CN102772406A - Novel application method of treating psoriasis by matrine - Google Patents
Novel application method of treating psoriasis by matrine Download PDFInfo
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- CN102772406A CN102772406A CN2012103021782A CN201210302178A CN102772406A CN 102772406 A CN102772406 A CN 102772406A CN 2012103021782 A CN2012103021782 A CN 2012103021782A CN 201210302178 A CN201210302178 A CN 201210302178A CN 102772406 A CN102772406 A CN 102772406A
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Abstract
The invention provides a novel application method of treating psoriasis by matrine, and belongs to the field of medicines. The application method comprises the following ways: 1, treating psoriasis by adopting oxymatrine injection intravenous drip; 2, treating psoriasis by adopting oxymatrine injection intravenous drip combined with black light irradiation; 3, treating psoriasis by adopting oral administration of oxymatrine tablets or capsules; and 4, treating psoriasis by externally applying oxymatrine ointment on an affected part. Compared with existing medicaments and methods for treating psoriasis, the novel application method can achieve unexpected curative effect, the cure rate is over 80 percent, and the novel application method is an innovation in treating psoriasis.
Description
Technical field
The invention belongs to drug world, particularly relate to oxymatrine and treat psoriatic purposes method.
Background technology
Psoriasis is the commonly encountered diseases of department of dermatologry, and frequently-occurring disease does not still have the ideal medicament of treating primary disease at present.The psoriatic cause of disease and pathogenesis are unclear as yet, generally believe that psoriasis is the disease of multifactorial inheritance of multiple factor interaction, cause at last that through immune-mediated co-channel keratinocyte breeds.It is relevant with adjusting, endocrine, neural Nervous and Mental Factors, dysbolismus, microcirculation and the hemorheology etc. of the propagation of heredity, immunity, infection, keratinocyte and differentiation that psoriasis is generally thought more.Psoriatic morbidity is relevant with antibacterial, fungus and viral infection.The physiological important feature of psoriasis pathology is that stratum basale keratinocyte propagation is quickened; Mitotic cycle shortens to 37.5 hours; Epidermal replacement time shortened to 3-4 days in 28 days by normal skin, and parakeratosis appears in histopathology, and keratinocyte is vegetative state.Psoriatic lesion place lymphocyte, monocyte infiltration are psoriatic important pathological characters, show this sick incidence and development of immune system participation.Psoriatic morbidity is relevant with antibacterial, fungus and viral infection.Psoriasis also can be with complication such as liver, eye, gastrointestinal tract, cardiovascular, kidney and metabolic diseases except that the skin infringement.
Psoriatic's state of an illness is shown effect repeatedly, and several years even take medicine decades, and effect is undesirable; Active drug Western medicine prepn often side effect is big and cost an arm and a leg; Psoriatic medicine of treatment and method mainly contain now: 1, antitumor drug such as methotrexate: methotrexate is a kind of folic acid reductase inhibitor, and DNA is synthetic in the time of can stoping epidermal cell proliferation, suppresses nuclear mitosis; The lymphopoiesis that can suppress to be activated in the body; Weakening the function and the chemotaxis that suppresses neutrophilic granulocyte of cd8 cell, be the psoriatic standard medication of whole body therapeutic, but its therapeutic dose and toxic dose is very approaching; Long-term prescription can cause liver popularity fibrosis and liver cirrhosis, so when using, note safety, the strict indication of selecting; 2, glucocorticoid: use glucocorticoid in generally not advocating at present; Because of effective dose often bigger; Can cause serious adverse; And after decrement or drug withdrawal, " knock-on " phenomenon can take place or bring out serious pustule type and erythrodermic psoriasis, generally only be used for erythrodermic, joint type or general property pustule type silver bits and use other medicines nonresponder; 3, tretinoin medicine: the psoriatic mechanism of this type of Drug therapy mainly is to regulate epidermis propagation and differentiation and immunologic function etc.Take separately or with the treatment of other therapy Combined application in the severe psoriasis, have than satisfactory effect, but but its teratogenesis tire take for a long time and blood fat rising, liver injury etc. can occur; 4, immunotherapy: mainly contain ciclosporin A, tacrolimus etc., its untoward reaction has nephrotoxicity, hypertension etc.; 5, biological products assay institute: like Embrel, Ah method's Saite etc., another big progress on the biological