CN114588141A - Medicine for treating psoriasis - Google Patents
Medicine for treating psoriasis Download PDFInfo
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- CN114588141A CN114588141A CN202210345062.0A CN202210345062A CN114588141A CN 114588141 A CN114588141 A CN 114588141A CN 202210345062 A CN202210345062 A CN 202210345062A CN 114588141 A CN114588141 A CN 114588141A
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- psoriasis
- medicament
- sulforaphene
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Abstract
A medicine for treating psoriasis, which belongs to the field of natural medicines. A series of experiments show that the sulforaphane reduces epidermal hyperplasia and inflammatory reaction of psoriasis-like mouse skin lesion parts induced by imiquimod; inhibiting human keratinocyte hyperproliferation and promoting apoptosis; relieves the symptoms of psoriasis and has obvious treatment effect on the psoriasis. The sulforaphane is isolated from brassica plants including (but not limited to): radish, broccoli, cabbage, mustard and horseradish, have natural components, are nontoxic, have obvious effect of treating psoriasis, are not easy to relapse after healing, and have wide application prospect in preparing medicaments for treating psoriasis.
Description
Technical Field
The invention relates to an application of a plant extract sulforaphane in preparation of drugs for treating psoriasis, belonging to the natural field.
Background
Psoriasis, commonly known as psoriasis, is a common chronic immunological inflammatory skin disease. The disease has the characteristics of long course of disease, easy relapse and difficult cure, and some cases even do not cure for all the time, thus seriously affecting the physiological and psychological health of patients. The psoriasis is also a very common disease, the prevalence rate accounts for about 2 to 4 percent of the world population, and the incidence rate of the psoriasis in China is on the rise year by year in recent years and is mostly young and strong. Psoriasis is a skin disease which is caused by interaction of multiple factors such as heredity, environment, immunity and the like, has complex etiology, and is mediated by immunity throughout the whole course of the disease. The typical pathological feature is the excessive proliferation of immune cell infiltrating dermis and epidermis and epidermal cells found in the skin lesion of psoriasis patients. After the immune cells are infiltrated, a large number of inflammatory factors such as IL-17, IL-23, IL-6, TNF-alpha, IL-1 beta and the like are secreted, and the inflammatory factors can promote the proliferation and abnormal differentiation of keratinocytes, break the homeostasis of the keratinocytes and further initiate psoriasis. The clinical symptoms are erythema and scales. It can be seen from the scalp and the extremities, all of which are usually attacked by diseases. The current treatment modalities for psoriasis are mainly symptomatic treatment to control the symptoms. The topical medicine is usually glucocorticoid, and the medicine is not easy to be used for a long time and is easy to recur after stopping taking the medicine. Methotrexate, cyclosporin A and abamectin A are commonly used for internal administration, and the medicines generally have large dosage and serious toxic and side effects for long treatment course, and damage liver function and kidney function. In recent years, some monoclonal antibodies and targeted drugs have been introduced, such as imazethapyr, adalimumab (anti-TNF-a) and secukinumab (anti-IL-17). The biological agents have very good curative effect but high price, and the long-term curative effect of the biological agents is still in the clinical research stage at present, so that the development of systemic treatment medicines with obvious curative effect, low toxicity and low price is still urgently needed. In recent years, Chinese medical workers have achieved great achievements in treating psoriasis by using traditional Chinese medicines, and the search of medicines for treating psoriasis from natural sources is considered as an effective way for researching the medicines.
Sulforaphane (SFE) is a natural active ingredient extracted from cruciferous plants such as radish. It has been reported that sulforaphane has biological activities of anti-inflammatory, anticancer, antioxidant, detoxifying and antibacterial. Based on the excellent properties of sulforaphane, there is a need to study its application in the treatment of psoriasis.
Disclosure of Invention
It is an object of the present invention to provide a composition for treating psoriasis that solves the problems presented in the background above.
The invention provides a preparation method of a composition for treating psoriasis, which comprises sulforaphene.
The present invention provides a sulforaphene as an effective compound, which is obtained from sporulated cabbage, cauliflower, chinese cabbage, kale, green broccoli sprouts, cabbage mustard, broccoli, kohlrabi, mustard, radish, sesames or watercress. The compound has definite therapeutic action on psoriasis.
