CN107998116B - Application of acetamide in anti-psoriasis medicine - Google Patents

Abstract

The acetamide has obvious effects on resisting inflammation, has obviously reduced levels of I L-17F and TNF-alpha in serum, and has high expression of I L-22, so that the acetamide has the effects of resisting inflammation and immunosuppression, has the effects of regulating nonspecific immunity and specific immunity, can increase the generation level of serum antibodies, can up-regulate the levels of I L-1 β and I L-6 in serum, can down-regulate the level of TNF- α in serum, and can obviously increase thymus coefficient, has obvious effects on resisting psoriasis, can down-regulate the levels of I L-17F and I L-23 in serum, and can be used as marker cytokines of psoriasis, and has an improvement effect on cells of epidermal layer, spinous layer and dermal layer.

Description

Application of acetamide in anti-psoriasis medicine

Technical Field

The invention relates to the technical field of medicines for immunoregulation, in particular to application of acetamide in an anti-psoriasis medicine.

Background

The immunity is generally divided into two types, innate immunity and adaptive immunity, the innate immunity has wide specificity, the recognition mechanism is conserved PAMP (pathogen-associated molecular pattern), and the receptor is PRR; the adaptive immunity has very accurate specificity, reflects the individual characteristics of pathogens, and has antigen recognition receptors of TCR and BCR. The innate immune response is the first line of defense of the host against pathogenic microorganisms and initiates and participates in the adaptive immune response; adaptive immunity is a highly effective defense mechanism against pathogenic microorganism infection with body availability and antigen specificity. In recent years, basic immunological research and clinical disease prevention and treatment are closely connected by domestic immunological research teams, and the novel academic view and breakthrough research progress are provided on serious diseases related to immunological mechanisms and affecting human health, such as infectious diseases, autoimmune diseases, tumors and the like.

Antibodies are glycoproteins which are mainly present in blood and tissue fluid and are also called immunoglobulin, are mainly produced by plasma cells generated by proliferation and differentiation of B cells stimulated by antigens, can be specifically combined with the antigens, and are important effector substances in humoral immunity. As early as 1890, in the work of Emil von Behring and his colleagues in Germany, it was found that the sera of animals immunized with the fire-extinguishing tetanus bacterium contain substances which neutralize the toxin, and the transfer of the sera of the immunized animals to other animals resulted in the development of specific immunity against tetanus bacterium, so that the production and mechanism of action of antibodies was slowly clear. With aging, the immune function of human body to foreign antigen is reduced, Whittingham finds that the IgG antibody produced by the first immunization is slow in the infiltration of the old human anti-bacterial body, and the titer of the IgG antibody after the second immunization is obviously lower than that of the young human. In 1975, the results of a hemolysin experiment in which sheep red blood cells were stimulated in mice of 0 to 45 months of age (corresponding to 0 to 105 years of age) demonstrated that the antibody levels of the mice increased gradually at 0 to 7.5 months of age (corresponding to 0 to 17.5 years of age), and decreased gradually at 7.5 to 45 months of age (corresponding to 17.5 to 105 years of age). Therefore, it is highly desirable to increase the levels of antibodies in the elderly, thereby improving the immunity of the elderly.

Cytokines are glycoproteins with molecular weights below 80 kd in vivo, and are present in very low amounts but act at pg levels.cytokines are generally produced when cells are stimulated, but may also spontaneously produce, for example, I L-1. the target cells are usually cells themselves or adjacent cells, and have the same activity or different cytokines have the same activity, and usually multiple cytokines form a network with each other to regulate and play a role.

In contrast, the immune organs of the elderly gradually degenerate with age, and it has been clinically proven that the thymus is about 11g at birth, the most at puberty (10-12 years old), about 35g, and has a sharp withdrawal after sexual maturity, and the weight is only 15g at 60 years old. The degeneration of immune organs also further confirms the cause of an imbalance in cytokine levels within immune cells.

Therefore, the present invention is necessary to provide an immunomodulator against the decline of immunity due to aging.

Psoriasis (psoriasis), on the other hand, is a chronic inflammatory proliferative skin disease that is cell and molecule mediated in association with the innate and adaptive immune systems.