preparation curing psoriasis history, but it costs an arm and a leg, and also has problems such as untoward reaction, needs further observational study, the exploitation novel formulation; 6, act on the medicine of nuclear receptor: liarozole is imidazole derivative, tretinoin analogies and tretinoin metabolism blocker; But do not belong to tretinoin; Bring into play curative effect through endogenous tretinoin amount in increase tissue and the blood, common side effect has pruritus, drying, cheilitis etc.; 7, antibiotic and vitamin medicaments: many clinically psoriatic generations are relevant with infected by microbes such as antibacterial, fungus, viruses with recurrence, can select anti-infective therapy for use to these cases.Report vitamin A, vitamin D are arranged
2, ampeptide elemente etc. is to psoriatic treatment; 8, black light irradiation treatment psoriasis is like the method for narrow spectrum UVB irradiation treatment.In sum, active drug is the big and easy relapse of side effect often, and biological preparation costs an arm and a leg and side reaction is also arranged, and uses very ideal of black light irradiation treatment effect merely.
Summary of the invention
The object of the invention will solve existing medicine and method exactly and treat defectives such as psoriasis poor effect, side effect are big, provides a kind of oxymatrine that adopts to treat psoriatic new purposes method.
Oxymatrine has direct antiinflammatory action, immunoregulation effect, inhibition tumor proliferation, induce differentiation and apoptotic effect, anti-virus sterilizing effect, anti-hypoxia, expansion blood vessel, blood fat reducing, arrhythmia, calmness, analgesic, lower the temperature, improve the hemorheological indexes effect.Oxymatrine (oxymatrine; OM) be a kind of alkaloid that extracts characteristic Chinese crude drug-cassia leguminous plant Herba Sophorae alopecuroidis (Sophore alopecuroides. L) from Ningxia Hui Autonomous Region; Oxymatrine has multiple pharmacologically active, and safety range is big, and toxicity is little; Absorbing better, is a kind of application prospect tcm product more widely.The central nervous system, oxymatrine has the effect of calmness, analgesia, analgesic, cooling; Digestive system has the anti-liver injury effect, effectively protects hepatocyte; Oxymatrine has antitumor action, can effectively suppress the propagation of human hepatoma cell strain HepG2, and have direct killing effect; Cardiovascular system, oxymatrine have anti-hypoxia, expand effects such as blood vessel, blood fat reducing, arrhythmia.The direct antiinflammatory action of oxymatrine: matrine is hormone-like effect to be arranged and the powerful anti-inflammatory agent that do not have hormone side effect; The immunoregulation effect of oxymatrine: oxymatrine has stronger immunoregulation effect, can be through its antiinflammatory action of influence performance to variation, cytokine and other inflammatory regulatory factor of host's antibody horizontal, immunocyte; Antitumor mechanism: oxymatrine has the inhibition tumor proliferation, induces differentiation and apoptotic effect; The anti-virus sterilizing effect of oxymatrine: it is active that oxymatrine has direct anti-virus sterilizing, and fungicidal spectrum is wider.The direct antiinflammatory action of oxymatrine can suppress the psoriasis inflammatory reaction, and the anti-virus sterilizing effect can be treated the psoriasis that causes by infecting, to the etiology and pathogenesis of onset of psoriasis; The immunoreation of oxymatrine scalable psoriasis; The propagation that suppresses keratinocyte, antioxidation, the psoriatic has tangible microcirculation and hemorheology to change; Its intensity of anomaly is relevant with the psoriatic state of an illness, and oxymatrine has the hemorheological effect of improvement.Oxymatrine has the effect of calmness, analgesia, analgesic, cooling, the psoriasis that scalable is caused by neural Nervous and Mental Factors the central nervous system.Psoriasis be prone to occur together liver, cardiovascular, and metabolic disease etc.; And treat psoriatic effective Western medicine side effect such as hepatorenal damage, blood fat increase are often arranged; Oxymatrine has the anti-liver injury effect; Effectively the protection hepatocyte has anti-hypoxia simultaneously, expands effects such as blood vessel, arrhythmia, blood fat reducing, effectively prevents the generation of psoriasis complication.Oxymatrine is as a kind of potential psoriasis medicine, and the treatment psoriasis has good application prospects.Concrete technical solution of the present invention is: the one, adopt the intravenous drip of oxymatrine injection; The 2nd, adopt the oxymatrine intravenous drip, cooperate the black light irradiation treatment simultaneously; The 3rd, adopt the treatment of oxymatrine tablet or capsule oral; The 4th, adopt oxymatrine ointment to smear the affected part external curing.
