effect;

[0038] Figure 2 Effects on spleen index in atopic dermatitis model mice;

[0039] Figure 3 Effects on ear swelling rate in atopic dermatitis model mice;

[0040] Figure 4 Effects on ear swelling rate in contact dermatitis model mice;

[0041] Figure 5 HE-stained pathological sections of ear skin of contact dermatitis model mice. DETAILED DESCRIPTION

[0042] It is worth noting that the raw materials used in the present invention are all common commercially available products, and their sources are not specifically limited.

[0043] The viscera of Chinese giant toad were obtained from Xichang Fuhua Jinchan Biotechnology Co., Ltd. Toad oil was prepared according to the method of Example 1 of Chinese invention patent application CN117126696 A, specifically: S1: Put the toad viscera into a meat grinder and mince it into toad viscera paste with a particle size of ≤5mm; S2: Take 30g of toad viscera paste and put it into a conical flask, place it in a constant temperature water bath at 80℃ and heat it for 45min, take it out and place it at room temperature, centrifuge it at 6000r / min for 15min, and separate toad oil. Triethanolamine (batch number 20230502) was purchased from Chengdu Huayi Pharmaceutical Excipient Manufacturing Co., Ltd. Glycerol (batch number 20230301) and dimethyl silicone oil (batch number 20230502) were purchased from Jiangxi Puyisheng Pharmaceutical Co., Ltd. Hyaluronic acid (sodium hyaluronate) (batch number 23072401-E) was purchased from Shandong Anhua Biopharmaceutical Co., Ltd. Potassium lauryl phosphate (batch number 119511001090) was purchased from Shandong Yousuo Chemical Technology Co., Ltd. Cetostearyl alcohol (batch number 20230502) and glyceryl monostearate (batch number YF20230201) were purchased from Jiangxi Alpha Hi-Tech Pharmaceutical Co., Ltd. Liquid paraffin (batch number 20230301) was purchased from Tianjin Damao Chemical Reagent Factory. Propylparaben and methylparaben were purchased from Jiangsu Zhenghong Biotechnology Co., Ltd. Carbomer U20 was purchased from Guangzhou Shengda Biotechnology Co., Ltd. Water was Wahaha purified water.

[0044] The composition and preparation of the toad oil cream base group, the toad oil cream low-, medium- and high-dose groups, and the toad oil group involved in the following experiments are as follows:

[0045] (1) Toad oil cream base

[0046] The components by weight are: 2 parts of cetostearyl alcohol, 1 part of glyceryl monostearate, 8 parts of liquid paraffin, 2 parts of dimethicone, 0.1 part of propylparaben, 0.1 part of carbomer, 7 parts of glycerol, 2 parts of potassium lauryl phosphate, 1 part of hyaluronic acid, 0.2 parts of methylparaben, 57 parts of water, and 0.1 part of triethanolamine. The preparation process is as follows: 1) cetostearyl alcohol, glyceryl monostearate, liquid paraffin, dimethicone and propylparaben are mixed and stirred for 12 minutes to obtain phase A emulsion; 2) carbomer, glycerol, potassium lauryl phosphate, hyaluronic acid, methylparaben and water are mixed and stirred for 15 minutes to obtain phase B emulsion; 3) phase A is added to phase B, heated to 85°C until completely dissolved, homogenized for 3 minutes, kept warm for 25 minutes, triethanolamine is added, and homogenized for 3 minutes.

[0047] (2) Low, medium and high dose groups of toad oil cream

[0048] Toad oil cream low-dose group (hereinafter referred to as RGJ low-dose group): 5 parts of toad oil were taken by weight and added into 95 parts of toad oil cream base, and homogenized for 3 minutes to obtain a toad oil cream with a mass fraction of 5% of toad oil.

[0049] Medium-dose group of toad oil cream (hereinafter referred to as RGJ medium-dose group): 10 parts of toad oil were taken by weight and added into 90 parts of toad oil cream base, and homogenized for 3 minutes to obtain a toad oil cream with a mass fraction of 10% of toad oil.

[0050] High-dose group of toad oil cream (hereinafter referred to as RGJ high-dose group): 20 parts of toad oil were taken by weight and added into 80 parts of toad oil cream base, and homogenized for 3 minutes to obtain a toad oil cream with a mass fraction of toad oil of 20%.