The histopathology of clinical psoriasis is mainly manifested by hyperproliferation of keratinocytes, thickening of the stratum spinosum, increase of inflammatory cells, and expansion of vascular hyperplasia. In addition, another characteristic of psoriasis is the expression of multiple cytokines at the site of the skin lesion. Dexamethasone is generally adopted for treating psoriasis at present, is an artificially synthesized corticosteroid and is a glucocorticoid hormone. However, the long-term use of large amounts of glucocorticoids can cause substance metabolism and water and salt metabolism disorders, and can lead to adrenocortical-like hyperfunction syndromes, such as edema, hypokalemia, hypertension, diabetes, thinning of the skin, full moon face, buffalo back, central obesity, hirsutism, acne, muscle weakness and muscular atrophy. For children, growth and development are affected by negative nitrogen balance caused by inhibition of growth hormone secretion.

Therefore, the invention also needs to provide a new medicine which can replace dexamethasone and is used for treating psoriasis.

However, no report has been made on the use of acetamide for immunomodulation, psoriasis.

Disclosure of Invention

The technical problem to be solved by the invention is to provide the application of acetamide in anti-inflammatory drugs, immunomodulators and anti-psoriasis drugs.

In order to solve the technical problems, the invention provides an application of acetamide in preparing anti-inflammatory drugs, wherein the structural formula of acetamide is as follows:

as an improvement of the scheme, the dosage of the acetamide is 0.2-2 g/kg.

Accordingly, the present invention provides the use of an acetamide for the preparation of an immunomodulator, the acetamide having the formula:

as an improvement of the scheme, the dosage of the acetamide is 0.7-6 g/kg. The concentration of the acetamide is 0.035-0.3 g/ml.

As a modification of the above, the immunomodulator is a non-specific immunomodulator; alternatively, the immunomodulator is a specific immunomodulator; or the immunomodulator has both nonspecific immunity and specific immunity functions.

Correspondingly, the invention discloses an application of acetamide in preparing anti-psoriasis drugs, wherein the structural formula of acetamide is as follows:

as an improvement of the scheme, the dosage of the acetamide is 0.7-2 g/kg.

The implementation of the invention has the following beneficial effects:

the invention utilizes acetamide micromolecule, the molecular weight of which is only 59.07, has obvious effects on anti-inflammation, immune bidirectional regulation and psoriasis resistance, and specifically comprises the following components:

firstly, acetamide has obvious effect on anti-inflammation, the levels of I L-17F and TNF-alpha in serum are both remarkably reduced, the expression of I L-22 is increased, and I L-22 belongs to members of I L-10 family, and is a cytokine which can be generated by both innate immunity and adaptive immunity of people, and the acetamide can be inferred to have the effects of anti-inflammation and immunosuppression by combining the reduction of the expression levels of tumor necrosis factor TNF-alpha generated by innate immunity and I L-17F generated by innate immunity, and plays a role in acquired immunity and adaptive immunity at the same time.

Acetamide can raise the serum antibody producing level of hypoimmunity model mouse and normal mouse, raise the level of I L-1 β and I L-6 in serum and lower the level of TNF- α in serum, and raise the thymus coefficient obviously.

The acetamide has obvious effect on resisting psoriasis, can reduce the expression level of I L-17F and I L-23, I L-17F and I L-23 in serum as psoriasis marker cytokines, and the reduction of the expression level indicates that the acetamide plays a role in T lymph immunity to improve the skin of psoriasis-like skin lesions.

Drawings

FIG. 1 is a graph of the change in the PASI score of animal skin;

FIG. 2A is a graph of the condition of the skin of an animal (A. blank control group; B. imiquimod model group; C. dexamethasone positive group);

FIG. 2B is a graph of animal skin conditions (D. acetamide high dose group; E. acetamide medium dose group; F. acetamide low dose group);

FIG. 3A shows HE stained sections of mice in each group treated for 12 days of skin pathology (A. blank control group; B. imiquimod model group; C. dexamethasone positive group);

fig. 3B shows HE stained sections of mice in each group treated for 12 days of skin pathology (d. acetamide high dose group; e. acetamide medium dose group; f. acetamide low dose group).

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be described in further detail with reference to the accompanying drawings.

There are many drugs and health products for enhancing immunity clinically, including levamisole, astragalus polysaccharide, active peptide of newborn bovine liver, etc., and there are many acetamide derivatives, or compounds containing acetamide, but there are few small molecular substances.

To this end, the present invention provides the use of an acetamide for the preparation of an immunomodulator, the acetamide having the formula:

acetamide is also named as acetoamide and has the molecular formula of CH₃CONH₂The molecular weight was only 59.07. A compound produced by substituting a hydroxyl group in acetic acid with an amino group.

The dosage of the acetamide is 0.7-6g/kg, and the concentration of the acetamide is 0.035-0.3 g/ml. Specifically, the dosage of the acetamide can be 0.7g/kg, 2g/kg and 6g/kg, but is not limited thereto. The concentration of the acetamide can be 0.035g/ml, 0.1g/ml and 0.3g/ml, but is not limited to the above.

Acetamide has regulating effect on both non-specific immunity and specific immunity. The immunomodulator is therefore a non-specific immunomodulator; alternatively, the immunomodulator is a specific immunomodulator; or the immunomodulator has both nonspecific immunity and specific immunity functions.

The role of acetamide in immunomodulation is further discussed below in connection with experiments

1. Grouping animals

Another 90 male KM mice are taken, after adaptive feeding for three days, are randomly divided into 8 groups of a blank control group, a cyclophosphamide model control group, a spleen aminopeptide non-model group, a spleen aminopeptide-cyclophosphamide model group, an acetamide high-dose non-model group, an acetamide high-dose, medium-dose and low-dose cyclophosphamide model group (namely, one non-model group is additionally arranged in the positive control group and the acetamide high-dose and medium-dose groups), and 10 mice are taken in each group. The animals of each group are administrated by gastric gavage, a blank control group and a cyclophosphamide model control group are administrated with distilled water, a spleen aminopeptide non-model group and a spleen aminopeptide-cyclophosphamide model group are administrated with spleen ampeptide, the dosage is set to be 0.8mg/kg, the high, middle and low dosages of tested samples acetamide are respectively 6g/kg, 2g/kg and 0.7g/kg, the acetamide samples are dissolved by distilled water, the concentrations of the high, middle and low dosages of acetamide are respectively 0.3g/ml, 0.1g/ml and 0.035g/ml, all animals are continuously administrated for 30 days, the administration volume is 20ml/kg, and the weight is measured for 1 time per week.

2. Detection of antibody production levels-serum hemolysin assay

Animals in each group were immunized by intraperitoneal injection of 0.2ml of 2% packed sheep red blood cells on the 25 th day of continuous administration. After 5 days, collecting 300-400 ul blood of all animal orbital veins in a centrifugal tube, standing at room temperature for about 1h, stripping coagulated blood from the tube wall to fully separate out serum, centrifuging at 3500rpm for 10min, and collecting the serum. Serum is diluted by multiple times by normal saline, serum with different dilutions (1: 2, 1:4, 1:8, 1:16, 1:32, 1:64, 1:128, 1:256, 1: 512) is respectively placed in a 96-hole round bottom cell plate, 100 mul of each hole is added, 100 mul of 0.5% (v/v) SRBC suspension is added, the mixture is mixed evenly, the mixture is placed in a wet flat disc and covered, the mixture is incubated for 3 hours at 37 ℃, the hemagglutination degree is observed, and the hemagglutination degree of the serum is generally recorded in 5 grades (0-IV).

Antibody level (S1 +2S2+3S3 … … nSn)

In the formula, 1, 2 and 3 … … n represent indexes of double dilution, S represents the grade of agglutination degree, and the larger the antibody volume number, the higher the serum antibody.

The 0-level red blood cells all sink and are concentrated at the bottom of the hole to form a compact round point shape, and the liquid around the hole is clear.

Most of the I-grade red blood cells are deposited at the bottom of the hole to form a round point shape, and a small amount of agglutinated red blood cells are arranged at the periphery of the hole.

The level II agglutinated red blood cells form a thin layer at the bottom of the hole, and a loose red spot can be obviously seen at the center.

The level III agglutinated red blood cells are uniformly spread at the bottom of the hole to form a thin layer, and a small red spot is invisible at the center.

The grade IV agglutinated erythrocytes are uniformly spread at the bottom of the hole to form a thin layer, and the clumps are sometimes rolled up.

3. Establishment of immune hypofunction mouse model

Except for the negative control group, one of the high dose group and the positive control group, the remaining 5 groups of mice were administered 3 days after the beginning of intraperitoneal injection of 80mg/Kg body weight of cyclophosphamide in large dose to each mouse on day 27.

4. Animal dissection and index determination

4.1 index determination

Enzyme linked immunosorbent assay (E L ISA) for detecting the content of TNF- α, I α 0-1 α 1, I L-6 and IFN-gamma in peripheral serum of mice, removing eyeballs from mice of each group in the last administration day, collecting blood, detecting the content of each cytokine and interferon in serum by double antibody sandwich E L ISA method, calculating the content of TNF- α, I L-1 β, I L-6 and IFN-gamma according to standard curve (taking the detection of the content of I L-1 β in serum as an example)

4.2 organ index measurement

After blood is taken from each group of mice, cervical vertebrae are dislocated and killed, the thymus and spleen which are main immune organs of the mice are taken, the weights are weighed, and the organ coefficients are calculated.

Example spleen factor = spleen mass (mg)/body mass (g) × 100%

5. Results of the experiment

5.1 antibody production levels

Compared with the blank group, the antibody in the model group is significantly inhibited (P < 0.01), the antibody level in the spleen aminopeptide non-model group, the acetamide high-dose non-model group and the acetamide medium-dose non-model group is significantly or even extremely significantly increased (P <0.05, P < 0.01); compared with the model group, the antibody level groups of the spleen aminopeptide model group and the acetamide high, medium and low dose model groups are all extremely obviously increased (P < 0.01), and the antibody production level changes in serum under different conditions are detailed in a table 2-1.

5.2 cytokine levels in serum

The serum I L- β of the spleen aminopeptide non-model group and the serum I L- β of the acetamide high-dose and medium-dose non-model groups are obviously increased compared with the blank group, and TNF- α is shown to be obviously reduced (P < 0.05), after the model is established, the serum I L- β level of the model group is obviously increased (P < 0.05) compared with the blank group, the residual indexes are not obviously changed (P < 0.05), the serum I L-6 level of the acetamide high-dose group in the drug group is obviously increased (P < 0.05) compared with the model group, and other indexes of the rest drug groups are not obviously changed (P > 0.05), and the level changes of cytokines and interferon in the serum are shown in a table 2-2.

Organ coefficients of spleen and thymus of immune organs

As shown in tables 2-3, after the cyclophosphamide-induced hypoimmunity mouse model was established, the thymus and spleen coefficients of the model group were significantly atrophic and significantly decreased (P < 0.01) compared to the blank group, but the thymus and spleen coefficients of each drug group were not different (P > 0.05) compared to the model group; the thymus coefficient of the acetamide high and medium dose non-model group is obviously improved compared with that of the blank group, the spleen coefficient is extremely obviously reduced (P < 0.05), and the thymus coefficient and the spleen coefficient of the spleen amino peptide non-model group are not significantly changed (P > 0.05).

6. Conclusion of the experiment

Acetamide can raise the serum antibody producing level of hypoimmunity model mouse and normal mouse, raise the level of I L-1 β and I L-6 in serum of normal animal, lower the level of TNF- α in serum, and increase thymus coefficient obviously after treating cyclophosphamide treated hypoimmunity animal model with acetamide.

The principle of the serum hemolysin is that the serum of animals immunized by Sheep Red Blood Cells (SRBC) is combined with a certain amount of SRBC, the hemolysin is released by immunocompetent lymphocytes at 37 ℃, and the surrounding sheep red blood cells can be dissolved in the presence of complement, so that a macroscopic hemolysis plaque is formed around each antibody forming cell. Body antibody production is associated with B lymphocytes. The research result of a serum hemolysin test indicates that acetamide can obviously increase the antibody level in serum for mice in both normal physiological state and low immune state, plays a role in enhancing immunity and has more obvious effect on normal mice. The medicines and health products for enhancing the immunity clinically comprise levamisole, astragalus polysaccharide, newborn bovine liver active peptide and the like, and also comprise a plurality of acetamide derivatives or compounds containing acetamide, but few small molecular substances are available.

Experimental results show that the level of I β 1-1 β in serum of normal mice subjected to dry acetamide prognosis is remarkably increased, the level of TNF- α is remarkably reduced, and the level of I L-6 in an acetamide high-dose model group is remarkably increased, wherein the possible reasons are that in normal mice, under the stimulation of exogenous sheep red blood cells, the inflammatory factors I L- β and TNF-alpha are both increased to certain levels, acetamide is a small molecular substance, acetamide can detoxify mice and fluoroacetamide poisoning and improve nerve cell injury, and can permeate blood brain barriers to stimulate neuroendocrine cascade reaction and cause release of steroid substances, so that the level of I L-1 β and TNF-alpha is reduced, but I L-1 can be continuously generated under physiological conditions, so the level still shows increase.

In the experiment, large dose of cyclophosphamide is used as a low-immunity model modeling agent, the modeling effect is obvious, and the significant atrophy of thymus and spleen of immune organs is mainly reflected, the biological activity of I L-6 comprises antiviral and anti-infection effects, in pathological organisms caused by cyclophosphamide, mononuclear macrophages, endothelial cells and fibroblasts under the long-term administration effect of acetamide secrete I L-6 in the process of infection of the organisms and enter blood, and the systemic immune system of the organisms is mobilized to participate in anti-infection reaction.

In conclusion, it can be seen from the results of the experiments that acetamide enhances immunity and may have some anti-inflammatory effect.

Accordingly, the present invention provides the use of an acetamide for the preparation of an anti-inflammatory medicament, the acetamide having the formula:

the dosage of the acetamide is 0.2-2 g/kg. Specifically, the dosage of the acetamide can be 0.2g/kg, 0.7g/kg and 2g/kg, but is not limited thereto.

The anti-inflammatory effects of acetamide are further discussed below in conjunction with experiments

1 method of experiment

1.1 therapeutic administration

The 60 KM mice are randomly divided into 6 groups of blank control group, model control group, dexamethasone positive control group and acetamide high, medium and low dose groups according to body weight, wherein each group comprises 10 mice, and the number of the mice is half of that of the male and female mice. Distilled water is infused into the blank control group and the model control group, dexamethasone injection is injected into the abdominal cavity of the dexamethasone positive control group, the dosage is 10mg/kg, acetamide is dissolved by distilled water, the high, medium and low dosages are respectively 2g/kg, 0.7g/kg and 0.2g/kg, and the drug is administered by gastric lavage. Animals in each group were dosed with the drug continuously for 7 days, 2 times a day, with 3 hours intervals between doses.

1.2 intraperitoneal injection of L PS to establish an inflammation mouse model

All animals are fasted for 12 hours without water prohibition after the last administration, and except a blank control group, the rest animals in each group are subjected to one-time intraperitoneal injection of L PS with the dose of 15mg/kg, so that an inflammation model mouse is established.

1.3E L ISA test serum cytokines TNF- α, I L-17F, I L-22 and I L-23

Injecting L PS into abdominal cavity of all animals for 3h, anesthetizing with ether, collecting blood from orbital venous plexus, standing at normal temperature for 30min, centrifuging at 3000 rpm for 10min after serum is separated out, and collecting upper layer serum at-80 deg.C for use in refrigerator.

The contents of various cytokines in the serum of all animals are measured by adopting an E L ISA kit, and the contents of various groups of TNF- α, I L-17F, I L-22 and I L-23 are converted according to a standard curve.

1.4 anatomical materials selection

After blood collection, the animal is killed by dislocation of cervical vertebrae, and immune organs such as thymus and spleen are dissected and taken out, weighed and the organ coefficient is calculated.

1.5 statistics and analysis

Statistical analysis was performed using SPSS 19.0, data to

S is represented by P<0.05 indicates a statistically significant difference, P<0.01 indicates a statistically significant difference.

2 results of the experiment

2.1 cytokine level expression in serum

Compared with a blank group, the average water levels of I L-17F, I L0, I L-22 and TNF- α in the serum of the L PS inflammation model group are remarkably increased, compared with the L PS inflammation model group, the levels of I L-17F and TNF- α in the serum of L PS inflammation model mice can be remarkably reduced by the dexamethasone positive group and the acetamide drug group, the levels of I L-22 (P <0.01 and P < 0.05) are increased, and the I L-23 in each drug group has no remarkable difference (P > 0.05), and the concrete table is shown in table 3-1.