Through zoopery oxymatrine being treated psoriatic mechanism below further specifies:
1, oxymatrine is to the influence of psoriasis mouse model serum il-2, IL-10 and TNF-alpha levels.
Purpose is the influence of research oxymatrine to psoriasis mouse model IL-2, IL-10 and TNF-alpha levels, inquires into the mechanism of its protection psoriasis mice.Method adopts injection estrogen to stimulate the outgrowth method of mouse vagina epithelial tissue to duplicate the psoriasis mouse model; Give the oxymatrine intervention of various dose simultaneously; Test after 10 days; Get mice serum and measure the content of IL-2, IL-10 and TNF-α, and observe oxymatrine the mitotic influence of mouse vagina epithelial cell.Oxymatrine 80,40 and 20mg.kg as a result
-1All can suppress the mouse vagina epithelium mitosis (
P<0.01), and reduce estrogen cycle mice serum IL-2, TNF-alpha content (
P<0.01); Oxymatrine 80 mg.kg
-1With 40 mg.kg-
1Can raise estrogen cycle mice serum IL-10 content (
P<0.01,
P<0.05).The conclusion oxymatrine has protective effect to experimental psoriasis, and this effect possibly and reduce serum il-2 and TNF-alpha levels with its inhibition epidermal cell proliferation, and rising IL-10 level is relevant.
Table 1 oxymatrine to the influence of estrogen cycle vagina epithelium mitosis model mice serum il-2, IL-10 and TNF-alpha levels (
, n=30)
| Group | Drug dose (mg.kg -1) | IL-2(ng/ml) | IL-10(ng/ml) | TNF-α(ng/ml) |
| Normal control | NS | 10.41±2.12 | 5.52±1.82 | 1.72±0.39 |
| Model | NS | 31.82±4.45 ** | 3.95±1.59 ** | 2.75±0.48 ** |
| MTX | 1 | 18.99±3.74 ** | 5.32±1.72 | 2.20±0.21 ** |
| OMT | 80 | 19.44±3.71 ** | 5.00±1.97 | 1.88±0.27 ▲▲ |
| ? | 40 | 22.56±4.01 ** ▲ | 4.83±1.82 ? | 1.97±0.31 ▲ |
| ? | 20 | 23.97±6.29 ** ▲ | 3.94±0.62 **▲▲ | 1.94±0.35 ▲ |
Compare with the normal control group
* P<0.05,
* P<0.01; Compare with model group
P<0.05,
P<0.01; Compare with the MTX group
▲ P<0.05,
▲ ▲ P<0.01.
Table 2 oxymatrine to the mitotic influence of estrogen cycle mouse vagina epithelium basal cell (
, n=30)
| Group | Drug dose (mg.kg -1) | Mitosis rate (%) |
| Normal control | NS | 5.77±1.08 |
| Model | NS | 25.00±1.59 ** |
| MTX | 1 | 14.20±1.17 ** |
| OMT | 80 | 11.33±0.66 ** ▲▲ |
| ? | 40 | 14.25±0.75 ** |
| ? | 20 | 17.42±0.88 ** ▲▲ |
Compare with the normal control group
* P<0.05,
* P<0.01; Compare with model group
P<0.05,
P<0.01; Compare with the MTX group
▲ P<0.05,
▲ ▲ P<0.01.
2, oxymatrine is to the antagonism of psoriasis mouse model oxidative stress.
Purpose is the antagonism of research oxymatrine to psoriasis mouse model oxidative stress, inquires into it and prevents and treats psoriatic mechanism.Method adopts injection estrogen to stimulate the outgrowth method of mouse vagina epithelial tissue to duplicate the psoriasis mouse model; Give the oxymatrine intervention of various dose simultaneously; Test after 10 days; Get mice serum and measure the content of SOD, MDA, GSH, T-AOC and NO, and observe oxymatrine the mitotic influence of mouse vagina epithelial cell.Oxymatrine 80,40 and 20mg.kg as a result
-1All can suppress the mouse vagina epithelium mitosis (
P<0.01); Oxymatrine 80mgkg can raise estrogen cycle mice serum SOD and T-AOC content (
P<0.05,
P<0.01), reduction MDA, GSH and NO content (
P<0.01); Oxymatrine 40mg/kg can reduce estrogen cycle mice serum MDA and NO content (
P<0.05,
P<0.01).The conclusion oxymatrine has protective effect to experimental psoriasis, and this effect possibly and reduce serum MDA, GSH and NO content with its inhibition epidermal cell proliferation, and the content of increased SOD and T-AOC is relevant.
Table 3 oxymatrine to the influence of estrogen cycle vagina epithelium mitosis model mice SOD in serum, MDA, GSH, T-AOC, NO (
, n=30)
Compare with the normal control group
* P<0.05,
* P<0.01; Compare with model group
P<0.05,
P<0.01; Compare with the MTX group
▲ P<0.05,
▲ ▲ P<0.01.
Table 4 oxymatrine to the mitotic influence of estrogen cycle mouse vagina epithelium basal cell (
, n=30)
| Groups | Dose(mg.kg -1) | Mitotic index（％） |
| Control | NS | 6.23±0.69 |
| Model | NS | 26.17±2.47 ** |
| MTX | 1 | 14.42±1.06 ** |
| OMT | 80 | 11.55±0.80 ** ▲▲ |
| ? | 40 | 14.75±0.94 ** |
| ? | 20 | 18.08±1.11 ** ▲▲ |
3, oxymatrine is to the influence of expression of the outgrowth mouse vagina epithelial cells of estrogen-induced proliferative NA and apoptosis.
Purpose is to inquire into the influence of oxymatrine to psoriasis model estrogen cycle mouse vagina epithelial cells propagation and apoptosis.Method adopts injection estrogen to stimulate the outgrowth method of mouse vagina epithelial tissue to duplicate the psoriasis mouse model; Give the oxymatrine intervention of various dose simultaneously; Test after 10 days, application SABC and end-labelling (TUNEL) detect respectively respectively organizes mouse vagina epithelial cells proliferative and antigen (PCNA) expression and apoptosis situation.The conclusion oxymatrine has protective effect to experimental psoriasis, this effect maybe with its reduction epidermis cell PCNA expression, promote apoptosis in epidermal cell relevant.
The influence (
) that table 5 oxymatrine is expressed estrogen cycle vagina epithelium mitosis model mice vaginal epithelial cell PCNA
Compare with the normal control group
* P<0.0714,
* P<0.01; Compare with model group
P<0.0714,
P<0.01; Compare with the MTX group
▲ P<0.0714,
▲ ▲ P<0.01.
Table 6 oxymatrine is to the influence (
) of estrogen cycle mouse vagina epithelium apoptotic index
P1 with matched group relatively;
P2 with model group relatively;
P3 with MTX group relatively
More than three part Study from oxymatrine to psoriasis antiinflammatory, antioxidation and suppress three parts of propagation; Verified that oxymatrine is to psoriatic therapeutical effect and mechanism of action; Find the new medicine of psoriasis, for oxymatrine is treated psoriasis and development and use provide experimental basis clinically.
The present invention has following remarkable result:
1, the present invention adopts oxymatrine to treat psoriatic new purposes, and compares with existing medicine, method and can obtain beyond thought curative effect, and cure rate reaches more than 80%, and this new purposes is an innovation to the treatment psoriasis.
2, adopting oxymatrine treatment psoriasis is fundamentally to start with; The hyper-proliferative that can suppress horn cell effectively improves psoriasis microcirculation and hemorheology and changes antiinflammatory; Effects such as immunomodulating recover psoriatic lesion; And can regulate each organ of human body comprehensively, cardiovascular and cerebrovascular vessel, liver, metabolic disease, central nervous system etc. are had regulating action, and can prevent and treat the psoriasis complication.
3, oxymatrine treatment psoriasis is in extensive range; Can be used for treating the complication of psoriasis vulgaris, psoriasis arthropathica, erythrodermic psoriasis, psoriasis pustulosa, each psoriasis pustulosa initiation; Like cardiovascular and cerebrovascular vessel, metabolism etc., also can treat various tumors, dermatitis and eczema etc.
4, oxymatrine treatment psoriasis safety range is big, and toxicity is little, fundamentally reverses psoriatic pathomechanism, prevents that complication from taking place, and reaches the optimal treatment boundary of treating both the principal and secondary aspects of a disease.
The specific embodiment
Select 203 routine patients; Clinical diagnosis meets psoriasis vulgaris, at 18-68 years old ages, has not accepted anti-psoriasis systematic treating in January; No photosensitive diseases; Serious viscera disease such as no hepatic and renal function injure, no active tuberculosis, hypertension, diabetes, cataract medical history are rejected trimester of pregnancy, women breast-feeding their children.The patient is divided into treatment group, combined group, irradiation group and matched group at random treats, carry out Comparison of therapeutic and evaluation then.The specific embodiment is following:
Embodiment 1,50 examples are organized in treatment, male 27 examples, women 23 examples, 20-68 years old ages, 40.32 years old mean age, course of disease January-26 year, average 2.42 years.Adopt the intravenous drip of oxymatrine injection, once a day, dosage 0.6g, 100 milliliters are carried out intravenous drip, around the course of treatment.
Embodiment 2,Combined group 53 examples, male 29 examples, women 24 examples, 19-67 years old ages, 40.12 years old mean age, course of disease January-24 year, average 2.32 years.Adopt oxymatrine intravenous drip (method is with embodiment 1), cooperate narrow spectrum UVB to the treatment of patient's focus skin exposure (adopting Waldmann UVB therapeutic instrument) simultaneously, predose is 0.25J/cm
2, increase general per 2 increase 0.02-0.03 J/cm later on gradually according to dermoreaction
2, the highest 0.66J/cm
2, 3 times weekly.Around also be the course of treatment.
Embodiment 3,Irradiation group 50 examples, male 26 examples, women 24 examples, 18-65 years old ages, 38.24 years old mean age, course of disease January-20 year, average 2.02 years.Adopt simple radiation modality, to the treatment of patient's focus skin exposure (adopting Waldmann UVB therapeutic instrument), predose is 0.25J/cm with narrow spectrum UVB
2, increase general per 2 increase 0.02-0.03 J/cm later on gradually according to dermoreaction
2, the highest 0.66J/cm
2, 3 times weekly, around also be the course of treatment.
Embodiment 4,Matched group 50 examples, male 26 examples, women 24 examples, 19-66 years old ages, 39.79 years old mean age, course of disease February-23 year, average 2.29 years.The employing ampeptide elemente is oral, around also be the course of treatment.
Show that through the X 2 test result 4 groups of therapeutic effect have significant difference (p < 0.001).Adjustment α=0.008 compares treatment group, combined group, irradiation group respectively with matched group, the result shows, treatment group, combined group, irradiation group therapeutic effect all significantly are better than matched group (p all < 0.001); Treatment group and combined group compare, (p>0.008); Treatment group and irradiation group compare, (p>0.008); Combined group and matched group have significant difference (p < 0.008).Explain that oxymatrine treatment psoriasis vulgaris has better curative effect, and the oxymatrine associating narrow spectrum UVB irradiation treatment more simple narrow spectrum UVB irradiation treatment effect of psoriasis vulgaris better (table 1).
Four groups of curative effect comparative examples of table 1 (%)
Treat preceding four groups of scoring there are no significant differences.After the treatment, four groups of scorings not identical entirely (P < 0.001) are checked demonstration in twos through LSD afterwards, and treatment group, combined group, irradiation group scoring all are significantly higher than matched group (p all < 0.001), there was no significant difference between treatment group, combined group, the irradiation group scoring.Relatively, four groups of equal significances of treatment back scoring reduce (table 2) before and after self.
Four groups of PASI scorings of table 2 comparison (x ± s)
| Group | The example number | Before the treatment (x ± s) | The treatment back (x ± s) | t | p |
| The treatment group | 50 | 11.66±5.55 | 2.91±2.98 | 9.831 | <0.001 |
| Combined group | 53 | 11.58±5.25 | 2.20±2.59 | 11.652 | <0.001 |
| Irradiation group | 50 | 11.69±5.41 | 3.81±3.98 | 8.300 | <0.001 |
| Matched group | 50 | 11.64±5.52 | 8.00±6.53 | 3.012 | 0.003 |
The untoward reaction situation: slight flushing 4 examples of skin appear in combined group, and wherein an example is felt slight causalgia, and incidence rate is 7.55%, and slight flushing 6 examples of skin appear in irradiation group, and incidence rate is 12%, two group of all influence treatment.Four groups of hematuria routines and biochemical routine are not all seen significantly unusually before and after the treatment, do not see that the untoward reaction of tangible system takes place.
Oxymatrine treatment psoriasis vulgaris curative effect is high, and safety is good, and the narrow spectrum UVB irradiation treatment psoriasis effect of oxymatrine associating is better, is worth the clinical wide popularization and application of carrying out.
Claims (5)
1. oxymatrine is treated psoriatic new purposes method, it is characterized in that using oxymatrine can treat psoriasis effectively.
2. oxymatrine according to claim 1 is treated psoriatic new purposes method, it is characterized in that adopting oxymatrine injection intravenous drip treatment psoriasis.
3. treat psoriatic new purposes method according to claim 1 and 2 described oxymatrines, it is characterized in that adopting the oxymatrine intravenous drip, cooperate black light irradiation treatment psoriasis simultaneously.
4. oxymatrine according to claim 1 is treated psoriatic new purposes method, it is characterized in that adopting oxymatrine tablet or capsule oral treatment psoriasis.
5. oxymatrine according to claim 1 is treated psoriatic new purposes method, it is characterized in that adopting oxymatrine ointment to smear affected part external curing psoriasis.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102973559A (en) * | 2012-12-03 | 2013-03-20 | 施惠娟 | Novel method of applying oxymatrine to treating eczematous dermatitis |
| CN111529753A (en) * | 2020-04-28 | 2020-08-14 | 宁夏医科大学总医院 | Oxymatrine-placenta mesenchymal stem cell hydrogel, preparation method and application |
| CN112843056A (en) * | 2021-04-08 | 2021-05-28 | 宁夏医科大学总医院 | Application of oxymatrine in reducing epidermal cell death caused by lipid toxicity of psoriasis patients |
-
2012
- 2012-08-23 CN CN201210302178.2A patent/CN102772406B/en active Active
Non-Patent Citations (1)
| Title |
|---|
| 周茹等: "氧化苦参碱对银屑病样小鼠模型氧化应激的拮抗作用", 《宁夏医科大学学报》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102973559A (en) * | 2012-12-03 | 2013-03-20 | 施惠娟 | Novel method of applying oxymatrine to treating eczematous dermatitis |
| CN111529753A (en) * | 2020-04-28 | 2020-08-14 | 宁夏医科大学总医院 | Oxymatrine-placenta mesenchymal stem cell hydrogel, preparation method and application |
| CN112843056A (en) * | 2021-04-08 | 2021-05-28 | 宁夏医科大学总医院 | Application of oxymatrine in reducing epidermal cell death caused by lipid toxicity of psoriasis patients |
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