CN109939223B - Application of interleukin 2 in preparation of medicine for treating pemphigus vulgaris oral erosion - Google Patents
Application of interleukin 2 in preparation of medicine for treating pemphigus vulgaris oral erosion Download PDFInfo
- Publication number
- CN109939223B CN109939223B CN201910281417.2A CN201910281417A CN109939223B CN 109939223 B CN109939223 B CN 109939223B CN 201910281417 A CN201910281417 A CN 201910281417A CN 109939223 B CN109939223 B CN 109939223B
- Authority
- CN
- China
- Prior art keywords
- oral
- erosion
- pemphigus vulgaris
- treatment
- recombinant human
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Landscapes
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention belongs to the field of medicine preparation, and particularly discloses application of interleukin 2 in preparation of a medicine for treating pemphigus vulgaris oral erosion. The invention creatively and externally applies the low-dose recombinant human interleukin 2 to the oral mucosa erosion surface caused by the pemphigus vulgaris, so that the oral mucosa erosion caused by the pemphigus vulgaris can be recovered quickly, and the pain can be effectively relieved.
Description
Technical Field
The invention belongs to the field of medicine preparation, and particularly relates to application of interleukin 2 in preparation of a medicine for treating pemphigus vulgaris oral erosion.
Technical Field
Pemphigus vulgaris is a common bullous skin disease in dermatology, and is characterized in that a large amount of blisters and bullous blisters appear on the skin and mucous membrane of the whole body, the blisters and the bullous blisters are extremely easy to break, and erosion faces are difficult to heal. Approximately 60% of pemphigus vulgaris patients can develop blisters and bullae of oral mucosa, and break spontaneously to form a long-lasting erosion face, and the oral erosion usually lasts for months to years with obvious tenderness, which seriously affects the eating, drinking and daily life of the patients and brings great pain to the mind and body of the patients [1 ]. Furthermore, a proportion of patients may only exhibit persistent erosion of the oral mucosa without any skin damage [1 ].
The current treatment of pemphigus vulgaris mainly depends on systemic application of glucocorticoid and/or immunosuppressant, and administration routes comprise oral administration and intravenous injection; also, treatment with intravenous immunoglobulin (IVIG) is combined with severe patients [1-3 ]. These treatments often have a more positive effect on pemphigus vulgaris skin lesions, but are less effective on oral mucosal lesions in most patients; even if the skin damage is controlled through regular treatment, oral erosion focus can still last for weeks to months and is difficult to heal, pain is obvious, and the life quality of patients is greatly influenced. In response to this situation, the clinical guidelines recommend basic fibroblast growth factor for external use on erosive surfaces, and gargle containing lidocaine, nystatin, and physiological sodium chloride solution can be used for gargling to promote healing, relieve pain, and prevent local infection [2], but these topical treatments are not satisfactory in promoting healing of oral erosion and relieving pain.
In recent years, some biological agents targeting B cells, such as anti-CD 20 monoclonal antibodies (including Rituximab (Rituximab), Veltuzumab (Veltuzumab), etc.), and invasive therapeutic approaches such as plasma replacement and immunoadsorption, all show positive therapeutic effects on pemphigus vulgaris [2-7], but the price of both is high, and the invasiveness of the latter, limits the use of a considerable number of patients; moreover, the therapeutic effect of these new treatments on pemphigus vulgaris oral mucosal erosion has not been reported in a large sample of clinical data with specificity [4 ]; individual case reports suggest that patients with pemphigus vulgaris who received better treatment with veltuzumab still have recurrent attacks of erosion of the oral mucosa during maintenance therapy [8 ]. Therefore, how to solve the problem of intractable oral erosion of pemphigus vulgaris patients is a problem to be paid urgent attention clinically.