[0051] (3) Toad oil group

[0052] Take 90 parts of olive oil and 10 parts of toad oil by weight, mix them, and homogenize for 3 minutes to obtain the product.

[0053] Experimental Example 1 Toad Oil Irritation Test

[0054] 1. Process

[0055] 1. Acute skin irritation test of test substance

[0056] (1) Animals: Fifteen adult guinea pigs were divided into five groups, namely, a blank group, an olive oil group, a toad oil cream base group, a toad oil group, and a toad oil cream group, with 3 animals in each group.

[0057] (2) Methods: The day before the experiment, the hair on the back of the guinea pigs was shaved with a depilatory cream and a shaver to an area of ​​2 cm*2 cm. On the first day of the experiment, 2 g each of olive oil, toad oil cream base, toad oil, and toad oil cream (toad oil cream with a toad oil mass fraction of 10%) was applied to the depilated area on the back of the guinea pigs. The skin was then applied to the guinea pigs’ backs with a medical PU film and medical tape for 24 h. After 24 h, the skin was washed with warm water and the condition of the guinea pigs’ back skin was observed 1 h, 24 h, and 36 h after washing.

[0058] 2. Multiple skin irritation tests of the test substance

[0059] The animals and groups were the same as those in the acute skin irritation test.

[0060] Methods: The day before the experiment, the hair on the back of the guinea pigs was shaved with a depilatory cream and a shaver, with an area of ​​2 cm*2 cm. On the day of the experiment, 2 g each of olive oil, toad oil cream base, toad oil, and toad oil cream (toad oil cream with a toad oil mass fraction of 10%) was applied to the depilated area on the back of the guinea pigs. Medical PU film and medical tape were applied to the back of the guinea pigs for 6 hours and washed with warm water. The experiment was continued for 7 days, and the skin condition of the guinea pigs was observed.

[0061] 2. Results

[0062] Whether in the acute skin irritation test or the multiple skin irritation test, the guinea pigs in the toad oil group showed slight edema and redness, while the guinea pigs in the toad oil cream group showed no edema and redness. Therefore, making toad oil into an ointment can reduce the irritation of toad oil to the skin. At the same time, since toad oil is greasy and difficult to spread evenly, its spreadability is significantly improved after it is made into an ointment.

[0063] Experimental Example 2 Effect on Atopic Dermatitis (AD)

[0064] 1. Materials and Methods

[0065] 1.1 Animals

[0066] 70 6-8 week old SPF grade male BALB / c mice (18-22 g).

[0067] 1.2 Reagents

[0068] 2,4-Dinitrochlorobenzene (DNCB), acetone, olive oil.

[0069] 1.3 Grouping and modeling

[0070] The mice were randomly divided into 7 groups, 10 mice in each group, and weighed, including blank group, model group, positive drug tacrolimus group, positive drug hydrocortisone group, and toad oil cream low-dose, medium-dose and high-dose groups.

[0071] The day before the experiment, hair removal cream and shaver were used to remove the hair on the back of mice, with an area of ​​2.5×2.5cm. On D1 and D2, 100 μL of 1% DNCB solution (solvent is acetone: olive oil = 3:1) was evenly and slowly applied to the shaved hair on the back of mice in the model group, positive drug group, and drug group using a pipette, and 20 μL was applied to the left ear of the mouse (15 μL inside, 5 μL outside), and the right ear and blank group were applied with the same amount of solvent. On D6, 100 μL of 0.5% DNCB solution was applied to the back and 20 μL of the left ear using a pipette, and the right ear and blank group were applied with the same amount of solvent, and applied every 2 days until D28. If the mouse showed inflammatory reactions such as redness, swelling, desquamation, scabs, bleeding, exudation, and scratching and rolling on the back, the model was considered to be successful.

[0072] 1.4 Administration

[0073] Drug treatment began on D29. The blank group and model group were applied with 40 mg of toad oil cream base, the positive drug tacrolimus group was applied with 40 mg of tacrolimus, the positive drug hydrocortisone group was applied with 40 mg of hydrocortisone butyrate, and the low-, medium-, and high-dose toad oil cream groups were applied with 40 mg of toad oil cream with a mass fraction of 5%, 10%, and 20%, respectively. The treatment was continued for 7 days, with drug treatment twice a day, and ended on D35.

[0074] 2. Observation indicators and measurement methods

[0075] 2.1 Atopic dermatitis score (SCORAD score)

[0076] According to the atopic dermatitis scoring table, the skin condition on the back of the mice was evaluated and scored before modeling and drug administration at D1 until the end of drug administration.

