CN113274346A - Application of mupirocin ointment - Google Patents
Application of mupirocin ointment Download PDFInfo
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Abstract
The invention discloses an application of mupirocin ointment. The invention explores effective external medicine for treating psoriasis according to pathogenesis of psoriasis. The mupirocin ointment (Baidobang) is safe, has no toxic or side effect, is stable, effective, economical and practical, effectively treats the skin damage such as erythema scale and the like of the psoriasis patients, and is a medicine choice with higher cost performance for the psoriasis patients.
Description
Technical Field
The invention belongs to the field of clinical external medicines, and particularly relates to an application of mupirocin ointment.
Background
Psoriasis is a chronic inflammatory disease characterized clinically by erythematosquamous lesions. Psoriasis can affect the skin of any part, usually on the forearm, lower leg and scalp. Psoriasis epidermis is significantly thickened (mainly thickening of the acanthocyte layer) compared to normal skin, with keratinocyte passage time of 4-5 days, 10 times faster than normal; the epidermis shows granular layer loss, hyperkeratosis and parakeratosis due to the failure of normal differentiation; neutrophils aggregate in the epidermis and the epidermis process extends. Psoriasis places a great burden on both the physiology and the psychology of the patient. Current research shows that numerous factors act on the development of psoriasis, including: genetic factors, environmental factors such as infection, stress, drugs, etc., and immune factors (such as T cells, cytokines, chemokine factors), etc. Common bacteria in the skin, such as staphylococcus aureus, candida, and malassezia, are associated with psoriasis pathogenesis. Compared with healthy people, the psoriasis skin lesion can separate a large amount of staphylococcus aureus pathogenic factor enterotoxin, which indicates that staphylococcus aureus participates in the pathological mechanism of psoriasis
Mupirocin (mupirocin) is a secondary metabolite isolated from P.fluorescens cultures that inhibits isoleucyl-tRNA synthetase (IleRS). Mupirocin ointment (baidobang) is used as topical antibiotic, and has inhibitory effect on gram-positive pathogens such as Staphylococcus aureus and Streptococcus pyogenes. Currently mupirocin ointment is mainly used externally to treat skin infection caused by gram-positive bacteria.
Mupirocin shows its safe and stable pharmaceutical properties during long-term use. However, the current treatment method of mupirocin for psoriasis is not fully researched, and the main reason is that the research is not comprehensive enough and the treatment method is not properly used.
Disclosure of Invention
The invention aims to provide application of mupirocin ointment aiming at the defects of the prior art.
The purpose of the invention is realized by the following scheme: an application of mupirocin ointment in preparing medicine for treating psoriasis is disclosed.
Further, the medicine is an external ointment.
The invention has the beneficial effects that: the mupirocin ointment can effectively relieve psoriasis skin lesions, is suitable for psoriasis patients, has simple and convenient treatment method, is economical and practical, has no toxic or side effect, and is suitable for daily treatment of the psoriasis patients.