[1] Zhao Zhang, Chinese clinical dermatology [ M ]. Phoenix publishing media group, Jiangsu science and technology publisher, 1 month and 1 day of 2010
[2] China physician Association dermatologist division autoimmune diseases sub-professional Committee, experts in diagnosis and treatment of pemphigus vulgaris, China dermatological journal, 2016,49(11):761-65
[3]Harman KE,Brown D,Exton LS,et al.British Association ofDermatologists’guidelines for the management of pemphigus vulgaris2017.British J Dermatol.2017,177:1170-1201.
[4]Pollmann R,Schmidt T,Eming R,et al.Pemphigus:a ComprehensiveReview on Pathogenesis,Clinical Presentation and Novel TherapeuticApproaches.Clin Rev Allergy Immunol.2018Feb；54(1):1-25.
[5]Behzad M1,
C,Kneisel A,et al.Combined treatment withimmunoadsorption and rituximab leads to fast and prolonged clinical remissionin difficult-to-treat pemphigus vulgaris.Br J Dermatol.2012Apr；166(4):844-52.
[6]Huang A,Madan RK,Levitt J.Future therapies for pemphigus vulgaris:Rituximab and beyond.J Am Acad Dermatol.2016Apr；74(4):746-53
[7]Baum S,Gilboa S,Greenberger S,et al.Adjuvant rituximab therapy inpemphigus:a single-center experience of 18cases.J Dermatolog Treat.2013Dec；24(6):427-30
[8]Ellebrecht CT,Choi EJ,Allman DM,et al.Subcutaneous veltuzumab,ahumanized anti-CD20antibody,in the treatment of refractory pemphigusvulgaris.JAMA Dermatol.2014Dec；150(12):1331-5.
Disclosure of Invention
The first object of the present invention is to provide a medicament for the treatment of pemphigus vulgaris oral erosion.
The second purpose of the invention is to provide an application of the recombinant human interleukin 2.
Aiming at the treatment of pemphigus vulgaris, the prior dermatologic authoritative textbooks, monographs, medical guidelines and expert consensus are systematically described, including the systemic use (i.e. oral administration, intravenous injection, subcutaneous injection, etc.) of glucocorticoid, immunosuppressant, intravenous immunoglobulin (IVIG), biological agent and other drugs, plasma replacement, immunoadsorption and other invasive treatments, and the wet dressing of skin erosion face, external anti-infection drug and other treatments, and these measures are usually effective in controlling the overall disease condition of pemphigus vulgaris, but in clinical practice, oral erosion of most patients still exists for a long time or repeatedly occurs after the skin lesions are basically healed. Aiming at oral erosion, the basic fibroblast growth factor recommended in clinical guidelines is externally applied topically, and gargle containing lidocaine, nystatin and physiological sodium chloride solution components and the like have not ideal effects on promoting healing of oral erosion and relieving pain.
The invention mainly aims at the clinical difficulty that the pemphigus vulgaris oral erosion is not cured for a long time, and provides a medicament for treating the pemphigus vulgaris oral erosion, which comprises a pharmaceutically effective dose of recombinant human interleukin 2.
The research of the invention finds that the medicine containing the recombinant human interleukin 2 can effectively treat the oral erosion of pemphigus vulgaris.
Preferably, the medicament is an external preparation for oral administration.
By directly and locally applying the external preparation containing the recombinant human interleukin 2 to the affected part, the healing process of oral erosion can be accelerated, the oral pain can be relieved, and the oral rehabilitation of patients suffering from pemphigus vulgaris can be promoted.
Further preferably, the medicament is a spray preparation, a liniment or a gargle; preferably a spray formulation.
Preferably, the medicament also comprises pharmaceutically acceptable auxiliary materials; the auxiliary material is further preferably an auxiliary material which is used for preparing interleukin 2 into spray and is beneficial to the adhesion of the medicine on the oral mucosa.
In the medicament, the recombinant human interleukin 2 is preferably a low-dose preparation.
Preferably, the dosage of the recombinant human interleukin 2 is 1-100 ten thousand units/mL; preferably 10 to 50 ten thousand units/mL. In the present invention, a medicament, particularly an external preparation, containing the low-dose recombinant human interleukin 2 has a good effect on the treatment of oral erosion due to pemphigus vulgaris.