[0077] Score erythema Edema dry ulcer 0 No erythema No edema No drying No ulcer 1 Faintly visible erythema Mild edema Slightly dry skin Mild epidermal ulcer 2 Patchy red papules Local edema with exudate Moderately dry, peeling Moderate epidermal ulcer 3 Dark red irregular protrusions Extensive edema, excessive exudation, and crusting Severe dryness of the epidermis with flaking Severe infected epidermal ulcer

[0078] 2.2 Ear swelling rate

[0079] 24 h after the last day of the experiment, the mice were killed by cervical dislocation, and the left and right ears were removed and weighed to calculate the ear swelling rate (ear swelling rate = right ear weight - left ear weight / left ear weight).

[0080] 2.3 Spleen index and thymus index

[0081] 24 hours after the last day of the experiment, the mice were weighed and killed by cervical dislocation. The spleen was removed and the fascia was removed. The blood on the surface of the organ was dried with filter paper and weighed. The spleen index was calculated according to the following formula:

[0082] Spleen index = spleen weight (g) / body weight (g) × 100%

[0083] 3. Results

[0084] 3.1 Skin epigenetic changes and atopic dermatitis scores in mice

[0085] The apparent changes of the skin of mice in each group are shown in Figure 1 . From the results, it can be seen that, except for the blank group, the back skin of mice in other groups showed atopic dermatitis (AD)-like symptoms to varying degrees. Among them, the symptoms of the model group were the most obvious, with obvious erythema, dryness, desquamation, scabs, etc., and the model was successfully established. After drug treatment, the dermatitis symptoms of the positive drug group and the low, medium and high dose groups of toad oil cream were effectively improved, erythema was reduced, and scabs and skin erosions gradually subsided.

[0086] The atopic dermatitis score results are shown in Table 1. According to the results, compared with the normal group, the score of the model group mice reached a peak on the 24th day of modeling (P < 0.01), indicating that the modeling was successful; after drug treatment, the atopic dermatitis scores of mice in each drug group were significantly reduced compared with the model group (P < 0.05 or P < 0.01), and the therapeutic effect of the low, medium and high dose groups of toad oil cream was better than that of the positive drug tacrolimus, and was similar to that of the hormone positive drug hydrocortisone butyrate.

[0087] Table 1 Atopic dermatitis score (x̅±s, n=10)

[0088] Time / Day 8 16 24 32 36 Blank Group 0 0 0 0 0 Model Group <![CDATA[5.17±0.75 a ]]> <![CDATA[7.00±0.63 a ]]> <![CDATA[9.67±0.52 a ]]> <![CDATA[8.50±0.55 a ]]> <![CDATA[7.83±0.41 a ]]> Tacrolimus group 4.67±1.03 7.0±0.63 9.33±0.52 <![CDATA[7.00±0.89 b ]]> <![CDATA[5.33±1.37 b ]]> Hydrocortisone butyrate group 4.83±1.17 7.33±0.52 9.33±0.52 <![CDATA[4.00±0.89 c ]]> <![CDATA[2.33±0.82 c ]]> RGJ low dose group 4.00±0.89 6.83±0.75 9.33±0.82 <![CDATA[5.50±0.55 c ]]> <![CDATA[3.83±0.75 c ]]> RGJ medium dose group 3.83±0.75 7.00±0.63 9.33±0.82 <![CDATA[5.67±0.82 c ]]> <![CDATA[4.17±0.75 c ]]> RGJ high dose group 4.00±0.63 7.00±0.89 9.67±0.52 <![CDATA[5.17±0.75 c ]]> <![CDATA[3.17±1.17 c ]]>

[0089] Note: Compared with the blank group, the model group a Indicates P < 0.01; compared with the model group, each drug group b Indicates P < 0.05, c Indicates P < 0.01.

[0090] 3.2 Spleen index

[0091] Effects on spleen index in atopic dermatitis model mice Figure 2 , compared with the blank group, ## Indicates P < 0.01; compared with the model group, * indicates P < 0.05, ** indicates P < 0.01, and *** indicates P < 0.001. According to the results, compared with the blank group, the spleen index of the model group increased, and the difference was statistically significant (P < 0.01). The spleen of the mice in the model group was hypertrophic, indicating that their immune function had problems. Compared with the model group, the spleen index of mice in each drug-treated group decreased significantly, and the low, medium, and high dose groups of toad oil cream were better than the tacrolimus group in reducing the spleen index of mice.