Drawings
FIG. 1 is a general graph of inhibition of dorsal skin lesions in imiquimod-induced psoriasis-like mice treated with the present invention in an SPF-rated environment; wherein, the blank control group is the group without medicine; imiquimod-positive control group, i.e., imiquimod-induced psoriasis-like mouse group; mupirocin + imiquimod is the mupirocin treatment group of the invention;
FIG. 2 is a graph showing the PASI score of imiquimod-induced psoriasis-like mice treated with the present invention in an SPF-scale environment; wherein a is erythema, b is scales, c is thickness, and d is PASI; PASI-Psoriasis Area and Severity Index (PASI) and Severity Index (psorias Area and Severity Index; a. b and c are evaluated according to 0-4 points, no-0 point, mild-1 point, moderate-2 point, severe-3 point, extremely severe-4 point, and a, b and c cumulative scores are used for the PASI comprehensive evaluation (0-12 points) of the d-chart. Imiquimod was a positive control group, i.e., an imiquimod-induced psoriasis-like mouse group; mupirocin + imiquimod is the mupirocin treatment group of the invention;
figure 3 is a graph showing the change in body weight of imiquimod-induced psoriasis-like mice treated with the present invention in an SPF-scale environment; wherein imiquimod is a positive control group, i.e., an imiquimod-induced psoriasis-like mouse group; mupirocin + imiquimod is the mupirocin treatment group of the invention;
FIG. 4 is a graph showing the histopathological features and epidermal thickness statistics of imiquimod-induced psoriasis-like mice treated in an SPF-level environment in accordance with the present invention; wherein, the blank control group is the group without medicine; imiquimod was a positive control group, i.e., an imiquimod-induced psoriasis-like mouse group; mupirocin + imiquimod-mupirocin treatment group of the invention;
FIG. 5 is a graph showing the expression of Ki67 in psoriasis-like mouse skin tissue induced by imiquimod in an SPF-grade environment in accordance with the present invention; wherein, the blank control group is the group without medicine; imiquimod was a positive control group, i.e., an imiquimod-induced psoriasis-like mouse group; mupirocin + imiquimod is the mupirocin treatment group of the invention;
FIG. 6 is a schematic representation of the treatment of Imquimod-induced psoriasis-like mouse skin tissue K14 in an SPF-scale environment in accordance with the practice of the present invention; wherein, the blank control group is the group without medicine; imiquimod was a positive control group, i.e., an imiquimod-induced psoriasis-like mouse group; mupirocin + imiquimod is the mupirocin treatment group of the invention;
FIG. 7 shows the treatment of psoriasis-like mouse skin tissue CD4 induced by imiquimod in SPF-grade environment according to the invention+Schematic representation of T cell infiltration; wherein, the blank control group is the group without medicine; imiquimod was a positive control group, i.e., an imiquimod-induced psoriasis-like mouse group; mupirocin + imiquimod is the mupirocin treatment group of the invention;
FIG. 8 is a graph of the treatment of Imquimod induced psoriasis like mouse skin tissue CD8 in an SPF grade environment in accordance with the invention+(iv) T cell infiltration; wherein, the blank control group is the group without medicine; imiquimod was a positive control group, i.e., an imiquimod-induced psoriasis-like mouse group; mupirocin + imiquimod is the mupirocin treatment group of the invention;
FIG. 9 shows that the treatment of psoriasis-like mouse skin tissue Ly6G induced by imiquimod in SPF-grade environment is performed according to the invention+Neutrophil infiltration; wherein, the blank control group is the group without medicine; imiquimod as a positive control, i.e. imiquimod-induced psoriasis-like smallA mouse group; mupirocin + imiquimod is the mupirocin treatment group of the invention;
FIG. 10 is a graph of the treatment of imiquimod induced psoriasis like mouse skin tissue CD103 in an SPF scale environment in accordance with the invention+TRMCell infiltration; wherein, the blank control group is the group without medicine; imiquimod was a positive control group, i.e., an imiquimod-induced psoriasis-like mouse group; mupirocin + imiquimod is the mupirocin treatment group of the invention;
the experimental data in the figure are analyzed and collated by SPSS20.0, without special indication, and expressed as mean. + -. standard deviation (mean. + -. SD). All experiments were repeated at least 3 times. The pairwise data comparison is performed by adopting a t test (Student's t-test); more than two groups of data are analyzed by one-way anova, and P <0.05 is considered to have statistical significance. P <0.05, P <0.01, P <0.001, P < 0.0001.
Detailed Description
In the invention, the mupirocin ointment is administrated by uniformly applying the bazedoary mupirocin ointment to the skin lesion of a cleaned psoriasis patient every day, and removing the mupirocin ointment after the affected part is coated and applied by an insurance film for 5 minutes.
The objects and effects of the present invention will become more apparent from the following detailed description of the embodiments of the present invention with reference to the accompanying drawings.