The invention also provides an application of the recombinant human interleukin 2 in preparing a medicament for treating pemphigus vulgaris oral erosion.
Preferably, the pharmaceutical composition is used for preparing the medicine for treating oral erosion in the treatment period of pemphigus vulgaris by glucocorticoid and/or immunosuppressant.
The application can be used for independently applying the recombinant human interleukin 2 to the treatment of oral erosion caused by pemphigus vulgaris, and can also be applied to patients who are using or use glucocorticoid and/or immunosuppressant, and the interaction of the recombinant human interleukin 2, the glucocorticoid and the immunosuppressant is utilized to synergistically improve the treatment effect.
Further preferably, said use is for the preparation of a medicament for external use to be applied to the face of pemphigus vulgaris oral erosion.
Still more preferably, the dosage of the recombinant human interleukin 2 for applying to the oral erosion surface of pemphigus vulgaris is 1-100 ten thousand units/mL, and preferably 10-50 ten thousand units/mL.
The research of the invention finds that the small dose of the recombinant human interleukin 2 is externally applied to the oral erosion surface of the pemphigus vulgaris locally, so that a good treatment effect can be achieved.
The recombinant human interleukin-2-containing compound is combined with pharmaceutically acceptable auxiliary materials to prepare the medicine.
The oral mucosa erosion caused by the pemphigus vulgaris has the characteristics of special property, troublesome treatment and long healing time. The invention creatively uses the low-dose recombinant human interleukin 2 at the affected part of oral mucosa erosion caused by the pemphigus vulgaris, so that the oral mucosa erosion caused by the pemphigus vulgaris can be recovered quickly, and the pain can be effectively relieved.
Advantageous effects
The method provides a tool for treating oral mucosa erosion caused by pemphigus vulgaris, and for patients who are ineffective in conventional treatment at present, after the recombinant human interleukin 2 external preparation is added on the basis of the original conventional treatment scheme, the pain is obviously relieved, and most of oral erosion which is not healed for a long time originally can be completely healed or basically healed within 2-4 weeks. The external preparation is obviously superior to the basic fibroblast growth factor local external application recommended by the current domestic guidelines in the aspects of alleviating oral pain and promoting the healing of oral erosion faces, and the local treatment methods such as gargle containing lidocaine, nystatin and physiological sodium chloride solution components.
Drawings
FIG. 1 is a comparative graph before and after treatment in example 1;
FIG. 2 is a comparative graph before and after treatment in example 2;
FIGS. 3 and 4 are comparative images before and after treatment in example 3;
FIG. 5 is a comparative image before and after treatment of example 4.
FIG. 6 is a comparative graph before and after treatment of example 5.
FIG. 7 is a comparative image before and after treatment of example 6.
FIG. 8 is a statistical chart of pain scores by Visual Analog Scale (VAS) in examples 1 to 6. VAS pain scores before and after pemphigus treatment with recombinant human interleukin 2. VAS pain scores were significantly decreased after two weeks of treatment with this drug compared to before treatment with recombinant human interleukin 2 (P <0.0001, N ═ 6), suggesting a reduction in pain.
Fig. 9 is a statistical chart of oral mucosal lesion severity scores in the autoimmune bullous skin disease severity scores (ABSIS) of examples 1-6. Severity scores for ABSIS oral mucosal lesions before and after recombinant human interleukin 2 treatment. Compared with the treatment before the recombinant human interleukin 2 is applied, the severity score of the ABSIS oral mucosa damage is obviously reduced after the treatment of the drug is applied for two weeks (P <0.05, N is 6), and the oral mucosa damage is reduced.
Fig. 10 is a statistical chart of oral mucosal lesion severity scores in Pemphigus Disease Area Index (PDAI) of examples 1-6. The severity of the oral mucosa damage of PDAI before and after recombinant human interleukin 2 treatment was scored. The PDAI oral mucosal lesion severity score decreased significantly after two weeks of treatment with this drug (P <0.05, N ═ 6) compared to before treatment with recombinant human interleukin 2, suggesting a reduction in oral mucosal lesions.
