阅读说明：本技术 一种含有沙利度胺与抗真菌药物的药物组合物及应用 (Pharmaceutical composition containing thalidomide and antifungal drug and application ) 是由 李玉叶 王睿睿 董荣静 张祎 于 2019-12-19 设计创作，主要内容包括：本发明公开了一种含有沙利度胺与抗真菌药物的药物组合物及其应用,该药物组合物含有沙利度胺与抗真菌药物,用于制备治疗艾滋病合并马尔尼菲篮状菌病的药物。该药物组合物,对于艾滋病合并马尔尼菲篮状菌病感染的小鼠的治疗作用强于单独使用抗真菌药物,同时也强于单独使用沙利度胺。本发明使得抗真菌药物的治疗剂量降低,对马尔尼菲篮状菌的抑制效果增强,有效地提高了治疗效果。(The invention discloses a pharmaceutical composition containing thalidomide and an antifungal drug and application thereof, wherein the pharmaceutical composition contains thalidomide and an antifungal drug and is used for preparing a drug for treating AIDS combined Marneffei panuliasis. The pharmaceutical composition has stronger therapeutic effect on mice infected with AIDS combined with Marneffei basketball disease than that of antifungal drugs used alone, and is also stronger than that of thalidomide used alone. The invention reduces the therapeutic dose of antifungal drugs, enhances the inhibition effect on Marneffei panulifera and effectively improves the therapeutic effect.)

1. A pharmaceutical composition containing thalidomide and an antifungal drug is characterized by consisting of the thalidomide and the antifungal drug.

2. The pharmaceutical composition containing thalidomide and antifungal agent of claim 1, wherein the molar ratio of thalidomide to antifungal agent is 1:12.5 to 1: 50.

3. The pharmaceutical composition containing thalidomide and an antifungal agent in accordance with claim 1, wherein the antifungal agent is fluconazole, voriconazole, itraconazole, amphotericin B, caspofungin, flucytosine, terbinafine or amorolfine.

4. The pharmaceutical composition of claim 1 or 3, comprising thalidomide and an antifungal agent, wherein said antifungal agent is amphotericin B.

5. The application of the pharmaceutical composition containing thalidomide and an antifungal drug according to any one of claims 1 to 4, which is characterized in that the pharmaceutical composition containing thalidomide and an antifungal drug is applied to preparation of a drug for treating AIDS combined Malneffeta.

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition containing thalidomide and an antifungal drug, and an application of the pharmaceutical composition in preparation of a drug for treating AIDS combined Marneffei panuli.

Background

Thalidomide was synthesized by CIBA pharmaceutical in 1954 and used as a sedative and antiemetic agent for the treatment of morning sickness in pregnant women. Similar to the chemical composition of barbiturates, thalidomide was the most popular anti-emetic agent of the time, due to its remarkable anti-emetic effect, and it was sold in at least 37 brands worldwide. But then it was reported that approximately 1 million children worldwide were born with the deformities associated with the use of thalidomide, and thus thalidomide withdrawn from the european and canadian markets in 1961 and 1962, respectively. Since 1961 the side effects of "seal malformation" were banned and seemed to have been forgotten or abandoned. Recently, it has been approved and used for various inflammatory, autoimmune and/or dermatological diseases, such as leprosy erythema nodosum, vascular lupus erythematosus, psoriasis and refractory inflammatory bowel disease, stomatitis, behcet's disease, prurigo nodularis, etc., and also as a new therapy for tumors, such as refractory multiple myeloma. There is no report on the use of this compound in fungal infectious diseases.

Thalidomide has immunomodulatory, anti-inflammatory, and anti-angiogenic effects, with unclear mechanisms, although it can modulate inflammatory cytokines such as TNF-a, interferon-gamma, interleukin 10 (IL-10), IL-12, cyclooxygenase 2 (COX-2), and the like. Thalidomide inhibits the production of TNF-a by enhancing the degradation of TNF-a mRNA in lipopolysaccharide-induced human monocytes and mouse macrophages. The previous clinical research shows that the peripheral blood TNF-a of patients with AIDS and Marneffei basket fungus is obviously increased, the TNF-a of the patients is further increased after the third day of treatment and is reduced after half a month of treatment, and the peripheral blood TNF-a of the patients who die due to ineffective treatment is obviously higher than that of the patients who are improved after the treatment. Whether the patient prognosis can be improved by inhibiting over-activated TNF-a or not, the combination use of thalidomide and an antifungal drug surprisingly achieves a good treatment effect on a Marneffei basket fungus infected mouse model, and the combination antifungal drug is expected to be used for treating AIDS combined with the Marneffei basket fungus.

Disclosure of Invention

The invention aims to provide a pharmaceutical composition containing thalidomide and an antifungal drug and application thereof in preparing a drug for treating AIDS combined Marneffei panulifera.

The purpose of the invention is realized as follows:

a pharmaceutical composition comprises thalidomide and antifungal agent.

The molar ratio of the thalidomide to the antifungal drug is 1:12.5-1: 50.

The antifungal drug is fluconazole, voriconazole, itraconazole, amphotericin B, caspofungin, flucytosine, terbinafine and amorolfine.

The antifungal agent is amphotericin B.

The pharmaceutical composition is applied to the preparation of medicines for treating AIDS combined Marneffei panoraria.

The invention has the advantages that:

1. the pharmaceutical composition has stronger therapeutic effect on AIDS combined Marneffei basket fungus than that of singly using antifungal drugs and simultaneously stronger than that of singly using thalidomide.

2. The invention reduces the therapeutic dose of antifungal drugs, enhances the inhibition effect on Marneffei panulifera, effectively reduces the systemic toxicity of amphotericin B, and ensures that the application of the amphotericin B becomes safer.

Drawings

FIG. 1 shows the weight curves group1-group5 of mice molded with cyclophosphamide, which were given with cyclophosphamide in the first three days and injected intraperitoneally with Marneffei basket mold in the fourth day. CTX is the group of Marneffei staphylium not given after cyclophosphamide is given in the first three days;

FIG. 2 shows that after the mice are successfully molded, the mice are respectively administered with a Thalidomide treatment group (Thalidomide group), an amphotericin B treatment group (AmB group), and a Thalidomide and amphotericin B treatment group (AmB + Thalidomide group), wherein a Model group (Model) is a drug-free group after molding;

FIG. 3 shows the survival rate of mice of different administration groups after the mice are successfully modeled. The Thalidomide treatment group (Thalidomide group), the amphotericin B treatment group (AmB group), the Thalidomide and amphotericin B treatment group (AmB + Thalidomide group), and the Model group (Model) is a drug-free group after Model building.

Detailed Description

The present invention is further illustrated but not limited in any way by the following examples, and any modifications made thereto are intended to fall within the scope of the present invention.

A pharmaceutical composition containing thalidomide and antifungal agent, and its application in preparing medicine for treating AIDS complicated with Marneffei basket fungus are provided.

The purpose of the invention is realized as follows:

a pharmaceutical composition comprises thalidomide and antifungal agent.

The molar ratio of the thalidomide to the antifungal drug is 1:12.5-1: 50.

The antifungal drug is fluconazole, voriconazole, itraconazole, amphotericin B, caspofungin, flucytosine, terbinafine and amorolfine.

The antifungal agent is amphotericin B.

The pharmaceutical composition is applied to the preparation of medicines for treating AIDS combined Marneffei panoraria.