Dividing the experimental mice into 3 groups, namely 1) blank control groups; 2) imiquimod group; 3) mupirocin + imiquimod group. The back of each of the three groups of mice is unhaired, and the back of the blank control group of mice is not smeared; the imiquimod group mice were evenly smeared with 62.5mg of 5% imiquimod cream (Sichuan mingxin) on the back; mupirocin + imiquimod group mice were first evenly coated with 62.5mg of 5% imiquimod cream (tetrakamincin) on the same back followed by 1mm thick mupirocin ointment (bazedoary) on the same site. The ointment was applied once a day for 6 consecutive days. The molding treatment was observed on day 7. Figure 1 is a general graph of model-making treated mice showing that compared to the placebo group, the efficacy of the imiquimod composition induces psoriasis-like lesions with typical clinical features of psoriasis such as erythema, scaling, etc. The mupirocin and imiquimod group had significantly reduced skin damage, as well as scales and erythema. Figure 2 the PASI score of the modelled treated mice shows that compared to the imiquimod group, the erythema and scaling scores of mupirocin + imiquimod group were significantly reduced after 3 days of modelling, and the thickness and PASI scores were significantly reduced the second day after modelling.
Weight: c57BL/6 mice at 6-8 weeks were weighed and randomized into 2 groups of 15 mice per group by body weight. Two groups of mice had their backs unhaired, and the imiquimod group of mice was evenly smeared with 62.5mg of 5% imiquimod cream (chuanmingxin) on their backs; mupirocin + imiquimod group mice were first evenly coated with 62.5mg of 5% imiquimod cream (tetrakamincin) on the same back followed by 1mm thick mupirocin ointment (bazedoary) on the same site. The ointment was applied once a day for 6 consecutive days. Daily continuous weighing and recording, see table 1.
Table 1: effect of drugs on animal body weight
Number of days | Imiquimod group body weight (g) | Mupirocin + imiquimod group body weight (g) |
0 | 17.623±0.747 | 17.458±0.822 |
1 | 15.505±0.5 | 15.383±0.665 |
2 | 14.843±0.423 | 14.53±0.785 |
3 | 13.773±0.578 | 14.02±0.901 |
4 | 13.613±0.76 | 13.885±0.768 |
5 | 13.58±0.757 | 13.693±0.778 |
6 | 13.568±0.763 | 13.64±0.781 |
As can be seen from table 1, the weight of the mupirocin + imiquimod group in the experimental group was not significantly different from that of the imiquimod group in the control group.
Figure 3 the results of body weight measurements in two groups of modeled mice showed no significant difference in body weight for mupirocin + imiquimod group compared to imiquimod group.
Skin thickness measurement: randomly dividing the mice into three groups, wherein each group comprises 15 mice, the backs of the three groups of mice are unhaired, and the backs of the mice in a blank control group are not smeared; the imiquimod group mice were evenly smeared with 62.5mg of 5% imiquimod cream (Sichuan mingxin) on the back; mupirocin + imiquimod group mice were first evenly coated with 62.5mg of 5% imiquimod cream (tetrakamincin) on the same back followed by 1mm thick mupirocin ointment (bazedoary) on the same site. The ointment was applied once a day for 6 consecutive days. After 6 days of smearing, skin tissues of skin lesions of three groups of mice were subjected to H & E staining, and the thickness of epidermis of three groups was measured, as shown in Table 2.
Table 2: skin thickness statistics
Group of | Skin thickness (micron) |
Blank control | 20.14±2.116 |
Imiquimod group | 52.71±7.889 |
Mupirocin + imiquimod group | 25±1.291 |
As can be seen from table 2, the epidermal thickness of the imiquimod group was significantly increased compared to the blank control group, and the mupirocin + imiquimod group was significantly decreased compared to the imiquimod group.
Fig. 4 shows histopathology of the model mouse, compared with the blank control group, the mice in the imiquimod group have obvious epidermal thickening, 6-7 layers of epidermal thickness, obvious increase of horny layer, dermal vascular proliferation and increase of inflammatory cell infiltration. The skin damage on the back of mice in the mupirocin and imiquimod group is obviously relieved, the epidermis is obviously thinned, and the performance is similar to that of a blank control group. And the statistics of the epidermal thickness show that compared with a blank control group, the imiquimod group is obviously increased, and compared with an imiquimod group, mupirocin and imiquimod group are obviously reduced.