Detailed Description
The recombinant human interleukin 2 is prepared into an external spray which is easy to adhere to the inner wall of an oral cavity, the medicine concentration is 10-50 ten thousand IU/ml, the spray is sprayed on the oral cavity erosion surface during treatment, 1-2 sprays are carried out every square centimeter every time, 2 times are carried out every day, and the spray lasts for several days to several weeks until the erosion surface is completely healed. For pemphigus vulgaris patients receiving systemic (oral, intravenous) glucocorticoid therapy, the existing systemic treatment scheme can be continued, and the treatment scheme is added to promote the healing of oral erosion and relieve pain.
Example 1:
some women, 61 years old, entered dermatology in Xiangya II Hospital, Zhongnan university, No. 144X 95, 8.22 days in 2018, in "oral cavity, pharyngeal erosion of 9 months, aggravated semimonth". The oral cavity and the pharyngeal mucosa of a patient are subjected to erosion and pain at multiple places, the pain is aggravated when the patient eats and drinks water, the erosion face is not healed for 9 months continuously, the traditional Chinese medicine is taken by the patient before hospitalization, and the treatment is carried out in local clinics (details are not shown), so that the effect is not good.
The pemphigus vulgaris is confirmed to be the pemphigus vulgaris after being admitted, through antibody detection of the pemphigus vulgaris, skin biopsy and direct immunofluorescence examination, as the patient refuses to use glucocorticoid and immunosuppressant, only recombinant human interleukin 2 is coated on the oral erosion part locally after being admitted, 10 ten thousand units are coated on the oral erosion part twice a day, the oral erosion part is basically healed after being treated for 10 days, and the pain is completely relieved (figure 1).
Example 2:
one of Liu, male, 82 years old, entered dermatology of Xiangya II university, Zhongnan university, No. 145X 73, 10 months and 6 days in 2018, 1 week aggravated by oral erosion. Patients have no obvious inducement to oral mucosa erosion and pain, the oral mucosa erosion and pain lasts for 2 months, and the patients are diagnosed in Hunan Yao hospital of the university of China and south in 2018, 9 and 29 days, the patients are diagnosed as 'pemphigus vulgaris and infected', and are treated by glucocorticoid (methylprednisolone 48 mg/day) and immunosuppressant (azathioprine 50mg bid), and the effect is poor.
After entering the dermatology department of Xiangya II Hospital of the university of Central and south China for 10 and 6 days in 2018, recombinant human interleukin 2 is added to be externally applied to the oral erosion part for 10 ten thousand units twice a day, the dosage of the original glucocorticoid is reduced to 40 mg/day of methylprednisolone, the original immunosuppressant (azathioprine) is stopped, the oral erosion part is improved after one week of treatment by the scheme, most of the erosion surface is covered by epithelium, and the pain is obviously relieved (figure 2).
Example 3:
one of Liu, male, 44 years old, entered the dermatology department of Xiang ya II university, Zhongnan university, No. 147X 54, 12 months and 3 days in 2018 for 40 days aggravated by 'repeated oral ulceration for 4 months'. The oral erosion of the patient is continued 4 months ago and is difficult to heal, the patient has improved after the treatment (detailed) in the local clinic, but the oral erosion recurs before 40 days, and the patient has no improvement after the treatment of local hospital glucocorticoid. Pemphigus vulgaris was confirmed by pemphigus antibody detection, skin biopsy and direct immunofluorescence after admission on day 3/12 in 2018.
After the oral cavity is admitted, recombinant human interleukin 2 is added to externally coat the oral cavity erosion part while maintaining the prior glucocorticoid treatment, 10 ten thousand units are used for each time, twice a day, after 1 week of treatment, the oral cavity erosion part is basically healed, the pain is obviously relieved, and the oral cavity erosion part is improved to be discharged (figures 3 and 4).
