CN117442672A - Compound medicine for treating chronic eczema and preparation method thereof - Google Patents
Compound medicine for treating chronic eczema and preparation method thereof Download PDFInfo
- Publication number
- CN117442672A CN117442672A CN202311670706.4A CN202311670706A CN117442672A CN 117442672 A CN117442672 A CN 117442672A CN 202311670706 A CN202311670706 A CN 202311670706A CN 117442672 A CN117442672 A CN 117442672A
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- eczema
- chronic eczema
- treating chronic
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Abstract
The invention relates to a compound medicine for treating chronic eczema and a preparation method thereof, wherein the compound medicine is prepared from 7 medicinal materials including viola yedoensis makino, flos clematis, chicory seed, humifuse euphorbia herb, rose, senna leaf and Abelmoschus manihot as raw materials, and the mixture is prepared by adding auxiliary materials into the raw materials respectively, fully and uniformly mixing the raw materials, extracting the raw materials by using a solvent, removing impurities, concentrating and drying the mixture. The animal experiment result shows that the medicine of the invention: can effectively improve symptoms such as eczema erythema, edema, moss and the like of a chronic eczema model of a rat caused by 2, 4-Dinitrochlorobenzene (DNCB), inhibit the increase of the percentage of blood mononuclear cells (MONO%), delay the skin damage process of the rat eczema in combination with pathological observation result analysis, and improve the skin damage symptoms. Has a certain protection effect on the rat eczema model. The compound medicine is based on Uygur medical theory and long-term famous medical clinical practice, combines modern researches, adopts a reasonable extraction method to dissolve out the effective components, enhances the medicine effect, improves the bioavailability and provides convenience for patients.
Description
Technical Field
The invention relates to a compound medicine for treating chronic eczema and a preparation method thereof, belonging to the technical field of medicines.
Background
Eczema (Eczema) is an inflammatory and allergic skin disease caused by a variety of internal and external factors. Rash is frequently and symmetrically developed in hands and feet, lower legs, fossa vaginalis, anus and the like. Western medicine classifies eczema into 3 types of acute eczema, subacute eczema and chronic eczema. Chronic eczema often persists from acute eczema and subacute eczema, and clinically manifests as pimples, scales, licheniform changes, paroxysmal severe itching and the like, and is repeatedly developed. Chronic Eczema (Chronic Eczema) refers to Eczema with Chronic, recurrent and difficult healing symptoms, and skin lesions are mainly characterized by lichenification and skin thickening, and are accompanied by polymorphic skin lesions such as pimples, crusts, scratches, pigment changes and paroxysmal itch. Patients with chronic eczema are easy to suffer from dysphoria, low sleep quality, poor interpersonal relationship and the like. The chronic eczema is mainly treated by 'controlling symptoms, reducing recrudescence and improving the life quality of patients', oral antihistamines, topical glucocorticoid preparations (topical corticosteroids, TCS) and the like, but the long-term use of the medicines can cause side effects such as drowsiness, somnolence, skin atrophy, pigment change, local irritation symptoms and the like, and even cause medicine dependence. The Uygur medical treatment of chronic eczema mainly uses internal regulation and external treatment, adopts conditioning or maturation and clearing therapy as key, and simultaneously carries out comprehensive treatment such as oral medicine therapy, external treatment therapy and the like, and simultaneously carries out comprehensive treatment combining diet management and emotion management. According to Uygur medical theory and clinical practice, the combination of modern researches is expected to develop a novel safe, effective and low-cost medicament for treating chronic eczema.
Reference is made to:
[1] liu Guohou, wang Qingliang, han Xinhai clinical researches on the treatment of chronic eczema with spleen deficiency and dampness accumulation by combining the decoction and the decoction of the dehumidification and the subtraction of the stomach and the fire needle [ J ]. International journal of Chinese traditional medicine, 2022,44 (9): 1001-1005.
[2] Xie Changcai, xu Nenggui, fu Wenbin, et al, needle punching was performed on the intervention effect of guinea pigs model for type IV allergy [ J ]. University of Guangzhou Chinese medical university, 2009,26 (02): 138-140+199.
[3] Li Changjiang, yang Xiqun, chen Deyu, etc. detection of IL-2, IL-5, IL-10 and EOS in blood of eczema patients and significance [ J ]. J.Chinese journal of dermatological diseases, 2007 (09): 537-538.
[4] Chen Lei A, li Zhongzheng, xi Jiang A clinical study of Fuzhi qing ointment in combination with levocetirizine for the treatment of chronic perianal eczema [ J ]. Modern medicine and clinic 2022,37 (01): 142-145.