Ki67 immunohistochemical staining: the 45 mice are randomly divided into 3 groups, each group comprises 15 mice, the backs of the three groups of mice are unhaired, and the backs of the mice in the blank control group are not smeared; the imiquimod group mice were evenly smeared with 62.5mg of 5% imiquimod cream (Sichuan mingxin) on the back; mupirocin + imiquimod group mice were first evenly coated with 62.5mg of 5% imiquimod cream (tetrakamincin) on the same back followed by 1mm thick mupirocin ointment (bazedoary) on the same site. The ointment was applied once a day for 6 consecutive days. After the modeling is finished, materials are taken, the proliferation index Ki67 is immunohistochemically, and the number of positive cells in each mm length range is counted, which is shown in Table 3.
Table 3: ki67 immunohistochemical staining statistics
Group of | Ki67 number of positive cells/mm |
Blank control | 25.2±7.12 |
Imiquimod group | 81.62±5.901 |
Mupirocin + imiquimod group | 43.19±6.564 |
As can be seen from Table 3, the number of positive cells in the imiquimod group was significantly increased compared to the blank control group, and the number of positive cells in the mupirocin + imiquimod group was significantly decreased compared to the imiquimod group.
FIG. 5 shows that the skin damage proliferation index Ki67 immunohistochemical staining of the model-making mice shows that the Ki67 positive staining of the imiquimod group mice is basically expressed in the whole layer of the epidermis basal layer, the positive staining dispersion of the blank control group is distributed in the epidermis basal layer, and the positive staining ratio of the mupirocin and the imiquimod group is reduced compared with that of the imiquimod group. The result of statistics of the Ki67 positive cell number shows that compared with the blank control group, the imiquimod group is obviously increased, and the positive cell number in the mupirocin + imiquimod group is obviously reduced compared with the imiquimod group, and the statistical difference is realized.
K14 immunohistochemical staining: the 45 mice are randomly divided into 3 groups, each group comprises 15 mice, the backs of the three groups of mice are unhaired, and the backs of the mice in the blank control group are not smeared; the imiquimod group mice were evenly smeared with 62.5mg of 5% imiquimod cream (Sichuan mingxin) on the back; mupirocin + imiquimod group mice were first evenly coated with 62.5mg of 5% imiquimod cream (tetrakamincin) on the same back followed by 1mm thick mupirocin ointment (bazedoary) on the same site. The ointment was applied once a day for 6 consecutive days. After the molding is finished, materials are taken for immunohistochemistry with a proliferation index K14, and the percentage of positive cells in each mm length range is counted, which is shown in Table 4.
Table 4: k14 immunohistochemical positive rate statistics
Group of | K14%/mm |
Blank control | 29.58±6.718 |
Imiquimod group | 82.32±4.507 |
Mupirocin + imiquimod group | 48.8±6.574 |
As can be seen from table 4, the percentage of positive cells in the imiquimod group was significantly increased compared to the blank control group, and the percentage of positive cells in the mupirocin + imiquimod group was significantly decreased compared to the imiquimod group.
Fig. 6 shows that K14 positive staining of mice in the imiquimod group is basically in the whole epidermis layer, K14 positive staining of the blank control group is in the basal epidermis layer, and the expression of mupirocin + imiquimod group is reduced compared with that of the imiquimod group. The results of statistics on the percentage of K14 positive cells show that K14 is significantly increased in the imiquimod group compared with the blank control group, and mupirocin + imiquimod is significantly decreased compared with the imiquimod group, and the statistical difference is obtained.
CD4+T cell immunofluorescence staining: the 45 mice are randomly divided into 3 groups, each group comprises 15 mice, the backs of the three groups of mice are unhaired, and the backs of the mice in the blank control group are not smeared; the imiquimod group mice were evenly smeared with 62.5mg of 5% imiquimod cream (Sichuan mingxin) on the back; mupirocin + imiquimod group mice were first evenly coated with 62.5mg of 5% imiquimod cream (tetrakamincin) on the same back followed by 1mm thick mupirocin ointment (bazedoary) on the same site. The ointment was applied once a day for 6 consecutive days. After the molding is finished, the material is taken out, the immunofluorescence staining of CD4 is carried out, and the number of positive cells in each mm length range is counted, which is shown in Table 5.