In the above application, the psoriasis is psoriasis vulgaris, erythrodermic psoriasis, arthrosis or pustular psoriasis. The psoriasis is in a progressive, quiescent or regressive phase.
In the above application, the object of the present invention is achieved by the following experimental schemes:
in the first scheme, an imiquimod-induced psoriasis-like mouse model is constructed, and three doses of high (75mg/kg), medium (50mg/kg) and low (25mg/kg) of sulforaphane are continuously administered for 7 days, and cyclosporine A is taken as a positive control group. Daily observation and recording of psoriasis mouse symptoms and identification of the model; then, histopathological evaluation and skin lesion inflammatory factor expression level measurement are carried out on the skin of the mouse.
In the second protocol, human immortalized keratinocytes were cultured and treated with drug in groups at a dose of 0-32 μ M for 24h, 48h and 72h, and the proliferative activity of the cells was examined with CCK 8; then, the cells were treated with 8. mu.M, 12. mu.M and 16. mu.M of sulforaphane for 24 hours, and after staining, the cell cycle distribution and apoptosis were observed.
In a third protocol, a group of psoriasis patients with associated symptoms was sought, with 60mg of sulforaphane per day, for 4-12 weeks, during which period stimulating diet, regular life and good working status were prohibited. The symptoms of psoriasis patients were observed and recorded regularly.
In the above applications, in order to evaluate the severity of psoriatic skin, the reference literature establishes a scoring system based on clinical PASI scores: the erythema, the scales and the thickening degree are independently scored according to the score of 0-4, and the scoring rule is as follows: 0-none, 1-mild, 2-moderate, 3-significant, and 4-very significant, and used to determine the severity of the skin.
In the above applications, the gist of the present invention resides in that the medicament alleviates epidermal hyperproliferation and skin inflammatory reactions; the skin damage degree is reduced; relieving erythema, scaling and infiltration of the skin; inhibiting the hyperproliferation of human epidermal keratinocytes.
Compared with the existing treatment medicines, the application of the sulforaphene in the preparation of the medicine for treating psoriasis has remarkable effect of treating psoriasis and relapse prevention after healing. The components are natural, nontoxic and free of side effect. Has low cost and can be used for a long time.
The present invention will be described in detail with reference to specific examples.
Drawings
FIG. 1 is a schematic representation of the clinical appearance of groups of mice A. general dorsal skin of groups of mice on day 7; panel b, PASI clinical score plots for 7 consecutive days in each group of mice. General observation results show that the back skin of the control mice is smooth and has no damage; thicker yellow and white scales can be obviously observed on the back of the model group mouse, the skin damage area is larger and almost completely covered, and the back can be seen to be thickened by severe erythema; the degree of skin damage was reduced in the mice of the sulforaphene-administered group and the positive drug-administered group, compared to the model group; symptoms of hypertrophy, scaling and erythema are alleviated; the clinical symptoms of psoriasis mice are obviously improved. The result of the PASI score shows that the PASI score of the control group mice is not changed; the skin of the back of other 5 groups of mice shows symptoms of scale, erythema and thickened skin damage from the 2 th to the 3 rd days, the skin damage degree gradually worsens from the 4 th to the 6 th days, the skin damage degree basically reaches the peak value on the 7 th day, the PASI score of the model group of mice is highest, and the skin damage degree is also the most serious. Compared with the SFE treatment group and the positive drug group and the model group, the psoriasis symptom of the mice is obviously relieved, the PASI score is obviously reduced (P is less than 0.05), and the phenomenon that the skin damage is relieved is obvious along with the higher the administration concentration of the sulforaphene.
Figure 2 skin histopathological evaluation of groups of mice graph a HE staining of skin tissue of groups of mice; panel b is a schematic representation of epidermal thickness for each group of mice. HE staining was visualized as a schematic with magnification up x 200, down x 400. Combining HE staining and a schematic diagram of the thickness of the epidermis of skin tissues, the epidermis layer of the skin of the control mouse is thinner, and cells in the dermis layer do not infiltrate; compared with a control group, the dorsal skin epidermal layer of the model group mouse is obviously thickened (P is less than 0.01), the thickening phenomenon of a spinous layer is very obvious, and the infiltration phenomenon of inflammatory cells of a dermal layer is also very obvious; compared with the model group, the symptoms of thickened dorsal skin epidermis, thickened spinous layer and inflammatory cell infiltration of dermal layer of the mice of the SFE treatment group and the positive drug group are obviously relieved (P is less than 0.05). HE staining can be clearly seen under a 400-fold mirror, and compared with a control group, the infiltration phenomenon of inflammatory cells in a model group is very obvious; the symptoms of inflammatory cell infiltration in the skin lesions of mice treated with SFE and mice treated with positive drug group are obviously improved.