[0092] 3.3 Ear swelling rate

[0093] Effects on ear swelling rate in atopic dermatitis model mice Figure 3 , compared with the blank group, ## Indicates P < 0.01; compared with the model group, * indicates P < 0.05, ** indicates P < 0.01. According to the results, compared with the blank group, the ear swelling rate of mice in the model group was significantly increased (P < 0.01); compared with the model group, the ear swelling rates of the positive drug group and the low, medium and high dose groups of toad oil cream were significantly decreased (P < 0.05 or P < 0.01), and the effects of the low and high dose groups of toad oil cream were equivalent to the tacrolimus group, and the effect of the medium dose group of toad oil cream was better, and the effect was equivalent to that of the hormone positive drug hydrocortisone.

[0094] According to the clinical and experimental research literature records, tacrolimus cream, the only drug currently indicated for external use to treat atopic dermatitis, and hydrocortisone cream, a glucocorticoid topical drug, were selected as positive control drugs to investigate the effect of the toad oil cream of the present invention on atopic dermatitis. According to the atopic dermatitis scoring results, the therapeutic effect of the toad oil cream of the present invention on atopic dermatitis is better than that of the positive drug tacrolimus, and is similar to that of the hormone positive drug hydrocortisone butyrate, showing good therapeutic effect and clinical expectations.

[0095] Experimental Example 3 Effect on Contact Dermatitis (ACD)

[0096] Materials and methods 1.1 Animals and reagents

[0097] 60 male SPF BALB / c mice (18-22 g) aged 6-8 weeks, 2,4-dinitrochlorobenzene, acetone, olive oil

[0098] 1.2 Grouping and modeling

[0099] Sixty mice were randomly divided into 6 groups, with 10 mice in each group, namely blank group, model group, positive drug group (compound dexamethasone acetate cream group), and toad oil cream low-dose, medium-dose and high-dose groups.

[0100] On D0, the mouse abdomen was shaved 3×3 cm. On D1, 100 μL and 20 μL of 5% DNCB solution (solvent is acetone: olive oil = 3:1) were evenly and slowly applied to the back and right ears of mice in the model group, positive drug group, and toad oil cream low, medium, and high dose groups using a pipette, and the blank group was applied with an equal amount of solvent solution. On D5, 100 μL and 20 μL of 1% DNCB solution were applied to the back and right ears of mice in the model group, positive drug group, and toad oil cream low, medium, and high dose groups, and the blank group was applied with an equal amount of solvent solution.

[0101] 1.3 Administration

[0102] On D5, 1 hour after the stimulation, the drug was administered for 2 consecutive days, three times a day. The blank group and the model group were smeared with 40 mg of toad oil cream base, the positive drug group was smeared with 40 mg of compound dexamethasone acetate cream, and the low, medium and high dose groups of toad oil cream were smeared with 40 mg of toad oil cream with a mass fraction of 5%, 10% and 20% of toad oil, respectively.

[0103] 24 h after the last day of the experiment, the mice were killed by cervical dislocation, and their ears were removed and weighed to calculate the ear swelling rate, which was calculated as follows: ear swelling rate = right ear weight - left ear weight / left ear weight.

[0104] Preparation of pathological sections by hematoxylin-eosin staining (HE): The damaged tissues of the right ears of mice in each group were taken and fixed in 4% paraformaldehyde solution. After being fixed in a good state, they were dehydrated, trimmed, embedded, sliced, stained with hematoxylin and eosin, and sealed. The pathological changes of the right ears were observed under a microscope.

[0105] 1.4 Results

[0106] (1) Ear swelling rate

[0107] The results of ear swelling rate of mice in each group are shown in Figure 4 , among which, compared with the blank group, ## Indicates P < 0.01; compared with the model group, * indicates P < 0.05, ** indicates P < 0.01.

[0108] According to the results, compared with the normal group, the ear swelling rate of mice in the model group was increased, and the difference was significant (P < 0.01); compared with the model group, the ear swelling rates of the positive drug group and the low-, medium- and high-dose groups of toad oil cream were significantly decreased (P < 0.05 or P < 0.01), among which the effect of the low-dose group of toad oil cream was more obvious than that of the medium- and high-dose groups, and was equivalent to the effect of the positive drug compound dexamethasone acetate cream.

[0109] (2) Ear pathology section

[0110] Pathological section results Figure 5 As shown. The pathological sections of the ear showed that the epidermis, dermis and subcutaneous structures of the skin tissue in the blank group were still functional; the epidermis showed mild keratinization; the dermis and subcutaneous tissue were well connected and undamaged; the subcutaneous appendages were still intact, and no obvious vascular dilation, congestion and lymphocyte infiltration were observed in the interstitium. Compared with the blank group, the epidermis, dermis and subcutaneous layers of the skin tissue in the model group were damaged in structure and function; the epidermis showed mild keratinization; the dermis and subcutaneous tissue were well connected and undamaged, and the subcutaneous soft tissue was loose and edematous; the interstitial blood vessels were dilated, congested and hemorrhagic; the lymphocyte infiltration was angular, and the surface was accompanied by scabs. Compared with the model group, the structural functions of the epidermis, dermis and subcutaneous layer of the skin tissue in the positive drug group and the low, medium and high dose groups of toad oil cream gradually began to repair; the epidermis showed mild keratinization, the repair of the dermis and subcutaneous tissue was further strengthened, the subcutaneous soft tissue was moderately loose and edematous; the subcutaneous appendages increased significantly; the interstitial blood vessels were slightly dilated and congested; and there was a small amount of lymphocyte infiltration.

[0111] According to the records of clinical and experimental research literature, the present invention selects a glucocorticoid external-use drug, compound dexamethasone acetate, as a positive control drug, and investigates the efficacy of the toad oil cream of the present invention. The experimental results show that low, medium and high doses of the toad oil cream all have good therapeutic effects on contact dermatitis, wherein the effect of the low-dose group of the toad oil cream is equivalent to that of the positive drug compound dexamethasone acetate cream. The toad oil cream of the present invention has an obvious therapeutic effect on contact dermatitis.

Claims

1. Use of toad oil cream in preparing a drug for treating dermatitis, characterized in that: The toad oil cream is composed of toad oil and a matrix, wherein the matrix is ​​composed of the following components by weight: 2 parts of cetostearyl alcohol, 1 part of glyceryl monostearate, 8 parts of liquid paraffin, 2 parts of dimethicone, 0.1 part of propylparaben, 0.1 part of carbomer, 7 parts of glycerol, 2 parts of potassium lauryl phosphate, 1 part of hyaluronic acid, 0.2 parts of methylparaben, 57 parts of water and 0.1 part of triethanolamine; the mass fraction of the toad oil in the toad oil cream is 5-20%; The preparation method of toad oil comprises the following steps: S1: crushing toad viscera to obtain toad viscera mince; S2: heating the toad viscera mince obtained in step S1 and then centrifuging to obtain toad oil; in step S2, the heating method comprises heating the toad viscera mince in water; the heating temperature is ≤95°C; the heating time is ≤60min; The preparation process of the toad oil cream is as follows: 1) cetostearyl alcohol, glyceryl monostearate, liquid paraffin, dimethyl silicone oil and propylparaben are mixed, and stirred for 12 minutes to obtain a phase A emulsion; 2) carbomer, glycerin, potassium lauryl phosphate, hyaluronic acid, methylparaben and water are mixed, and stirred for 15 minutes to obtain a phase B emulsion; 3) phase A is added to phase B, heated to 85°C until completely dissolved, homogenized for 3 minutes, kept warm for 25 minutes, triethanolamine is added, and homogenized for 3 minutes to obtain the toad oil cream base, and toad oil is added to the toad oil cream base and homogenized to obtain.

2. The use according to claim 1, characterized in that The medicament is used to treat atopic dermatitis or contact dermatitis.

3. The use according to claim 1, characterized in that The drug is used to improve erythema, crusting and skin erosion caused by atopic dermatitis.

4. The use according to claim 1, characterized in that The medicament is used to improve the change of spleen index caused by atopic dermatitis.

5. The use according to claim 1, characterized in that: The drug is used to improve the inflammatory condition of ear swelling caused by contact dermatitis.

6. The use according to claim 1, characterized in that: The mass fraction of the toad oil in the toad oil cream is 5%.

7. The use according to claim 1, characterized in that The mass fraction of the toad oil in the toad oil cream is 10%.

8. The use according to claim 1, characterized in that The mass fraction of the toad oil in the toad oil cream is 20%.

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