[5]Furue M，Kadono T.New therapies for controlling atopic itch[J].The J Dermatol，2015Sep；42(9):847-50.
[6]Leung DY，Boguniewicz M，Howell MD，et al.New insights into atopic dermatitis[J].J Clin Invest，2004，113(3):651.
[7]Gittler JK，Shemer A，Suarez Farinas M，et al.Progressive activation of T(H)2/T(H)22cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis[J].J Allergy Clin Immunol，2012Dec；130(6):1344-54.
[8] Kong Xiaoxiu the pharmacodynamics and anti-inflammatory mechanism analysis of thalidomide cream for treating dermatitis eczema [ J ], 2019,6 (92): 154-155.
[9] Effects of Portulaca oleracea extract on expression of TNF-alpha and IL-4 in skin of acute eczema rats [ J ]. J.Chinese journal of immunology, 2014,30 (12): 1637-1640+1646.
[10] Wang Lu effects of thalidomide on skin lesions and serum IL-2, TNF-alpha, IL-12, IL-4 levels in elderly eczema patients [ J ]. J. Modern medicine and health Care electronics, 2020,4 (02): 183-185.
Disclosure of Invention
The invention aims at providing a compound medicine for treating chronic eczema and a preparation method thereof, wherein the compound medicine is prepared from 7 medicinal materials including viola diffusa, flos clematis, chicory seed, humifuse euphorbia herb, rose, senna leaf and Abelmoschus, and is prepared by respectively adding auxiliary materials including sodium benzoate and ethylparaben, mixing uniformly, extracting by using a solvent, removing impurities, concentrating and drying. The compound medicine is based on Uygur medical theory and long-term famous medical clinical practice, combines modern researches, adopts a reasonable extraction method to dissolve out the effective components, enhances the medicine effect, improves the bioavailability and provides convenience for patients.
The compound medicine for treating chronic eczema takes 100g as a base number, is prepared from the following raw materials of 5-30 parts of viola yedoensis makino, 5-30 parts of trollius chinensis, 5-30 parts of chicory seed, 5-30 parts of humifuse euphorbia herb, 5-30 parts of rose, 10-20 parts of senna leaf, 10-20 parts of Abamenia, 0.1-0.3% of auxiliary material sodium benzoate and 0.03-0.05% of ethylparaben, and comprises the following specific operations:
a. mixing and crushing 5-30 parts of screened viola diffusa, 5-30 parts of trollius chinensis, 5-30 parts of chicory seed, 5-30 parts of humifuse euphorbia herb, 5-30 parts of rose, 10-20 parts of senna leaf and 10-20 parts of Abelmoschus manihot to 10 meshes, and decocting with 4-20 times of water for 1-4 times for 30-60 minutes to obtain a mixed solution;
b. and d, precipitating the mixed solution obtained in the step a by using ethanol, wherein the concentration of the ethanol precipitation is 40-80%, filtering, recovering and concentrating, and uniformly mixing with 0.1-0.3% of sodium benzoate and 0.03-0.05% of ethylparaben by mass percent of auxiliary materials to obtain the compound medicine for treating chronic eczema.
The preparation method of the compound medicine for treating chronic eczema comprises the following steps:
a. mixing and crushing 5-30 parts of screened viola diffusa, 5-30 parts of trollius chinensis, 5-30 parts of chicory seed, 5-30 parts of humifuse euphorbia herb, 5-30 parts of rose, 10-20 parts of senna leaf and 10-20 parts of Abelmoschus manihot to 10 meshes, and decocting with 4-20 times of water for 1-4 times for 30-60 minutes to obtain a mixed solution;
b. and d, precipitating the mixed solution obtained in the step a by using ethanol, wherein the concentration of the ethanol precipitation is 40-80%, filtering, recovering and concentrating, and uniformly mixing with auxiliary materials of 0.1-0.3% of sodium benzoate and 0.03-0.05% of ethylparaben to obtain the compound medicine for treating chronic eczema.
The compound medicine for treating chronic eczema is used for preparing medicines with the effects of cooling blood, clearing heat, astringing, relieving itching and reducing swelling.
The compound medicine for treating chronic eczema is used for preparing medicines for treating inflammation, pruritus, flushing, red swelling, erosion and seepage.
The invention relates to a compound medicine for treating chronic eczema and a preparation method thereof, and animal experiment results show that: can effectively improve symptoms such as eczema erythema, edema, mossiness and the like of a chronic eczema model of a rat caused by DNCB, inhibit the increase of MONO% in blood, delay the progress of eczema skin lesions of the rat by combining with pathological observation result analysis, and improve the skin lesion symptoms.