Example 4:
li Yi (a certain amount of Li, female, 65 years old) entered the dermatology department of Xiang ya II university, Zhongnan university, No. 145 x 77, 10.15 days of 2018 because "the whole body is scattered on the erosion face with oral ulceration for half a year". Pemphigus vulgaris was confirmed by antibody detection of pemphigus, skin biopsy, and direct immunofluorescence examination. Prednisone 45mg qd is orally taken in clinic, the skin is improved, but the erosion and pain of oral lips and mucous membrane in oral cavity are not controlled.
After the administration, the recombinant human interleukin 2 is locally and externally coated on the oral erosion part while the existing dose of glucocorticoid treatment is maintained, 10 ten thousand units per time and 1 time per day are carried out, the pain of the oral mucosa is relieved after 2 weeks of treatment, the erosion surface begins to shrink, and the erosion of the oral lips is basically healed. When the double-consultation is carried out at the 4 th week and the 8 th week, the pain is obviously relieved, the erosion of the lips is healed, and the erosion surface of the mucous membrane in the oral cavity is obviously reduced (figure 5).
Example 5:
xuan one, male, 48 years old, entered dermatology department of Hunan Yao-II university, Zhongnan university, No. 145X 94, 10 and 9 days in 2018 because "the whole body is scattered on the erosive surface with oral erosion in 2 months". Before the patient is admitted to the hospital, the patient is hospitalized in a hospital in Xinjiang, and then the glucocorticoid (methylprednisolone 20 mg/day + prednisone 10 mg/day, the total amount is converted into prednisone 35 mg/day), the immunosuppressant (mycophenolate mofetil 500mg tid oral) and tripterygium glycosides tablet 20mg tid are systematically used, so that the external halometasone ointment and polymyxin B ointment are not obviously improved.
After admission to hospital in Xiangya II Hospital, the university of China and south China, recombinant human interleukin 2 is added and is locally coated on the oral erosion surface for 10 ten thousand units/time twice a day, while the treatment medicines and the dosage of the original glucocorticoid, immunosuppressant and the like are unchanged, and the scheme has the advantages that the skin and the oral erosion surface are obviously reduced and improved after 2 weeks of treatment, and the pain is obviously relieved (figure 6).
Example 6:
xiao Yi, female, 52 years old, entered Fuke Zhongnan university Xiangya II Hospital dermatology, hospitalization number 144X 83, 8 months and 31 days in 2018 for "repeated oral ulceration for 6 years, erythema on face and chest and blisters 3 days". The patient has repeated oral erosion in nearly 6 years and is difficult to heal, and the ulcer can still last for months and appear repeatedly after taking the traditional Chinese medicine for many times for treatment; the patient is diagnosed in the department of stomatology in Xiangya hospital in 2018, 5 and 28 days, and is diagnosed as recurrent oral ulcer, and is orally treated by immunomodulatory drugs such as thalidomide, total glucosides of paeony and the like, so that the effect is poor. Pemphigus vulgaris was confirmed by antibody detection of pemphigus vulgaris, skin biopsy and direct immunofluorescence examination after admission to hospital on day 31, 8/2018.
Because the patient refuses to use glucocorticoid and immunosuppressant, only the recombinant human interleukin 2 is locally coated on the oral erosion part for 10 ten thousand units/time twice a day after admission, and the recombinant human interleukin 2 is simultaneously injected subcutaneously for once every other day, with 80 ten thousand IU each time, after 2 weeks of treatment, the skin and the oral erosion part are basically healed, the pain is obviously relieved, and the oral erosion part is completely healed after 4 weeks of treatment (figure 7).