FIG. 3 is a schematic representation of the effect of sulforaphane on the expression of inflammatory factors associated with skin lesions in psoriatic mice. The detection result of the ELISA kit shows that compared with the control group, the expression levels of IL-1 beta, IL-6, IL-17A, IL-23 and TNF-alpha protein at the skin lesion parts of mice in the IMQ model induction group are obviously increased (P is less than 0.05). Indicating that IMQ can induce inflammatory response in mice. Compared with a model group, the expression level of the inflammatory factors is remarkably reduced (P < 0.05) along with the increase of the dosage of the sulforaphane, and the inhibition effect of SFE on the cytokines is almost in dosage dependence. The expression of inflammatory factors in the skin lesions of the mice with the positive drug group is also obviously reduced. The results indicate that SFE and positive drugs can alleviate psoriasis symptoms by inhibiting the expression of inflammation.
FIG. 4 is a schematic representation of the effect of sulforaphene on the proliferative activity of keratinocytes. CCK8 test shows that after different concentrations of sulforaphane (0-32 mu M) act on human keratinocytes, the proliferation activity of the cells is reduced along with the increase of the concentration of the drug and the prolonging of the acting time.
FIG. 5 is a schematic representation of the effect of sulforaphene on the periodic distribution of keratinocytes. According to the cell cycle detection result, after the sulforaphene with different concentrations acts on the human keratinocytes, the cell cycle distribution is obviously changed, the cells in the S phase are obviously increased (P is less than 0.01) and the proportion of the cells in the S phase is higher along with the increase of the concentration of the SFE medicament compared with the control group. It is presumed that the inhibitory effect of sulforaphene on the proliferative activity of keratinocytes may induce the achievement of S-phase arrest of cells.
FIG. 6 is a schematic representation of the effect of sulforaphene on apoptosis in keratinocytes. According to the apoptosis detection result, compared with the control group, after the sulforaphene with different concentrations acts on human keratinocytes, the number of apoptotic cells is obviously increased (P is less than 0.01), and the proportion of apoptotic cells is higher along with the increase of the concentration of the SFE medicament. It is presumed that the inhibitory effect of sulforaphene on the proliferative activity of keratinocytes can be achieved by inducing apoptosis.
Detailed Description
The following examples will help to understand the present invention, but they are only for illustrative purposes, and the described examples are only a part of the examples of the present invention, not all of them. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Examples of the drug action
Example one
1. Grouping and administration of mice
60 SPF clean grade female BALB/c mice, 6 to 8 weeks old, weigh approximately 20 g. Removing back hair, and removing residual hair with depilatory cream. An area of 2cm by 3cm of skin was exposed and acclimatized for 3 days.
The mice were then randomized into 6 groups of 10 mice each, and the grouping and dosing method was as follows:
control group: vaseline cream was applied daily I times a day for 7 consecutive days, forming a negative control with imiquimod cream.
Model group: mice were coated on their backs with 5% Imiquimod (IMQ) cream (for induction of psoriasis) 62.5 mg/mouse/day 1 time daily for 7 consecutive days.
Administration group 1; in the low-dose sulforaphane group (25mg/kg), the back of the mouse is coated with 62.5 mg/mouse/day of 5% imiquimod cream, 1 time a day and 7 days continuously. Adding 2.5mg/mL sulforaphene water solution, and performing intragastric administration, 200 μ L each time, 1 time daily for 7 days. The two medicines are separated by more than 4 h.
Administration group 2: in the sulforaphene medium dose group (50mg/kg), the back of the mouse is coated with 62.5 mg/mouse/day of 5% imiquimod cream, 1 time a day and 7 days continuously. Adding 5mg/mL sulforaphene water solution, and performing intragastric administration at a dose of 200 μ L each time, 1 time daily for 7 days. The two medicines are separated by more than 4 h.
Administration group 3: in the high-dose sulforaphane group (75mg/kg), the back of the mouse is coated with 62.5 mg/mouse/day of 5% imiquimod cream, 1 time a day and 7 days continuously. Adding 7.5mg/mL sulforaphene water solution, and performing intragastric administration, 200 μ L each time, 1 time per day, and continuously for 7 days. The two medicines are separated by more than 4 h.
Administration group 4: cyclosporine A positive control (25mg/kg), mice were coated with 5% imiquimod cream on their backs at 62.5 mg/mouse/day 1 time daily for 7 consecutive days. Adding 2.5mg/mL cyclosporin A water solution, and performing intragastric administration at a dose of 200 μ L each time, 1 time daily for 7 days. The two medicines are used at an interval of more than 4 h.
2. Psoriasis-like mouse PASI score determination
The recording was daily by means of digital photography. To assess the severity of back skin inflammation, the reference literature establishes a scoring system based on clinical PASI scores as follows:
(1) skin area scoring: the whole body is divided into 4 parts of head and neck, upper limbs, trunk and lower limbs. The percentage of the above-mentioned portion in the body surface area is 10%, 20%, 30% and 40%, respectively. The area of skin lesions was scored for 4 sites (A). The skin lesion area scores were performed on 4 sites, respectively, with the following criteria: no rash 0, no rash 1-9%, no rash 2-10-29%, no rash 3-30-49%, no rash 4-50-69%, no rash 5-70-89%, and no rash 6-90-100%.
(2) Evaluation of clinical severity: the score of each part was obtained according to the above 4 parts, and each part was obtained according to the following 3 skin lesion clinical characteristics.
Erythema (E): red or dark red inflammatory plaques, fading of pressure.
Infiltration (I): the skin damage tends to spread around, the boundary is blurred, and the pressure is substantial.
Desquamation of epidermis, scale (D): refers to the exfoliation of epidermal cells.
The skin lesion severity scoring rules are as follows: 0-none, this sign is not confirmed by careful observation. Mild, this sign can be confirmed but needs to be carefully observed. 2-moderate, this sign is more obvious and immediately identifiable. Heavy at 3, this sign is evident. 4, extremely heavy, this sign is very evident.
(3) The formula: PASI score ═ head E + head I + head D × head a × 0.1+ (upper E + upper I + upper D) × upper a × 0.2+ (trunk E + trunk I + trunk D) × trunk a × 0.3+ (lower E + lower I + lower D) × lower a × 0.4. The PASI score was used to determine the severity of the skin and the scoring results are shown in table 1 and figure 1.
Table 1 psoriasis mouse clinical presentation on day 7 (X ± s.d., n ═ 10)
Note that: # P < 0.05 shows that the difference is significant compared to the control group; p < 0.05 and P < 0.01 indicate that the differences were significant compared to the model group.
As can be seen from table 1: compared with a normal control group, the skin lesion PASI score of the model group is obviously increased (P < 0.01). Compared with the model group, the PASI score of the mice in the last 4 groups is obviously reduced (P is less than 0.01). The dose dependence of the sulforaphane on psoriasis treatment was seen by the sequentially decreasing PASI scores of the dosing groups 1, 2 and 3. The PASI scores of the administration groups 2 and 3 are lower than those of the positive control group, and the efficacy of the sulforaphane is better than that of the first-line drug cyclosporine a in the current market.
FIG. 1 is a schematic representation of the observation of clinical performance of groups of mice. In fig. 1, group a is a normal control group, group B is a psoriasis model group, group C is a sulforaphene low dose group, group D is a sulforaphene medium dose group, group E is a sulforaphene low dose group, and group F is a positive control group. As can be seen from figure 1, compared with the group A, psoriasis-like lesions such as obvious erythema, scale, epidermal hyperproliferation and the like can be observed on the skin of the back part of the mice in the group B, and the PASI score is obviously increased (P is less than 0.05); compared with the B group of mice, the C, D, E, F group of mice has obviously improved back skin damage, obviously reduced erythema, scale and epidermal hyperproliferation phenomena and obviously reduced PASI score (P is less than 0.05). And the improvement degree of skin damage is more obvious along with the increase of the dosage of the sulforaphene. The symptoms in groups D and E were significantly less than those in group F mice. Therefore, the efficacy of the sulforaphene is judged to be better than that of the first-line drug cyclosporin A in the current market.
4. Skin histopathological detection
Mice were sacrificed at coccygeal fracture on day 8 post model preparation. The skin lesion tissue with the size of 0.5cm multiplied by 1cm is taken and placed in formalin fixing solution, and the degree of the skin lesion, the thickness of the epidermis and the infiltration condition of inflammatory cells are observed after HE staining.
Fig. 2 evaluation of skin histopathology of groups of mice in fig. 1, group a is a normal control group, group B is a psoriasis model group, group C is a sulforaphene low dose group, group D is a sulforaphene medium dose group, group E is a sulforaphene low dose group, and group F is a positive control group; a denotes the epidermal layer, b denotes the dermal layer, c denotes the boundary between the epidermal layer and the dermal layer; → to inflammatory cell infiltration. The HE staining shows that the epidermis of the skin of the normal control group mouse is complete, the boundary of each layer is clear, and no obvious inflammatory cell infiltration is seen in the dermis. Compared with the group A, the dorsal skin epidermal layer of the mice in the group B is obviously thickened, the spinous layer is especially obviously thickened, and the inflammatory cell infiltration phenomenon of the dermal layer is also very obvious. Compared with B, C, D, E, F mice had significantly relieved symptoms of thickened epidermis, thickened spinous layer and inflammatory cell infiltration in the dermal layer of the dorsal skin. HE staining can clearly see under a 400-fold mirror that the infiltration phenomenon of inflammatory cells of mice in group B is very obvious compared with that in group a; compared with B, the symptom of inflammatory cell infiltration in the skin lesion of C, D, E, F mice is obviously improved. The epidermal thickness of the skin tissue of the mice is shown in a schematic diagram, and compared with the group A, the epidermal layer thickening phenomenon of the mice in the group B is very obvious (P is less than 0.01); compared with B, C, D, E, F mice had significantly relieved symptoms of thickening of the epidermal layer (P < 0.05). The symptoms of epidermal hyperplasia and inflammatory cell infiltration were less severe in mice of groups D and E than in mice of group F. Therefore, the efficacy of the sulforaphene is judged to be better than that of the first-line drug cyclosporin A in the current market.
5. Psoriasis-associated inflammatory factor detection
The psoriasis is a chronic inflammatory skin disease, inflammatory cells infiltrate into epidermis and dermis which are typical pathological features, and after the inflammatory cells infiltrate into the epidermis and the dermis, a large amount of inflammatory factors are secreted to act on keratinocytes, so that the excessive proliferation and abnormal differentiation of the keratinocytes are promoted, and the occurrence and the development of the psoriasis are promoted.
Inflammatory factor detection in psoriasis-like mouse skin tissue: mice were sacrificed at coccygeal fracture on day 8 post model preparation. Tissue factor protein is extracted from 20 mg-sized skin lesion tissues, and then an ELISA kit is used for detecting the expression of inflammatory factors related to psoriasis, the result is shown in figure 3, and compared with a control group, the expression levels of IL-1 beta, IL-6, IL-17A, IL-23 and TNF-alpha protein at the skin lesion parts of mice in an IMQ model induction group are obviously increased (P is less than 0.05). Indicating that IMQ can induce the inflammatory reaction of the mice. Compared with a model group, the expression level of the inflammatory factors is remarkably reduced (P < 0.05) along with the increase of the dosage of the sulforaphane, and the inhibition effect of SFE on the cytokines is almost in dosage dependence. The inhibition effect of SFE on the expression level of the inflammatory factor is superior to that of the first-line medicament cyclosporin A on the market at present.
Example two
Firstly, sulforaphene (the purity is higher than 95%) is dissolved in DMSO to prepare 40mM stock solution, the stock solution is placed in a refrigerator with the temperature of minus 80 ℃, and incomplete culture medium is used for gradient dilution to different concentrations for later use during experiments.
1. Cell growth activity assay
Culturing human immortalized keratinocyte, inoculating the cells on a 96-well plate when the cells grow to the logarithmic growth phase, wherein the inoculation density is 5000/empty, and the inoculation volume is 100 mu L. Culturing in an incubator containing 5% carbon dioxide at 37 deg.C for 24 h. Then, drug-containing media were prepared to a final concentration of 32. mu.M, 28. mu.M, 24. mu.M, 20. mu.M, 16. mu.M, 12. mu.M, 8. mu.M, 4. mu.M. The complete culture medium is discarded, 100 mu L of the drug-containing culture medium is added into each space for incubation for 24h, 48h and 72h, and DMSO is used as a negative control. After waiting for the corresponding time point, 10. mu.L of CCK8 was added to each well, and after incubation for 4h, the OD 450 value of each well was measured by a microplate reader. The experiment was repeated 3 times and the average was taken. Relative cell survival rate ═ experimental-blank/control-blank) x 100%. And drawing a cell growth curve according to the cell survival rate.
Figure 4 is a schematic representation of the effect of sulforaphane on the proliferative activity of keratinocytes. SFE has significant inhibitory effect on proliferation of human keratinocytes. The CCK8 detection shows that: after different concentrations of sulforaphane act on human keratinocytes, the proliferation activity of the cells is reduced with the increase of the concentration of the drug and the prolongation of the acting time. Shows that the inhibition effect of the sulforaphene on the proliferative activity of the keratinocytes has the characteristics of time dependence and concentration dependence.
2. Cell cycle distribution assay
Cells were plated in 96-well plates at a density of 10000 cells/empty. Culturing in an incubator containing 5% carbon dioxide at 37 deg.C for 24 h. When the cells are plated at 60-70%, the cells are treated with drug-containing culture media with the concentrations of 8 muM, 12 muM and 16 muM for 24 h. According to the cell cycle detection kit specification, cells are singly dyed, the detection result is shown in figure 5, according to the cell cycle detection result, after different concentrations of the sulforaphane act on human keratinocytes compared with a control group, the cell cycle distribution is obviously changed, the cells in the S phase are obviously increased (P is less than 0.01), and the proportion of the cells in the S phase is higher along with the increase of the concentration of the SFE medicament. It is presumed that the inhibitory effect of sulforaphene on the proliferative activity of keratinocytes may induce the achievement of S-phase arrest of cells.
3. Apoptosis assay
Cells were plated in 96-well plates at a density of 10000 cells/empty. Culturing in an incubator containing 5% carbon dioxide at 37 deg.C for 24 h. When the cells are plated at 60-70%, the cells are treated with drug-containing culture media with the concentrations of 8 muM, 12 muM and 16 muM for 24 h. According to the apoptosis detection kit specification, cells are doubly stained, the detection result is shown in figure 6, according to the apoptosis detection result, when different concentrations of the sulforaphane act on human keratinocytes compared with a control group, apoptotic cells are obviously increased (P is less than 0.01), and the proportion of apoptotic cells is higher along with the increase of the concentration of the SFE medicament. It is presumed that the inhibitory effect of sulforaphene on the proliferative activity of keratinocytes can be achieved by inducing apoptosis.
EXAMPLE III
1. Case selection
The Chinese and western medicine diagnosis standards for psoriasis are met: 100 patients, 67 men and 33 women in the group; age 18 to 65 years, mean age (34.6 ± 2.2) years; the course of disease is 1 month to 7 years, and the average course of disease (3.4 +/-1.5) years; the traditional Chinese medicine, glucocorticoid and immunosuppressant are not used for systemic treatment 1 month before the visit; patients with skin lesions less than 30% of body surface area (i.e. a PASI score between 5-10).
2. Method of administration
All patients were equally divided into two groups according to the random number table method:
treatment group (50 people): the control group is treated with Raphani semen with 20mg each time for 3 times daily. The medicine is taken for 4 weeks as a course of treatment, and the treatment lasts for 1-3 courses.
Control group (50 persons): the control group is treated with cyclosporin A for symptoms, 50mg each time, 3 times daily. The medicine is taken for 4 weeks as a course of treatment, and the treatment lasts for 1-3 courses.
3. Index of therapeutic effect
The Psoriasis Area and Severity Index (PASI) of the patients was scored after 1-3 treatment courses (as in table 2).
Table 2 PASI score comparison (X ± S, n ═ 50)
Note that: p < 0.05 indicates that the difference was significant compared to the control group.
As can be seen from the above table: after 1-3 courses of treatment, the skin lesions of the two groups have obvious difference in severity. The PASI score of the treatment group after treatment is obviously lower than that of the control group (P is less than 0.05), and the treatment effect of the sulforaphane on the psoriasis is proved to be better than that of the first-line treatment drug cyclosporin A on the market at present.
4. Clinical efficacy evaluation criteria
Calculating the formula: n ═ 100% (pre-treatment score-post-treatment score) ×
The clinical cure is as follows: the skin lesions basically disappear, the clinical symptoms disappear, and n is more than or equal to 90 percent. The effect is shown: the most of the skin damage is removed, the clinical symptoms are obviously relieved, and the n is more than 89% and more than or equal to 60%. Improvement: the skin lesion is partially removed, and the clinical symptoms are changed, wherein the ratio of 59% to n is more than or equal to 30%. And (4) invalidation: the skin lesion is not obviously relieved, the clinical symptoms are not relieved or worsened, and n is less than 30 percent
TABLE 3 comparison of clinical efficacy of two groups of patients
Note that: p < 0.05 indicates that the difference was significant compared to the control group.
As can be seen from the above table, the total effective rate of the treatment group is 92%, which is obviously higher than 84% (P < 0.05) of the control group. The treatment group had a significant rate of 68% which was significantly higher than the control group by 52% (P < 0.05). The drug effect of the treatment is obviously higher than that of the control group.
Example four
(1) Crushing or homogenizing 100kg of radish seeds, adding 2000L of deionized water with the volume being 20 times that of the crushed radish seeds, stirring and hydrolyzing for 5 hours at room temperature, adding hydrochloric acid to adjust the pH value of the hydrolysate to 2.0, standing overnight, and centrifuging to obtain 2000L of the radish seed hydrolysate serving as a supernatant; (2) extracting the sulforaphene hydrolysate obtained in the step (1) by using 6000L of ethyl acetate for 3 times, wherein 2000L of ethyl acetate is used each time, recovering sulforaphene in the hydrolysate, collecting 6000L of ethyl acetate extraction layer, distilling under reduced pressure at 40 ℃ and the vacuum degree of-0.08 MPa to obtain 200L of sulforaphene crude extract, and recovering ethyl acetate; (3) adding the sulforaphene crude extract obtained in the step (2) into a molecular distillation device for primary molecular distillation, removing residual ethyl acetate, water and low-boiling-point impurity components in the sulforaphene crude extract, and collecting heavy components flowing out of the distillation wall of the primary molecular distillation device to obtain 2000g of primary molecular distillation heavy components; the conditions of the first-order molecular distillation are as follows: the temperature of the raw material is kept at 60 ℃, the vacuum degree is 2000Pa, the distillation temperature is 100 ℃, the feeding flow rate is 2mL/min, the temperature of a condensation surface is 0 ℃, and the rotating speed of a film scraper is 400 rpm; (4) adding the primary molecular distillation heavy component obtained in the step (3) into a molecular distillation device for secondary molecular distillation, removing high-boiling-point impurity components in the primary molecular distillation heavy component, and collecting light components flowing out of a condensation surface of the secondary molecular distillation device to obtain 1000g of a sulforaphene product with the purity of more than 98%; the secondary molecular distillation conditions were: the temperature of the raw material is kept at 70 ℃, the vacuum degree is 0.I Pa, the distillation temperature is 110 ℃, the feeding flow rate is 1mL/min, the temperature of a condensation surface is 0 ℃, and the rotating speed of a film scraper is 450 rpm.
EXAMPLE five
Mixing 100g of the sulforaphene extract prepared by the above method with 19.9kg of dextrin in 100L of deionized water, dissolving, and spray drying. Setting the air inlet temperature of spray drying at 180 ℃, adjusting the air outlet temperature at 80 ℃, adjusting the liquid inlet speed at 5L/h, collecting the product, preparing the sulforaphene spray drying powder, granulating by using a granulator, and subpackaging by using an automatic particle packaging machine at 2g to obtain sulforaphene granules with the sulforaphene content of 0.5% (mass fraction, the percentage content which is not explained in the following text is mass fraction).
Example six
Mixing 100g of the sulforaphene extract prepared by the method with 9.9kg of dextrin in 50L of deionized water, dissolving, performing spray drying to prepare sulforaphene spray-dried powder, and subpackaging by 1g to obtain sulforaphene granules with the content of 1%.
EXAMPLE seven
Mixing 100g of the sulforaphene extract prepared by the above method with 1.9kg of dextrin in 10L of deionized water, dissolving, and spray drying to obtain sulforaphene spray-dried powder with content of 5%. Adding 50g of magnesium stearate, 500g of puffing king and 2.45kg of micro cellulose into the dry powder, uniformly mixing the powder, carrying out dry granulation, and tabletting the medicine-containing granules obtained by granulation to prepare 500mg of oral tablets containing 2% of sulforaphene.
Example eight
Mixing 200g of the sulforaphene extract prepared by the method with 1.8kg of dextrin in 10L of deionized water for dissolving, then performing spray drying to prepare sulforaphene spray-dried powder with the content of 10%, adding 50g of magnesium stearate, 500g of overrun and 2.45kg of microcrystalline cellulose, mixing and tabletting to prepare 500mg of each sulforaphene oral tablet containing 4% of sulforaphene.
Example nine
Mixing 100g of the sulforaphene extract prepared by the method with 0.9kg of dextrin in 5L of deionized water for dissolving, then performing spray drying to prepare sulforaphene spray-dried powder with the content of 10%, adding 100g of magnesium stearate, 100kg of swelling powder I and 7.9kg of microcrystalline cellulose, mixing and tabletting to prepare 500mg of oral tablets containing 1% of sulforaphene.
Claims (10)
1. A medicament for the treatment of psoriasis, characterized by: at least including sulforaphene or a plant extract including sulforaphene.
2. The medicament of claim 1, wherein: the plant extract is obtained from broccoli, cabbage, cauliflower, Chinese cabbage, kale, green broccoli sprout, cabbage mustard, broccoli, kohlrabi, mustard, radish, sesamum indicum or watercress.
3. The medicament of claim 1, wherein: the sulforaphene or the plant extract comprising sulforaphene is administered by injection or orally.
4. The medicament of claim 3, wherein:
(1) the daily dosage of the sulforaphene is 0.5 to 1.5 mg/capsule, and the administration time is 1 week.
(2) The daily dosage of the sulforaphene is 20-150 mg/person, and the administration time is 1-24 weeks.
5. The medicament of claim 1, wherein: the sulforaphane is used alone or together with adjuvants to make into composition.
6. The medicament of claim 5, wherein: the composition is in the form of a pharmaceutical, nutraceutical, food or cosmetic.
7. The medicament of claim 1, wherein: the sulforaphane is used alone or in combination with other drugs.
8. The medicament of claim 7, wherein: said combination is selected from: in combination with surgery, in combination with one or more western medicines, in combination with Chinese herbal medicines, in combination with radiotherapy, in combination with gene therapy or in combination with bioregulators.
9. The medicament of claim 1, wherein: the method is characterized in that: the psoriasis is psoriasis vulgaris, erythrodermic psoriasis, arthrosis or pustular psoriasis; the psoriasis is in a progressive, quiescent or regressive phase.
10. The medicament of claim 1, wherein: the medicament is a medicament for relieving epidermal hyperproliferation and inflammatory reaction; or a drug for relieving skin erythema, phosphorus debris and infiltration; or a drug that reduces the extent of skin damage.
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CN115089606A (en) * | 2022-06-30 | 2022-09-23 | 安徽医科大学 | Zinc/cerium composite nano material, preparation method thereof and application thereof in psoriasis treatment |
CN117442695A (en) * | 2023-10-25 | 2024-01-26 | 陕西省中医医院 | A Chinese medicinal composition for treating psoriasis, and its preparation method |
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CN115089606A (en) * | 2022-06-30 | 2022-09-23 | 安徽医科大学 | Zinc/cerium composite nano material, preparation method thereof and application thereof in psoriasis treatment |
CN115089606B (en) * | 2022-06-30 | 2023-09-26 | 安徽医科大学 | Zinc/cerium composite nano material, preparation method thereof and application thereof in psoriasis treatment |
CN117442695A (en) * | 2023-10-25 | 2024-01-26 | 陕西省中医医院 | A Chinese medicinal composition for treating psoriasis, and its preparation method |
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