Drawings
FIG. 1 is a graph showing the effect of the present invention on DNCB-induced skin lesions in a model of chronic eczema in rats;
FIG. 2 is a picture of the effect of the invention on DNCB-induced skin histopathology of a chronic eczema model of rats, wherein a is the normal group of male rats (% HE×100, pathological description: -, normal); b is the normal group of female rats (female, HE×100, pathological description: -, normal); c is a male rat model group (female parent, HE×100, pathological description ++, epidermic/dermal focal cell edema, massive inflammatory cell infiltration); d is female rat model group (female, he×100, pathological description: ++, numerous inflammatory cell infiltrates of epidermis \ dermis); e is a male rat positive drug group (, he×100, pathological description: ++, numerous inflammatory cell infiltrates of epidermis \ dermis); f is a female rat positive drug group (female, HE×100, pathological description: -, normal skin tissue and complete tissue structure); g is male rats, the administration group of the invention is male, HE×100, pathological description is +, epidermis has no obvious change and a small amount of inflammatory cells infiltrate; h is female rats and is the administration group (-, HE×100, pathological description-skin tissue is normal, and tissue structure is complete).
Detailed Description
Example 1 based on 100g
a. Mixing and crushing 5 parts of screened viola diffusa, 10 parts of flos clerodendri mollis, 15 parts of chicory seed, 30 parts of humifuse euphorbia herb, 30 parts of rose and 10 parts of senna leaf, and 10 parts of Abamenia herb, decocting with 4 times of water for 1 time for 30-60 minutes to obtain a mixed solution;
b. and d, precipitating the mixed solution obtained in the step a by using ethanol, wherein the concentration of the ethanol precipitation is 40%, filtering, recovering and concentrating, uniformly mixing with 0.1% of sodium benzoate and 0.05% of ethylparaben by mass percent of auxiliary materials, sterilizing, and canning to obtain the compound medicine for treating chronic eczema.
Example 2 based on 100g
a. Extracting 10 parts of screened viola diffusa, 5 parts of flos clerodendri mollis, 30 parts of chicory seed, 5 parts of humifuse euphorbia herb, 15 parts of rose and 15 parts of senna leaf with 10 times of water for 2 times, and decocting for 1-4 times for 30-60 minutes each time to obtain a mixed solution;
b. and d, precipitating the mixed solution obtained in the step a by using ethanol, wherein the concentration of the ethanol precipitation is 50%, filtering, recovering and concentrating, uniformly mixing with 0.3% of sodium benzoate and 0.03% of ethylparaben by mass percent of auxiliary materials, sterilizing, and canning to obtain the compound medicine for treating chronic eczema.
Example 3 based on 100g
a. Decocting 30 parts of screened viola diffusa, 20 parts of flos clerodendri mollis, 5 parts of chicory seed, 10 parts of humifuse euphorbia herb, 5 parts of rose and 20 parts of senna leaf with 15 times of water for 3 times, wherein the time for each time is 30-60 minutes, so as to obtain a mixed solution;
b. and d, precipitating the mixed solution obtained in the step a by using ethanol, wherein the concentration of the ethanol precipitation is 60%, filtering, recovering and concentrating, uniformly mixing with 0.2% of sodium benzoate and 0.04% of ethylparaben by mass percent of auxiliary materials, sterilizing, and canning to obtain the compound medicine for treating chronic eczema.
Example 4 based on 100g
a. 25 parts of screened viola diffusa, 30 parts of water lily flower, 20 parts of chicory seed, 20 parts of humifuse euphorbia herb, 20 parts of rose and 15 parts of senna leaf, and 20 parts of Abamenia herb are decocted with 20 times of water for 4 times, wherein the time for each time is 30-60 minutes, so as to obtain a mixed solution;
b. and d, precipitating the mixed solution obtained in the step a by using ethanol, wherein the concentration of the ethanol precipitation is 80%, filtering, recovering and concentrating, uniformly mixing with 0.15% of sodium benzoate and 0.035% of ethylparaben by mass percent of auxiliary materials, sterilizing, and canning to obtain the compound medicine for treating chronic eczema.
Example 5
1 materials and methods
1.1 laboratory animals
Clean SD rats used for the experiments were all supplied by the animal experiment center of Xinjiang university of medical science (license number: SCXK (New) 2018-0002). Animals were kept in the animal house of Uygur medical institute, uygur autonomous region in Xinjiang, as a barrier environment. The experimental facility license SYXK (new) 2018-0001. The animals are adaptively fed in the week before the experiment, the relative humidity is 40% -60%, the temperature is 20-24 ℃,12h illumination is alternated, purified water is freely drunk, large mouse quasi-pellet feed (supplied by Beijing family Australian feed limited company, chengdu Shuo experimental animal limited company, beijing family Australian feed production license number is Beijing feed (2018) 06073, experimental animal production license number is SCXK (Beijing) 2019-0003. Chengdu Shuo experimental animal production license number is SCXK (Sichuan) 2019-028, SPF grade rat and mouse maintenance feed is supplied). The animal experiment scheme in the research is approved by the ethical committee of the Uygur autonomous region Uygur medical hospital in Xinjiang, and all animal experiment operations accord with the 3R principle of experimental animals and the related ethical standard requirements of the welfare of the experimental animals at home and abroad;
1.2 experimental drugs:
1.2.1 medicines, reagents and instruments:
the medicinal materials are all obtained from unified government procurement of herbal medicine houses of Uygur autonomous region of Xinjiang, and all reach clinical medication standards;
sartorius CPA124S electronic balance, germany. Dehydrating: KDTS3D, kinhua Instrument and Equipment Co., ltd (EQ 2016-038) in Zhejiang. TP1020, leica (EQ 2016-039), germany. Embedding: KD-BMII, jinhua Kodi instruments and equipment Co., ltd (EQ 2016-034) in Zhejiang. KD-BMII, jinhua Kedi Instrument Co., ltd (EQ 2018-030) in Zhejiang. Slicing: RM2235, germany LEICA (EQ 2016-032). RM2245, leICA, germany (EQ 2016-033). Spreading and baking slices: KZPG-1A, tianjin Tianli aircraft electric company Limited (EQ 2016-040). And (3) a microscope: DM4000, leica (EQ 2016-037), germany. A low-speed high-capacity centrifuge, TDL-5-A, shanghai Anting scientific instrument factory, IL-4, IL-22, TNF-alpha, INF-gamma test box, nanjing build biological engineering research all company. XT-2000iv,Sysmex corporation; KOBE, JAPAN is available from Shenzhen Michael technologies Co., ltd;
1.2.2 preparation of experimental drug:
test agent: the invention relates to a compound medicine for treating chronic eczema; the daily dosage of the adult is 60g, and the concentration of the crude drug is 0.620 g/ml; converted into a mouse dosage of 6.2g/kg and a dosing volume of 10ml/kg;
positive control drug: positive control group: cetirizine hydrochloride tablet, abbreviated as ciclovir. Suzhou Dongrui pharmaceutical Co., ltd (pharmacy purchase date: 14 th of 2020); production date: 20191102; lot number: 191144202; specification 10 mg 12 tablets/box;
and (3) molding agent: 2, 4-Dinitrochlorobenzene (DNCB), shanghai Jiedang chemical technology Co., ltd., batch number: 97-00-7.
The preparation method of the molding agent comprises the following steps: the composition was used in the form of 7% DNCB acetone solution. Positive control group preparation method: when in use, the animal drinking water is used for preparing 0.2mg (calculated by cetirizine hydrochloride)/mL solution, and the magnetic stirrer is continuously and evenly mixed for administration when in administration, and the administration volume is 10mL/Kg;
1.3 method:
1.3.1 grouping and administration of animals:
the adaptive period of SPF-class SD rats of 5-7 weeks old is ended, the weight of animals is called the next day, the animals are randomly divided into 2 groups according to weight layering, 10 animals are respectively in a normal group, 50 animals are in a model group, and the male and female animals are half. After the modeling is finished, about 30 rats are modeled in a model group, animal weights are weighed the next day, animals are randomly divided into 3 groups (1/cage) according to model grading layering, and the model group, the positive control group and the administration group are respectively 10 animals per group and each half of the animals are male and female;
the molding method comprises the following steps: the back skin A, B of the rat is provided with an electric shaver for removing the animal neck and back (A) and back hair (B), wherein the area of the A is 2cm multiplied by 2cm, and the area of the B is 4cm multiplied by 4cm; the skin of the rat is coated with 100 mu L of 7%2, 4-Dinitrochlorobenzene (DNCB) acetone solution by a pipetting gun at the A site, and the rat is sensitized, so that the itching of the rat is severe, the scratching and rolling actions occur frequently, and the duration is about 2 hours; after 1 week 200 μl of 7%2, 4-Dinitrochlorobenzene (DNCB) acetone solution was applied at B for excitation; 1 time of excitation is performed every 5 days, each time of excitation can see severe itching of rats, and the behavior of grabbing and rolling frequently occurs; the skin at the position B gradually shows erythema, papule, edema, scratch and desquamation, after each excitation, the skin damage condition is recorded and scored, until after 6 excitation, the skin damage at the back of each mouse shows erythema, papule, crusting and exudation, the excitation is stopped, the preparation of the model is successful, and the model lasts for not less than 9 days;