Example 7:
pain due to erosion of the oral mucosa in pemphigus patients can be assessed for severity by VAS pain scoring. The VAS is a Visual analog Scale/Score (VAS for short), which is sensitive and comparable. A 10cm transverse line is drawn on the paper, and one end of the transverse line is 0, so that no pain is caused; the other end is 10, which represents the most pain; the middle part shows different degrees of pain, and the patient selects one number from the 11 numbers according to the pain degree to evaluate the pain degree at the moment, wherein the larger the number is, the more severe the pain is. In this example, in 6 cases (examples 1 to 6) of pemphigus vulgaris patients treated with recombinant human interleukin 2 locally and orally, the VAS pain score was significantly reduced after 2 weeks of treatment compared to that before treatment, and the difference was statistically significant (p < 0.001) (fig. 8, table 1).
TABLE 1
Example 8:
autoimmune bullous skin disease severity score (ABSIS) is an international general scoring system for evaluating severity of pemphigus for objective and accurate evaluation of disease, and includes skin lesion severity score and oral mucosa lesion severity score. The higher the score, the more severe the damage to the skin or mucosa. In 6 cases (examples 1 to 6) of pemphigus vulgaris patients treated with recombinant human interleukin 2 locally and externally in oral cavity, ABSIS oral mucosa lesion severity scores were calculated before and after treatment, and the results suggest that the ABSIS oral mucosa lesion severity scores after 2 weeks of treatment were significantly lower than those before treatment, and the differences had statistical significance (p < 0.05) (fig. 9, table 2).
TABLE 2
Example 9:
the Pemphigus Disease Area Index (PDAI) is an internationally recognized indicator of pemphigus disease severity score for objective assessment of disease, including severity scores for skin lesions and oral mucosal lesions. The higher the score, the more severe the damage to the skin or mucosa. Oral cavity topical recombinant human interleukin 2 treatment 6 patients (examples 1 to 6) of pemphigus vulgaris with oral mucosal erosion as the main component, PDAI oral mucosal lesion severity score was calculated before and after treatment, and the results suggest that PDAI oral mucosal lesion severity score after 2 weeks of treatment was significantly lower than before treatment, with statistical significance of the difference (p < 0.05) (FIG. 10, Table 3)
TABLE 3
In conclusion, the traditional Chinese medicine composition is suitable for patients with pemphigus vulgaris who are treated by conventional medicines and have no effect on oral mucosal erosion, and after the traditional Chinese medicine composition is locally treated by the method, the oral erosion is recovered rapidly (most patients can be basically cured within 2-4 weeks), and the pain is greatly relieved, so that the treatment method has an obvious and rapid treatment effect on the oral mucosal erosion caused by the pemphigus vulgaris.
Claims (6)
1. An application of recombinant human interleukin 2 in preparing the medicines for treating the oral erosion of pemphigus vulgaris is disclosed.
2. Use according to claim 1, for the preparation of a medicament for the treatment of oral erosions during pemphigus vulgaris with glucocorticoids and/or immunosuppressants.
3. Use according to claim 1 or 2, for the preparation of a medicament for external application to the wounds of pemphigus vulgaris oral erosions.
4. Use according to claim 3, for the preparation of a medicament for administration to the oral erosion face of pemphigus vulgaris at a dose of 1 to 100 ten thousand units/mL of recombinant human interleukin 2.
5. Use according to claim 3, for the preparation of a medicament for administration to the oral erosion face of pemphigus vulgaris at a dose of between 10 and 50 ten thousand units/mL of recombinant human interleukin 2.