Organ coefficient changes in immune organs

As shown in Table 3-2, L PS inflammation model group and the blank control group have no significant difference in immune organ thymus coefficient and spleen coefficient (P > 0.05) in the acetamide high, medium and low dose groups and the model control group, while dexamethasone positive group and the model group have significantly reduced organ coefficient (P < 0.01) in the thymus and spleen.

3. Conclusion of the experiment

The levels of TNF- α, I L-17F, I L-22 and I L-23 in serum of mice injected with L PS in abdominal cavities are all obviously increased, which indicates that an inflammation mouse model is established, after the test drug is subjected to dry pretreatment, proinflammatory factors TNF- α and I L-17F are obviously reduced, anti-inflammatory cytokines I L-22 are increased, acetamide can regulate specific and non-specific immune functions, and indicates that acetamide has anti-inflammatory and immune regulation effects, plays a role in acquired immunity and adaptive immunity at the same time, and is suitable for treating autoimmune diseases such as systemic lupus erythematosus (S L E), Rheumatoid Arthritis (RA), psoriasis, vitiligo and the like.

L PS is composed of lipid A, core polysaccharide and specific polysaccharide, wherein lipid A is the main component of endotoxin toxicity and biological activity and has no species specificity, so that the toxic effects of different strains caused by endotoxin are similar.

The experiment uses L PS intraperitoneal injection with small dose to prepare a mouse inflammation model, stimulates the immune system in a mouse, L PS is a strong agonist of tumor necrosis factor, the obvious increase of TNF-alpha in an animal of the experiment model proves that the inflammation model is established, under the induction of L PS, I L-17F is also included, which belongs to proinflammatory factor like the former, and under the action of acetamide administration, the I L-17F and the TNF-alpha level in serum are obviously reduced, I L-22 belongs to members of I L-10 family, is a cytokine which can be generated by both inherent immunity and adaptive immunity in human body, is classified into the anti-inflammatory cytokine, participates in resisting acetamide, plays roles in defense and protection, can not only assist T lymphocyte 17 secretion, but also T lymphocyte 22 or natural killer cell 22 to generate clinical effect, and experiment I L-22 can generate clinical effect, and the anti-inflammatory immune response of psoriasis and atopic dermatitis, and the immune response to the increase of tumor necrosis factor I2-493, and the immune response to the immune factor 2-17F, and the immune response to the tumor necrosis factor, and the immune response to the increase of the tumor necrosis factor.

Correspondingly, the invention discloses an application of acetamide in preparing anti-psoriasis drugs, wherein the structural formula of acetamide is as follows:

the dosage of the acetamide is 0.7-2 g/kg.

The effect of acetamide in combating psoriasis, and in particular in treating psoriasis induced by imiquimod, an immunologically related disease, is discussed further below in connection with the experiments.

Skin lesion severity change and skin PASI score

1. The normal control mice had smooth and consistent skin thickness, and no abnormal change in skin with increasing time of administration. In contrast, in the psoriasis model mice induced by imiquimod, the skin appeared scaly and thickened after the intervention of imiquimod, but in the experiment, the skin of the animal did not have obvious erythema, so the PASI score of the animal = scaly score + thickened score, the PASI score reached the peak after the application of imiquimod to the 5 th day, and the specific results are shown in fig. 1, fig. 2A and fig. 2B and tables 4-1.

2. Cytokine expression levels in serum

Compared with a blank control group, the levels of I L-17F, I L-23 and TNF- α of the model group are remarkably up-regulated, the level of I L-22 is remarkably down-regulated (P is less than 0.01, P is less than 0.05), the level of I L-17F is remarkably reduced compared with the imiquimod model group after the intervention treatment of the imiquimod-induced psoriasis mice by high and medium doses of dexamethasone and acetamide (P is less than 0.05), and the level of TNF- α in serum of the dexamethasone positive group and the level of I L-23 and TNF- α in serum of the acetamide are remarkably reduced on average (P is less than 0.01, P is less than 0.05).

3. Pathological changes in dorsal lesions in mice

The results of 200-fold and 400-fold observation of the HE stained pathological section under a microscope show that the skin of the control mouse is not abnormal. Compared with the control group, the mouse of the imiquimod model group has obvious thickening of the epidermis layer, hyperkeratosis and parakeratosis of the horny layer, and is accompanied with the appearance of Munro micro-abscess, thickening of the acantho layer, inflammatory cells and epidermal cell fragments in the acantho layer, and obvious expansion and distortion of capillary vessels, but no obvious overflow of red blood cells (as shown in figure 3A). After intervention treatment of dexamethasone and acetamide on the imiquimod-induced psoriasis-like model mouse, the skin epidermal thickness of the dexamethasone-positive group is obviously lower than that of the model group, hyperkeratosis is reduced, the acanthosis is thinned, no obvious vasodilatation and Munro micro-abscess exist, and the method is remarkably different from the model group. The epidermal layer of the mice in the acetamide high, medium and low dose groups is thinned, the spinous layer is still thicker, but no remarkable Munro micro-abscess, telangiectasia and inflammatory cell infiltration exist, and the specific result is detailed in the following figure 3B.

It should be noted that fig. 3A shows HE stained sections of mice treated for 12 days of skin pathology (a. blank control group, b. imiquimod model group, c. dexamethasone positive group); fig. 3B shows HE stained sections of mice in each group treated for 12 days of skin pathology (d. acetamide high dose group; e. acetamide medium dose group; f. acetamide low dose group). In each set of graphs, the upper graph is the result at 200 times magnification, and the lower graph is the result at 400 times magnification.

4. Conclusion of the experiment

After the intervention treatment of acetamide on the psoriasis model mouse induced by imiquimod, the level of cytokine I L-17F in serum can be obviously reduced, the skin is improved, and the acetamide has a treatment effect on the psoriasis model mouse and is realized by inhibiting T lymphocyte mediated immunity.

In the experiment, the acetamide has obvious treatment effect on the skin of an imiquimod-induced psoriasis model mouse through skin damage performance and PASI score trend change, and inhibits the model skin damage under the condition that the skin psoriasis of a model group animal is more and more serious, and the skin epidermis is smooth and has no obvious scales through visual observation. For the diagnosis of psoriasis, except for approximate visual observation, pathological sections are relative gold standards, and the pathological section picture of skin lesions of each acetamide drug group mouse in the experiment shows that acetamide has an improvement effect on cells of an epidermal layer, a spinous layer and a dermal layer of a model mouse, and has the advantages of remarkable curative effect, thinning of the epidermal layer and no remarkable Munro micro-abscess, capillary vessel dilatation and inflammatory cell infiltration.

The occurrence, development and recovery of psoriasis are related to various cytokines, namely factors related to humoral immunity and cellular immunity, and the cytokines can be directly secreted by the body or stimulated by procytokines. The central link of immune response in psoriasis is mainly NF-_ҚB. In addition, the dosage of the acetamide can also induce the expression reduction of I L-23 in the serum, I L-23 is generated in bone marrow cells, can promote the proliferation and differentiation of Th17 lymphocytes and further induce the generation of I L-17, and the reduction of the expression level of the I L-17F and the I L-23 is taken as a marker cytokine of the psoriasis, which indicates that the acetamide plays a role in T lymph immunity to improve the skin with psoriasis-like skin lesion.

In conclusion, the acetamide micromolecule provided by the invention has obvious effects on anti-inflammation, immune bidirectional regulation and psoriasis resistance.

Furthermore, the acetamide can be combined with medically acceptable auxiliary materials to form various dosage forms of medicines, such as tablets, paste, sprays, capsules or pills. The method for preparing the drug by acetamide is specifically explained below by taking a tablet as an example.

Tablet, taking acetamide with purity higher than 99.9%, adding ethanol, stirring for dissolving, making into ethanol solution of extract, taking appropriate amount of β -cyclodextrin, adding appropriate amount of water, stirring, adding ethanol solution of extract under stirring, high-speed shearing and stirring to form suspension, standing for precipitation, adding appropriate amount of starch, mixing, pulverizing, sieving, granulating, drying, and coating with sugar.

When acetamide is prepared into other preparations, reference is made to the prior art.

While the invention has been described in connection with what is presently considered to be the most practical and preferred embodiment, it is to be understood that the invention is not to be limited to the disclosed embodiment, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims.

Claims (2)

1. The application of acetamide in the preparation of anti-psoriasis drugs is characterized in that the acetamide has the structural formula:

it is achieved by inhibiting T lymphocyte-mediated immune function.

2. The use according to claim 1, wherein the amount of acetamide is 0.7 to 2 g/kg.

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