Table 5: CD4+T cell immunofluorescence staining positive cell count
Group of | CD4 positive cell number/mm |
Blank control | 20.6±4.336 |
Imiquimod group | 104±20.74 |
Mupirocin+ imiquimod group | 41.6±9.633 |
As can be seen from Table 5, the imiquimod group CD4+T cells were significantly increased relative to the blank control group, mupirocin + imiquimod group CD4+T cells were significantly reduced compared to imiquimod group.
FIG. 7 model mouse skin lesion CD4+T cell immunofluorescent staining showed that more CD4 was present in the dermis of the imiquimod group mice+T cells, a fraction of the epidermis also expressed CD4, whereas dermal CD4 was found in the placebo and mupirocin + imiquimod groups+T cells express less. The statistical results showed that the blank control group and mupirocin + imiquimod group CD4 compared to imiquimod group 104. + -. 20.74+T cell number was 20.6. + -. 4.336 (P)<0.05) and 41.6. + -. 9.633 (P)<0.05), indicating CD4+T cell infiltration was significantly reduced.
CD8+T cell immunofluorescence staining: the 45 mice are randomly divided into 3 groups, each group comprises 15 mice, the backs of the three groups of mice are unhaired, and the backs of the mice in the blank control group are not smeared; the imiquimod group mice were evenly smeared with 62.5mg of 5% imiquimod cream (Sichuan mingxin) on the back; mupirocin + imiquimod group mice were first evenly coated with 62.5mg of 5% imiquimod cream (tetrakamincin) on the same back followed by 1mm thick mupirocin ointment (bazedoary) on the same site. The ointment was applied once a day for 6 consecutive days. After the molding is finished, the material is taken out, the immunofluorescence staining of CD8 is carried out, and the number of positive cells in each mm length range is counted, which is shown in table 6.
Table 6: CD8+T cell immunofluorescence staining positive cell count
Group of | CD8 positive cell number/mm |
Blank control | 29.4±4.45 |
Imiquimod group | 71±11.49 |
Mupirocin + imiquimod group | 29.4±6.504 |
As can be seen from Table 6, the imiquimod group CD8+T cells were significantly increased relative to the blank control group, mupirocin + imiquimod group CD8+T cells were significantly reduced compared to imiquimod group.
FIG. 8 model mouse skin lesion CD8+T cell immunofluorescent staining showed more CD8 in the dermis of mice in the imiquimod group+T cells, a portion of the epidermis, also express CD 8. The statistical results show that the blank control group and the mupirocin + imiquimod group are CD8+T cell number 29.4. + -. 4.45 (P)<0.05) and 29.4. + -. 6.504 (P)<0.05), whereas in the imiquimod group 71 ± 11.49, the increase was significant. The results demonstrate that mupirocin treatment can reduce imiquimod-induced skin lesions CD8 in a mouse psoriatic dermatitis model+Infiltration of T cells.
Ly6G+Performing immunofluorescence staining on the neutrophils: the 45 mice are randomly divided into 3 groups, each group comprises 15 mice, the backs of the three groups of mice are unhaired, and the backs of the mice in the blank control group are not smeared; the imiquimod group mice were evenly smeared with 62.5mg of 5% imiquimod cream (Sichuan mingxin) on the back; mupirocin + imiquimod group mice were first evenly coated with 62.5mg of 5% imiquimod cream (tetrakamincin) on the same back followed by 1mm thick mupirocin ointment (bazedoary) on the same site. The ointment was applied once a day for 6 consecutive days. After the molding is finished, the material is taken, the immunofluorescence staining of Ly6G is carried out, andthe number of positive cells per mm length was counted and is shown in Table 7.
Table 7: ly6G immunofluorescent staining positive cell number statistics
Group of | Ly6G positive cells/mm |
Blank control | 22.2±5.167 |
Imiquimod group | 127.2±18.14 |
Mupirocin + imiquimod group | 32.8±6.301 |
As can be seen from Table 7, the imiquimod group Ly6G+The neutrophil granulocytes were significantly increased compared to the blank control group, mupirocin + imiquimod group Ly6G+The neutrophils were significantly reduced compared to the imiquimod group.
FIG. 9 model mouse skin lesion Ly6G+Neutrophil immunofluorescence staining showed that Ly6G was located on the cell surface, and that the expression of Ly6G was abundant in the spinous process of dermis in mice in imiquimod group, whereas the expression of Ly6G in dermis in blank control group and mupirocin + imiquimod group was significantly reduced. The statistics of the number of Ly6G positive cells showed that the numbers of 22.2 + -5.167 (P) in the blank control group and mupirocin + imiquimod group were respectively higher than 127.2 + -18.14 in the imiquimod group<0.05) and 32.8. + -. 6.301 (P)<0.05). The results suggest that mupirocin treatment can reduce imiquimod-induced neutrophil infiltration in the dermis of psoriatic dermatitis mouse model skin lesions.
CD103+TRMAnd (3) cell immunohistochemical staining: the 45 mice are randomly divided into 3 groups, each group comprises 15 mice, the backs of the three groups of mice are unhaired, and the backs of the mice in the blank control group are not smeared; the imiquimod group mice were evenly smeared with 62.5mg of 5% imiquimod cream (Sichuan mingxin) on the back; mupirocin + imiquimod group mice were first evenly coated with 62.5mg of 5% imiquimod cream (tetrakamincin) on the same back followed by 1mm thick mupirocin ointment (bazedoary) on the same site. The ointment was applied once a day for 6 consecutive days. After the modeling is finished, the material is taken out for immunohistochemical staining of CD103, and the number of positive cells in each mm length range is counted, which is shown in Table 8.
Table 8: CD103+TRMStatistics of positive cell numbers in immunohistochemical staining of cells
Group of | CD103 positive cell number/mm |
Blank control | 10.6±2.702 |
Imiquimod group | 31±9.381 |
Mupirocin + imiquimod group | 16.2±2.588 |
As can be seen from Table 8, the imiquimod group CD103+TRMThe cells were significantly increased compared to the blank control group, and the mupirocin + imiquimod group CD103+TRMThe cells were significantly reduced compared to the imiquimod group.
FIG. 10 model mouse skin lesion CD103+TRMImmunohistochemical staining of cells showed that CD103 (positive staining in brown) was localized to the cell surface, with less expression in the dermis of the placebo and mupirocin + imiquimod groups, and more positive expression of dermal CD103 in the imiquimod group. Statistics of CD103 positive cells showed 10.6 + -2.702 (P) in the blank control group and mupirocin + imiquimod group, respectively, compared to 31 + -9.381 in the imiquimod group<0.05) and 16.2. + -. 2.588 (P)<0.05). The results suggest that mupirocin treatment can reduce T in the dermis of an imiquimod-induced psoriatic dermatitis mouse model skin lesionRMThe number of the cells.
Figures 1, 2, 4, 5, 6, 7, 8, 9, 10 all illustrate the positive role of mupirocin ointment in the treatment of psoriasis. Figure 3 shows that there was no significant difference in mouse body weight compared to imiquimod group during psoriasis treatment with mupirocin ointment, indicating that the present invention had no significant effect on the body weight of experimental mice.
To summarize: the mupirocin ointment can obviously reduce the PASI score after model building, reduce the epidermal thickness, reduce the pathological manifestations of psoriasis-like tissues, reduce the expression of proliferation indexes K14 and Ki67 and reduce inflammatory cells in the skin lesions of the mouse model of psoriasis-like dermatitis induced by imiquimod, such as CD4+T cell, CD8+T cell, neutrophil and TRMAnd (4) infiltrating. Has good therapeutic effect on psoriasis and has no obvious effect on body weight.
The above embodiments are intended to illustrate rather than to limit the invention, and any modifications and variations of the present invention are within the spirit of the invention and the scope of the claims.
Claims (2)
1. An application of mupirocin ointment in preparing medicine for treating psoriasis is disclosed.
2. The use of claim 1, wherein the medicament is a topical ointment or the like.
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2021
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