route and method of administration: dehairing is carried out once before sensitization in the molding period, and dehairing is carried out 1 time per week in the administration period; gastric lavage administration, same as clinical administration route, administration time and frequency: dosing in the morning; frequency of administration: dosing period 1 time daily: continuous administration for 14 days;
1.3.2 observation and detection:
(1) General state observation: the content is observed: observing and recording the general conditions, hair color, activities, gait, mind states, stool and other conditions of animals every day;
(2) Weight of: modeling 0, 8, 15, 22, 29, 35 (D0) and weighing the animals on days D0, 7, 14;
(3) Food intake: modeling 0, 8, 15, 22, 29, 35 (D0) and weighing the animals on days D0, 7, 14;
(4) And (3) appearance index observation: the appearance index plays an important role in clinical diagnosis of eczema and is also a direct index of success or failure of animal models. After the eczema animal model is successfully prepared, the animal has itching, skin damage, erythema, reduced glossiness of fur, reduced activity and the like with different degrees; (1) itching conditions: eczema is often accompanied by itching, and the itching response of animals can be observed. Such as observing the number of times of licking the itching part of the mice within 10min, the duration of each itching, and the like; (2) skin lesions are local: skin lesion morphology, skin lesion area size, skin exudation, degree of edema, etc.; (3) gloss of fur. Measuring instrument: and taking a picture by a camera and observing by naked eyes. Measurement frequency: molding for days 1, 5, 10, 15, 20, 25, 30, 35, and dosing for days 0, 8, and 14, as detailed in Table 1;
TABLE 1 hierarchical table of eczema symptoms
(5) Fasted, anesthetized, sacrificed: stopping feeding and water for 10-16 hours, injecting 4ml/Kg of 1% pentobarbital sodium into abdominal cavity to perform anesthesia (dosage is 40 mg/Kg), collecting blood after anesthesia according to the following method, cutting abdominal aorta and continuously wiping abdominal cavity blood with cotton ball after blood collection is completed, until animal blood is completely put and dies; because a certain time is needed for processing animals, in order to avoid the influence of different fasted time on detection data and also to reduce the operation error between groups, animals are sacrificed by adopting a serpentine sequence method, namely, one animal in four groups is sacrificed in each round;
(6) Organ weight and coefficient: the following organs were weighed, and the organ coefficients (g organs/100 g body weight) were calculated according to the fasted body weight of each animal: spleen and thymus. If compared with the control group, the weight of the administration group is obviously changed, which may cause obvious change of organ coefficients; at this time, the heart brain factor (g organs/g brain weight 100%) can be calculated and analyzed. Provided that there should be no significant difference in brain weights for each group;
(7) Hematology assay: white blood cell count (WBC), percent Lymphocyte (LYM), percent Neutrophil (NEUT), percent Eosinophil (EOS), percent BASO, percent monocyte (monono%) and platelet count (PLT);
(8) Serum index determination: after blood collection, the mixture is placed into a disposable centrifuge tube, and centrifuged at 3000rpm for 10min after standing for at least 30min, and the supernatant is serum. Measurement indexes include IL-4, IL-22, TNF-alpha and INF-gamma;
(9) Skin pathology examination: the method comprises the following steps: after anesthesia, the animals are sacrificed by bleeding, the appearance of the animals and the skin (the administration position) are observed visually, the skin is fixed by 10% neutral formalin, embedded by paraffin and sectioned; staining with HE (haematomxylin & Eosin), and observing histomorphology with a microscope; description of pathology: the local skin pathological change of the eczema model is an observation index commonly adopted in experimental research, and the mirror of the local skin tissue is visible after the model is successfully prepared: excessive and incomplete keratinization of epidermis, intracellular edema and blisters, thickening of the acantha layer, prolongation of the skin process, and no blisters; dermal layer capillary expansion, congestion, or peripheral lymphocyte-based inflammatory cell infiltration with slightly increased collagen in the upper dermis; the local skin pathological change of eczema is a reliable index for judging the skin damage degree, and the pathological semi-quantitative grading reference standard is "-" which indicates that skin tissues are normal and the tissue structure is complete; "+" indicates no obvious change of epidermis, and a small amount of inflammatory cells infiltrate in the upper part of dermis; "++" indicates epidermofocal cellular edema, massive inflammatory cell infiltration in the upper dermis; "+++". Representing epidermis a reticulate pattern of lesions, the upper part of dermis is infiltrated by a plurality of inflammatory cells;
1.4 statistical treatment:
statistical tests were performed with SPSS26.0 using one-way analysis of variance (ANOVA): firstly, comparing the overall average values of all groups, and judging that no difference in statistical significance exists among all groups if P is more than or equal to 0.05; otherwise, continuing to perform a many-to-one comparison between the administration group and the control group, and using the LSD method for the variance alignment and Tamhane's T for the variance alignment according to the variance alignment test result 2 A method; for ease of comparison, the dosing group data compare the percentage of mean change and coefficient of variation (standard deviation/mean 100%) to the control group; the significance level of the statistical test is 0.05;
2 results and analysis:
2.1 general state observations:
in quarantine period and adaptation period, all animals do not die, 10 animals do not meet the condition of group entering or deviate from average value greatly after molding, are removed and killed, all animals in administration period do not die, the activities, gait and the like of the animals are normal, abnormal secretion of mouth, nose and eyes is avoided, abnormal changes such as dyspnea and the like are not seen, and gastrointestinal reactions such as vomiting and diarrhea are not seen; body weight and food intake during modeling and dosing, no statistical differences (P < 0.05) occurred for each group compared to the control group;
2.2 appearance index observation:
2.2.1 during molding:
after sensitization of the model group in zone a, the skin abnormality continued until day 10 resolved; after B-zone excitation, the apparent score increased significantly, but fluctuated over time. Score increased upon re-challenge; as shown in tables 2 and 3;
TABLE 2 apparent scoring of the A region (sensitized region) of rats of each group during modeling
Note that: comparison with model control group ** P<0.01；
TABLE 3 apparent scoring of the B region (excitation region) of rats of each group during modeling
Note that: comparison with model control group ** P<0.01；
2.2.2 dosing period:
after day 14 of dosing, there was a significant decrease in apparent scores for each dosing group compared to the model group, the differences were statistically significant (P < 0.01), as shown in table 4;
TABLE 4 apparent scores of zone B (challenge zone) for rats of each group during dosing period
Note that: comparison with the blank control group ## P<0.01; comparison with model control group * P<0.05， ** P<0.01。
End of dosing, blank group: the skin of the back of the rat is light red, fine, smooth and tender, soft in texture and clear in skin texture. Chronic eczema model group: the skin damage of the back of the rat is obvious, and skin erythema, infiltration, scaling, crusting, rough thickening, pigmentation and scratch can be seen, and the diagnosis standard of chronic eczema is still met. Each dosing group: compared with the model group, the back skin damage of the rats in each administration group is improved, and erythema, infiltration, scaling, crusting and the like are obviously reduced or resolved, as shown in figure 1;
2.3 organ weight and coefficient:
2.3.1 spleen weight and coefficient:
compared with a blank control group, the spleen weight of the rats in the model group is obviously increased, and the difference has statistically significant significance # P<0.05). Compared with the model group, the spleen weight of each group of rats is slightly reduced, but the difference has no significance in statistics; compared with a blank control group, the spleen coefficient of the rats in the model group is obviously increased, and the difference has statistically significant significance ## P<0.01 A) is provided; compared with the model group, the spleen coefficient of the positive control group rats is obviously reduced, and the difference has statistically significant significance (P)<0.05 A) is provided; as shown in table 5;
table 5 spleen weights and spleen indices for each group of rats during the dosing period
Note that: comparison with the blank control group # P<0.05， ## P<0.01; comparison with model control group * P<0.05。
2.3.2 thymus weight and coefficient:
compared with the blank control group, the thymus weight and coefficient of the rats in the model group are slightly reduced, but the difference has no statistically significant meaning (P is more than 0.05); compared with the model group, the thymus weight and coefficient of each group of rats were slightly reduced, but the differences were not statistically significant (P > 0.05), as shown in table 6;
TABLE 6 thymus weights and thymus indexes of rats of each group in the administration period
2.3.3 liver weight and coefficient:
compared with the blank control group, the liver weight and coefficient of the rats in the model group are slightly reduced, but the difference has no statistically significant significance (P is more than 0.05); compared with the model group, the liver weight and coefficient of each group of rats are slightly increased or decreased, but the difference has no statistically significant meaning (P > 0.05); as shown in table 7;
TABLE 7 liver weights and liver indices for groups of rats during the dosing period
Note that: comparison with the blank control group # P<0.05；
2.4 hematology assay:
compared with a blank control group, the LYMPH percent of the model group is obviously reduced, the MONO percent is obviously increased, the EO percent is obviously increased, and the differences have statistically significant significance ## P<0.01 A) is provided; compared with the model group, the WBC of the rat in the administration group of the invention is obviously increased, and the difference has statistically significant significance * P<0.05 A) is provided; the positive control group, NEUT%, was significantly elevated, the differences were statistically significant (respectively: * P<0.05 A) is provided; the MONO% of the positive control group and the administration group of the invention is obviously reduced, and the difference has statistically significant significance ** P<0.01 A) is provided; as shown in tables 8, 8-1;
table 8 rat hematology index detection
Note that: comparison with model control group * P<0.05。
TABLE 8-1 rat hematology index detection(subsequent)
Note that: comparison with the blank control group ## P<0.01; comparison with model control group ** P<0.01。
2.5 serum index determination:
compared with a blank control group, the model group has slightly raised TNF-alpha and IFN-gamma, slightly reduced IL-4 and IL-22, but the difference has no statistically significant meaning, and compared with the model group, the administration group has significantly raised TNF-alpha and statistically significant meaning ** P<0.01 A) is provided; the positive control group showed significantly reduced IL-22, and the differences were statistically significant (respectively: * P<0.05、 ** P<0.01 As shown in table 9;
TABLE 9 rat serum index detection
Note that: comparison with model control group * P<0.05， ** P<0.01；
2.6 dermatopathology examination:
normal group rats had normal skin stratum corneum, epidermis layer, dermis layer thickness; the pathological section of the model group rat has pathological manifestations of chronic eczema, such as hyperkeratosis, hypokeratosis, hypertrophic granular layer, hypertrophic acantha layer and numerous inflammatory cell infiltration of epidermis/dermis. After 14d of the medicine is used, the invention group and the positive control group can inhibit excessive keratinization, insufficient keratinization, thickening of a granular layer and thickening of a acantha layer, and the infiltration of epidermal/dermal inflammatory cells is improved;
wherein: the number of animals with the model group skin damage degree of "++" + + + ", the skin/dermis infiltration of numerous inflammatory cells is 6, the positive control group and the administration group of the invention are respectively 4 or 2, wherein the improvement condition of the infiltration of the epidermal/dermal inflammatory cells of the administration group of the invention is better;
the number of animals healed by the model group, the positive control group and the administration group of the invention is 1, 6 or 5 respectively, wherein the number of animals healed by the positive medicine group and the administration group of the invention is relatively large, and each group has obvious difference with the skin pathology classification (P < 0.05);
the invention can delay the eczema skin lesion process of rats, improve the skin lesion symptom, mainly control the skin lesion to have no obvious change and little inflammatory cell infiltration, and the invention administration group is relatively better than other groups according to the analysis of pathological observation results, and the results are shown in fig. 2 and table 10;
TABLE 10 grading the skin histopathological examination of DNCB-induced chronic eczema model of rats by the inventive formulation
The study utilizes 2, 4-Dinitrochlorobenzene (DNCB) to induce SD rats to construct a chronic eczema model, and the skin damage, blood, serum and pathological changes are observed. The result shows that the skin and pathological tissue of the molding module are obviously more seriously changed than those of a normal control group, thus showing that the molding is successful; spleen, thymus and liver coefficients are important indicators reflecting humoral immunity, and directly or indirectly reflect the immune function state of the organism. Compared with the blank control group, the spleen coefficient of the rats in the model group is obviously increased, and the eczematoid pathological change is obvious. Compared with the model group, the spleen coefficient of the positive control group rats is obviously reduced; however, the coefficients of spleen, thymus and liver are not changed in the administration group, so that the influence of the administration group on humoral immunity is probably low or the experiment time is long, and the normal level is recovered, and the administration group is required to be further studied later;
chronic immune inflammatory injury is one of important pathogenesis of chronic eczema, and the research shows that after detecting blood measurement and inflammatory factor measurement in serum,the 2, 4-Dinitrochlorobenzene (DNCB) causes the significant increase of MONO% in the blood of the chronic eczema model rats, the eosinophil percentage (EOS%) tends to increase, and the positive medicine and the administration group of the invention can obviously reduce the blood MONO% value of the eczema model rats. It has been shown that DNCB ex-use sensitization and repeated excitation methods replicate guinea pig type IV allergy model monocytes, eosinophil numbers are significantly increased, and Eosinophil (EOS) of eczema patients are higher than normal, and in the course of eczema patients, activated mast cells can induce activation, proliferation and differentiation of human eosinophil, can promote maturation of eosinophil, mature eosinophil can release ECP (eosinophil cationic protein), induce mast cells to release histamine, mediate eosinophil percentage (EOS%) and keratinocyte destruction, so that monocyte percentage (MONO%) and eosinophil percentage (EOS%) play an important role in the pathogenesis of eczema. Cetirizine hydrochloride tablet in the study is taken as a positive control drug and is antihistamine H 1 Receptor antagonists, inhibiting leukotriene B production by leukocytes 4 Thus inhibiting the delayed phase of anaphylactic reaction, compared with a model group, the relative indexes of the administration group and the positive control group are reduced, inflammatory cell infiltration is reduced, NEUT% and IL-22 are reduced, and the chronic eczema is influenced in the same way;
chronic eczema has a complex pathogenesis and plays an important role in immune imbalance, especially Th1/Th2 imbalance. IFN-gamma is mainly secreted by Th1 cells, and can inhibit IL-4 secretion by Th2 cells and IgE production by B cells; IL-4 is mainly secreted by Th2 cells, mainly inhibits the functions of Th1 cells, promotes B cells to generate IgE, and mutually inhibits and antagonizes the two to maintain the balance of Th1/Th 2; normal human IFN- γ, IL-4 expression levels remain in a relatively balanced state, but chronic eczema patients lose this balance. Previous studies have shown that Th2 signals dominate the acute phase of disease, while in the chronic phase Th2 is shifted to predominantly Th1 signals; it was found that in chronic eczema patients, the IL-4 level was not statistically significant nor significantly elevated from the normal control group. The improvement of IL-4 of a mice/guinea pigs chronic dermatitis/eczema model induced by Dinitrochlorobenzene (DNCB) is also reduced, and the method has no unified standard. In addition, there are papers reporting that IL-4 is not decreased but is increased after treatment of eczema patients, which is consistent with the results of the study.
In conclusion, the compound medicine for treating chronic eczema and the preparation method thereof provided by the invention can effectively improve symptoms such as eczema erythema, edema, lichenification and the like of a rat chronic eczema model caused by Dinitrochlorobenzene (DNCB), inhibit the increase of the blood mononuclear cell percentage (MONO%), delay the skin damage process of the rat eczema in combination with pathological observation result analysis, and improve the skin damage symptoms.
Claims (4)
1. The compound medicine for treating chronic eczema is characterized by taking 100g as a base number, and is prepared from the following raw material medicines of 5-30 parts of viola yedoensis makino, 5-30 parts of trollius chinensis, 5-30 parts of chicory seed, 5-30 parts of humifuse euphorbia herb, 5-30 parts of rose, 10-20 parts of senna leaf, 10-20 parts of Abamenia robusta, 0.1-0.3% of auxiliary material sodium benzoate and 0.03-0.05% of ethylparaben, wherein the specific operation comprises the following steps:
a. mixing and crushing 5-30 parts of screened viola diffusa, 5-30 parts of trollius chinensis, 5-30 parts of chicory seed, 5-30 parts of humifuse euphorbia herb, 5-30 parts of rose, 10-20 parts of senna leaf and 10-20 parts of Abelmoschus manihot to 10 meshes, and decocting with 4-20 times of water for 1-4 times for 30-60 minutes to obtain a mixed solution;
b. and d, precipitating the mixed solution obtained in the step a by using ethanol, wherein the concentration of the ethanol precipitation is 40-80%, filtering, recovering and concentrating, and uniformly mixing with 0.1-0.3% of sodium benzoate and 0.03-0.05% of ethylparaben by mass percent of auxiliary materials to obtain the compound medicine for treating chronic eczema.
2. The preparation method of the compound medicine for treating chronic eczema is characterized by taking 100g as a base number and comprises the following steps:
a. mixing and crushing 5-30 parts of screened viola diffusa, 5-30 parts of trollius chinensis, 5-30 parts of chicory seed, 5-30 parts of humifuse euphorbia herb, 5-30 parts of rose, 10-20 parts of senna leaf and 10-20 parts of Abelmoschus manihot to 10 meshes, and decocting with 4-20 times of water for 1-4 times for 30-60 minutes to obtain a mixed solution;
b. and d, precipitating the mixed solution obtained in the step a by using ethanol, wherein the concentration of the ethanol precipitation is 40-80%, filtering, recovering and concentrating, and uniformly mixing with 0.1-0.3% of sodium benzoate and 0.03-0.05% of ethylparaben by mass percent of auxiliary materials to obtain the compound medicine for treating chronic eczema.
3. Use of a compound medicament for treating chronic eczema according to claim 1 or 2 in preparing medicament for cooling blood, clearing heat, astringing, relieving itching and detumescence.
4. Use of a compound medicament for treating chronic eczema according to claim 1 or 2 in the preparation of a medicament for treating inflammation, itching, flushing, red swelling, erosion and infiltration.
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