6. The use according to claim 1, wherein a pharmaceutical composition comprising recombinant human interleukin 2 in combination with a pharmaceutically acceptable excipient is used for the preparation of said medicament.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2019102717524 | 2019-04-04 | ||
| CN201910271752 | 2019-04-04 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109939223A CN109939223A (en) | 2019-06-28 |
| CN109939223B true CN109939223B (en) | 2020-04-07 |
Family
ID=67012808
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910281417.2A Active CN109939223B (en) | 2019-04-04 | 2019-04-09 | Application of interleukin 2 in preparation of medicine for treating pemphigus vulgaris oral erosion |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109939223B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103501825A (en) * | 2011-05-02 | 2014-01-08 | 免疫医疗公司 | Ultrafiltration concentration of allotype selected antibodies for small-volume administration |
| CN107257686A (en) * | 2014-12-18 | 2017-10-17 | 普林斯匹亚生物制药公司 | The treatment of pemphigus |
| CN107343888A (en) * | 2017-07-13 | 2017-11-14 | 中国医学科学院病原生物学研究所 | A kind of hydroxycholesterol oxycholesterol 25HC and application thereof |
-
2019
- 2019-04-09 CN CN201910281417.2A patent/CN109939223B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103501825A (en) * | 2011-05-02 | 2014-01-08 | 免疫医疗公司 | Ultrafiltration concentration of allotype selected antibodies for small-volume administration |
| CN107257686A (en) * | 2014-12-18 | 2017-10-17 | 普林斯匹亚生物制药公司 | The treatment of pemphigus |
| CN107343888A (en) * | 2017-07-13 | 2017-11-14 | 中国医学科学院病原生物学研究所 | A kind of hydroxycholesterol oxycholesterol 25HC and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| 2017年国内自身免疫相关性皮肤病研究进展;陆前进等;《临床皮肤科杂志》;20181231;第47卷(第12期);第826-830页 * |
| Involvement of T(H)1/T(H)2 cytokines in the pathogenesis of autoimmune skin disease-pemphigus vulgaris.;Satyam A et al.;《Immunol Invest》;20091231;第38卷(第6期);第498-509页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109939223A (en) | 2019-06-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Edwards et al. | Sweet's syndrome with multifocal sterile osteomyelitis | |
| US11938099B2 (en) | Use of tapinarof for the treatment of atopic dermatitis | |
| JP2022510377A (en) | Composition for treatment of the condition | |
| Shafran et al. | Topical undecylenic acid for herpes simplex labialis: a multicenter, placebo-controlled trial | |
| CN109939223B (en) | Application of interleukin 2 in preparation of medicine for treating pemphigus vulgaris oral erosion | |
| US4605556A (en) | Composition and method for treating erythematodes and mycosis | |
| Yco et al. | Pyoderma gangrenosum involving the head and neck | |
| CA2318125C (en) | Methods and kits for treating vulvovaginal candidiasis with miconazole nitrate | |
| Malik et al. | Anal involvement in pemphigus vulgaris | |
| CN111821423B (en) | Application of interleukin 2 in treating chronic idiopathic urticaria | |
| HARRELL et al. | A study of North American blastomycosis and its treatment with stilbamidine and 2-hydroxystilbamidine | |
| Haddad et al. | Streptomycin in bubonic plague | |
| WO2017147475A1 (en) | Method and composition for treating cancer or skin lesion using a vaccine | |
| US7700613B2 (en) | Use of 7-t-butoxyiminomethylcamptothecin for the preparation of a medicament for the treatment of uterine neoplasms | |
| KR20210044805A (en) | Wart treatment | |
| CN110327354B (en) | Application of diosgenin in treatment and prevention of psoriasis | |
| WO2020143393A1 (en) | Use of red nocardia cell wall skeleton for preparing pharmaceutical for treating lichen planus | |
| WO2022103352A1 (en) | The use of intravenous immunoglobulin in the preparation of a drug for the treatment of cutis verticis gyrata disease | |
| Reddy | Drug Corner Efficacy and Safety of Human Placental Extract (HPE) in Women with Cervical Erosion | |
| Kawen et al. | Rifampicin and Trimethoprim Sulfamethoxazole plus intralesional antimony compared with antimony alone in treatment of cutaneous leishmaniasis | |
| KR20240089762A (en) | Compositions and methods for treating mucositis | |
| Goodfellow et al. | Histiocytosis X with unusual facial and axillary ulceration responding to topical nitrogen mustard | |
| Crisostomo et al. | The great mimicker: A case report of an extensive pyoderma gangrenosum in a 39-year-old Filipino female treated with systemic corticosteroids and antibiotics | |
| Roed-Petersen | Miconazole in the treatment of oral candidosis | |
| SU1395328A1 (en) | Method of treatment of diffusion neurodermite |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |